indication

For the treatment of HIV-1 with advanced immunodeficiency together with antiretroviral nucleoside analogues.

pharmacology

Saquinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Saquinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

mechanism of action

Saquinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

toxicity

Probably experience pain in the throat

biotransformation

Hepatic

absorption

Absolute bioavailability averages 4%

route of elimination

In vitro studies using human liver microsomes have shown that the metabolism of saquinavir is cytochrome P450 mediated with the specific isoenzyme, CYP3A4, responsible for more than 90% of the hepatic metabolism. Only 1% of saquinavir is excreted in the urine, so the impact of renal impairment on saquinavir elimination should be minimal.

drug interactions

Abacavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Saquinavir. The antiviral response should be closely monitored.

Alprazolam: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, alprazolam.

Amiodarone: The protease inhibitor, saquinavir, may increase the effect and toxicity of amiodarone.

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atorvastatin: Saquinavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if saquinavir is initiated, discontinued or dose changed.

Bromazepam: Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if saquinavir is initiated, discontinued or dose changed. Dosage adjustments may be required.

Chlordiazepoxide: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, chlordiazepoxide.

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Clonazepam: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, clonazepam.

Clorazepate: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, clorazepate.

Cyclosporine: The protease inhibitor, saquinavir, may increase the effect of cyclosporine.

Dantrolene: Saquinavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if saquinavir is initiated, discontinued or dose changed.

Darunavir: Decreased levels of darunavir

Delavirdine: Increases the effect of saquinavir and hepatic toxicity

Diazepam: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, diazepam.

Dihydroergotamine: The protease inhibitor, saquinavir, may increase the effect and toxicity of the ergot derivative, dihydroergotamine.

Efavirenz: Efavirenz decreases the effect of saquinavir

Eplerenone: This CYP3A4 inhibitor increases the effect and toxicity of eplerenone

Ergotamine: The protease inhibitor, saquinavir, may increase the effect and toxicity of the ergot derivative, ergotamine.

Erlotinib: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Estazolam: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, estazolam.

Fentanyl: The protease inhibitor, saquinavir, may increase the effect and toxicity of fentanyl.

Flurazepam: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, flurazepam.

Fusidic Acid: The protease inhibitor, saquinavir, may increase the effect and toxicity of fusidic acid.

Indinavir: Possible antagonism of action

Ketoconazole: Ketoconazole may increase the effect and toxicity of saquinavir.

Lovastatin: Saquinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.

Midazolam: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, midazolam.

Nevirapine: Decreases the effect of saquinavir

Pimozide: The protease inhibitor, saquinavir, may increase the effect and toxicity of pimozide.

Ranolazine: Increased levels of ranolazine - risk of toxicity

Rifabutin: Rifabutin decreases the effect of saquinavir

Rifampin: Rifampin decreases the effect of saquinavir

Tacrolimus: The protease inhibitor, Saquinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Saquinavir therapy is initiated, discontinued or altered.

Tadalafil: Saquinavir may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.

Tamoxifen: Saquinavir may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.

Tamsulosin: Saquinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Saquinavir is initiated, discontinued, or dose changed.

Telithromycin: Saquinavir may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.

Temsirolimus: Saquinavir may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.

Teniposide: The strong CYP3A4 inhibitor, Saquinavir, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Saquinavir is initiated, discontinued or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Tiagabine: The strong CYP3A4 inhibitor, Saquinavir, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Saquinavir is initiated, discontinued or dose changed.

Tipranavir: Tipranavir, co-administered with Ritonavir, may decrease the plasma concentration of Saquinavir. Consider alternate therapy.

Tolterodine: Saquinavir may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.

Topotecan: The p-glycoprotein inhibitor, Saquinavir, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.

Tramadol: Saquinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.

Trazodone: The protease inhibitor, Saquinavir, may increase the efficacy/toxicity of Trazodone by inhibiting Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Saquinavir is initiated, discontinued or dose changed.

Triazolam: The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, triazolam.

Trimipramine: The strong CYP3A4 inhibitor, Saquinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Saquinavir is initiated, discontinued or dose changed.

Vardenafil: Saquinavir, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.

Venlafaxine: Saquinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Saquinavir is initiated, discontinued, or dose changed.

Verapamil: Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Saquinavir is initiated, discontinued or dose changed.

Vinblastine: Saquinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Saquinavir is initiated, discontinued or dose changed.

Vincristine: Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Saquinavir is initiated, discontinued or dose changed.

Vinorelbine: Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Saquinavir is initiated, discontinued or dose changed.

Voriconazole: Voriconazole may increase the serum concentration of saquinavir by decreasing its metabolism. Saquinavir may increase the serum concentration of voriconazole. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.

Zolpidem: Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if saquinavir is initiated, discontinued or dose changed.

Zonisamide: Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if saquinavir is initiated, discontinued or dose changed.

Zopiclone: Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if saquinavir is initiated, discontinued or dose changed.