Indinavir Sulfate

Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: [1S-[1α(R*),2α]]-2,3,5-trideoxy-N-(2,3-dihydro -2-hydroxy-1H-inden-1-yl)-5-[2-[[(1,1-dimethylethyl)amino]carbonyl]-4 -(3-pyridinylmethyl)-1-piperazinyl]-2-(phenylmethyl)-d-erythro-pentonamide sulfate (1:1) (salt)
Molecular Formula: C36H47N5O4
CAS Number: 157810-81-6
Brands: Crixivan

Introduction

Antiretroviral; HIV protease inhibitor (PI).1 2 3 6 7

Uses for Indinavir Sulfate

Treatment of HIV Infection

Treatment of HIV infection in conjunction with other antiretrovirals.1

Indinavir not recommended for initial regimens in antiretroviral-naive adults and adolescents because of inconvenient dosing regimen and fluid requirements.200

Indinavir with low-dose ritonavir (ritonavir-boosted indinavir) not recommended for initial therapy in adults and adolescents because of high incidence of nephrolithiasis.200

Slideshow: Flashback: FDA Drug Approvals 2013

Regimens containing indinavir not recommended for initial antiretroviral regimens in pediatric patients because of limited data.201

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with increased risk for transmission of the virus.94 97 199 Used in conjunction with other antiretrovirals.199

Postexposure prophylaxis of HIV infection in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

Indinavir Sulfate Dosage and Administration

Administration

Oral Administration

Administer orally.1

Administer with water 1 hour before or 2 hours after a meal.1 Alternatively, administer with some other liquid (e.g., skim milk, juice, coffee, tea) or with a light meal (e.g., dry toast with jelly, apple juice, coffee with skim milk and sugar; corn flakes with skim milk and sugar).1 Do not administer with a meal high in calories, fat, and protein.1

To ensure adequate hydration, patients should drink at least 1.5 L (approximately 48 ounces) of liquids daily (i.e., every 24 hours).1 4

Dosage

Available as indinavir sulfate; dosage expressed as indinavir.1

Pediatric Patients

Treatment of HIV Infection
Oral

Optimal dosage not established.1 (See Pediatric Use under Cautions.)

Adults

Treatment of HIV Infection
Oral

800 mg every 8 hours.1

If ritonavir-boosted indinavir is used, 800 mg twice daily with low-dose ritonavir (100 or 200 mg twice daily) has been recommended.200

Postexposure Prophylaxis of HIV
Occupational Exposure
Oral

800 mg twice daily boosted with low-dose ritonavir (100 mg twice daily).199 Alternatively, 800 mg every 8 hours (without low-dose ritonavir).199

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.199

Nonoccupational Exposure
Oral

800 mg twice daily boosted with low-dose ritonavir (100 or 200 mg every 12 hours).198 Alternatively, 800 mg every 8 hours (without low-dose ritonavir).198

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.198

Special Populations

Hepatic Impairment

Treatment of HIV Infection
Oral

Mild to moderate hepatic impairment due to cirrhosis: 600 mg every 8 hours.1 200

Renal Impairment

Treatment of HIV Infection
Oral

Dosage adjustment not necessary.200

Geriatric Patients

Select dosage with caution.1

Cautions for Indinavir Sulfate

Contraindications

  • Known hypersensitivity to indinavir or any ingredient in the formulation.1

  • Concomitant use with drugs highly dependent on CYP3A4 for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, alprazolam, amiodarone, cisapride, ergot alkaloids, oral midazolam, pimozide, sildenafil used for treatment of pulmonary arterial hypertension [PAH], triazolam, lovastatin, simvastatin).1 (See Specific Drugs and Food under Interactions.)

Warnings/Precautions

Warnings

Renal and GU Effects

Nephrolithiasis/urolithiasis,1 4 26 sometimes associated with substantial renal impairment, acute renal failure, or pyelonephritis with or without bacteremia, reported.1

Adequate hydration recommended for all patients receiving indinavir.1 Risk of nephrolithiasis/urolithiasis may be greater with ritonavir-boosted indinavir compared with indinavir (without low-dose ritonavir).1

If signs and symptoms of nephrolithiasis/urolithiasis (flank pain, with or without hematuria or microscopic hematuria) occur, temporary interruption (e.g., for 1–3 days) or discontinuance of therapy may be considered.1

Interstitial nephritis with medullary calcification and cortical atrophy reported in patients with asymptomatic severe leukocyturia (≥100 cells per high power field).1 Monitor patients who have asymptomatic severe leukocyturia (i.e., perform frequent urinalysis); further diagnostic evaluation may be needed.1 Consider discontinuing indinavir in patients with severe leukocyturia.1

Interactions

Concomitant use with certain drugs not recommended or requires particular caution.1 (See Specific Drugs and Food under Interactions.)

