The List of Safe Drugs During Pregnancy & Lactation

Review Artcle

Safe Drugs During Pregnancy and Lactation S.B. Puranik 1, Imran Khan*1, Mohit Joshi2 and Mahvash Iram3 1

Biocon Limited Bangalore, 2Srinivas College of Pharmacy Mangalore, 3 Al-Ameen College of Pharmacy, Pharmacy, Hosur road Bangalore, Karnataka, India-560027

ABSTRACT Pregnancy is the carrying of one or more offspring, known as a fetus or embryo, inside the womb of a female. Lactation describes the secretion of milk from the mammary glands, the process of providing milk to the young, and the period of time that a mother lactates to feed her young one. This process occurs in all female mammals, in humans it is commonly referred to as breastfeeding or nursing. This paper summarizes the factors determining fetal damage and lists the problems associated with some drugs frequently encountered during Pregnancy and Lactation. Keywords: Pregnancy, lactation, safe drugs, fetal damage.

INTRODUCTION

Drugs that a pregnant woman takes can Pregnancyy is the carrying of one or more affect the fetus in several ways. They can Pregnanc offspring, known as a fetus or embryo, inside act directly on the fetus causing damage the womb of a female. Lactation describes or abnormal development leading to birth the secretion secretion of milk from the mamm mammary  ary  defects or death. Drugs can also alter the by constrictglands, the process of providing milk to the function of the placenta usually by b lood supyoung, and the period of time that a mother ing blood vessels and reducing the blood lactates to feed her young one. This process ply of oxygen and nutrients to the fetus from mother and thus resulting in a baby that is occurs in all female mammals, in humans it underdeveloped.. Moreover is commonly referred to as breastfeeding or underweight and underdeveloped nursing. Medical scientists divide 40 weeks they can cause the muscles of the uterus to of pregnancy into 3 trimesters. The rst tri- contract forcefully; indirectly injuring the fetus by reducing the blood supply or trigmester is for weeks 0–12; the second is for 1 gering pre-term labor and delivery.3 Women 13–28 weeks, and the third for weeks 29–40. 2 9–40.  The hazards hazards of exposing the human fetus to overestimate the risk of drug use and other drugs have become increasingly apparent in exposures during pregnancy. Perception of  the last 15 years, during the time when drug  risk may impact a woman’s decision to take a needed drug during pregnancy manifesting  usage has steadily increased. Even though a  various ous other other complicatio complications. ns. There There is a paudirect cause-and-effect relationship between  vari city of research on this topic in the literature. certain commonly used drugs and fetal dis Therefore, ore, it is import important ant for healt health h care orders or malformations has been difcult  Theref to establish, the principle of avoidance of  providers to use evidence-based informaall but essential medications in pregnancy  tion, to reduce unnecessary anxiety, and to and in the potentially pregnant has become ensure safe and appropriate treatment during  increasingly important. This paper summa- pregnancy.4 This article is a summary regardrizes the factors determining fetal damage ing fetal and neonatal risk of prescription drugs, over-the counter medications, vitaand lists the problems associated with some 2 mins and vaccines.5 Survey has conrmed drugs frequently encountered in practice. RGUHS J Pharm Sci | Vol 3 | Issue 1 | Jan–Mar, 2013

Received Date : 11-12-2012 Revised Date : 15-02-2013 Accepted Date : 28-02-2013

DOI: 10.5530/rjps.2013.1.4 Address for correspondence Mr. Imran Ahmad Khan 

Biocon India Ltd, 20th KM, Hosur Road, Electronic City, Bangalore- 560100, Karnataka (India) Tel. 011-91- 9900434646 E-mail: [email protected]

www.rjps.in

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S.B. Puranik. et al .: .: Pregnancy and Lactation......

that at present, some drugs are often more widely used in pregnancy than is justied by the knowledge available.6

