Clinical Manual for Management of the HIV-Infected ... - myCME.com

3–28 | Clinical Manual for Management of the HIV-Infected Adult/2006
Nonnucleoside Reverse Transcriptase Inhibitors
Antiretroviral Drug Pharmacokinetics in Pregnancy Concerns in Pregnancy Rationale for Recommended Use in Pregnancy
Recommended Agents
Nevirapine (Viramune) Pharmacokinetics not significantly
altered in pregnancy; no change in
dose indicated.
Not Recommended
No evidence of human teratogenicity.
Increased risk of symptomatic, often rashassociated,
and potentially fatal liver toxicity
among women with CD4 counts >250 cells/
µL when first initiating therapy; unclear
whether pregnancy increases risk.
Efavirenz (Sustiva) No studies in human pregnancy. FDA Pregnancy Class D; significant
malformations (anencephaly, anophthalmia,
cleft palate) were observed in 3 (15%) of
20 infants born to cynomolgus monkeys
receiving efavirenz during the first trimester
at a dose giving plasma levels comparable to
systemic human therapeutic exposure. Three
cases were reported of neural tube defects
in humans after first-trimester exposure;
relative risk is unclear.
Delavirdine (Rescriptor) No studies in human pregnancy. Rodent studies indicate potential for
carcinogenicity and teratogenicity
(see Table 1).
Protease Inhibitors
Because of the increased risk of potentially lifethreatening
hepatotoxicity in women with high CD4
counts, nevirapine should be initiated in pregnant
women with CD4 counts >250 cells/µL only if benefit
clearly outweighs risk. Women who begin pregnancy on
nevirapine regimens and are tolerating them well may
continue therapy, regardless of CD4 count.
Use of efavirenz should be avoided in the first trimester,
and women of childbearing potential must be counseled
regarding risks and avoidance of pregnancy. Because
of the known failure rates of contraception, alternate
regimens should be strongly considered in women of
childbearing potential. Use after the second trimester of
pregnancy can be considered if other alternatives are not
available and if adequate contraception can be assured
postpartum.
Given lack of data and concerns regarding teratogenicity in
animals, delavirdine is not recommended for use in human
pregnancy unless alternatives are not available.
Antiretroviral Drug Pharmacokinetics in Pregnancy Concerns in Pregnancy Rationale for Recommended Use in Pregnancy
PI class concerns Hyperglycemia, new onset or exacerbation of
diabetes mellitus, and diabetic ketoacidosis
reported with PI use; unclear if pregnancy
increases risk. Conflicting data regarding
preterm delivery in women receiving PIs.
Recommended Agents
Lopinavir/ritonavir
(Kaletra)
Pharmacokinetic (PK) studies of
standard ritonavir dose of lopinavir/
ritonavir capsules (3 capsules twice
daily) during 3rd trimester indicated
levels were significantly lower than
during postpartum period and in
nonpregnant adults; an increased
dose of 4 capsules of lopinavir/
ritonavir twice daily starting in the
3rd trimester resulted in adequate
lopinavir exposure; by 2 weeks
postpartum, standard dosing was
again appropriate. PK studies of
the new lopinavir/ritonavir tablet
formulation are under way, but data
are not yet available.
No evidence of human teratogenicity. Welltolerated,
short-term safety demonstrated in
phase I/II studies.
The capsule formulation is no longer available. PK
studies of the new tablet formulation are under way,
but there are currently insufficient data to make a
definitive recommendation regarding dosing during
pregnancy. Some experts would administer standard
dosing (2 tablets twice daily) throughout pregnancy and
monitor virologic response and lopinavir drug levels, if
available. Other experts, extrapolating from the capsule
formulation PK data, would increase the dose of the tablet
formulation during the 3rd trimester (from 2 tablets
to 3 tablets twice daily), returning to standard dosing
postpartum. Once-daily lopinavir/ritonavir dosing is not
recommended during pregnancy because there are no
data to address whether drug levels are adequate with
such administration.