Fortovase

Fortovase by Roche is scheduled to be discontinued on February 15, 2006 (before production of this book) therefore, we have maintained all information pertaining to Fortovase in this monograph. 

Saquinavir soft gelatin capsules Fortovase) and saquinavir mesylate capsules Invirase) are not bioequivalent and cannot be used interchangeably. 

Fortovase Six 200 mg capsules 3 times daily taken with a meal or up to 2 hours after a meal. When used in combination with nucleoside analogs, do not reduce the dosage of saquinavir, as this will lead to greater than dose-proportional decreases in saquinavir plasma levels. 

Elderly In general, take caution when dosing Fortovase in elderly patients because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. 

Fortovase should be used for the initiation of saquinavir therapy (see Administration and Dosage) because Fortovase capsules provide greater bioavailability and efficacy than Invirase. For patients taking Invirase capsules with a viral load below the limit of quantification, a switch to Fortovase is recommended to maintain a virologic response. For patients taking Invirase capsules who have not had an adequate response or are failing therapy, if saquinavir resistance is clinically suspected, then do not use Fortovase. If resistance to saquinavir is not clinically suspected, consider a switch to Fortovase. 

Nelfinavir (Viracept) Nevirapine (Viramune) Raltegravir (Isentress) Ritonavir (Norvir) Saquinavir (Fortovase, Invirase)... 

Saquinavir is a potent inhibitor of HIV-1 and HIV-2 protease. Fortovase, a soft gel preparation of saquinavir, has largely replaced saquinavir mesylate capsules (Jnvirase) because it has improved bioavailability. Saquinavir is usually well tolerated and most frequently produces mild gastrointestinal side effects. 

Brand Name(s) Fortovase, Invirase CfiemicalClass Protease inhibitor, HIV... 

HIV infection in combination with other antiretrovirals PO (Fortovase) 1,200 mg 3 times a day or 1,000 mg twice a day in combination with ritonavir 100 mg twice a day. PO (Invirase) 1,000 mg (5X200 mg or 2X500 mg) twice a day in combination with ritonavir 100 mg twice a day. Dosage adjustments when given in combination therapy Delavirdine Fortovase 800 mg 3 times a day Lopinavir/ritonavir-. Fortovase 800 mg twice a day Nelfinavir. Fortovase 800 mg 3 times a day or 1,200 mg twice a day. Ritonavir. Fortovase or Invirase 1,000 mg twice a day... 

Invirase and Fortovase not considered bioequivalent no food effect on Invirase when taken with ritonavir take Fortovase with large meal... 

Hugen PW, Burger DM, Koopmans PP, et al. Saquinavir soft-gel capsules (Fortovase) give lower exposure than expected, even after a high-fat breakfast. Pharm World Sci 2002 24(3) 83-86. 

Oral (Invirase) 200 mg hard gel capsules, 500 mg tablets Oral (Fortovase) 200 mg soft gel capsules Stavudine... 

Saquinavir is available as Invirase, which is its hard gelatin form, and Forto-vase, which is its soft gelatin form. In combination with other antiretroviral agents and another protease inhibitor ritonavir, Invirase is recommended for the treatment of HIV infection, and due to its low bioavailability, considerably higher doses are recommended. The two preparations, Invirase and Fortovase, are not bioequivalent and could not be used interchangeably. Although Fortovase can be used as a sole protease inhibitor in a combination therapy, Invirase could be used only in combination with ritonavir. 

Fortovase Satjuitiiivir Medium chain mono-and diglyccrides Povidone and dt-alpha tocopherol ... 

The ability of lipid vehicles (either in the pharmaceutical formulation or in food) to enhance the absorption of lipophilic drugs has been well known for many years. Recently, successful bioavailability enhancement utilizing lipid-based formulations has been accomplished with the immunosuppressive agent cyclosporine A (Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ), and for the two HIV protease inhibitors ritonavir (Norvir, Abbott Laboratories, IL) and saquinavir (Fortovase, Roche Pharmaceuticals, Nutley, NJ). Consequently, considerable interest in lipid-based formulations has been aroused. 

In its original formulation as a hard gel capsule (saquinavir-H Invirase), oral saquinavir was poorly bioavailable (about 4% in the fed state). It was therefore largely replaced in clinical use by a soft gel capsule formulation (saquinavir-S Fortovase), in which absorption was increased approximately threefold. However, reformulation of saquinavir-H for once-daily dosing in combination with low-dose ritonavir (see Ritonavir) has both improved antiviral efficacy and decreased the gastrointestinal side effects typically associated with saquinavir-S. Moreover, coadministration of saquinavir-H with ritonavir results in blood levels of saquinavir similar to those associated with saquinavir-S, thus capitalizing on the pharmacokinetic interaction of the two agents. 

Both formulations of saquinavir should be taken within 2 hours after a fatty meal for enhanced absorption. Saquinavir has a large volume of distribution but is 98% protein-bound penetration into the cerebrospinal fluid is negligible. The elimination half-life is 12 hours. Excretion is primarily in the feces. Reported adverse effects include gastrointestinal discomfort (nausea, diarrhea, abdominal discomfort, dyspepsia these are more common with Fortovase) and rhinitis. Although refrigeration is recommended for storage, the capsules are stable at room temperature for up to 3 months. 

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