drug used in lactation and pregnancy

1. DRUGS USED IN LACTATION AND PREGNACY
INTRODUCTION
Drug use during pregnancy and lactation requires special consideration because both the
mother and the child are affected. Few drugs are considered safe, and drug use is generally
contraindicated. Many pregnant or lactating women take drugs for acute or chronic disorders
or habitual use of alcohol and tobacco. During the first trimester drugs can produce
congenital malformation (teratogenesis) and the period of greatest risk is from the third to
eleven week of pregnancy. Teratogenicity is the ability of a substance to cause abnormal fetal
development when taken by pregnant women. During the second and third trimester drugs
can affect the growth or functional development of the fetus, or they have toxic effects on
fetal tissues. Drugs given shortly before them or during labour can have adverse effects on
labour or neonate after after delivery. Although the benefits of breast-feeding are widely
recognized, pharmacists, Physicians and other health professions may advise mothers not to
breast-feed when taking medications. This may be considered a prudent action to avoid
harming the breast-fed infant; however, practical experience and available data show that
compatibility between pharmacologic treatment and breast-feeding is often possible. In fact,
given the immunologic and other benefits of breast-feeding, it may be more beneficial for the
infant to be breast-fed even when mothers must use medications. Also, methods have been
developed for ensuring the safety of medications while breast-feeding
PRICIPLE OF THERAPY
Give medications only when clearly indicated, weighing benefits to the mother against the
risks to the fetus. Any drugs used during pregnancy should be given in the lowest effective
doses and for the shortest effective time. The choice of drug should be based on the stage of
pregnancy and drug information
 Where possible use non drug therapy.
 Prescribing drugs only when definitely needed.
 Choose the drug having the best safety record over time.
 Avoid newer drug, unless safety is clearly established.
 Over the counter drug cannot be assumed to be safe.
 As far as possible, avoid medication in the initial 10 weeks of gestation.
 Use the lowest effective dose.
 Use drugs for the shortest period necessary.
Live virus vaccines (measles, mumps, polio, rubella) should be avoided because of possible
harmful effects to the fetus. Inactive virus vaccines (influenza, rabies, hepatitis B) and
toxoids (diphtheria, tetanus) are considered safe for use. Hyper immune globulins can be
given to pregnant women who are exposed to hepatitis B, rabies, tetanus, or varicella.
Drug Effects On The Fetus
Overall, effects are determined mainly by:
1. The type and amount of drugs
2. The duration of exposure
3. The level of fetal growth and development when exposed to the drugs
Drug Categories in Pregnancy
Category A:
Adequate studies in human demonstrate no risk.

2. Category B:
Animal studies indicate no risk, but there are no adequate studies in human. Animal studies
show adverse effects, but adequate studies in human have not demonstrated a risk.
Category C:
A potential risk, when:
Animal studies have not been performed or, Animal studies indicated no adverse effects and,
there are no data from human studies. These drugs may be used when potential benefits
outweigh the potential risks.
Category D:
There is evidence of human fetal risk, but the potential benefits to the mother may be
acceptable.
Category X:
Studies in animals or humans or adverse reaction reports or both have demonstrated fetal
abnormalities. The risk of use in a pregnant woman clearly outweighs any possible benefit.
Pregnancy-Associated Problems
1. Anemia
2. Constipation
3. Gastroesophageal Reflux
4. Gestational Diabetes
5. Nausea & Vomiting
6. Pregnancy-Induced Hypertension
A. Anemia
Three types of anemia are common during pregnancy:
1. Physiologic –results from expanded blood volume
2. Iron- deficiency—iron preparation should be given with food to avoid gastric
irritation. Citrus juice enhances absorption
3. Megaloblastic---caused by folic acid deficiency
B. Gastro-esophageal Reflux
Often occurs in the later months of pregnancy. Non-pharmacologic interventions (eating
small meals; avoiding gas producing food and drinks) are recommended. Antacids may be
used if necessary. Because little systemic absorption occurs. Cimetidine, ranitidine, or
sucralfate may also be used.
C. Constipation
Constipation occurs from decreased peristalsis. Preferred treatment, if effective, is to increase
exercise and intake of fluids and high-fiber foods. If a laxative is required, a bulk forming
agent is the most physiologic because it is not absorbed. A stool softener or an occasional
saline laxative (milk of magnesia) may also be used. Mineral oil should be avoided because it
interferes with absorption of fat-soluble vitamins. Reduced absorption of vitamin K can lead
to bleeding in newborns. Castor oil should be avoided because it can cause uterine
contractions. Strong laxatives or any laxative used in excess may initiate uterine contractions
and labor.
D. Gestational Diabetes
Some women first show signs of diabetes during pregnancy. This is called gestational
diabetes. Women without risk factors, or whose initial test was normal, should be tested
between 24 and 28 weeks of gestation. Initial management includes nutrition and exercise
interventions and calorie restriction for obese women. If drug is necessary, recombinant
human insulin is needed to keep blood sugar levels as nearly normal as possible. Oral
antidiabetic drugs are generally contraindicated, although acarbose, metformin, and miglitol

