MIGRAINE RELIEF 342 MG TABLETS PL 12063/0071 · PDF fileMIGRAINE RELIEF 342 MG TABLETS PL 12063/0071 UKPAR TABLE OF CONTENTS Lay Summary ... A description and flow-chart of the manufacturing

UKPAR Migraine Relief 342mgTablets PL 12063/0071

1

MIGRAINE RELIEF 342 MG TABLETS PL 12063/0071

UKPAR

TABLE OF CONTENTS Lay Summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

Page 12

Steps taken after authorisation – summary

Page 13

Summary of Product Characteristics Page 14

Product Information Leaflet

Page 21

Labelling Page 27


2


LAY SUMMARY The MHRA granted Wrafton Laboratories Limited a Marketing Authorisation (licence) for the medicinal product Migraine Relief 342 mg Tablets (PL 12063/0071). This is a General Sales List medicine (GSL) used to relieve pain from headaches and migraines.

Migraine Relief Tablets contain the active ingredient Ibuprofen Lysinate which belongs to a group of medicines known as non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs provide relief by changing the body’s response to pain, swelling and high temperature.

The test product was considered the same as the reference product Nurofen Migraine Pain (Crookes Healthcare Ltd) based on the bioequivalence study submitted and no new safety issues arose as a result of this study. No new or unexpected safety concerns arose from this application and it was therefore judged that the benefits of taking Migraine Relief 342 mg Tablets outweigh the risks; hence Marketing Authorisations have been granted.


3


SCIENTIFIC DISCUSSION

TABLE OF CONTENTS Introduction

Page 4

Pharmaceutical assessment

Page 5

Preclinical assessment

Page 7

Clinical assessment (including statistical assessment)

Page 8

Overall conclusions and risk benefit assessment Page 11


4

INTRODUCTION Based on the review of the data on quality, safety and efficacy, the UK granted a marketing authorisation for the medicinal product Migraine Relief 342 mg Tablets (PL 12063/0071) on 16th April 2007. The product is a General Sales List (GSL) medicine. The application was submitted as an abridged application according to Article 10.1 of Directive 2001/83/EC, as amended, and has been shown to be a generic medicinal product of the reference product Nurofen Migraine Pain (PL 00327/0125) granted to Crookes Healthcare Ltd on 27th July 2000. This product in turn demonstrated equivalence to the innovator product, Dolormin Migraene Zeepfchen Tablets, authorised in Germany in November 1989 and as such the 10-year period of data exclusivity has now expired.

The product contains the active ingredient ibuprofen lysinate. The mode of action is believed to be through the inhibition of cyclooxygenase (COX), thus inhibiting prostaglandin synthesis. There are at least 2 variants of cyclooxygenase (COX-1 and COX-2). Ibuprofen lysinate inhibits both COX-1 and COX-2. It appears that it’s analgesic, antipyretic and anti-inflammatory activities are achieved principally through COX-2 inhibition.


5

PHARMACEUTICAL ASSESSMENT

DRUG SUBSTANCE

Ibuprofen Lysinate INN: Ibuprofen Lysinate

Chemical Name: Lysine salt of 2(4-isobutylphenyl)propionic acid CAS No: 57469-76-8 Molecular formula: C19H32N2O4 Molecular weight: 352.48 Physical form: White powder Solubility: It is soluble in water (1%w/v) and in methanol (1%w/v). Ibuprofen Lysinate is not known to exhibit polymorphism. An appropriate in-house specification has been provided and is found to be satisfactory. Analytical methods have been appropriately validated and are satisfactory for ensuring compliance with the relevant specifications. Active ibuprofen lysinate is stored in appropriate packaging. The specifications and typical analytical test reports are provided and are satisfactory. Batch analysis data are provided for three production batches and comply with the proposed specification. Satisfactory certificates of analysis have been provided for working standards used by the active substance manufacturer and finished product manufacturer during validation studies. Appropriate stability data have been generated supporting a retest period of 24 months, with no specific storage instructions.

DRUG PRODUCT Other ingredients Other ingredients consist of pharmaceutical excipients, namely crospovidone, copovidone magnesium stearate, microcrystalline cellulose and opadry II white. All excipients used comply with their respective European Pharmacopoeial monograph, with the exception of opadry II white which complies with an in-house specification and this is acceptable. Satisfactory certificates of analysis have been provided for all excipients. None of the excipients used contain material of animal or human origin. There were no novel excipients used and no overages. Dissolution and impurity profiles Dissolution and impurity profiles of drug product were found to be similar to those for the reference product.


