POSITIVELY AWARE MARCH/APRIL 2011
brand name: Intelence
common name: etravirine
class: Non-nucleoside reverse transcriptase inhibitor
(non-nucleoside, NNRTI, or non-nuke)
manufacturer: Tibotec Therapeutics | (877) REACH-TT (732-2488), www.intelence-info.com
Standard dose: One 200 mg tablet, or 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: $919.78 / month
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 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 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, 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 Plavix, Biaxin (clarithromycin), Dilantin (phenytoin), phenobarbital, 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 taken 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 with caution when combined with antifungals (fluconazole and voriconazole). 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 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, 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 is not approved for people taking HIV therapy for the first time, although that use is being explored. 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 showed evidence of tremendous potency, 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. Benefits in this group, however, have not been established. Tibotec has also developed another NNRTI, rilpivirine (TMC 278), for treatment-naïve people (first time on HIV therapy), which may have pharmacologic advantages over Intelence (see rilpivirine, page 34). 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. See rilpivirine/Truvada, page 38. Some physicians are prescribing Intelence 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. The new 200 mg tablets that became available early this year are dissolvable, and decrease pill burden. See package insert for more complete information on potential side effects and interactions.
Doctor’s comments
Intelence is the newest of the NNRTIs, and it 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 the tablets start to dissolve before they’ve been swallowed. One way of dealing with this is to dissolve the tablets in water, and then drink the water with your other pills. Once-daily dosing is probably possible because of the long half-life of the drug, but it hasn’t been studied or approved for once-daily dosing. It also hasn’t been studied or approved for initial therapy, though it could be an option for some people who were infected with NNRTI-resistant virus. 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, MD, MPH
Activist’s comments
Newest of the non-nukes, Intelence is effective against typical non-nuke resistance. It saved many lives when it was released at the same time as Isentress and Prezista—allowing many salvage patients to finally have two or three new drugs to construct an effective regimen. It’s taken twice daily with food, and because it can lower drug levels of PIs, they need to be boosted with Norvir. The only major side effect is a possible rash. It may never replace Sustiva, but it doesn’t have Sustiva’s sleep and lipid problems, and has been a lifesaving drug for many patients who had run out of options. —Jeff Taylor