3. are almost safe. These women may revert to a nondiabetic state when pregnancy ends. They
are at increased risk for development of overt diabetes within 5 to 10 years. Gestational
diabetes usually subsides within 6 weeks after delivery.
E. Nausea & Vomiting
Dietary management and maintaining fluid and electrolyte balance are recommended.
Antiemetic drugs should be given only if nausea and vomiting are severe enough to threaten
the mother’s nutritional status. Dimenhydrinate, 50 mg every 3 to 4 hours, are thought to
have low teratogenic risks. Pyridoxine (vitamin B6) also may be helpful 10 to 25 mg daily.
F. Pregnancy Induced Hypertension
Pregnancy-induced hypertension includes preeclampsia and eclampsia.
They endanger the lives of mother and fetus.
Preeclampsia occurs during the last 10 weeks of pregnancy, during labor, or within the first
48 hr after delivery. It is manifested by edema, hypertension, and proteinuria. Drug therapy
includes IV hydralazine or labetalol for blood pressure and magnesium sulfate for seizures.
Eclampsia, occurs if preeclampsia is not treated effectively. Delivery of the fetus is the only
known cure for preeclampsia or eclampsia.
DRUGS USED IN PREGNACY
1. ANALGESICS AND INFLAMMATORY DRUS
DRUGS D NATURE OF EFFECT HHFGGFGGHHMDMCCDDD
Acetaminophe
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Acetaminophen is analgesic antipyretic of choice for use near term.
Aspirin Maternal – aspirin use late in gestation can cause increased bleeding at delivery and
delay the onset of labour. Neonatal – prolong constriction of ductus arteriosus,
pulmonary hypertension, platelet function, and bleeding, intracranial hemorrhage.
Indomethacin
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Premature closure of ductus arteriosus, neonatal pulmonary hypertension.
Ibuprofen Similar to aspirin and indomethacin.
Diclofenac Inhibition of labor, prolongation of pregnancy and suppression of fetal renal function.
If use in the 3rd trimester close to delivery,persistent pulmonary hypertension of the
newborn may occur.
Piroxicam Inhibition of labour, prolongation of pregnancy. If use in the 3rd trimester close to
delivery, persistent pulmonary hypertension of the newborn may occur.

 ANTICOAGULANT
Heparin Heparin is usually the drug of choice for anticoagulation during pregnancy, especially
during the 1st trimester and intrapartum.
Warfarin Warfarin may produce the “Fetal Warfarin Syndrome” or “Warfarin Embryopathy” include
nasal hypoplasia, neonatal respiratory distress, axial skeleton and proximal femur are
affected, spontaneous abortion, stillbirths, CNS defects.
 ANTIMICROBIAL DRUGS
Penicillins Penicillins are without teratogenic risk.

