POSITIVELY AWARE MARCH/APRIL 2011
brand name: Viramune
common name: nevirapine
class: Non-nucleoside reverse transcriptase inhibitor
(non-nucleoside, NNRTI, or non-nuke)
manufacturer: Boehringer-Ingelheim | www.viramune.com, (800) 274–8651
Standard dose: One 200 mg tablet daily for two weeks, then full dose of one 200 mg tablet twice daily, with or without food, with no dietary restrictions. Frequently prescribed as two 200 mg tablets once a day, although once-daily dosing is not FDA approved. Dose for children 15 days or older is 150 mg/m2 once daily for 14 days, then 150 mg/m2 twice daily thereafter, not to exceed 400 mg. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. For dialysis patients, an additional dose of 200 mg is required after each dialysis. A 50 mg/5 ml oral suspension is also available.
AWP: $614.24 / month, $133.02 for 240 ml solution (50 mg/5 ml)
Potential side effects and toxicity
Most common side effects include headache, nausea, vomiting, fever, and rash. 14-day lead-in dosing reduces the risk of rash. Severe rash, including Stevens-Johnson syndrome, while rare, can be life-threatening; notify your health care provider immediately. Seek medical attention right away if you experience blistering, mouth sores, conjunctivitis (redness or inflammation of the eye, or pink eye, which if untreated may result in permanent vision loss), swelling, muscle or joint aches, fever, or malaise (general ill feeling). Do not increase dose if rash develops during dose escalation or if you develop any rash accompanied by the above listed conditions. Once-daily lead-in dose should not exceed 28 days. An alternative drug should be considered at this time. An increase in liver enzyme levels has been observed and in rare instances, hepatitis has developed. In such cases, it may be necessary to stop taking Viramune until liver function returns to normal. Permanently discontinue it if abnormalities return. Rarely, severe and life-threatening liver damage, including fatal cases, has 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 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. 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
Do not take with Intelence, Rescriptor, Reyataz, rilpivirine, Sustiva, or St. John’s wort. Rifampin should not be used with Viramune; Mycobutin is the recommended alternative for tuberculosis treatment. Use with caution with midazolam, triazolam, cisapride, fluconazole, or ergot medications used for migraine headaches (Wigraine, Methergine, and Cafergot), Cordarone, lidocaine or disopyramide, carbamazepine, ethosuxomide, or clonazepam, calcium channel blockers (Procardia and others), immunosuppressants, Coumadin. Do not use with Biaxin or Nizoral. Viramune decreases methadone levels; dose adjustment may be necessary to avoid withdrawal symptoms. Can reduce levels of protease inhibitors; dose adjustment may be needed if they are taken together. Kaletra should be increased to three tablets twice a day in treatment-experienced. Use caution with anti-convulsants: Dilantin, phenobarbital, and Tegretol. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. During the first six weeks of therapy, prednisone should be avoided; it can cause increased severity and incidence of rash.
More information
An extended release formula that can be taken once a day is in the works, but many providers already prescribe once-daily dosing with the current formulation. Monitor liver function tests and signs of rash during first six months. Do not ignore yellowing of your eyes or skin, as this may be a sign of a severe liver effect. A recent study found no correlation between CD4 count and risk of liver toxicity with nevirapine among women in Zambia, Thailand, and Kenya. 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. If at any time of treatment you stop Viramune for more than seven days, you will need to start at the lower dose for two weeks and then increase back up to twice-daily dosing. Viramune should not be used for PEP (post-exposure prophylaxis). Be careful when stopping Viramune, so that you avoid 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 taken 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 taken 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. See package insert for more complete information on potential side effects and interactions.
Doctor’s comments
Viramune (nevirapine) is a component of the vast majority of first-line regimens worldwide, in part because of the low cost of generic nevirapine. It has not been as popular in the United States, however, in part because of the stronger clinical data with Sustiva, but also because of its greater early toxicity. It’s listed as an alternative NNRTI in the DHHS and IAS-USA guidelines. Viramune can cause skin rashes and liver toxicity during the first few weeks, which can be severe and even life-threatening. The risk is greatest when it’s started in people with high CD4 counts: above 250 in women and above 400 in men). Below those CD4 thresholds, the risk is low, and the long-term safety is excellent, with less lipid elevation than with Sustiva. Viramune should be started at half-dose (200 mg once daily) and increased to the full dose (200 mg twice daily) after two weeks only if there is no rash or liver enzyme elevation. Compared to Sustiva, resistance to Viramune is somewhat more likely to cause cross-resistance to Intelence. —Joel Gallant, MD, MPH
Activist’s comments
Originally a twice-daily drug, by press time, the FDA is expected to have approved the new once-daily XR (extended release) formula that may help it regain some market share back from Sustiva. When starting, it will still need a 14-day lead-in period, and the same “black box” warnings about serious skin rash and liver damage in women with over 250 T-cells and men with over 400 T-cells still apply. However, recent studies have shown that people undetectable on another regimen can safely switch to Viramune, regardless of CD4 count. That, and its metabolically friendly profile (i.e., better cholesterol and triglyceride levels), make it a useful option for those who can’t tolerate the crazies from Sustiva or Atripla. The same caveats as for Sustiva about stopping the drug apply with Viramune as well. —Jeff Taylor
