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.
Stocrin (Merck Sharp & Dohme)
50 mg, 100 mg and 200 mg capsules
Approved indication: HIV infection
Australian Medicines Handbook Section 5.3.4
The treatment of HIV infection often requires the patient to take a combination of drugs several times a day.1 Efavirenz is anon-nucleoside reverse transcriptase inhibitor which only needs to be given once a day. After absorption the peak plasma concentration is reached in 3-5hours, but efavirenz is eliminated slowly. It has a half-life of 40-55 hours with only 1% being excreted unchanged in the urine. Cytochrome P450 is involved in the metabolism of efavirenz and the drug induces liver enzymes. There is therefore a potential for interactions with many drugs including indinavir, cisapride, triazolam, rifampicin, macrolide antibiotics and oral contraceptives. Liver enzymes should be monitored in patients with liver disease.
There have been three main trials of efavirenz. They have involved untreated and previously treated patients.
One study of 450 patients compared the combination of zidovudine, lamivudine and indinavir with zidovudine, lamivudine and efavirenz, or indinavir and efavirenz. After 24 weeks the proportion of patients with reduced concentrations of HIVRNA was greatest for those who had taken the three-drug combination containing efavirenz.
Another trial, involving 184 patients, studied the addition of efavirenz or a placebo to a combination of indinavir and two nucleoside analogue reverse transcriptase inhibitors. After 24 weeks a greater proportion of the patients taking efavirenz had significantly less viral RNA.
The third trial studied efavirenz in combination with nelfinavir (a protease inhibitor). The 196 patients took two nucleoside reverse transcriptase inhibitors plus efavirenz or nelfinavir, or efavirenz and nelfinavir. After 24 weeks theCD4 count increased, but there were no significant differences between the treatment groups. The four-drug regimen produced the greatest proportion of patients with low concentrations of viral RNA.
The most common adverse effects of efavirenz are skin rashes. Although Stevens-Johnson syndrome has been reported, less than 2% of the patients in the clinical trials had to stop taking efavirenz because of skin rashes.
Patients also commonly develop symptoms related to the nervous system. These include dizziness, headache, insomnia, nightmares and altered concentration. Approximately 3% of patients in the trials stopped the drug because of these symptoms.
There is little information about viral resistance to efavirenz. It should never be used as monotherapy and is probably unlikely to work in patients who have developed resistance to nevirapine or delavirdine.