Intelence

Common Name: etravirine

Brand Name: Intelence

Class: non-nucleoside analogs (also called non-nucleoside reverse transcriptase inhibitors, NNRTIs or non-nukes)

Standard dose: Two 100 mg tablets twice daily, with food. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $876.82 / month

Manufacturer contact: Tibotec Therapeutics, 1 (877) REACH-TT (732-2488), www.tibotectherapeutics.com

Potential side effects and toxicity: The most common side effects seen in Phase 3 studies were rash (19%), diarrhea (18%), nausea (15%), headache (11%), and nasopharyngitis (symptoms similar to a cold) (11%). Last year, the warning on the drug label was strengthened to include reports of hypersensitivity (allergic-like) reactions, which sometimes occur with hepatic (liver) failure, and fatality due to Stevens-Johnson Syndrome, erythema multiforme, and toxic epidermal necrolysis (TEN), all skin disorders. These are very rare side effects. The FDA reported, "Discontinue Intelence immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, malaise (general ill feeling), fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema [swelling], hepatitis, and eosinophilia [increased levels of the white blood cell eosinophil, a sign of an allergic reaction])." In addition, levels of liver enzymes called transaminases should be monitored. Rash is associated with all of the current non-nukes.

Potential drug interactions: Do not take Intelence with Biaxin, Dilantin (phenytoin), phenylbarbital, rifampin, St. John's wort, or Tegretol (carbamazepine). Intelence should not be used with unboosted (without Norvir) PIs (Intelence may cause a significant alteration in the levels of the PI), or with Sustiva, Viramune, Rescriptor, or full-dose (600 mg twice daily) Norvir (Intelence levels are lowered with each of these). Should also not be taken with Aptivus/Norvir (Intelence level is lowered 76% with Aptivus), Reyataz/Norvir, or Lexiva/Norvir. Intelence has been studied and can be used without dose adjustment with the boosted protease inhibitors Prezista/Norvir and Invirase/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 (when it becomes available), but Selzentry does require dose adjustment to 600 mg twice a day with Intelence when used without a boosted PI, or 150 mg twice a day if given with both Intelence and Prezista 600 mg twice a day. In people who've failed therapy with other NNRTIs, Intelence should not be taken only with NRTIs (including Viread). Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). Monitor the effectiveness of Coumadin (warfarin) and adjust dose if needed. Do not take Intelence with Mycobutin if you're on a Norvir-boosted PI. If you're not, Mycobutin dose should be 300 mg once daily. No interaction was found between Intelence and the acid suppressants ranitidine (Zantac and others) or Prilosec (omeprazole). Intelence can also be safely combined with methadone and Viagra.

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. In fact, an estimated 7% of newly infected individuals in the U.S. are infected with an NNRTI-resistant virus. The second-generation NNRTI 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 in Sustiva failures (where the HIV mutation K103N is more likely present, and which does not affect Intelence activity). Intelence is generally tolerable. Diarrhea is a commonly reported side effect in studies, but the incidence is no higher than with a placebo. 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. The FDA granted traditional approval for Intelence in November 2009, based on 48-week data from two Ph. 3 studies, DUET-1 and DUET-2. Tibotec is also developing another NNRTI, rilpivirine (TMC278), for treatment-naive people (first time on HIV therapy), which may have pharmacologic advantages over Intelence, including the ability to dose once a day. Last year, the company reached an agreement with Gilead, maker of Emtriva and Viread, to combine rilpivirine with those two drugs into a regimen in one pill. Woo-hoo! Some physicians are prescribing Intelence as 4 tablets once daily to increase adherence. Some patients complain of hard-to-swallow large chalky pills. Those unable to swallow the tablets can stir them in a glass of water until there's a milky appearance and drink the solution. Rinse the glass with water a few more times and swallow the rinse each time to make sure you get the full dose. Please see package insert for more complete potential side effects and interactions.

Doctor

Intelence (etravirine) is the newest non-nucleoside and 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 na?ve to HIV therapy, though there are some small studies exploring this issue. There is extensive cross-resistance among the first three drugs approved in the NNRTI class. This means that virologic breakthrough when taking one NNRTI would lead to resistance to the other two "first generation NNRTIs." However, etravirine is a "second generation" NNRTI, which means that, unlike the previously available agents in the class, resistance to other NNRTIs usually does not confer resistance to etravirine. Resistance testing should be performed for appropriate use of this drug, however, as there are some patterns of resistance more associated with the use of nevirapine that can cause some degree of cross-resistance to this drug. Etravirine is well tolerated in our patient population with the main side effect being a rash which occurs in no more than 10% of those who take it -- rarely is the rash severe enough that someone must discontinue taking the drug but it does occur. There are some drug-drug interactions with this drug and some protease inhibitors, though most of the trials used this agent with darunavir and that combination is an important and effective option for patients whose HIV is resistant to "first generation" agents. -- Cal Cohen, M.D.

Activist

The first non-nuke that is effective against typical non-nuke resistance. This drug met an enormous need for those with traditional non-nuke resistance and, along with the integrase inhibitor Isentress (which became available at about the same time), has saved many lives of those who were resistant to practically everything. It needs to be taken twice a day with food. If you're taking a PI, it must be boosted with Norvir because Intelence lowers PI levels. And, like most other non-nukes, it can cause rash. This is nonetheless a very important drug for salvage patients. This will never become the next Sustiva, but it has proven a lifesaving drug for many who had run out of options. -- Jeff Taylor