4. Cephalosporins Cephalosporins are thought to be without teratogenic risk.
Erythromycin Pregnant women are at increased risk for hepatotoxicity caused by
erythromycin estolate. There is no evidence that erythromycin is harmful to
the fetus.
Aminoglycosides Congenital hearing loss, deafness.
Chloramphenicol Tetracyclines have been reported to cause congenital abnormalities,
particularly staining of the teeth and retardation of the developing skeletal
system.
Fluoroquinolones
(e.g.Ciprofloxacin,
Norfloxacin,
Ofloxacin)
Fluoroquinolones were shown to cause erosion of the cartilage and other
arthropathies in fetuses. These drugs should not be used in pregnancy.
Sulfonamides
(e.g.Sulfadiazine )
Evidence associating sulfonamide use near term with
hyperbilirubinemia, hemolytic anemia (in G-6-PD deficiency), competition of
albumin site-neonatal kernicterus.
Co-Trimoxazole Do not use at term to avoid kernicterus in the new born and use during
pregnancy only if risk outweigh the benefits since folic acid metabolism may
be effected.
Metronidazole The manufacturer and the Centers for Disease Control (CDC) consider
metronidazole to be contraindicated during 1st trimester in patients with
trichomoniasis. Use for trichomoniasis during the
2nd and 3rd trimester may be acceptable if alternate therapies have failed.
4. CARDIOVASCULAR DRUGS E4hfhhfh
d DRUGS NATURE OF EFFECT
Antiarrhythmics
-Amiodarone
-Digoxin
Digoxin is not a teratogen. It may be given to pregnant
women to treat fetal CHF and supraventricular
tachycardia. Maternal digitalis toxicity has been
associated with fetal toxicity.
ß-Adrenergic blocking
agents
-Atenolol
-Pindolol
-Metoprolol
-Propranolol
These agents are thought to be generally safe in
pregnancy but these have also been associated with
intrauterine growth retardation and neonatal
hypoglycemia and hypotension.
Angiotensin-converting
enzyme (ACE) inhibitors
(e.g. Captopril, enalapril, lisinopril,
fosinopril)
Fetal abnormalities, including death can be caused and
these drugs should not be used in pregnancy.
Calcium – channel
blocking agents(e.g.Nifedipine, diltiazem,
verapamil)
A small, transient decrease in uterine activity occurred
with all verapamil) doses.
Diuretics
-Hydrochlorothiazide
(HCTZ)
-Furosemide
Neonatal hypoglycemia, hyponatremia, hypokalemia and
thrombocytopenia.
Crosses the placenta. Increases fetal urine production,
electrolyte disturbances reported.

5. -Amiloride 5 mg.+ HCTZ
50 mg. (Moduretic®)
Animal studies using amiloride alone had not shown
adverse effects in the fetus but in human studies some
newborns had hypospadias, renovascular hypertension.
Isosorbide dinitrate No reports on the use in human pregnancy. If produces
embryotoxicity in rabbits.
Hydralazine Hydralazine is the parenteral drug of choice used in
pregnancy.
Methyldopa Antihypertensive of choice used in pregnancy.
Reserpine Produces edema of the nasal mucosa in the neonate,
hypothermia and bradycardia.
H
5. GASTROINTESTINAL DRUGS
DRUGS NATURE OF EFFECT
Antacid
-Magnesium
hydroxide
-Aluminium
hydroxide
-Sucralfate
The safety of antacid use during the 1st trimester of pregnancy has not been
established. 2nd and 3rd trimester use appears to be without adverse effects.
Sucralfate is poorly absorbed and no adverse effects to the fetus have been
reported.
Antiulcer
H2-blocker
-Cimetidine
-Famotidine
-Ranitidine
-Nizatidine
Proton-Pump Inhibitor
-Omeprazole
Crosses the placenta. Available evidence suggests safe useduring pregnancy and
breast-feeding.
Laxative
-Bulk laxatives
(psyllium)
- Mineral oil
- Castor oil
These are agent of choice.
Mineral oil should be avoided. Castor oil may cause pelvic congestion.
Metoclopramide Crosses the placenta. Available evidence suggests safe use during pregnancy
and breast-feeding.
Drugs used in Lactation
Although the benefits of breast-feeding are widely recognized, pharmacists, Physicians and
other health professions may advise mothers not to breast-feed when taking medications. This
may be considered a prudent action to avoid harming the breast-fed infant; however, practical
experience and available data show that compatibility between pharmacologic treatment and
breast-feeding is often possible. In fact, given the immunologic and other benefits of breast-
feeding, it may be more beneficial for the infant to be breast-fed even when mothers must use
medications. Also, methods have been developed for ensuring the safety of medications while
breast-feeding

