Side-effects

The commonest side-effects experienced by people taking nevirapine (Viramune) are rash, nausea, fatigue, headache, vomiting, diarrhoea, abdominal pain, and muscle pain.

Approximately 16% of people starting nevirapine will get a rash in the form of red blotches, itchy lumps, and/or speckles on the skin. This usually appears after one to four weeks of treatment and goes away after two to four weeks. Thereafter, most people experience very few or no side-effects.

Prophylactic concurrent treatment with antihistamines during the first two weeks of nevirapine therapy has been shown to reduce the risk of rash.¹ However, treatment with the corticosteroid prednisolone has no effect on the number of people experiencing rash, and can increase its severity.^{2 3}

The rash can be treated in many cases with antihistamines. Beginning treatment with nevirapine at the same time as abacavir (Ziagen) is not recommended as both drugs can cause rashes, and it can be difficult to tell which drug is causing the reaction.

Women seem to be at greater risk than men of developing the mild and severe forms of rash associated with nevirapine.^{4 5 6 7}

People experiencing severe rash or a rash accompanied by fever, blistering, sores in the mouth, conjunctivitis, facial swelling, muscle or joint aches, or general malaise should consult a doctor, who may advise them to stop taking nevirapine.

The US FDA in 2008 issued safety labelling revisions for nevirapine tablets and oral solution following a number of serious hepatic events and skin reactions. Hepatic failure may be linked to a hypersensitivity reaction, resulting in severe rash (~7%), fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, renal dysfunction, and only rarely, Stevens-Johnson syndrome or toxic epidermal necrolysis. Most serious adverse events in the US occurred after nevirapine treatment as part of a post-exposure prophylaxis regimen in healthcare workers.

A two-week induction stage of nevirapine at 200mg/day (150mg in children) can often reduce the occurrence of rash. If there is rash and no other symptoms, the dose should not be escalated until the rash is resolved. The lead-in time should not exceed four weeks; if rash is still unresolved, an alternative regimen is suggested.

If severe hepatic, skin, or hypersensitivity reactions occur, nevirapine therapy should not be resumed. There are cases of hepatic injury even after discontinuation. 

In addition to rash, liver toxicity can be a problem in people beginning nevirapine. ^{8 9 10 11} The greatest risk of liver toxicity occurs in the first six weeks of treatment. Some experts advise doing a liver panel at baseline, at week two when the nevirapine dose is increased, and then two weeks after that. The first 18 weeks on therapy require vigilance, particularly the first six weeks, which is the time of greatest risk.

For this reason, nevirapine should not be included in a post-exposure prophylaxis regimen to prevent HIV infection.¹² Pregnant women may also be at particular risk of developing liver toxicity when starting nevirapine treatment.^{13 14} One sizable US study even found that while pregnancy posed a risk for liver toxicity in women, nevirapine use did not.¹⁵

Less than 1% of patients in clinical trials have stopped nevirapine treatment due to liver toxicity. While elevated liver enzymes are more common in people with hepatitis co-infection, these individuals are not at increased risk of liver toxicity.

If moderate or severe abnormalities in liver enzymes occur, nevirapine should be interrupted, only to be restarted when liver enzyme levels return to baseline. Nevirapine can start again at an initial dose of 200mg a day and liver enzymes should be closely monitored. The dose should be increased to 400mg a day with caution after extended monitoring.

In early 2004, Boehringer Ingelheim updated their safety warning based on a retrospective review of safety data. They stated that women with CD4 counts above 250 cells/mm³ were at 12-fold greater risk of nevirapine-related liver toxicity than men and that women with CD4 cell counts above this level who are new to treatment should start nevirapine with caution, as should men with CD4 cell counts above 400 cells/mm³. This warning remains in the prescribing information. However, several subsequent studies have reached different conclusions.  One prospective cohort study of women in Zambia, Thailand and Kenya found that abnormal liver function tests at baseline, not CD4 cell counts, best predicted severe liver damage and associated rash in the first 24 weeks after starting antiretroviral therapy including nevirapine.¹⁶

European data suggest that it is safe for people who have experienced good increases in their CD4 cell counts on another antiretroviral regimen to subsequently switch to nevirapine even when the CD4 count is above the level recommended for initiating treatment with the drug.^{17 18} Based on these data, the European Medicines Agency has advised that people with HIV who have an undetectable viral load can safely switch to nevirapine at any CD4 cell count.

Symptoms of liver toxicity include nausea, loss of appetite, fatigue, liver tenderness or swelling, malaise, yellowing of the whites of the eyes, dark greenish-brown urine, yellowing of the skin (jaundice), and greyish or white stools.

High-density lipoprotein (HDL or ‘good’) cholesterol may rise in people taking nevirapine and overall, nevirapine appears to have a better lipid profile than efavirenz. ^{19 20 21}