Journal of the Malta College of Pharmacy Practice · Isabel Stabile, Jean Karl Soler 50. 2 Journal of the Malta College of Pharmacy Practice Issue 14 Summer 2008 Hypertension - Coronary

Issue 14 Summer 2008 Journal of the Malta College of Pharmacy Practice 1

Journal of the Malta Collegeof Pharmacy Practice

Issue 14 Summer 2008ISSN 1811-9514

www.mcppnet.org

Diversityinpractice Editorial 3

Insulininthemanagementofdiabetesmellitus RuthTheuma 6

Long-actingbeta2-adrenoreceptoragonists: salmeterolandformoterol LornaMarieWest 11

Probiotics:which,whenandwhy? ValerieVella 15

Aninternationaloverviewofsomepharmacistprescribingmodels AntonellaP.Tonna,DerekStewart,DorothyMcCaig 20

Prescribinganddispensingchecklists DGPublicHealthRegulation 26

CodeofEthicsforthePharmaceuticalProfession PharmacyCouncilMalta 28

ThePharmaceuticalUnit VanessaBugeja 32

TheimpactofEUlegislationonmedicinesinMalta VanessaBugeja 34

Policyprinciplesforacompetitivehealthcareenvironment PRIMA 40

EUtwinning:‘Light’ JosephBusuttil 47

Primarycare:quovadis? IsabelStabile,JeanKarlSoler 50

2 Journal of the Malta College of Pharmacy Practice Issue 14 Summer 2008

Once dailyHypertension - Coronary artery disease - CHF5to10 mg

Coversylis a long-acting ACE in-

hibitor. International nonproprietaryname: Perindopril. Indications: Essential hyperten-

sion. Stable coronary artery disease: reduction in risk of cardiacevents in patients with a history of myocardial infarction and/or revascularization.

Treatment of symptomatic heart failure. Dosage and administration: Coversyl should be takenin the morning before food. Hypertension: 5 mg once daily then the dose may be increased to 10 mg after 1

month of treatment to improve blood pressure control or in case of concomitant stable coronary artery disease. Stable coro-nary artery disease: A starting dose of 5 mg for 2 weeks is recommended, then uptitration to 10 mg once daily, depending on ac-

ceptability. Congestive heart failure: Coversyl should be started under close medical supervision at a starting dose of 2.5 mg.This may be increased to 5 mg once blood pressure acceptability has been demonstrated. Elderly patients: start treatment at 2.5 mg

daily. Contraindications: Children. Pregnancy. Lactation. Patients with a history of hypersensitivity to Coversyl. Precautions: Assess renalfunction before and during treatment where appropriate. Renovascular hypertension. Surgery/anesthesia. Renal failure: the dose should be cautiouslyadjusted in accordance with the creatinine clearance (refer to complete data sheet). Symptomatic hypotension is rarely seen, but is more likely involume-depleted patients, those receiving diuretics, or with the first two doses. In diuretic-treated patients, stop the diuretic 3 days before start-ing Coversyl. A diuretic may later be given in combination if necessary; potassium-sparing diuretics are not recommended. Combination withneuroleptics or imipramine-type drugs may increase the hypotensive effect. Serum lithium concentrations may rise during lithium therapy.Side effects: Rare and mild, usually at the start of treatment. Cough, fatigue, asthenia, headache, disturbances of mood and/or sleep havebeen reported. Less often, taste impairment, epigastric discomfort, nausea, abdominal pain, and rash. Reversible increases in blood ureaand creatinine may be observed. Proteinuria has occurred in some patients. Rarely, angioneurotic edema and decreases in hemoglobin,red cells, and platelets have been reported. Composition: Each tablet contains 5 mg or 10 mg of the arginine salt of perindopril.Presentation: Canister of 30 tablets of Coversyl 5 mg. Canister of 30 tablets of Coversyl 10 mg. As prescribing information may varyfrom country to country, please refer to the complete data sheet supplied in your country. Les Laboratoires Servier - France. Correspondent:Servier International, 22, rue Garnier 92578 Neuilly-sur-Seine Cedex, France. www.servier.com

Also available under the brand names Aceon ®, Acertil ®, Armix®, Coverene®, Coverex ®, Coversum®, Prestarium ®, Prexanil®, Prexum ®, Procaptan ®

1. Myers MG; Perindopril multicentre dose-response study group. A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24hafter dosing. Can J Cardiol. 1996;12:1191-1196. 2. Morgan T, Anderson A. Clinical efficacy of perindopril in hypertension. Clin Exp Pharmacol Physiol. 1992;19:61-65. 3. Lechat P, Granham SP, Desche P, et al. Efficacy and acceptability of perindopril in mild-to-moderate chronic congestive heart failure. Am Heart J. 1993;126:798-806. 4. Bounhoure JP, Bottineau G, Lechat P, et al. Value of perindopril in the treatment of chronic congestive heart failure: multicentre double-blind placebo-con-trolled study. Clin Exp Hypertens. 1989;A11(suppl 2):575-586. 5. The EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery diseaseInvestigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomized, double-blind, placebo con-trolled, multicentre trial (the EUROPA study). Lancet. 2003;362:782-788.

1 tablet daily

Hypertension 1,2

Heart failure 3,4

Stable coronary artery disease 5

New indicationStable coronary artery disease:reduction in risk of cardiac events

in patients with history of myocardialinfarction and/or revascularization

Demonstrated efficacyin 3 indications1-5

For more information: www.coversyl.com

SI/DTC - 09_CO_0

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Once dailyHypertension - Coronary artery disease - CHF

5to10 mg










1 tablet daily

Hypertension 1,2

Heart failure 3,4






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Once dailyHypertension - Coronary artery disease - CHF5to10 mg










1 tablet daily

Hypertension 1,2

Heart failure 3,4






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Issue 14 Summer 2008 Journal of the Malta College of Pharmacy Practice �

Issue 14 Summer 2008

ISSN1811-9514

TheOfficialPublicationoftheMaltaCollegeofPharmacyPractice

c/oDepartmentofPharmacy,UniversityofMalta,Msida

Tel:(356)23402908Fax:(356)25401157

Email:[email protected]

ChairpersonofPublicationsLornaMarieWest BPharm(Hons), MSc Clin Pharm (Aberdeen)

EditorinChiefMariaCordina BPharm(Hons), PhD(QUB)

EditorialBoard

MarketingEditorAngeliquePaceBPharm(Hons)

MembersClaudeFarrugiaBPharm(Hons), PhD(UIC), MRSC

SandraMifsudBonniciBPharm(Hons), BA, LP

PatriciaVellaBonannoBPharm(Hons), MSc(Belfast) PhD

The opinions expressed in this publication are those of the respective authors and do not

necessarily reflect the opinions of the editor or publisher.

AdvertisingPolicyapplicable to all official publications

of the Malta College of Pharmacy PracticeAdvertisers are liable for the contents

of any of their advertisements publishedaccording to the instructions. The advertisers shall indemnify and hold harmless the Malta College of Pharmacy Practice against and from any and all claims, damages, liabilities, costs and expenses whatsoever, including counsel fees, arising from

the content of any of their advertisements.

InstructionstoAuthorsBeforesubmittinganarticletoTheJournaloftheMaltaCollegeofPharmacyPractice,pleasereadandcarefullyfollowtheinstructionstoauthors

whicharefoundatwww.mcppnet.org

TheCouncilPresident

MariaCordinaBPharm(Hons), PhD(QUB)

SecretaryRuthTheumaBPharm(Hons), MSc Clin Pharm (Aberdeen)

RegistrarCharlotteCarabottCastagnaBPharm(Hons)

ChairpersonofPublicationsLornaMarieWest BPharm(Hons), MSc Clin Pharm (Aberdeen)

TreasurerAngelaBorgBarthetBPharm(Hons), MSc(Pub Health)

Diversity in practice

Following years of hard work we are pleased to announce that The Malta College of Pharmacy Practice has been included in the Fourth Schedule of the Health Care Profession Act as a professional organisation representing the Pharmacy Profession.

MariaCordinaBPharm(Hons), PhD(QUB)

EditorEmail:[email protected]

While the College fulfilled all the criteria necessary for inclusion from its inception, accomplishing the deed, proved to be somewhat of an arduous task. Nevertheless, we are very pleased with the outcome and look forward to continuing our service to the profession.

This edition of the Journal illustrates the growth and diversity of the profession in Malta as a reflection of the international scene and the transitions in our country. Through the Journal, the Malta College of Pharmacy Practice aims to support the profession in all its facets and to encourage good communication between practitioners, scientists, regulators and other healthcare professionals with the ultimate aim of improving patient care.

One such transition is Malta’s accession to the EU. This event brought with it significant upheaval within the pharmaceutical sector as documented in the paper entitled ‘The impact of EU legislation on medicines in Malta’. Due to EU legislation Malta has faced significant challenges relating to availability of medicines which possibly had an impact on rational drug use. On a more positive note, we read that Malta will benefit from a Twinning project with the Netherlands, through which the Registrar of the Pharmacy Council together with registrars’ of other regulating bodies, as well as council members, will benefit from intensive training on the relevant EU Directives related to the respective professions. The discussion during the

Editorial

JournaloftheMaltaCollegeofPharmacyPractice

Front photo: Allegory ‘Arzeney’ tile, painted and glazed earthenware (circa 1910), The German Museum of Pharmacy, Heidleberg Castle


recent launch of this project brought to light a number of issues that require further clarification, highlighting the importance of the proposed training.

The management of diabetes using insulin is a highly topical issue. This paper provides an update based on current evidence thus supporting rational use of drugs. Additionally practical information with regards to the delivery and administration of insulin is also provided. It is essential for health care professionals to be well versed in the latter aspects and address them during patient interventions. Successful management is highly dependent not only on drug action but also on delivery and administration.

The paper comparing long-acting beta2-adrenoreceptor agonists aims to dispel any misconceptions about these commonly used medicines in the management of asthma and COPD. While both formoterol and salmeterol fall within the same classification there are a number of distinct pharmacological differences between the two which have a significant impact on management and patient outcomes. Healthcare professionals dealing with NHS medicines should find this paper of particular interest due to the recent availability of formotorol instead of salmeterol on the local NHS.

Probiotics appear to be generating

significant interest in the medical literature with a number of claims being made. The author identifies these and provides a clear picture regarding evidence, or the lack of it, relating to these claims.

Various countries have evolved and adopted different models of prescribing, pharmacist prescribing being one of them. The paper on pharmacist prescribing reviews the different models of pharmacist prescribing in the USA, UK and other countries. In Malta we still pertain to the traditional prescribing model, which, nevertheless, necessitates attention. The College fully endorses Legal Notice (L.N.) 292 of 2006, Medicines Act, Prescription and Dispensing Requirements Rules, 2006 as illustrated in a previous editorial of this Journal. We are further offering our support to DG Public Health Regulation by publishing the Checklist for prescribing and dispensing, based on the above Legal Notice, which has recently been circulated to healthcare professionals. We strongly urge health care professionals to abide by this LN in the interest of patient safety.

In our quest to enhance communication between the different sectors of the pharmaceutical profession, we have invited a paper from PRIMA, the Pharmaceutical Research and Development Industry Malta Association. This organisation is

Editorial

a member of The European Federation of Pharmaceutical Industries and Associations (EFPIA) which represents the research-based pharmaceutical industry operating in Europe. We would like to take this opportunity to encourage further submissions from all sectors of the pharmaceutical industry.

The importance of having a strong and well structured primacy care system is addressed in the paper entitled Primary Care: QuoVadis? It also stresses the need to adopt a multidisciplinary approach to patient care. The authors have taken the opportunity to introduce The Mediterranean Institute of Primary Care (MIPC) which is a newly formed non-governmental organization aimed at supporting research and training within the domain of primary care in the Mediterranean region.

On a final note we would like to congratulate the Pharmacy Council on the publication of the revised Code of Ethics of the Pharmaceutical Profession. The updated Code reflects the current trends in practice; it especially highlights the profession’s shift from a product to a patient-oriented one. We have included The Code in the Journal primarily to support the Council’s work and to further encourage pharmacists to read and practice by the code.


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Insulin in the management of diabetes mellitus

Insulin is an essential drug used in the treatment of both type 1 and type 2 diabetes mellitus. Depsite this, insulin remains one of the drugs that is disliked by most patients and health-care professionals. It is also a drug that is vey commonly implicated in medication errors. Pharmacists are in an ideal position to give the appropriate information on insulin to patients with diabetes mellitus every time that they come to the pharmacy. More and more patients are being switched to insulin analogues, which have greatly improved the management of diabetes.

RuthTheumaBPharm(Hons), MSc Clin Pharm(Aberdeen)

Senior Clinical Pharmacist, Mater Dei Hospital, Tal-Qroqq, MaltaSecretary, Malta College of Pharmacy PracticeEmail:[email protected]

KeywordsInsulin, type 1 diabetes mellitus, type 2 diabetes mellitus, insulin analogues, insulin delivery

IntroductionDiabetes mellitus refers to a group

of metabolic diseases characterised by hyperglycaemia.

It results from defects in insulin secretion, insulin action, or both.1 Insulin is secreted from the beta-cells of the pancreas and is the hormone needed to enable

glucose to enter the cells and provide energy.2 Insulin is also important in keeping blood glucose levels within the acceptable limits.2 Thus in patients with diabetes, exogenous insulin given as a replacement, forms a very important strategy in the management of both type 1 and type 2 diabetes.

Insulinintype1diabetesType 1 diabetes results from a cellular-

mediated autoimmune destruction of the beta-cells of the pancreas with consequent insulin deficiency.1 Insulin is required for survival to prevent ketoacidosis, coma and death,� thus the term ‘insulin-dependent diabetes’ was previously coined to this type of diabetes.

Insulinintype2diabetesAlthough insulin was originally

developed for the treatment of type 1 diabetes, it has gained more importance in the management of hyperglycaemia in type 2 diabetes. Guidelines suggest that insulin should not be used as last-line treatment when other therapies fail. It should be used early on as an additional therapy to lifestyle interventions and metformin.4 Alvarsson et al5 showed that earlier insulin use in patients with type 2 diabetes, in contrast to sulphonylurea therapy, helps preserve beta-cell function and promotes better metabolic control with less chance of hypoglycaemia. In the second year of the study, the effectiveness of the oral hypoglycaemic agents that increase beta-cell function decreased, supporting the concept that beta-cells wear out if they are continuously overworked.� This is not the case when insulin is given as treatment earlier on since it may temporarily prolong endogenous insulin secretion.

Insulin offers an expected decrease in glycosylated heamoglobin (HbA1c) of 1.� – 2.�%; which is the largest expected decrease in HbA1c when compared to other therapies, making it the most effective of diabetes medications in lowering blood glucose.4 It is also inexpensive when compared to other classes of anti-diabetic agents.4 There is no dose limit with insulin treatment and relatively larger doses are required to overcome the insulin resistance of type 2 diabetes when compared to doses used in type 1.4

Insulin improves the lipid profile but is associated with weight gain of around 2 to 4 kg.4 This weight is partly due to the correction of glycaemia (which presents with weight loss) and partly due to the reduction of glycosuria.4 Insulin-induced hypoglycaemia is less frequent in type 2 than in type 1 diabetes.4

Therapeutics


Therapeutics

BasalandprandialinsulinIt is convenient to think of the insulin

dose requirement in physiologic terms consisting of “basal” and “prandial”. Basal insulin refers to background exogenous insulin given per unit of time necessary to prevent unchecked gluconeogenesis and ketogenesis.6 Basal insulin is the intermediate- or long- acting component of an insulin regimen. Prandial insulin, on the other hand, refers to the insulin that is necessary to cover meals.6 This is represented by short- or rapid-acting insulins. In most insulin dose regimens, the intermediate- or long- acting insulins are given together with short- or rapid-acting insulins once or twice daily in order to mimic the physiological pattern of endogenous insulin as secreted by the pancreas.

Typesofinsulin

Since the landmark discovery of insulin by Fredrick Banting and Charles Best in 1922, huge steps have been made in research and development of insulin preparations.2 Early insulin preparations were purified quite crudely from porcine or bovine pancreatic tissue. Today, insulin is mostly made biosynthetically by recombinant DNA technology or genetic engineering of human sequence insulin.

Recent advances on human insulin resulted in the development of the insulin analogues.� These analogues are a genetically engineered form of insulin in which certain amino acids are substituted for those found naturally on an insulin molecule to improve their pharmacokinetic profiles.� There are two types of insulin analogues, the rapid-acting analogues and the long-acting analogues.

Rapid-acting insulin analogues are absorbed faster from the injection site when compared to the conventional soluble insulin.� Thus they readily supply a bolus of prandial insulin required to deal with postprandial elevations in blood glucose. Currently there are three rapid-acting analogues namely aspart, glulisine, and lispro. The more rapid onset of action of these analogues is an advantage over regular human soluble insulin. The latter has to be injected �0-4� minutes before meals to ensure that peak concentrations coincide with the elevated post-prandial glucose levels. In practice patients might tend to inject their insulin at meal times, or on the contrary, inject insulin and then skip or refuse the meal, with the possibility of a hypoglycaemic event. These problems were overcome with the development of the rapid-acting insulins which can be given just before meals.

Long-acting insulin analogues, that is, insulin glargine and insulin detemir are released slowly over time and thus present a constant level of basal insulin or background insulin for the day.� Insulin glargine is designed to have low solubility at neutral pH. It is completely soluble at the acidic pH of the injection solution.8

After injection into the subcutaneous tissue, the acidic solution is neutralised leading to the formation of micro-precipitates from which small amounts of insulin glargine are continuously released, providing a smooth, peakless, predictable concentration/time profile with a prolonged duration of action. On the other hand, insulin detemir has a prolonged duration of action since it self-associates strongly at the injection site and binds to albumin via the fatty acid side-chain.9 Thus detemir is released more slowly to peripheral target tissues.

Several studies that compared rapid-acting insulin analogues with short-acting soluble insulin, and long-acting insulin analogues with isophane insulin, have suggested that insulin analogues reduce hypoglycaemia, particularly at night.10

Several insulin preparations are available locally. The conventional ones are listed in Table 1, whereas the insulin analogues are listed in Table 2.

Table1.Conventionalinsulinsavailablelocally11,12,13

Typeofinsulin Example Colour Onsetofaction(hours)

Peakofaction(hours)

Durationofaction(hours)

Short-acting Soluble insulin Yellow 0.� 1.�-�.� �.0-8.0

Intermediate-acting Isophane insulin Light green 1.0-2.0 4.0-12.0 16.0-��.0Intermediate- and short acting mixtures Biphasic isophane insulin Brown 0.� 2.0-8.0 24.0

Table2.Insulinanaloguesavailablelocally14,15,16,17

Typeofinsulin Examples Onsetofaction(hours)

Peakofaction(hours)

Durationofaction(hours)

Rapid-acting Insulin aspart Insulin lispro

0.2�0.2�-0.�0

1.0-�.00.�-2.�

�.0-�.0 �.0-6.�

Long-acting Insulin glargine 1.00 none 24.0

Rapid- and intermediate-acting Biphasic insulin lispro 0.2� 1.0-4.0 1�.0-24.0


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Malta (MAH): Local Representative of the MAH:Novartis Pharmaceuticals UK Ltd, Novartis Pharma Services,Frimley Business Park, Frimley, Camberly PO Box 124,Surrey GU16 7SR, Valletta VLT 1000, MaltaUnited Kingdom Tel: +356 2298 3217


Practicepoints

• Insulin should not be used as last-line therapy in type 2 diabetes mellitus but early on as an additional therapy to lifestyle interventions and metformin since it preserves pancreatic function.

• Insulin analogues are produced from genetic engineering of the insulin molecule and are associated with reduced hypoglycaemia especially during the night.

• Rapid-acting insulin analogues can be given immediately before a meal or shortly after if necessary and thus are classified as ‘prandial’ insulins. They are important to cover the glucose elevations brought about when meals are consumed.

• Long-acting insulin analogues offer a constant ‘basal’ level of insulin and are designed in a way so as to offer a peakless concentration of insulin in the body.

• Although the syringe and vial are the mostly used insulin delivery system, the insulin pen is discreet, less painful when injecting insulin and easier to use especially for patients with decreased visual acuity.

Similar preparations of insulin regardless of manufacturer have the same colour on the label. This universal colour code was agreed upon by major insulin manufacturers following an initiative by the International Diabetes Federation (IDF).18 Such a colour code helps to reduce confusion for patients with diabetes especially since patients might recognize the type of insulins from the colour on the label. Colour coding also proves helpful for patients who have to buy insulin abroad or from a different source. All parties are now actively working together to produce a colour code for insulin analogues.

