Intelence
Non-Nucleoside Reverse Transcriptase Inhibitor
Common Name: etravirine
Brand Name: Intelence
Class: non-nucleoside analog (also called non-nucleoside reverse transcriptase inhibitor, NNRTI or non-nuke)
Standard dose: Two 100 mg tablets twice a day, with food. Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $817.50
Manufacturer contact: Tibotec Therapeutics, 1 (877) REACH-TT (732-2488), www.tibotectherapeutics.com
AIDSInfo:
1 (800) HIV–0440 (448–0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: The most common side effects seen in the Phase 3 DUET studies were rash (19%), diarrhea (18%), nausea (15%), and headache (11%). The rashes seen with etravirine were generally mild to moderate and resolved with continued dosing.
Potential drug interactions: Intelence should not be used with unboosted (without Norvir and, in rare cases, Rescriptor) PIs (Intelence lowers their levels), Aptivus (Intelence level is lowered 76% with Aptivus), or with Sustiva, Viramune or full-dose (600 mg twice daily) Norvir (Intelence levels are lowered with each of these). Intelence has been studied and can be used without dose adjustment with the boosted protease inhibitors Prezista/Norvir and Invirase/Norvir. Should not be taken with Reyataz/Norvir, Lexiva/Norvir, or Aptivus/Norvir. Since Kaletra increases Intelence blood levels, use together with caution. Intelence may be taken without dose adjustment with Isentress and the experimental integrase inhibitor elvitegravir, but Selzentry does require dose adjustment to 600 mg twice a day with Intelence when used without a boosted PI. In people with failed therapy with other NNRTIs, Intelence should not be taken only with NRTIs (including Viread). No interaction was found with the acid suppressants ranitidine (Zantac and others) or Prilosec (omeprazole) when taken with Intelence. There was also no interaction with methadone and Intelence.
Tips: Intelence is a badly needed drug in the NNRTI class. The older NNRTIs can develop resistance quickly, and with only one mutation in the virus. The second-generation Intelence was developed to have a higher genetic barrier to drug resistance. It has shown significant viral load reduction in people with drug resistance to Sustiva or Viramune, although it may work better for Sustiva failure (people with the HIV mutation K103N). Sustiva and Viramune are known for potency and tolerability compared to the protease inhibitors, although they have the potential for very negative side effects. Remember also that Sustiva should not be taken during pregnancy and that Viramune may lead to liver damage or life-threatening rash. Intelence is likewise generally tolerable. Diarrhea is a commonly reported side effect in studies, but the incidence is not higher than the comparative arms. Intelence showed a nearly 2 log drop in viral load (99% reduction in circulating virus) in a 7-day monotherapy study with people taking HIV meds for the first time, evidence of tremendous potency. Benefits in this group, however, have not been established. In another early study in people with NNRTI resistance, Intelence substituted for 7 days for the failing NNRTI led to about a 1 log drop (90% reduction) in viral load. One Phase 2 study was stopped, however, when Intelence didn’t perform as well as the protease inhibitors in the comparator group of people, but in this study Intelence was not taken with other active drugs in the regimen. In a Phase 2b study presented at the 2006 International AIDS Society meeting, 199 individuals with documented NNRTI resistance were randomized to receive either Intelence or another type of drug regimen (a comparator). The viral load reduction in people receiving an Intelence regimen was significantly greater than in the comparator group with optimized therapy. Published Phase 3 DUET studies demonstrated good activity when combined with Prezista in treatment-experienced people with NNRTI resistance. At 48 weeks, a significantly greater number (61%) treated with Intelence than placebo (40%) reached an undetectable (less than 50 copies) viral load. These are encouraging results. It is important to remember that as the clinical studies are being completed, we will find out more information about this drug. Tibotec is also developing another NNRTI, rilpivarine (TMC-278), for treatment-naïve people (first time on HIV therapy), which may have pharmacologic advantages over Intelence, including the ability to dose once a day. Those unable to swallow the tablets can stir them in water until there’s a milky appearance and drink the solution. Please see package insert for more complete potential side effects and interactions.
Doctor
Intelence (etravirine) was approved in 2008 for use in combination with other antiretroviral drugs for therapy-experienced individuals (two tablets twice daily following a meal). It is not approved for those individuals who are naïve to HIV therapy. There is extensive cross-resistance among the drugs in the NNRTI class. Failure with one NNRTI may lead to all others in the class being ineffective. Etravirine is a second generation NNRTI and, unlike the currently available agents in the class, resistance to other NNRTIs does not necessarily confer resistance to etravirine. Resistance testing should be performed for appropriate use of this drug. Etravirine has been fairly well tolerated in our patient population. The general side effects of nausea, rash, and diarrhea have not been a major issue. I believe that drug interactions with etravirine, however, are an issue. When this drug is prescribed as part of HAART therapy, all drugs being taken (including over the counter) should be evaluated for a potential interaction with etravirine. For example, St. John’s wort will reduce the level of etravirine in the bloodstream and levels of erectile dysfunction drugs may be reduced if used with etravirine. This antiretroviral should not be used in combination with others in the NNRTI class (remember, this includes Atripla). Etravirine has been a welcome addition to our antiretroviral armamentarium, but its use must be implemented with care in order to ensure a successful outcome of therapy. —Frank M. Graziano, M.D., Ph.D.
Activist
Approved by the FDA in January 2008, Intelence is a “second generation” non-nuke—the first approved since Sustiva in 1998. Ten years is a long time in the world of ARVs, but Intelence seems to have been worth the wait. Before Intelence, if you developed resistance to any one of the non-nukes (Viramune, Sustiva, and Rescriptor), you developed cross-resistance to the entire class. That isn’t the case with Intelence: it is an active drug against NNRTI resistant strains of HIV. Basically, it restores the ability to interfere with the specific reverse transcription process in the HIV lifecycle where NNRTIs are designed to work. Intelence is a twice-daily drug, but so what? For the time being, it has a good side effect profile. Not yet indicated, approved, or recommended for initial therapy. —Morris Jackson
