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.
Invirase (Roche Products)
200 mg capsules
Indication: HIV infection
Most of the effective antiviral drugs are analogues of nucleic acids and act in a similar way.1 Saquinavir interferes with a different stage of the life-cycle by inhibiting the enzyme HIV protease. This reduces viral replication and infectivity.
Saquinavir is taken 3 times a day. Food increases absorption so the dose should be taken within two hours of a meal. Bioavailability is low (4%) because of incomplete absorption and extensive first-pass metabolism. Most of the metabolites are excreted in the faeces. As the metabolism of saquinavir involves the P450(CYP3A4) system, it has the potential for interaction with several other drugs such as nifedipine, terfenadine and ketoconazole. In theory, it should not interact with drugs metabolised by the CYP2D6 system such as many antidepressants.
The activity and safety of saquinavir has been investigated in relatively short studies using surrogate end-points such as CD4 cell counts. In a 16-weekstudy of previously untreated HIV positive patients, saquinavir increased cell counts with the maximum increase at around week 4.2 This study and other evidence are insufficient to allow the use of saquinavir as monotherapy. It has only been approved for use in combination with other antiretroviral agents. An ongoing study suggests that saquinavir and zalcitabine may be more efficacious than either drug used alone.
Saquinavir is much more active against viral protease than human proteases so it has a reasonable safety profile. The most common adverse effects are asthenia, headache and diarrhoea.
- Locarnini S. Antiviral drugs - mechanisms of action. Aust Prescr 1993;16:78-81.
- Kitchen VS, Skinner C, Ariyoshi K, Lane EA, Duncan IB, Burckhardt J, et al. Safety and activity of saquinavir in HIV infection. Lancet 1995;345:952-5.