differing contexts, times, and methods, in a eld where knowledge is often based on scanty information. 14 This analysis of a large nation-wide cohort of pregnant women women Database available for the information showed that during pregnancy drugs were prescribed to  A Motherisk symposium on establishing benchmarks most women, even when vitamins, minerals, iodide and iron for the evaluation of medications during during pregnancy   we  were re omitted omitted.. Magnesiu Magnesium m and iron seeme seemed d to ha have ve been been  was held on May 10, 2006, under the auspices of the over-prescribed. On the other hand, the ofcial recommenCanadian Society of Pharmacology and Therapeutics. dation for iodide substitution, to prevent thyroid diseases in From that symposium came a consensus on the need mother and child, was insufciently implemented. In our for collection and analysis analysis of data on fetal safety and opinion, regular analysis of prescription data can identify  identify  ongoing post-marketing surveillance, which in turn potential harmful therapies and focal points where guideled to the establishment of Case Med-Pregnancy-the Med-Pregnancy-the lines are needed and can check their implementation. 15 Canadian Alliance for Safe and Effective Medication How drugs act on fetus during Pregnancy and Breastfeeding. 7 Safefetus.com is a complete database of worldwi worldwide de Medications should be avoided by all women who are medications medicati ons (generic & trade) providing information on or might become pregnant. While some medications are har mful when taken during pregnancy, pregnancy, the the drugs’ indications indications,, fetal risk, breastfeeding risk, dur- known to be harmful 8 safety of most medications take taken n by pregnant women ing pregnancy, according to the FDA. has been difcult to determine. The effects depend on  The lat latest est edi edition tion is the reso resourc urcee for for any prac practici ticing ng Obst Obsteemany factors, viz. How much medication was taken, trician/Gynecologist, family physician, midwife, or phar when during the pregnancy the medication was taken, macist who prescribes medicinal products to or evaluates other health conditions a woman might have and other environmental or occupational exposures in women who medications a woman takes. 16 are or may become pregnant. Based on the highly successfetus’s blood vessels are contained in tiny  ful German editions of this reference, reference, the up-to-date drug  Some of the fetus’s hair like projections (villi) of the placenta that extend listings have been revised into a handy pocket guide color mother’s blood passes tabbed for quick access to important information. 9 Anti- into the wall of the uterus. The mother’s biotics were the most dispensed prescribed drug during  through the space surrounding the villi (intervillous pregnancy, and the proportion of women lling prescrip- space). Only a thin membrane (placental membrane) tions with antibiotics increased further during the lactating  separates the mother’s blood in the intervillous space period reaching almost 14%. The most prescribed antibi- from the fetus’s blood in the villi. Drugs in the mother’s blood can cross this membrane into blood vessels in the otic drugs were β-lactam and penicillins. Similar ndings 10 11 12  villi and pass through the umbili umbilical cal cord to the the fetus fetus.. The  weree reporte  wer reported d in a Norwe Norwegian gian and a German study. 17 process of drug transfer is shown in Figure 1. Fifth edition of “Drugs in Pregnancy and Lactation”, Lactation”, by Briggs GG, Freeman RK, Yaffee SJ is the source which Most drugs that go into the body will also go into the milk, consideration of its effect contains information on drug effects during both preg- so before any medication is taken, consideration nancy and lactation. The monographs are comprehensive on baby and whether or not it has any effects on lactation needs to be done. While most medications are safe to take and up to date and include information from sources that  while  whi le bre breast astfee feedin ding, g, it’s wis wisee to tal talkk to the doc doctor tor bef before ore tak tak-are difcult for practicing physicians to locate. 13 ing. Some drugs do not harm the baby, but may affect the  The need need for furth further er informa informatio tion n on drug utiliz utilizati ation on patmilk volume by suppressing the milk-making hormones. terns during pregnancy in different countries was assessed On the other hand, some conditions (i.e., hypothyroidism) by reviewing literature. The resulting prole, from 13 identi ed studies, was that, pregnant women used an average of  4.7 drugs. The most commonly ingested medications were  vitam  vit amins ins and iro iron n prepa preparat ration ionss (alm (almost ost all wo wome men), n), ana analgelgesics, antiemetics and antacids. However, important variables (such as date of surveillance; country; size of involv involved ed population; habits; physiopathological and demographic characteristics), differently taken into account in each selected study, made it impossible to construct a comprehensive, detailed, up-to-date picture about drug utilization during  pregnancy. The evaluation conrmed the need for and value of systemat systematic ic permanent surveillance surveillance of drug utilization in pregnancy,, so as to avoid the use of data obtained in widely  pregnancy Figure 1: Drug transfer to Fetus through Umbilical cord. 22

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S.B. Puranik. et al .: .: Pregnancy and Lactation......

can interfere with ability to make milk, and medications to treat the problem will improve milk production. There are three issues to consider when considering taking medication while breastfeeding viz. is the drug needed, will the drug affect baby, will the drug affect ability to make milk. 18 More than 90% of pregnant women take prescripprescription or nonprescription (over-the-counter) drugs or use social drugs (such as tobacco and alcohol) or illicit drugs at some time during pregnancy. In general, drugs, unless absolutely necessary, should not be used during pregnancy because many can harm the fetus. About 2 to 3% of all birth defects defects result from the use of drugs other than alcohol. Drugs that a pregnant woman takes during pregnancy can affect the fetus in several ways, viz. they can act directly on the fetus, causing damage, abnormal development (leading to birth defects), or death, they can alter the function of the placenta, usually by causing blood

 vessels  vesse ls to constric constrictt and thus reduc reducing ing the supply supply of ox oxyygen and nutrients to the fetus from the mother. Sometimes the result is a baby that is underweight and underdeveloped, they can cause the muscles muscles of the uterus to contract forcefully, indirectly injuring the fetus by reducing its blood supply or triggering preterm labor and delivery. Concern about the safety of foreign compounds administered administered to pregnant women has been increasingly evident since thalidomide. The direct response to this misadventure led to the promulgation promulgation of the drug regulations of 1962 in the United States. According to these regulations, a drug must be demonstrated to be safe and effective for the conditions of use prescribed in its labeling, including including dosage level and patient populations for whom the drug dr ug is intended.19 Over the years, far too many women have been wrongly  told they had to stop breastfeeding. breastfeeding. The decision about continuing breastfeeding breastfeeding when the mother takes a drug,

Table 1: List of Safe Drugs during Pregnancy and Lactation20 Sl. No.