6

Manufacture A description and flow-chart of the manufacturing method has been provided. In-process controls are appropriate considering the nature of the product and the method of manufacture. Process validation has been carried out on three batches. The results are satisfactory. Finished product specification The finished product specification is satisfactory. Acceptance limits have been justified with respect to conventional pharmaceutical requirements and, where appropriate, safety. Test methods have been described and have been adequately validated, as appropriate. Batch data have been provided and comply with the release specification. Certificates of analysis have been provided for any working standards used. Container Closure System Product is packaged in either white opaque PVC/PVdC blisters with aluminium foil; or white opaque triplex blisters with aluminium foil, both types of blisters are packed in cardboard cartons. Specifications and certificates of analysis for all packaging types used have been provided. These are satisfactory. All primary product packaging complies with EU legislation regarding contact with food. The product is packaged in sizes of 12 tablets for both types of blister packs. Stability Finished product stability studies have been conducted in accordance with current guidelines. Based on the results, a shelf-life of 3 years has been set, which is satisfactory. There are no special storage conditions require for this medicinal product and this is satisfactory. Patient Information Leaflet This is satisfactory and is consistent with the reference product. The marketing authorisation holder has provided a commitment to update the marketing authorisation with a package leaflet in compliance with Article 59 of Council Directive 2001/83/EC and that the leaflet shall reflect the results of consultation with target patient groups, no later than 1st July 2008. Conclusion A Marketing Authorisation was granted for this application.


7

PRECLINICAL ASSESSMENT No new preclinical data have been supplied with these applications and none are required for an application of this type.


8

CLINICAL ASSESSMENT

INTRODUCTION AND BACKGROUND This application is an abridged application for Migraine Relief 342mg Tablets submitted under Article 10.1 of Directive 2001/83/EC, as amended. The application cross-refers to Nurofen Migraine Pain (PL 00327/0125) granted to Crookes Healthcare Ltd in July 2000. INDICATIONS For the relief of headache and migraine pain.

The indications proposed are consistent with those for the cross- reference product and is therefore satisfactory.

DOSE & DOSE SCHEDULE For oral administration and short-term use only.

Adults, elderly and children over 12 years: Initial dose, one or two tablets, to be taken with water then if necessary, one or two tablets every four hours.

Do not exceed six tablets in any 24 hours.

Leave at least 4 hours between doses

Not recommended for children under 12 years of age.

Consult your doctor if symptoms persist or worsen, or if the product is required for more than 10 days.

CLINICAL PHARMACOLOGY PHARMACODYNAMIC PROPERTIES ATC code: MO1A

Ibuprofen lysine is the lysine salt of ibuprofen. Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans ibuprofen reduces inflammatory pain, swellings and fever.

Furthermore, Ibuprofen reversibly inhibits platelet aggregation.

PHARMACOKINETIC PROPERTIES

Most pharmacokinetic data obtained following the administration of ibuprofen acid also apply to ibuprofen lysine.

Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is both rapid and complete via the kidneys.

Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak levels are observed after 1 – 2 hours. These times may vary with different dosage forms.

The half life of Ibuprofen is about two hours.

In limited studies, Ibuprofen appears in the breast milk in very low concentrations


9

BIOEQUIVALENCE/BIOAVILABILITY A bioequivalence study was carried out, and the test and reference products shown to be bioequivalent (within the customary 90% confidence intervals) for the appropriate pharmacokinetic criteria. Ibuprofen is rapidly and almost completely absorbed when administered orally. The lysine salt is absorbed somewhat faster than the free acid with a time to peak serum level generally within one hour. With single, oral, solid doses up to 800mg, in adults, a linear relationship exists between the amount of drug administered and the integrated area under the plasma drug concentration vs. time curve. Above 800mg, however, the area under the curve increase is less than proportional to the increase in dose. Food does not affect the extent of absorption of Ibuprofen, however, the maximum concentration (Cmax) is reduced and the time to maximum concentration (tmax) is prolonged if Ibuprofen is taken with food. One bioequivalence study has been conducted in support of this application: an open label, laboratory blind, single dose, randomised, two way crossover study comparing the bioavailability of the proposed Migraine Relief Caplets product with Nurofen Migraine Pain in male and female subjects. Satisfactory certificates of analysis have been provided for the test and reference batches. More than an average of 70% of ibuprofen is released from each test and reference batch within 40 minutes in the dissolution test. Test product: Ibuprofen Lysine tablet, Wrafton Laboratories Ltd., UK) Reference product: Nurofen Migraine Pain, Crookes Healthcare, Nottingham, UK) Table 4: Bioavailability results (geometric means) from an open label, laboratory blind, single dose, randomised, two way crossover study comparing the bioavailability of the proposed Migraine Relief Caplets product with Nurofen Migraine Pain in male and female subjects. Ln transformed; ANOVA, with a washout period of at least 7 days.

