saquinavir

CLINICAL USE

Protease inhibitor:Treatment of HIV infection in combination with other antiviral drugs

DOSE IN NORMAL RENAL FUNCTION

With low dose ritonavir: 1 g twice daily

PHARMACOKINETICS

Molecular weight :670.8

%Protein binding :98

%Excreted unchanged in urine : <4

Volume of distribution (L/kg) :10

half-life – normal/ESRD (hrs) :13.2

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unlikely to be dialysed. Dose as in normal renal function

HD :Unlikely to be dialysed. Dose as in normal renal function

HDF/high flux :Not dialysed. Dose as in normal renal function

CAV/VVHD :Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antibacterials: rifampicin and rifabutin can reduce saquinavir levels by 80% and 40% respectively (metabolism accelerated); increased hepatoxicity with rifampicin; concentration possibly increased by quinupristin/dalfopristin; avoid with telithromycin in severe renal and hepatic failure

Antidepressants: concentration reduced by St John’s wort – avoid

Anti-epileptics: carbamazepine, phenobarbital, primidone and phenytoin can reduce saquinavir levels

Antimalarials: avoid concomitant use with artemether/lumefantrine

Antipsychotics: possibly increased risk of ventricular arrhythmias with pimozide and sertindole – avoid concomitant use; possibly inhibits aripiprazole metabolism – reduce aripiprazole dose

Antivirals: tipranavir and efavirenz can reduce saquinavir levels; nelfinavir can cause an increase in levels of both nelfinavir and saquinavir; concentration increased by atazanavir, indinavir, lopinavir and ritonavir; reduced darunavir concentration
Anxiolytics and hypnotics: midazolam plasma concentration possibly increased (prolonged sedation) – avoid

Ciclosporin: concentration of both drugs increasedCilostazol: concentration of cilostazol possibly increased – avoid concomitant use

Ergot alkaloids: risk of ergotism – avoid Lipid-lowering drugs: increased risk of myopathy with simvastatin – avoid; possibly increased myopathy with atorvastatin
Omeprazole: AUC of saquinavir increased by 82% (increased risk of toxicity)

Tacrolimus: possibly increased tacrolimus concentration – may need to reduce dose

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

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Comments

Administer within 2 hours after meal

OTHER INFORMATION

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