Name of the Drug

Category

1.

Acetaminophen

Used for pain relief  

2.

Acyclovir and valacyclovir

Antiviral for herpes infections

3.

Antacids

Used to treat upset stomachs

4.

Bupivacaine

A local anesthetic

5.

Caffeine

A stimulant

6.

Clotrimazole

Used to treat yeast and fungal infections

7.

Cephalosporins

Antibiotics for lung, ear, skin, urinary tract, throat, and bone infections

8.

Contraceptives (progestin-only)

Used for birth control

9.

Corticosteroids

Used to treat inammation of joints and other conditions

10.

Decongestant nasal sprays

Used to treat stuffy noses

11.

Digoxin

Used to treat heart problems

12.

Erythromycin

Used for skin and respiratory infections

13.

Fexofenadine

Antihistamine for allergies and hay fever  

14.

Fluconazole

Used to treat yeast infections

15.

Hepar in in an and Lo Low mo molecular we weight he hepar in ins (enoxaparin, dalteparin, tinzaparin)

Used to prevent blood from clotting

16.

Ibuprofen

Used for pain relief  

17.

Inhalers, br bronchodilators, an and co corticosteroids

Used fo for as asthma

18.

Insulin

For diabetes; dosage required may drop up to 25 percent during lactation

19.

Laxatives, bu bulk-forming an and st stool so softening

Used to to tr treat co constipation

20.

Lidocaine

A local anesthetic

21.

Loratadine

Antihistamine for allergies and hay fever  

22.

Magnesium sulfate

Used to treat preeclampsia and eclampsia

23.

Methyldopa

Used to treat high blood pressure

24.

Methylergonovine (short courses)

Used to prevent or control bleeding after ch childbirth

25.

Metoprolol

A beta-blocker used to treat high blood pressure

26.

Miconazole

Used to treat yeast infections

27.

Nifedipine

Used for high blood pressure and Reynaud’s syndrome of the nipple

28.

Penicillins

Used to treat bacterial infections

29.

Propranolol

A beta blocker used to treat heart problems, and high blood pressure

30.

Theophylline

Used to treat asthma and bronchitis

31.

Tretinoin

Cream used for acne

32.

Elotroxin

Used to treat thyroid problems

33.

Vaccines (except smallpox and yellow fever)

—

34.

Vancomycin

An antibiotic

35.

Verapamil

Used for high blood pressure

36.

Warfarin

Used to treat or prevent blood clots

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S.B. Puranik. et al .: .: Pregnancy and Lactation......

Table 2: List of Probably Safe Drugs in Usual Doses20 Sl. No.

Name of the Drug

Category

1.

 ACE inhibitors

Used to treat high blood pressure

2.

Anticholinergic agents

Used to treat intestinal and gall bladder spasms; may reduce milk supply

3.

Anticonvulsants

Used for seizures and mood disorders

4.

Antihistamines

May reduce milk supply and cause infant drowsiness or fussiness

5.

Antituberculars

Used to treat tuberculosis

6.

Azathioprine

Used to suppress the immune system following organ transplants

7.

Barbitur at ates (e (exc ep ept Ph Phenobarbit al al)

For se sedation an and te tension headaches

8.

Bupropion

For depression

Clindamycin

Used to treat abdominal and vaginal infections

10.

9.

Oral de decongestants

Used to treat congestion associated with colds or allergies; often reduces milk supply

11.

Ergonovine (short course)

Used to treat ut uterine bleeding. Ma May reduce milk supply.

12.

Fluconazole

Antifungal

13.

Gadolinium

Contrast agent for MRI studies

14.

Haloperidol

Used to treat psychosis

15.

Histamine H2 blockers

Used to treat stomach problems

16.

Labetalol

Used for high blood pressure; caution with preterm babies

17.

Hydrochlorothiazide (low doses)

Diuretic for high blood pressure

18.

Lorazepam

Used to treat anxiety

19.

Methimazole

Used for hyperthyroidism; less than 20 mg/day is probably safe

20.

Metoclopramide

Used for gastrointestinal problems and to increase milk supply

21.

Midazolam

Sedative used in anesthesia

22.

Naproxen

Used for pain relief; okay if baby is at least 1 month old

23.

Oxazepam

Used to treat anxiety

24.

Paroxetine

Used to treat depression

25.

Phenothiazines

antipsychotic and antihistaminic

26.

Propofol

Sedative used in anesthesia

27.