Test parameter Test product

Reference product

Point estimate Test/reference

90% confidence intervals (%)

Single dose (day 1) fasted:

AUC0-∞ (µg h/ml) 67.15 68.01 98.73 92.66 - 105.21 AUC0-t (µg h/ml) 64.67 65.65 98.50 92.29 - 105.13 Cmax (µg/ml) 25.83 24.34 106.14 92.19 - 122.21 Cmax (µg/ml) outlier excluded*

99.08 91.67 - 107.09

*Volunteer 0110403 was excluded from the analysis as a statistical outlier For the comparison Test product vs Reference product the 90% t-confidence interval of the ln-transformed data for Cmax was 92.19% - 122.21%, indicating bioequivalence for the rate of ibuprofen absorption within the acceptance limits 80% - 125%. The 90% t-confidence intervals of the ln-transformed data for AUC0-t and AUC0-∞ were 92.29% - 105.13% and 92.66% - 105.21% respectively, indicating bioequivalence for the extent of ibuprofen absorption within the acceptance limits of


10

80% - 125% with adequate statistical power. It can be expected that these formulations will behave similarly in therapeutic use. The analytical method used to analyse the plasma samples from the subjects involves the extraction of Ibuprofen and internal standard Indometacin from plasma with ether:hexane. Extracts were reconstituted with mobile phase and the HPLC system (λ=220nm). The precision at the LOQ, defined by the % coefficient of variation(%CV) was 1.60%. The accuracy at the LOQ ranged from 106.40% to 111.40%. The mean % accuracy at the LOQ was 109.45%. The method has been validated. EFFICACY No new data on the efficacy of ibuprofen lysinate are submitted and none are required for this type of application.

SAFETY No new data on the efficacy of ibuprofen lysinate are submitted and none are required for this type of application.

EXPERT REPORT The expert report is written by a suitably person and is satisfactory. SUMMARY OF PRODUCT CHARACTERISTICS This is satisfactory.

PATIENT INFORMATION LEAFLET This is satisfactory. CONCLUSIONS The applicant appears to have demonstrated bioequivalence. A marketing authorisation should be granted for this product.


11

OVERALL CONCLUSION AND RISK BENEFIT ASSESSMENT QUALITY The important quality characteristics of Migraine Relief 342mg Tablets are well defined and controlled. The specifications and batch analytical results indicate consistency from batch to batch. There are no outstanding quality issues that would have a negative impact on the benefit/risk balance. PRECLINICAL No new preclinical data were submitted and none are required for applications of this type. EFFICACY Ibuprofen Lysinate is a well known drug and has been used in the relief of headaches and migraine pain for many years. Bioequivalence has been demonstrated between the applicant’s Migraine Relief 342mg Tablets and Nurofen Migraine Pain (Crookes Healthcare Ltd. No new or unexpected safety concerns arise from these applications.

The SPC, PIL and labelling are satisfactory and consistent with that for Nurofen Migraine Pain. RISK BENEFIT ASSESSMENT The quality of the product is acceptable and no new preclinical or clinical safety concerns have been identified. The bioequivalence study supports the claim that the applicant’s product and the cross- reference product are interchangeable. Extensive clinical experience with ibuprofen lysinate is considered to have demonstrated the therapeutic value of the compound. The risk benefit is, therefore, considered to be positive.


12


STEPS TAKEN FOR ASSESMENT

1 The MHRA received the marketing authorisation applications on 31st March

2005.

2 Following standard checks and communication with the applicant the MHRA considered the applications valid on 16th September 2005.

3 Following assessment of the applications the MHRA requested further information relating to the quality dossiers on 6th December 2005, 12th April 2006 and 12th October 2006.

4 The applicant responded to the MHRA’s requests, providing further information on 24th January 2006, 28th July 2006 and 1st December 2006 for the quality sections.

5 The applications were determined on 16th April 2007.


13


STEPS TAKEN AFTER AUTHORISATION - SUMMARY

Date submitted

Application type

Scope Outcome

25/05/2007 Patient Information Leaflet

To add Morrison Supermarkets PLC as an own label supplier

Approved on 26/07/2007


14

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT Paramed Migraine Relief 342mg Tablets

Superdrug Migraine Relief 342mg Tablets

Sainsbury’s Migraine Relief 342mg Tablets

Boots Headache & Migraine 342mg Tablets

Morrisons Migraine Relief 342mg Tablets

Tesco Migraine Relief 342mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

200mg Ibuprofen (as Ibuprofen Lysine 342 mg)

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet. White, capsule - shaped tablet.