6. Drug Effects In Lactation
Most drugs have not been tested in nursing women and their effect on infant is unknown.
Maternal drug use during lactation should be cautious. There is some degree of risk with any
systemic medication ingested by the mother.
The dose reaching the infant is proportional to the mother’s drug concentration. In many
instances, the infant may not receive sufficient drug to produce adverse effects. Most
prescription drugs taken only when needed, are thought to be safe.
Analgesics - aches and pain
The drugs ibuprofen, diclofenac, indomethacin and naproxen have an acceptably low infant
dose and are considered safe to use. Aspirin is contraindicated only because of the theoretical
risk of Reye's syndrome. Both paracetamol and codeine are safe alternatives, although
combinations containing codeine 30mg should be used cautiously
Antihistamines - allergies and hayfever
Sedating antihistamines such as dexchlorpheniramine or diphenhydramine may be used but
the baby should be observed for sedation or irritability. Of the non-sedating antihistamines,
loratadine and desloratadine are transferred into breast milk in very small amounts and are
considered safe. Fexofenadine and cetirizine should be avoided as they have not been studied.
Nasal sprays containing beclomethasone, fluticasone or budesonide may be used while
breastfeeding. Eye drops containing antazoline and naphazoline are considered safe to use

7. Anti-infectives
In general, these drugs have the potential to cause changes in bowel flora and infants should
be observed for adverse gastrointestinal effects such as diarrhoea and thrush. Penicillins
(amoxycillin, flucloxacillin), cephalosporins (cephalexin), and macrolides (erythromycin and
roxythromycin) are considered safe. Metronidazole is considered safe in doses up to 400mg
three times a day, although it may give the milk a bitter taste. With a single high dose of
metronidazole, milk should be expressed and discarded for 24 hours after the dose. Talk to
your doctor or pharmacist for further advice
Oral contraceptives
The progesterone-only "minipill" is the preferred oral contraceptive for breastfeeding women
as transfer to milk is minimal and lactation is not affected. The combined oestrogen-
progesterone pill may decrease the quantity and alter the composition of milk
Anthelmintics - worms
Pyrantel and mebendazole are considered safe as they are poorly absorbed from the
gastrointestinal tract and are unlikely to be transferred to breast milk in clinically significant
amounts
Anticoagulants:
Heparins (unfractionated and low molecular weight) are considered 'safe' since these agents
have a large molecular weight and do not cross into breast milk to a significant extent. They
are also poorly absorbed. Warfarin is also considered to be compatible with breastfeeding as
transfer is low, and adverse effects and changes in prothrombin time have not been detected
in breastfed infants. However, it would be prudent to monitor the infant's prothrombin time
during treatment
Anticonvulsants:
Carbamazepine, phenytoin and sodium valproate are generally considered to be compatible
with breastfeeding although the infant should be observed for evidence of central nervous
system depression. Available data on the safety of lamotrigine in breastfeeding suggest that
transfer into breast milk may be considerable and therapeutic concentrations have been
detected in breastfed infants. There are insufficient published data to comment on the safety
of gabapentin in breastfeeding.
Antidepressants:
Selective serotonin reuptake inhibitors (SSRIs) transfer into breast milk to varying extents.
Paroxetine is reported to have the lowest transfer into breast milk (weight-adjusted infant
dose 1-3%). Fluoxetine transfers to a greater extent (weight-adjusted infant dose ≤ 14%) and
its active metabolite, norfluoxetine, has a long half-life of one to two weeks and may
accumulate in a breastfed infant. Data on citalopram (weight-adjusted infant dose
approximately 5%) suggest that the relative infant dose of citalopram is intermediate between
paroxetine and fluoxetine. Based on these data, paroxetine is the preferred SSRI in
breastfeeding women.

