The topic of "drug safety in pregnancy" The topic of "drug safety in pregnancy" embraces the effect of drugs on the embraces the effect of drugs on the pregnancypregnancy, , foetusfoetus or or neonateneonate, and the , and the effects of the pregnancy on drug effects of the pregnancy on drug disposition. Almost all drugs cross the disposition. Almost all drugs cross the placenta to some extent and may pose placenta to some extent and may pose risk to the developing foetus. A few risk to the developing foetus. A few exceptions exist exceptions exist (e.g. insulin, heparin)(e.g. insulin, heparin) which are very large molecules that do which are very large molecules that do not cross biological membranes readilynot cross biological membranes readily

Drugs taken by a pregnant Drugs taken by a pregnant woman reach the fetus woman reach the fetus primarily by crossing the primarily by crossing the placenta, the same route taken placenta, the same route taken by oxygen and nutrients, which by oxygen and nutrients, which are needed for the fetus's are needed for the fetus's growth and development. Drugs growth and development. Drugs that a pregnant woman takes that a pregnant woman takes during pregnancy can affect the during pregnancy can affect the fetus in several waysfetus in several ways

**They can act directly on the fetus, causing They can act directly on the fetus, causing damage, abnormal development (leading damage, abnormal development (leading to birth defects), or deathto birth defects), or death..

**They can alter the function of the placenta, They can alter the function of the placenta, usually by causing blood vessels to narrow usually by causing blood vessels to narrow (constrict) and thus reducing the supply of (constrict) and thus reducing the supply of oxygen and nutrients to the fetus from the oxygen and nutrients to the fetus from the mother. Sometimes the result is a baby mother. Sometimes the result is a baby that is underweight and underdevelopedthat is underweight and underdeveloped . .

**They can cause the muscles of the uterus They can cause the muscles of the uterus to contract forcefully, indirectly injuring to contract forcefully, indirectly injuring the fetus by reducing its blood supply or the fetus by reducing its blood supply or triggering preterm labor and deliverytriggering preterm labor and delivery

•Some of the fetus's blood Some of the fetus's blood vessels are contained in tiny vessels are contained in tiny hairlike projections (villi) of the hairlike projections (villi) of the placenta that extend into the placenta that extend into the wall of the uterus. The mother's wall of the uterus. The mother's blood passes through the space blood passes through the space surrounding the villi (intervillous surrounding the villi (intervillous space). Only a thin membrane space). Only a thin membrane (placental membrane) separates (placental membrane) separates the mother's blood in the the mother's blood in the intervillous space from the intervillous space from the fetus's blood in the villi. Drugs in fetus's blood in the villi. Drugs in the mother's blood can cross this the mother's blood can cross this membrane into blood vessels in membrane into blood vessels in the villi and pass through the the villi and pass through the umbilical cord to the fetusumbilical cord to the fetus

The Food and Drug Administration (FDA) created the following rating system in 1979 to categorize the potential risk to

the fetus for a given drug  .Category A:    Controlled human studies have demonstrated no fetal risk Category B:    Animal studies indicate no fetal risk, but no human studies                        OR adverse effects in animals , but adequate studies in pregnant women have not demonstrated a risk to the fetus during the first trimester of pregnancy and there is no evidence of risk in the last two trimester

•Category C:    No adequate human or animal studies,                        OR adverse fetal effects in animal studies, but no available human data..The benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. Category D:    Evidence of fetal risk, but benefits outweigh risks. Category X:    Evidence of fetal risk. Risks outweigh any benefits

Hyperacidity, reflux, ulcersAlginates/antacids Category C

H2receptor antagonistCimetidine, famotidine, ranitidine ,

nizatidine Category B Proton pump inhibitorLansoprazole, Rabeprazole, pantoprazole Category B Except

omeprazole Category CAntispasmodicsAtropine ,hyoscine-N-

butylbromide(Buscopan) Category C

LaxativesLaxatives

LactuloseLactulose Category BCategory B

Bisacodyl Bisacodyl Category CCategory CAntidiarrhoeals

Diphenoxylate,LoperamideDiphenoxylate,Loperamide Category CCategory C

5Aminosalicylic acid Derivative5Aminosalicylic acid Derivative

Mesalazine ,SulfasalazineMesalazine ,Sulfasalazine Category BCategory B

AntihypertensivesAntihypertensivesMethyldopa Category B Sodium nitroprusside, Clonidine, Diazoxide Category C

Hydralazine Category C Following intravenous administration, hydralazine has been associated with fetal distress and fetal arrhythmia in the last trimester of pregnancy .

