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Active ingredient: Saquinavir - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Anti-HIV Agents

Dosage Forms

  • Capsules

Brands / Synonyms

Fortovase; Invirase; ROC; Saquinavir Mesylate; Saquinavir [Usan] ; SQV

Indications

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.

Absorption

Absolute bioavailability averages 4%

Toxicity

Probably experience pain in the throat

Biotrnasformation / Drug Metabolism

Hepatic

Contraindications

CONTRAINDICATIONS

INVIRASE may be used only if it is combined with ritonavir, which significantly inhibits saquinavir's metabolism and
provides plasma saquinavir levels at least equal to those achieved with FORTOVASE.

INVIRASE is contraindicated in patients with clinically significant hypersensitivity to saquinavir or to any of the
components contained in the capsule.

INVIRASE/ritonavir should not be administered concurrently with terfenadine, cisapride, astemizole, pimozide, triazolam,
midazolam or ergot derivatives. Inhibition of CYP3A4 by saquinavir could result in elevated plasma concentrations of
these drugs, potentially causing serious or life-threatening reactions, such as cardiac arrhythmias or prolonged sedation.

INVIRASE when administered with ritonavir is contraindicated in patients with severe hepatic impairment.

INVIRASE should not be administered concurrently with drugs listed drug interaction section and drugs below

Drugs That Are Contraindicated With INVIRASE/Ritonavir

Drug Class
Drugs Within Class That Are Contraindicated With INVIRASE

Antiarrhythmics
Amiodarone, bepridil, flecainide, propafenone, quinidine

Antihistamines
Astemizole, terfenadine

Ergot Derivatives
Dihydroergotamine, ergonovine, ergotamine, methylergonovine

Antimycobacterial Agents
Rifampin*

GI Motility Agent
Cisapride

Neuroleptics
Pimozide

Sedative/Hypnotics
Triazolam, midazolam

*INVIRASE used as a sole protease inhibitor

Drug Interactions

DRUG INTERACTIONS

Several drug interaction studies have been completed with both INVIRASE and FORTOVASE. Observations from drug interaction studies
with FORTOVASE may not be predictive for INVIRASE. Because ritonavir is coadministered, prescribers should also refer to the
prescribing information for ritonavir regarding drug interactions associated with this agent.

The metabolism of saquinavir is mediated by cytochrome P450, with the specific isoenzyme CYP3A4 responsible for 90% of the hepatic
metabolism. Additionally, saquinavir is a substrate for P-Glycoprotein (Pgp). Therefore, drugs that affect CYP3A4 and/or Pgp, may
modify the pharmacokinetics of saquinavir. Similarly, saquinavir might also modify the pharmacokinetics of other drugs that are
substrates for CYP3A4 or Pgp.

Drugs that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse events
are listed CONTRAINDICATIONS. Additional drugs that are not recommended for coadministration with INVIRASE and ritonavir are included
below. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of
interaction and potential for serious events or loss of efficacy.

When coadministering INVIRASE/ritonavir with any agent having a narrow therapeutic margin, such as anticoagulants, anticonvulsants,
and antiarrhythmics, special attention is warranted. With some agents, the metabolism may be induced, resulting in decreased
concentrations.
Drugs That Should Not Be Coadministered With INVIRASE/Ritonavir

Drug Class: Drug Name
Clinical Comment


Antiarrhythmics: Amiodarone, bepridil, flecainide, propafenone, quinidine
CONTRAINDICATED due to potential for serious and/or life-threatening reactions.

Antihistamines: astemizole*, terfenadine*
CONTRAINDICATED due to potential for serious and/or life-threatening cardiac arrhythmias.

Ergot Derivatives: Dihydroergotamine, ergonovine, ergotamine, methylergonovine
CONTRAINDICATED due to potential for serious and life-threatening reactions such as acute ergot toxicity characterized by peripheral
vasospasm and ischemia of the extremities and other tissues.

Antimycobacterial Agents: rifampin
CONTRAINDICATED since the coadministration of this product with saquinavir in an antiretroviral regimen reduces the plasma concentrations
of saquinavir.

Garlic Capsules
Garlic capsules should not be used while taking saquinavir (FORTOVASE) as the sole protease inhibitor due to the risk of decreased
saquinavir plasma concentrations.

No data are available for the coadministration of INVIRASE/ritonavir or FORTOVASE/ritonavir and garlic capsules.

GI Motility Agent: cisapride*
CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias.

Herbal Products: St. John’s wort (hypericum perforatum)
WARNING coadministration may lead to loss of virologic response and possible resistance to INVIRASE or to the class of protease
inhibitors.

HMG-CoA Reductase Inhibitors: lovastatin, simvastatin
WARNING potential for serious reactions such as risk of myopathy including rhabdomyolysis.

Sedatives/Hypnotics: triazolam, midazolam
CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory
depression.

* No longer marketed in the US.

Drugs That Are Mainly Metabolized by CYP3A4

Although specific studies have not been performed, coadministration with drugs that are mainly metabolized by CYP3A4 (eg, calcium channel
blockers, dapsone, disopyramide, quinine, amiodarone, quinidine, warfarin, tacrolimus, cyclosporine, ergot derivatives, pimozide,
carbamazepine, fentanyl, alfentanyl, alprazolam, and triazolam) may have elevated plasma concentrations when coadministered with saquinavir;
therefore, these combinations should be used with caution. Since INVIRASE is coadministered with ritonavir, the ritonavir label should be
reviewed for additional drugs that should not be coadministered.

Inducers of CYP3A4

Coadministration with compounds that are potent inducers of CYP3A4 (eg, phenobarbital, phenytoin, dexamethasone, carbamazepine) may result
in decreased plasma levels of saquinavir.

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