Protease Inhibitors: Saquinavir
Contents Introduction Information cards Hard gelatin capsule Soft gelatin capsule Pharmacokinetics Dosing Side effects Drug interactions

Introduction

The information represented on this drug does not necessarily correspond with the information that can be found in the Belgian scientific leaflet.
In December of 1995, the FDA granted accelerated approval for the use of saquinavir (in its initial hard gel formulation) in combination with one or more nucleoside analogues in patients with advanced HIV disease. It is not approved as monotherapy. Because of problems with the initial hard-gel formulation, a new soft-gel formulation was developed. Saquinavir-soft gel capsule was approved by the FDA in 1997. (106)

Hard gelatin capsule:

Abbreviation(s):  Generic name: Brand name: SQV saquinavir Invirase®		USA (FDA) Adult approval date: Pediatric approval date: December 6, 1995 No pediatric labeling
Pharmaceutical co.: Hoffmann- La Roche		Belgium: Reimbursable since April 1997
	Active Ingredient	Dosage form; Route		Strength
	Saquinavir mesylate	Capsule; Oral		200MG

Soft gelatin capsule:
 

Abbreviation(s):  Generic name: Brand name: SQV saquinavir Fortovase®		USA (FDA) Adult approval date: Pediatric approval date: November 7, 1997 No pediatric labeling
Pharmaceutical co.: Hoffmann- La Roche		Belgium: Not yet a price neither reimbusable.

Saquinavir is heavily metabolized by the P450 CYP3A isoenzyme.(106,118) Although the in vitro activity of this compound is very good, its in vivo activity in its initial hard gel formulation is limited by first-pass metabolism and subsequent low bioavailability (4%). (100,106) Compared to the hard gel formulation, the soft gel formulation has at least threefold greater bioavailability. (106)

Dosing

The starting dosage is 600 mg for Invirase® every 8 hours, preferably taken with a high-fat meal.(100,111)

Side effects

Of the available protease inhibitors, saquinavir-hard gel capsule may be the best tolerated. Reported side effects are diarrhea, nausea, gastrointestinal discomfort, and rash, all typically mild and relatively uncommon. Experience with saquinavir-soft gel capsule is limited. Early studies indicated that the drug is associated with diarrhea, nausea, and other gastrointestinal symptoms. (106)

Drug interactions

Drugs that induce cytochrome P450 3A4 isoform activity can enhance the metabolism of saquinavir, thus leading to reduced blood levels. Rifampin, a known inducer of P450 3A4, decreases the AUC of saquinavir by 80%. Rifabutin may has a similar effect and decreases the AUC of saquinavir by 40%. Phenobarbital, phenytoin, dexamethasone and carbamazepine will also lower the concentration of saquinavir. In contrast, drugs that inhibit the cytochrome P450 system, such as ketoconazol may increase plasma concentrations of saquinavir.(118) Grapefruit juice can also increase the AUC of saquinavir by aproximately 220%. (106,114)
 
 

Interactions with other antiretroviral agents

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