Small
Study Shows Etravirine (Intelence) Appears Safe during Pregnancy
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| SUMMARY:
In a small case series of 5 pregnant women, use
of the next-generation non-nucleoside reverse
transcriptase inhibitor (NNRTI) etravirine
(Intelence) was not associated with any fetal
abnormalities or birth defects, and pharmacokinetic
data showed that no dose adjustment was necessary,
researchers reported last week at the 12th European
AIDS Conference (EACS 2009).
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By
Liz Highleyman
The
NNRTI class of antiretroviral drugs can have different effects
during pregnancy. Nevirapine
(Viramune) is safe for pregnant women with low CD4 counts,
has not been associated with fetal harm, and is commonly
used in resource-limited settings to prevent mother-to-child
HIV transmission. Efavirenz
(Sustiva), however, is considered contraindicated during
pregnancy because it has been linked to birth defects in
animals and humans.
Researchers
from Tibotec conducted a study to evaluate available pharmacokinetic
(PK) and safety data regarding etravirine use by pregnant
women in a compassionate use program prior to the drug's
approval. Previous animal studies revealed no fetal or newborn
abnormalities.
The
analysis included 5 women who gave birth to 6 infants (including
1 set of twins). The mothers' ages ranged from 19 to 42
years. All women received etravirine as part of a combination
regimen that contained ritonavir-boosted darunavir
(Prezista); 2 also received enfuvirtide
(Fuzeon). Infants received prophylactic antiretroviral
drugs to prevent mother-to-child HIV transmission.
Within
this group, 3 women were exposed to etravirine throughout
their pregnancies, while 2 took the drug only during the
third trimester. Drugs are least likely to cause fetal damage
during the third trimester, but this is when pharmacokinetic
changes are most likely due to increased body mass and blood
volume.
Pharmacokinetic
assessments were performed using blood samples collected
pre-dosing and 1, 3, 6, and 12 hours post-dosing during
the third trimester. The women were followed until delivery
and, whenever possible, umbilical cord blood samples were
obtained.
Results
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Etravirine
blood levels and PK parameters -- including peak (highest),
trough (lowest), and steady-state drug concentrations
-- were similar to those observed in non-pregnant adults. |
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3
of the 5 women underwent Caesarean sections (1 pre-term
due to twins), while 2 had normal vaginal deliveries. |
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3
mothers had undetectable HIV RNA at delivery (no data
was available for the remaining 2 women). |
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1
baby had undetectable viral load at delivery and 2 (twins)
had undetectable viral load at 4 months (no data was
available for the remaining 3 infants). |
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All
babies were generally healthy. |
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1
infant was born with an accessory auricle (a minor abnormality
of the outer ear), but was otherwise normal. |
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There
were no other malformations or abnormal findings. |
Based on these findings, the researchers concluded, "Etravirine
pharmacokinetics in five pregnant women were comparable
to those of non-pregnant adults suggesting no etravirine
dose adjustment is needed during the third trimester."
"Although
data on exposure to etravirine during pregnancy is limited,
this data suggests that etravirine may not have an effect
on fetal or neonatal toxicity," they added.
11/20/09
Reference
P
Izurieta, TN Kakuda, A Clark, and others. Safety and pharmacokinetics
of etravirine in pregnant HIV-infected women. 12th European
AIDS Conference. Cologne, Germany. November 11-14, 2009.
Abstract PE 4.1/6.