Hemolytic Anemia

Acute hemolytic anemia, including fatalities, reported.1

If acute hemolytic anemia occurs, take appropriate measures to treat the condition (including discontinuance of indinavir).1

Hepatic Effects

Acute hepatitis sometimes resulting in hepatic failure and death reported; causal relationship not established.1 116 Generally has occurred in patients with confounding medical conditions and/or receiving concomitant drugs.1

Elevated indirect bilirubin, infrequently associated with increased serum AST (SGOT) or ALT (SGPT) concentrations, reported.1 4 17 23

Hyperglycemic Effects

Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of PIs; diabetic ketoacidosis has occurred.1 120 121 122 123

Monitor blood glucose and initiate or adjust dosage of oral hypoglycemic agent or insulin as needed.1

General Precautions

HIV Resistance

Possibility of HIV resistance to indinavir and possible cross-resistance to other PIs.1 Effect of indinavir therapy on subsequent therapy with other PIs under investigation.1

Hemophilia A and B

Spontaneous bleeding noted with PIs; causal relationship not established.1 40 119

Use caution in patients with a history of hemophilia type A or B.1 40 119 Increased hemostatic (e.g., antihemophilic factor) therapy may be needed.1

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]);1 this may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.1

Specific Populations

Pregnancy

Category C.1

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 202

Not recommended in HIV-infected pregnant women.1 Because of inconvenient dosing regimen and potential to cause nephrolithiasis, some experts state indinavir should only be used in pregnant women when preferred and alternative agents cannot be used.202

Hyperbilirubinemia, generally reported as an increase in indirect bilirubin, has occurred in patients receiving indinavir; it is not known whether use in a pregnant woman during the perinatal period can exacerbate physiologic hyperbilirubinemia in the neonate.1

Optimal dosage during pregnancy not established.202 Substantially decreased plasma indinavir concentrations reported during pregnancy.1 202 (See Special Populations under Pharmacokinetics.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1 202

Pediatric Use

Only limited data available regarding use in pediatric patients.1 When other HIV PIs cannot be used, consider limited data and increased risk of nephrolithiasis before using indinavir.1

Hyperbilirubinemia reported in patients receiving indinavir;1 4 17 23 201 because of risk associated with hyperbilirubinemia (kernicterus), some experts state do not use in neonates.201

Has been used in a limited number of HIV-infected children ≥3 months of age.1 124 125 151 152 166 173 201 Nephrolithiasis/urolithiasis reported more frequently in pediatric patients than in adults.1

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.1

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Hepatic Impairment

Dosage adjustment recommended in patients with hepatic impairment due to cirrhosis.1 (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Nausea, abdominal pain, headache, nephrolithiasis/urolithiasis, asymptomatic hyperbilirubinemia.1

Interactions for Indinavir Sulfate

Metabolized by CYP3A4.1

Inhibits CYP3A4 and, to a lesser extent, CYP2D6.1

Does not inhibit CYP1A2, 2C9, 2E1, or 2B6.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A4 with possible alteration in metabolism of indinavir and/or other drug.1

Specific Drugs and Food

Drug or Food

Interaction

Comments

Alfuzosin

Potential for increased alfuzosin concentrations that could result in hypotension1

Concomitant use contraindicated1

Antiarrhythmic agents (amiodarone, systemic lidocaine, quinidine)

Possible increased antiarrhythmic agent concentrations; potential for serious and/or life-threatening effects1

Amiodarone: Concomitant use contraindicated1

Systemic lidocaine, quinidine: Use concomitantly with caution; monitor plasma antiarrhythmic concentrations1

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Possible decreased indinavir concentrations; possible decreased antiretroviral effectiveness1

No change in plasma concentrations of carbamazepine167

Carbamazepine, phenobarbital, phenytoin: Use concomitantly with caution1

Antifungals, azoles (fluconazole, itraconazole, ketoconazole, voriconazole)

Fluconazole: Decreased indinavir AUC;74 145 no effect on fluconazole AUC74 145

Itraconazole: Possible increased concentrations of both drugs1 128

Ketoconazole: Increased indinavir concentrations1

Voriconazole: No clinically important effect on pharmacokinetics of either drug129