Propylthiouracil (PTU)

Used to treat hyperthyroidism

28.

Quinidine

Used to treat heartbeat irregularities

29.

Quinolone antibacterials

Treatment of urinary tract infections

30.

Salicylates (occasional use)

Used for pain relief  

31.

Sertraline

Used to treat depression

32.

Spironolactone

Used to treat high blood pressure

33.

Sumatriptan

Used to treat migraines

34.

Tetracyclines < 14 days

Used to treat acne and urinary tract infections

35.

Trazodone

Used for depression and sleep

36.. 36

Tric Tr icycl yclic ic ant antid idep epre ress ssan ants ts (av (avoi oid d doxe doxepi pin) n)

Used Use d to tre treat at dep depre ressi ssion on;; nortr nortrip iptyl tylin ine e pref prefer erre red d

37.

Verapamil

Used for high blood pressure

Table 3: List of Potentially Hazardous Drugs in Usual Doses 20 Sl. No.

Name of the Drug

Category

1.

Acebutolol

A beta blocker used to treat high blood pressure and abnormal heart rhythms.

2.

Atenolol

A beta blocker used to treat high blood pressure and abnormal heart rhythms.

3.

Anti An tihi hist stam amin ine e/d /de eco con nge gest sta ant co com mbi bin nat atio ions ns

Use Us ed to to tre treat at co cold lds s and and al alle lerg rgie ies; s; ma may y re redu duce ce mi milk lk su sup ppl ply y

4.

Benzodiazepines

Used to treat anxiety and for sleep (lorazepam, oxazepam preferred)

5.

Chlorthalidone

Diuretic used to treat high blood pressure; may reduce milk supply

6.

Citalopram

Antidepressant; can cause infant drowsiness

7.

Clonidine

Used to treat high blood pressure, may reduce milk supply

8.

Contraceptives (estrogen-containing)

Used for birth control; may reduce milk supply

Doxepin

Used to treat depression

10.

9.

Ergotamine

Used to treat migraines

11.

Ethosuximide

Used to treat epilepsy

12.

Fluorescein IV

Used to diagnose retinal problems

13.

Fluoxetine

Used to treat depression

14.

Iodinated contrast media

Used to examine kidneys; withhold breastfeeding temporarily

15.

Lamotrigine

Used for seizures and mood disorders (Continued)

24

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Table 3: (Continued) Sl. No.

Name of the Drug

Category

16.

Lithium (monitor infant serum levels)

Used to treat bipolar disease

17.

Metronidazole

An antibiotic used to treat some intestinal and genital infections

18.

Nadolol

A beta blocker used to treat high blood pressure and heart problems

19.. 19

Narcot Narc otic ics, s, es espe peci cial ally ly me mepe peri ridi dine ne in ad addi dict cts s and and high doses with newborns

Used for pain (one tablet every six hours maximum; watch for drowsiness)

20.

Nefazodone

Used for depression

21.

Nicotine

Smoking can reduce milk supply

22.

Nitrofurantoin

Used to treat urinary tract infections (safe if the baby is at least 1 month old)

23.

Phenobarbital, anticonvulsant doses

Sedative and anticonvulsant

24.

Piroxicam

Used to treat arthritis and pain

25.

Primidone

Used to treat seizures

26.

Reserpine

Used to treat hypertension

27.

Sotalol

Used to treat heart problems

28.. 28

Thia Th iazi zide de di diur uret etic ics, s, lo long ng-a -acti cting ng or hi high gh do dose ses s

Forr hig Fo high h bl bloo ood d pr pres essu sure re or ed edem ema; a; hi high gh do dose se ma may y re redu duce ce mi milk lk su supp pply ly

29.

Venlafaxine

Used to treat depression

Table 4: List of Drugs not Safe to take in Usual Doses in Pregnancy and Lactation20 Sl. No.

Name of the Drug

Category

1.

Amantadine

Used to treat the u or Parkinson’s disease

2.

Amiodarone

Used to treat heart problems

3.

Antilipemics (excluding resins)

Used to lower the level of cholesterol in the blood

4.

Antineoplastic agents

Used to treat cancer  

5.

Aspirin (large doses)

Used to treat arthritis

6.

Cocaine

Narcotic Analgesic

7.

Chlorampenicol

Used to treat serious infections

8.

Clozapine

Used to treat schizophrenia

9.

Dipyrone (dipironain Mexican drugs)

Used for pain and inammation

10.

Gold Salts

Used to treat arthritis

11.

Iodide products

Used for douching or as an expectorant

12.

Iodine, radioactive

Used to diagnose and treat hyperthyroidism

13.

Lipid-lowering drugs

Used to lower the level of fats in the blood

14.

Metamizole (Dipyrone)

 Analgesic/anti-inammatory

15.

Salicyclates, large doses

Used to treat arthritis

Table 5: Problems Associated with Commonly Used Drugs Sl. No.

Category

Examples

Problem

1.