Calcium channel blockers Calcium channel blockers Category C

Angiotensin converting enzyme (ACE) inhibitors Angiotensin converting enzyme (ACE) inhibitors && Angiotensin II receptor antagonists (ARAs) Angiotensin II receptor antagonists (ARAs) Category D

These agents may cause pharmacological These agents may cause pharmacological effects such as bradycardia in the fetus and effects such as bradycardia in the fetus and newborn infantnewborn infant..

1--Non selective B1+B2 blockadeNon selective B1+B2 blockade: : Propranolol, Timolol (Propranolol, Timolol ( Category C 1st,D Category C 1st,D 2nd &3rd trimester2nd &3rd trimester) Sotalol ) Sotalol (Category B (Category B 1st,D 2nd &3rd trimester)1st,D 2nd &3rd trimester)

22--selective B1 Blockadeselective B1 Blockade: : atenolol Category atenolol Category DD, Metoprolol, esmolol,Bisoprolol, Metoprolol, esmolol,Bisoprolol (Category C 1st,D 2nd &3rd trimester)(Category C 1st,D 2nd &3rd trimester)

33--Non selective B+alpha1 blockadeNon selective B+alpha1 blockade Carvedilol,labetalol Carvedilol,labetalol ((Category C )Category C )

Carbonic anhydrase inhibitorCarbonic anhydrase inhibitorAcetazolamide Acetazolamide Category CCategory CThiazides, related diureticsThiazides, related diuretics : : Category DCategory D

loop diureticsloop diuretics:: Ethacrynic acid Ethacrynic acid BB, Bumetanide& , Bumetanide& Furosemide Furosemide CCThese drugs may cause electrolyte disturbances in These drugs may cause electrolyte disturbances in the fetus. Neonatal thrombocytopenia has been the fetus. Neonatal thrombocytopenia has been reported with thiazides and related diuretics. reported with thiazides and related diuretics. Loop diuretics, like frusemide and bumetanide, Loop diuretics, like frusemide and bumetanide,

are probably also associated with this riskare probably also associated with this risk . .Potassium sparing diureticsPotassium sparing diureticsAmiloride, triamterene Amiloride, triamterene Category BCategory BThese drugs may result in electrolyte These drugs may result in electrolyte disturbances in the fetusdisturbances in the fetus

LignocaineLignocaine Category BCategory BAdenosine, disopyramide, procainamide , Adenosine, disopyramide, procainamide ,

Flecainide, MexiletineFlecainide, Mexiletine Category CCategory CQuinidinQuinidine:This drug is structurally similar to quinine, e:This drug is structurally similar to quinine, which in high doses, has been shown to cause which in high doses, has been shown to cause fetal damage. It has been used to treat fetal fetal damage. It has been used to treat fetal cardiac arrhythmiacardiac arrhythmia Bretylium tosylateBretylium tosylate Category CCategory CThis drug carries the potential for fetal hypoxia This drug carries the potential for fetal hypoxia associated with maternal hypotensionassociated with maternal hypotension..