Onset, peak, and duration of action are approximate for each insulin product, as there may be variability depending on each individual, the injection site, and the individual’s exercise program.16

InsulindeliverydevicesFor optimal control of patients with

diabetes, insulins do not only have to match the endogenous insulin as closely as possible but they must also be formulated and delivered in a way so as to encourage patient adherence.

For many years, the vial and syringe were the standard means of delivering insulin and locally this method is the most popular especially among patients with Type 2 diabetes. However, the syringe carries a stigma and not all patients are

comfortable to use it. This has implications for compliance and glycaemic control.

The introduction of insulin pens in 198� has offered several advantages to the patient:1�

• discreet and appears less ‘medical’• injection is less painful since needle is

shorter• less time consuming • easier to use especially for patients who

have impaired eyesight or coordination• more accurate dosing with an audible

click when the dose is dialed• less wastage of insulin

Better adherence after conversion to pen (��% vs �6%), reduced likelihood of

hypoglycaemia episodes, and a decreased likelihood of emergency department visits have been documented.19 Insulin pens however are more expensive than the vial and syringe. Insulins cannot be mixed in an insulin pen since only one cartridge at a time can be put in the pen and thus the patient would have to take more injections.

Pens are available in two different forms, with either replaceable cartridges or disposable pre-filled cartridges.

CounsellingpatientsoninsulinInsulin should be stored in a

refrigerator at 2-80C as suggested by the manufacturers.20 However, injecting cold insulin can be painful to the patient. To overcome this problem, many providers suggest storing the vial or cartridge of insulin which is in use at room temperature. Insulin kept at room temperature has a shelf life of one month and patients should be advised to write the date of first puncturing on the container. The extra supplies of insulin which are not in use should however be stored in a fridge. Insulin should not be stored in extreme heat (e.g. direct sunlight) or in extreme cold (e.g. in the freezer). Insulin pens should not be stored in the fridge.

Other counselling points that should be communicated to patients whilst dispensing insulin are found in Panel 1.

ConclusionBesides counselling the patient with

diabetes on storage conditions for their insulin, pharmacists are in a unique

Panel1.Insulindispensingpracticepoints

1. Insulin should be stored in the fridge; the vial or cartridge in use should be kept at room temperature and has a shelf life of 4-6 weeks once punctured.8,9,11-14,1� The insulin pen should never be refrigerated.

2. Soluble and isophane insulins can be mixed together in a syringe; soluble insulin is drawn up first and the total volume made up by adding the isophane insulin.12 Insulin analogues should not be mixed together.8,14

�. The 1mL insulin syringe is graduated in 100 units of insulin; the insulin pen gives an audible click every time that it is turned and 1 click is equivalent to 1 unit of insulin being drawn up from the cartidge to the pen.1�

4. Injection sites should be rotated amongst deltoid, thigh and abdomen; injection in the abdominal wall enures a faster absorption than other injection sites.12

�. Soluble insulin, isophane insulin and the biphasic isophane should all be injected half an hour before meals; insulin aspart, insulin lispro and biphasic insulin lispro should be given 1� minutes before a meal but if necessary also immediately before or soon after a meal; insulin glargine can be given once daily at any time but at the same time each day. 8,11,1�,14,1�,21

Therapeutics


position to provide clinical input into the management of this chronic condition. Pharmacists may review self-monitoring blood glucose readings of patients, help in the calculation and titration of insulin doses, identify patients with type 2 diabetes who may benefit from the addition of insulin to their regimens, teach the injection technique and provide counselling on avoiding, recognizing and treating hypoglycaemia.�

The time when the patient comes for refill of insulin at the pharmacy, is an opportunity for pharmacists to discuss insulin use and diabetes in general and to try to motivate the patients. Surprisingly, less than 40% of patients with diabetes

know their HbA1c levels and only 2�% accurately reported that value.22 It is important for patients to know what their HbA1c level is so that they know whether their diabetes is improving or worsening. Patients should also be knowledgeable about the relationship between poor glycaemic control and health risks.�

Insulin is in general disliked by the majority of patients. Barriers to its use include a belief that insulin causes complications or death, fear of hypoglycaemia and weight gain, perception of insulin treatment as complicated and difficult, and a feeling of failure from their part if insulin is initiated.1�

Thus the advantages of adding insulin earlier on in their treatment should be translated to the patient and goals of treatment should be made clear. Patients should be made aware of the advantages of the insulin analogues in mimicking the endogenous insulin system and also in their association of less hypoglycaemic events and less weight gain reports. Moreover, patients with diabetes should be reassured that the initiation of insulin is not a sign of treatment or condition failure. It should be explained to them that diabetes is a chronic condition and that insulin helps to preserve pancreas function.1�

Pharmacists are now more than ever in a good position to make a difference in the life of a patient with diabetes.

1. American Diabetes Association (ADA), 200�. Diagnosis and classification of diabetes mellitus. Diabetes Care, �0 (1), pp. S42-S4�

2. International Diabetes Federation (IDF), 2008. About Insulin [online] Available from: http://www.idf.org/home/index.cfm?printpage=1&node=1�96 [Accessed on 16th May 2008]

�. World Health Organisation (WHO), 1999. Definition, diagnosis and classification of diabetes mellitus and its complications [online] Available from: http://www.staff.ncl.ac.uk/philip.home/who_dmg.pdf [Accessed on 12th February 200�]

4. Nathan, D.M., Buse, J.B., Davidson, M.B., et al., 2006. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care, 29(8), pp. 196�-19�2

�. Alvarsson, M., Sundkvist, G., Lager, I., et al., 200�. Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care, 26, pp. 22�1-22��

6. Clement, S., Braithwaite, S.S., Magee, M.F., et al., 2004. Management of diabetes and hyperglycemia in hospitals. Diabetes Care, 2�, pp. ��-�9�

�. Joffe, D.L., 2008. When, why and how to use insulin analogs (& with other agents), including patient-driven titration. U.S. Pharmacist, pp. 2�-2�

8. Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Lantus 100 units/ml solution for injection. 2006 [online] Available from http://www.emc.medicines.org.uk [Accessed on 2�rd June 200�]

9. Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Levemir 100 units/ml 200� [online] Available from http://www.emc.medicines.org.uk [Accessed on 28th May 2008]

10. National Prescribing Centre, 200�. The role of newer insulins in diabetes: Summary. MeReC bulletin, 10 (�), pp. 1

11. Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Actrapid 100 IU/ml solution for injection 200� [online] Available from http://www.emc.medicines.org.uk [Accessed on 2�th May 2008]

12. British Medical Association and the Royal Pharmaceutical Society of Great Britain, 200�. Insulins. British National Formulary, Number �4. Great Britain: The Pharmaceutical Press, pp. ��6-�6�

1�. Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Mixtard �0 100 IU/ml 200� [online] Available from http://www.emc.medicines.org.uk [Accessed on 29th May 2008]

14. Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Novorapid 100 U/ml 2006 [online] Available from http://www.emc.medicines.org.uk [Accessed on 2�rd June 2008]

1�. Marcus, A., 2008. Diabetes care – insulin delivery in a changing world. Medscape Journal of Medicine, 10(�), pp. 120

16. Food and Drug Administration (FDA), 2001. Insulin preparations [online] Available from: http://www.fda.gov/fdac/features/2002/chrt_insulin.html [Accessed on 16th May 2008]

1�. Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Humalog Mix2� 100 U/ml 200� [online] Available from http://www.emc.medicines.org.uk [Accessed on 29th May 2008]

18. International Diabetes Federation (IDF), 2008. Insulin colour code [online] Available from: http://www.idf.org/home/index.cfm?printpage=1&unode=C�6�F� [Accessed on 16th May 2008]

19. Lee, W.C., Balu, S., Cobden, D., et al., 2006. Medication adherence and the associated health-economic impact among patients with type 2 diabetes mellitus converting to insulin pen therapy: an analysis of third-party managed care claims data. Clinical Therapeutics, 28, pp. 1�12 -1�2�

20. American Diabetes Association (ADA), Insulin storage and syringe safety information [online] Available from: http://www.diabetes.org/utils/printthispage.jsp?PageID=TYPEID [Accessed on 16th May 2008]

21. Electronic Medicines Compendium for the Professional. Specific Product Characteristics. Insulatard 100 IU/ml 200� [online] Available from http://www.emc.medicines.org.uk [Accessed on 2�th May 2008]

22. Heisler, M., Piette, J.D., Spencer, M., et al., 200�. The relationship between knowledge of recent HbA1c values and diabetes care understanding and self-management. Diabetes Care, 28, pp. 816-822

References

Therapeutics


Long-acting beta2-adrenoreceptor agonists: salmeterol and formoterol

The long-acting beta2-adrenoreceptor agonists salmeterol and formoterol, given by inhalation, have a bronchodilating effect lasting for at least 12 hours after a single administration. They complement but not substitute inhaled glucocorticoids in the management of asthma and are also used in the management of chronic obstructive pulmonary disease (COPD).

LornaMarieWestBPharm(Hons), MSc Clin Pharm(Aberdeen)

Senior Clinical Pharmacist, Mater Dei Hospital, Tal-Qroqq, MaltaChairperson of Publications, Malta College of Pharmacy PracticeEmail:[email protected]

KeywordsFormoterol, salmeterol, long acting beta2-adrenoreceptor agonist, asthma, COPD

IntroductionInhaled short-acting beta2-

adrenoreceptor agonists have been used for over 40 years in the treatment of asthma. They are considered as first-line therapy for asthma treatment as they provide rapid bronchodilation and protect against stimuli, such as exercise, allergen, or pollutants that cause bronchoconstriction in asthmatic patients.1 Salmeterol and formoterol are the first two drugs of a new generation of

long-acting beta2-adrenoreceptor agonistsgiven by inhalation with bronchodilating effects lasting for at least 12 hours after a single administration. Both of these drugs have become important complements in the regular management of asthmatic patients who are not sufficiently controlled with inhaled glucocorticoids.2 Also, regular use of a long-acting beta2-adrenoreceptor agonist improves health status in patients with COPD.�

PharmacologicaldifferencesFormoterol and salmeterol have similar

pharmacological properties: both are highly selective and potent beta2-adrenoreceptor agonists, with relaxant effects on bronchial smooth muscle in vitro. However, some significant pharmacological differences between these drugs have been documented in vitro and in patients, as shown in Table 1.2

Formoterol has a more rapid onset of action than salmeterol, which may make formoterol suitable for symptom relief as well as symptom prevention in the management of asthma. However, the long-term safety of regular treatment with formoterol at higher doses per day than those recommended by the manufacturer has not been established.� Therefore, it is imperative to instruct the patient that formoterol should ONLY be used every 12 hours.

DosecomparisonIn most adult patients treated with

inhaled long-acting beta2-adrenoreceptor agonists, symptoms will be satisfactorily controlled on �0mcg salmeterol twice daily or 12mcg formoterol twice daily. If these drugs are used in higher doses, attention must be paid to side effects.� Studies in adult patients with mild-to-moderate asthma showed that salmeterol �0mcg8, and formoterol, 12 and 24mcg9, administered from a metered-dose inhaler were safe and had a low degree of cardiac effects. However, studies10,11 comparing the cardiovascular effects of formoterol and salmeterol administered at the recommended single doses in patients suffering from chronic obstructive pulmonary disease (COPD) with preexisting mild-to-moderate arrhythmias and hypoxaemia suggested that formoterol 24mcg induces a statistically significant increase in heart rate when compared with placebo and formoterol 12mcg, and salmeterol �0mcg. Additionally both formoterol 12mcg and salmeterol �0mcg have a significantly greater effect than placebo, but there were no differences between these two treatments.

Beta2-adrenoreceptor agonists can decrease plasma potassium levels by stimulation of beta2-adrenoreceptors in the

Therapeutics


liver and skeletal muscle. With the 24mcg dose, but not the 12mcg dose, formoterol produces a statistically significant decrease in serum potassium levels in patients with mild-to-moderate asthma. Also, salmeterol in doses up to a �0mcg was not found to modify the serum potassium level, whereas there was a trend toward a decrease in potassium with a 100mcg dose in patients with mild-to-moderate asthma.

Moreover, doses higher than 12mcg in the case of formoterol and �0mcg in the case of salmeterol do not improve FEV1 further, thus not showing dose-dependent effects of the drugs on this measurement. Therefore, formoterol produces little additional effect in dosages beyond 12mcg twice daily. Salmeterol produces little additional effect in dosages beyond �0mcg twice daily but does produce more side effects.� Therefore, the recommended single dose of salmeterol �0mcg and formoterol 12mcg allows a relatively higher safety margin than salmeterol 100mcg and formoterol 24mcg.10

Formoterolandsalmeterolasadd-ontherapyinasthma

Studies have shown that adding a long-acting beta2-adrenoreceptor agonist to patients who are not controlled with inhaled glucocorticoids only, statistically significantly decreases exacerbations and hospitalizations in these patients.1� These studies have also shown that in patients with persistent asthma combining salmeterol or formoterol with a median of 400mcg of beclomethasone or equivalent results in greater improvement from baseline in FEV1, in symptom-free days

and in the daytime use of rescue beta2-adrenoreceptor agonists than prescribing a higher dose of inhaled glucocorticoids only (median of 800 to 1000mcg per day of beclomethasone or equivalent).14 However, long acting inhaled beta2–adrenoreceptor agonists should only be prescribed as add on therapy in asthmatic patients who are already taking inhaled glucocorticoids.1� It is important that formoterol or salmeterol should not be used as monotherapy in asthma as these medications do not appear to influence the airway inflammation in asthma.16 Results from the Salmeterol-Multi Centre Asthma Research Trial (SMART) showed that patients who did not use inhaled glucocorticoids with salmeterol

Salmeterol Formoterol

Onsetofaction 1�-�0 minutes 1-� minutes

Duration Up to 12 hours Up to 12 hours

Efficacy Partial agonist Full agonist (higher efficacy)

Peakbronchodilation 1-2 hours �0 minutes

Dropinserumpotassium Drop in serum K+ Possible larger drop in serum K+

Fingertremor Pronounced More pronounced

HeartrateandQ-Tcintervals No significant difference compared to formoterol

No significant difference compared to salmeterol

Table1.Pharmacologicaldifferencesbetweenformoterolandsalmeterol2,4,5,6

had a higher incidence of asthma-related adverse events than patients who did use inhaled corticosteroids with salmeterol.1,1�-19

When administered as an aerosol by a metered-dose inhaler or when inhaled as a powder via a dry-powder inhaler, formoterol and salmeterol have the property of retaining a bronchodilatory effect for up to 12 hours, which accounts for their use in patients with nocturnal asthma. Moreover, the long duration of action permits for a twice daily treatment frequency, rather than every 4 hours as with short-acting beta2-ardrenoreceptor agonists thereby encouraging patient adherence to treatment.2

1. Before prescribing add-on therapy, practitioners should assess adherence, inhaler technique and attempt to eliminate trigger factors.

2. The first choice as add-on therapy to inhaled steroids in adults and children (�-12 years) is an inhaled long-acting beta2-adrenoreceptor agonist (formoterol or salmeterol).�. If there is no response to treatment the drug should be discontinued.

Table2.Criteriaforintroductionofadd-ontherapy15

Table3.Advantagesofformoterolandsalmeterolasadd-ontherapy16

1. Improve symptom scores2. Decrease nocturnal asthma �. Improve lung function4. Decrease the use of short-acting inhaled beta2-adrenoreceptor agonists�. Reduce the number of exacerbations6. Achieve clinical control of asthma in more patients, more rapidly, and at a lower dose of inhaled glucocorticosteroids than when inhaled glucocorticosteroids are given alone. �. May be used to prevent exercise-induced bronchospasm since they provide a longer protection than rapid-acting inhaled beta2-adrenoreceptor agonists.

Therapeutics

Issue 14 Summer 2008 Journal of the Malta College of Pharmacy Practice 1�


Advantagesoflong-actingbeta2-adrenoreceptoragonists

Addition of long-acting inhaled beta2-adrenoreceptor agonists to a daily regimen of inhaled glucocorticoids in asthmatic patients has various advantages, as listed in Table �.

Long-actingbeta2-adrenoreceptoragonistsinCOPD

In COPD, airflow is obstructed during expiration, thus causing dyspnoea. In contrast to asthma, the airflow obstruction is not reversible and usually progresses over time.20 The major goals of bronchodilator therapy in COPD are to prevent exacerbation, achieve symptom relief, improve pulmonary functions and, in the long term, enhance the quality of life.19 Results of systematic reviews or large randomized clinical trials indicate that long-acting beta2-adrenoreceptor agonists in patients suffering from COPD without asthma, statistically significantly reduce airflow obstruction and symptoms. However, the clinical significance is unclear and careful consideration of the costs and benefits of long-acting beta2-adrenoreceptor

1. O’Byrne PM, Adelroth E. 2 Déjà Vu. Chest 2006: 129(1): �-�

2. van Noord JA, Smeets JJ, Raaijmakers JAM, et al. Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action. European Respiratory Journal 1996: 9: 1684-1688

�. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease 200�: �1

4. Palmqvist M, Ibsen T, Mellen A, et al. Comparison of the relative efficacy of formoterol and salmeterol in asthmatic patients. American Journal of Respiratory and Critical Care Medicine 1999: 160: 244-249

�. Formoterol. http://emc.medicines.org.uk/emc/ Last accessed on 28th May 2008

6. Koda-Kimble MA, Young LY. Asthma. Applied Therapeutics. The Clinical Use of Drugs. Lipincott Williams & Wilkins, USA, 2001: 21-29

�. Eccles M, Rousseau N, Higgins B, et al. Evidence based guideline on the primary care management of asthma. Family Practice 2001: 18(2): 22�-229

8. Adolfsson LE, Lundgren M, Tilling B, et al. Short-term safety and tolerability of double-dose salmeterol/fluticasone propionate in adult asthmatic patients. Clinical Drug Investigation 200�: 2�(4): 2�1-241

• Patients with asthma given salmeterol or formoterol should always initially be prescribed an inhaled glucocorticoids.1�

• Patients should be monitored closely during early treatment.1�

• Long-acting beta2-adrenoreceptor agonists should ONLY be used every 12 hours.• A dose of �0mcg salmeterol twice daily is comparable to 12mcg formoterol

twice daily.• Inhaler technique should always be reviewed prior to making any changes in

the patient’s treatment.• Different brands of long-acting inhaled beta2-adrenoreceptor agonists have

different licensing properties. Some of these preparations are not licensed for certain age groups. It is imperative to always refer to specific manufacture recommendations prior to prescribing long-acting inhaled beta2-adrenoreceptor agonists.

PracticePoints

agonists in patients without asthma is needed before using these drugs in COPD.21

DeliveryInhaled long-acting beta2-

adrenoreceptor agonists may be delivered via a metered dose inhaler or a dry powder inhaler. It is essential that health care professionals proactively engage in instructing patients on inhaler technique.

An inhaler should only be prescribed after the patient has received the necessary training and has demonstrated his/her ability to use the device properly. Regular assessment of inhaler technique is imperative as inappropriate technique leads to inadequate delivery resulting in suboptimal control. Information regarding training of inhaler technique may be accessed at www.ginasthma.com.22

References

9. Maesen FP, Smeets JJ, Gubbelmans HL, et al. Formoterol in the treatment of nocturnal asthma. Chest 1990: 98: 866-8�0

10. Cazzola M, Imperatore F, Salzillo A, et al. Cardiac effects of formoterol and salmeterol in patients suffering from COPD and preexisting cardiac arrhythmias and hypoxemia. Chest 1998: 114(2): 411-41�

11. Till MD. Cardiovascular and metabolic effects of eformoterol in adults. British Journal of Clinical Practice 199�: 81(suppl): 2-�

12. Nelson HS, Dorinsky PM. Safety of long-acting -agonists. Annals of Internal Medicine 2006: 14�(9): �06

1�. Ernst P, Mclvor A, Ducharme FM, et al. Safety and effectiveness of long-acting inhaled -agonist bronchodilators when taken with inhaled corticosteroids. Annals of Internal Medicine 2006: 14�(9): 692-694

14. Greenstone IR, Ni Chroinin MN, Masse V, et al. Combination of inhaled long-acting beta2-agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma. http://www.cochrane.org/reviews/en/ab00��.html Last accessed on 24th May 2008

1�. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: A national clinical guideline. SIGN 2008: ��-�9

16. Global Initiative for Asthma. GINA report, global strategy for asthma management and prevention 200�: �0-�1

1�. Salmeterol (Serevent) and Formoterol (Oxis, Foradil) in asthma management. Current Problems in Pharmacovigilance 2006: �1: 6

18. Nelson HS, Weiss ST, Bleecker ER, et al. The Salmeterol Multicenter Asthma Research Trial: A comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006: 129(1): 1�-26

19. Cortocosteroids should be used with 2 long-acting agonists. Australian Adverse Drug Reactions Bulletin 2004: 2�(�): 11

20. Gibson PG. Management of chronic obstructive pulmonary disease. Australian Prescriber 2001: 24: 1�2-1��

21. Celik G, Kayacan O, Beder S, et al. Formoterol and salmeterol in partially reversible chronic obstructive pulmonary disease: a crossover placebo-controlled comparison of onset and duration of action. Respiration 1999: 66: 4�4-4�9

22. How to use the Turbohaler. http://www.ginasthma.com Last accessed on 26th April 2008

Therapeutics


Therapeutics

IntroductionThe World Health Organisation

(WHO) has defined probiotics as ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host’.1 Most often, the bacteria come from two groups, Lactobacillus or Bifidobacterium. Within each group, there are different species (for example, Lactobacillus acidophilus and Bifidobacterium bifidus), and within each species, different strains (or varieties).2 Locally as in the rest of Europe, probiotics are available in foods such as milk, yoghurts and butter, combined with vitamins and minerals or sold alone. In recent years consumption of probiotics has been attributed to a multitude of benefits ranging from the treatment of diarrhoea to anticancer effects. Although such claims are in abundance, evidence from clinical trials to support such claims is lacking.

