Rifampin in pregnancy and breastfeeding


Risk Factor: CM
Class: Anti-infectives/ Antituberculosis

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary

Fetal Risk Summary

Reproduction studies with rifampin in mice and rats at doses greater than 150 mg/kg produced spina bifida in both species and cleft palates in the mouse fetuses (1). Teratogenicity in rodents has been reported with oral doses 15 to 25 times the human dose (2). Studies with pregnant rabbits revealed no evidence of teratogenicity (1).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 20 newborns had been exposed to rifampin during the 1st trimester (F. Rosa, personal communication, FDA, 1993). No major birth defects were observed (one expected).

No controlled studies have linked the use of rifampin with congenital defects (3,4). One report described nine malformations in 204 pregnancies that went to term (5). This incidence, 4.4%, is similar to the expected frequency of defects in a healthy nonexposed population but higher than the 1.8% rate noted in other tuberculosis patients (5): Anencephaly (1 case) Hydrocephalus (2 cases) Limb malformations (4 cases) Renal tract defects (1 case) Congenital hip dislocation (1 case) Several reviews have evaluated the available treatment of tuberculosis during pregnancy (6,7 and 8). All concluded that rifampin was not a proven teratogen and recommended use of the drug with isoniazid and ethambutol if necessary. Other reports on the use of the agent in pregnancy have observed no fetal harm (9,10).

Rifampin crosses the placenta to the fetus (11,12 and 13). At term, the cord:maternal serum ratio ranged from 0.120.33 (12). In a second case involving pregnancy termination at 13 weeks’ gestation, the fetal:maternal ratio 4 hours after a 300-mg dose was 0.23 (11).

Rifampin has been implicated as one of the agents responsible for hemorrhagic disease of the newborn (14). In one of the three infants affected, only laboratory evidence of hemorrhagic disease of the newborn was present, but in the other two, clinically evident bleeding was observed. Prophylactic vitamin K1 is recommended to prevent this serious complication (see Phytonadione).

Rifampin may interfere with oral contraceptives, resulting in unplanned pregnancies (see Oral Contraceptives) (15).

Breast Feeding Summary

Rifampin is excreted into human milk. In one report, the concentrations were 13 g/mL with about 0.05% of the daily dose appearing in the milk (16). In another study, milk levels were 3.44.9 g/mL, 12 hours after a single 450-mg oral dose (17). Maternal plasma samples averaged 21.3 g/mL, indicating a milk:plasma ratio of about 0.20. These amounts were thought to represent a very low risk to the nursing infant (18). No reports describing adverse effects in nursing infants have been located. The American Academy of Pediatrics considers rifampin to be compatible with breast feeding (19).



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