FORTOVASE SUMMARY
FORTOVASE®
(saquinavir)
SOFT GELATIN CAPSULES
FORTOVASE brand of saquinavir is an inhibitor of the human immunodeficiency virus (HIV) protease. FORTOVASE is available as beige, opaque, soft gelatin capsules for oral administration in a 200-mg strength (as saquinavir free base).
FORTOVASE is indicated for use in combination with other antiretroviral agents for the treatment of HIV infection. This indication is based on studies that showed increased saquinavir concentrations and improved antiviral activity for FORTOVASE 1200 mg tid compared to INVIRASE 600 mg tid.
In treatment-naive and treatment-experienced patients, the efficacy of FORTOVASE (with or without ritonavir coadministration) has not been compared against the efficacy of antiretroviral regimens currently considered standard of care.
When used in combination with other antiretroviral agents, FORTOVASE and INVIRASE have been shown to decrease plasma HIV RNA levels and increase CD4 cell counts in an open-label randomized study (NV15355) in treatment-naive, HIV-infected patients. In addition, in a randomized, double-blind study (NV14256) in ZDV-experienced, HIV-infected patients, a combination regimen of FORTOVASE and HIVID was shown to be superior to either INVIRASE or HIVID monotherapy in decreasing the cumulative incidence of clinical disease progression to AIDS-defining events or death. It should be noted that HIV treatment regimens that were used in the initial clinical studies of INVIRASE are no longer considered standard of care.
FORTOVASE 1000 mg bid coadministered with ritonavir 100 mg bid was studied in a heterogeneous population of 148 HIV infected patients (MaxCmin 1 study). At baseline 42 were treatment naive and 106 were treatment experienced (of which 52 had an HIV RNA level <400 copies/mL at baseline). Results showed that 91/148 (61%) subjects achieved and/or sustained and HIV RNA level <400 copies/mL at the completion of 48 weeks.
Study NV15182 was an open-label safety study of FORTOVASE in combination with other antiretroviral agents in HIV-infected patients. The 48-week safety results from this study are displayed in the ADVERSE REACTIONS section.
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NEWS HIGHLIGHTS
Published Studies Related to Fortovase (Saquinavir)
Gemini: a noninferiority study of saquinavir/ritonavir versus lopinavir/ritonavir as initial HIV-1 therapy in adults. [2009.04.01]
INTRODUCTION:: Direct comparison of the efficacy and safety of different agents is needed to guide selection of optimal treatment regimens for therapy-naive HIV-1-infected patients... CONCLUSIONS:: In treatment-naive, HIV-1-infected patients, SQV/r treatment was noninferior in virologic suppression at 48 weeks to LPV/r treatment and offered a better triglyceride profile.
Pharmacokinetics and safety of saquinavir/ritonavir and omeprazole in HIV-infected subjects. [2008.06]
We investigated the pharmacokinetics and safety of saquinavir/ritonavir when administered with omeprazole simultaneously and 2 h apart to human immunodeficiency virus (HIV) subjects. Saquinavir/ritonavir 12-h pharmacokinetics was assessed with and without omeprazole 40 mg... In the presence of omeprazole, saquinavir plasma exposure is significantly increased in HIV-infected subjects whether administered simultaneously or 2 h apart.
Long-term efficacy and safety of first-line therapy with once-daily saquinavir/ritonavir. [2008]
BACKGROUND: The aim of this study was to assess the long-term efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (NRTIs)... CONCLUSION: First-line highly active antiretroviral therapy with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy.
Viral Decay Dynamics in HIV-Infected Patients Receiving Ritonavir-Boosted Saquinavir and Efavirenz With or Without Enfuvirtide: A Randomized, Controlled Trial (HIV-NAT 012). [2006.11.01]
The availability of enfuvirtide enables assessment of whether human immunodeficiency virus (HIV) decay can be enhanced by targeting reverse transcriptase, protease, and fusion. We performed a 12-week study of 22 patients randomized to receive ritonavir-boosted saquinavir and efavirenz with (the 3-target arm) or without (the 2-target arm) enfuvirtide.
Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5. [2005.12]
OBJECTIVE: Saquinavir, a widely prescribed human immunodeficiency virus 1 protease inhibitor, has a low and variable oral bioavailability that has been attributed to extensive first-pass extraction mediated by hepatic or intestinal cytochrome P450 (CYP) 3A4 and intestinal P-glycoprotein (P-gp). The polymorphic CYP3A5 has also been shown to influence the saquinavir metabolite/parent urinary ratio, suggesting a role for CYP3A5... CONCLUSIONS: The CYP3A5*1 genotype is associated with increased saquinavir CL/F. This does not appear to reflect intestinal CYP3A5 expression and presumably reflects the contribution of hepatic CYP3A5. The interaction with Seville orange juice in subjects not expressing CYP3A5 supports a role for intestinal CYP3A4. However, the modest nature of the interaction, combined with the inability to detect a correlation between CL/F and CYP3A4 enterocyte content, supports our recent in vitro work suggesting a smaller contribution of intestinal CYP3A4 than has been assumed.
Clinical Trials Related to Fortovase (Saquinavir)
A 48-Week, Randomised, Study to Describe the Pharmacokinetic Profile and Durability of Atazanavir-Saquinavir-Ritonavir Once Daily and Describe the Pharmacokinetic Profile of Saquinavir-Ritonavir Using Saquinavir 500mg Formulation: the ASK-500 Study [Active, not recruiting]
Saquinavir and Atazanavir are drugs used in combination therapy to treat HIV disease.
Saquinavir is currently available in a 200 milligram capsule. Most individuals currently on
saquinavir require to take 5 tablets twice a day. In an attempt to reduce this number of
pills, a new capsule has been developed containing 500 milligrams of saquinavir. This study
will assess: i) blood drug levels in individuals taking both saquinavir formulations, ii)
blood drug levels in individuals taking both saquinavir formulations when given with
atazanavir, iii) 48 weeks of follow up for individuals receiving the new saquinavir
formulation with atazanavir as HIV therapy.
The Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year [Completed]
To determine, in HIV-infected patients, whether switching to a new soft gelatin capsule
formulation of saquinavir or to indinavir following prolonged use of the original hard
capsule formulation of saquinavir results in an acute decrease in plasma HIV RNA.
Resistance to anti-HIV agents occurs with increasing duration of use. In vitro studies have
shown that cross-resistance occurs among protease inhibitors, although no clinical trials
have been conducted to examine antiretroviral activity with sequential use of protease
inhibitors or to determine whether saquinavir resistance can be overcome with higher
concentrations of the drug.
A Study of Saquinavir Soft Gel Capsules (SGC) Used in Combination With Two Other Anti-HIV Drugs in Patients With HIV-Associated Kidney Disease [Completed]
The purpose of this study is to compare the safety and effectiveness of saquinavir SGC plus
stavudine (d4T) plus lamivudine (3TC) with that of saquinavir SGC plus nelfinavir plus d4T in
patients with HIV-associated kidney disease. This study examines whether these drug
combinations are effective in preventing kidney disease from progressing to a stage where it
is immediately life threatening. This study also examines the effect these drug combinations
have on the level of HIV detected in these patients. Finally, this study evaluates the drug
level (the amount of drug found in the body) of these two combinations in patients with
kidney disease.
Comparison of Ro 31-8959 Plus Zidovudine (AZT) Versus AZT Plus Zalcitabine (ddC) Versus Ro 31-8959 Plus AZT Plus ddC [Completed]
A Study of Saquinavir Soft Gelatin Capsules Combined With Other Anti-HIV Drugs in HIV-1 Infected Patients [Completed]
To examine the efficacy of saquinavir SGC (soft gel capsules) in combination with other
antiretrovirals in HIV-1 infected patients currently treated with saquinavir HGC (hard gel
capsules) measured by the absolute change in plasma HIV-1 RNA during the 24 weeks of study
treatment.
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