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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Appendix B: Drug Characteristics Tables

Characteristics of Protease Inhibitors

(Last updated:2/12/2013; last reviewed:2/12/2013)

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Appendix B, Table 3. Characteristics of Protease Inhibitors
Generic Name (Abbreviation)/ Trade Name Formulations Dosing Recommendations
(For dosage adjustment in hepatic insufficiency, see Appendix B,
Table 7
.)
Elimination Serum Half-Life Storage Adverse Events
(Also see Table 13.)
Atazanavir (ATV)/
Reyataz
100, 150, 200, and 300 mg capsules ARV-naive patients:
400 mg once daily, or
(ATV 300 mg + RTV 100 mg) once daily
With TDF or in ARV experienced patients:
(ATV 300 mg + RTV 100 mg) once daily
With EFV in ARV-naive patients:
(ATV 400 mg + RTV 100 mg) once daily
For recommendations on dosing with H2 antagonists and PPIs, refer to Table 15a. Take with food
CYP3A4 inhibitor and substrate Dosage adjustment in patients with hepatic insufficiency is recommended. (see Appendix B, Table 7).  7 hours Room temperature
(up to 25ºC or 77ºF)
  • Indirect hyperbilirubinemia
  • PR interval prolongation: First degree symptomatic AV block reported. Use with caution in patients with underlying conduction defects or on concomitant medications that can cause PR prolongation.
  • Hyperglycemia
  • Fat maldistribution
  • Possible increased bleeding episodes in patients with hemophilia
  • Cholelithiasis
  • Nephrolithiasis
  • Skin rash (20%)
  • Serum transaminase elevations
  • Hyperlipidemia (especially with RTV boosting)
Darunavir (DRV)/
Prezista
75, 150, 300, 400, 600, and 800 mg tablets 100 mg/mL oral suspension ARV-naive patients or ARV-experienced patients with no DRV mutations:
(DRV 800 mg + RTV 100 mg) once daily
ARV-experienced patients 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 hours (when combined with RTV) Room temperature
(up to 25ºC or 77ºF)
  • Skin rash (10%): DRV has a sulfonamide moiety; Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and erythrema multiforme have been reported.
  • Hepatotoxicity
  • Diarrhea, nausea
  • Headache
  • Hyperlipidemia
  • Serum transaminase elevation
  • Hyperglycemia
  • Fat maldistribution
  • Possible increased bleeding episodes in patients with hemophilia
Fosamprenavir (FPV)/
Lexiva (a prodrug of amprenavir [APV])
  • 700 mg tablet
  • 50 mg/mL oral suspension
ARV-naive patients:
FPV 1400 mg BID, or
(FPV 1400 mg +
RTV 100–200 mg) once daily, or
(FPV 700 mg + RTV 100 mg) BID
PI-experienced patients (once-daily dosing not recommended):
(FPV 700 mg + RTV 100 mg) BID
With EFV:
(FPV 700 mg + RTV 100 mg) BID, or
(FPV 1400 mg + RTV 300 mg) once daily
Tablet: Take without regard to meals (if not boosted with RTV tablet) Suspension: Take without food FPV with RTV tablet: Take with meals
APV is a CYP3A4 substrate, inhibitor, and inducer. Dosage adjustment in patients with hepatic insufficiency recommended (see Appendix B, Table 7). 7.7 hours (APV) Room temperature
(up to 25ºC or 77ºF)
  • Skin rash (12%–19%): FPV has a sulfonamide moiety.
  • Diarrhea, nausea, vomiting
  • Headache
  • Hyperlipidemia
  • Serum transaminase elevation
  • Hyperglycemia
  • Fat maldistribution
  • Possible increased bleeding episodes in patients with hemophilia
  • Nephrolithiasis
Indinavir
(IDV)/
Crixivan
100, 200, and 400 mg capsules 800 mg every 8 hrs Take 1 hour before or 2 hours after meals; may take with skim milk or low-fat meal With RTV:
(IDV 800 mg + RTV 100–200 mg) BID
Take without regard to meals
CYP3A4 inhibitor and substrate

