Last Updated June 10, 2016
HIV protease inhibitor antiretroviral
100 mg capsules; 80 mg/mL oral solution (contains 43% alcohol*)
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 and 2D6. Inhibits CYP 450 3A4 and 2D6 enzyme. Half-life: 3-5 hours.
- 600 mg twice daily. Gradual dose escalation may provide relief from nausea: 300 mg twice daily for 1 day, 400 mg twice daily for 2 days, 500 mg twice daily for 1 day, then 600 mg twice daily. When used as a booster for other PIs, see specific drug profile.
- Primarily used in combination with other PIs as a drug concentration booster at 100-400 mg once to twice daily, depending on the concomitant PI.
- Take with food.*
Use in Renal or Hepatic Insufficiency*:
- No dose adjustment for renal dysfunction.
- Refer to primary PI for recommendations on hepatic dysfunction.
Use in Pregnancy and Breastfeeding*: Category B. Excretion in breast milk unknown.
Use in Children: > 2 years: initially (to minimize nausea) 250 mg/m² twice daily, increased gradually over 1 week to 350 mg/m² twice daily, up to a maximum of 600 mg twice daily.
US Prescribing Information Boxed Warning*: coadministration of ritonavir with several classes of medications may result in serious and/or life-threatening adverse events due to ritonavir increasing the concentrations of medications (including sedative hypnotics, antiarrhythmics, or ergo alkaloid preparations). Ritonavir is a potent inhibitor of CYP 450 3A4 and 2D6.
In adults, primarily used in low-dose form as a booster because of toxicity.
Oral solution is bitter in taste; tolerability can be increased by mixing with milk, icing mouth before administration, or coating mouth with peanut butter.
Many drug–drug interactions; for details, see the database entry for the concomitant PI (ritonavir is primarily administered in adults with a concomitant PI).
- Amiodarone, clozapine, colchicine, dextropropoxyphene, pethidine, pimozide, and quinidine: potential for life-threatening adverse events; avoid concomitant use.
- Anticonvulsants: carbamazepine levels may increase markedly. Limited data on concurrent use with phenytoin or phenobarbital; close monitoring is required.
- Ergot alkaloids and derivatives: increased plasma levels of ergot alkaloids may lead to acute ergot toxicity; avoid concomitant use.
- HMG CoA reductase inhibitors metabolized by CYP 3A4 (simvastatin, lovastatin, atorvastatin): increased risk of myopathy. Simvastatin should be avoided and atorvastatin used with caution.
- Ketoconazole: large increase in ketoconazole plasma concentrations.
- Macrolides (eg, clarithromycin, erythromycin): plasma levels of macrolides may be increased.
- Oral contraceptives: plasma levels of ethinyl-estradiol reduced; may cause pill failure.
- Rifabutin: increased plasma levels of rifabutin, requiring dose adjustment (decrease to 150 mg every other day†).
- Sedatives and hypnotics (eg, diazepam, midazolam, triazolam, clorazepate, and zolpidem): potential for extreme sedation and respiratory depression; avoid concomitant use.
- Sildenafil, tadalafil, vardenafil: plasma levels increased by PIs, with increased risk of adverse events.
- St John’s wort: plasma concentrations of PIs reduced, resulting in loss of therapeutic effect and development of resistance.
Considerations for Special Populations
See above for pregnancy and lactation.
Gastrointestinal symptoms (intolerance, nausea, vomiting, diarrhoea), paraesthesias (circumoral and extremities), hyperlipidemia, hepatitis, hyperglycaemia including new-onset and exacerbation of existing diabetes, taste perversion, fat maldistribution, possible increased bleeding in patients with haemophilia.*
*Information from US prescribing information.
†Recommendation from Southern African HIV Clinician Society Guidelines.