Brand name: Intelence
Generic name: etravirine, or ETR
Class: Non-nucleoside reverse transcriptase inhibitor (non-nucleoside, NNRTI, or non-nuke)
Manufacturer: Janssen Therapeutics, www.intelence-info.com, (800) JANSSEN (526-7736)
Standard Dose: One 200 mg tablet, or two 100 mg tablets, twice a day, with food. People unable to swallow pills can dissolve tablets in water. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose.
Potential side effects and toxicity: Intelence is generally tolerable. The most common side effects include nausea, rash, and peripheral neuropathy. Drug label warns of hypersensitivity (allergic-like) reactions, which sometimes occur with 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 advised, "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 [eye inflammation], facial edema [swelling], hepatitis, and eosinophilia [increased levels of the white blood cells called eosinophils, 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. See chart for potential drug class side effects.
Potential drug interactions: Non-nukes interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Intelence should not be taken with Sustiva, Viramune, Rescriptor, or full-dose (600 mg twice daily) Norvir (Intelence levels are lowered with each of these). It should not be taken with unboosted (without Norvir) PIs, or with Aptivus/Norvir, Reyataz/Norvir, or Lexiva/Norvir. It can, however, be taken with Prezista/Norvir, Kaletra, and Invirase/Norvir. It can be taken with the integrase inhibitor Isentress. Taking it with Selzentry requires a Selzentry dose adjustment to 600 mg twice daily when used without a boosted PI. Adjust Selzentry dose to 150 mg twice daily if taken with both Intelence and Prezista 600 mg/Norvir 100 mg twice a day. In people who've failed therapy with other NNRTIs, Intelence should not be taken only with NRTIs. Do not take with Dilantin (phenytoin), phenobarbital, rifampin, Tegretol (carbamazepine), and the herb St. John's wort. Use with caution when combined with antifungals (fluconazole and voriconazole). Monitor the effectiveness of Coumadin (warfarin) and adjust dose if needed. Alternatives to Plavix should be considered when used with Intelence. Biaxin (clarithromycin) may be used in cases of MAC (a form of tuberculosis), in which alternatives like azithromycin should be considered. 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 acid suppressants (Prilosec, Zantac, and others). Intelence can be safely combined with methadone. Intelence can also be safely combined with Viagra, Cialis, and Levitra, though a higher dose of these drugs may be needed to achieve the same clinical effect.
More information: Intelence is a very important addition to the NNRTI class. The older NNRTIs can develop resistance quickly, and with only one mutation in the virus. In fact, some individuals in the U.S. are newly infected with an NNRTI-resistant virus. The second-generation NNRTI Intelence was developed to have a higher genetic barrier to drug resistance. It is not approved for people taking HIV therapy for the first time, although that use is still being explored and small studies to date have shown good efficacy and safety in comparison to Sustiva-based regimens. 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). In patients who have experienced virologic failure on an NNRTI-containing regimen, do not use Intelence in combination with only a nucleoside backbone. Janssen has another NNRTI for treatment-naïve people (first time on HIV therapy); see Edurant. Some physicians are prescribing Intelence once daily to increase adherence, although not FDA approved, based on supportive data. 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 the tablets are completely dissolved and then 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. The new 200 mg tablets are also dispersable, and decrease pill burden. Comparative studies between the 100 mg and 200 mg tablets showed a high rate of patient preference for the 200 mg tablets because they were easier to swallow. See package insert for more complete information on potential side effects and interactions.
Intelence is a true "second-generation" agent, in that it often works after Viramune or Sustiva have failed. There are some exceptions: People who continued to take NNRTIs (especially Viramune) long after their virus had developed NNRTI resistance may have cross-resistance to Intelence. But Intelence will be active for the majority, and fortunately, it's a safe and well-tolerated drug, which has recently been made simpler by the approval of a 200 mg tablet, which is taken twice a day. Intelence tablets can be a little chalky, and people who aren't good at quickly swallowing pills sometimes complain that they start to dissolve before they've been swallowed. One way of dealing with this is to dissolve them in water, and then drink the water with your other pills. Taking the entire dose once a day is probably okay because of the long half-life of the drug, but it hasn't been studied or approved for once-daily dosing. Intelence is usually combined with a boosted protease inhibitor, but can't be given with all of them because of drug interactions. It's been best studied in combination with Prezista/Norvir.
-- Joel Gallant, M.D., M.P.H.
One of the newer non-nukes, Intelence is useful, but an "also ran" for me. It will go down in history as the "just in time" life preserver for many people. It was a new option along with Isentress and Prezista for many salvage clients needing a new "breath of life" in their therapies. Along with most of the newer agents, it has a low pill burden, few side effects (most notably rash), and is still effective when other non-nukes have bit the dust. Without the vivid dreams/CNS problems of Sustiva, and lacking the lipid problems too, it has enough useful characteristics to stay in play for a few years to come.
-- Joey Wynn