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.
Crixivan (Merck Sharp & Dohme)
200 mg and 400 mg capsules
Indication: HIV infection
The approval of indinavir was based on surrogate end-points, such as CD4 cell counts, as there are no results from controlled clinical trials investigating the effect of indinavir on the progression of HIV infection.
Like saquinavir, indinavir is an inhibitor of HIV protease. While saquinavir is approved for use in combination with other antiretroviral drugs, indinavir can be used as monotherapy if combination therapy is inappropriate.
Indinavir is taken 3 times a day. As absorption is significantly reduced by food, the patient should take the drug with water one hour before or two hours after a meal. Indinavir is mainly metabolised and is rapidly eliminated with a half-life under two hours. This metabolism involves the P450 system so there is the potential for interactions with drugs such as ketoconazole, rifabutin and sertraline. The product information advises that indinavir should not begiven concurrently with drugs which are substrates for cytochrome CYP3A4 if there is a potential for serious adverse effects. Competitive inhibition of their metabolism increases the risks of adverse interactions with drugs such as terfenadine, astemizole, alprazolam and triazolam.
The evaluation of indinavir was based on studies lasting up to 24 weeks; other studies are ongoing. A study comparing zidovudine, indinavir and a combination of the two found that surrogate end-points were more favourable with combination therapy. As monotherapy, indinavir appears to be more effective than zidovudine. A combination of indinavir, zidovudine and didanosine was also more favourable than a combination of zidovudine and didanosine.
Approximately 5% of the patients taking indinavir alone in clinical trials stop the drug because of adverse effects. Common adverse reactions include fatigue, nausea, diarrhoea, headache, dry skin, rashes and altered taste. Patients should drink at least 1.5 L of fluid a day to reduce the risk of nephrolithiasis.
Liver function is altered with approximately 10% of patients developing hyperbilirubinaemia.
There are no adequate or well controlled studies of treatment in pregnant women and indinavir has not been approved for use in children under 12 years old. The long-term safety and efficacy of indinavir are unknown.