Pharmacokinetics
Oral absorption: c. 4%
C
max 1200 mg thrice daily: c. 1–2.2 mg/L
C
min 1200 mg thrice daily: c. 0.1–0.22 mg/L
Plasma half-life: c. 7–12 h
Volume of distribution: c. 700 L
Plasma protein binding: c. 98%
Absorption and distribution
It is poorly absorbed and penetrates poorly into the CNS. The semen:plasma ratio is 0.04. It is not known if it is distributed into human breast milk.
Metabolism and excretion
It is metabolized via CYP3A4, principally to mono- and dihydroxylated derivatives. Around 88% of the dose is excreted in feces and 1% in urine. Caution should be exercised in severe renal impairment and moderate hepatic impairment; use in decompensated hepatic impairment is contraindicated.
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: increased risk of ventricular arrhythmias
with alfentanil, fentanyl and methadone - avoid.
Anti-arrhythmics: increased risk of ventricular
arrhythmias with amiodarone, disopyramide,
dronedarone, flecainide, lidocaine or propafenone -
avoid.
Antibacterials: increased risk of ventricular
arrhythmias with clarithromycin, dapsone,
erythromycin or moxifloxacin - avoid; increased
risk of ventricular arrhythmias with delamanid;
concentration of rifabutin increased; rifampicin and
rifabutin can reduce saquinavir levels by 80% and
40% respectively (metabolism accelerated); increased
hepatoxicity with rifampicin - avoid; concentration
of both drugs increased with fusidic acid.
Anticoagulants: avoid with apixaban and
rivaroxaban.
Antidepressants: increased risk of ventricular
arrhythmias with trazodone or tricyclics - avoid;
concentration reduced by St John’s wort - avoid.
Antiepileptics: carbamazepine, phenobarbital,
and phenytoin and possibly primidone can reduce
saquinavir levels.
Antifungals: concentration increased by ketoconazole
- avoid.
Antihistamines: increased risk of ventricular
arrhythmias with mizolastine - avoid.
Antimalarials: avoid with piperaquine with
artenimol; use artemether/lumefantrine with
caution; increased risk of ventricular arrhythmias
with quinine - avoid.
Antipsychotics: increased risk of ventricular
arrhythmias with clozapine, haloperidol or
phenothiazines - avoid; possibly increased risk
of ventricular arrhythmias with pimozide and
quetiapine - avoid; possibly inhibits aripiprazole
metabolism - reduce aripiprazole dose; possibly
increases lurasidone concentration - avoid.
Antivirals: tipranavir and efavirenz can reduce
saquinavir levels; increased risk of ventricular
arrhythmias with atazanavir or lopinavir - avoid;
concentration increased by indinavir and ritonavir;
reduced darunavir concentration; concentration
of maraviroc increased, consider reducing dose of
maraviroc.
Anxiolytics and hypnotics: midazolam concentration
possibly increased (prolonged sedation) - avoid with
oral midazolam.
Beta-blockers: increased risk of ventricular
arrhythmias with sotalol - avoid.
Ciclosporin: concentration of both drugs increased.
Cytotoxics: possibly increases concentration of
axitinib, ibrutinib and panobinostat, reduce dose
of axitinib, ibrutinib and panobinostat; possibly
increases bosutinib, cabazitaxel, ceritinib and
docetaxel concentration - avoid or consider reducing
dose; possibly increases concentration of crizotinib
and everolimus - avoid; avoid with lapatinib,
olaparib and pazopanib; reduce dose of ruxolitinib.
Dapoxetine: increased risk of toxicity - avoid.
Domperidone: possibly increases risk of ventricular
arrhythmias - avoid.
Ergot alkaloids: risk of ergotism - avoid.
Guanfacine: concentration possibly increased - halve
guanfacine dose.
Lipid-lowering drugs: increased risk of myopathy
with rosuvastatin and simvastatin - avoid; possibly
increased myopathy with atorvastatin; avoid with
lomitapide.
Naloxegol: possibly increases naloxegol concentration
- avoid.
Orlistat: absorption possibly reduced by orlistat.
Pentamidine: increased risk of ventricular
arrhythmias - avoid.
Ranolazine: possibly increases ranolazine
concentration - avoid.
