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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: April 8, 2015; last reviewed: April 8, 2015)

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

Also available as a component of fixed-dose combination.
Reyataz:
  • 100, 150, 200, and 300 mg capsules
  • 50 mg single packet oral powder
In ARV-Naive Patients:
  • (ATV 300 mg plus RTV 100 mg) once daily; or
  • ATV 400 mg once daily
With TDF or in ARV-Experienced Patients:
  • (ATV 300 mg plus RTV 100 mg) once daily
With EFV in ARV-Naive Patients:
  • (ATV 400 mg plus RTV 100 mg) once daily
Take with food. For recommendations on dosing with H2 antagonists and PPIs, refer to Table 19a.  
CYP3A4 inhibitor and substrate; weak CYP2C8 inhibitor; UGT1A1 inhibitor

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
  • Increase in serum creatinine (with COBI)
Evotaz
(ATV/c)
Evotaz:
  • (ATV 300 mg plus COBI 150 mg) tablet
Evotaz:
  • 1 tablet once daily 
  • Take with food.
With TDF:
  • Not recommended for patients with baseline CrCl< 70 mL/min (see Appendix B, Table 7 for the equation for calculating CrCl). 
ATV: as above

COBI: substrate of CYP3A, CYP2D6 (minor); CYP3A inhibitor
Darunavir (DRV)
Prezista

Also available as a component of fixed-dose combination.
  • 75, 150, 600, and 800 mg tablets
  • 100 mg/mL oral suspension
In ARV-Naive Patients or ARV-Experienced Patients with No DRV Mutations:
  • (DRV 800 mg plus RTV 100 mg) once daily
In ARV-Experienced Patients with One or More DRV Resistance Mutations:
  • (DRV 600 mg plus RTV 100) mg BID

Unboosted DRV is not recommended.

Take with food.

CYP3A4 inhibitor and substrate

CYP2C9 inducer
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
  • Increase in serum creatinine (with COBI)
Prezcobix
(DRV/c)
Prezcobix:
  • (DRV 800 mg plus COBI 150 mg) tablet
Prezcobix:
  • 1 tablet once daily 
  • Take with food.

Not recommended for patients with one or more DRV resistance-associated mutations.

With TDF:

  • Not recommended for patients with baseline CrCl< 70 mL/min (see Appendix B, Table 7  for the equation for calculating CrCl). 
DRV: As above

COBI: substrate of CYP3A, CYP2D6 (minor); CYP3A inhibitor

Fosamprenavir (FPV)
Lexiva (a prodrug of amprenavir [APV])
  • 700 mg tablet
  • 50 mg/mL oral suspension
In ARV-Naive Patients:
  • FPV 1400 mg BID, or
  • (FPV 1400 mg plus RTV 100–200 mg) once daily, or
  • (FPV 700 mg plus RTV 100 mg) BID
In PI-Experienced Patients (Once-Daily Dosing Not Recommended):
  • (FPV 700 mg plus RTV 100 mg) BID
With EFV:
  • (FPV 700 mg plus RTV 100 mg) BID, or
  • (FPV 1400 mg plus 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 is 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 plus RTV 100–200 mg) BID
  • Take without regard to meals.
CYP3A4 inhibitor and substrate

Dosage adjustment in patients with hepatic insufficiency is recommended (see Appendix B, Table 7).
1.5–2 hours Room temperature (15º to 30ºC or 59º to 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 plus RTV 50 mg), or
  • (LPV 100 mg plus RTV 25 mg)

Oral Solution:
  • Each 5 mL contains (LPV 400 mg plus RTV 100 mg).
  • Oral solution contains 42% alcohol.
  • (LPV 400 mg plus RTV 100) mg BID,
    or
  • (LPV 800 mg plus RTV 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 plus 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 to 30ºC or 59º to 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 (or Enhancer) 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; Inducer of CYPs 1A2, 2C8, 2C9, and 2C19 and UGT1A1
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.
  • 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 substrate 1-2 hours Room temperature (15º to 30ºC or 59º to 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.
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

CYP2D6 inhibitor; CYP3A4, 1A2, and 2C19 inducer

Net effect when combined with RTV (CYP3A4, 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, and the 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; ATV/c = atazanavir/cobicistat; AV = atrioventricular; BID = twice daily; COBI = cobicistat; CYP = cytochrome P; DRV = darunavir; DRV/c = darunavir/cobicistat; EFV = efavirenz; FPV = fosamprenavir; GI = gastrointestinal; IDV = indinavir; LPV = lopinavir; LPV/r = lopinavir/ritonavir; 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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