Glyceryl trinitrateGlyceryl trinitrate Category BCategory B

Isosorbide dinitrate, isosorbide mononitrate Isosorbide dinitrate, isosorbide mononitrate CategoryCategory C C

The physiological hyperlipidaemia of pregnancy The physiological hyperlipidaemia of pregnancy does not require treatmentdoes not require treatment..Cholestyramine,colestipol,Gemfibrozil,ClofibrateCholestyramine,colestipol,Gemfibrozil,Clofibrate

Category CCategory C

Cardiac inotropic agentsCardiac inotropic agentsDigoxin and other cardiac glycosides Digoxin and other cardiac glycosides Category CCategory C

Adrenergic stimulantAdrenergic stimulantterbutalineterbutaline Category BCategory B

Adrenaline, ephedrine, salbutamol, Dobutamine, Adrenaline, ephedrine, salbutamol, Dobutamine, phenylephrine, , pseudoephedrinephenylephrine, , pseudoephedrine

DopamineDopamine Category CCategory C

Dipyridamole, sildenafil citrateDipyridamole, sildenafil citrate Category B Category B ,,

Betahistine, isosorbide dinitrate, oxpentifylline, Betahistine, isosorbide dinitrate, oxpentifylline, phentolamine, phentolamine, Isoxsuprine Isoxsuprine Category CCategory CMaternal isoxsuprine administration for Maternal isoxsuprine administration for prevention of premature labour has been prevention of premature labour has been associated with tachycardia, hypoglycaemia, associated with tachycardia, hypoglycaemia, hypocalcaemia and hypotension in the hypocalcaemia and hypotension in the neonateneonate..

Antimigraine preparationsAntimigraine preparations

Naratriptan, sumatriptan, zolmitriptanNaratriptan, sumatriptan, zolmitriptan Category cCategory c

All of these agents can produce placental haemorrhage All of these agents can produce placental haemorrhage and subsequent prematurity and fetal lossand subsequent prematurity and fetal loss..Antiplatelet agentAntiplatelet agent,,Ticlopidine,Clopidogrel Ticlopidine,Clopidogrel Category Category B B

AbciximabAbciximab Category CCategory CLow molecular weight heparinLow molecular weight heparinDalteparin, danaparoid, enoxaparin, nadroparinDalteparin, danaparoid, enoxaparin, nadroparin , ,

Category BCategory BOtherOther Heparin Heparin Category CCategory C . .

tranexamic acid Category Ctranexamic acid Category C Fibrinolytic agentsFibrinolytic agents

Alteplase, urokinase ,ReteplaseAlteplase, urokinase ,Reteplase Category CCategory CStreptokinase Category CStreptokinase Category COnly minimal amounts of streptokinase cross the Only minimal amounts of streptokinase cross the placenta. Streptokinase-specific antibodies are placenta. Streptokinase-specific antibodies are found in fetal bloodfound in fetal blood

Analgesics, antipyreticsAnalgesics, antipyreticsNSAIDSNSAIDS Paracetamol category BParacetamol category Bpiroxicam ibuprofen, indomethacin B in 1ST tri, D 3rd tripiroxicam ibuprofen, indomethacin B in 1ST tri, D 3rd triDiclofenac,ketoprofen, ketorolac, mefenamic acid, naproxen , Diclofenac,ketoprofen, ketorolac, mefenamic acid, naproxen , celecoxib ,Meloxicom, Aspirin celecoxib ,Meloxicom, Aspirin Category CCategory C/D3RD tri/D3RD triThese agents inhibit prostaglandin synthesis and, when given These agents inhibit prostaglandin synthesis and, when given during the latter part of pregnancy, may cause closure of the during the latter part of pregnancy, may cause closure of the fetal ductus arteriosus, fetal renal impairment, inhibition of fetal ductus arteriosus, fetal renal impairment, inhibition of platelet aggregation, and delay labour and birth. Continuous platelet aggregation, and delay labour and birth. Continuous treatment with NSAIDs during the last trimester of pregnancy treatment with NSAIDs during the last trimester of pregnancy should only be given on sound indications. During the last few should only be given on sound indications. During the last few days before expected birth, agents with an inhibitory effect on days before expected birth, agents with an inhibitory effect on prostaglandin synthesis should be avoidedprostaglandin synthesis should be avoided..Opioid analgesicsOpioid analgesicsOpioid analgesics may cause respiratory depression in the Opioid analgesics may cause respiratory depression in the newborn infant. Withdrawal symptoms in newborn infants newborn infant. Withdrawal symptoms in newborn infants have been reported with prolonged use of this class of drugshave been reported with prolonged use of this class of drugs . .

