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Indinavir

Class: HIV Protease Inhibitors
- 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

Medically reviewed by Drugs.com on Feb 8, 2021. Written by ASHP.

Introduction

Antiretroviral; HIV protease inhibitor (PI).

Uses for Indinavir

Treatment of HIV Infection

Treatment of HIV infection in adults, adolescents, and pediatric patients; used in conjunction with other antiretrovirals.

Experts state indinavir not recommended for initial treatment regimens in antiretroviral-naive adults and adolescents because of inconvenient dosing regimen, fluid requirements, and toxicities (e.g., nephrolithiasis, crystalluria).

Indinavir with low-dose ritonavir (ritonavir-boosted indinavir) not recommended for initial therapy in antiretroviral-naive adults and adolescents because of fluid requirements and toxicities (e.g., nephrolithiasis, crystalluria).

Indinavir (with or without low-dose ritonavir) not recommended for initial treatment regimens in antiretroviral-naive pediatric patients because of high incidence of hematuria, sterile leukocyturia, and nephrolithiasis in children.

Indinavir Dosage and Administration

Administration

Oral Administration

Administer orally.

Administer with water 1 hour before or 2 hours after a meal. 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). Do not administer with a meal high in calories, fat, and protein.

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

Dosage

Available as indinavir sulfate; dosage expressed as indinavir.

Pediatric Patients

Treatment of HIV Infection
Oral

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

Adults

Treatment of HIV Infection
Oral

800 mg every 8 hours.

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

Special Populations

Hepatic Impairment

Treatment of HIV Infection
Oral

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

Renal Impairment

Treatment of HIV Infection
Oral

Dosage adjustment not necessary.

Geriatric Patients

Select dosage with caution.

Cautions for Indinavir

Contraindications

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

  • 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). (See Specific Drugs and Food under Interactions.)

Warnings/Precautions

Warnings

Renal and GU Effects

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

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

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.

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

Interactions

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

Hemolytic Anemia

Acute hemolytic anemia, including fatalities, reported.

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

Hepatic Effects

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

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

Hyperglycemic Effects

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

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

General Precautions

HIV Resistance

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

Hemophilia A and B

Spontaneous bleeding noted with PIs; causal relationship not established.

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

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 jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

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.

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.

Specific Populations

Pregnancy

Category C.

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Experts state ritonavir-boosted indinavir not recommended for initial treatment regimens in antiretroviral-naive pregnant women because of potential to cause kidney stones and hyperbilirubinemia. In addition, data insufficient to recommend appropriate dosage of ritonavir-boosted indinavir for pregnant women.

Experts state indinavir (without low-dose ritonavir) not recommended at any time in pregnant women. Substantially decreased plasma indinavir concentrations reported during pregnancy. (See Absorption: Special Populations under Pharmacokinetics.)

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.

Lactation

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

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

Pediatric Use

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

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

Has been used in a limited number of HIV-infected children ≥3 months of age. Nephrolithiasis/urolithiasis reported more frequently in pediatric patients than in adults.

Geriatric Use

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

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

Hepatic Impairment

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

Common Adverse Effects

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

Interactions for Indinavir

Metabolized by CYP3A4.

Inhibits CYP3A4 and, to a lesser extent, CYP2D6.

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

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.

Specific Drugs and Food

Drug or Food

Interaction

Comments

Alfuzosin

Potential for increased alfuzosin concentrations that could result in hypotension

Concomitant use contraindicated

Antiarrhythmic agents (amiodarone, systemic lidocaine, quinidine)

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

Amiodarone: Concomitant use contraindicated

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

Anticoagulants, oral

Rivaroxaban: Possible increased rivaroxaban concentrations; may increase bleeding risk

Warfarin: Possible altered warfarin concentrations

Rivaroxaban: Avoid concomitant use

Warfarin: Monitor INR, especially when initiating or discontinuing indinavir; adjust warfarin dosage as needed

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Possible decreased indinavir concentrations; possible decreased antiretroviral effectiveness

No change in plasma concentrations of carbamazepine

Carbamazepine, phenobarbital, phenytoin: Use concomitantly with caution

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

Fluconazole: Decreased indinavir AUC; no effect on fluconazole AUC

Itraconazole: Possible increased concentrations of both drugs

Ketoconazole: Increased indinavir concentrations

Voriconazole: No clinically important effect on pharmacokinetics of either drug

Fluconazole: Dosage adjustments not needed

Itraconazole: Use concomitantly with caution; reduce indinavir dosage to 600 mg every 8 hours; consider monitoring itraconazole concentration to guide dosage adjustments; itraconazole dosage >200 mg daily not recommended in those receiving ritonavir-boosted indinavir unless itraconazole concentrations used to guide dosage

