Drug Detail

Saquinavir

Last Updated June 10, 2016

Trade Names

Invirase

Drug Classification

HIV protease inhibitor antiretroviral

Formulations

200 mg capsules

Indications and Pharmacology

Indication: treatment of HIV infection when combined with other antiretrovirals.

Mechanism of action*: inhibits cleavage of viral gag-pol polyproteins precursors into functional proteins by binding to the HIV protease enzyme.

Pharmacokinetics*: metabolized in the liver by CYP 3A4. Inhibits CYP 450 3A4 enzyme. Half life: 7-12 hours.

Dosage

Adult Dose:

  • Saquinavir 1000 mg + ritonavir 100 mg twice daily or
  • Saquinavir 400 mg + ritonavir 400 mg twice daily.
  • Unboosted saquinavir is not recommended.
  • Take with food or within 2 hrs after a meal.*

Use in Renal or Hepatic Insufficiency*:

  • No dose adjustment for renal dysfunction.
  • No dosage adjustment for mild to moderate hepatic dysfunction. Do not use in severe hepatic dysfunction.

Use in Pregnancy and Breastfeeding*: Category B. Excretion into breast milk is not known.

Use in Children: No recommended use in children.

Warnings

Very poor bioavailability: should only be used with ritonavir to boost levels into therapeutic range.

Combination of saquinavir and ritonavir may prolong QT and PR intervals. Should not be used with class 1a or 111 antiarrhythmic drugs.

Drug–Drug Interactions

Contraindicated: amiodarone, bepridil, dofetilide, flecainide, lidocaine, propafenone, quinidine, lovastatin, simvastatin, rifampin, cisapride, pimozide, oral midazolam, triazolam, trazodone, dihydroergotamine, ergonovine, ergotamine, methylergonovine, alfuzosin, sildenafil for pulmonary arterial hypertension, clarithromycin, erythromycin, halofantrine, pentamidine, atazanavir, tacrolimus, chlorpromazine, sertindole, clozapine, haloperidol, mesoridazine, phenothiazines, thioridazine, ziprasidone, dapsone, disopyramide, quinine.*

Increased concentrations of concomitant medication: warfarin, tricyclic antidepressants, ketoconazole, itraconazole, clarithromycin, rifabutin (dose rifabutin 150 mg every other day), alprazolam, clorazepate, diazepam, flurazepam, bosentan, digoxin, calcium channel blockers, fluticasone, atorvastatin, sildenafil, tadalafil, vardenafil, colchicine, salmeterol, fusidic acid, ritonavir, quetiapine, midazolam, cyclosporine, rapamycin. fentanyl, alfentanil, vincamine.*

Decreased concentrations of concomitant medication: methadone, warfarin, ethinyl estradiol.*

Increased concentrations of saquinavir with concomitant medication: streptogramin antibiotics, fusidic acid, proton pump inhibitors, nefazodone.*

Decreased concentrations of saquinavir with concomitant medication: carbamazepine, phenobarbital, phenytoin, dexamethasone, St John’s wort, garlic supplements.*

Drug interactions between saquinavir and other antiretrovirals:*

Considerations for Special Populations

See above for pregnancy and lactation.

Adverse Effects

Gastrointestinal symptoms (intolerance, nausea, diarrhoea), QT interval prolongation (Torsades de pointes has been reported, if QT interval ≥ 450 msec saquinavir should not be given), headache, increased liver enzymes, hyperlipidaemia, hyperglycaemia, fat maldistribution, possible increased bleeding in patients with haemophilia, PR interval prolongation.*

*Information from US prescribing information.
Recommendation from Southern African HIV Clinician Society Guidelines.