Drug Detail

Darunavir

Last Updated June 10, 2016

Trade Names

Prezista

Drug Classification

HIV protease inhibitor antiretroviral

Formulations

300 mg, 600 mg tablets

Indications and Pharmacology

Indication: treatment of HIV infection in combination 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 CYP 450 3A4. Half-life: 15 hours (with ritonavir). Inhibits CYP 3A4 enzyme.

Dosage

Adult Dose:

  • Antiretroviral therapy-experienced patients: 600 mg twice daily with ritonavir 100 mg twice daily and with food.
  • PI-naive patients: 800 mg once daily with ritonavir 100 mg once daily with food.
  • Unboosted darunavir should not be given.
  • Darunavir/ritonavir should not be dosed concomitantly with rifampicin or rifapentine.*
  • If darunavir/ritonavir administered concomitantly with rifabutin, rifabutin dose should be decreased* (see Drug–Drug Interactions).

Use in Renal or Hepatic Insufficiency: No dose adjustment in renal dysfunction or mild to moderate hepatic impairment. Not recommended in severe hepatic impairment.

Use in Pregnancy and Breastfeeding: Safety and efficacy have not been demonstrated. It is not known whether darunavir is excreted in human milk.

Use in Children: Not registered for paediatric use in South Africa.

Warnings

See Drug–Drug Interactions.

Drug–Drug Interactions

Contraindicated*: colchicine, dronedarone, ranolazine, lovastatin, simvastatin, rifampicin, cisapride, pimozide, midazolam, triazolam, dihydroergotamine, ergotamine, methylergonovine, St John’s wort, alfuzosin, sildenafil for pulmonary arterial hypertension.

Increased concentrations of concomitant medication*: bosentan, carbamazepine, digoxin, trazodone, tricyclic antidepressants, antiarrhythmics, itraconazole, clarithromycin, itraconazole, ketoconazole, rifabutin (dose rifabutin 150 mg every other day), lumefantrine, diazepam, buspirone, estazolam, parenterally administered midazolam, zoldipem,  diltiazem, verapamil, amlodipine, felodipine, nicardipine, nifedipine, inhaled or systemic corticosteroids, atorvastatin, pravastatin, rosuvastatin, simvastatin, tadalafil, vardenafil, avanafil, sildenafil, colchicine, lovastatin, salmeterol, apixaban, dabigatran etexilate, rivaroxaban, dasatinib, nilotinib, vinblastine, vincristine, quetiapine, risperidone, thioridazine, carvedilol, metoprolol, timolol, cyclosporine, tacrolimus, sirolimus, simeprevir.

Decreased concentrations of concomitant medication*: methadone, warfarin, ethinyl estradiol, norethindrone, phenytoin, phenobarbital, paroxetine, sertraline, voriconazole, boceprevir, telaprevir, artemether.

Increased concentrations of darunavir with concomitant medication*: itraconazole, etoconazole, posaconazole, rifabutin, simeprevir.

Decreased concentrations of darunavir with concomitant medication*: phenobarbital, phenytoin, dexamethasone, boceprevir, telaprevir, rifapentine.

Drug interactions between darunavir and other antiretrovirals*:

Considerations for Special Populations

See above for pregnancy and lactation; see above for children and adolescents.

Adverse Effects

Skin rash (sulphonamide moiety), Stevens-Johnson syndrome, hepatotoxicity, headache, nausea, diarrhoea, hyperlipidaemia, liver enzyme elevation, hyperglycaemia, fat maldistribution, gynaecomastia, diabetes, anorexia, fatigue, possible increased bleeding in haemophilia patients.

*Information from US prescribing information.
Recommendation from the Southern African HIV Clinicians Society guidelines.