Table 23. Preclinical and Clinical Data Relevant to Use of Antiretrovirals in Pregnancy

Antiretroviral Drug FDA Pregnancy Category * Placental Passage
[Newborn:Maternal
Drug Ratio]
Long-Term Animal Carcinogenicity Studies Rodent Teratogen
zidovudine + C Yes (human) [0.85] Positive (rodent, vaginal tumors) Positive (near lethal dose)
zalcitabine C Yes (rhesus) [0.30 - 0.50] Positive (rodent, thymic lymphomas) Positive (hydrocephalus at high dose)
didanosine B Yes (human) [0.5] Negative (no tumors, lifetime rodent study) Negative
stavudine C Yes (rhesus) [0.76] Positive (rodent, liver and bladder tumors) Negative (but sternal bone calcium decreases)
lamiduvine C Yes (human) [~1.0] Negative (no tumors, lifetime rodent study) Negative
abacavir C Yes (rats) Not completed Positive (anasarca and skeletal malformations at 1000 mg/kg [35x human exposure] during organogenesis)
saquinavir B Unknown Not completed Negative
indinavir C Yes (rats) ("Significant" in rats, low in rabbits) Not completed Negative (but extra ribs in rats)
ritonavir B Yes (rats) [mid-term fetus, 1.15; late-term fetus, 0.15 - 0.64] Positive (rodent, liver tumors) Negative (but cryptorchidism in rats) +#
nelfinavir B Unknown Not completed Negative
amprenavir C Unknown Not completed Positive (thymic elongation; incomplete ossification of bones; low body weight)
lopinavir/ ritonavir C Lopinavir - yes (rats) [0.08 at 6 hrs post-dose] Lopinavir - not completed. Ritonavir - see above Negative (but delayed skeletal ossification and increase in skeletal variations in rats at maternally toxic doses)
nevirapine C Yes (human) [~1.0] Not completed Negative
delavirdine C Yes (rats) [late-term fetus, blood, 0.15; late-term fetus, liver 0.04] Positive (rodent, liver and bladder tumors) Ventricular septal defect
efavirenz C Yes (cynomolgus monkeys, rats, rabbits) [~1.0] Not completed Anencephaly; anophthalmia; microphthalmia (cynomolgus monkeys)

* FDA Pregnancy Categories are: A - Adequate and well-controlled studies of pregnant women fail to demonstrate a risk to the fetus during the first trimester of pregnancy (and there is no evidence of risk during later trimesters); B - Animal reproduction studies fail to demonstrate a risk to the fetus and adequate but well-controlled studies of pregnant women have not been conducted; C - Safety in human pregnancy has not been determined, animal studies are either positive for fetal risk or have not been conducted, and the drug should not be used unless the potential benefit outweighs the potential risk to the fetus; D - Positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experiences, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks; X - Studies in animals or reports of adverse reactions have indicated that the risk associated with the use of the drug for pregnant women clearly outweighs any possible benefit.

+ Despite certain animal data showing potential teratogenicity of ZDV when near-lethal doses are given to pregnant rodents, considerable human data are available to date indicating that the risk to the fetus, if any, is extremely small when given to the pregnant mother beyond 14 weeks gestation. Follow-up for up to 6 years of age for 734 infants born to HIV-infected women who had in utero exposure to ZDV has not demonstrated any tumor development (228). However, no data are available on longer follow-up for late effects.

+# These effects seen only at maternally toxic doses.

* FDA Pregnancy Categories are: A - Adequate and well-controlled studies of pregnant women fail to demonstrate a risk to the fetus during the first trimester of pregnancy (and there is no evidence of risk during later trimesters); B - Animal reproduction studies fail to demonstrate a risk to the fetus and adequate but well-controlled studies of pregnant women have not been conducted; C - Safety in human pregnancy has not been determined, animal studies are either positive for fetal risk or have not been conducted, and the drug should not be used unless the potential benefit outweighs the potential risk to the fetus; D - Positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experiences, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks; X - Studies in animals or reports of adverse reactions have indicated that the risk associated with the use of the drug for pregnant women clearly outweighs any possible benefit.

+ Despite certain animal data showing potential teratogenicity of ZDV when near-lethal doses are given to pregnant rodents, considerable human data are available to date indicating that the risk to the fetus, if any, is extremely small when given to the pregnant mother beyond 14 weeks gestation. Follow-up for up to 6 years of age for 734 infants born to HIV-infected women who had in utero exposure to ZDV has not demonstrated any tumor development (228). However, no data are available on longer follow-up for late effects.

+# These effects seen only at maternally toxic doses.

From: Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents

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