Fluconazole: Dosage adjustments not needed145

Itraconazole: Use concomitantly with caution;128 reduce indinavir dosage to 600 mg every 8 hours 1

Ketoconazole: Reduce indinavir dosage to 600 mg every 8 hours1

Voriconazole: Dosage adjustments not needed129

Antimycobacterials

Isoniazid: No change in indinavir AUC ; no clinically unimportant increases in isoniazid AUC1 74

Rifabutin: Decreased indinavir concentrations and AUC; substantially increased rifabutin concentrations and AUC1

Rifampin: Decreased indinavir concentrations; possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance1 148

Rifapentine: Possible decreased indinavir concentrations200

Isoniazid: Dosage adjustments not needed1

Rifabutin: Increase indinavir dosage to 1 g every 8 hours and reduce rifabutin dosage to 50% of usual dosage1

Rifampin: Concomitant use contraindicated1 148

Rifapentine: Concomitant use not recommended200

Atazanavir

Potential for additive hyperbilirubinemia1 203

Concomitant use contraindicated1 200

Avanafil

Possible increased avanafil concentrations and AUC188

Do not use concomitantly188

Benzodiazepines

Pharmacokinetic interaction with alprazolam, midazolam, or triazolam; potential for prolonged or increased sedation or respiratory depression1

Alprazolam, oral midazolam, triazolam: Concomitant use contraindicated1

Parenteral midazolam: Use with caution in monitored setting where respiratory depression and/or prolonged sedation can be managed;1 consider reduced parenteral midazolam dosage, especially if more than a single dose used1

Bosentan

Possible increased bosentan concentrations1

Initiate or adjust bosentan dosage to 62.5 mg once daily or every other day based on individual tolerability1

Calcium-channel blocking agents, dihydropyridine (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine)

Possible increased concentrations of calcium-channel blocking agent; potential for increased or prolonged therapeutic or adverse effects of the cardiac drug1

Use concomitantly with caution; clinical monitoring recommended1

Cisapride

Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1

Concomitant use contraindicated1

Colchicine

Increased colchicine concentrations1

Patients with renal or hepatic impairment: Avoid concomitant use1

Colchicine for treatment of gout flares: Use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later; repeat dose no earlier than 3 days later1

Colchicine for prophylaxis of gout flares: Decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 mg once daily1

Colchicine for treatment of familial Mediterranean fever (FMF): Use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily)1

Corticosteroids (fluticasone)

Fluticasone nasal spray/oral inhalation: Possible increased fluticasone concentrations1

Fluticasone nasal spray/oral inhalation: Use concomitantly with caution; consider alternatives to fluticasone, especially when long-term use of the corticosteroid is anticipated

Ritonavir-boosted indinavir: Concomitant use not recommended unless potential benefits outweigh risk of systemic corticosteroid adverse effects1

Co-trimoxazole

Interaction unlikely1

Dosage adjustments not needed1

Darunavir

Ritonavir-boosted darunavir: Increased concentrations and AUCs of darunavir and indinavir204

No in vitro evidence of antagonistic antiretroviral effects204

Ritonavir-boosted darunavir: Appropriate dosages for concomitant use with indinavir not established204

Delavirdine

Delavirdine inhibits indinavir metabolism and may increase indinavir concentrations; no effect on delavirdine pharmacokinetics1 144

Use reduced indinavir dosage of 600 mg every 8 hours with usual delavirdine dosage of 400 mg 3 times daily1 212

Didanosine

Buffered didanosine (Videx): Substantially decreased indinavir concentrations and AUC if administered simultaneously147

Didanosine delayed-release capsules (Videx EC): No effect on indinavir concentrations and AUC217

In vitro evidence of synergistic antiretroviral effects1

Buffered didanosine (Videx): Administer 1 hour after indinavir147

Efavirenz

Decreased indinavir AUC; no clinically important effect on efavirenz concentrations or AUC1 213

In vitro evidence of additive antiretroviral effects213

Optimum dosage for concomitant use not established; increasing indinavir dosage to 1 g every 8 hours does not compensate for increased indinavir metabolism due to efavirenz1 213

Emtricitabine

No effect on pharmacokinetics of either drug218

Enfuvirtide

In vitro evidence of additive to synergistic antiretroviral effects223

Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)

Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)1

Concomitant use contraindicated1

If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving indinavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible201

Estrogens/Progestins

Oral hormonal contraceptives: Increased AUC of ethinyl estradiol and norethindrone reported1

Etravirine

Indinavir (without low-dose ritonavir): Possible decreased indinavir concentrations214

No in vitro evidence of antagonistic antiretroviral effects214

Do not use concomitantly without low-dose ritonavir214

Fosamprenavir

Fosamprenavir (without low-dose ritonavir): Possible increased concentrations of amprenavir (active metabolite of fosamprenavir); effect on indinavir concentrations not well established

Ritonavir-boosted fosamprenavir: Concomitant use not evaluated205

In vitro evidence of additive antiretroviral effects205

Fosamprenavir (with or without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established205

Grapefruit juice

Decreased indinavir AUC and concentrations1

Histamine H2-receptor antagonists (cimetidine)

Pharmacokinetic interaction unlikely with cimetidine1

Dosage adjustment not needed1

HMG-CoA reductase inhibitors (statins)

Atorvastatin, lovastatin, rosuvastatin, simvastatin: Increased concentrations of the antilipemic agents; increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis1

Atorvastatin: Carefully titrate atorvastatin dosage and use lowest necessary dosage1

Lovastatin: Concomitant use contraindicated1

Rosuvastatin: Carefully titrate rosuvastatin dosage and use lowest necessary dosage1

Simvastatin: Concomitant use contraindicated1

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Cyclosporine, sirolimus, tacrolimus: Possible increased concentrations of the immunosuppressive agent1

Lamivudine

Concomitant use of lamivudine, zidovudine, and indinavir: Increased indinavir concentrations and AUC and decreased lamivudine concentrations and AUC1

Lopinavir/ritonavir

Increased indinavir concentrations207 207

In vitro evidence of additive to synergistic antiretroviral effects207

Use indinavir 600 mg twice daily with lopinavir 400 mg/ritonavir 100 mg twice daily; lopinavir once-daily regimen not studied in patients receiving indinavir207

Macrolides (clarithromycin)

Increased indinavir and clarithromycin AUCs1

Appropriate dosages for concomitant use with respect to safety and efficacy not established1

Maraviroc

No in vitro evidence of antagonistic antiretroviral effects224

Recommended maraviroc dosage is 150 mg twice daily224

Methadone

Indinavir (without low-dose ritonavir): Pharmacokinetic interactions unlikely1 200

Ritonavir-boosted indinavir: Opiate withdrawal is unlikely, but may occur200

Indinavir (without low-dose ritonavir): Dosage adjustments not needed200

Ritonavir-boosted indinavir: Monitor for opioid withdrawal and increase methadone dosage as clinically indicated200

Nelfinavir

Increased AUCs of both drugs208

In vitro evidence of antagonistic antiretroviral effects209

Appropriate dosages for concomitant use with respect to safety and efficacy not established1 208

Nevirapine

Decreased indinavir concentrations and AUC215

In vitro evidence of additive to synergistic antiretroviral effects215

Appropriate dosages for concomitant use with respect to safety and efficacy not established1 215

Pimozide

Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1

Concomitant use contraindicated1

Quinupristin and dalfopristin

Possible increased indinavir concentrations169

Raltegravir

In vitro evidence of additive to synergistic antiretroviral effects225

Rilpivirine

Possible increased rilpivirine concentrations; not expected to affect indinavir concentrations226

Ritonavir

Increased concentrations of indinavir and ritonavir;200 1 209 concomitant low-dose ritonavir used to therapeutic advantage (ritonavir-boosted indinavir)200

Incidence of renal effects (nephrolithiasis) may be higher when ritonavir and indinavir used concomitantly compared with usual dosage of indinavir alone1

Ritonavir-boosted indinavir: Some experts suggest indinavir 800 mg twice daily with ritonavir 100 or 200 mg twice daily200

Saquinavir

Substantially increased saquinavir concentrations1 210

Appropriate dosages for concomitant use with respect to safety and efficacy not established 1 210

St. John’s wort (Hypericum perforatum)

Decreased indinavir concentrations; possible loss of virologic response and increased risk of indinavir resistance1

Concomitant use not recommended1

Salmeterol

Possible increased salmeterol concentrations and increased risk of salmeterol-associated adverse cardiovascular effects, including QT interval prolongation, palpitations, and sinus tachycardia1