Anti An ti-- an anxi xiet ety y dr drug ug

Diaz Di azep epam am

When th When the e dr drug ug is ta take ken n la late te in pr preg egna nanc ncy y, de depr pres essi sion on,, irritability, shaking, and exaggerated reexes in the newborn

2.

Antibiotics

Chloramphenicol

Gray baby syndrome In women or fetuses with glucose-6-phosphate dehydrogenase (G6PD) deciency, deciency, the breakdown of red blood cells

Fluoroquinolones (such as ciprooxacin, Fluoroquinolones ooxacin, levooxacin, and noroxacin)

Possibility of joint abnormalities (seen only in animals)

Kanamycin

Damage to the fetus’s ear, resulting in deafness(ototoxicity)

Nitrofurantoin

In women or fetuses with G6PD deciency, the breakdown of red blood cells

Streptomycin

Damage to the fetus’s ear, resulting in deafness(ototoxicity)

Sulfonamides (such assulfasalazine and trimethoprim-sulfamethoxazole )

When the drugs are given late in pregnancy, jaundice and possibly brain damage in the newborn (much less likely with sulfasalazine) In women or fetuses with G6PD deciency, the breakdown of red blood cells

Tetracycline

Slowed bone growth, permanent yellowing of the teeth, and increased susceptibility to cavities in the baby Occasionally,, liver failure in the pregnant woman Occasionally (Continued)

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S.B. Puranik. et al .: .: Pregnancy and Lactation......

Table 5: (Continued) Sl. No. 3.

4.

5.

6.

Category

Examples

Problem

Anticoagulants

Heparin

When the drug is taken for a long time, osteoporosis and a decrease in the number of platelets in the pregnant woman

Warfarin

Birth defects Bleeding problems in the fetus and the pregnant woman

Carbamazepine

Some risk of birth defects Bleeding problems in the newborn, which can be prevented if pregnant women take vitamin K orally every day for  a month before delivery or if the newborn is given an injection of vitamin K soon after birth

Phenytoin & Phenobarbital

Same as those for carbamazepine

Trimethadione

Increased risk of miscarriage in the woman High (70%) risk of birth defects, including a cleft palate and defects of the heart, face, skull, hands, or abdominal organs

Valproate Valproa te

Some (1%) risk of birth defects, including a cleft palate and defects of the heart, face, skull, spine, or limbs

 Angiotensin-converting enzyme (ACE) inhibitors

When the drugs are taken late in pregnancy, kidney damage in the fetus, a reduction in the amount of uid around the developing fetus (amniotic uid), and defects of  the face, limbs, and lungs

Beta-blockers

When some beta-blockers are taken during pregnancy, a slowed heart rate and low blood sugar level in the fetus and possibly slowed growth

Thiazide diuretics

A decrease in the levels of oxygen, sodium, and potassium and in the number of platelets in the fetus’s blood Slowed growth

 Actinomycin

Possibility of birth defects (seen only in animals)

Busulfan

Birth defects such as underdevelopmen underdevelopmentt of the lower jaw, cleft palate, abnormal development of the skull bones, spinal defects, ear defects, and clubfoot Slowed growth

Chlorambucil, Cyclophosphamide, Mercaptopurine & Methotrexate

Same as those with busulfun

Vincristine & Vinblastine

Possibility of birth defects (seen only in animals)

Anticonvulsants

Antihypertensive

Chemotherapy drugs

7.

Mood-stabilizing drug

Lithium

Birth defects (mainly of the heart), lethargy, reduced muscle tone, poor feeding, underactivity of the thyroid gland, and nephrogenic diabetes insipidus in the newborn

8.

Non-steroidal  Aspirin and other salicylates anti-inammatory Ibuprofen, Naproxen drugs (NSAIDs)

When the drugs are taken in large doses, a delay in the start of labor, premature closing of the connection between the aorta and artery to the lungs (ductus arteriosus),  jaundice, and and (occasionally) (occasionally) brain damage damage in the fetus and bleeding problems in the woman during and after delivery and in the newborn When the drugs are taken late in pregnancy, a reduction in the amount of uid around the developing fetus

9.

Oral antihyperglycemic drugs

Chlor pr pr op opamide & Tolbutamide

A ver y low le lev el el of of su sugar in in th the bl blood of of th the ne newborn Inadequate control of diabetes in the pregnant woman When the drug is taken early in pregnancy by a woman with type 2 diabetes, possibility of increased risk of birth defects

10.

Sex hormones

Danazol & Synt he hetic proges titin (but not the low doses used in oral contraceptives)

When this drug is taken very early in pregnancy pregnancy,, masculinization of a female fetus’s genitals, sometimes requiring surgery to correct

Diethylstilbestrol (D (DES)

Abnormalities of of th the ut uterus, me menstrual pr problems, an and an increased risk of vaginal cancer and complications during pregnancy in daughters  Abnormalities of the penis in sons sons

Etretinate

Birth defects, such as heart defects, small ears, and hydrocephalus (sometimes called water on the brain)

Isotretinoin

Same as those for etretinate Mental retardation Risk of miscarriage

11.

