Antiretroviral Agents in HIV-1 (trial)

17 Table 5C. Characteristics of Protease Inhibitors (PIs) (cont'd) Drug Formulation Dosing Recommendations Elimination Serum Half-life Storage Adverse Events Lopinavir/ritonavir (LPV/r) Kaletra ® Tablets: (LPV 200 mg + RTV 50 mg) or (LPV 100 mg + RTV 25 mg) Oral solution: Each 5 mL contains (LPV 400 mg + RTV 100 mg ) Oral solution contains 42% alcohol LPV/r 400 mg/100 mg bid or LPV/r 800 mg/200 mg once daily ▶ Once-daily dosing is NOT recommended for patients with ≥3 LPV-associated mutations, pregnant women, or patients receiving EFV, NVP, FPV, NFV, carbamazepine, phenytoin, or phenobarbital. With EFV or NVP (PI-naive or PI- experienced pts): LPV/r 500 mg/125 mg tablets bid (use a combination of two LPV/r 200 mg/50 mg tablets + one LPV/r 100 mg/25 mg tablet to make a total dose of LPV/r 500 mg/125 mg ) or LPV/r 533 mg/133 mg oral solution bid Tablet: Take without regard to meals Oral solution: Take with food CYP3A4 inhibitor and substrate 5–6 h Oral tablet is stable at room temperature. Oral solution is stable at 2 º –8 º C until date on label and is stable when stored at room temperature (up to 25 º C or 77 º F) for 2 mo. ▶ GI intolerance, nausea, vomiting, diarrhea ▶ Asthenia ▶ Hyperlipidemia (especially hypertriglyceridemia) ▶ Elevated serum transaminases ▶ Hyperglycemia ▶ Fat maldistribution ▶ Possible increased bleeding episodes in pts with hemophilia ▶ PR interval prolongation ▶ QT interval prolongation and torsades de pointes have been reported; however, causality could not be established Nelfinavir (NFV) Viracept ® 250, 625 mg tablets 50 mg/g oral powder 1,250 mg bid or 750 mg tid ▶ Take with food CYP2C19 and 3A4 substrate— metabolized to active M8 metabolite; CYP3A4 inhibitor 3.5–5 h Room temperature (15 º –30 º C/ 59 º –86 º F) ▶ Diarrhea ▶ Hyperlipidemia ▶ Hyperglycemia ▶ Fat maldistribution ▶ Possible increased bleeding episodes in pts with hemophilia ▶ Serum transaminase elevation Ritonavir (RTV) Norvir ® 100 mg tablets 100 mg capsules 80 mg/mL oral solution As pharmacokinetic booster for other PIs: 100–400 mg per day in 1–2 divided doses (refer to other PIs for specific dosing recommendations) (not FDA- approved) Tablet: Take with food Capsule and oral solution: Take with food, if possible, to improve tolerability CYP3A4 >2D6 substrate; potent 3A4, 2D6 inhibitor 3–5 h Refrigerate capsules. Capsules can be le at room temperature (up to 25 º C or 77 º F) for up to 30 days. Tablets do not require refrigeration. Oral solution should not be refrigerated; store at room temperature 20 º –25 º C (68 º –77 º F). ▶ GI intolerance, nausea, vomiting, diarrhea ▶ Paresthesias—circumoral and extremities ▶ Hyperlipidemia (especially hypertriglyceridemia) ▶ Hepatitis ▶ Asthenia ▶ Taste perversion ▶ Hyperglycemia ▶ Fat maldistribution ▶ Possible increased bleeding episodes in pts with hemophilia Saquinavir (SQV) Invirase ® a 500 mg tablets or 200 mg hard gel capsules (SQV 1,000 mg + RTV 100 mg ) bid ▶ Unboosted SQV is NOT recommended ▶ Take within 2 hours aer a meal CYP3A4 inhibitor and substrate 1–2 h Room temperature (15 º –30 º C/ 59 º –86 º F) ▶ GI intolerance, nausea, and diarrhea ▶ Headache ▶ Elevated transaminase enzymes ▶ Hyperlipidemia ▶ Hyperglycemia ▶ Fat maldistribution ▶ Possible increased bleeding episodes in pts with hemophilia ▶ PR interval prolongation ▶ QT interval prolongation, torsades de pointes have been reported. Patients with pre-SQV QT interval >450 msec should NOT receive SQV (see full guideline for details). Continued on next page

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