Probiotics:which, when and why?

The normal gut microflora, aside from aiding digestion, provides protection against pathogenic organisms. Probiotics have been manufactured with the idea of maximising the effect of gut microflora, also known as “good bacteria”, thus reducing the risk of infection. This theory has proved scientists right on several occasions however stronger evidence is necessary to establish the efficacy, safety and cost-effectiveness of these products.

ValerieVellaBPharm(Hons), MSc Clin Pharm(Aberdeen), MPharmS

Senior Clinical Pharmacist, Mater Dei Hospital, Tal-Qroqq, MaltaEmail:[email protected]

Keywordsprobiotics, lactobacillus, diarrhoea, infection, immunity, allergy

Claim1:Preventionandtreatmentofdiarrhoeaa) Treatment of Clostridium difficile-

associated colitis in adults Mechanism: probiotics restore the

microbial balance of the gastrointestinal tract altered by infection with C. difficile.

Studies: Four studies have evaluated the use of probiotics in conjunction with conventional antibiotics (e.g. metronidazole and vancomycin) for the treatment of recurrence or an initial episode of C. difficile colitis in adults. Only one study has demonstrated significant benefits in patients receiving S. boulardii.3

Conclusion:The evidence to support the use of probiotics with conventional treatment for C. difficile colitis is scanty and there is no evidence at all to support the use of probiotics as monotherapy for the treatment of C. difficile colitis.�

b) Probiotics for the prevention of antibiotic-associated diarrhoea (AAD)

Mechanism: antibiotics alter the microbial balance within the gastrointestinal tract and probiotics work via restoration of the gut microflora. It is also thought that probiotics release inhibitory substances that stall the growth of pathogenic bacteria responsible for the diarrhoea.

Studies: there are ten studies conducted on around 2000 children who were receiving short-term probiotics co-administered with antibiotics to prevent AAD. These trials included treatment with various probiotics including Saccharomyces boulardii, Lactobacilli spp. and Bifidobacterium spp. Results of these studies show statistically significant results favouring probiotics over controls.4 There are only two small studies conducted in adults, and only one of these utilising the Lactobacillus strain has shown some efficacy.�

Conclusion:Although results are very promising, the routine use of probiotics for the prevention of paediatric AAD is not recommended until further trials determine the strain and dose required.4 In adults the evidence is very limited because the group sizes of the trials were small and significant effects could have been missed.

c) Traveller’s diarrhoea Mechanism:probiotics restore the gut

flora. Studies:three studies investigated

whether Lactobacillus strains can prevent traveller’s diarrhoea. In one of the studies treatment with probiotics reduced the incidence of diarrhoea significantly from 40% to 24%. In the other study the incidence of diarrhoea was not statistically significant between the probiotic group and the placebo group. A double-blind placebo controlled study using L. acidophilus strains showed no difference in the incidence of traveller’s diarrhoea.�

Conclusion:the effect of probiotics on the incidence of traveller’s diarrhoea seems to depend on the bacterial stain and the destination of the travellers and needs further study.�


• Long- Lasting Relief (1)

• Ocular Surface Protection (2)

• Patients’ preferred choice (3)

Thanks, Doctor!Start with Systane®

Stay with Systane®

(1) Aguilar, A, Cohen, S, Christensen, M. Duration of the efficacy of Systane Lubricant Eye Drops in dry eye patients. Poster presented at World Ophthalmology Congress, Sao Paolo 2006. (2) Christensen MT, Stein JM, Stone RP, Meadows DL. Evaluation of the effect on tear film break-up time extension by artificial tears in dry eye patients. Presented at: 23rd Biennial Cornea Research Conference; October 3-4, 2003; Boston, Mass. (3) Torkildsen G MD, Colby K MD, PhD, Corbin G, OD. The Effect of Systane Compared to Marketed Artificial Tears on Drop Preferente American Academy of Optometry, Denver 2006.

• Long- Lasting Relief (1)

• Ocular Surface Protection (2)

• Patients’ preferred choice (3)

Thanks, Doctor!Start with Systane®

Stay with Systane®

(1) Aguilar, A, Cohen, S, Christensen, M. Duration of the efficacy of Systane Lubricant Eye Drops in dry eye patients. Poster presented at World Ophthalmology Congress, Sao Paolo 2006. (2) Christensen MT, Stein JM, Stone RP, Meadows DL. Evaluation of the effect on tear film break-up time extension by artificial tears in dry eye patients. Presented at: 23rd Biennial Cornea Research Conference; October 3-4, 2003; Boston, Mass. (3) Torkildsen G MD, Colby K MD, PhD, Corbin G, OD. The Effect of Systane Compared to Marketed Artificial Tears on Drop Preferente American Academy of Optometry, Denver 2006.

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d) Diarrhoea caused by rotavirus Mechanism:rotavirus infection

causes gastroenteritis characterised by acute diarrhoea and vomiting and is a leading cause of death and disease among children worldwide. Probiotics are thought to restore the gut microflora following rotavirus infection.

Studies:Several studies have shown that consumption of Lactobacillus GG shortened the duration of diarrhoea from �.� to 2.� days in children. B. bifidum and S. thermophilus, also reduced the incidence of diarrhoea in a double-blind, placebo-controlled trial in �� hospitalised infants.� Studies with Enterococcus species also showed beneficial effects however L. acidophilus failed to show significant differences in recovery times in diarrhoea caused by rotavirus.�

Conclusion:The strongest evidence for shortening of the diarrhoeal phase of rotavirus infection was with the consumption of Lactobacillus GG.2,�

Claim2:TreatmentofHelicobacterpyloriInfection

Mechanism:Probiotics may compete directly with H. pylori, possibly through the inhibition of adherence, as well as produce

metabolites and antimicrobial molecules such as bacteriocins, which inhibit H. pylori growth. Only animal and in vitro data has supported these properties.2

Studies:Seven of nine human studies showed an improvement of H. pylori gastritis and decrease in H. pylori density after administration of probiotics.6 The addition of probiotics to standard antibiotic treatment improved H. pylori eradication and reduced treatment associated side effects. This success however seems to be attributed to the fact that more patients completed the eradication treatment rather than because of eradication H. pylori infection by probiotic treatment alone.6-8

Conclusion:Based on current data, even though an effect against H. pylori has been described, probiotics cannot be considered as an alternative to standard anti-H. pylori treatment. Nevertheless, their use in association with standard anti-H. pylori treatment may be advisable, as they are able to improve patient compliance by reducing antibiotic-related adverse events, thus increasing the number of patients completing the eradication therapy.

Claim3:ManagingLactoseIntoleranceMechanism: microbial β-galactosidase

in live yoghurt hydrolyses lactose allowing

better digestion and absorption of glucose and galactose thus reducing the symptoms associated with lactose intolerance.2,9,10

Studies: A large number of human studies in which consumption of fresh yoghurt with live cultures was compared with consumption of a pasteurised product with heat killed bacteria demonstrated better lactose digestion and absorption as well as reduction of gastrointestinal symptoms with the fresh yoghurt.2 The efficacy of probiotics is dependent on the ability of lactobacilli to release β-galactosidase and this is limited by the fact that not all lactobacilli have the same ability to release this enzyme.2,10

Conclusion: Some probiotics maybe effective in alleviating the signs and symptoms of this condition, although further trials of specific strains and concentrations are necessary.

Claim4:LoweringofbloodcholesterolMechanism: Probiotic bacteria ferment

food-derived indigestible carbohydrates to produce short-chain fatty acids in the gut, which can then cause a decrease in the systemic levels of blood lipids by inhibiting hepatic cholesterol synthesis and/or redistributing cholesterol from plasma to the liver. Other bacteria may interfere with

Table1.Summaryofevidencefortheuseofprobiotics

Claim Evidence

Prevention of Clostridium difficile-associated colitis in adults No evidence for monotherapy with probiotics

Prevention of antibiotic-associated diarrhoea Evidence limited but very promising

Prevention of traveller’s diarrhoea Insufficient evidence

Treatment of diarrhoea caused by rotavirus Strong evidence especially in paediatrics

Treatment of Helicobacter pylori infection Good evidence for use in conjunction with standard anti-H.pylori treatment

Managing lactose intolerance Strong evidence in favour of probiotics in alleviating signs and symptoms of lactose malabsorption

Lowering of blood cholesterol Insufficient evidence

Treatment of vaginal infections Insufficient evidence

Anticancer effects Insufficient evidence

Management of inflammatory bowel diseaseGood evidence for pouchitis and maintenance of remission but larger trials are needed to assess their value in other inflammatory bowel disorders

Prevention and treatment of atopic diseases Strong evidence for probiotic use in high risk infants

Enhancement of the immune function Strong evidence for shortening duration of common colds

Prevention of preterm labour Insufficient evidence

Therapeutics


cholesterol absorption from the gut.11

Studies: In 19�4 a paper published in the American Journal of Clinical Nutrition reported that consumption of probiotics in the form of fermented milk was associated with reduced serum cholesterol in the Maasai people.12 Other studies in 19�0’s have utilised inadequate sample sizes and excessive quantities of the product thus producing equivocal findings.1� More recent studies, which are of better quality with redesigned standards, have failed to provide convincing and consistence evidence that strains of L acidophilus and L. bulgaris have lowering-cholesterol efficacy in man.� A meta-analysis of controlled short-term studies has shown that consumption of yoghurt containing Enterococcus faecium is effective in reducing both total and low-density lipoprotein (LDL) cholesterol by 4% and �% respectively. Whether the effects are sustained over time remains to be proven.2 Consumption of food products containing L plantarum 299v has also been reported to lower total and LDL cholesterol in subjects with moderately raised cholesterol levels. Additionally subjects consuming 200ml of milk fermented with L casei TMC0409 and S thermophilus TMC 1�4� daily showed significant increases in high density lipoprotein after four and eight weeks of supplementation.2

Conclusion: The lasting effect of probiotics on serum cholesterol is inconclusive.

Claim5:TreatmentofvaginalinfectionsMechanism:lactic acid bacteria

predominate in the normal vaginal flora, generating an acidic pH, which inhibits the growth of other organisms that can cause vaginal infections.9

Studies:Over the years there have been a number of clinical trials evaluating the ability of orally or intravaginally administered lactobacilli to inhibit the vaginal colonization by yeasts and prevent the recurrence of vulvovaginal candidiasis. In most of these studies the difference in risk of developing vaginal candidiasis in patients on probiotics compared to those who took placebo was small and not significantly different. Additionally a study investigating the use of lactobacilli in the prevention of post-antibiotic vulvovaginitis

failed to show any significant advantage of using probiotics in conjunction with antibiotics.14

Conclusion:Although several studies have shown that oral consumption of probiotics can alter vaginal microflora, most of these had either a flawed methodology or a very small sample size thus providing limited evidence to support the effectiveness of probiotic preparations.

Claim6:AnticancereffectsMechanism: regular, long-term

consumption of probiotics has been suggested to protect against bowel cancer. The basis for this is that the acid pH in the colon generated by probiotics could inhibit the transformation of procarcinogen to active carcinogensand reducing the absorption of mutagens from the intestine.9

Studies:consumption of probiotics (Lactobacillus salivarius) has been associated with a reduced incidence of colonic adenocarcinoma in mice. Other studies in animal models have also shown probiotics to reduce intestinal inflammation, which has been associated with an increased incidence of colorectal cancer. Human studies have demonstrated the ability of probiotics to decrease the activity of some bacterial enzymes, which play an important role in cancer development as they hydrolyse carcinogenic compounds.2,�,1�

Conclusion:Large-scale trials are still required to support the implications of probiotics in the field of colorectal cancer.

Claim7:Managementofinflammatoryboweldisease

Mechanism:it is claimed that patients with inflammatory bowel disease such as Crohn’s disease and ulcerative colitis may have an abnormal gut microflora in terms of both the organisms and their ability to adhere to the gut wall.9 Probiotics can potentially reduce the population of abnormal bacteria and reverse any problems of adhesion. Additionally probiotics may help to improve gut immune function.2,9

Studies: A recent systematic review in ulcerative colitis concluded that significant difference in effectiveness have been reported for different types of strains in species of bacteria and yeasts and it seems that Bifidobacteria are likely to give the

best results.16 There is some degree of evidence that probiotics added to standard therapy may provide modest reduction of disease activity in patients with mild to moderately severe ulcerative colitis.16,1�

Seven small studies have investigated the use of probiotics in the induction or maintenance of remission in Crohn’s disease. One of the probiotics investigated was VSL#� a patented combination of eight probiotic strains, including bifidobacteria and lactobacillus. Although outcomes have included an increase in relapse free time and a reduction in inflammation such differences were not statistically significant.18

Conclusion:Larger trials are needed to assess whether the use of probiotics can reduce the relapse of inflammatory bowel disease and/or maintain patients in remission and to see whether they are safer than the traditional anti-inflammatory drugs.

Claim8:Preventionandtreatmentofatopicdiseases

Mechanism:it is thought that optimising gut flora might reduce the risk of allergic disease by preventing increase in gut permeability associated with infection or by stimulating anti-allergic immunological responses.

Studies:A randomised double blind, placebo-controlled trial carried out in �4 infants showed no significant benefit for the use of probiotic bacteria in infants with atopic dermatitis. In another similar study 1,2�� pregnant women and their babies were evaluated for the cumulative incidence of allergic diseases (eczema, asthma, allergic rhinitis and food allergies). Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases by age 2 years but significantly prevented eczema especially atopic eczema.19

Conclusion: the prevention of atopic eczema in high-risk infants seems possible by modulating their gut miroflora of infants with probiotics.19

Claim9:Enhancementoftheimmunefunction

Mechanism: Specific strains of lactic acid bacteria, when consumed in sufficient

Therapeutics


•Probiotics should not be taken with hot beverages. Temperatures above �0oC denature the bacteria rendering the product ineffective.

•There is limited evidence supporting some uses of probiotics. Much more scientific knowledge is needed about probiotics, including about their safety and appropriate use.•Effects found from one species or strain of probiotics does not necessarily hold true for others.•Immunocompromised patients should not be exposed to probiotics, as safety in this group of patients has not yet been established.

PracticePointsnumbers are able to alter some aspects of natural and acquired immune responses.

Studies: A recent double blind randomised controlled trial has studied 4�9 healthy adults during two winter/spring periods. The patients were supplemented with a daily preparation of vitamins and minerals with or without probiotics lactobacilli and bifidobacteria. Whilst the intake of the probiotic had no effect on the incidence of common colds, it significantly shortened common cold episodes and reduced the severity of symptoms.20

Conclusion:A three-month consumption of probiotics may reduce the severity of common colds and reduce the duration by almost 2 days.20

Claim10:Probioticsforpreventingpretermlabour

Mechanism:�0% to �0% of pregnant females who go into labour too soon were found to have an infection and it is thought that this is what stimulates labour.21

Studies: there have been two trials involving a total of 108 women. In one trial the probiotics were given orally whereas the other utilised yoghurt used vaginally by

women diagnosed with bacterial vaginosis in early pregnancy. Pooled results showed an 81% reduction in the risk of genital infection with the use of probiotics.21

Conclusion:although probiotics appear to treat vaginal infections in pregnancy there is currently insufficient evidence to justify the use of probiotics to reduce the risk of preterm birth.21,22

AdverseEffectsProbiotics are generally considered to be

safe with side effects if any being mild and digestive such as bloating.9 However some probiotic species have been rarely isolated

from infectious sites although these appear mainly in patients with serious underlying diseases and/or immunosuppression.2� They could also cause unhealthy metabolic activities such as over-stimulation of the immune system.2�

ConclusionIt is expected that in the future, new,

well characterised, scientifically proven probiotic strains with specific health benefits will be developed. In addition, further well-designed clinical trials should provide health care professionals with sufficient evidence for the rational use of probiotics.

1. FAO/WHO (2002). Guidelines for the Evaluation of Probiotics in Food. [Online] Available from: ww.fao.org [Accessed 26 April 2008]

2. Gill HS, Guarner F. Probiotics and human health: a clinical perspective. Postgraduate Medical Journal 2004; 80:�16-�26.

�. Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database of Systematic Reviews 2008; Issue 1. Art. No.: CD004611

4. Johnston BC, Supina AL, Ospina M, Vohra S. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database of Systematic Reviews 2008; Issue 2. Art. No.: CD00482�

�. D Roos NM, Katon MB. Effects of probiotic bacteria on diarrhea, lipid metabolism, and carcinogenesis: a review of papers published between 1988 and 1998. American Journal of Clinical Nutrition 200�; �1:40�-411.

6. Lesbros-Pantoflickova D, Corthesy-Theulaz I, Blum AL. Helicobacter pylori and probiotics. J Nutr 200�; 1��:812S-818S.

�. Franceschi F, Cazzato A, Nista EC, Scarpellini E, Roccarina D, Gigante G, Gasbarrini F, Gasbarrini A. Role of probiotics in patients with Helicobacter pylori infection. Helicobacter 200�; 12:�9-6�.

8. Gottelan M, Brunser O, Cruchet S. Systematic review: are probiotics helpful in controlling gastric colonization by Helicobacter pylori? Aliment Pharmacol Ther 2006; 2�:10��-1086.

9. Mason P. Probiotics: are they worth taking? The Pharmaceutical Journal 200�; 2�8:��-��6.

10. Montalto M, Curigliano V, Santoro L, Vastola M, Cammarota G, Manna R, Gasbarrini A, Gasbarrini G. Management and treatment of lactose malabsorption. World Journal of Gastroenterology 2006; 12:18�-191.

11. Pereira DI, Gibson GR. Effects of consumption of probiotics and prebiotics on serum lipid levels in humans. Crit Rev Biochem Mol Biol 2002; ��:2�9-281.

12. Mann GV, Spoerry A. Studies of a surfactant and cholestemia in the Maasai. Am J Clin Nutr 19�4; 2�:464-469.

1�. Taylor GR, Williams CM. Effects of probiotics and prebiotics on blood lipids. British Journal of Nutrition 1998; 80:S22�-2�0.

14. Falagas ME, Betsi GI, Athanasiou S. Probiotics for prevention of recurrent vulvovaginal candidiasis: a review. Journal of Antimicrobial Chemotherapy 2006; �8:266-2�2

1�. Geier MS, Butler RN, Howarth GS. Probiotics, Prebiotics and Synbiotics – A role in Chemoprevention for Colorectal Cancer? Cancer Biology & Therapy 2006; �:126�-1269

16. Mallon P, McKay D, Kirk S, Gardiner K. Probiotics for induction of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 200�; Issue 1. Art. No.: CD00��

1�. Zigra PI, Maipa VE, Alamanos YP. Probiotics and remission of ulcerative colitis: a systematic review. The Netherlands Journal of Medicine 200�; 6�:411-418.

18. Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall F. Probiotics for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews 2006; Issue 4. Art. No.: CD004826

19. Kukkonen K, Savilahti E, Haahtla T, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Kuitunen T. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic disease: a randomized, double-blind, placebo-controlled trial. Journal of Allergy and Clinical Immunology 200�; 119:192-198

20. De Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Lau C, Hampe J, Schreiber S, Heller K, Schrezenmeir J. Probiotic bacteria reduced duration and severity but no the incidence of common cold episodes in a double blin, randomised controlled trial. Vaccine 2006; 10:44-46

21. Othman M, Neilson JP, Alfirevic Z. Probiotics for preventing preterm labour. Cochrane Database of Systematic Reviews 200�; Issue 1. Art. No.: CD00�941

22. Reid F. Bocking A. The potential for probiotics to prevent bacterial vaginosis and preterm labor. American Journal of Obstetric Gynecology 200�; 189:1202-1208

2�. Graf C, Sarasin FP. Efficacy and safety of probiotics. Rev Med Suisse 200�; 129:2��0-2��4

References

Therapeutics


This review aims to provide an overview of models of pharmacist prescribing outside and within the UK. Since pharmacist prescribing was pioneered in the US, most of the literature available originates within the US. Where little information was found in the literature, pharmacy societies were contacted to provide further information. Both the Australian and South African societies responded; however no information was obtained from Canada. Overall, little information is available from Canada and South Africa particularly since pharmacist prescribing in the latter case has been withdrawn. Table 1 accompanies the text below and aims to summarise different modes of pharmacist prescribing.

