Drug Detail

Atazanavir

Last Updated June 10, 2016

Trade Names

Reyataz, Aspen Atazanavir

Drug Classification

HIV protease inhibitor antiretroviral

Formulations

150 mg, 200 mg capsules

Indications and Pharmacology

Indication: treatment of HIV infection in combination with other antiretrovirals; postexposure prophylaxis when lopinavir/ritonavir or efavirenz are not well tolerated (also 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: 7 hours (without ritonavir), 9-18 hours (with ritonavir). Food enhances bioavailability and reduces pharmacokinetic variability.

Dosage

Adult Dose:

  • Atazanavir 300 mg + ritonavir 100 mg once daily: all patients.
  • Atazanavir 400 mg once daily:
    • Antiretroviral therapy–naive patients (South African Formulary recommends use of unboosted atazanavir only in patients intolerant of ritonavir).
    • Unboosted atazanavir may not be used in combination with efavirenz or tenofovir.
    • Should not be prescribed concomitantly with rifampicin.*
    • When either atazanavir or atazanavir/ritonavir prescribed with rifabutin, rifabutin dose should be reduced (see Drug–Drug interactions).

Take with food.*

See below for caution with stomach acid–suppressing medications.*

Use in Renal or Hepatic Insufficiency: 

  • Patients on dialysis: atazanavir 300 mg plus ritonavir 100 mg once daily.*
  • Moderate liver impairment: 300 mg once daily.
  • Avoid in severe liver impairment.

Use in Pregnancy and Breastfeeding: No recommendation.

Use in Children: Optimal dose not established.

Warnings

See Drug–Drug Interactions.

A mild or moderate maculopapular rash can develop in the first 3 weeks of therapy; if severe rash occurs, discontinue therapy.

Drug–Drug Interactions

Contraindicated*: lovastatin, simvastatin, rifampicin, cisapride, pimozide, midazolam, triazolam, dihydroergotamine, ergonovine, ergotamine, methylergonovine, St John’s wort, nevirapine, alfuzosin, irinotecan, sildenafil for pulmonary arterial hypertension, indinavir.

Atazanavir with stomach acid–suppressing agents*:

  • Antacids: give atazanavir at least 2 hours before or 1 hour after antacids or buffered medications.
  • H2 receptor antagonists (H2RA):
    • Atazanavir/ritonavir: H2RA dose should not exceed dose equivalent of famotidine 40 mg twice daily in antiretroviral therapy (ART)–naive patients or 20 mg twice daily in ART-experienced patients. Give atazanavir 300 mg + ritonavir 100 mg once daily simultaneously or 10 hours after the H2RA. If using tenofovir and H2RA in ART-experienced patients, use atazanavir 400 mg + ritonavir 100 mg.
    • Atazanavir (unboosted): H2RA single dose should not exceed a dose equivalent of famotidine 20 mg or total daily dose equivalent of famotidine 20 mg twice daily in ART-naive patients. Give at least 2 hours before or at least 10 hours after the H2RA.
  • Proton pump inhibitors (PPIs):
    • Atazanavir/ritonavir: PPIs should not exceed a dose equivalent to omeprazole 20 mg daily in PI-naive patients. PPIs should be administered at least 12 hours before atazanavir/ritonavir. PPIs are contraindicated in PI-experienced patients.
    • Atazanavir (unboosted): PPIs are not recommended in patients receiving unboosted atazanavir.

Increased concentrations of concomitant medication*: antiarrhythmics, buprenorphine, warfarin, carbamazepine, trazodone, tricyclic antidepressants, itraconazole, ketoconazole, voriconazole, clarithromycin, rifabutin (dose rifabutin 150 mg every other day†…; monitor for antimycobacterial activity and consider therapeutic drug monitoring), diltiazem, midazolam, felodipine, nifedipine, nicardipine, verapamil, fluticasone, ethinyl estradiol (without ritonavir), norgestimate, norethindrone, atorvastatin, lovastatin, pitavastatin, rosuvastatin, salmeterol, simvastatin, sildenafil, tadalafil, vardenafil, colchicine, quetiapine, bosentan, cyclosporine, sirolimus, tacrolimus.

Decreased concentrations of concomitant medication*: phenytoin, phenobarbital, voriconazole, ethinyl estradiol (with ritonavir). 

Increased concentrations of atazanavir with concomitant medication*: clarithromycin. 

Decreased concentrations of atazanavir with concomitant medication*: antacids, buprenorphine (do not coadminister atazanavir without ritonavir), carbamazepine, phenobarbital, phenytoin, omeprazole, H2-receptor antagonists, bosentan, voriconazole.

Drug interactions between atazanavir and other antiretrovirals*: 

  • Efavirenz: do not coadminister with unboosted atazanavir; atazanavir dose is 400 mg once daily + ritonavir 100 mg once daily.
  • Nevirapine: do not coadminister.
  • Tenofovir: do not coadminister with unboosted atazanavir; atazanavir dose is 300 mg once daily + ritonavir 100 mg once daily.

Considerations for Special Populations

See above for pregnancy and lactation.

Adverse Effects

Nausea, jaundice (due to unconjugated hyperbilirubinemia), abdominal pain, headache, lipodystrophy, diarrhoea, vomiting, dyspepsia, rash, dizziness, insomnia, peripheral neuropathy.

Potential for dyslipidemia and gastrointestinal effects lower than with other PIs.

*Information from US prescribing information.
Recommendation from Southern African HIV Clinician Society Guidelines, 2014.