Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Viramune (Boehringer Ingelheim)
200 mg tablets
Indication: HIV infection
Nevirapine is an inhibitor of HIV-1 reverse transcriptase. As it binds directly to the enzyme, its action differs from that of a nucleoside analogue such as zidovudine.1
If nevirapine is used alone, the virus quickly develops resistance to the drug. Accordingly, nevirapine should be prescribed in combination with two other antiviral drugs.
In patients who have not been previously treated, the combination of nevirapine, zidovudine and didanosine has been compared with nevirapine and zidovudine, and zidovudine and didanosine. After 52 weeks, the CD4 lymphocyte count had improved significantly more in the patients given the combination of 3 drugs. Concentrations of viral RNA were also significantly lower.
Nevirapine was also studied in patients who had taken nucleoside analogues. Combining nevirapine with zidovudine and didanosine maintains theCD4 count longer than zidovudine plus didanosine and lowers the concentration of viral RNA.2
Treatment begins with a single 200 mg dose increasing to twice daily after 14 days. The tablet is well absorbed and has a high bio availability. Food has no significant effect on absorption. Nevirapine is metabolised by the cytochrome P450 system so there is a potential for an interaction with other drugs metabolised by this system. As nevirapine induces its own metabolism, its clearance increases during the first few weeks of treatment. This reduces the half-life from 45 hours to 25-30 hours.
Nevirapine has not been evaluated in patients with liver disease; however, liver function is commonly affected. All patients should have their liver function monitored during treatment.
The most common adverse effect is rash. When compared with those treated with zidovudine and didanosine, 35% of patients taking nevirapine developed a rash. This rash was considered to be severe or life-threatening(e.g. Stevens-Johnson syndrome) in almost 7% of patients. Most of the severe rashes erupt in the first month of treatment. A quarter of the patients with severe rashes will need admission to hospital.
Approximately 7% of patients have to stop treatment because of rashes. Patients may also discontinue treatment because of other adverse effects such as fever and hepatitis. Patients may also experience headache, nausea and vomiting.
Although nevirapine has some beneficial effects, these start to decline after the first few weeks of treatment. At present, there is no evidence of an improvement in clinical end points such as survival. Nevirapine has to be used with two other antiviral drugs because combination with zidovudine alone does not alter the emergence of resistance. There are no results of trials combining nevirapine and protease inhibitors, but the drugs do interact. Until more data become available, the best way to use nevirapine in combined regimens will remain unclear.
