General Information

Invirase (saquinavir mesylate) is an HIV-1 protease inhibitor.

Invirase is specifically indicated for use in combination with ritonavir and other antiretroviral agents for the treatment of HIV-1 infection in adults (over the age of 16 years).

Invirase is supplied as a tablet for oral administration. Invirase must be used in combination with ritonavir because ritonavir significantly inhibits saquinavir’s metabolism to provide increased plasma saquinavir levels.

The standard recommended dose of Invirase is 1,000 mg twice daily in combination with ritonavir 100 mg twice daily.

For treatment-naïve patients initiating treatment with Invirase/ritonavir, the recommended starting dose of Invirase is 500 mg twice daily with ritonavir 100 mg twice daily for the first 7 days of treatment. After 7 days, the recommended dose of Invirase is 1,000 mg twice daily with ritonavir 100 mg twice daily.

Patients switching immediately (no washout period) from treatment with another ritonavir containing regimen or from a nonnucleoside reverse transcriptase inhibitor (NNRTI) based regimen (not including delavirdine, rilpivirine) should initiate and continue Invirase/ritonavir at the standard recommended dose of 1,000 mg twice daily with ritonavir 100 mg twice daily. For patients switching from a regimen containing delavirdine, the recommended dose is 500 mg twice daily with ritonavir 100 mg twice daily for the first 7 days of treatment.

Ritonavir should be taken at the same time as Invirase.

Invirase and ritonavir should be taken within 2 hours after a meal.

For patients already taking ritonavir 100 mg twice daily as part of their antiretroviral regimen, no additional ritonavir is needed.

Clinical Results

The FDA based its approval of saquinavir on clinical trials comparing three drug combinations in more than 900 HIV-infected individuals: saquinavir with AZT, saquinavir with ddC, and saquinavir with both AZT and ddC. The primary measure of drug effect was changes in patients’ CD4 cell counts, an indication of immune system strength. Values greater than 800 per milliliter of blood are normal in healthy individuals.

Over 16 weeks of treatment, CD4 cell counts increased an average of 30-40 cells per milliliter in subjects on saquinavir in combination with ddC, AZT or AZT plus ddC. Effects were attributable to combinations of saquinavir and a nucleoside analogue to which a subject had not been previously exposed. Saquinavir doses of less than 600 mg three times a day did not produce increases in CD4 cell counts. The duration of CD4 cell increases is not fully determined, although in general the increase lasted for at least the 16 weeks of the trials.

Mechanism of Action

Invirase (saquinavir) is an inhibitor of HIV-1 protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of viral polyprotein precursors into individual functional proteins found in HIV-1 particles. Saquinavir is a peptide-like substrate analogue that binds to the 23 protease active site and inhibits the activity of the enzyme. Saquinavir inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature noninfectious viral particles.