Skin treatments

(Continued) 26

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Table 5: (Continued) Sl. No.

Category

Examples

Problem

12.

Thyr Th yro oid dru rugs gs

Meth Me thim ima azo zole le

An en enla larg rged ed or und nder era act ctiv ive e th thyr yroi oid d gl gla and in th the e fe fetu tus s Scalp defects in the newborn An enlarged or underactive thyroid gland in the fetus Destruction of the thyroid gland in the fetus When the drug is given near the end of the 1st trimester, very overactive and enlarged thyroid gland in the fetus An overactive and enlarged thyroid gland in the fetus Potential infection of the placenta and developing fetus

Propylthiouracil Radioactive iodine

13.

Vaccines (live virus)

Triiodothyronine Vaccine for German measles (rubella) and chickenpox (varicella) Vaccines for measles, mumps, polio, or  yellow fever 

Potential but unknown risks

for example, is far more involved than whether the baby  are A, B, C, D and X. Generally speaking, drugs that fall  will get any in the milk. milk. It also involves involves taking into con- into either class A or B are considered safe and are routinely  sideration the risks of not breastfeeding, for the mother, used. There may be exceptions. 21 The American Academy  the baby and the family, as well as society. On the other of Pedi Pediatrics atrics has given given a selected list of some approved approved hand, it should be taken into consideration that some drugs by them for the use in breastfeeding mothers (AAP babies may refuse to take the bottle completely, so that list revised 8/04). This list is for general information only. havee class classied ied thes thesee drugs drugs in in followi following ng catego categories ries..22 the advice to stop is not only wrong, but often impracti-  They hav cal as well. On top of that it is easy to advise the mother to pump her milk while the baby is not breastfeeding, Table 6: Drugs Category Based on AAP22 but this is not always easy in practice and the mother Lactation Risk Categories Pregnancy Risk Categories may end up painfully engorged. So it is necessary to • L1 (safest) •  A (controlled studies show no risk) know which drugs are safe for consumption during  • L2 (safer) • B (no evidence of risk in humans) humans) (moderately safe) • C (risk cannot be ruled out) pregnancy and lactation or the alternative alternativess for that drug. • L3 (moderately • L4 (possibly hazardous) • D (positive evidence evidence of risk) Medications Medica tions are grouped into 1 of 5 categories based on • L5 (contraindicated) • X (contraindicated in pregnancy) pregnancy) the potential for producing birth defects. The categories Table 7: List of Commonly Used Drugs during Pregnancy & Lactation Based on Risk Category22 Generic Name

Pregnancy Risk Category

Lactation Risk Category

 Acetaminophen

B

L1

Colchicine

D

L4

Nefopam

–

NR

–

L2

Analgesics

Non-Steroidal Anti-Infammatory Drugs (NSAIDs)  Azapropazone (apazone) (apazone) Dipyrone (banned in the US & UK)

–

NR

Flufenamic acid

–

NR

Ibuprofen

B (1st, 2nd trim.) D (3rd trim.)

L1

Indomethacin

B (1st, 2nd trim.) D (3rd trim.)

L3

Ketorolac

B (1st, 2nd trim.) D (3rd trim.)

L2

Mefenamic acid

–

NR

Naproxen

B

L3, L4 (for chronic use)

Phenylbutazone

–

NR

Piroxicam

B

L2

Suprofen

–

NR

Tolmetin

C

L3

Butorphanol

B (1st, 2nd trim.), D (3rd trim.)

L3

Codeine

C

L3

Fentanyl

B

L2

Meperidine

B

L2 L3 (if used early postpartum)

Methadone & Morphine

B

L3

Propoxyphene

C

L2

Narcotic Analgesic

(Continued) RGUHS J Pharm Sci | Vol 3 | Issue 1 | Jan–Mar, 2013

27

S.B. Puranik. et al .: .: Pregnancy and Lactation......

Table 7: (Continued) Generic Name

Pregnancy Risk Category

Lactation Risk Category

C

L2

Anesthetics Halothane & Lidocaine Methohexital

B

L3

Thiopental

C

L3

Cimetidine (Antacid)

B

L2

Cisapride (GI tract stimulant)

C

L2

 –

L1

B

L1

 Antacids and gastrointestinal drugs drugs

Domperidone (used for nausea & vomiting, stimulates lactation) Antibiotic  Amoxicillin  Aztreonam

