TIPS TO REMEMBER Intelence
- Intelence should be used in treatment-experienced patients with resistance to NNRTIs and other antiretrovirals.
- The recommended dosage of Intelence is 200 mg twice daily with food.
- The most commonly occurring adverse effects of Intelence include rash and nausea.
- Intelence belongs to Pregnancy Category B.
HIV and AIDS patients harboring drug-resistant virus may find that a newly approved antiretroviral offers some hope when little
else does. The non-nucleoside reverse transcriptase inhibitor, etravirine (Intelence) from Tibotec Pharmaceuticals, is the
first NNRTI to be granted regulatory approval in almost a decade and, according to the manufacturer, is the first to show
activity against virus strains that are already resistant to other drugs in the same class.
"Etravirine will make a difference because there is resistance in this class of drugs," said Joel Zive, Pharm.D., owner of
Zive Pharmacy, Bronx, N.Y., and an HIV specialist. Use of NNRTIs as part of combination HIV treatment has been limited by
cross-resistance between drugs, where resistance to one agent typically meant resistance to the others within the class. "There
doesn't appear to be cross-resistance now, but that is not to say it won't happen," Zive said of the new drug.
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Etravirine was granted accelerated approval for use in combination with other antiretrovirals for the treatment of HIV-1 infection
in treatment-experienced adult patients, who have evidence of viral replication and strains resistant to an NNRTI and other
retroviral agents. The approval was based on 24 weeks of pooled treatment data from the DUET-1 and DUET-2 studies. Patients
in the treatment arm received etravirine 200 mg twice daily plus a background regimen (BR), while the other participants received
BR only. In order to be eligible for the trial, patients had to have a viral load of 5,000 copies/ml or greater, while taking
an antiretroviral regimen for at least eight weeks, and with evidence of at least one NNRTI resistance-associated mutation
and three or more primary protease inhibitor (PI) mutations.
Study results showed 59.8% patients in the etravirine arm achieved undetectable viral load (<50 copies/ml) while only 40.2%
met the goal in the BR arm. A significantly greater mean increase in CD4+ cell count was also seen in the etravirine group,
81 versus 64 cells/mm3. DUET-1 and DUET-2 study results were published in two separate articles in the July 7, 2007, issue
of The Lancet. Just recently, Tibotec released 48-week data that also showed significant differences in etravirine-treated patients compared
with BR only. Undetectable viral load was achieved in 60% and 61% in patients on etravirine compared with 39% and 41% on BR
in DUET-1 and DUET-2, respectively. CD4+ cell counts also increased significantly in patients on etravirine compared with
BR after 48 weeks of treatment.
The most common adverse events, occurring in >10% of patients, were rash and nausea. According to Tibotec, the rash is typically
mild to moderate, occurred in the second week of treatment, and generally resolved within a few weeks of therapy. Adverse
events that occurred in 2% or more patients included diarrhea, abdominal pain, nausea, vomiting, peripheral neuropathy, fatigue,
headache, and hypertension. Stevens-Johnson Syndrome, hypersensitivity reactions, erythema multiforme, and immune reconstitution
syndrome were reported, but their incidence was rare.
According to the prescribing information, etravirine should not be taken with ritonavir (Norvir, Abbott) in combination with
tipranavir (Aptivus, Boehringer Ingelheim), fosamprenavir (Lexiva, GSK), or atazanavir (Reyataz, Bristol-Myers Squibb); PIs
administered without ritonavir; or other NNRTIs. Co-administration of etravirine with CYP3A4, CYP2C9, and/or CYP2C19 inducers
or inhibitors may alter the efficacy or adverse-reaction profile of etravirine, and substrates of the same enzymes may also
be affected when co-administered with etravirine.
Tibotec Pharmaceuticals has placed the introductory wholesale pricing for etravirine at $21.80 per day, or close to $8,000
per patient, per year. Prescribing information can be accessed at
http://www.intelence-info.com/.
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