Indinavir Pregnancy and Breastfeeding Warnings

Brand names: Crixivan

Indinavir Pregnancy Warnings

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus; use of unboosted indinavir is not recommended during pregnancy.

AU TGA pregnancy category: B3
US FDA pregnancy category: C

Comments:
-A pregnancy exposure registry is available.

Animal studies have failed to reveal evidence of teratogenicity in rabbits and dogs, but have revealed evidence of teratogenicity in rats. Of treatment-related external, visceral, and skeletal changes, none were seen in rabbits or dogs at maternal exposures comparable to or slightly higher than human exposure while skeletal changes (increased incidence of supernumerary ribs [at exposures at or below human exposure] and cervical ribs [at exposures comparable to or slightly higher than human exposure]) were observed in rats; no treatment-related external or visceral changes were seen in rats. Fetal plasma drug levels were 1% to 50% of maternal plasma levels, depending on the species and dosage. There are no controlled data in human pregnancy.

Placental transfer to the fetus has been reported as minimal (cord to maternal plasma ratio about 0.12).

Hyperbilirubinemia (reported primarily as elevated indirect bilirubin) has occurred during treatment with this drug. It is unknown whether perinatal maternal dosing will exacerbate physiologic hyperbilirubinemia in neonates; according to some authorities, use of this drug in pregnant women at the time of delivery should be carefully considered. According to some experts, minimal placental transfer lessens this concern.

An optimal dosing regimen has not been determined for use of this drug during pregnancy. In 2 trials of the pharmacokinetics of unboosted indinavir (800 mg every 8 hours), significantly lower drug plasma levels were observed during pregnancy than postpartum. Due to the considerably lower antepartum exposures seen in these trials and the limited data in this patient population, the use of unboosted indinavir in HIV-infected pregnant patients is not recommended. Insufficient data available for definitive dosing recommendations of this drug plus ritonavir during pregnancy. According to some experts, this drug must be used with low-dose ritonavir boosting during pregnancy.

To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com

The APR has received prospective reports of over 440 exposures to regimens containing this drug (over 280 exposed in the first trimester; over 160 exposed in the second/third trimester) resulting in live births; there was no significant difference in the overall risk of birth defects for this drug compared with the background birth defect rate of 2.7% in the US reference population. Enough first trimester exposures have been monitored to detect at least a 2-fold increased risk of overall birth defects; no such increases detected. The prevalence of birth defects with first trimester and second/third trimester exposures was 2.4% and 1.8%, respectively.

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 C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

See references

Indinavir Breastfeeding Warnings

Breastfeeding is not recommended during use of this drug; if replacement feeding is not an option, a different drug may be preferred.

Excreted into human milk: Yes

Comments:
-The effects in the nursing infant are unknown.
-The US CDC, American Academy of Pediatrics, and manufacturer advise HIV-infected women not to breastfeed to avoid postnatal transmission of HIV to a child who may not yet be infected.
-Local guidelines should be consulted if replacement feeding is not an option.

During the first 5 days postpartum, milk was collected just before and 2 hours after dosing in 1 woman using this drug (600 mg twice a day) as part of highly-active antiretroviral combination therapy. Milk drug levels ranged between 90% and 540% of maternal serum level; further details regarding the timing or actual breast milk levels not provided.

See references

Further information

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