B

L2

Cefadroxil, Cefazolin, Cefoxitin & Ceftazidime

B

L1

Cefotaxime

B

L2

Cefprozil

C

L1

Ceftriaxone

B

L2

Ciprooxacin

C

L3

Clindamycin

B

L3

Erythromycin

B

L1, L3 early postnatal

Gentamicin & Ooxacin

C

L2

Kanamycin

D

L2

Fleroxacin, Moxalactam & Sulbactam

–

NR

Nitrofurantoin

B

L2

Penicillin

B

L1

Streptomycin

D

L3

Carbamazepine & Sulsoxazole

C

L2

Tetracycline

D

L2

Ticarcillin

B

L1

Trimethoprim/sulfamethoxazole

C

L3

Bishydroxycoumarin (dicumarol)

–

NR

Warfarin

D

L2

Ethosuximide

C

L4

Magnesium sulfate

B

L1

Phenytoin & Valproic acid

D

L2

Fluconazole & Ketoconazole

C

L2

Antihistamine Dexbrompheniramine maleate with d-isoephedrine

–

NR

Fexofenadine

C

L2

Loratadine

B

L1

Terfenadine

–

NR

Triprolidine

C

L1

Anticoagulant

Anticonvulsant

Antifungal

Antiviral  Acyclovir

C

L2

Interferon-alpha

C

L2

C

L5

Dyphylline & Theophylline

C

L3

Terbutaline

B

L2

Estradiol

X

L3 (may interfere with milk production)

Clogestone

–

NR

Arthritis Medication Gold salts Asthma Medication

Contraceptives/Hormones

(Continued) 28

RGUHS J Pharm Sci | Vol 3 | Issue 1 | Jan–Mar, 2013

S.B. Puranik. et al .: .: Pregnancy and Lactation......

Table 7: (Continued) Generic Name

Pregnancy Risk Category

Lactation Risk Category

Contraceptive pill with estrogen/progesterone

X

L3 (may interfere with milk production)

Levonorgestrel & Norethynodrel

X

L2

Medroxyprogesterone

D

L1, L4 (if used rst 3 days postpartum)

Progesterone

–

L3

Anti-Tussive Codeine

C

L3

Noscapine

–

NR

Decongestants Pseudoephedrine

C

L3 (for acute use), L4 (for chronic use)

Diabetes Medication Note: Insulin has not been reviewed by the AAP. AAP. Pregnancy risk c ategory = B; Lactation r isk category = L1. Tolbutamide

D

L3

B

L2

Anti-Diarrheal Loperamide

Note: Pepto-Bismol & Kaopectate (bismuth subsalicylate is the active ingredient in both) are not recommended for routine use by nursing mothers, due to the association of salicylates with Reyes syndrome in children. Diuretics  Acetazolamide

C

L2

Bendroumethiazide

D

L4 (may inhibit lactation)

Chlorothiazide & Chlorthalidone

D

L3

Hydrochlorothiazide & Spironolactone

D

L2

–

L1

Disopyramide & Quinidine

C

L2

Flecainide & Procainamide

C

L3

Mexiletine

B

L2

Antihypertensive Captopril

D

L3 (if used after 30 days)

Diltiazem/Diltiazem HCL

C

L3

Galactagogues Domperidone  Antiarrhythmic/Antihypertensive/Cardiac Stimulant Antiarrhythmics

Enalapril/Enalapril Maleate

C (1st trim.), D (2nd, 3rd trim.)

L2

Hydralazine, Labetalol & Methyldopa

C

L2

Minoxidil

C

L2 (topically), L3 (orally)

Nadolol

C

L4

Nifedipine

C

L2

Oxprenolol

–

NR

Propranolol, Timolol & Verapamil

C

L2

Sotalol

B

L3

Cardiac Stimulants Digoxin

C

L2

Laxatives Cascara/Cascara Sagrada

C

L3

Danthron

–

NR

Magnesium sulfate

B

L1

Senna

–

L3

Anti-Malarial Chloroquine

C

L3

Hydroxychloroquine

C

L2

Pyrimethamine

C

L4

Quinine

D

L2

Diagnostic agents Diatrizoate

–

NR

Fluorescein

C

L3

Gadopentetic (Gadolinium)

C

L2 (Continued)

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S.B. Puranik. et al .: .: Pregnancy and Lactation......

Table 7: (Continued) Generic Name

Pregnancy Risk Category

Lactation Risk Category

Iohexol, Metrizoate & Metrizamide

B

L2

Iopanoic acid

D

L2

Migraine Medication Sumatriptan

C

L3

Sedatives Chloral hydrate

C

L3

Methyprylon (withdrawn from use in US & Canada)

–

NR

Bromide

D

L5

Secobarbital

D

L3

Sleep Aids Zolpidem/Zolpidem Tartrate

B

L3

C

L2

D

L3

D

L2

Thiouracil

–

NR

Levothyroxine

A

L1

Tuberculosis Cycloserine & Isoniazid

C

L3

Ethambutol

B

L2

Rifampin

C

L2

Steroids Prednisone, Prednisolone & Methylprednisolone [high dosage methylprednisolone] Thyroid Carbimazole & active metabolite of carbimazole (Methimazole) Propylthiouracil

Vitamins B-1 (thiamin)

–

NR

B-12 (Cyanocobalamin)

A

L1

B-6 (pyridoxine)

A

L2; L4 in high doses (may inhibit lactation)

D, vitamin

A

L3 (do not overdose)

Folic acid

A (1st, 2nd trim.), C (3rd trim.)

