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Table of Contents

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:5/1/2014)

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Appendix B, Table 3. Characteristics of Protease Inhibitors (PIs)
Generic Name (Abbreviation)/ Trade Name Formulations Dosing Recommendationsa Elimination/ Metabolic Pathway Serum Half-Life Storage Adverse Eventsb
Atazanavir (ATV)
Reyataz
100, 150, 200, and 300 mg capsules ARV-Naive Patients:
  • ATV 300 mg + RTV 100 mg once daily; or
  • ATV 400 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
Take with food.

For recommendations on dosing with H2 antagonists and PPIs, refer to Table 18a.
CYP3A4 inhibitor and substrate

Dosage adjustment in patients with hepatic insufficiency is recommended (see Appendix B, Table 7).
 7 hours Room temperature
(up to 25º C or 77º F)
  • 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
  • Cholelithiasis
  • Nephrolithiasis
  • Renal insufficiency
  • Serum transaminase elevations
  • Hyperlipidemia (especially with RTV boosting)
  • Skin rash
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 1 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
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:
  • Without RTV tablet: Take without regard to meals.
  • With RTV tablet: Take with meals.
Oral Suspension:
  • Take without food.
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% to 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 hours

Take 1 hour before or 2 hours after meals; may take with skim milk or a 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
Ritonavir-Boosted Lopinavir 
(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 2 LPV/r 200 mg/50 mg tablets + 1 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 to 8º C (36º to 46º F) until date on label and is stable for up to 2 months when stored at room temperature (up to 25º C or 77º F). 
  • 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 PK Booster for Other PIs
  • 100–400 mg per day in 1 or 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 25º C or 77º F) for up to 30 days. 

Oral solution should not be refrigerated; store at room temperature (20º to 25º C/68º to 77º 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 patients with hemophilia
Saquinavir
(SQV)
Invirase

500 mg tablet

200 mg 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 6).
Tipranavir
(TPV)
Aptivus

250 mg capsule

100 mg/mL oral solution

TPV 500 mg + RTV 200 mg BID

Unboosted TPV is not recommended.

With RTV Tablets
  • Take with meals.
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 (25º C or 77º F) 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% to 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
a For dosage adjustment in hepatic insufficiency, see Appendix B, Table 7.
b Also see Table 14.

Key to Acronyms: 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 = ritonavir-boosted lopinavir; msec = millisecond; NFV = nelfinavir; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; PPI = proton pump inhibitor; RTV = ritonavir; SQV = saquinavir; TDF = tenofovir disoproxil fumarate; TID = three times a day; TPV = tipranavir

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