Table 7-6 Preclinical and Clinical Data Relevant to the Use of Antiretovirals During Pregnancy
(See Safety and Toxicity of Individual Antiretroviral Drugs in pregnancy for more detail on drugs)
| Antiretroviral Drug |
FDA pregnancy
category † |
Placental passage
[newborn:mother drug ratio] |
Long-term animal
carcinogeniticy studies
|
Animal
teratogen studies |
| Nucleoside and nucleotide analogue reverse transcriptase inhibitors |
| Abacavir (Ziagen, ABC) |
C |
Yes (rats) |
Positive (malignant and non-malignant tumors of liver, thyroid in female rats, and preputial and clitoral gland of mice and rats) |
Positive (rodent anasarca and skeletal malformations at 1000 mg/kg (35x human exposure) during organogenesis; not seen in rabbits) |
| Didanosine (Videx, ddI) |
B |
Yes (human) [0.5] |
Negative (no tumors, lifetime rodent study) |
Negative |
| Emtricitabine (Emtriva, FTC) |
B |
Unknown |
Not completed |
Negative |
| Lamivudine (Epivir, 3TC) |
C |
Yes (human) [~1.0] |
Negative (no tumors, lifetime rodent study) |
Negative |
| Stavudine (Zerit, d4T) |
C |
Yes (rhesus monkey) [0.76] |
Positive (mice and rats, at very high dose exposure, liver and bladder tumors) |
Negative (but sternal bone calcium decreases in rodents) |
| Tenofovir DF (Viread) |
B |
Yes (rat and monkey) |
Not completed |
Negative (osteomalacia when given to juvenile animals at high doses) |
| Zalcitabine (HIVID, ddC) |
C |
Yes (rhesus monkey) [0.30–0.50] |
Positive (rodent, thymic lymphomas) |
Positive (rodent hydrocephalus at high dose) |
| Zidovudine (Retrovir, AZT, ZDV) |
C |
Yes (human) [0.85] |
Positive (rodent, noninvasive vaginal epithelial tumors) |
Positive (rodent near-lethal dose) |
| Non-nucleoside reverse transcriptase inhibitors |
Delavirdine
(Rescriptor) |
C |
Unknown |
Positive (hepatocellular adenomas and carcinomas in male and female mice but not rats, bladder tumors in male mice) |
Positive (rodentventricular septal defect) |
| Efavirenz (Sustiva) |
D |
Yes (cynomologus monkey, rat, rabbit) [~1.0] |
Positive (increased hepatocellular adenomas and carcinomas and pulmonary alveolar/bronchiolar adenomas in female but not male mice) |
Positive (cynomologus monkeyanencephaly, anophthalmia, micro-ophthalmia) |
| Nevirapine (Viramune) |
C |
Yes (human) [~1.0] |
Positive (hepatocellular adenomas and carcinomas in mice and rats) |
Negative |
| Protease inhibitors |
| Amprenavir (Agenerase) |
C |
Unknown |
Positive (hepatocellular adenomas and carcinomas in male mice and rats) |
Negative (but deficient ossification and thymic elongation in rats and rabbits) |
| Atazanavir |
B |
Unknown |
Not completed |
Negative |
| Fosamprenavir (Lexiva) |
C |
Unknown |
Positive (increased benign and malignant liver tumors in male rodents) |
Negative (deficient ossification with amprenavir but not fosamprenavir) |
| Indinavir (Crixivan) |
C |
Minimal (humans) |
Positive (thyroid adenomas in male rats at highest dose) |
Negative (but extra ribs in rodents) |
| Lopinavir/Ritonavir (Kaletra) |
C |
Unknown |
Not completed |
Negative (but delayed skeletal ossification and increase in skeletal variations in rats at maternally toxic doses) |
| Nelfinavir (Viracept) |
B |
Minimal (humans) |
Positive (thyroid follicular adenomas and carcinomas in rats) |
Negative |
| Ritonavir (Norvir) |
B |
Minimal (humans) |
Positive (rodent, liver adenomas and carcinomas in male mice) |
Negative (but cryptorchidism in rodents) |
| Saquinavir (Fortovase) |
B |
Minimal (humans) |
Not completed |
Negative |
| Fusion inhibitors |
| Enfuvirtide (Fuzeon) |
B |
Unknown |
Not done |
Negative |