4 CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS

For the relief of headache and migraine pain.

4.2 POSOLOGY AND METHOD OF ADMINISTRATION

For oral administration and short-term use only.

Adults, elderly and children over 12 years: Initial dose, one or two tablets, to be taken with water then if necessary, one or two tablets every four hours.

Do not exceed six tablets in any 24 hours.

Leave at least 4 hours between doses

Not recommended for children under 12 years of age.

Consult your doctor if symptoms persist or worsen, or if the product is required for more than 10 days.

4.3 CONTRAINDICATIONS

Hypersensitivity to Ibuprofen or any of the constituents of the product. Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) associated with aspirin or other non-steroidal anti-inflammatory drugs. Patients with a history of, or existing peptic ulceration. History of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors (see Section 4.5 Interactions). Severe hepatic failure, renal failure or heart failure (see Section 4.4 Special warnings and precautions for use). Last trimester of pregnancy (see Section 4.6 Pregnancy and lactation)


15

4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease. Undesirable effects may be minimised by using the minimum effective dose for the shortest possible duration. The elderly are at increased risk of the serious consequences of adverse reactions. Systemic lupus erythematosus and mixed connective tissue disease - increased risk of aseptic meningitis (see section 4.8 Undesirable effects). Chronic inflammatory intestinal disease (ulcerative colitis, Crohn’s disease) – as these conditions may be exacerbated (See section 4.8 Undesirable effects). Hypertension and/or cardiac impairment as renal function may deteriorate and/or fluid retention occur. Renal impairment as renal function may further deteriorate (See section 4.3 Contraindications and Section 4.8 Undesirable effects)

Hepatic dysfunction (See section 4.3 Contraindications and Section 4.8 Undesirable effects)

There is limited evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.

Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events.

Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of gastrotoxicity or bleeding, such as corticosteroids, or anticoagulants such as warfarin or anti-platelet agents such as aspirin (see section 4.5 Interactions).

When gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see GI and cardiovascular risks below).

Cardiovascular and cerebrovascular effects

Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high doses (2400mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. ≤ 1200mg daily) is associated with an increased risk of myocardial infarction.


16

The label will include:

Please read the enclosed leaflet before taking this product.

Do not take if you:

• have or have ever had a stomach ulcer, perforation or bleeding

• are allergic to ibuprofen or any of the other ingredient of the product, aspirin or otherrelated painkillers

• are taking other NSAID painkillers, or aspirin, with a daily dose above 75 mg.

• are in the last 3 months of pregnancy.

Speak to a pharmacist or your doctor before taking this product if you

• Have asthma, liver, heart, kidney or bowel problems

• Are in the first 6 months of pregnancy

If symptoms persist or worsen, consult your doctor.

4.5 INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF

INTERACTION Ibuprofen should not be used in combination with:

Aspirin: Unless low-dose aspirin (not above 75mg daily) has been advised by a doctor, as this may increase the risk of adverse reactions (See section 4.3 Contraindications). Other NSAIDS: As these may increase the risk of adverse effects (See section 4.3 Contraindications). Ibuprofen should be used with caution in combination with: Anticoagulants: NSAIDS may enhance the effects of anti-coagulants, such as warfarin (See section 4.4). Antihypertensives and diuretics: NSAIDs may diminish the effect of these drugs. Corticosteroids: May increase the risk of adverse reactions in the gastrointestinal tract (See section 4.4 Special warnings). Lithium: There is evidence for potential increases in plasma levels of lithium.

Methotrexate: There is a potential for an increase in plasma methotrexate.

Zidovudine:

There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

4.6 PREGNANCY AND LACTATION

Whilst no teratogenic effects have been demonstrated in animal studies, the use of Migraine Relief Caplets should, if possible, be avoided during the first six months of pregnancy.


17

During the third trimester, Ibuprofen is contraindicated as there is a risk of premature closure of the foetal ductus arteriosus with possible persistent pulmonary hypertension. The onset of labour may be delayed and duration of labour increased with an increased bleeding tendency in both mother and child (see Section 4.3 – Contraindications).

In limited studies, Ibuprofen appears in breast milk in very low concentration and is unlikely to affect the breast fed infant adversely.

See Section 4.4 regarding female fertility.

4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

None expected at recommended doses and duration of therapy.

4.8 UNDESIRABLE EFFECTS Hypersensitivity reactions have been reported and these may consist of:

(a) Non-specific allergic reactions and anaphylaxis

(b) Respiratory tract reactivity, eg asthma, aggravated asthma, bronchospasm, dyspnoea

(c) Various skin reactions, e.g. pruritus, urticaria, angioedema and more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme)

The following list of adverse effects relates to those experienced with ibuprofen at OTC doses, for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.

