The FDA (USA) has established 5 categories to indicate the potential of systematically absorbed drug for causing birth defects. The key differentiation among the categories rests upon the reliability of documentation and the risk:benefit ratio (Lacy et al., 1998).
Controlled studies in pregnant women fail to demonstrate a risk to the fetus in the first trimester with no evidence of risk in later trimesters. The possibility of fetal harm appears remote.
Examples: Folic acid, T4, Magnesium sulfate (inj.!)
PRC B: The animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal-reproduction studies have shown an ARs (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester and there is no evidence of later trimesters. Examples: penicillins, erythromycin, paracetamol, lidocaine.
PRC C: The studies in animals have revealed ARs on the fetus (teratogenic, embryocidal or other effects) and there are no controlled studies in women, or studies in women are not available. Drug should be given only if the potential benefits justify the potential risk to the fetus.
Examples: atropine, adrenaline, thiopental, bisoprolol.
PRC D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g. if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used are ineffective.).
Examples: phenytoin, valproate, diazepam, cyclophosphamide.
PRC X: Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience, or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit . The drug is contraindicated in women who are or may become pregnant.
Examples: thalidomide, estrogens, isotretionoin, ergometrine.
LACTATION RISK CATEGORIES (LRC) (Hale, 2004; 2008):
L1 – safest: Paracetamol, Ibuprofen, Epinephrine.
Diclofenac, Fentanyl, Cetirizine,
Acarbose, Acetylsalicylic acid,
Indometacin, Codeine, Morphine, Midazolam, Triazolam,
Colchicine, Lithium, Ergobrevine,
ACE inhibitors (enalapril etc.)
Goodman & Gilman's The Pharmacologic
Basis of Therapeutics - 11th Ed. (2006)
A : controlled studies show no risk
B : no evidence of risk in humans
C : risk cannot be ruled out
D : positive evidence of risk
X : contraindicated in pregnancy
L1 : safest
L2 : safer
L3 : moderately safe
L4 : possibly hazardous
L5 : contraindicated