Fentanyl,morphineFentanyl,morphine,, pethidine,tramadol ,Codeine pethidine,tramadol ,CodeineCategory CCategory C

Hypnotics and sedativesHypnotics and sedativesBarbiturates & Benzodiazepines : Barbiturates & Benzodiazepines : Category DCategory D

Antipsychotic agentsAntipsychotic agentsPhenothiazines (Phenothiazines (Chlorpromazine, trifluoperazine Chlorpromazine, trifluoperazine Category CCategory C))Butyrophenones Butyrophenones (( haloperidol haloperidol Category CCategory C))

When given these in high doses during late pregnancy have When given these in high doses during late pregnancy have caused prolonged neurological disturbances in the newborn caused prolonged neurological disturbances in the newborn infant infant AntidepressantsAntidepressantsSelective serotonin reuptake inhibitors (SSRIsSelective serotonin reuptake inhibitors (SSRIs))

FluoxetineCategory CFluoxetineCategory C Monoamine oxidase inhibitorMonoamine oxidase inhibitorphenelizineCategory CphenelizineCategory CCNS stimulantsCNS stimulants

Caffeine Category CCaffeine Category C Antiparkinson agentsAntiparkinson agents

Amantadine, carbidopa, levodopa, selegiline CategoryAmantadine, carbidopa, levodopa, selegiline Category C C

The risk of having an abnormal child as a result of The risk of having an abnormal child as a result of antiepileptic medication is far outweighed by the dangers antiepileptic medication is far outweighed by the dangers to the mother and fetus of uncontrolled epilepsyto the mother and fetus of uncontrolled epilepsy..It is recommended thatIt is recommended that::

**womenwomen on antiepileptic drugs (AEDs) receive prepregnancy on antiepileptic drugs (AEDs) receive prepregnancy counselling with regard to the risk of fetal abnormalitiescounselling with regard to the risk of fetal abnormalities ; ;

**AEDAEDs should be continued during pregnancy and s should be continued during pregnancy and monotherapy should be used if possible at the lowest monotherapy should be used if possible at the lowest effective dose as risk of abnormality is greater in women effective dose as risk of abnormality is greater in women taking combined medicationtaking combined medication ; ;

**folic acid supplementationfolic acid supplementation (5mg) should be commenced (5mg) should be commenced four weeks prior to and continue for twelve weeks after four weeks prior to and continue for twelve weeks after conceptionconception ; ;

((Carbamazepine,phenytoin,sodium valeproate Carbamazepine,phenytoin,sodium valeproate Category DCategory D))GabapentinGabapentin Category CCategory C

Dimenhydrinate, diphenhydramine, Dimenhydrinate, diphenhydramine, metoclopramide ,ondansetron metoclopramide ,ondansetron Category BCategory BPhenothiazines :Phenothiazines :Prochlorperazine, Prochlorperazine, promethazine, Category Cpromethazine, Category CWhen given in high doses during late When given in high doses during late pregnancy, phenothiazines have caused pregnancy, phenothiazines have caused prolonged neurological disturbances in the prolonged neurological disturbances in the infantinfant..OthersOthersDomperidoneDomperidone Category Category C C

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Muscle relaxantsMuscle relaxantsBaclofen, botulinum type A , Dantrolene, methocarbamol, Baclofen, botulinum type A , Dantrolene, methocarbamol, orphenadrineorphenadrine

Physostigime , QuininePhysostigime , Quinine Category CCategory C

Agents used in gout and hyperuricaemiaAgents used in gout and hyperuricaemia probenecid Category Bprobenecid Category B

Allopurinol Allopurinol Category CCategory CSulfinpyrazone Sulfinpyrazone CategoryCCategoryC (D if near term) (D if near term)

CorticosteroidsCorticosteroidsSystemicSystemic Category C Category C::TopicalTopical Category C Except ophthalmic suspension of Category C Except ophthalmic suspension of triamcinolone Dtriamcinolone D Inhalation/IntranasalInhalation/IntranasalCategory CCategory C Except Budesonide Except Budesonide Category Category BBThe benefits of asthma control outweigh any potential for an The benefits of asthma control outweigh any potential for an adverse pregnancy outcomeadverse pregnancy outcome..