8. Most tricyclic antidepressants are considered to be compatible with breastfeeding due to low
transfer into breast milk and this is supported by extensive usage data. Moclobemide has low-
transfer into breast milk and is considered compatible with breastfeeding.
Social drugs:
These have particular problems because the dose and pattern of usage are uncontrolled. In
addition most have relatively high infant doses. Infant exposure following maternal ethanol
ingestion may be as high as 20% and has been associated with impaired psychomotor
development. Alcohol consumption should be minimised during lactation (e.g. by
withholding breastfeeding for about two hours after ingestion of a standard alcoholic drink).
Caffeine exposure may be as high as 34% of the weight-adjusted maternal dose and side
effects such as restlessness and irritability have been reported in infants exposed via breast
milk.
Nicotine has been detected in the plasma of breastfed infants, and smoking is best avoided by
breastfeeding mothers. The use of nicotine replacement therapy (e.g. transdermal delivery
systems) in breastfeeding mothers should be considered in terms of risks and benefits.
However, as a general rule, the short-term use of nicotine replacement therapy is far
preferable than continued smoking.
Cardiovascular
DRUG NATURE OF EFFECT
Amiodarone Avoid in breastfeeding.
Atenolol Avoid in favour of antihypertensives with
lower infant exposure
Captopril Considered safe.
Digoxin Considered safe
Diltiazem Unlikely to be problematical in
breastfeeding
Enalapril Considered safe.
Metoprolol Probably safe
Propranolol Probably safe
Quinapril Considered safe.
Verapamil Considered safe.

9. REFERENCES
1. Atkinson HC, Begg EJ, Darlow BA. Drugs in human milk. Clinical pharmacokinetic
considerations. Clinical Pharmacokinetics 1988; 14:217-40.
2. Bennett PN and the WHO Working Group, editors. Drugs and human lactation. 2nd
edition. Amsterdam: Elsevier, 1997.
3. Ilett KF, Kristensen JH, Begg EJ. Drug distribution in human milk. Australian
Prescriber 1997; 20(2):35-40.
4. Speight TM, Holford NHG, editors. Avery's Drug Treatment. 4th edition. Auckland:
Adis International Ltd, 1997.
5. Barbara GW, Joseph TD, Terry LS, Cynthia WH. Pharmacotherapy Handbook. 2nd
ed.Stamford (CT): Appleton & Lange; 2000.
6. Charles FL, Lora LA, Morton PG, Leonard LL. Drug Information Handbook. 8th ed.
Hudson (OH):Lexi-Comp; 2000-2001.
7. Gerald GB, Roger KF, Sumner JY. Drugs in Pregnancy and Lactation. 5th ed.
Baltimore (MD): Lippincott Williams & Wilkins; 1998.
8. Philip OA, James EK. Handbook of Clinical Drug Data. 8th ed. Stamford (CT):
Appleton & Lange; 1997-1998.
9. Robert JB. Effects of Certain Prenatal Drugs on the Fetus and Newborn. Pediatrics in
Review 2002 Jan; 23(1):17-23.