Isoniazid / pyrazinamide / rifampin Pregnancy and Breastfeeding Warnings

Brand names: Rifater

Isoniazid / pyrazinamide / rifampin Pregnancy Warnings

Use is recommended during pregnancy only if the potential benefit outweighs the possible risk to the fetus.

US FDA pregnancy category: Not assigned.

Risk Summary: Some animal models given combinations of isoniazid, pyrazinamide, and rifampin had an increased rate of chromosomal lymphocyte aberrations.

Comments:
-When administered during the last few weeks of pregnancy, rifampin can cause postnatal hemorrhages in the mother and infant for which treatment with vitamin K may be indicated.
-Rifampin may affect the reliability of oral or other systemic hormonal contraceptives; advise patients to use alternative birth control methods during treatment.
-Both isoniazid and rifampin have been reported to cross the placental barrier; rifampin has appeared in cord blood.

Animal studies have revealed evidence of teratogenicity (including cleft palate and spina bifida) with use of rifampin at doses 0.2 to 2 times the maximum recommended human (MRH) dose. Imperfect osteogenesis and embryotoxicity in animals were also reported at oral rifampin doses about 3 times the MRH dose. Isoniazid may exert an embryocidal effect; however, no isoniazid-related congenital anomalies have been found in animal reproduction studies in mammalian species. Animal studies have not been reported with pyrazinamide. There are no controlled data in human pregnancy.

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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Isoniazid / pyrazinamide / rifampin Breastfeeding Warnings

A decision should be made to discontinue breastfeeding or to discontinue this drug, taking into account the importance of this drug to the mother.

Excreted into human milk: Yes

Comments:
-The US Centers for Disease Control and Prevention and other professional organizations state breastfeeding should not be discouraged in women taking any of the active components found in this drug.
-The American Academy of Pediatrics considers isoniazid and rifampin compatible with breastfeeding.
-The WHO classifies this combination drug as compatible with breastfeeding; the breastfed infant should be monitored for jaundice.
-Limited data indicates that the low levels of isoniazid and rifampin in breastmilk would not be expected to cause any adverse effects in breastfed infants; however, monitor infants for rare instances of jaundice.
-Instruct breastfeeding mothers to administer the one-daily dose of this combination drug before the infant's longest sleep period to decrease the dose the infant receives.
-Advise nursing mothers to concomitantly take 25 mg of oral pyridoxine daily and to give their breastfed infants 1 mg/kg of pyridoxine daily during treatment with this combination drug.

There is a theoretical risk of convulsions and neuropathy (associated with pyridoxine/Vitamin B6 deficiency) in breastfed infants of mothers taking isoniazid. In mothers given single oral doses of isoniazid, average peak drug levels in breastmilk occurred at 2 to 3 hours after the dose: 2.1 mg/L (200 mg dose), 5.4 to 5.5 mg/L (300 mg dose), and 9 to 10.6 mg/L (600 mg dose). The breastfed infants of mothers who took isoniazid 300 mg once daily for at least 34 days received about 0.3% to 1.2% of the maternal-adjusted dosage of isoniazid.

After a single 150 mg oral dose of rifampin, drug levels in breastmilk 4 hours after the dose ranged from 0 to 1.8 mL. After a single oral dose of 450 mg, breastmilk levels 12 hours after the dose ranged from 3.4 to 4.9 mg/L.

Normal development was observed in 4 breastfed children (ages 3.9 to 5.1 years) of mothers who received isoniazid and/or rifampin throughout pregnancy and postpartum as part of a multi-drug treatment regimen for tuberculosis; only hyperactivity in 1 child and a mild speech delay in another were noted.

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Further information

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