Hypersensitivity reactions:

Uncommon: Hypersensitivity reactions with urticaria and pruritus.

Very rare: Severe hypersensitivity reactions. Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).

Exacerbation of asthma and bronchospasm.

Gastrointestinal:

Uncommon: Abdominal pain, nausea and dyspepsia.

Rare: Diarrhoea, flatulence, constipation and vomiting.

Very rare: Peptic ulcer, perforation or gastrointestinal haemorrhage, sometimes fatal, particularly in the elderly. Exacerbation of ulcerative colitis and Crohn’s disease (See section 4.4).

Nervous System:

Uncommon: Headache

Renal:

Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum urea and oedema.

Hepatic:

Very rare: Liver disorders.

Haematological:

Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

Skin:

Uncommon: Various skin rashes


18

Very rare: Severe forms of skin reactions such as erythema multiforme and epidermal necrolysis can occur.

Immune System:

In patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis, such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed (See section 4.4)

Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.

Clinical trial and epidemiological data suggest that use of ibuprofen (particularly at high doses 2400mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

4.9 OVERDOSE

In children ingestion of more than 400 mg/kg may cause symptoms. In adults the dose response effect is less clear cut. The half-life in overdose is 1.5-3 hours.

Symptoms

Most patients who have ingested clinically important amounts of NSAIDs will develop no more than nausea, vomiting, epigastric pain, or more rarely diarrhoea. Tinnitus, headache and gastrointestinal bleeding are also possible. In more serious poisoning, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation and disorientation or coma. Occasionally patients develop convulsions. In serious poisoning metabolic acidosis may occur and the prothrombin time/ INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur. Exacerbation of asthma is possible in asthmatics.

Management

Management should be symptomatic and supportive and include the maintainance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.

5 PHARMACOLOGICAL PROPERTIES 5.1 PHARMACODYNAMIC PROPERTIES

Ibuprofen lysine is the lysine salt of ibuprofen. Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans ibuprofen reduces inflammatory pain, swellings and fever.

Furthermore, Ibuprofen reversibly inhibits platelet aggregation.

ATC code: MO1A

5.2 PHARMACOKINETIC PROPERTIES

Most pharmacokinetic data obtained following the administration of ibuprofen acid also apply to ibuprofen lysine.

Ibuprofen is rapidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is both rapid and complete via the kidneys.


19

Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak levels are observed after 1 – 2 hours. These times may vary with different dosage forms.

The half life of Ibuprofen is about two hours.

In limited studies, Ibuprofen appears in the breast milk in very low concentrations

5.3 PRECLINICAL SAFETY DATA

No relevant information additional to that contained elsewhere within the SmPC.

6 PHARMACEUTICAL PARTICULARS 6.1 LIST OF EXCIPIENTS

Core

Crospovidone

Copovidone

Microcrystalline Cellulose

Magnesium Stearate

Coat

Opadry II White*

* Contains the constituents; polyvinyl alcohol, titanium dioxide, macrogol and talc.

6.2 INCOMPATIBILITIES

Not applicable

6.3 SHELF LIFE

36 months

6.4 SPECIAL PRECAUTIONS FOR STORAGE

This medicinal product does not require any special storage conditions.

6.5 NATURE AND CONTENTS OF CONTAINER

A blister pack consisting of white opaque PVC/PVdC blister with aluminium foil. The blisters are packed in cardboard cartons.

Or

A blister pack consisting of white opaque triplex blister with aluminium foil.

The blisters are packed in cardboard cartons.

Pack sizes: 12 tablets

6.6 SPECIAL PRECAUTIONS FOR DISPOSAL

Not applicable.

7 MARKETING AUTHORISATION HOLDER

Wrafton Laboratories Ltd Wrafton Braunton Devon EX33 2DL


20

8 MARKETING AUTHORISATION NUMBER(S)

12063/0071

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 16/04/2007 10 DATE OF REVISION OF THE TEXT

16/04/2007


21


PATIENT INFORMATION LEAFLET


22


23


24


25


26


27

MIGRAINE RELIEF 342 MG TABLETS

PL 12063/0071 LABELLING


28


29


30


31

Documents

MIGRAINE RELIEF 342 MG TABLETS PL 12063/0071 · PDF fileMIGRAINE RELIEF 342 MG TABLETS PL 12063/0071 UKPAR TABLE OF CONTENTS Lay Summary ... A description and flow-chart of the manufacturing