Ketoconazole: Reduce indinavir dosage to 600 mg every 8 hours

Voriconazole: Dosage adjustments not needed; concomitant use with ritonavir-boosted indinavir not recommended unless potential benefits outweigh risks; if used with ritonavir-boosted indinavir, consider monitoring voriconazole plasma concentrations

Antimycobacterials (bedaquiline, isoniazid, rifabutin, rifampin, rifapentine)

Bedaquiline: Possible increased bedaquiline concentrations; clinical importance unknown

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

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

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

Rifapentine: Possible decreased indinavir concentrations

Bedaquiline: Use concomitantly with ritonavir-boosted indinavir with caution and only if potential benefits outweigh risks; monitor for corrected QT (QTc) interval prolongation and liver dysfunction

Isoniazid: Dosage adjustments not needed

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

Rifampin: Concomitant use contraindicated

Rifapentine: Concomitant use not recommended

Antipsychotics (pimozide, quetiapine)

Pimozide: Potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)

Quetiapine: Increased quetiapine concentrations expected

Pimozide: Concomitant use contraindicated

Quetiapine: Initiate quetiapine at lowest dosage and titrate as needed; if initiating indinavir in patients receiving quetiapine, reduce quetiapine to one-sixth of original dosage; monitor for efficacy and adverse effects of quetiapine

Atazanavir

Potential for additive hyperbilirubinemia

Concomitant use contraindicated

Avanafil

Possible increased avanafil concentrations and AUC

Do not use concomitantly

Benzodiazepines

Alprazolam, midazolam, triazolam: Pharmacokinetic interaction; potential for prolonged or increased sedation or respiratory depression

Diazepam: Possible increased diazepam concentrations

Oral midazolam, triazolam: Concomitant use contraindicated

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

Diazepam: Consider alternative benzodiazepine with less potential for pharmacokinetic interaction (e.g., lorazepam, oxazepam, temazepam)

Bosentan

Possible increased bosentan concentrations

In patients already receiving indinavir, initiate bosentan at dosage of 62.5 mg once daily or every other day based on individual tolerability

In patients already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating indinavir; after ≥10 days of indinavir, resume bosentan at dosage of 62.5 mg once daily or every other day based on individual tolerability

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 drug

Use concomitantly with caution; clinical monitoring recommended; adjust dosage of the calcium-channel blocking agent based on clinical response and toxicities

Cisapride

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

Concomitant use contraindicated

Colchicine

Increased colchicine concentrations

Patients with renal or hepatic impairment: Avoid concomitant use

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 later

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 daily

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)

Corticosteroids (beclomethasone, budesonide, dexamethasone, fluticasone, methylprednisolone, prednisolone, prednisone, triamcinolone)

Beclomethasone (orally inhaled, intranasal): Clinically important pharmacokinetic interactions not expected

Budesonide or fluticasone (orally inhaled, intranasal): Increased corticosteroid concentrations; may result in adrenal insufficiency or Cushing's syndrome

Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations; may result in adrenal insufficiency or Cushing's syndrome

Budesonide or prednisone (systemic): Increased corticosteroid concentrations; may result in adrenal insufficiency or Cushing's syndrome; budesonide (systemic) may decrease indinavir concentrations

Dexamethasone (systemic): Possible decreased indinavir concentrations

Budesonide or fluticasone (orally inhaled, intranasal): Do not use concomitantly unless potential benefits of inhaled or intranasal corticosteroid outweigh risks of systemic corticosteroid adverse effects; consider alternative (e.g., beclomethasone)

Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Do not use concomitantly; consider alternative nonsteroidal therapies; if intra-articular corticosteroid required, use alternative antiretroviral that does not alter CYP3A4 activity (e.g., dolutegravir, raltegravir)

Budesonide or prednisone (systemic): Do not use concomitantly unless potential benefits outweigh risks of systemic corticosteroid adverse effects

Dexamethasone (systemic): Use concomitantly with caution; consider alternative corticosteroid for long-term use

Co-trimoxazole

Interaction unlikely

Dosage adjustments not needed

Darunavir

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

No in vitro evidence of antagonistic antiretroviral effects

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

Delavirdine

Delavirdine inhibits indinavir metabolism and may increase indinavir concentrations and AUC; no effect on delavirdine pharmacokinetics