Practice

An international overview of some pharmacist prescribing modelsAntonellaP.TonnaMSc, MRPharmS

PhD student, ad hoc Lecturer, School of Pharmacy, Faculty of Health and Social Care,The Robert Gordon University, Aberdeen, Scotland, UKEmail: [email protected]

DerekStewartPhD, MRPharmS

Senior Lecturer, School of Pharmacy, Faculty of Health and Social Care, The Robert Gordon University, Aberdeen, Scotland, UK

DorothyMcCaigPhD

Senior Lecturer, School of Pharmacy, Faculty of Health and Social Care, The Robert Gordon University, Aberdeen, Scotland, UK

KeywordsPharmacist prescribing, independent, supplementary, patient safety

PharmacistprescribingintheUnitedStates

Pharmacist prescribing has been driven by a necessity to improve health care delivery, with the inability of pharmacists to prescribe resulting in time and cost impediments to the delivery of patient care. There are two models of pharmacist prescribing in the United States (US) – dependent or independent prescribing authority.1 Dependent prescribing authority implies that the pharmacist prescribing authority is delegated by an independent prescriber, usually a physician, on the basis that the pharmacist is capable of performing the delegated duties. The two have shared responsibility for the patient’s overall outcome usually defined through a collaborative drug therapy management (CDTM) agreement where the physician diagnoses and makes treatment decisions and the pharmacist selects, monitors, modifies or discontinues drug therapy as indicated in the agreement. The CDTM may take various forms such as general written protocols, policies or procedures or protocols for each specific patient.2 Independent prescribing authority implies that the prescriber is authorised to prescribe all drugs without the supervision of another health care professional.1 The American College of Clinical Pharmacists (ACCP) argues that prescribing within current health-care systems can no longer be independent due to the complexity of drug regimens. It defines prescribing as encompassing a broader set of activities including selecting, initiating, monitoring, continuing, modifying and administering medications. The role of a pharmacist within a CDTM is consequently advocated since this makes use of the expertise of both the physician and the pharmacist.�

The extent of the pharmacist prescribing authority depends on whether the setting they are practising is within the remit of state or federal law. The state law, which changes from one state to another, usually favours a model where the pharmacist is a dependent prescriber and therefore prescribing is based on protocols or physician-defined care plans. Many states that have introduced pharmacy prescribing have opted for this model and include California, Kansas, Mississippi, Nevada,


1-4

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Favourable safety and tolerability profile in approximately 4,000 treated smokers6

References: 1 Gonzales D. et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained –release bupropion and placebo for smoking cessation. A randomized controlled trial. JAMA 2006;296(1):47-55. 2. Jorenby DE et al. Efficacy of varinicline, an an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation. A randomized controlled trial. JAMA 2006; 296(1):58-63. 3. Gonzales DH et al. A pooled analysis of varicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs. bupropion, and placebo,β2 nicotinic acetylcholine receptor partial agonist, J Med Chem 2005; 48:3474-3477. 6. CHAMPIX Summary of Product Characteristics.

§ Based on Minnesota Nicotine Withdrawal Scale (MNWS), Brief Questionnaire of Smoking Urges and modified Cigarette Evaluation Questionnaire.


New Mexico, North Dakota, Oregon, South Dakota, Texas and Washington.1 By the end of 200�, �8 states allowed pharmacist prescribing for various CDTM (compared to 14 states at the end of 1996).2 This expansion in pharmacist prescribing has been due to further evolvement of the health-care system including greater awareness of patient safety, further data showing improved health-care outcomes with pharmacist participation, increasing age of the population and increased need for management of chronic diseases and increased patient self-participation and shared responsibility for their health care.2 To ensure greater cohesiveness, it has been recommended that prescribing authority should be obtained on a national level, embracing all areas of pharmacy practice.4 Examples of dependent prescribing authority may be found in both primary and secondary care. In ambulatory care settings, pharmacists assume responsibility for the management of chronic conditions such as hypertension, asthma, diabetes, hyperlipidaemia and psychiatric disorders.� Within a hospital environment, pharmacists

may adjust infusions of heparin therapy against a written protocol agreed by a physician or assume responsibility for in- and out-patient pain management, including prescribing of adjunct therapy such as anti-emetics, antihistamines, laxatives and benzodiazepines.6 Hospital pharmacists may also be involved in automatic therapeutic substitution to ensure that only drugs on the formulary are prescribed.6 The American Society of Health Care System Pharmacists (ASHP) has included pharmacist prescribing under CDTMs as one of its goals in the 201� initiative. For hospital inpatients to achieve best use of medicines it aims to have 90% of hospitals having pharmacists manage medication therapy in collaboration with other members of the healthcare team. This also holds for non-hospital patients such as clinic and home-care settings.� Independent prescriptive authority at state level is in place in Florida, though pharmacists may only prescribe from a limited formulary and against strict protocols including anti-emetic preparations, antidiarrhoeals and smoking cessation products.1,�,8 There has however been little updating of the

formulary and consequently many of the items on the formulary have become over-the-counter medicines.6

The federal government is keener to expand the prescribing authority of the pharmacist and move towards pharmacist independent prescribing. This may be implemented within a federal institution irrespective of the state laws and regulations.1 A directive of the Veteran Affairs (VA) Department lays this down clearly ...”Because states cannot regulate the activities of the federal government, or its employees when acting within the scope of their federal employment, except by congressional consent, state laws and regulations relating to medication orders and prescriptions do not affect scope of practice statements under this directive.” 9 Within the VA department, clinical pharmacy specialists have worked as independent providers prescribing medicines, reviewing and ordering laboratory tests, performing venepuncture, analyzing lab and diagnostic test data, performing physical examinations and assisting in management of medical emergencies, adverse drug reactions, acute

Practice

Table1.Asummaryofdifferentprescribingmodels

Country Prescribingmodel Description

US Dependent prescribingAuthority is delegated to the pharmacist by an independent prescriber (usually a physician). The shared responsibility is described through a collaborative drug therapy management. Model favoured by the state law.

Independent prescribing The pharmacist is allowed to prescribe all drugs without the supervision of another health care professional. Model favoured by the federal law.

South AfricaProviding prescription only medication at pharmacist’s own discretion

Aimed at making medicine more accessible to rural communities. This model has been withdrawn and is not currently in place though its status is being reviewed.

Canada Dependent or delegate prescribing

Prescribing based on a collaborative therapy agreement with a physician. Model favoured by most provinces.

Independent prescribing Prescribing outwith a collaborative agreement which is limited mainly to emergency contraception.

Australia None Still under development.

UK Supplementary prescribingThe pharmacist may prescribe for a diagnosed condition, within the agreement set out with the independent prescriber and the patient in a Clinical Mangement Plan (CMP).

Independent prescribingThe pharmacist may prescribe any drug independently, whether for a diagnosed or undiagnosed condition, without the need for a CMP or partnership with an independent prescriber.


Practice

and chronic conditions and administering medicines.10 Totally independent prescribing authority was pioneered by Florida VA pharmacists in outpatient clinics.11 This expanded role of the pharmacy specialist has been used as a model for other federal agencies such as the US Army and the Indian Health Service.1,12 One of the main barriers to pharmacist prescribing in the US has been the pharmaceutical industry since pharmacists were perceived as more likely to prescribe generics than doctors.6

The American College of Physicians and American Society of Internal Medicine have issued a position statement on the expanding role of the pharmacist in which reference is made to pharmacist prescribing.1� This supports physician-directed pharmacist-physician collaborative practice agreements but limits these to the involvement of the pharmacist in patient education and hospital rounds. It categorically states, “...we need to ensure that physicians control prescriptive rights and have the final approval over all patient care decisions.” It goes on to comment about pharmacist independent prescribing and does not support this, claiming that there is no evidence that this will benefit the patient and that pharmacists are not trained to initiate therapy. It again emphasises that “this is clearly an area that should remain under physician authority.”

Prior to the expansion of this role of the pharmacist, in the early 1980s, studies were undertaken to prove the advantages of pharmacists to a clinical service. This extended role of the pharmacist within a clinical service is now generally accepted as an integral part of health care and looking into the cost effectiveness or cost benefit comparisons with physician prescribing is no longer seen as a priority in many institutions.6 Training for pharmacists to prescribe is not centralised and pharmacist prescribers need to be credentialed within their employing institution.14

PharmacistprescribinginSouthAfricaPharmacists working in rural

communities in South Africa were previously issued with a permit 22A12 allowing them to provide prescription only medicines based on their own discretion. This was issued

following completion of the Primary Care Drug Therapy Course (PCDT). The aim was to provide a service to patients in rural communities where most patients go to the pharmacy before seeing a doctor and usually have no prescription. At this point, the main barrier towards expanding the number of medicines that may be dispensed by the pharmacist was the medical profession who seemed to show “...fierce and organised resistance.” 1� More recently, the Department of Health in South Africa has withdrawn all these permits from pharmacists and the South African Pharmacy Council is now looking at ways to take the PCDT training forward. [personal communication]

PharmacistprescribinginCanadaPharmacist prescribing in Canada

is limited and varies across provinces. Where pharmacist prescribing occurs, this is mainly dependent or delegated prescribing based on a collaborative prescribing model involving an agreement between a pharmacist and a physician.16 Some states such as British Columbia, Saskatchewan and Quebec, support independent pharmacist prescribing of emergency contraception.16 The Canadian Society of Hospital Pharmacists advocates collaborative prescribing within health care facilities arguing that this makes use of the diagnostic expertise of the physician and the pharmacotherapy expertise of the pharmacist.1� It also claims that this will provide improved patient outcomes and increases the successful and efficient delivery of pharmaceutical care.18

PharmacistprescribinginAustraliaPharmacist prescribing has been a topic

of discussion and debate in Australia with a perception that Australia has been slow to catch on to this approach to prescribing.19 The Society of Hospital Pharmacists of Australia supports extending prescribing rights to pharmacists provided that these are competency based.20 Extension of the roles of and services provided by pharmacists are being proposed to make better use of the pharmacists’ knowledge and improve consumer access to medicines without compromising patient safety.21

PharmacistprescribingintheUKThe main drive towards the development

of pharmacist prescribing in the UK, has been a desire to make greater use of the skills and specialisation of different health care professionals by creating a more flexible system to prescribe, supply and administer medicines. This was the focus of the final ‘Crown Report’ published in 1999 which made recommendations on the potential expansion of prescribing roles of health care professionals.22,2� This subsequently led to changes in legislation resulting in extending prescribing privileges to pharmacists.

There are two models of pharmacist prescribing in the UK: pharmacist supplementary prescribing (previously referred to as dependent prescribing in the ‘Crown Report’) and pharmacist independent prescribing. Legislation was amended in 200� to permit pharmacist supplementary prescribing (SP); supplementary prescribing is defined as: “A voluntary partnership between the responsible independent prescriber and a supplementary prescriber, to implement an agreed patient specific clinical management plan with the patient’s agreement, particularly but not only in relation to prescribing for a specific non-acute medical condition or health need affecting the patient.”24 The clinical management plan (CMP) is central to supplementary prescribing since it forms the basis for patient management within the agreed framework. It needs to be drawn up for each patient with agreement reached between the independent prescriber, the supplementary prescriber and the individual patient. The clinical management plan must make reference to the class(es) of drug(s) or drug(s) to be prescribed. Independent pharmacist prescribing (IP) was introduced in May 2006 following amendments to legislation; an independent prescriber is defined as: “...a practitioner responsible for the assessment of patients with undiagnosed or diagnosed conditions and for decisions about the clinical management required, including prescribing.”2�

As may be expected, due to the novelty of the subject, there is not much evidence available around pharmacist



Practice

prescribing in the UK. This has been the subject of a recently published review26

where the authors aimed to summarise the literature to date on pharmacist prescribing and to explore the main areas of care and practice settings including any benefits and limitations. Tonna et al report that the delivery of pharmacist SP and plans for service development were identified in different health care settings which may be divided into four models: community, hospital, primary care settings and the primary/secondary care interface.26,2� Narrative reports show that within secondary care, SP was being applied across various specialities including the adjustment of aminoglycoside dosages as part of therapeutic drug monitoring, to facilitate patient discharge on a cardiac unit, and as part of a clinical nutrition team. Reports of pharmacist-led prescribing clinics also emerge from primary care with pharmacist involved in hypertension and clinical risk reduction clinics.

Initial research reports that almost �0% of pharmacist supplementary prescribers self-reported prescribing with pharmacists reporting both benefits of and barriers to implementing SP.28,29

Research involving other health care professionals has indicated that

• Pharmacist prescribing was pioneered in the US. Recent developments within the UK also allow pharmacist prescribing.

• The main driving force has been a need for greater patient access to medication and a better use of the pharmacist’s skills.

• There are two main forms of pharmacist prescribing: dependent or supplementary prescribing, where collaboration or agreement with a physician is essential, and independent prescribing without the need for formal collaboration with another health care professional.

• To be registered prescribers, pharmacists need to complete accredited training programmes. Accreditation is nation-wide in the UK while this varies between states and institutions in the US.

PracticePoints

encroachment of traditional roles likely to occur due to the advent of pharmacist prescribing may also be a barrier.�0,�1 A small scale study has concluded that patients are likely to favourably accept pharmacist prescribing�2, with another study showing potential favourable outcomes of pharmacist prescribing.�� There is no research yet available about practices involving pharmacist independent prescribing.

Most of the literature from the UK focuses on pharmacists’ perceptions of supplementary prescribing, with little information referring to other stakeholders, including patients. There is also limited published research focusing on clinical and economic outcomes of pharmacist SP.

ConclusionWith the exception of the US, where

pharmacist prescribing has been pioneered, this is a rapidly changing aspect of pharmacy practice. This is particularly so in the UK, where the recent advent of pharmacist IP is likely to create more opportunities for pharmacy involvement and expansion of the pharmacist role. It is likely that the research and the body of evidence around pharmacist prescribing will therefore expand over the coming years.

1. Boatwright DE. Legal aspects of expanding prescribing authority for pharmacists. Am J Health Sys Pharm. 1998;��:�8�-94.

2. Hammond RW, Schwartz AH, Campbell MJ, Remington TL, Chuck S, Blair MM, et al. ACCP position statement; collaborative drug therapy management by pharmacists - 200�. Pharmacotherapy. 200�;2�:1210-2�.

�. Carmichael JM, O’Connell MB, Devine B, Kelly W, Ereshelsky L, Linn WD, et al. ACCP position statement - collaborative drug therapy management by pharmacists. Pharmacotherapy. 199�;1�:10�0-61.

4. Steffen WM. Prescriptive authority for pharmacists. US Pharm. 199�;22:82-4.

�. Williams RF, Moran EL, Bottaro SDI, Dydek GJ, Caoulette ML, et al. Pharmaceutical services in the united states army. Am J Health Syst Pharm. 199�; �4:��-8.

6. Farrell J, North-Lewis P, Cross M. Pharmacist prescribing in the united states. Pharm J. 199�;2�9:18�-90.

References

�. American Society of Health System Pharmacists. 201� health-system pharmacy initiative, 200�. Available from: www.ashp.org/201�

[2 July 2008, date last accessed]8. Magill-Lewis J. More states seek prescriptive

authority for pharmacists. Drug Topics. 2000;144:��.

9. Establishing Medication Prescribing Authority for Clinical Nurse Specialists, Nurse Practitioners, Clinical Pharmacy Specialists and Physician Assistants. Department of Veterans Affairs, 200�.

10. Clause S, Fudin J, Mergner A, Lutz JL, Lavanaugh MM, et al. Prescribing privileges among pharmacists in veterans affairs medical centres.

Am J Health Syst Pharm. 2001;�8:114�-�.11. Ukens C. Florida VA pharmacists pioneer

independent prescribing. Hospital Pharmacist Report. 199�;11:��.

12. Paavola FG, Dermanoski KR, Pittman RE. Pharmaceutical services in the United States public health service. Am J Health Syst Pharm. 199�;�4:�66-�2.

1�. American College of Physicians - American Society of Internal Medicine. Pharmacist scope of practice. Ann Intern Med. 2002;1�6:�9-8�.

14. Hobson R, Sewell G. Risks and concerns about supplementary prescribing:Survey of primary and secondary care pharmacists. Pharm World Sci. 2006; 28:�6-90

1�. Gilbert L. Pharmacy’s attempts to extend its roles: Case study in South Africa. Social Science and Medicine. 1998;4�:1��-64.

16. Alberta College of pharmacists. Pharmacist prescribing: An international overview, 200�. Available from: http://pharmacists.ab.ca/college/default.aspx [2 July 2008, date last accessed]

1�. Canadian Society of Hospital Pharmacists. Statement on pharmacist prescribing, 2001.

18. Canadian Society of Hospital Pharmacists. Pharmacist prescribing within a health care facility: Frequently asked questions. 2001.


Practice

Prescribing and dispensing checklistsPrescriber’sPrescriptionChecklist

Writing must be in ink

Writing must be legible

Name and signature of prescriber

Address and contact details of prescriber

Medical Council registration number

Full name and age of patient

Locality of patient

Name, dose and dosage form of medicine

Quantity of medicine

Duration of treatment

Instructions on how to take medicine

Period of duration for a repeat prescription

Instructions to indicate when the patient can only be administered a branded product

Pharmacist’sPrescriptionChecklist

Prescription is in ink and legible

Date of issue of prescription

Name, address and other details of prescriber

Medical Council registration number

Signature of prescriber

Full name, age and locality of patient

Name, dose, dosage form of medicine

Quantity of medicine and duration of treatment

Instructions on how to take medicine

Period of duration for a repeat prescription

Expiry of 10 days for antibiotics

Expiry of 6 months unless repeat prescriptions

Indications of use or exhaustion of prescription

Possibility or necessity of substitution

As issued by Director General Public Health Regulation - Malta MSOC/HEC Circular No. �/08 DH File No.1211/08

19. Hanes C, Bajorek B. Pharmacist prescribing: Is Australia behind the times? Australian Journal of Pharmacy. 2004;8�:680-1.

20. The Society of Hospital Pharmacists of Australia. Position statement. National competencies for the prescribing of medicines. 200�.

21. Emmerton L, Marriott J, Bessell T, Nissen L. Improving australians’ access to prescription medicines. Monash University; University of Queensland, Australia, 200�.

22. Review of prescribing, supply and administration of medicines. A report on the supply and administration of medicines under group protocols. London: Department of Health. 1998. Available from: www.dh.gov.uk/en/Publicationsandstatistics/Lettersandcirculars/Healthservicecirculars/DH_4004108 (2 July 2008, date last accessed).

2�. Crown J. Review of prescribing, supply and administration of medicines. Final report. London: Department of Health, 1999. www.dh.gov.uk/assetRoot/04/0�/�1/��/040��1��.pdf

[2 July 2008, date last accessed]

24. MLX 284: Proposals for supplementary prescribing by nurses and pharmacists and proposed amendments to the prescription only medicines (human use) order 199�. 2002. Available from: www.mhra.gov.uk [2 July 2008, date last accessed]

2�. MLX �21: Consultation on proposals to introduce independent prescribing by pharmacists. England: MHRA. 200�. Available from: www.mhra.gov.uk/home/groups/comms-ic/documents/publication/con00�684.pdf [2 July 2008, date last accessed]

26. Tonna A, Stewart D, West B, McCaig D. Pharmacist prescribing in the UK - a literature review of current practice and research. J Clin Pharm Ther. 200�;�2:�4�-�6.

2�. Bellingham C. Prescribing:New opportunities for all. Pharm J. 200�;2�1:��0.

28. George J, McCaig D, Bond C, Cunnigham S, Diack L, Watson A, et al. Supplementary prescribing: Early experiences of pharmacists in Great Britain. Ann Pharmacother. 2006;40:184�-�0.

29. George J, McCaig D, Bond C, Cunnigham S, Diack L, Stewart D. Benefits and challenges of prescribing training and implementation: Preceptions and early experiences of RPSGB prescribers. Int J Pharm Prac. 200�;1�:2�-�0.

�0. Lloyd F, Hughes C. Pharmacists’ and mentors’ views on the introduction of pharmacist supplementary prescribing: A qualitative evalation of views and context. Int J Pharm Prac. 200�;1�:�1-�.

