AIDS Committee of Windsor: HIV Treatment Information

Summary
Nevirapine is a type of anti-HIV drug called a non-nucleoside reverse transcriptase inhibitor. The most common side effect is a skin rash. Nevirapine is taken twice a day, with or without food.

What is nevirapine?
Nevirapine, sold under the brand name Viramune, is a type of antiretroviral drug called a non-nucleoside reverse transcriptase inhibitor. Antiretroviral drugs fight HIV infection by interfering with the life cycle of the virus. At each stage of this cycle, chemicals called enzymes help the virus make copies of itself (replicate). Some drugs can inhibit (slow down or stop) the actions of these enzymes. When these enzymes can't perform effectively, the virus does not replicate as efficiently, thus slowing the progression of HIV disease.

How does nevirapine work?
HIV infects cells and then replicates with the help of its own enzymes. In the first stage of replication, the enzyme reverse transcriptase converts the genetic material of the virus (RNA) to match the genetic material of the cell (DNA). Non-nucleoside reverse transcriptase inhibitors (NNRTIs or "non-nukes") like nevirapine interfere directly with the action of the reverse transcriptase enzyme, preventing it from working properly.

Combination therapy
For many people, combination therapy with three or more anti-HIV drugs can improve CD4+ counts and viral load measures, as well as reduce opportunistic infections. The International AIDS Society–USA suggests that a combination of nevirapine plus two nucleoside analogues may be a useful first combination for treating HIV.

Health Canada has granted conditional approval for the sale of nevirapine. This approval is based on studies that showed a statistically significant (that is, not due to chance alone) drop in viral load and increase in CD4+ count when nevirapine was combined with AZT and ddI. No clinical benefit (improved survival, decreased opportunistic infections) of nevirapine was clearly shown in clinical trials. To receive unconditional approval to market nevirapine, the manufacturer must submit to Health Canada study results that show clinical benefit.

Drug resistance and cross-resistance
Over time, as HIV makes copies of itself, the virus can change its structure. These changes, or mutations, allow HIV to resist the effects of antiretroviral drugs. Resistance to non-nukes, when used alone, appears as early as two weeks after treatment begins. Combining nevirapine with at least two other drugs may delay the development of drug resistance. To limit the risk of resistance, all antiretroviral drugs should be taken every day, exactly as prescribed. This strict schedule is necessary because resistant virus can develop if the level of drug in the blood drops. This may happen if doses are delayed or skipped.

It's generally believed that all non-nukes may be cross-resistant. This means that, if HIV becomes resistant to one non-nuke, it will also be able to resist the effects of the other non-nukes. In other words, if the virus has become resistant to nevirapine, it will probably be resistant to delavirdine and efavirenz.

Side effects
Rash is the most commonly reported side effect of nevirapine, usually occurring in the first six weeks of taking nevirapine. To help reduce the risk of rash, the manufacturer recommends starting nevirapine at 200 milligrams (mg) daily for two weeks, then increasing to the full dose of 400 mg daily. Anyone who develops a rash while using nevirapine should consult their doctor as soon as possible. If the rash is accompanied by fever, skin blisters, itching or burning eyes, swelling, muscle or joint pain, or general malaise, nevirapine must be stopped.

A severe rash could be a sign of Stevens-Johnson syndrome. This is a rare allergic reaction that can damage skin and mucous membranes so seriously that it may be fatal. At least 63 people have developed Stevens-Johnson syndrome while using nevirapine.

Severe, life-threatening, even fatal, liver damage (hepatitis) has occured in people treated with nevirapine. If blood tests show moderate to severe increases in the liver enzymes ALT or AST, nevirapine must be stopped until the enzymes return to baseline levels. Physical symptoms of hepatitis can include nausea, loss of appetite, yellowing of the skin (jaundice), itchiness, and pain in the upper right side of the body.

Other side effects include fever, nausea, and headache.

To date, there have been no reports of side effects unique to women.

Drug interactions
Nevirapine is metabolized (broken down and processed) by the liver through the actions of the p450 cytochrome enzymes. Taking nevirapine with drugs that are metabolized the same way may change blood levels of each drug. As a result of these drug interactions, blood levels of some drugs may drop too low to be of benefit, or they may rise so high they cause serious side effects. Dosages of other drugs may therefore have to be raised or lowered, or some drugs may have to be changed.

The manufacturer has reported that nevirapine may interact with rifampin, rifabutin, and birth control pills. Nevirapine should not be used with ketoconazole (Nizoral). This drug can cause blood levels of methadone to drop so low that people experience withdrawal symptoms. Methadone users may have to increase their dose if they take nevirapine. If you're starting a new drug, check with your doctor or pharmacist about potential interactions with nevirapine.

Nevirapine and protease inhibitors
Studies suggest that there are no problems with interactions between nevirapine and ritonavir. Nevirapine decreases levels of both saquinavir hard-gel capsules (Invirase) and indinavir in the blood by about 30%. Such a decrease is usually not enough to make a difference in the effectiveness of a drug. But, since only about 4% of the amount of Invirase swallowed actually gets used by the body, the combination of saquinavir and nevirapine should be avoided. Indinavir users may want to consider taking an additional 600 mg daily, although this may not be necessary.

Dosage
The recommended dose of nevirapine is 200 mg every 12 hours, with or without food. Nevirapine treatment should be started at a dose of 100 mg every 12 hours. If no rash develops after 14 days, then the full dose of 200 mg every 12 hours can be taken.

Availability
Nevirapine received conditional marketing approval in September 1998. This conditional approval may affect provincial drug coverage.

This information was provided by the Community AIDS Treatment Information Exchange (CATIE). For more information, contact CATIE at 1-800-263-1638.