Concomitant use not recommended1

Sildenafil

Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)1

Sildenafil (Revatio) for treatment of PAH: Concomitant use with indinavir contraindicated;1 safe and effective dose for concomitant use not established1

Sildenafil for treatment of erectile dysfunction: Do not exceed sildenafil dosage of 25 mg once every 48 hours; use caution and closely monitor for sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)1

Stavudine

No clinically important change in indinavir concentrations or AUC; decreased concentrations and increased AUC of stavudine1

Tadalafil

Increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)1

Tadalafil (Adcirca) for treatment of PAH: In patients receiving indinavir, initiate or adjust tadalafil dosage to 20 mg once daily and then increase to 40 mg once daily based on individual tolerability1

Tadalafil for treatment of erectile dysfunction: In patients receiving indinavir, do not exceed tadalafil dosage of 10 mg once every 72 hours; use caution and closely monitor for tadalafil-related adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection, syncope)1

Tadalafil for treatment of benign prostatic hyperplasia: Do not exceed tadalafil dosage of 2.5 mg once daily200

Tenofovir

Slight increase in tenofovir concentrations and decrease in indinavir concentrations; no effect on AUC of either drug221

In vitro evidence of additive to synergistic antiretroviral effects221

Theophylline

Pharmacokinetic interactions unlikely1

Trazodone

Possible increased trazodone concentrations;1 nausea, dizziness, hypotension, and syncope reported when trazodone and ritonavir were used concomitantly1

Use concomitantly with caution; consider decreased trazodone dosage1

Vardenafil

Increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection); decreased indinavir concentrations1

Vardenafil for treatment of erectile dysfunction: In patients receiving indinavir, do not exceed vardenafil dosage of 2.5 mg once every 24 hours; use caution and closely monitor for vardenafil-related adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1

Venlafaxine

Decreased indinavir concentrations; no change in venlafaxine concentrations1

Clinical importance unknown1

Zidovudine

Slightly increased indinavir concentrations and AUC; slightly increased zidovudine AUC and decreased zidovudine peak concentrations1

In vitro evidence of synergistic antiretroviral effects1

Indinavir Sulfate Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract; peak plasma concentrations attained within 1 hour.37 38 1

Food

Presence of food in the GI tract can substantially decrease the extent of absorption of oral indinavir.1 38

Administration with a substantial meal (48.6 g fat, 31.3 g protein; 784 kcal) decreases AUC and peak plasma concentrations by 77 and 84%, respectively; administration with a light meal (e.g., dry toast with jelly, apple juice, coffee with skim milk and sugar; corn flakes with skim milk and sugar) is not associated with clinically important changes in AUC or peak or trough plasma concentrations.1 135

Special Populations

Pediatric patients: Limited data indicate pharmacokinetic profile not comparable to that reported in adults.1

Hepatic impairment: AUC 60% higher in adults with cirrhosis and mild to moderate hepatic impairment compared with adults with normal hepatic function.1

Pregnant women: AUC 74% lower in pregnant women receiving indinavir (without low-dose ritonavir) compared with nonpregnant patients.1

Distribution

Extent

Not fully characterized.65

Distributed into CSF in low concentration in adults21 or children.125 132 134

Not known whether crosses the placenta.66

Not known whether distributed into human milk;1 distributed into milk in rats.1

Plasma Protein Binding

60%.1

Elimination

Metabolism

Metabolized by CYP3A4.1

Elimination Route

Excreted principally in the feces (83%) as unabsorbed drug or metabolites.1

Half-life

1.8 hours.1 37 38

Special Populations

Half-life prolonged in patients with hepatic impairment.1 Half-life of 2.8 hours reported in adults with cirrhosis and mild to moderate hepatic impairment.1 Pharmacokinetics not studied in patients with severe hepatic impairment.1

Pharmacokinetics not studied in renal impairment.1

Stability

Storage

Oral

Capsules

15–30°C in tightly closed containers.1 Protect from moisture.1 Dispense and store in original container; the desiccant should remain in the original bottle.1

Actions and Spectrum

  • Pharmacologically related to other PIs (e.g., atazanavir, darunavir, fosamprenavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir); differs structurally from these drugs and also differs pharmacologically and structurally from other currently available antiretrovirals.2 3

  • Active against HIV-1 and HIV-2.1 2 3 6 7 16

  • Inhibits replication of HIV-1 and HIV-2 by interfering with HIV protease.1 2 3 6 7