�1. Buckley P, Grime J, Blenkinsopp A. Inter- and intra- professional perspectives on non-medical prescribing in an NHS trust. Pharm J. 2006;2��:�94-8.

�2. Smalley L. Patients’ experience of pharmacist-led supplementary prescribing in primary care. Pharm J. 2006;2�6:�6�-9.

��. Shulman R, Jani Y. Comparison of supplementary prescibers’ and doctors’ compliance with guidelines for drug dosing in haemofilitration on an intensive care unit. Pharm J. 200�;2�4:492-�.


IndraftingtheCodethesub-committeetookintoconsideration:• FIP Statement of Professional Standards

on Codes of Ethics for Pharmacists, 2004;•Oviedo Convention, Council of Europe;• The Charter of Fundamental Human

Rights of the EU. Dec 2000;• Common Values of the Liberal Professions

in the European Union, CEPLIS, Jul 200�;• Vottero LD. Code of Ethics for

Pharmacists. Am J Health-Syst Pharm 199�; • Ciappara MA. Pharmacist-patient

Relationship: Ethical Issues. MPhil dis, 1999; • Code of Ethics, Pharmacy Council of New Zealand, 2004;• Code of Ethics for Pharmacists

and Pharmacy Technicians, Royal Pharmaceutical Society of Great Britain, Aug 200�;

• Code of Professional Conduct, Pharmaceutical Society of Australia, 1998;

• Ethical guidelines for Pharmacists, The Swedish Pharmaceutical Association, 199�;• Code of Ethics for Pharmacists, American

Pharmaceutical Association, 1994;• Codice Deontologico, Federazione Ordini

Farmacisti Italiani;• Code de Deontologie des Pharmaciens,

Ordre National des Pharmaciens, 199�;• Code of Ethics, Alberta Pharmaceutical

Association;• Code of Ethics of various professions

in Malta;• Ethics and the Pharmaceutical Profession,

Pharmacy Board, 19�4;•Karta tad-Drittijiet u tar-

Responsabilitajiet tal-Pazjent, St Luke’s Hospital, Sept 2001.

A new Code of Ethics for the Pharmaceutical ProfessionMaryAnneCiapparaBPharm,MPhil

Chairperson, Ethics Subcomittee, Pharmacy Council MaltaEmail:[email protected]

The new Code sets out the principles that are to guide and direct pharmacists, qualified persons and pharmacy technicians in the practice of the profession. These principles are intended to apply to all sectors of the profession.

The requirements of the new Code reflect key issues for the profession such as providing truthful, accurate and objective information; encouraging and empowering patients to be involved in decisions about their care and to manage their condition; communicating and collaborating with colleagues; and exercising professional judgement in the interests of patients and society.

TheCodeofEthicsisdividedinto5sections.Theseare:1. Relationship with patients and society;2. Responsibilities towards the profession;�. Inter-and Intra-professional

relationships; 4. Relationship with the regulatory and

administrative authorities;�. Promotion and advertising.

The subcommittee in charge of drafting a new Code of Ethics for the Pharmaceutical Profession addressed the matter in a transparent and inclusive manner and engaged the profession and the public throughout the process. The first draft of the Code was sent to the stakeholders, to all registered pharmacists and pharmacy technicians and to a number of patient organisations for their comments. Furthermore, the general public, through a press release was also informed about the draft code and asked to comment.

In November 200�, the Council agreed that meetings should be set up with the stake holders to discuss the latest draft of the Code of Ethics. The draft Code was placed on the website of the Pharmacy Council and brought it to the attention of all registered pharmacists and pharmacy technicians. This was done to foster and encourage an open dialogue on such an important matter.

Throughout the process the responses, both from the consultations and individual members, were positive and contributed to shaping the new Code

The Pharmacy Council has rewritten the Code of Ethics for the Pharmaceutical Profession in response to developments within the Profession, the shift in the practice of the profession from being focused on medicines to becoming patient-centred and patients’ rights and responsibilities.

Regulatory/Policy


Code of Ethics for the Pharmaceutical ProfessionPharmacyCouncilMalta

Email: [email protected]

PreambleThe Code of Ethics for the

pharmaceutical profession publicly sets out the principles that are mandatory on registered pharmacists, qualified persons and pharmacy technicians in their professional and personal conduct.

The Code of Ethics is being issued by the Pharmacy Council in accordance to the provisions made under Article 16(d) of the Health Care Professions Act, 200� which provides that one of the functions of the Pharmacy Council shall be to prescribe and maintain professional and ethical standards for pharmacists and pharmacy technicians and qualified persons and which came into force on 21st November 200�.

The principles express the responsibilities and professional values that are fundamental and inherent to the pharmaceutical profession. They reflect and support the developments in the profession, the patient-centred practice and take into consideration patients’ rights and responsibilities.

They are intended to guide and direct pharmacists, qualified persons and

pharmacy technicians in their relationships with patients, colleagues, regulatory and administrative authorities and society.

They form the basis for a consistent high quality professional service which safeguards and promotes the well-being of patients and society and maintains public confidence in the profession. They also inform patients and society of the standard of behaviour that is to be expected from members of the pharmaceutical profession.

Pharmacists, qualified persons and pharmacy technicians should make these principles an integral part of their professional life and aspire to the highest possible standard of conduct. They should avoid any action or omission, within their sphere of responsibilities, which would prejudice the provision of a pharmaceutical service; or cause harm to the patient/client or society; or impair confidence in and respect for the profession.

The Code is to be read in conjunction with current legislation that is applicable either directly or indirectly to the pharmaceutical profession and to guidelines issued by the Pharmacy Council.

StatusoftheCodeofEthicsThe Principles expressed in the Code

are mandatory. All registered pharmacists, qualified persons and pharmacy technicians, irrespective of their area of practice are to abide by this Code. Their professional and personal conduct will be judged against this Code. Failure to comply with these principles or infamous conduct may lead to disciplinary sanction and could put their registration and licence to practise at risk

The Pharmacy Council wishes to be clearly understood that the Disciplinary Committee will take into account the Code when considering any case that appears before them, but not limited solely to the matters mentioned in it. The Code does not constitute and is not intended to constitute a complete enumeration of the offences that may entail disciplinary action. Nothing in this Code is to be limit the discretion of the Disciplinary Committee in reaching a determination in any case in accordance to the facts brought before it.

ApplyingtheseprinciplesPharmacists and qualified persons have

overall responsibilities for pharmaceutical services they render, in their area of practice. Pharmacy technicians have responsibilities for the work they render to support, develop and/or provide these pharmaceutical services. Pharmacists, quantified persons, and pharmacy technicians are responsible for their actions, and legally and ethically accountable for them.

In their practice of the profession, pharmacists, qualified persons, and pharmacy technicians are expected to apply the principles of the Code when deciding on a course of action and must be able to justify their actions and decisions they take (if asked to do so). In situations where there are conflicting principles they must evaluate the risks and benefits associated with each course of action and decide what is most appropriate in the interests of patients and society.

Regulatory/Policy


1. Relationship with patients and society

1.1RespecthumandignityMembers of the pharmaceutical

profession, in the practice of their profession must carry out their role with respect for life*.

They must respect and protect the dignity of individuals, respect their physical and mental integrity and their rights.

They must respect the personal and cultural differences, beliefs and values of patients/clients; and must not be judgemental nor impose their beliefs and convictions on them. They must treat all those who seek their professional services with courtesy and with due consideration.

1.2Establishandpreserve afiduciaryrelationship

Members of the pharmaceutical profession must endeavour to establish and maintain a professional relationship with their patients.

Members of the pharmaceutical profession must uphold the trust granted

Memberofthepharmaceuticalprofession:refers topharmacists, qualified persons and pharmacy technicians who are regulated by the Pharmacy Council.

Pharmacist: The term ‘pharmacist’ encompasses, but is not limited to, the following areas of practice: managing pharmacist, community pharmacist, locum pharmacist, clinical pharmacist, hospital pharmacist, pharmacist working in the advertising and marketing of medicinal products including medical representation, responsible pharmacists in wholesale distribution of medicinal products, pharmacists working in industry not including qualified persons, pharmacists practising in regulatory affairs, administration, policy making, academia and in research and development.

Patients: individuals or groups, whether healthy or ill, who have access to or are affected directly or indirectly by a particular professional service/ medicinal product from a member of the pharmaceutical profession.

Society: refers to the general public. Colleagues: refers to professionals from the pharmaceutical profession or other

professions.Authorities: refers to those entities defined as such by Legislation.Healthcareteam: refers to the team made up of doctor/s, pharmacist/s and other

health care professions who are taking care of patient/s.Pharmaceuticalservices: services rendered by members of the pharmaceutical

professions.

Definitions

to them by patients and society and build confidence in their commitment and competence to achieve the desired objective and maintain their trust.

1.3Promotetheinterest andwellbeingofthepatient

Members of the pharmaceutical profession, irrespective of their area of practice, whether they have direct or indirect contact with patients, must have as their prime objective the well-being, best interest and safety of patients.

They must place concern for the well-being of the patient at the centre of their practice.

Members of the pharmaceutical profession must safeguard patient’s access to safe medicinal products which are of good quality and efficacy.

Pharmacists must provide individualized care in an emphatic, compassionate and prudent manner.

Such care must be based on scientific knowledge after taking into consideration the patient’s perception and needs, in the context of societal interests.

1.4Actwithhonestyandintegrityandwithconvictionofconscience

Members of the pharmaceutical profession must act with honesty, integrity and with conviction of conscience in their professional relationships.

They must honour commitments, agreements and arrangements for the provision of their services. They must not abuse of their professional position or abuse the vulnerability of others.

Members of the pharmaceutical profession must, to the best of their abilities, provide truthful, accurate and objective and current information in a manner which is easily understood by patients, society and colleagues.

By their actions, they must not mislead nor make any claims that cannot be justified.

Members of the pharmaceutical profession must respect patients’ wishes not to be given information. However, possible consequences of this refusal must be outlined.

Members of the pharmaceutical profession must act with conviction of conscience. They have no obligation to offer or provide a professional service in ways which conflict with their own personal, moral or religious beliefs. In such situations the patient/client must be informed that they cannot render such a service.

1.5Respectpatients’autonomy

Pharmacists must encourage and empower patients, or in certain circumstances their carers/guardians, to actively participate in decisions about their health and care, and to manage their condition. This must be done, when appropriate, in partnership with other members of the healthcare team, and entails an open dialogue.

Pharmacists must respect patients’ right to choose whether or not to actively participate in these decisions.

1.6RespectandsafeguardconfidentialityMembers of the pharmaceutical

profession must respect and safeguard confidentiality and must not disclose voluntarily to others, and must take appropriate measures to prevent

* The Charter of Fundamental Human Rights of the EU,2000. Universal Declaration of Human Rights, United Nations, 1948. A Declaration of the promotion of patients’ rights in Europe, World Health Organization, 1994.

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�0 Journal of the Malta College of Pharmacy Practice Issue 14 Summer 2008

unauthorised access to, any information and facts entrusted or made known to them in the exercise of their profession except with the informed consent (preferably in writing) of the patient, when permitted to do so by law or in exceptional circumstances.

Members of the pharmaceutical profession must strive to respect privacy whilst providing consultations.

1.7Givethesamededicationandcaretoall

Members of the pharmaceutical profession must give the same dedication, care and attention to everyone without discrimination.

In rendering a pharmaceutical service they must ensure that the individual needs of their patients are met, taking into consideration societal interest.

1.8ServestheneedsofsocietyMembers of the pharmaceutical

profession must be attentive and sensitive to the well-being and healthcare needs of society.

Members of the pharmaceutical profession should act with fairness and equity in the allocation of any health resources made available to them.

Members of the pharmaceutical profession must endeavour to promote measures designed to prevent ill health, and to promote healthy lifestyles.

2. Responsibilities towards the profession

2.1UpholdthedignityoftheprofessionMembers of the pharmaceutical

profession must strive to uphold the dignity and respect of the profession.

Members of the pharmaceutical profession must maintain high standards of personal and professional conduct in conformity with their role as members of the pharmaceutical profession and abstain from any behaviour or activity likely to bring the profession in disrepute or undermine public confidence in, and respect for, the profession even outside the exercise of the profession.

2.2ExerciseprofessionaljudgementMembers of the pharmaceutical

profession must preserve their professional autonomy and exercise professional judgement in the interests of patients and society, within the parameters of their responsibilities, after taking into account all the relevant circumstances. They must not accept to practise under conditions in which this freedom may be compromised.

Members of the pharmaceutical profession must not allow personal interests, commercial interests such as incentives and targets, technical constraints or other conflicts of interest that may impair their professional judgements.

Members of the pharmaceutical profession should be prepared to challenge their colleague’s decisions if they believe that these decisions compromise the wellbeing and safety of patients and society. This without prejudice to the holding of good relationships between them.

2.3PersonalprofessionalresponsibilityMembers of the pharmaceutical

profession, when rendering professional services, are professionally responsible and ethically and legally accountable for their decisions, behaviour and any services/work done under their supervision.

Members of the pharmaceutical profession must ensure that:• All legislation, applicable to their area of

practice is abided by at all times, • They have the requisite skills and

knowledge to undertake, perform or provide services in their area of practice. When additional knowledge or expertise is required they must refer or consult with others who possess the necessary competence,

• They and other personnel in their employment or under their supervision have sufficient language competence to communicate effectively,

• Their practice procedures are accomplished with care and attention and in line with codes and standards of practice applicable to their area of practice,

• They have access to the facilities, equipment and material necessary to provide services to professionally

accepted standards. They must raise concerns, and take appropriate actions if policies, systems, work load and working conditions compromise the standard of practice, patient care or public safety,

• Before accepting and during employment they must disclose any conscientious objection, or conflict of interest and other factors which may affect their ability to render certain professional services.

• They comply with the Guidelines in their area of practice issued by the Pharmacy Council and the Regulatory Authorities,

• They practice only if they are competent to do so and must declare to the Pharmacy Council, employer or relevant authority any circumstances that call to question their fitness to practice or bring the profession into disrepute, including ill health that impairs ability to practice, and any criminal convictions.

• They conduct research in accordance to the relevant Research Ethics Guidelines and with the authorisation of the appropriate research ethics committee.

• If any tasks are to be delegated by them they are delegated to persons, who to their knowledge have the required qualifications, competence and skills to undertake these tasks effectively and efficiently and who comply with work instructions and are authorised to perform these tasks. There must be appropriate supervision.

2.4Developandmaintain competencetopractice

Members of the pharmaceutical profession must develop and maintain professional competence relative to their area/s of practice so as to be able to provide an effective and adequate pharmaceutical service which is of high quality, up to date and evidence based.

2.5Contributetothedevelopment oftheprofession

Members of the pharmaceutical profession must strive to be innovative in their endeavours to develop the pharmaceutical services they render to patients and society in line with their needs.

2.6Educateandtrainfuturemembers ofthepharmaceuticalprofession

Members of the pharmaceutical profession should endeavour to assist in the education,

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Issue 14 Summer 2008 Journal of the Malta College of Pharmacy Practice �1

training and professional formation of future generations of the pharmaceutical profession, and other professions.

Members of the pharmaceutical profession must serve as role models for future members of the pharmaceutical profession. They must foresee how their attitudes and dispositions towards patients, colleagues, and other stake holders would influence the attitude of future members of the pharmaceutical profession and to present model standards of professional behaviour.

3. Inter- and intra-professional relationships

3.1CooperatewithcolleaguesMembers of the pharmaceutical

profession must establish and maintain good professional relationships with colleagues and respect their competences, responsibilities, professional autonomy and conscience.

Members of the pharmaceutical profession must communicate and collaborate with colleagues to ensure that optimal care, treatment and service is provided to patients and to society.

In interacting with colleagues, Members of the pharmaceutical profession must contribute their technical and scientific expertise so as to facilitate a reciprocal exchange of knowledge and information. They should endeavour to contribute to the development, education and training of their colleagues.

Members of the pharmaceutical profession must avoid any action that can jeopardize the relationship of a patient with colleagues or impair confidence in them. They must also avoid any action which can impair confidence in any profession.

Commercial or financial interests must not motivate or undermine the professional relationship with other colleagues to obtain advantages to the detriment of patients.Members of the pharmaceutical profession must not prevent in any way a patient’s free choice of another health care professional or service provider.

Members of the pharmaceutical profession must assist colleagues who need their support or seek their advice.

In situations where members of the

pharmaceutical profession have good reason to believe that a colleague may not be fit to practice the profession due to ill health, or other circumstances that impairs his/her ability to practice, or bring the profession into disrepute, they must act immediately to safeguard patients, society and the profession.

3.2Maintaingoodprofessionalrelationshipwithemployersandserviceproviders

Members of the pharmaceutical profession should endeavour to maintain good professional relationships with their employers, service providers and stakeholders, in the best interest of patients and society.

4. Relationship with the regulatory and administrative authorities

4.1Collaboratewiththecompetent authoritiesandinstitutions

Members of the pharmaceutical profession must assist and collaborate with the competent authorities and institutions in a relationship based on mutual trust and respect to reach their objectives and to safeguard public health.

5. Promotion and advertising

5.1Patientsandpublictofreelychoosetheirpharmacistorserviceprovider

Members of the pharmaceutical profession must not promote or conduct any activities that limit or prevent in any way patients and public to freely choose their pharmacist or service provider.

They must abstain from all competition which undermines collegiality or misleads patients.

Members of the pharmaceutical profession must not use their honorary titles and position; whether elective, administrative or academic to depreciate others. It is contrary to public interest and to the dignity of the profession for pharmacists to secure patients or promote one’s professional advantage to the exclusion of others. This being however

understood that pharmacists may advertise as per guidelines issued by the Pharmacy Council in local publications in support of their community.

5.2Personallyresponsiblefor publicationsandeducational materialundertheirname

Members of the pharmaceutical profession engaged in publishing material suitable for the public and colleagues in any form whatsoever, printed or audio shall be responsible for any improper or undue self advertising. This does not, however, apply to books on scientific or professional material or to articles or correspondence in professional journals.

Entries in normal type in telephone directories are permitted according to the guidelines issued by the Pharmacy Council.

5.3Promotionofmedicalproducts andotherproducts

It is expressly forbidden for a member of the pharmaceutical profession to use his/her professional status to promote or endorse or in any other manner support publicly any product or medicinal or otherwise.

Members of the pharmaceutical profession must not participate in promotional methods that encourage patients and society to equate medicines with ordinary items of commerce.

5.4Pharmaceuticalservicesrendered tothepublic

Pharmaceutical services must not be promoted or advertised in such a way as to draw direct or indirect comparison with other service providers or discredit others.

Members of the pharmaceutical profession must not use financial incentives to encourage patients to use their services or purchase their medicinal products in preference to that offered by other members of the profession. Such prohibited incentives may include but are not limited to:• Offering standard discounts to clients on

medicinal products and pharmacy only items;

• Exhibiting medicinal products prices at less than the recommended retail prices.

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The national availability of medicines is monitored by the Pharmaceutical Unit. The Malta Medicines List (MML) is kept updated with all the medicines authorised to be placed on the market. The list is a national formulary which includes those medicines authorised by the local Medicines Authority as well as those authorised by the European Medicines Agency which are imported and placed on the Maltese market. Such monitoring together with the implementation of the ‘Guidelines for the supply of medicinal products for human use through processes which are not covered by the Medicines Act, 200� and its subsidiary legislation’, ensure that the public’s pharmaceutical needs are met.

The MML provides information useful for both the health care professional and the patient, with the aim of improving the rational use of medicines. According to the World Health Organisation (WHO), rational medicines use requires that patients

The Pharmaceutical UnitVanessaBugejaBPharm(Hons), PQ Dip(Nutrition & Dietetics)

Pharmacist, Pharmaceutical Unit, Public Health RegulationEmail:[email protected]

KeywordsMedicinal products, legislation, policy, Malta Medicines List

The unit implements local legislation and fulfils international obligations with respect to narcotic drugs, psychotropic substances and precursor chemicals. It is also responsible for the development and setting of policies in various pharmaceutical areas, as well as for the implementation and monitoring of the set policies.

receive medications appropriate to their clinical needs, in doses that meet their individual requirements, for an adequate period of time, and at the lowest possible cost to them and their community. The Pharmaceutical Unit has the mission of empowering health professionals and consumers to use medicine in a therapeutically sound and cost-effective manner.

Following European Union accession, Malta transposed the EU legislation into the Medicines Act 200� and its subsidiary legislation, so that the medicinal products available are all up to the European Union standards of quality i.e. as demanded by the Directive 2001/8�/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use.

By ensuring the quality, safety and efficacy of medicinal products, patient safety is enhanced. The Pharmaceutical Unit supports such regulations and deals with medicine policies which safeguard the patients’ rights and wellbeing, and which boost the healthcare professionals’ confidence in the medicinal products available, from their manufacture to administration and use by the patient.

