Saquinavir soft gelatin capsule: a comparative safety review

The HIV-1 protease inhibitor (PI) saquinavir is available as a soft gelatin capsule (SGC) formulation. At the recommended dosage of saquinavir SGC (1200mg 3 times daily), this formulation provides around 8-fold greater exposure than the established hard gelatin capsule (HGC) formulation at the recommended dosage of 600mg 3 times daily. As with the HGC formulation, the most common adverse events seen with saquinavir SGC are gastrointestinal symptoms (e.g. diarrhoea, abdominal discomfort and nausea). Some of these may occur with a slightly higher frequency with the SGC than with the HGC formulation. Saquinavir SGC has only a minimal effect on nonfasting serum lipid and cholesterol levels. Like other PIs, saquinavir is metabolised by the cytochrome P450 (CYP) 3A4 isoenzyme and is susceptible to interactions with inducers (e.g. rifabutin and rifampicin) and inhibitors (e.g. clarithromycin and ketoconazole) of this enzyme. Ritonavir, nelfinavir, indinavir and delavirdine, all CYP3A4 inhibitors, greatly increase saquinavir plasma concentrations and the therapeutic implications of these interactions continue to be evaluated. While saquinavir is the least potent CYP 3A inhibitor among the PIs, several drugs (notably terfenadine, astemizole and cisapride) should not be given in combination with saquinavir. Therefore, although the SGC formulation enhances saquinavir exposure, it has a similar safety profile to the HGC formulation.