  • HIV-1 with reduced susceptibility to indinavir have been selected in vitro and have emerged during therapy with the drug.1 3 8 9 10 12 13 14 15 51

  • Varying degrees of cross-resistance occur among PIs.1 4 7 9 10 11 13 39 168 209

  • Cross-resistance between indinavir and nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) unlikely since the drugs have different target enzymes and mechanisms of action.1

Advice to Patients

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.1 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinicians. 1

  • Importance of using indinavir in conjunction with other antiretrovirals—not for monotherapy.1

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.1

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.1 200

  • Importance of reading patient information provided by the manufacturer.1

  • Importance of taking on an empty stomach or with a light meal.1

  • Importance of drinking 1.5 L of liquids daily.1

  • Advise patients that if a dose is missed, take the next dose at regularly scheduled time.1 Do not take a double dose to make up for the missed dose.1

  • Importance of storing indinavir in the original container; the desiccant should remain in the bottle.1

  • Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products (e.g., St. John’s wort), and any concomitant illnesses.1

  • Advise patients receiving selective phosphodiesterase type 5 (PDE5) inhibitors (e.g., avanafil, sildenafil, tadalafil, vardenafil) that they may be at increased risk of PDE5 inhibitor-associated adverse effects (e.g., hypotension, syncope, visual disturbances, priapism) and that any symptoms should be promptly reported to their clinician.1 188 Indinavir should not be used in patients receiving avanafil for treatment of erectile dysfunction188 or sildenafil for treatment of PAH.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise HIV-infected women not to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Indinavir Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

100 mg (of indinavir)

Crixivan

Merck

200 mg (of indinavir)

Crixivan

Merck

400 mg (of indinavir)

Crixivan

Merck

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Crixivan 200MG Capsules (MERCK SHARP & DOHME): 360/$475.98 or 1080/$1,414.95

Crixivan 400MG Capsules (MERCK SHARP & DOHME): 90/$239.99 or 270/$719.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 25, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Merck Sharp & Dohme. Crixivan (indinavir sulfate) capsules prescribing information. Whitehouse Station, NJ; 2012 Apr.

2. Dorsey BD, Levin RB, McDaniel SL et al. L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor. J Med Chem. 1994; 37:3443-51. [PubMed 7932573]

3. Vacca JP, Dorsey BD, Schleif WA et al. L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor. Proc Natl Acad Sci USA. 1994; 91:4096-100. [PubMed 8171040]

4. Anon. New drugs for HIV infection. Med Lett Drugs Ther. 1996; 38:35-8. [PubMed 8606677]

6. Vella S. Rationale and experience with reverse transcriptase inhibitors and protease inhibitors. J Acquir Immune Defic Syndr Hum Retrovirol. 1995; 10(Suppl 1):S58-61.

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207. Abbott Laboratories. Kaletra (lopinavir/ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

208. ViiV Healthcare. Viracept (nelfinavir mesylate) tablets and oral powder prescribing information. Research Triangle Park, NC; 2012 Apr.

209. Abbott Laboratories. Norvir (ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

210. Genentech USA. Invirase (saquinavir mesylate) capsules and tablets prescribing information. South San Francisco, CA; 2012 Feb.

212. ViiV Healthcare. Rescriptor (delavirdine mesylate) tablets prescribing information. Research Triangle Park, NC; 2010 Sep.

213. Bristol-Myers Squibb. Sustiva (efavirenz) capsules and tablets prescribing information. Princeton, NJ; 2012 Jun.

214. Janssen. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2012 Mar.

215. Boehringer Ingelheim. Viramune (nevirapine) tablets and oral suspension prescribing information. Ridgefield, CT; 2011 Nov.

217. Bristol-Myers Squibb. Videx EC (didanosine) delayed-release capsules enteric-coated beadlets prescribing information. Princeton, NJ; 2011 Nov.

218. Gilead Sciences. Emtriva (emtricitabine) capsules and oral solution prescribing information. Foster City, CA; 2012 Jul.

221. Gilead Sciences. Viread (tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2012 Jan.

223. Genentech USA. Fuzeon (enfuvirtide) for injection prescribing information. South San Francisco, CA; 2011 Aug.

224. ViiV Healthcare. Selzentry (maraviroc) tablets prescribing information. Research Triangle Park, NC; 2011 Nov.

225. Merck Sharp & Dohme. Isentress (raltegravir) film-coated tablets and chewable tablets prescribing information. Whitehouse Station, NJ; 2012 Apr.

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

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