Intelence

Generally well tolerated, but most common side effects of moderate to severe intensity in adults include rash as well as numbness, tingling, or pain in the hands or feet. 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, general malaise [general ill feeling], fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, or angioedema). Levels of liver enzymes called transaminases should be monitored. Rash is associated with all of the current NNRTIs, but if you develop a rash from Intelence, you may still be able to take one of the other NNRTIs. In pediatric patients ages 2–18, the frequency, type, and severity of adverse drug reactions were comparable to those observed in adult subjects, except for rash, which was observed more frequently. In ages 6–18, rash of moderate intensity or greater (Grade 2 or greater) was reported more frequently in girls than boys (20.3% versus 5.4%). Half of the children 2–6 years old experienced rash of any grade, whereas rash of moderate intensity or greater was reported in 10% of adults. Rash is typically described as mild to moderate, pruritic (itchy), with pimple-like skin eruptions. For pediatric patients, rash usually appeared in the second week of therapy and generally resolved within a week. Discuss discontinuing etravirine if fever, blistering, or severe reaction occurs.

If Intelence is taken in combination with a protease inhibitor, the PI must be boosted with low-dose Norvir. Intelence should be avoided with Tivicay unless administered with one of the following combinations: Reyataz/Norvir, Prezista/Norvir, or Kaletra. Taking it in combination with Selzentry requires a Selzentry dose adjustment to 600 mg twice daily when used without a boosted PI, and 150 mg twice daily when used with a boosted PI. Do not take Intelence with Tegretol, Luminal, Dilantin, Priftin, Rifadin, or the herb St. John’s wort. Use with caution when combined with the antifungals Diflucan and Vfend. Dose adjustments of the antifungals ketoconazole, itraconazole, and posaconazole may be needed. Dose adjustments of certain cholesterol medications may be needed based on clinical response, including Lipitor, Lescol, Mevacor, Livalo, and Zocor. Monitor the effectiveness of Coumadin (warfarin) and adjust dose as needed based on clinical response. Alternatives to Plavix should be considered when used with Intelence. Alternatives to clarithromycin—such as azithromycin—should be considered for treatment of MAC. Lower Valium dose may be needed. Use caution with systemic dexamethasone or consider alternatives. Intelence can be taken with rifabutin (Mycobutin) 300 mg daily; however, it should be avoided by people who are also taking a boosted PI. Concentrations of some antiarrhythmics may be decreased when co-administered with Intelence. Intelence and antiarrhythmics should be co-administered with caution. Drug concentration monitoring is recommended, if available. Intelence can be safely combined with methadone or buprenorphine with additional monitoring for potential signs of withdrawal. Intelence can also be safely combined with Viagra, Cialis, and Levitra, though a dosage adjustment of Viagra may be necessary. Interaction with Harvoni has not been studied, but based on the metabolism, a clinically significant interaction is not expected. Taking with Zepatier is not recommended. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions which are not listed here.

For people who have had virologic failure on an NNRTI-containing regimen, do not use Intelence in combination with a nucleoside backbone alone. Although taking once daily is not FDA approved, some providers have prescribed Intelence once daily (two of the 200 mg tablets) based on clinical trials that showed that once-daily Intelence was not inferior to Sustiva-based regimens. In Europe, it is approved as a once-daily medication. Once-daily dosing may improve adherence. Although the DHHS recommendation for Intelence specifies drug resistance strains before taking it, the drug label does not—you do not need to have drug resistance before taking Intelence. The TRIO study reported the combination of Intelence with Prezista/Norvir and Isentress in highly treatment-experienced people was successful in getting many people to undetectable. Some people complain of hard-to-swallow, large chalky pills; see dissolving instructions in dose section or package insert. For individuals with HIV-2, commonly found in some other countries, an NNRTI would not be recommended, as HIV-2 is inherently resistant to NNRTIs. DHHS guidelines do not recommend using etravirine in treatment-naïve people who are pregnant. Individuals who become pregnant while taking etravirine may continue taking Intelence if viral suppression is effective and the regimen is well tolerated. The pharmacokinetics (PK) of etravirine are not significantly altered during pregnancy, and no dosage adjustment is necessary. The PK data demonstrated that exposure to total etravirine was generally higher during pregnancy compared with postpartum levels. Etravirine is known to have a variable (moderate to high) level of transfer across the human placenta, although insufficient data exist to evaluate the effects on a fetus. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; go to apregistry.com.

Dr. Melanie Thompson:

Etravirine was never approved for initial therapy and largely has been superseded by rilpivirine and doravirine, both of which can be taken once daily with lower pill burden and many fewer drug interactions. It cannot be taken with lenacapavir, atazanavir/cobicistat, or dolutegravir (unless darunavir + ritonavir is also taken). It can increase levels of many drugs for heart rhythm abnormalities and the anticoagulant warfarin. It should not be taken with many drugs for tuberculosis, seizures, or hepatitis C or St. John’s wort. Among the statins, only pitavastatin and rosuvastatin should be taken with etravirine. Given the many other excellent options available, there are few reasons to use etravirine today.

Activist Joey Wynn:

Intelence is approved for use only in highly treatment-experienced people. Compared to today’s selection of ARV regimens, there is no longer a niche for this option in my opinion.