Antiretroviral Agents in HIV-1 (trial)

14 Selecting a Treatment Regimen Table 5C. Characteristics of Protease Inhibitors (PIs) Drug Formulation Dosing Recommendations Elimination Serum Half-life Storage Adverse Events Atazanavir (ATV) Reyataz ® 100, 150, 200, 300 mg capsules ARV-naive pts: 400 mg once daily or (ATV 300 mg + RTV 100 mg ) once daily With TDF or for ARV-experienced pts: (ATV 300 mg + RTV 100 mg ) once daily With EFV in treatment-naive pts: (ATV 400 mg + RTV 100 mg ) once daily CYP3A4 inhibitor and substrate Dosage adjustment in hepatic insufficiency recommended 7 h Room temperature (up to 25 º C or 77 º F) ▶ Indirect hyperbilirubinemia ▶ Prolonged PR interval—first-degree symptomatic AV block in some pts ▶ Use with caution in pts with underlying conduction defects or on concomitant medications that can cause PR prolongation ▶ Hyperglycemia ▶ Fat maldistribution ▶ Possible increased bleeding episodes in pts with hemophilia ▶ Nephrolithiasis ▶ Skin rash (20%) ▶ Serum transaminase elevations ▶ Hyperlipidemia (especially with RTV boosting ) Darunavir (DRV) Prezista ® 75, 150, 400, 600 mg tablets ARV-naive pts or ARV-experienced patients with no DRV mutations: (DRV 800 mg + RTV 100 mg ) once daily ARV-experienced pts with at least one DRV mutation: (DRV 600 mg + RTV 100 mg ) bid ▶ Unboosted DRV is NOT recommended ▶ Take with food CYP3A4 inhibitor and substrate 15 h (when combined with RTV) Room temperature (up to 25 º C or 77 º F) ▶ Skin rash (10%)—DRV has a sulfonamide moiety; Stevens-Johnson syndrome and erythrema multiforme have been reported ▶ Hepatotoxicity ▶ Diarrhea, nausea ▶ Headache ▶ Hyperlipidemia ▶ Transaminase elevation ▶ Hyperglycemia ▶ Fat maldistribution ▶ Possible increased bleeding episodes in pts with hemophilia Fosamprenavir (FPV) Lexiva ® (a prodrug of amprenavir) 700 mg tablet or 50 mg/mL oral suspension ARV-naive pts: ▶ FPV 1,400 mg bid or ▶ (FPV 1,400 mg + RTV 100–200 mg ) once daily or ▶ (FPV 700 mg + RTV 100 mg) bid PI-experienced pts (once-daily dosing NOT recommended): ▶ (FPV 700 mg + RTV 100 mg) bid With EFV: ▶ (FPV 700 mg + RTV 100 mg ) bid or ▶ (FPV 1,400 mg + RTV 300 mg ) once daily (not FDA-approved) ▶ Take without regard to meals (if not boosted with RTV tablet) ▶ Suspension: Take without food ▶ FPV w/ RTV tablet: Take with meals Amprenavir is a CYP3A4 substrate, inhibitor, and inducer Dosage adjustment in hepatic insufficiency recommended 7.7 h (amprenavir) Room temperature (up to 25 º C or 77 º F) ▶ Skin rash (19%) ▶ Diarrhea, nausea, vomiting ▶ Headache ▶ Hyperlipidemia ▶ Transaminase elevation ▶ Hyperglycemia ▶ Fat maldistribution ▶ Possible increased bleeding episodes in pts with hemophilia ▶ Nephrolithiasis Indinavir (IDV) Crixivan ® 100, 200, 400 mg capsules 800 mg q8h ▶ Take 1 h before or 2 h aer meals; may take with skim milk or low-fat meal With RTV: (IDV 800 mg + RTV 100–200 mg ) bid (not FDA-approved) ▶ Take without regard to meals CYP3A4 inhibitor and substrate Dosage adjustment in hepatic insufficiency recommended 1.5–2 h Room temperature (15 º –30 º C/ 59 º –86 º F) Protect from moisture ▶ Nephrolithiasis ▶ GI intolerance, nausea ▶ Indirect hyperbilirubinemia ▶ Hyperlipidemia ▶ Headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, and hemolytic anemia ▶ Hyperglycemia ▶ Fat maldistribution ▶ Possible increased bleeding episodes in pts with hemophilia

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