Figure1.FunctionsofthePharmaceuticalUnit

Narcotic drugs, psychotropic

substances, precursor chemicals

Pharmaceutical policy, legislation and communication, policy

administration

Pharmaceutical care, therapeutic guidelines,

standards and guidelines

Rational use ofmedicines; publichealth impact ofmedicines use

National medicines availability and use

PharmaceuticalUnit,PublicHealth

RegulationDivision

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Issue 14 Summer 2008 Journal of the Malta College of Pharmacy Practice ��


IntroductionToday pharmaceutical policy is a

global concern, with the overall goal of achieving rational medicines use. Such goal

The impact of EU legislation on medicines in Malta

The impact of EU accession on the medicines in Malta has been quite strong, especially with regards to the availability of medicines. The new regulations affected many policies either by totally changing them or by highlighting the need for action and change. EU legislation has brought difficult changes which however promise to be fruitful once there is agreement of all key players and necessary action is taken and systems are implemented so that Malta can operate within the EU legislative framework with the aim of ensuring availability and affordability of high quality medicines and their rational use.

VanessaBugejaBPharm(Hons), PQ Dip(Nutrition & Dietetics)

Pharmacist, Pharmaceutical Unit, Public Health Regulation Division, MaltaEmail:[email protected]

KeywordsEU accession, rational use, quality, availability, affordability

makes policy analysis issues dynamic and constantly under evolution.1 Pharmaceutical policy is both problem solving and policy making. So policy analysis is both a tool

of the problem-solving process and the democratic process.2 It is the process of predicting impacts of possible policies and evaluating past policies.1 The value of policy analysis lies in its contribution to the understandings that citizens have of issues and therefore to the making of policies with outcomes supported by the public. 2

Pharmaceutical policies made on national, international, supranational or global level, will always ultimately affect everyone.� The Europeanisation of medicines regulation harmonises the standards of regulatory evaluation in order to accommodate a single European pharmaceutical market, and thus eliminates conflicting regulatory decisions made by national authorities in the European Union (EU).1 Member states have the challenge of strengthening their capacity to manage the complexities of relevant trends, options for change, evidence assessment, setting of priorities, drafting and implementing action plans, measuring outcomes and taking corrective action.4

Following EU accession in May 2004, Malta faced its own challenges in the pharmaceutical area. Accession brought with it a change in the legislation regarding medicinal products for human use (Table 1). EU legislation regarding good manufacturing practice, importation and parallel importation, marketing authorisations, packaging and labeling, wholesale distribution, reimbursement and selection of medicines, clinical trials, pharmacovigilance and advertising had to be transposed into the Maltese legislation. Thus, new regulations were established.

The quality, access, and rational use of medicines were effected, especially by the newly introduced procedures by which medicinal products are placed on the Maltese market. Between 1998 and 2002 the procedure involved the submission of a World Health Organisation (WHO) Certificate of Pharmaceutical Product (CPP).� Products registered with a CPP were included in the transition list which was drawn up in November 2002. The products were bound to benefit from a derogation. The derogation period in which products in the transition

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list could be registered via a Provisional Marketing Authorisation (PMA) followed by a Marketing Authorisation (MA), ended in December 2006.

Upon accession into the EU, medicinal products could be placed on the Maltese market not only through the PMA-MA process but also through the Mutual Recognition Procedure (MRP). From February 200� Article 126a of Directive 2001/8� on the Community code relating to medicinal products for human use, as amended by Directive 2004/2�/EC of the European Parliament and of the council of �1st March 2004, could be used, while starting from November 200�, the Decentralised Procedure (DCP) could also be used.6

A legislative framework is necessary for the implementation and enforcement of policies. The legal basis for the control of activities in the public and private pharmaceutical sectors can only be provided by legislation and regulations.� EU legislation can and does have an impact on medicines and health. On the other hand, national governments attempt to retain control.8

Public oversight and stewardship are required for the production and

distribution of medicines (Table 2). Unlike other goods and services, medicines have to be regulated so that the market is successful and safe for the users.11 Medicines regulation operates within a legal framework and is based on the application of medical, scientific and technical knowledge and skills. It involves interactions with various stakeholders whose economic, social and political motives may differ, making the implementation of regulation quite challenging.12

An efficient regulatory system for medicines provides timely access to effective treatments for patients and protects patient safety. The patients, doctors, pharmacists, government and the pharmaceutical industry share a common interest which is ensuring that the system is efficient, transparent and robust and makes decisions based on sound scientific evidence.1� They access quality and rational use of medicines depend on such a regulatory system.

The issue of the impact of EU legislation on the access, quality and rational use of medicines was looked at from three approaches so as to obtain a holistic picture. The types and number

of authorisations were reviewed, local newspapers were scanned, and group discussions with major stakeholders were held.

The impact was multifaceted. The regulatory changes triggered actions and reactions from the main stakeholders including the Malta Chamber of Pharmacists, the Malta Chamber of Commerce and Enterprise (CoCE), the Malta Chamber for Small and Medium Enterprises (GRTU), the Federation of Industry (FOI) and the government. The affects of EU legislation on the various pharmaceutical areas were discussed, agreements reached and necessary action taken to amend and improve the situation.

QualityofmedicinesPoor quality medicines are ineffective,

harmful and can result in therapeutic failure. The availability of high quality medicines promotes and ensures confidence in health systems, health professionals, pharmaceutical manufacturers and distributors. A strong national regulatory authority is the key to the effective regulation of manufacture, trade and use of medicines and therefore the protection and promotion of public health.12

Prior to accession, Malta had �020 EU and non-EU products placed on the market via a WHO CPP. The latter was not enough to ensure the good quality, safety and efficacy of medicines available in Malta.14 EU regulatory regime and the registration of medicinal products via PMA, MA, 126a, MRP or DCP brought with it an improvement in the quality, safety and efficacy of products (Table �).

The implementation of EU legislation was considered a painful process which safeguards the community, by ensuring that the medicines available are of a certain standard and quality and of known impact on patients. Non-EU generic products may be of good quality but the EU legislation and standards provide safeguards for professionals and patients.

However, there is not sufficient scientific evidence in terms of patient outcomes to support this claim of better quality and therefore better outcomes in Malta. In spite of complaints on the drugs which were available in the years previous

Table1.Maltesepharmaceuticallegislation

LegislationcoveringmedicinalproductsandpharmaceuticalactivitiesinMalta

1. The Medicines Act, 200�, and its subsidiary legislation (mainly covers regulation of medicines and pharmaceutical activities)2. Dangerous Drugs Ordinance 19�9 (narcotic drugs)�. Medical and Kindred Professions Ordinance 1901 (psychotropic substances)

Table2.PharmaceuticalRegulatoryBodies

Bodiessafeguardingthequality,accessandrationaluseofmedicinesinMalta

The MedicinesAuthority (MA) in Malta is the National Competent Authority for the regulation of medicines for human use and has the mission “to contribute to the protection of public health in Malta through regulation of the safety, quality and efficacy of medicines for sale or supply on the Maltese market.”9

The PharmaceuticalUnit, within the Public Health Regulation Division of the Ministry for Social Policy, is responsible for and co-ordinates the administrative and technical aspects of legislation, policies and guidelines regarding pharmaceutical policy on a national level.10

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to EU accession, the quality of the drugs in question was never checked.

AccesstogoodqualitymedicinesAccess is defined as the ability to

obtain health care, as determined by factors such as the availability and affordability of goods and services.1� Medicines can be essential to save lives, reduce suffering, and improve the functioning and well-being of people who have access to them. Access to affordable and appropriately used high-quality medicines boosts both the productivity and economy.�

AvailabilityPost-EU accession, the number of

medicinal products which had a marketing authorization in Malta, was quite less than the approximate ��0 products which were previously available on the market (Table �). EU legislation and medicines registration caused a negative impact on the availability of medicine, as confirmed by Galea in September 200�.14 Some stakeholders blamed EU directives for the reduction in medicines availability because importers and their suppliers failed to register new medicines, while others believed shortages

were increasing from pre accession and continued post accession. Following the stakeholders indication of the need for a system that guarantees availability and choice, the government set up a commission to study medicine status and give recommendations. Eventually, authorization via 126a was introduced and registration fees were amended so as to improve availability and promote competition.

LabellingandpackagingStakeholders were concerned with the

cost implications of the labeling regulations

Table3.AuthorisationsissuedformedicinalproductsinMalta

PeriodTypeofauthorizationormedicinalproductlist

Number

May2004Derogation List / WHO CPPa

182� different active ingredients�020 medicinal products�162 medicinal products from EU��0 medicinal products on the private market

UptoDecember2004 PMAb 2200 medicinal products

Year2005MRPc 6% (108 out of 1��0 applications)DCPd �% (1 out of 22 applications)

JanuarytoMay2006MRP 10% (22 out of 211 applications)DCP �% (� out of 1�4 applications)

May2006PMA 22�0 medicinal products

MAe ��0 medicinal products1299 under process

November2006 126a listf 1��6 medicinal products��6 active ingredients

UptoMarch2007

126a authorisationsg� authorisations 10� applications under process

MA

14�� from PMA-MA process148 from MRP process19 from line extensions (PMA-MA)1 national

MRP/DCP 1�2 under processUnlicensedh 1�2 medicinal products

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a. World Health Organisation Certificate of Pharmaceutical Product;b. Provisional Marketing Authorisation; c. Mutual Recoginition Procedure; d. Decentralised Procedure; e. Marketing Authorisation; f. list of medicinal products with no authorisation and therefore medicinal products not marketed in Malta. N.B. Some were

being imported directly by the Government Pharmaceutical Services through Article 20 of Medicines Act, 200�; g. authorisation through Article 126a of Directive 2001/8� as amended by Directive 2004/2�/EC; h. authorisation for the use of products which are not registered in Malta in line with DH Circular 2�0/06 Guidelines for the

supply of medicinal products for human use through processes which are not covered by the Medicines Act, 200� and its subsidiary legislation.


requirements. Labelling issues could have induced companies not to register products thus resulting in reduced availability and increased prices. The language issue was solved by an agreement to have either one of the two official national languages, Maltese or English, used for packaging and labelling.

Registrationsystemandregistrationfees

EU accession brought with it what has been called a cumbersome bureaucratic registration process, as predicted in the study by Vella Bonanno (200�).� Malta suffered a shortage of medicines because the pharmaceutical companies were finding it too expensive to register their products for a small market of 400,000 people.

The government had been assured that registration costs were not high. But, pharmaceutical companies withdrew due to labour intensive, disproportionate costs and registration fees. The stakeholders were concerned with the impact that the strict implementation of EU legislation was having on the access to medicines. On the other hand, the well-run registration system attracted pharmaceutical manufacturers to Malta, as it provided the necessary regulatory support crucial for sustaining the local industry.

Eventually, the EU introduced a clause to overcome the problem of reduced availability through the issuing of a qualified licence (authorization via article 126a). However, up to mid May 2006, no one had applied for this simpler registration procedure. The industry had to be pressured for medicines to be registered in Malta. Between January 200� and June 2006, Malta was included only in 1�0 applications for MRP and in 8 applications for DCP. The problem of high registration and variation fees was solved by an agreement on a system of uncomplicated fees comprising only a Lm�0 (€116.4�) annual registration fee.

LocalmanufacturingindustryEU legislation provided strong support

through the Medicines Authority for the local manufacturing industry, and the latter

grew steadily as the benefits of the local industry were adequately acknowledged and safeguarded. Discussions led to the provision of a mechanism which ensures availability and overall reduced prices for the local consumers, while still keeping the regulatory frameworks which govern medicinals in Malta.

Affordability/pricingUpon EU accession, the prices of

medicines in Malta increased drastically. Cheap reasonably priced medicines were replaced by expensive ones. The mark-ups for the wholesale dealer and pharmacists were no longer regulated and instead were left up to market forces. Where, due to these same market forces, only one medicine is available, monopoly resulted.

The regulatory system was blamed for the elimination of competitor products so that originator more expensive products remain. Availability and affordability are highly linked as decreased number of products leads to decreased competition and therefore increased prices.14 The need to promote the use of generics became evident, as this would cut down costs and increase choice and accessibility.

Discussions led to consideration of reference pricing to control prices and of a system which favours the importation of generics. The Consumer Competition Division (CCD) within the former Ministry for Competitiveness and Communications (MCMP) was to monitor prices and discussions were held to establish a system whereby action could be taken as necessary to induce the market forces to interact and thus abolish price increases.

RationaluseofmedicinesWHO states that rational use requires

patients to receive medications appropriate to their needs, in doses that meet individual requirements, for an adequate period of time, and at the lowest possible cost. This is essential for the promotion of quality care and cost-effective therapy. Rational use ensures that medicines are used only when needed and that patients understand what medicines are for and how to use them.16 At the same time the concept of rational use of

medicines should be applied in a contextual manner.1�

Pricing,internet,counterfeitmedicinesThe problem of expensive medicines

is at times solved by buying through the internet at one third of the local price because all one needs is a prescription. This aids rational use as doctors can prescribe medicines recommended by clinical guidelines even if they are not available on the Maltese market or are too expensive for low-income patients. However, the significant risk of counterfeit medicines exists. In Malta there is not enough awareness on this problem, and it is of concern that prescribers are recommending online buying to patients.

Availabilityandchoice

The rational use of medicines in Malta, though supported by the new legislation, was limited by the unavailability of medicines resulting from the implementation of this same legislation. Following EU accession there was a reduced consumer choice of children’s medicine and of dosage types. Consumers did not find their medicines and believed they were being offered inferior alternatives.

Compared to the British National Formulary (BNF), the Malta Medicines List (MML) was limited thus affecting choice and rational use of medicines.18 Similarly, the Government Formulary List (GFL) was also considered to be limited.19 However, following EU accession, the transposition of the Transparency Directive (EU Council Directive 89/10�/EEC of 21st December 1988) gave the medicines agents the possibility of having their products introduced on the list.20

Culture,habitsandpracticeThe medicines available through EU

brought to the fore issues of changes in practice e.g. the use of suppositories, when most other EU countries use tablets, soluble tablets or syrup. Authorisation via 126a aids maintenance of usual preparations when a change in culture, habit or practice is not accepted.

Regulatory/PolicyRegulatory/Policy


Generics,rationalprescribingandsubstitution

The EU system ensures generics are chemically, biologically and clinically equivalent, and of high quality and so can be used with full confidence. The local industry argued that the promotion of generic dispensing, patient awareness on generics and knowledge on the available generic substitutes would ensure rational use and affordability. In Malta the use of generics is supported by legislation which allows substitution of medicines so that pharmacists may offer an alternative brand or cheaper generic equivalent.21

SummaryofProductCharacteristics(SPC)/PatientInformationLeaflet(PIL)

EU legislation promotes dissemination of information, but more enforcement as regards the distirubution of SPCs to doctors was considered necessary. The dispensing of PILs with the medicine pack was also not being enforced and practiced by everyone. Awareness on the use of medicines could be improved by empowering people in line with the safeguards of EU legislation.

POMandOTCFollowing EU accession, the OTC range

available became smaller. This was probably due to products not being registered and due to the new classification of products into POM and OTC. This classification may in certain cases reduce irrational use, but in others it disrupts the usual rational practice.

1. Traulsen JM, Almarsdottir AB. The argument for pharmaceutical policy. Pharm World Sci 200�; 2�:�-12

2. Shulock N. The Paradox of Policy Analysis: If it is not used, why do we produce so much of it? Journal of Policy Analysis and Management 1999; 18 (2):226-244

�. Traulsen JM, Almarsdottir AB. Pharmaceutical policy and the lay public. Pharm World Sci 200�; 2�: 2��-2��

4. Averginos ED, Koupidis SA, Filippou DK. Impact of European Union enlargement on health professionals and health care systems. Health Policy 2004; 69: 40�-408

�. Vella Bonanno P. The Managed Entry of New Drugs into a National Health Service: A case study for Malta. Aberdeen: Centre for Partnerships in Medicines for Health; 200�

6. Marketing Authorisations. In: Medicines Authority, Malta; 200�. Available at: http://medicinesauthority.gov.mt/marketingauth.htm

�. WHO, Harvard Medical School and Harvard Pilgrim Health. Using indicators to measure country pharmaceutical situations: Fact Book on WHO Level I and Level II monitoring indicators. Geneva: WHO; 2006

8. Duncan B. Health policy in the European Union: how it’s made and how to influence it. Br Med J 2002; �24:102�-�0

9. Medicines Authority, Malta; 200�. Available at: http://medicinesauthority.gov.mt

10. National Medicines Policy & Audit Unit, Malta; 200�. Available at: http://www.sahha.gov.mt/entities/nmpau.html

11. WHO. The World Medicines Situation. Geneva: WHO; 2004

12. WHO. Effective medicines regulation: ensuring safety, efficacy and quality. WHO Policy Perspectives on Medicines 200�; �. Available at: http://www.who.int/medicines/publications/policyperspectives/en/index.html

References

• The pharmaceutical policy arena deals with conflicting goals of maximizing access, ensuring quality, minimising costs and promoting rational use of medicines.2�

• The evaluation of the change in policies brought about by EU legislation, can drive policy learning by being integrated into ongoing discussions, by sustaining the advocacy of evidence and by helping policy makers think.24

• EU accession has ensured that medicines available in Malta are of high quality.• EU legislation had a negative impact on access to medicines in Malta but

discussions led to reflexive learning and policy making with the aim of improving the situation, while maintaining the other benefits of the EU regulatory regime.

• The use of medicine which can seem irrational in certain contexts, may in other contexts seem quite rational. 1�

PracticePoints

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Both prescribers and patients resist change. Patients often could not understand why a good medicine to which they were used, is no longer available, or why they need a prescription to buy it.

AdvertisingandpromotionThe fact that industry can market OTCs

directly to consumers, has increased the emphasis on this target group.� The ease with which the OTCs could be advertised was compensating for the reduced availability of OTCs. Aggressive advertising was resulting in presumably informed consumers asking the pharmacist for a specific product rather than for advice.

The Legal Notice �80 of 200�, Medicines Act 200�, entitled Medicinal Products (Advertising) Regulations governs advertising and promotion with the healthcare professionals and the public.22

However, the regulations do not cover the communication between pharmaceutical companies and patient organizations. This could be due to the fine line between information and advertising.

ConclusionThe conflicting goals of access, quality

and rational use of medicines, make broad qualitative and quantitative knowledge essential for good pharmaceutical policymaking.2� The implementation of EU legislation in Malta, caused a decrease in the availability and affordability of medicines, an improvement in the quality of medicines, and conflicting positive and negative effects on the rational use of medicines. Such contribution to practical reason and informed discourse, can be appreciated and expanded to reshape and make better policies.2


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1�. Breckenridge A, Woods K. Medicines regulation and the pharmaceutical industry. Br Med J 200�; ��1:8�4-6

14. Galea C. Regulating the policies of medicines in small states with special reference to The Maltese Islands. [Dissertation] University of Malta; 200�.

1�. Glossary. In: Pharmaceutical Pricing and Reimbursement Information; 200�. Available at: http://ppri.oebig.at/index.aspx?Navigation=r|4-

16. WHO. How to develop and implement a national drug policy. 2nd ed. Geneva: WHO; 2001

1�. Traulsen JM, Almarsdottir AB. Rational use of medicines – an important issue in pharmaceutical policy. Pharm World Sci 200�; 2�: �6-80

18. Malta Medicines List. In: National Medicines Policy and Audit Unit, Malta; 200�. Available at: http://www.sahha.gov.mt/pages.aspx?page=814

19. Government Formulary List. In: National Medicines Policy & Audit Unit, Malta; 200�. Available at: http://www.sahha.gov.mt/pages.aspx?page=�40

20. Procedures. In: National Medicines Policy & Audit Unit, Malta; 200�. Available at: http://www.sahha.gov.mt/pages.aspx?page=64�

21. Bugeja V. Medicines: mere generic facts. Journal of the Malta College of Pharmacy Practice, 200�; 1�:42-44.

22. Maltese Legislation. In: Medicines Authority, Malta; 200�. Available at: http://medicinesauthority.gov.mt/legislation.htm

2�. Almarsdottir AB, Traulsen JM. Studying and evaluating pharmaceutical policy – becoming a part of the policy and consultative process. Pharm World Sci 2006; 28: 6-12

24. Sanderson I. Evaluation, policy learning and evidence-based policy making. Public Administration 2002; 80 (1): 1-22


Industry

The research-based pharmaceutical industry understands the pressures on European governments to ensure effective management of the limited resources allocated to healthcare, including pharmaceuticals. However, these pressures frequently result in short-term, and often punitive, pharmaceutical cost-containment measures, which bring only temporary relief, while reducing patient benefit and undermining the industry’s R&D efforts.

