| TABLE
2. Preclinical and clinical data relevant to the use of antiretrovirals
in pregnancy* (see Safety
and Toxicity of Individual Antiretroviral Drugs in Pregnancy
for more detail on drugs) |
| Antiretroviral
drug |
Food
and Drug Administration (FDA) pregnancy category |
Placental
passage
(Newborn:mother drug ratio) |
Long-term
animal carcinogenicity studies |
Animal
teratogen studies |
| Nucleoside
analogue reverse transcriptase inhibitors |
|
Zidovudine
(Retrovir, AZT, ZDV)
|
C |
In
humans
[0.85] |
Positive
(rodent, noninvasive vaginal epithelial tumors) |
Positive
(rodent-near lethal dose)
|
|
Zalcitabine
(HIVID, ddC)
|
C |
Yes
(rhesus monkey)
[0.30-0.50] |
Positive
(rodent, thymic lymphomas) |
Positive
(rodent-hydrocephalus at high dose)
|
|
Didanosine
(Videx, ddI)
|
B |
Yes
(human)
[0.5] |
Negative
(no tumors, lifetime rodent study) |
Negative
|
|
Stavudine
(Zerit, d4T)
|
C |
Yes
(rhesus monkey)
[0.76] |
Not
completed |
Negative
(but sternal bone calcium decreases in rodents)
|
|
Lamivudine
(Epivir, 3TC)
|
C |
Yes
(human)
[~1.0] |
Negative
(no tumors, lifetime rodent study) |
Negative
|
|
Abacavir
(Ziagen, ABC)
|
C |
Yes
(rats) |
Not
completed |
Positive
(rodent anasarca and skeletal malformations at 1000 mg/kg
[35x human exposure] during organogenesis; not seen in rabbits)
|
| Non-nucleoside
reverse transcriptase inhibitors |
|
Nevirapine
(Viramune)
|
C |
Yes
(human)
[~1.0] |
Not
completed |
Negative
|
|
Delavirdine
(Rescriptor)
|
C |
Unknown |
Not
completed |
Postive
(rodent-ventricular septal defect)
|
|
Efavirenz
(Sustiva)
|
C |
Yes
(cynomologus monkey, rat, rabbit)
[~1.0] |
Not
completed |
Positive
(cynomologus monkey-anencephaly, anophthalmia, microophthalmia)
|
| Protease
inhibitors |
|
Indinavir
(Crixivan)
|
C |
Yes
(rats, rabbits)
[substantial in rats, low in rabbits] |
Not
completed |
Negative
(but extra ribs in rodents)
|
|
Ritonavir
(Norvir)
|
B |
Yes
(rats)
[mid-term fetus, 1.15; late-term fetus, 0.15-0.64] |
Positive
(rodent, liver adenomas and carcinomas in male mice) |
Negative
(but cryptochidism in rodents)
|
|
Saquinavir
(Fortovase)
|
B |
Minimal
(rats, rabbits) |
Not
completed |
Negative
|
|
Nelfinavir
(Viracept)
|
B |
Unknown |
Not
completed |
Negative
|
|
Amprenavir
(Agenerase)
|
C |
Unknown |
Not
completed |
Negative
(but deficient ossification and thymic elongation in rats
and rabbits)
|
|
Lopinavir/Ritonavir
(Kaletra)
|
C |
Unknown |
Not
Completed |
Negative
(but delayed skeletal ossification and increase in skeletal
variations in rats ar maternally toxic doses)
|
|
FDA
pregnancy categories: |
| |
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 and 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. |
|
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