Pituitary hormonesPituitary hormonesCorticotrophinCorticotrophin Category CCategory C

AntidiureticsAntidiureticsDesmopressin, vasopressinDesmopressin, vasopressin Category BCategory B

Hypoglycaemic agents (oral)Hypoglycaemic agents (oral)It is important to achieve strict normoglycaemia during It is important to achieve strict normoglycaemia during pregnancy. This may best be achieved by conversion to pregnancy. This may best be achieved by conversion to insulin therapyinsulin therapy..

Alpha-glucosidase inhibitorAlpha-glucosidase inhibitor e.g: Acarbose e.g: Acarbose Category BCategory BBiguanide Biguanide e.g: Metformine.g: Metformin Category BCategory B

The sulphonylureThe sulphonylure Chlorpropamide, glibenclamide, Chlorpropamide, glibenclamide, gliclazide, glimepiride, glipizide, tolazamide, gliclazide, glimepiride, glipizide, tolazamide, tolbutamide tolbutamide Category CCategory CThe sulphonylureas may enter the fetal circulation and The sulphonylureas may enter the fetal circulation and may cause neonatal hypoglycaemiamay cause neonatal hypoglycaemia..Thyroid hormonesThyroid hormones

Liothyronine, thyroxineLiothyronine, thyroxine Category ACategory A

Agents affecting calcium and bone Agents affecting calcium and bone metabolismmetabolism

Biphosphonate derivativeBiphosphonate derivative: Alendronate: Alendronate Category CCategory CCalcitonin , CalcitriolCalcitonin , Calcitriol Category CCategory C

Other hormonal agentsOther hormonal agents..Octreotide Octreotide Category BCategory B..Pituitary inhibitorsPituitary inhibitors

BromocriptineBromocriptine Category BCategory B CabergolineCabergoline Category BCategory B

Bladder function disordersBladder function disordersAlpha 1 blockerAlpha 1 blocker Alfuzosin B, Tamsulosin B Alfuzosin B, Tamsulosin B Doxazosin C Prazosin C, TerazosinDoxazosin C Prazosin C, TerazosinCC

AntimicrobialsAntimicrobials

Probable safeProbable safe

11--Cephalosporins(B)Cephalosporins(B)

22--Pencillins(B)Pencillins(B)

33--Erythromycin(B)Erythromycin(B)

((other than estolateother than estolate))

Prescribe with cautionPrescribe with caution 11--AminoglysidesAminoglysides© ©

22--Antitubercular drugs (c)Antitubercular drugs (c)33--chloramphenicolchloramphenicol

44--clindamycin (c)clindamycin (c) 55--dapsone(especially at term)dapsone(especially at term)

66--lincomycinlincomycin 77--metronidazole(7)metronidazole(7)

88--Nitrofurantion(Contraindicated at term)(B)Nitrofurantion(Contraindicated at term)(B)99--Sulphobamides(Contraindicated at term)Sulphobamides(Contraindicated at term)

1010--TrimethoprimTrimethoprim©©1111--T-S(Contraindicated at term)(B)T-S(Contraindicated at term)(B)

1212--VancomycinVancomycin©©

ContraindicationContraindicationErythromycin estolateErythromycin estolate

Nalidixic acid & other quinolonesNalidixic acid & other quinolones©©Tetracycline(D)Tetracycline(D) Topical vaginal medicationTopical vaginal medicationClindamycin, clotrimazole, , nystatin Category BClindamycin, clotrimazole, , nystatin Category Beconazole, miconazole econazole, miconazole CategoryCategory c c

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Antifungal AgentsAntifungal Agents Amphotericin, Terbinafine, NystatinAmphotericin, Terbinafine, Nystatin Category BCategory B

Fluconazole , griseofulvin, itraconazole, ketoconazoleFluconazole , griseofulvin, itraconazole, ketoconazole Category CCategory C