The industry has an important contribution to make to Europe. Innovative

Policy principles for a competitive healthcare environment

Governments across the world are looking for ways to balance a number of competing policy goals including economic growth; industrial development; attraction of foreign direct investment; advances in education, science and technology; overall budgetary control; and complex and evolving healthcare needs.

PharmaceuticalResearchandDevelopmentIndustryMaltaAssociation(PRIMA)

PRIMA is an affiliate of the European Federation of Pharmaceutical Industries and Associations (EFPIA)

KeywordsInnovative medicines, competition, sustainable healthcare, empowered patients

medicines contribute enormous social benefits and reassurance for individual citizens through improved healthcare - as seen in increased life expectancy and the treatment of cancer, diabetes, asthma and other diseases. Innovative medicines also enable healthy working populations to work longer, and healthier elderly populations to make fewer demands upon social security systems; and they enable more efficient use of healthcare budgets. The pharmaceuticals sector provides substantial investment in research and development,

leading to high quality jobs for science graduates, unrivalled job multiplier benefits, and support for the academic research community. This contribution must be nurtured.

Market-based pricing for reimbursed pharmaceuticals, in which companies are free to set prices and there are no supply-side or demand-side controls, remains the industry’s preferred solution to meeting the needs of patients and society’s demand for better medical treatments. At the same time, industry also recognises the challenges involved in finding approaches that can function within the context of social healthcare systems.

Industry believes better balance between competition in the pharmaceutical marketplace and government regulation is both possible and necessary. The aim is to identify how the market structure for pharmaceuticals can work in a manner that encourages competitiveness; is adapted to future, more personally-tailored medicines; and ensures patient access to innovative medicines. There are a number of elements that effectively deliver sustainable and efficient healthcare systems. Governments and industry should work together to identify steps that should be taken to strike a better balance.

Industry believes that only a collaborative and concerted multi-stakeholder approach can enhance progress in medicine for the best benefit of patients, who should be at the heart of healthcare systems. Sustainable solutions need to be weighed against three key objectives for improving patient outcomes: (1) optimal use of resources to maintain sustainable financing of healthcare, (2) access to medicines for patients and (�) reward for innovation. In each country, these goals will be addressed differently. However, industry believes that a set of core principles can guide policy approaches.

This paper sets out elements for a more balanced environment. Not all of these elements may be relevant or appropriate to every country. However, governments should be encouraged to review some, if not all, of them, as they consider how best to meet the challenge of establishing a healthcare policy that meets the needs of all key stakeholders, namely patients (who want



Figure1.Creatingacompetitivehealthcareenvironmentforthepharmaceuticalindustry–Overview

Sustainablehealthcarefunding

• Diversified sources of funding to alleviate public finances• Integrated look at pharmaceutical expenditure and impact of pharmaceutical

spending on overall savings rather than “silo-budgeting”• Increased use of patient co-payments (with safety nets)• Efficient use of generics through price competition• Focus on both treatment and prevention of disease• Increased efficiencies in the healthcare system• Efficient distribution mechanisms• Sufficient funding into healthcare to maintain high levels of healthcare quality• Create funding efficiency through investing into innovative and effective

treatments and interventions• Encourage screening, disease prevention programmes, and health promotion

Informedandempoweredpatients

• Dissemination of high-quality information on disease prevention and available treatments by reliable sources, including pharmaceutical industry

• Increased patient involvement in decisions affecting medicines registration and evaluation, provision of healthcare, funding issues, priority-setting

• Transparent patient funding

Increasedchoiceandavailabilityoftreatments

• Rapid market access and patient availability of new medicines

• Rational prescribing with freedom of choice for physicians and guidance to optimise patient treatment choices

Creatingabalancedenvironment

• Unmet medical need is addressed• Patients have access to the most

appropriate medicines• Innovation is supported, delivered,

and rewarded• Healthcare is sustainable• Environment is predictable and

transparent• Healthcare priorities and policies

are identified and set transparently and through dialogue

Acompetitivemarketplace

• Competition based on value and price• Market rewards added value appropriately • Recognition of innovation and added value in pharmaceuticals

through effective, fair and high-quality evaluation mechanisms clearly separate from regulatory approval

• Greater predictability and transparency in pricing and reimbursement through priority-setting and early dialogue between pharmaceutical industry and payers

• Proper recognition of IPRs in pricing systems • Faster patient access to new medicines through implementation of

Recommendation � but also Recommendation 6 of the G10• Proper respect of timelines as set out in the Transparency Directive• IP protection

Aviableclimateforinvestment

• Protection of intellectual property rights through appropriate legal frameworks

• An Attractive Fiscal/Economic Climate• Access to Skills,• Supportive Climate for Science• Strategic government approaches – no kneejerk reactions• Industry – government dialogue• Predictability and market stability

Industry


Industry

rapid access to the best treatments), payers (who want to deliver quality healthcare to their citizens and manage budgets) and the industry (which wants to secure a return on investment that will incentivise further innovation benefiting patients).

A vision for a balanced environment - key elements

1.Governmenteffortsinmeetinghealthcareprioritiesshouldbesupportedbyimprovedandearlierdialogue

Governments should ensure that the right infrastructure is in place for defining treatment priorities within individual disease areas and for identifying disease management targets. Industry and government should discuss these health priorities and targets as part of a long-term strategic agenda for the industry and not just as part of short-term cost-containment measures. This will enable the development of new medicines that address unmet need, clarify disease prioritisation, and ensure patients get access to medicines that improve their lives.

Increased predictability for all parties will be delivered through earlier and more in-depth interactions to discuss evidence that payers require in order to support reimbursement discussions. At present, dialogue generally starts once the indications for a medicine have been approved and the data generated. It is often conducted in a manner that lacks predictability and coherence.

2.Industryandgovernmentshouldestablishmorestructuredformsofdialogue

Industry believes that dialogue platforms should be launched at national level, bringing together the pharmaceutical industry, government, patients and other stakeholders to address issues of relevance to healthcare as well as pharmaceutical industry competitiveness. Industry believes that current approaches fail to address the more fundamental problem of how to

maintain current quality of healthcare provision and treatment with innovative medicines in a context of demographic change and increased demand. Structural change is needed, and measures can best be identified in cooperation between the key actors involved.

3.Healthcarefundingshouldbeadequateandsustainable

Resources should be allocated where quality is achieved and public health outcomes are maximised. Ways of achieving this include:• Improvedprevention - chronic

diseases are among the most prevalent, costly and preventable of all healthcare problems. While prevention is an investment that can incur up-front costs, evidence shows that over time health care outcomes will be improved and significant new spending avoided.

• Improvingefficiency - efficient practice (prevention, diagnosis, treatment, and rehabilitation) will lead to savings for the healthcare system as a whole. Policies for appropriate usage of medicines in both qualitative and quantitative terms should be promoted and implemented, with a view to freeing up resources for use elsewhere in the system and delivering better outcomes.

• Integratingcareofchronicdiseasesandviewingdrugbudgetsinthecontextofhealthcareoverall – a more comprehensive view of the contributions of various components of the health care system to efficient health care interventions should be adopted. Governments currently tend to focus on medicines expenditures.

• Developinggreaterawarenessofthecost-effectivenessofinnovativemedicines - governments should identify savings and redirect expenditures towards innovative drugs. The key objective should be to

allow access to advanced health care technologies, while ensuring that usage is targeted and cost-effective.

• Recognisingtheimportanceandvalueofcomprehensivevaccinationprogrammesinthecontextofinvestingincost-effectivepreventativecare.

• Strengthening/establishingprimarycareservicesandavoidingmisuseandoveruseofmedicalservices - an efficient ambulatory care system should be developed. This includes a general practitioner referral system, the development of community care centres with focus on health promotion and disease prevention, further development of the role of pharmacists and the nursing profession, and the creation of effective incentives for all healthcare actors to deliver the highest standards.

• Promotingappropriateuseofover-the-counterproducts.

• Newfundingsourcesshouldbeconsidered- systems in which the government is the sole purchaser of medicines are likely to be unsustainable in the medium to long-term. Governments should look at new funding options, including a greater role for private health insurance, appropriate tax-based measures, and greater pressure on the generics and distribution sectors to increase efficiency.

4.Pricingandreimbursementpoliciesshouldreflectthetruevalueof“innovation”

Where payers seek value for money, pharmaceutical companies require reward for delivering value. The reward society gives to an innovative medicine should reflect the value it delivers to patients, healthcare systems, and society at large. This reward can come in different forms, e.g. price level, unrestricted access to the patient population defined

* ‘generic’ being defined as a medicine based on an active substance that is out of patent and which is marketed under a different name from that of the original branded medicine.


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as needing new therapy, therapeutic guidelines recognising a new therapy, and speed of access.

The nature of drug development, however, remains highly unpredictable. There is no guarantee that the first drug to market will be the best (nor how any individual patient will respond to any particular drug). Some new medicines will be revolutionary breakthroughs. Others will deliver incremental benefits over existing treatments, be it in efficacy, improved tolerability or improved mode of administration. Reward for value must therefore be provided for stepwise advances in therapy.

5. Toolsformeasuring“innovation” shouldbeappropriate The evaluation of a medicine’s

value must deliver a reasonable balance between the interests of payers, patients, physicians, and industry. Health technology assessment (HTA) is one of the tools, when appropriately defined and applied, that can contribute to an assessment of clinical effectiveness and cost-effectiveness of new medicines and new technologies (including medical devices). The goal of the HTA process should be to improve patient care and physician decision-making. Certain key principles should underpin any HTA system.• HTAs should be based on a clear,

sophisticated and clinically differentiated view of what constitutes value

• HTAs should be transparent and balanced

• HTAs should be based on early and inclusive dialogue, including with patients

• Evaluations should allow new data to be considered

• Comprehensive understanding of the benefits of a drug in disease management is needed

• Payers should commit to rewarding added value and HTA outcomes should be implemented

• HTA should apply to all healthcare interventions

• Assessment should take place at the national level

• HTA should remain separate from regulatory review

• HTA bodies should have a process to handle appeals of their decisions by stakeholders efficiently.

• Evaluations should take into account the full range of value, including indirect benefits (societal view)

• HTA should use different types of evidence

6.Increasedaccesstoinformationforpatientsshouldbeactivelyencouraged

Citizens and patients should be at the centre of many key aspects of healthcare as well as medicines policy – such as assessments of value, decisions on access, and allocation of funding. This can only work, however, if there is sufficient information available to them - patients should be given the ability to make choices, and should receive the information to choose wisely.

Industry should be involved in this initiative. Disease education and vaccines information campaigns are an example of how responsible, approved information from the industry to the public can fulfil a number of objectives: raising public awareness of the existence of a safe and effective vaccine; educating the public of the risks attached to non-vaccination; allowing important savings to be achieved for healthcare systems by preventing disease; encouraging proper compliance with courses of treatment; and contributing to society’s overall “wellness”.

7.Marketpricingfornon-reimbursedmedicinesshouldbeallowed

Governments should only negotiate for the prices of what they purchase or reimburse; sales outside the state reimbursement system should be subject to the normal rules of market pricing. This will help to manage problems of market distortion and parallel trade. Market distortions, and potential safety hazards for patients, can also be addressed through improvements in the integrity and security of the supply chain.

Industry

8.Off-patent/genericmedicinesshouldplayanappropriatepartintreatmentoptions

Appropriate use of multi-source products (off-patent and generics*) can deliver healthcare savings and free up resources. However, a more competitive market is required to enable multi-source products to yield the savings they promise. Prices of multi-source products should be competitive, reflecting the limited innovation and investment that goes into their development. Policies encouraging the use of multi-source products should be implemented in full respect of physicians’ prescribing freedom.

9.Distributionsystemsshould operateefficiently Distribution margins can have a large

impact on the dispensing behaviour of pharmacists, the creation of competitive off-patent markets and the savings created for healthcare systems. As a general rule, we believe that free market dynamics are the best way to ‘regulate’ prices along the pharmaceutical value chain, including ex-factory prices. Free market conditions for distribution services should always go hand-in-hand with free market conditions for pharmaceutical manufacturers. Where controls are imposed on margins, the structures of the wholesale and retail margins should reflect economic reality as much as possible when compensating for the services provided.

10.UseofOTCproductsshould beencouraged Policies encouraging the use of over-

the-counter medicines should be actively implemented where medicines provide a clear health benefit to patients for minor, self-limiting indications or diseases where medical supervision is not needed, and are sufficiently safe to warrant OTC status. These policies should include Government support for products with a long history of safe use being switched from prescription to non-prescription. The advertising and promotion of these products should also be liberalised, to realise cost-savings for the healthcare system.


11.Effectiveregulatorysystems shouldbeenhanced A well-regarded registration process

for new pharmaceutical products that enables medicines to gain international credibility by passing stringent criteria on quality, safety and efficacy will encourage pharmaceutical companies to conduct clinical trials and launch innovative products early. Key regulations should be conducive to the development and early adoption of innovative new drugs.

12.IPshouldberespected A strong legal framework on

intellectual property rights creates a desirable environment for research and development. Enactment and enforcement of international patent protection and registration data exclusivity to reward innovation and allow funding of R&D in an era of escalating technology development costs is a key factor. Therapeutic reference pricing – which

groups patented medicines with older off patent medicines for purposes of setting a single reimbursement price – represents an infringement on basic IP rights because of its impact in curtailing the effective period of protection offered by a patent.

13.Stronganti-counterfeitinglawsandenforcementshouldbeputintoplace There are increasing examples of

counterfeit medicines entering the legitimate supply chain, an issue of increasing concern for the Community. Measure should be put in place to prevent counterfeit medicines from reaching patients. The European Commission should issue a Regulation for ensuring the safety and integrity of the supply chain including measures such as a ban on repackaging, an unique system of identification and coding of pharmaceutical products throughout Europe, a notification of corrupt products and strict liability rules for all distributors and retailers of medicines.

14.Supportforthesciencebase There needs to be a more concerted

effort at EU level to encourage cooperation and research in the pharmaceutical field. There are a number of broader environmental issues that should be addressed in Europe in order to maintain attractiveness for R&D investment:• Europe must deliver appropriately

skilled staff. The speed of the change in R&D has translated into essential skills being in short supply. Training in leading-edge technologies is key if the right quantity and quality of scientists is made available.

• EU should provide funding to develop academic expertise in biomarker and surrogate technologies and the application of these technologies in drug development.

• Access to new ideas and technology through links with the academic research base and with biotech SMEs is important. Clusters of research and training institutions, suppliers of key inputs (e.g. software), venture capital providers and other related entities are essential to facilitate linkages and partnerships.

Industry


ProfessionalActivities

The twinning project is based upon receiving Twinning ‘light’ assistance from a Member State, in this case the Netherlands. A team of experts will be providing training and technical support to the Regulatory Bodies, those being the Pharmacy Council, the Medical Council, the Council for Nurses and Midwives, the Council for the Professions complementary to medicine and the Specialist Accreditation Committee and their respective staff (i.e. five Registrars, one Assistant Director and around sixty Council members) to discharge their duties competently and in

EU twinning: ‘Light’Project for the Health Care Professionals’ Competent Authorities on the Free Movement of Health Care Professionals

On Thursday 29th May 2008 a Twinning ‘light’ Project was launched on “The Free Movement of Health Care Professionals” under the 2006 Transition Facility Programme for Malta. This project was signed with the Netherlands through the Dutch agency Vilans.

JosephBusuttilBA(Hons), Dip Mangt St

Registrar, Pharmacy Council MaltaEmail: [email protected]

KeywordsRegulatory bodies, training, General System Directives, Sectoral Directive

line with relevant EU directives. The three General Systems Directives concerned are 89/48/EEC, 99/42/EC and 92/�1/EEC. In addition new Directive 200�/�6/EC, which has been transposed into Maltese law, and is replacing the sectoral Directives ��/4�2, ��/4��, �8/686, �8/68�, 80/1�4, 80/1��, 8�/4�2, 8�/4�� and 9�/16. This project will consist of a series of tasks to achieve the desired objectives, mainly in the form of an organisational review, production of manuals of procedures and training seminars together with assistance in the setting up of an Information Centre.

AssistancesoughtfromaMemberStateMalta is seeking assistance from the

Netherlands to provide short-term experts (STEs) to deliver the necessary assistance in Malta.

The project has been subdivided into the following activities:

Activity1:ProvisionoftrainingandtechnicalexpertisetoestablishthehumanresourcecapacitytoimplementtherelevantDirectives

This is aimed to train Council members and Registrars on Directive 200�/�6/EC and other relevant acquis in the field of free movement of health care professionals together with its implementation in the local health care system.

Activityoutcome:Relevant health care professionals trained on the implementation of Directive 200�/�6/EC.

Activity2:ReviewofcurrentMalteseadministrativestructuresandprocedures

This activity shall comprise a review of current Maltese administrative structures and procedures in relation to EU best practice in the area of mutual recognition of health care professionals. The review will be based on a comparative analysis between the national administrative structures of Malta and two other EU Member States.

Activityoutcome:Recommendations on changes to the structures and administrative procedures of the Regulatory Councils and the national legislation in order to comply with Directive 200�/�6/EC delivered.

Activity3:DevelopmentofproceduresandsystemsfortheefficientimplementationoftheDirectives

Assistance is required to develop the necessary procedures and systems in order to allow efficient implementation of the Directives. This will be done by means of a series of three discussion workshops in which the Registrars and Council members will work with the STEs to elaborate detailed Standard Operating Procedures (SOP) related to all regulated healthcare professionals in Malta.

The result will be the production of Standard Operating Procedures compiled


1. Manuals of Standard Operating Procedures in line with EU Regulations produced for the five Regulatory Councils.

2. Recommendations on changes to the structures and administrative procedures of the Regulatory Councils and the national legislation in order to comply with Directive 200�/�6/EC delivered.

�. An Information Centre on the free movement of healthcare professionals for use by EU nationals set up.

4. Relevant health care professionals trained on the implementation of Directive 200�/�6/EC.

Table1.Mandatoryresultsandbenchmarksoftwinning‘light’project

into manuals required for the competent function of each Council.

Activityoutcome:Manuals of Standard Operating Procedures in line with EU Regulations produced for the five Regulatory Councils.

Activity4:AssistanceintheimplementationoftherequirementsoftherelevantDirectivesforthemutualrecognitionofqualificationsforcertainhealthcareprofessionals

This activity aims to deliver assistance in the implementation of the requirements of the relevant Directives for the mutual recognition of qualifications for healthcare professionals in the following professions: pharmacist, medical doctor, dentist, general care nurse and midwife.

This will include advice on the setting up of an Information Centre for use by EU nationals on the free movement of healthcare professionals.

Activityoutcome:An Information Centre on the free movement of healthcare professionals for use by EU nationals set up.

Activity5:DisseminationofinformationontheresultsofimplementationoftheDirective

To inform and educate health care professionals on the results of implementation of the Directive, a 2-day seminar will be organised for all stakeholders who are mainly health care professionals (under the old general system). Participants from the different professional groups will take part in order to be informed and educated on the new systems in place.

Activityoutcome:contributes to training on directive.

Activity6:DisseminationofinformationontheresultsofimplementationoftheDirective

To inform and educate health care professionals on the results of implementation of the Directive, a 2-day seminar will be held for health care professionals under the old sector-specific Directives ��/4�2, ��/4��, �8/686, �8/68�, 80/1�4, 80/1��, 8�/4�2, 8�/4�� and 9�/16.

This activity aims to disseminate knowledge on the new Directive and the systems in place to key representatives from the medical, dental, general care nursing, midwifery and pharmacy professions.

Activityoutcome:contributes to training on directive

Activity7:StudyVisitsThe Registrars will be visiting the

relevant competent authorities in the Netherlands to gain first hand experience on the relevant systems adopted and the implementation of the directive from their end. The Registrars will also be attending a three day seminar in Maastricht on the free movement of Health Care Professionals.

ConclusionThis training has long been awaited

and thus has been welcomed by all the Councils involved. This project will at least assist the Councils in their decision making process and is considered a step in the right direction for the Councils to gain more professional expertise in the field of the free movement of health care professionals.

One hopes that this project will reach its desired objectives and eventually also lead to further capacity building in the Councils themselves to enable them to function more autonomously and in a more professional manner.




Primary care: quo vadis?

“Across the globe doctors are miserable because they feel like hamsters on a treadmill. They must run faster just to stand still. In Britain they must see ever more patients, fill in more forms, and sit on more committees just to keep the NHS afloat. In the government sponsored, single payer system in Canada, the mandatory insurance systems in Japan or continental Europe, or the managed care systems in the United States, doctors feel that they have to see more patients to maintain their incomes. But systems that depend on everybody running faster are not sustainable. The answer must be to redesign health care.” Ian Morrison, Richard Smith, BMJ 2000;321:1541-1542 (23 December)

IsabelStabileLRCP, MRCS, FRCOG, PhD

Executive Director, Mediterranean Institute of Primary CareEmail: [email protected]

JeanKarlSolerMD, MSc, MMCFD

Executive Director, Mediterranean Institute of Primary Care

KeywordsPrimary care, health care systems, health care reform

Whatisprimarycareandwhatisuniqueaboutit?