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

Didanosine

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

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

In vitro evidence of synergistic antiretroviral effects

Buffered didanosine (Videx): Administer 1 hour after indinavir

Efavirenz

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

In vitro evidence of additive antiretroviral effects

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 efavirenz

Emtricitabine

No effect on pharmacokinetics of either drug

Enfuvirtide

In vitro evidence of additive to synergistic antiretroviral effects

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

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

Concomitant use contraindicated

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 possible

Estrogens/Progestins

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

Etravirine

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

No in vitro evidence of antagonistic antiretroviral effects

Do not use concomitantly without low-dose ritonavir

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 evaluated

In vitro evidence of additive antiretroviral effects

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

Grapefruit juice

Decreased indinavir AUC and concentrations

Histamine H2-receptor antagonists (cimetidine)

Pharmacokinetic interaction unlikely with cimetidine

Dosage adjustment not needed

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 rhabdomyolysis

Atorvastatin: Carefully titrate atorvastatin dosage and use lowest necessary dosage

Lovastatin: Concomitant use contraindicated

Pitavastatin: Dosage adjustments not needed

Rosuvastatin: Carefully titrate rosuvastatin dosage and use lowest necessary dosage

Simvastatin: Concomitant use contraindicated

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

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

Monitor concentrations of the immunosuppressive agent

Lamivudine

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

Lopinavir/ritonavir

Increased indinavir concentrations

In vitro evidence of additive to synergistic antiretroviral effects

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

Macrolides (clarithromycin)

Increased indinavir and clarithromycin AUCs

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

Maraviroc

No in vitro evidence of antagonistic antiretroviral effects

Recommended maraviroc dosage is 150 mg twice daily

Methadone

Indinavir (without low-dose ritonavir): Pharmacokinetic interactions unlikely

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

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

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

Nelfinavir

Increased AUCs of both drugs

In vitro evidence of antagonistic antiretroviral effects

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

Nevirapine

Decreased indinavir concentrations and AUC

In vitro evidence of additive to synergistic antiretroviral effects

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

Quinupristin and dalfopristin

Possible increased indinavir concentrations

Raltegravir

In vitro evidence of additive to synergistic antiretroviral effects

Rilpivirine

Possible increased rilpivirine concentrations; not expected to affect indinavir concentrations

Ritonavir

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

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

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

St. John’s wort (Hypericum perforatum)

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

Concomitant use not recommended

Saquinavir

Substantially increased saquinavir concentrations

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

Salmeterol

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

Concomitant use not recommended

Sildenafil

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

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

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)

Simeprevir

Possible altered (increased or decreased) simeprevir concentrations

Concomitant use not recommended

Stavudine

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

Tadalafil

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

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 tolerability

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)

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

Tenofovir

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

In vitro evidence of additive to synergistic antiretroviral effects

Theophylline

Pharmacokinetic interactions unlikely

Trazodone

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

Use concomitantly with caution; consider decreased trazodone dosage

Tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline)

Increased concentrations of tricyclic antidepressant expected

Use lowest possible antidepressant dosage in patients receiving ritonavir-boosted indinavir; titrate antidepressant dosage based on clinical assessment and/or antidepressant concentrations

Vardenafil

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

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)

Venlafaxine

Decreased indinavir concentrations; no change in venlafaxine concentrations

Clinical importance unknown

Zidovudine

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

In vitro evidence of synergistic antiretroviral effects

Indinavir Pharmacokinetics

Absorption

Bioavailability

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

Food

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

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.

Special Populations

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

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

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

Distribution

Extent

Not fully characterized.

Distributed into CSF in low concentration in adults or children.

When used without low-dose ritonavir in pregnant women, only minimal amounts of indinavir crossed the placenta.

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

Plasma Protein Binding

60%.

Elimination

Metabolism

Metabolized by CYP3A4.

Elimination Route

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

Half-life

1.8 hours.

Special Populations

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

Pharmacokinetics not studied in renal impairment.

Stability

Storage

Oral

Capsules

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

Actions and Spectrum

  • Active against HIV-1 and HIV-2.

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

  • HIV-1 with reduced susceptibility to indinavir have been selected in vitro and have emerged during therapy with the drug.

  • Varying degrees of cross-resistance occur among PIs.

Advice to Patients

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

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

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

  • 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. 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.

  • Importance of reading patient information provided by the manufacturer.

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

  • Importance of drinking 1.5 L of liquids daily.

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

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

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

  • 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.

  • 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. Indinavir should not be used in patients receiving avanafil for treatment of erectile dysfunction or sildenafil for treatment of PAH.

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Indinavir Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

200 mg (of indinavir)

Crixivan

Merck

400 mg (of indinavir)

Crixivan

Merck

AHFS DI Essentials™. © Copyright 2022, Selected Revisions February 17, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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