Pharmacy & Therapeutics- August 2008 - (Page 491) DRUG FORECAST continued from page 447 (Cordarone, Wyeth), and quinidine(e.g., Quinora), may be decreased with coadministration of etravirine. Because warfarin (Coumadin, Bristol-Myers Squibb) concentrations may be increased with etravirine, the International Normalized Ratio (INR) should be closely monitored in these patients. Common inducers of the CYP 450 enzymes, such as carbamazepine (Tegretol, Novartis), phenobarbital, and phenytoin (Dilantin, Pfizer) may cause decreased plasma concentrations of etravirine, resulting in a possible loss of therapeutic effect. Because of the loss in efficacy, drug combinations with CYP 450 enzyme inducers should be avoided. Etravirine can also interact with medications used to treat mycobacterial infections and tuberculosis. Clarithromycin (Biaxin, Abbott), rifampin (Rifadin, Aventis), and rifabutin (Mycobutin, Pfizer) can decrease etravirine concentrations. 6 Agents used to treat thrush, such as fluconazole (Diflucan, Pfizer), ketoconazole (Nizoral, Janssen), itraconazole (Sporanox, PriCara/Janssen/Ortho-McNeil), and voriconazole (Vfend, Pfizer) may require dosage adjustments when used in combination with etravirine. Patients should be advised to avoid over-the-counter herbal medications without the consent of their doctor. The concomitant use of etravirine and St. John’s wort, for instance, can result in decreased plasma concentrations of etravirine. Statins that can be administered with etravirine without any need for dosage adjustments include atorvastatin (Lipitor, Pfizer) fluvastatin (Lescol, Novartis), pravastatin (Pravachol, BristolMyers Squibb), and rosuvastatin (Crestor, Astra Zeneca). All patients should be advised to consult their doctor or pharmacist before adding any drug to their regimen while taking etravirine.6,7 an empty stomach because of the possibility of decreased efficacy. The type of food does not affect the exposure of etravirine in the body. Tablets should be swallowed whole and not chewed. Patients with difficulty swallowing may place the tablets in a glass of water. After the tablet is dispersed, patients should stir the milky mixture to ensure that the tablet is completely dissolved, and they should drink the mixture immediately. The patient should rinse the glass several times with water and should drink the contents to ensure that the entire dose has been consumed. Etravirine should be stored at room temperature (25° C or 77° F) in the original bottle. The bottle should be tightly closed to protect against moisture. No dosage adjustment is necessar y for patients with mild-to-moderate kidney or liver disease. Because of the drug’s high protein binding affinity, it is not likely to be removed from the body by hemodialysis or peritoneal dialysis.6 strains raise great concern among treatment-experienced patients. Patients receiving HAART are finding few treatment options as gene mutations continue to develop. The NNRTI class plays a vital par t in HIV-1 therapy; never theless, resistance can quickly develop after therapy begins. Etravirine is the first second-generation NNRTI that has proved efficacious in treating highly resistant HIV infection. Etravirine’s mechanism of action differs from that of other drugs in its class. Its molecular flexibility allows it to bind to reverse transcriptase in multiple conformations. Even when mutations are present, etravirine can exert activity toward the enzymes. New clinical trials are in the process of recruiting participants for further studies to test the safety and efficacy of etravirine in treatment-naive adults and pediatric patients. Etravirine’s availability in the U.S. offers patients a second chance at using NNRTIs in their drug regimens. PREGNANCY CATEGORY The FDA has classified etravirine as a Pregnancy Category B medication. In animal studies, a dose of 400 mg/day (the normal adult dose) provided no evidence of harm to the fetus. Etravirine should not be used in pregnancy unless the benefits outweigh the risks to the fetus. The CDC recommends that all HIV-infected mothers avoid breast-feeding to reduce the risk of passing the virus on to the newborn.6 REFERENCES 1. Barclay L. Guidelines revised for use of antiretroviral agents in teens and adults with HIV-1. Medscape Medical News, February 2008. 2. Tibotec’s Intelence (Etravirine, TMC125) is approved by FDA. Poz Magazine, Januar y 18, 2008. Available at: www.poz. com/articles/intelence_etravirine_TMC 125_761_13870.shtml. Accessed May 17, 2008. 3. FDA approves Intelence (etravirine) for HIV combination therapy. Medical News Today, Januar y 22, 2008. Available at: www.medicalnewstoday.com/articles/94 656.php. Accessed May 17, 2008. 4. Madruga J, Cahn P, Grinsztejn B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 2007;370: 29–38. 5. Lazzarin A, Campbell T, Clotet B, et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1– infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 2007;370: 39–48. 6. Etravirine (Intelence), package insert. Raritan, NJ: Tibotec, Inc.; January 2008. 7. AIDS Meds & Poz. Intelence (etravirine TMC125). Available at: www.aidsmeds. com. Accessed May 17, 2008. 8. Red Book. Montvale, NJ: Thomson Healthcare, Inc.; April 2008 Update. 9. Hirschel B, Perneger T. No patient left behind: Better treatments for resistant HIV infection. Lancet 2007;370:3–5. I COST In the U.S., the average wholesale price (AWP) of etravirine 200 mg (two 100-mg tablets) twice daily is $798 for a one-month supply. The AWPs for a month’s supply of the approved firstgeneration NNRTIs are $598 for efavirenz (Sustiva) and $393 for nevirapine (Viramune).8 DOSAGE AND ADMINISTRATION In combination with other antiretroviral agents, etravirine is indicated for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults who have evidence of viral replication and HIV-1 strains that are resistant to an NNRTI or to other antiretroviral agents. Etravirine is available as 100-mg tablets. The recommended dose is 200 mg (two 100-mg tablets) taken twice daily after a meal. Etravirine should not be taken on CONCLUSION Innovation in HIV therapy was once considered to be at a standstill, and it was thought that there would be no further scientific or economic incentives for future progress. Newly approved drugs such as etravirine have dispelled this myth and have proved to be effective and well tolerated.8 Viral replication and HIV-1–resistant Vol. 33 No. 8 • August 2008 • P&T® 491 http://www.poz.com/articles/intelence_etravirine_TMC125_761_13870.shtml http://www.poz.com/articles/intelence_etravirine_TMC125_761_13870.shtml http://www.poz.com/articles/intelence_etravirine_TMC125_761_13870.shtml http://www.medicalnewstoday.com/articles/94656.php http://www.medicalnewstoday.com/articles/94656.php http://www.aidsmeds.com http://www.aidsmeds.com
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