Not recommended

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned

Risk Summary: There is no data to inform a drug-associated risk in pregnant women; based on animal data, may cause fetal harm.

Comments:
-If used during pregnancy, women should be advised of the possible risk to the fetus.

In animal studies, developmental toxicity has been observed at clinically relevant doses. Administration to rats during organogenesis resulted in decreased fetal growth at the highest dose tested; the no-effect dose for embryofetal developmental toxicity was approximately equal to the recommended human daily dose (RHDD) on a mg/m2 basis. In rabbits, embryofetal mortality was increased at the high dose, fetal body weight decreased and morphological variations increased at all but the lowest dose tested. The no-effect dose for embryofetal developmental toxicity was found to be less than the RHDD. Maternal toxicity occurred at the highest dose tested in rats and rabbits. When administered to male and female rats prior to and during mating and to female rats throughout gestation and lactation, increased embryofetal mortality and decreased postnatal offspring viability, growth, and functional development occurred at the high dose (13 times human exposure). The no-effect dose for pre- and postnatal developmental toxicity was found to be approximately equal to the RHDD on a mg/m2 basis. There are no controlled data in human pregnancy.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

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This drug and its metabolites have been found in the milk of lactating rats at levels 2.5-fold higher than those appearing in maternal plasma. Drug levels were measured for a single-women starting therapy at 50 mg orally twice a day while breastfeeding her 18-month old infant. On day 3 of her therapy, a pre-dose sample (collected before her first dose of the day) measured 33.8 mcg/L; the peak concentration was 229.5 mcg/L measured at 2 hours post-dose; an average drug concentration of 94.4 mcg/L was calculated (an estimated 1.6% of the maternal weight-adjusted dose). Drug metabolites were not measured. Some manufacturers recommend against use during breastfeeding due to the potential for serious adverse reactions. Other authorities suggest caution due to the low levels of drug in breastmilk, especially if the infant is older than 2 months of age.

Benefit should outweigh risk

Excreted into human milk: Yes

Comments: The effects in the nursing infant are unknown.

See references