L1

K-1, vitamin (Phytonadione)

C

L1

Riboavin/B2

A

L1

Miscellaneous  Acitretin (Anti-psoriasis)

–

NR

 Alcohol/Ethanol

D

L3

 Allopurinol

C

L2

 Antimony

–

NR

 Atropine (Anticholinergic, drying agent) agent)

C

L3

 Azapropazone/apazone  Azapropazone/apazon e (Antirheumatic)

–

L2

Baclofen (muscle relaxant)

C

L2

Barbiturate

–

NR

Caffeine

B

L2

Carbetocin (Antihemorrhagic)

–

NR

Chloroform

–

NR

Cisplatin (Anti-cancer)

D

L4

Dapsone (Antileprosy)

C

L4

Hydroxychloroquine (Antirheumatic, lupus)

C

L2

Iodine & Iodides (povidone-iodine, e.g., in a vaginal douche)

 –

NR

C

L3

Ivermectin (Antiparasitic) Nalidixic acid (Urinary Anti-infective)

B

L4

Norsteroids

–

NR

Pyridostigmine (Muscle stimulant)

C

L2

Scopolamine (Motion sickness)

C

L3

Sulfapyridine

–

NR

Timolol (glaucoma med)

D

L3

*NR: Not Reviewed. This drug has not yet been reviewed by the AAP. 30

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S.B. Puranik. et al .: .: Pregnancy and Lactation......

CONCLUSION Drugs should be avoided by all women who are or might become pregnant. While some medications are known to be harmful har mful when taken during pregnancy, pregnancy, the safety of most medications medications taken by pregnant women has been difcult to determine. The effects depend on many factors, viz. How much medication was taken,  when during the pregnancy the medication was taken, other health conditions a woman might have and other medications a woman takes? Some of the fetus’s fetus’s blood  vessels are contained in tiny hair like projections (villi) of the placenta that extend extend into the wall of the uterus.  The mother’s blood passes through through the space space surrounding the villi (intervillous space). Only a thin membrane (placental membrane) separates the mother’s blood in the intervillous space from the fetus’s blood in the  villi. Drugs in the mother’ mother’ss blood can cross this membrane into blood vessels in the villi and pass through the umbilical cord to the fetus. Most drugs that go into the body will also go into the milk, so before any medication is taken, consideration consideration of its effect on baby and whether or not it has any effects on lactation must be made. made.

5.

Gerald G. Briggs, Roger K. Freeman and Sumner J. Drugs in Pregnancy and Lactation. CMAJ, 1987 VOL 136:507.

6.

Medication during pregnancy: an intercontinental cooperative study. Collaborative Group on Drug Use in Pregnancy (C.G.D.U.P.). Int J Gynaecol Obstet 1992; 39(3):185–96.

7.

Davis DB. Drugs in pregnancy--the issues for 2010. J Popul Ther Clin Pharmacol 2010; 17(3):332–5.

8. 9.

http://www.safefetus.com/. 25.05.2011. 12:45pm. Christof Schaefer, Schaefer, Paul Peters WJ, Richard KM. Drugs During During Pregnancy and Lactation Treatment Options and Risk Assessment. Elsevier Science & Technology; second edition. Netherland.

10.

Engeland A, Bramness JG, Daltveit AK, Rønning M, Skurtveit S, Furu K. Prescription drug use among fathers and mothers before and during

11.

pregnancy. Br J Clin Pharmacol 2008; 65(5):653–60. Amann U, Egen-Lappe V, V, Strunz-Lehner C, Hasford J. Antibiotics in pregnancy: analysis of potential risks and determinants in a large German statutory sickness fund population. Pharmacoepidemiol Drug Saf 2006; 15(5):327–37.

12.

Olof Stephansson et al. Drug use during pregnancy in Sweden – assessed by the Prescribed Drug Register and the Medical Birth Register. Clinical Epidemiology 2011: 3 43–50.

13.

Briggs GG, Freeman RK, Yaffee SJ. Drugs in Pregnancy and Lactation. 5th edition. Publisher Baltimore Williams & Wilkins; 1998.

14.

Bonati M, Bortolus R, Marchetti F, F, Romero M, Tognoni G. Drug use in pregnancy: an overview of epidemiological (drug utilization) studies. Eur J Clin Pharmacol 1990; 38(4):325–8.

15.

Egen-Lappe V, V, Hasford J. Drug prescription in pregnancy: analysis of  a large statutory sickness fund population. Eur J Clin Pharmacol 2004; 60(9):659–66.

16.

http://www.cdc.gov/ncbddd/pregnancy_gateway/meds/index.html. 25.05.2011. 05:45pm.

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