POZ IRELAND
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POZ IRELAND
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SAQUINAVIR Fortovase® (Roche) Approved for use in HIV infection in combination with other antiviral drugs. DESCRIPTION: Saquinavir is a protease inhibitor. STATUS: The hard-gel capsule formulation (Invirase, SQVhc) is poorly absorbed when given orally (from 0% when fasting to 4% after a full fatty meal), but the soft-gel capsule formulation (Fortovase, SQVsgc) has increased bioavailability. Dose (Fortovase): 1,200 mg (six 200-mg soft gel capsules) three times daily. Data indicate that 1,600-mg Fortovase twice daily with two NRTIs may confer similar antiretroviral potency. Food helps absorption. Dose (Invirase): The initial formulation of saquinavir was Invirase 600 mg (three 200-mg hard capsules) three times daily taken with a full meal. Because of low saquinavir blood levels, this formulation was superseded by the better-absorbed Fortovase formulation. Invirase cannot be substituted for Fortovase. It should not be used as a single protease inhibitor (PI) without pharmacokinetic enhancement. Either Invirase or Fortovase may be combined with ritonavir. The traditional saquinavir/ritonavir dose for both formulations is 400/400 mg twice daily, although alternative Fortovase/ritonavir formulations are under investigation. Paediatric: Not determined. Neonates: Not determined. SIDE EFFECTS: GI disturbances (nausea, bloating and diarrhoea) are the most common side effects. Elevated liver function test levels have been noted. Metabolic abnormalities, redistribution of body fat and diabetes are associated with all the protease inhibitors to varying degrees. The combination of ritonavir and saquinavir has shown synergistic antiretroviral effect, and is recommended as a first-line therapy. RESISTANCE: The potential for cross-resistance with other protease inhibitors is not clear. In one study 29% of patients developing resistance to saquinavir were cross resistant to other protease inhibitors. (NFV, RTV) Studies suggest that people with extensive saquinavir experience have less response to indinavir than protease-naive people. INTERACTIONS: Saquinavir is associated with several important drug interactions. Saquinavir should not be taken with Terfenadine, Cisapride, Astemizole, Triazolam, Midazolam or Ergot derivatives, because it could lead to serious and/or life-threatening reactions such as cardiac arrhythmias. Clarithromycin and Fortovase led to a decrease in clarithromycin levels by 45%. Delavirdine increases levels of Invirase fivefold. No data are available on delavirdine with Fortovase. Ketoconazole increases levels of saquinavir threefold. The manufacturer does not recommend a dose adjustment of either drug. Indinavir with Fortovase led to a 364% increase in saquinavir plasma. No safety or efficacy data are available for this combination. Nelfinavir with Fortovase resulted in a minor increase in nelfinavir plasma and a 392% increase in saquinavir concentrations. This combination is under clinical investigation. Nevirapine: Nevirapine with Invirase resulted in a 24% decrease in saquinavir. Rifampin and Rifabutin must not be taken with saquinavir. Ritonavir and saquinavir (Invirase) dramatically increases the levels of saquinavir. Saquinavir levels with Invirase (400 mg BID) plus ritonavir (400 mg BID) are similar to those achieved with Fortovase (400 mg BID) and ritonavir (400 mg BID). Comparing SQV/RTV with SQV/NFV in people who failed with IDV. The responses were comparable. (ACTG 235)
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