Primary care is the provision of integrated, high-quality, accessible health care services by clinicians who are accountable for addressing a full range of personal health and health care needs, developing a sustained partnership with patients, practicing in the context of family and community, and working to minimize disparities across population sub-groups. The core attributes of primary care include1:• It serves as a point of first contact for

the patient, playing a key role in access to care and in coordinating care for patients who use multiple providers or specialists;

• It is holistic and comprehensive, focusing on the whole person and taking into account his or her social context;

• Uncertainty is a common attribute of clinical decision making in primary care;

• Primary care practice is information intensive;

• Opportunities to promote health and prevent disease are intrinsic to primary care;

• A sustained personal relationship between patient and clinician is a key aspect of primary health care, emphasizing the importance of compassion, continuity, and communication between provider and patient.

Primary care has a critical role to play in each country’s health system. It enhances links within the sector both vertically, between primary and secondary care and public health services, and horizontally, among the various health professionals (family doctors, pharmacists, nurses, physiotherapists, occupational therapists, speech language therapists etc) working at the primary level. It provides a platform for the care continuum and is critically important in managing chronic conditions, where successful health outcomes are influenced by continuity and personalized care. Lastly, it enables multisectoral responses to be made, by linking the health system with the social and education sectors.




There is good evidence that the strength of a country’s primary care system is significantly associated with improved population health outcomes (as measured by indicators such as all-cause mortality rates), even after controlling for population health determinants at macro- and micro-levels (GDP per capita, physician/population ratio, per capita income, alcohol and tobacco consumption, etc.).2 More specifically, the increased availability of primary care is associated with higher patient satisfaction, reduced aggregate spending on health care for a given outcome, better access and accessibility, and enhanced equity.� However, it is important to realize that the expansion of primary health care services may not always reduce costs because previously unmet needs are identified, access to services is improved, thus expanding service utilization.

Despite the evidence for primary care, resource allocation in most countries still favours hospitals and specialist care. This is partly due to perceptions about what primary care is, what it has to offer4, and its development as a control function to reduce costs or access to secondary care�,6, rather than its positive contribution to health gain. This explains the paradox of the attractiveness of primary care on empirical grounds and its lack of appeal to national policy-makers and healthcare professionals, who see it as a low-grade activity with little effect on mortality and serious morbidity and a predominant role in triage of access to hospitals.

The role of primary care should not be defined in isolation but in relation to the constituents of the health system. Primary and secondary care, generalist and specialist, all have important roles in the health system. They are not mutually exclusive, but rather necessary ingredients for any system. However, technological advances, improved education and training, broadening of the primary care team roles and membership, different demand patterns due to health transition, and changing social attitudes mean primary care has a greater role to play than before, and resource allocation needs to flow in its favour.

The Mediterranean Institute of Primary Care (MIPC) is a newly formed non-governmental organization financed by a trust held with the Bank of Valletta aimed at supporting research and training within the domain of primary care in the Mediterranean region.

The aim of the research programme within the MIPC is to support, commission, coordinate and conduct policy-relevant research studies on primary care, and relevant clinical, preventive and public health policies, and on systems to improve the evidence-base that drives quality primary health care services, within the Mediterranean setting. The aim of the training programme within the MIPC is to provide educational opportunities for clinicians and trainees to maintain clinical skills and develop new skills in performing research and to support the development of primary care providers as creative and independent investigators in primary care research.

The MIPC welcomes members from all Mediterranean countries and from all the disciplines that form the primary care team. In addition to family doctors, members include pharmacists, nurses, physiotherapists among others. Enquires about membership should be directed to [email protected]

TheMediterraneanInstituteofPrimaryCare

PrimaryCare:QuoVadisConferenceThe Medical Association of Malta (MAM) and the newly-formed

Mediterranean Institute of Primary Care (MIPC) jointly collaborated in organising an International Conference entitled “Primary Health Care - Quo Vadis?” on May 24, 2008. The highly successful Conference was supported by sponsorship from Bial and involved doctors in all specialties, as well as medical policymakers, regulators and educators in a discussion about primary care in Malta and in other countries, and the strengths, weaknesses and opportunities in various models of primary health care. The Conference was opened by the MAM president Dr. Martin Balzan and was well attended by general practitioners across the island as well as by high-level Government officials. Among the guest speakers were H.E. President Emeritus Prof. Guido de Marco, the Hon. Dr Joseph Cassar, Parliamentary Secretary for Health and Dr Denis Vella Baldacchino, Director of Primary Health Care. Other guest speakers included Prof Frank Dobbs, University of Ulster, and Prof Henk Lamberts and Dr Inge Okkes, formerly of the University of Amsterdam. Streaming of Hon. Dr. Joseph Cassar’s speech can be found at www.mam.org. The Mediterranean Institute of Primary Care and the Medical Association of Malta plan to hold a second International Conference on primary care later this year.

Conference

Between ��% and 8�% of people in a general population require only primary-care services within a period of a year. The remaining proportion requires referral to secondary care for short-term consultation (perhaps 10-12%) or to a tertiary care specialist for unusual problems (�-10%). In Malta, ninety-five percent of episodes of care start and end in the family doctor’s office.� It is frustrating that many of the conditions resulting in preventable hospital admissions are ones which are

easily managed in the community setting. For example, diabetes and cardiovascular disease, which account for a significant proportion of preventable hospital admissions, can be successfully treated by GPs and a primary care team.

Thegate-keepingfunctionThe first-contact feature of primary

care implies that patients do not visit specialists without a recommendation from their primary-care practitioner.


ATACOR A4 1 4/29/08 9:46:53 AM


1. Modified from Institute of Medicine 1994. Committee on the Future of Primary Care, Division of Health Care Services. “Defining Primary Care: An Interim Report.” Institute of Medicine, 1994. & Starrfield B. Primary Care: Concept, Evaluation and Policy. New York: Oxford University Press; 1992.

2. Starfield B, Shi L, Macinko, J. Contribution of primary care to health systems and health. The Milbank Quarterly 200�: 8�(�):4��–�02.

In 200�, more than two-thirds of the 111,688 people attending the emergency department at Mater Dei went there without first consulting their family doctor.8 Since specialists are much greater users of tests and procedures, and since all such interventions have a finite risk of iatrogenic

complications (as well as a cost-inflating effect), the interposition of primary care is protective for patients in reducing both unnecessary procedures and adverse events. In many parts of the western world (particularly in the United States), the first-contact aspect of primary care is regarded

References

�. Atun R. What are the advantages and disadvantages of restructuring a health care system to be more focused on primary care services? Copenhagen, WHO Regional Office for Europe, 2004 (Health Evidence Network report; http://www.euro.who.int/document/e8299�.pdf, accessed 28 Nov 200�).

4. Mullan F. The “Mona Lisa” Of Health Policy: Primary Care At Home and Abroad. Health Affairs 1998: 1�.

�. Gervas J, Perez Fernandez M, Starfield B. Primary Care, financing and gate-keeping in Western Europe. Family Practice 1994: 11:�0�-1�.

6. Delnoji D et al. Does general practitioner gate-keeping curb health expenditure? Journal of Health Services Research and Policy 2000: �:22-26.

�. Okkes IM, Oskam SK, Lamberts H. ICPC in the Amsterdam Transition Project. CD-Rom. Amsterdam: Academic Medical Center/University of Amsterdam, Department of Family Medicine, 200�. Also downloadable at: www.transitieproject.nl.

8. Department of Information (http://www.doi.gov.mt/EN/press_releases/2008/0�/pr0��.asp, (accessed 28 May 2008).

9. Starfield B. Is primary care essential? The Lancet 1994 �44: 1129-��.


as a threat to free choice and therefore incompatible with a market (competitive) approach to the delivery of health services. A reasonable compromise might be to ensure free choice of primary-care source where there is a sufficient supply of primary-care personnel to permit choice.9


1. Type of manuscriptsThe Journal of the Malta College of Pharmacy

Practice publishes the following categories of papers in any field related to pharmacy:

a. Review articles/update papers. Manuscripts should not exceed 1�00 words (excluding references).

b. Continuing education papers. These should not exceed �000 words (excluding references). The authors should define 2-� educational aims per article. Authors should also provide 10 evaluation questions as true or false statements.

c. Papers pertaining to local/EU regulatory or policy issues. These papers should be brief and informative.

d. The Journal may accept original research papers. These should not exceed �000 words (excluding references).

e. The Journal may also publish other material which it deems to be of educational interest.

The authors are encouraged to use figures and tables, however these should not exceed � and the number of references should not exceed �0. Authors are encouraged to consult with the Editor-in-Chief if they require an exception to these limits.

Manuscripts will be reviewed by at least two anonymous independent referees. Authors may suggest names of expert reviewers or request that certain reviewers be excluded, however selection remains a prerogative of the Editors. Authors may include supplementary material to facilitate the review process. If a paper is cited in press and is required for evaluation of the submitted manuscript, authors should, upon request by the Editor-in-Chief, be able to provide three copies for use by the referees.

Manuscripts will be processed on the understanding that they have not been previously published in any language anywhere and are not under simultaneous consideration by another publisher. Authors are responsible for all statements in their work, including changes made by the copy editor prior to the final proof being accepted by the author.

2. Manuscript submissionManuscripts should be submitted by electronic

mail to email: [email protected] together with a covering letter from the corresponding author.

3. Copyright transfer and conflict of interest

A statement transferring copyright from the authors (or their employers, if they hold the copyright) to The Malta College of Pharmacy Practice will be required before the manuscript can be accepted for publication. The Editors will supply the necessary forms for this transfer.

Every author is responsible for disclosing any commercial or other association that might pose a conflict of interest related to the subject of the review. A statement to this effect is to be signed by each author on an appropriate form.

4. Permission for reproduction of tables and illustrations

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5. Organisation of manuscriptThe manuscript should be typed using 12pt font

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Authors must also include � practice/key points to emphasise important points that readers should remember.

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7. KeywordsA list of 4-6 key words for indexing purposes is to

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8. AbbreviationsAbbreviations should be used sparingly. A notation

section, listing all nonstandard abbreviations used, should be provided on a separate page before the references section. The metric system is to be used for all measurements. Metric abbreviations should be expressed in lowercase letters without periods (cm, ml). All symbols used in equations and formulae should be defined. When symbols are used extensively, a list of all symbols in the notation section should be included.

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Journalarticle

1. Author’s surname Author’s first name or initial. Title of article. Title of the Journal Year of publication; Volume Number (Issue number): Page numbers of article.

2. Withrow R, Roberts L. The videodisc: Putting education on a silver platter. Electronic Learning 198�: 1(�):4�-4.

Book

1. Author’s surname Author’s first name or initial. Title of the Book. Edition [if not first]. Place of publication: Publisher’s name; Year of publication.

2. Groenewegen D. The Real Thing?: The Rock Music Industry and the Creation of Australian Images. Golden Square, Victoria: Moonlight Publishing; 199�.

Contributiontoabook

1. Author’s surname Author’s first name or initial. Title of chapter. In: Editor’s surname Editor’s first name or initial, editor. Title of the Book. Edition [if not first]. Place of publication: Publisher’s name; Year of publication.

2. Blaxter P. Social health and class inequalities. In: Carter C, Peel J, editors. Equalities and Inequalities in Health. 2nd ed. London: Academic Press; 19�6.

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absolutely necessary, footnotes should be denoted using symbols and should be typed at the bottom of the page to which they refer. Place a line above the footnote, so that it is set off from the text. Use the appropriate symbol for citation in the text.



Low

ers LD

L-C I

Raise

s HD

L-C

IR

ed

uce

s Trig

lycerid

es

CR

ESTO

R®...

(rosu

vastatin)

TH

E MO

ST EFFEC

TIV

ESTA

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FOR

LO

WER

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LDL-C

1-8

Ab

breviated

Prescribing

Information C

RESTOR

®Refer to the full Sum

mary of Prod

uct Characteristics b

efore prescrib

ing. P

resentatio

n:

Film-coated

tablets containing

5mg

, 10mg

, 20mg

,or 40m

g of rosuvastatin. Ind

ications: In patients unresp

onsive to diet and

other non-pharm

acological m

easures, CRESTO

R is indicated

for prim

ary hypercholesterolaem

ia (including

heterozygous fam

ilial hyper cholesterolaem

ia), homozyg

ous familial hyp

ercholesterolaemia, or m

ixed d

yslipid

aemia. D

osag

e:The recom

mend

ed start d

ose is 5 or 10 mg

daily (includ

ingthose b

eing sw

itched from

other statins). The choice of start dose should

take into account the individ

ual patient’s

cholesterol level and future card

iovascular risk as well as the p

otential riskfor ad

verse reactions. A d

ose adjustm

ent to the next dose level can b

e mad

e after 4 weeks, if necessary. The m

aximum

daily d

ose is 40mg

. A final titration to the m

aximum

dose of 40 m

gshould

only be consid

ered in p

atients with severe hyp

ercholesterolaemia at hig

h cardiovascular risk (in p

articular those with fam

ilial hypercholesterolaem

ia), who d

o not achieve theirtreatm

ent goal on 20 m

g, and

in whom

routine follow-up

will b

e perform

ed. Sp

ecialist supervision is recom

mend

ed w

hen the 40 mg

dose is initiated

. Doses m

ay be g

iven at any time of

the day w

ith or without food

. Elderly:A

start dose of 5 m

g is recom

mend

ed in p

atients >70 years. No other d

ose adjustm

ent is necessaryin relation to ag

e. Dosage in patients w

ith renalinsufficiency:The recom

mend

ed start d

ose is 5 mg

in patients w

ith mod

erate renal imp

airment (creatinine clearance <60 m

l/min). The 40 m

g d

ose is contraindicated

in patients w

ith mod

eraterenal im

pairm

ent. The use of Crestor in p

atients with severe renal im

pairm

ent is contraindicated

for all doses. C

hildren: Safety and efficacy have not b

een established

. Race:Increased system

icexp

osure in Asian sub

jects. Recomm

ended

starting d

ose 5mg

. Crestor 40m

g is contraind

icated in such p

atients. Dosage in patients w

ith pre-disposing factors to myopathy:The recom

mend

edstart d

ose is 5 mg

in these patients. The 40 m

g d

ose is contraindicated

in some of these p

atients (see Contraind

ications). Con

tra-ind

ication

s:H

ypersensitivity to any of the ing

redients;

active liver disease or unexp

lained p

ersistent elevations in serum transam

inases and any serum

transaminase > 3 x up

per lim

it of normal; severe renal im

pairm

ent; myop

athy; concomitant

ciclosporin; p

regnancy and

breast-feed

ing; w

omen of child

-bearing

potential not using

contraception. In ad

dition C

restor 40mg

is contraindicated

with concom

itant fibrates, and

in patients

with p

redisp

osing factors for m

yopathy /rhab

dom

yolysis (refer to SPC). W

arnin

gs an

d p

recautio

ns:

Renal effects:Proteinuria w

hich in most cases d

ecreases or disap

pears sp

ontaneouslyon continued

therapy – a causal relationship

to Crestor has not b

een established

. An assessm

ent of renal function should b

e considered

during

routine follow-up

of patients treated

with

CRESTO

R 40 mg

. Haem

aturia has been ob

served very rarely. M

uscle effects:Patients with sig

ns and sym

ptom

s of myop

athy should b

e asked to rep

ort their symp

toms im

med

iately and should

have their creatine kinase (CK

) levels monitored

. CRESTO

R should b

e discontinued

if CK

levels are marked

ly elevated or, if m

uscle symp

toms are severe and

cause daily d

iscomfort. Risk of

myositis and

myop

athy may increase w

hen adm

inistered w

ith certain other drug

s, comb

ination of CRESTO

R with g

emfib

rozil is not recomm

ended

for this reason and the b

enefit versus risk

considered

when com

bining

Crestor w

ith fibrates and

niacin. Very rare cases of rhabd

omyolysis have b

een reported

with the use of ezetim

ibe and

HM

G-C

oA red

uctase inhibitors. C

RESTOR,

as with other H

MG

-CoA

reductase inhib

itors, should b

e prescrib

ed w

ith caution in patients w

ith pre-d

isposing

factors for myop

athy or rhabd

omyolysis. C

RESTOR should

not be used

inp

atients with an acute, serious cond

ition sugg

estive of myop

athy or pred

isposing

to the develop

ment of renal failure second

aryto rhab

dom

yolysis. Rarely ,rhab

dom

yolysis, occasionallyassociated

with im

pairm

ent of renal function has been rep

orted w

ith all doses and

in particular d

oses >20mg

. Liver effects:C

RESTOR should

be used

with caution in p

atients with a history

of liver disease and

/or alcoholism. Liver function tests should

be carried

out, prior to, and

3 months follow

ing the initiation of treatm

ent. CRESTO

R should b

e discontinued

or the dose red

ucedif the level of serum

transaminases is g

reater than 3-times the up

per lim

it of normal. The rep

orting rate of serious hep

atic events is higher at the 40m

g d

ose. The concomitant use of

rosuvastatin in HIV

patients receiving

protease inhib

itors is not recomm

ended

. Preg

nan

cy and

lactation

:C

RESTOR is contraind

icated in p

regnancy and

lactation. Drug

interactions:C

RESTOR is neither an inhib

itor nor inducer of cytochrom

e P450 isoenzymes. C

RESTOR m

ay potentiate the anticoag

ulant effect of Vitam

in K antag

onists (e.g. w

arfarin). Decrease in C

RESTOR

levels seen when co-ad

ministered

with erythrom

ycin or antacids containing

aluminium

and m

agnesium

hydroxid

e. Increase in oral contraceptive level and

hormone rep

lacement therap

ylevel is seen w

hen co-adm

inistered w

ith CRESTO

R. Concom

itant use of CRESTO

R and g

emifib

rozil resulted in a 2-fold

increase in rosuvastatin Cm

ax. Concom

itant use of Crestor and

ezetimib

eresulted

in no change in A

UC

or Cm

ax for either drug

; however a p

harmacod

ynamic interaction in term

s of adverse events cannot b

e ruled out. Protease inhib

itors. Un

desirab

le effects:C

omm

on: headache, d

izziness, constipation, nausea, ab

dom

inal pain, m

yalgia, and

asthenia. Uncom

mon: p

ruritus, rash and urticaria. Rare: m

yopathy,

rhabd

omyolysis, hyp

ersensitivityreactions includ

ing ang

iodem

a, increased hep

atic transaminases, p

ancreatitis. Very rare: jaundice, hepatitis, haematuria, polyneuropathy and m

emory loss and arthralgia. O

ther usuallytransient side effects: elevation in C

K levels, proteinuria. Legal C

ategory:PO

M. M

arketin

g A

uth

orisatio

n N

um

ber (s):PA

970/57/1-4. Mark

eting

Au

thorisatio

n H

old

er:AstraZ

enecaU

K Ltd, 600 Capability G

reen, Luton, LU1 3LU

, UK. Further inform

ation is available on request from: A

straZeneca Pharm

aceuticals (Ireland) Ltd., College Park H

ouse,20 Nassau Street, D

ublin

2Telep

hone: (01) 6097100; Up

dated

04/08 Crestor is a trad

emark of the A

straZeneca g

roup of com

panies. Licensed

from Shionog

i & C

o Ltd, O

saka, Japan. U

RN

no.

08/0361. Date o

fPrep

aration

:M

ay 2008. Referen

ces: 1. Jones PH, D

avidson MH

, Stein EA et al. A

m J C

ardiol 2003; 92 (2): 152-160. 2. Schuster H, Barter P ,

Stender S et al. Am

Heart J 2004; 147 (4): 705-

712. 3. Ballantyne C et al. A

m H

eart J 2006; 151 (5):975.e1-975.e9. 4. Faergeman O

et al. Atheroscler Suppl 2006; 7(3):580, A

bs Th-P16394. 5. Clearfield M

et al. Atheroscler Suppl 2005;

6(1), Abs W

16-p-014:104. 6. Leiter LA et al. Eur H

eart Journal 2005; 26(1):581 Abs P3503; 7. Blasetto JW

, Stein EA, Brow

n WV et al. A

m J C

ardiol 2003; 91(Suppl): 3C-10C

; 8. Crestor Sm

PC.

CV/CRE/�9/08/Adv

Documents

Journal of the Malta College of Pharmacy Practice · Isabel Stabile, Jean Karl Soler 50. 2 Journal of the Malta College of Pharmacy Practice Issue 14 Summer 2008 Hypertension - Coronary