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PART I       Principles of Pharmacology

TABLE 3-6 
Toxic Effects of Drugs During Pregnancy
MOST SUSCEPTIBLE PERIOD*

SECOND
DRUG TOXIC EFFECT TO FETUS FIRST TRIMESTER TRIMESTER THIRD TRIMESTER TERM

Anticancer drugs Cleft palate, extremity defects, severe ✓

stunting, death
Chloramphenicol Gray syndrome, death ✓
Cortisone Cleft palate ✓
Coumarin anticoagulants Hemorrhage, death
Diazepam Cleft palate, respiratory depression ✓ ✓
Local anesthetics Bradycardia, respiratory depression ✓
Lysergic acid diethylamide Chromosomal damage, stunted growth ✓
Opioid analgesics Respiratory depression, neonatal death ✓
Potassium iodide Goiter, mental retardation
Quinine Deafness, thrombocytopenia ✓ ✓
Sex steroids Masculinization, vaginal carcinoma
(delayed)
Streptomycin Eighth cranial nerve damage, micromelia,
multiple skeletal abnormalities
Tetracyclines Inhibition of bone growth, tooth
discoloration, micromelia, syndactyly
Thalidomide Phocomelia, multiple defects ✓
Thiazide diuretics Thrombocytopenia, neonatal death ✓ ✓

Adapted from Underwood T, Iturrian EB, Cadwallader DE: Some aspects of chemical teratogenesis, Am J Hosp Pharm 27:115-122, 1970.
*Coumarins and other drugs with no indication mark are approximately evenly toxic throughout pregnancy.

TABLE 3-7 
U.S. Food and Drug Administration Pregnancy Risk Categories
CATEGORY DEFINITION EXAMPLE DRUGS

A Adequate and well-controlled studies have failed to show a risk to the Levothyroxine, magnesium sulfate (injectable),
fetus in the first trimester of pregnancy (and there is no evidence of sodium fluoride*
risk in later trimesters)
B Either (1) adequate and well-controlled studies have failed to show a Acetaminophen,* amoxicillin and clavulanate,
risk to the fetus in the first trimester of pregnancy, and there is no cefaclor, erythromycin, lidocaine, naproxen,
evidence of risk in later trimesters, but animal reproduction studies penicillin V*
have shown an adverse effect on the fetus; or (2) human studies are
lacking, but animal studies have failed to show a risk to the fetus
C No adequate and well-controlled studies have been performed in Atropine, bupivacaine, butorphanol, codeine,
pregnant women, but animal reproduction studies are lacking or diflunisal, epinephrine, hydrocortisone
have shown an adverse effect on the fetus. Potential benefit may (topical), mepivacaine, morphine, thiopental
warrant use of the drug in pregnant women despite potential risk
D Positive evidence exists of human fetal risk based on adverse reaction Aspirin,* hydrocortisone (systemic),*
data from investigational or marketing experience or studies in lorazepam, midazolam, pentobarbital,
humans. Potential benefit may warrant use of the drug in pregnant valproic acid
women despite potential risk
X Studies in animals or humans have shown fetal abnormalities, or there Ergotamine, estradiol, isotretinoin,
is positive evidence of human fetal risk based on adverse reaction temazepam, triazolam, warfarin
data from investigational or marketing experience, or both, and the
potential risk of the drug in pregnant women clearly outweighs the
potential benefit

Adapted from USP dispensing information—drug information for the health care provider, ed 26, Rockville, MD, 2006, The United States Pharmacopeial
Convention, Inc.
*Estimated ranking based on current information and FDA category definitions.