Antiviral agentsAntiviral agentsAciclovir, Didanosine , ritonavir, valaciclovirAciclovir, Didanosine , ritonavir, valaciclovir Category BCategory B

Indinavir, foscarnet, lamivudine zidovudine Indinavir, foscarnet, lamivudine zidovudine Category CCategory C AnthelminticsAnthelmintics

PraziquantelPraziquantel Category BCategory B Albendazole, mebendazoleAlbendazole, mebendazole Category CCategory C

Respiratory systemRespiratory system

AntitussiveAntitussiveOpium alkaloids and derivatives: codeine, dextromethorphan, Opium alkaloids and derivatives: codeine, dextromethorphan, dihydrocodeine, dihydrocodeine, Category CCategory CExpectorants and mucolyticsExpectorants and mucolyticsAmmonium chloride, bromhexine, guaiphenesin, Ammonium chloride, bromhexine, guaiphenesin,

ipecacuanhaipecacuanha , ,Category CCategory CDecongestantsDecongestants

Phenylephrine, pseudoephedrinePhenylephrine, pseudoephedrine Category CCategory CInhalational agentsInhalational agentsBronchospasm relaxantsBronchospasm relaxants

Terbutaline, Ipratropium bromide Sodium cromoglycateTerbutaline, Ipratropium bromide Sodium cromoglycate , ,Category BCategory B Ephedrine, isoprenaline, salbutamol, , theophylline Ephedrine, isoprenaline, salbutamol, , theophylline

derivativesderivatives CategoryCategory C C

Preventive aerosols and inhalationsPreventive aerosols and inhalations budesonide Category Bbudesonide Category B

Beclomethasone, , fluticasone, salmeterol Beclomethasone, , fluticasone, salmeterol Category CCategory CThe benefits of asthma control outweigh any The benefits of asthma control outweigh any potential for an adverse pregnancy outcomepotential for an adverse pregnancy outcome..

Other respiratory agentsOther respiratory agentsAcetylcysteine , montelukast, zafirlukast Acetylcysteine , montelukast, zafirlukast Category BCategory B Allergy and immune systemAllergy and immune systemAntihistaminesAntihistaminesCetirizine , fexofenadine Chlorpheniramine, Cetirizine , fexofenadine Chlorpheniramine, triprolidine ,hydroxyzine , promethazinetriprolidine ,hydroxyzine , promethazine Category CCategory C Loratadine ,Cyclizine,Meclizine Loratadine ,Cyclizine,Meclizine clemastine ,cyproheptadine , diphenhydramineclemastine ,cyproheptadine , diphenhydramine , ,

Category BCategory B

Neuromuscular blocking agentsNeuromuscular blocking agentsAtracurium, SuxamethoniumAtracurium, Suxamethonium Category CCategory C

Detoxifying agents, antidotesDetoxifying agents, antidotesAcetylcysteine (intravenous) Acetylcysteine (intravenous) Category BCategory B

digoxin immune fab, Desferrioxamine, digoxin immune fab, Desferrioxamine, flumazenil , Naloxoneflumazenil , Naloxone Category CCategory C

Drugs used in myasthenia gravisDrugs used in myasthenia gravis neostigmineneostigmine CategoryCCategoryC

Pyridostigmine Pyridostigmine Category BCategory B

**Folic acidFolic acid CategoryCategory A A

**Vitamin AVitamin A CategoryCategory(A/C dose exceeding RDA (A/C dose exceeding RDA recommended dose)recommended dose)

* * Vitamin CVitamin C Category Category A/Cdose exceeding RDA A/Cdose exceeding RDA recommended doserecommended dose))

**Vitamin EVitamin E Category Category A/C dose exceeding RDA A/C dose exceeding RDA recommended doserecommended dose))

**Vitamin BVitamin B CategoryCategory A/Cdose exceeding RDA A/Cdose exceeding RDA recommended doserecommended dose))

**Vitamin DVitamin D CategoryCategoryCC**Vitamin KVitamin K Category Category C C