March/April 2009
Common Name: nevirapine (NVP)
Brand Name: Viramune
Class: non-nucleoside analog (also called non-nucleoside reverse transcriptase inhibitor, NNRTI, or non-nuke)
Standard dose: One 200 mg tablet daily for two weeks, then full dose of one 200 mg tablet twice daily, no food restrictions, may be taken with or without food; frequently prescribed as two 200 mg tablets once a day, although once-daily dosing is not FDA approved. Take missed dose as soon as possible but do not double up on your next dose. For dialysis patients, an additional dose of 200 mg is required after each dialysis.
AWP: $535.21 / month
Manufacturer contact: Boehringer-Ingelheim,
www.viramune.com, 1 (800) 274-8651
AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov
Potential side effects and toxicity: Most common side effects include headache, nausea, vomiting, fever, and rash. 14-day lead-in dosing reduces the frequency of rash. Severe rash, including Stevens-Johnson syndrome, while rare, can be life-threatening; notify your health care provider immediately. If you experience blistering, mouth sores, conjunctivitis (redness or inflammation of eye, or pink eye, which if untreated may result in permanent vision loss), swelling, muscle or joint aches, fever or general malaise (general ill feeling), you may need to stop all medications, so seek medical attention right away. Do not increase dose if rash develops during dose escalation or if you develop any rash accompanied by the above listed conditions. Label change last year states that dose escalation should not last longer than 28 days. An increase in liver enzyme levels has been observed and in rare instances, the development of hepatitis. May need to stop taking Viramune until liver function returns to normal. Permanently discontinue it if abnormalities return. Rarely, severe and life-threatening hepatotoxicity (liver damage), including fatal cases, have occurred. Women with CD4 counts greater than 250 T-cells, including pregnant women, and men with more than 400 T-cells have a higher risk of serious hepatotoxicity (liver damage), with women being at greater risk. The package insert says Viramune should not be started in these groups unless the benefit outweighs the risk. But the liver damage can happen to anybody. The highest risk period is within the first six weeks of treatment, but patients should be monitored closely for the first 18 weeks.
Potential drug interactions: Caution should be used with midazolam, triazolam, fluconazole, or ergot medications, used for migraine headaches (Wigraine, Methergine, and Cafergot), St. John's wort, Cordarone, lidocaine or disopyramide, carbamazepine, ethosuxomide, or clonazepam, calcium channel blockers (Procardia, diltiazem, verapamil), immunosuppressants, or the blood thinner Coumadin (warfarin). Do not use with Biaxin (clarithromycin) or Nizoral (ketoconazole). Viramune decreases methadone levels; dosing adjustment may be necessary to avoid withdrawal symptoms. Viramune can reduce levels of protease inhibitors; dose adjustment may be needed if they are taken at the same time. Kaletra should be increased to three tablets twice a day in people who previously took HIV drugs. Viramune interacts with rifampin, requiring dose adjustment, and caution is advised with Mycobutin. The effectiveness of birth control pills may be decreased; women and their male partners should consider the use of alternative contraception methods with barrier. During the first six weeks of therapy, prednisone should be avoided. It can cause increased severity and incidence of rash.
Tips: Monitor liver function tests and signs of rash during first six months. The increased period of risk for liver injury is primarily in the first 18 weeks of taking Viramune. Do not ignore yellowing of your eyes or skin, as this may be a sign of a severe liver effect. Studies show that Viramune crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. Lead-in dosing has been shown to lessen the risk of rash. If at any time of treatment you stop Viramune for seven days, you will need to start at the lower dose for two weeks and then increase back up to twice-daily dosing. Be careful when stopping Viramune, so that you avoid the rapid development of HIV resistance to it -- check with your doctor or pharmacist first. It is usually recommended that you continue your other HIV medications for several days after stopping Viramune. Viramune has also been shown to have a positive impact on triglycerides and cholesterol levels. When given around the time of labor, Viramune has demonstrated effectiveness in preventing the transmission of HIV from mother to child, but there was an increase in HIV drug resistance when given alone. The use of at least one other HIV drug helped to cut down the incidence of resistance, and women have been shown to experience effectiveness with the drug six months after giving birth. Viramune was updated from Pregnancy Class C to Class B in 2007, meaning that it was found to be even safer. Single- or two-dose Viramune may be used for babies born to HIV-positive mothers. Mothers should not breastfeed their infants while taking Viramune. Please see package insert for more complete potential side effects and interactions.
Doctor
Viramune (nevirapine) was approved for twice-daily dosing in 1996. It was the first drug approved in the NNRTI class. All of the issues with use of nevirapine are outlined in my comments on the other NNRTIs. To avoid rash, the drug should be taken as one pill per day for two weeks before going to the full dose of one pill twice daily. Interestingly, with all the potential problems with nevirapine, it is still an effective and relatively safe drug. While we do not start as many individuals on nevirapine now as previously, a good 5% of my patients still take it as part of HAART therapy and are doing well. I believe this speaks well of the efficacy and durability of this drug. In Africa, nevirapine is used only as a component of the fixed dose combination Triomune (3TC/d4T/nevirapine). -- Frank M. Graziano, M.D., Ph.D.
Activist
Viramune was the first of the non-nukes and continues to hold its own against Sustiva. It is particularly effective with pregnant women in preventing HIV mother-to-child transmission, and does not affect the central nervous system. But Viramune can seriously mess with the liver in both male and female treatment-naive patients. Studies have shown increased serious hepatic (liver) events in those with higher pre-treatment CD4 counts: greater than 250 in women and 400 in men. Why? Who knows? -- Morris Jackson