Animal studies have revealed evidence of teratogenicity at exposures higher than the recommended clinical dose. In rabbits, low incidences of malformations (microphthalmia, absent incisors) were seen at ombitasvir exposures 4-fold higher than AUC exposure at recommended clinical dose. In mice, open eyelid occurred at a higher rate in fetuses of dams given ombitasvir (relationship unclear); the major ombitasvir human metabolites (inactive) were not teratogenic in mice at exposures about 26 times higher than in humans at recommended clinical dose. In mice, low incidences of malformations (open eyelids) were seen at paritaprevir/ritonavir exposures 32/8-fold higher than human exposure at recommended clinical dose. In rats, paritaprevir/ritonavir had no effect on embryofetal viability or fertility at exposures 2- to 8-fold higher than human exposure at recommended clinical dose. Minimal transfer of ombitasvir- and paritaprevir-derived materials through the placenta occurred in pregnant rats. There are no controlled data in human pregnancy.

Pregnancy must be avoided in female patients and female partners of male patients using a ribavirin-containing regimen. All animal species exposed to ribavirin have shown significant teratogenic and/or embryocidal effects. Females of reproductive potential and their male partners should not receive ribavirin unless they are using effective contraception during therapy and for up to 7 months after therapy.

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.

Use of a ribavirin-containing regimen is contraindicated in pregnant women and in the male partners of women who are pregnant.
-According to some authorities: This drug should not be used during pregnancy or in females of reproductive potential not using effective contraception.

US FDA pregnancy category: Not assigned.

Risk summary: No adequate data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-Coadministration with ethinyl estradiol is contraindicated.
-If applicable, the manufacturer product information for ribavirin should be consulted regarding use during pregnancy and use in females and males of reproductive potential.
-Effective contraception is required during ribavirin therapy and for up to 7 months after the last dose; local protocol should be consulted regarding contraception timing.

See references

LactMed: Some experts recommend against breastfeeding when this drug is used with ribavirin.
-According to some authorities: A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Unknown (ombitasvir, paritaprevir); Yes (ritonavir)
Excreted into animal milk: Yes (ombitasvir, paritaprevir [and its hydrolysis product M13])

Comments:
-Neither ombitasvir nor paritaprevir has been studied in nursing mothers receiving treatment for hepatitis C virus infection.
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this product.
-The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this product or the mother's underlying condition should be considered.
-The manufacturer product information for ribavirin should be consulted (if applicable).

OMBITASVIR, PARITAPREVIR:
Amounts of ombitasvir and paritaprevir in breast milk are most likely very low as both components are highly bound to maternal plasma proteins.

RITONAVIR:
Measurable levels of ritonavir are excreted in milk and low levels can be found in the blood of some breastfed infants. No side effects have been reported in breastfed infants.

In 1 study, nursing mothers used ritonavir as part of a clinical trial to evaluate maternal-to-child transmission of HIV infection. Doses, dose regimens, and breast milk collection times were not provided. Ritonavir was not detected in any of 60 breast milk samples.

A total of 23 milk samples were obtained (at birth, 1 month, 3 months, and/or 6 months postpartum) from 9 mothers using lopinavir 400 mg plus ritonavir 100 mg twice a day as part of combination antiretroviral therapy. Their breastfed infants had a total of 6 blood samples analyzed at 1 month, 3 months, and/or 6 months postpartum. Milk samples and infant blood samples were collected at about 4.5 hours (range: 3.5 to 6 hours) after the previous maternal dose and about 30 minutes (range: 20 to 60 minutes) after nursing. The ritonavir level in breast milk averaged 79 mcg/L (range: 31 to 193 mcg/L). The ritonavir plasma level in infants averaged 7 mcg/L (range: 0 to 138 mcg/L), which was about 12% (range: 11% to 40%) of the maternal serum level.

Starting at delivery, 30 mothers used zidovudine 300 mg, lamivudine 150 mg, lopinavir 400 mg, and ritonavir 100 mg orally twice a day; they were studied at 6, 12, or 24 weeks postpartum (10 at each time). Infants could breastfeed freely during the study period. On the study day, breast milk samples and maternal and infant plasma samples were collected before the maternal morning dose (about 14.9 hours after the prior evening dose) and 2, 4, and 6 hours after the maternal dose. Detectable quantities (at least 10 mcg/L) of ritonavir were found in 112 of 121 breast milk samples; breast milk level averaged 79 mcg/L over the 6 hours. Ritonavir was undetectable (less than 10 mcg/L) in all of the 115 infant plasma samples.

At 3-hour intervals before cesarean section, 9 women with HIV infection received 3 doses of lopinavir 200 mg, ritonavir 150 mg, zidovudine 300 mg, lamivudine 50 mg; breast milk samples were collected at about 25 hours postpartum. Milk level averaged 240 mcg/L (range: 98 to 402 mcg/L) for ritonavir in the 8 women where it was quantified.

Ritonavir was measured in 117 breastfed (90% exclusive) infants whose mothers were using lopinavir plus ritonavir for HIV infection during pregnancy and postpartum. At 8 and 12 weeks postpartum, none of the infants had detectable ritonavir plasma levels. At 12 weeks postpartum, ritonavir was detectable in hair samples of 91% of infants; concentration averaged 0.15 ng/mg of hair (range: 0.03 to 0.42 ng/mg). According to author interpretation, infant exposure to ritonavir during breastfeeding is negligible.

See references