Dosage adjustment in patients with hepatic insufficiency recommended (see Appendix B, Table 7).
1.5–2 hours Room temperature (15º–30ºC / 59º–86ºF) Protect from moisture
  • Nephrolithiasis
  • GI intolerance, nausea
  • Hepatitis
  • Indirect hyperbilirubinemia
  • Hyperlipidemia
  • Headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, and hemolytic anemia
  • Hyperglycemia
  • Fat maldistribution
  • Possible increased bleeding episodes in patients with hemophilia
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 patients):
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 hours Oral tablet is stable at room temperature. Oral solution is stable at 2º–8ºC (36º–46ºF) until date on label and is stable for up to 2 months when stored at room temperature (up to 25ºC or 77ºF).
  • GI intolerance, nausea, vomiting, diarrhea
  • Pancreatitis
  • Asthenia
  • Hyperlipidemia (especially hypertriglyceridemia)
  • Serum transaminase elevation
  • Hyperglycemia
  • Insulin resistance/diabetes mellitus
  • Fat maldistribution
  • Possible increased bleeding episodes in patients 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 and 625 mg tablets
  • 50 mg/g oral powder
1250 mg BID or
750 mg TID
Dissolve tablets in a small amount of water, mix admixture well, and consume immediately. Take with food
CYP2C19 and 3A4 substrate—metabolized to active M8 metabolite;
CYP 3A4 inhibitor
3.5-5 hours Room temperature (15º–30ºC / 59º–86ºF)
  • Diarrhea
  • Hyperlipidemia
  • Hyperglycemia
  • Fat maldistribution
  • Possible increased bleeding episodes in patients with hemophilia
  • Serum transaminase elevation
Ritonavir
(RTV)/
Norvir
  • 100 mg tablet
  • 100 mg soft gel capsule
  • 80 mg/mL oral solution
Oral solution contains 43% alcohol
As pharmacokinetic booster for other PIs:
100–400 mg per day in 1–2 divided doses (refer to other PIs for specific dosing recommendations)
Tablet: Take with food Capsule and oral solution: To improve tolerability, take with food if possible.
CYP3A4 >2D6 substrate;
potent 3A4, 2D6 inhibitor
3-5 hours Tablets do not require refrigeration. Refrigerate capsules. Capsules can be left at room temperature (up to 25ºC or 77ºF) for up to 30 days. Oral solution should not be refrigerated; store at room temperature (20º–25ºC/ 68º–77ºF).
  • GI intolerance, nausea, vomiting, diarrhea
  • Paresthesias (circumoral and extremities)
  • Hyperlipidemia (especially hypertriglyceridemia)
  • Hepatitis
  • Asthenia
  • Taste perversion
  • Hyperglycemia
  • Fat maldistribution
  • Possible increased bleeding episodes in patients with hemophilia
Saquinavir
(SQV)/
Invirase
  • 500 mg tablets
  • 200 mg hard gel capsule
(SQV 1000 mg + RTV 100 mg) BID Unboosted SQV is not recommended. Take with meals or within 2 hours after a meal CYP3A4 inhibitor and substrate 1-2 hours Room temperature (15º–30ºC/ 59º–86ºF)
  • GI intolerance, nausea, and diarrhea
  • Headache
  • Serum transaminase elevation
  • Hyperlipidemia
  • Hyperglycemia
  • Fat maldistribution
  • Possible increased bleeding episodes in patients 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 Table 5b).
Tipranavir
(TPV)/
Aptivus
  • 250 mg capsule
  • 100 mg/mL oral solution
(TPV 500 mg + RTV 200 mg) BID Unboosted TPV is not recommended. TPV taken with RTV tablets: Take with meals TPV taken with RTV capsules or solution:
Take without regard to meals
CYP P450 3A4 inducer and substrate Net effect when combined with RTV (CYP 3A4, 2D6 inhibitor) 6 hours after single dose of TPV/r Refrigerate capsules. Capsules can be stored at room temperature (25ºC or 77ºF) for up to 60 days. Oral solution should not be refrigerated or frozen and should be used within 60 days after bottle is opened.
  • Hepatotoxicity: Clinical hepatitis (including hepatic decompensation and hepatitis-associated fatalities) has been reported; monitor patients closely, especially those with underlying liver diseases.
  • Skin rash (3%–21%): TPV has a sulfonamide moiety; use with caution in patients with known sulfonamide allergy.
  • Rare cases of fatal and nonfatal intracranial hemorrhages have been reported. Risks include brain lesion, head trauma, recent neurosurgery, coagulopathy, hypertension, alcoholism, use of anti-coagulant or anti-platelet agents (including vitamin E).
  • Hyperlipidemia
  • Hyperglycemia
  • Fat maldistribution
  • Possible increased bleeding episodes in patients with hemophilia

Key to Abbreviations: APV = amprenavir, ARV = antiretroviral, ATV = atazanavir, AV = atrioventricular, BID = twice daily, CYP = cytochrome P, DRV = darunavir, EFV = efavirenz, FPV = fosamprenavir, GI = gastrointestinal, IDV = indinavir, LPV = lopinavir, LPV/r = lopinavir + ritonavir, msec = millisecond, NFV = nelfinavir, NVP = nevirapine, PI = protease inhibitor, PPI = proton pump inhibitor, RTV = ritonavir, SQV = saquinavir, TDF = tenofovir disoproxil fumarate, TID = three times a day, TPV = tipranavir