Indinavir Sulfate

Name: Indinavir Sulfate

Side effects

Clinical Trials In Adults

Nephrolithiasis/urolithiasis, including flank pain with or without hematuria (including microscopic hematuria), has been reported in approximately 12.4% (301/2429; range across individual trials: 4.7% to 34.4%) of patients receiving CRIXIVAN at the recommended dose in clinical trials with a median follow-up of 47 weeks (range: 1 day to 242 weeks; 2238 patient-years follow-up). The cumulative frequency of nephrolithiasis events increases with duration of exposure to CRIXIVAN; however, the risk over time remains relatively constant. Of the patients treated with CRIXIVAN who developed nephrolithiasis/urolithiasis in clinical trials during the double-blind phase, 2.8% (7/246) were reported to develop hydronephrosis and 4.5% (11/246) underwent stent placement. Following the acute episode, 4.9% (12/246) of patients discontinued therapy. (See WARNINGS and DOSAGE AND ADMINISTRATION, Nephrolithiasis/Urolithiasis.)

Asymptomatic hyperbilirubinemia (total bilirubin ≥ 2.5 mg/dL), reported predominantly as elevated indirect bilirubin, has occurred in approximately 14% of patients treated with CRIXIVAN. In < 1% this was associated with elevations in ALT or AST.

Hyperbilirubinemia and nephrolithiasis/urolithiasis occurred more frequently at doses exceeding 2.4 g/day compared to doses ≤ 2.4 g/day.

Clinical adverse experiences reported in ≥ 2% of patients treated with CRIXIVAN alone, CRIXIVAN in combination with zidovudine or zidovudine plus lamivudine, zidovudine alone, or zidovudine plus lamivudine are presented in Table 10.

Table 10: Clinical Adverse Experiences Reported in ≥ 2% of Patients

Adverse Experience Study 028 Considered Drug-Related and of Moderate or Severe Intensity Study ACTG 320 of Unknown Drug Relationship and of Severe or Life-threatening Intensity
CRIXIVAN Percent
(n=332)		 CRIXIVAN plus Zidovudine Percent
(n=332)		 Zidovudine Percent
(n=332)		 CRIXIVAN plus Zidovudine plus Lamivudine Percent
(n=571)		 Zidovudine plus Lamivudine Percent
(n=575)
Body as a Whole
  Abdominal pain 16.6 16.0 12.0 1.9 0.7
  Asthenia/ fatigue 2.1 4.2 3.6 2.4 4.5
  Fever 1.5 1.5 2.1 3.8 3.0
  Malaise 2.1 2.7 1.8 0 0
Digestive System
  Nausea 11.7 31.9 19.6 2.8 1.4
  Diarrhea 3.3 3.0 2.4 0.9 1.2
  Vomiting 8.4 17.8 9.0 1.4 1.4
  Acid regurgitation 2.7 5.4 1.8 0.4 0
  Anorexia 2.7 5.4 3.0 0.5 0.2
  Appetite increase 2.1 1.5 1.2 0 0
  Dyspepsia 1.5 2.7 0.9 0 0
  Jaundice 1.5 2.1 0.3 0 0
Hemic and Lymphatic System
  Anemia 0.6 1.2 2.1 2.4 3.5
Musculoskeletal System
  Back pain 8.4 4.5 1.5 0.9 0.7
Nervous System/ Psychiatric
  Headache 5.4 9.6 6.0 2.4 2.8
  Dizziness 3.0 3.9 0.9 0.5 0.7
  Somnolence 2.4 3.3 3.3 0 0
Skin and Skin Appendage
  Pruritus 4.2 2.4 1.8 0.5 0
  Rash 1.2 0.6 2.4 1.1 0.5
Respiratory System
  Cough 1.5 0.3 0.6 1.6 1.0
  Difficulty breathing/ dyspnea/ shortness of breath 0 0.6 0.3 1.8 1.0
Urogenital System
  Nephrolithiasis/ urolithiasis 8.7 7.8 2.1 2.6 0.3
  Dysuria 1.5 2.4 0.3 0.4 0.2
Special Senses
  Taste perversion 2.7 8.4 1.2 0.2 0
*Including renal colic, and flank pain with and without hematuria

In Phase I and II controlled trials, the following adverse events were reported significantly more frequently by those randomized to the arms containing CRIXIVAN than by those randomized to nucleoside analogues: rash, upper respiratory infection, dry skin, pharyngitis, taste perversion.

Selected laboratory abnormalities of severe or life-threatening intensity reported in patients treated with CRIXIVAN alone, CRIXIVAN in combination with zidovudine or zidovudine plus lamivudine, zidovudine alone, or zidovudine plus lamivudine are presented in Table 11.

Table 11: Selected Laboratory Abnormalities of Severe or Life-threatening Intensity Reported in Studies 028 and ACTG 320

  Study 028 Considered Drug-Related and of Moderate or Severe Intensity Study ACTG 320 of Unknown Drug Relationship and of Severe or Life-threatening Intensity
CRIXIVAN Percent
(n=329)		 CRIXIVAN plus Zidovudine Percent
(n=320)		 Zidovudine Percent
(n=330)		 CRIXIVAN plus Zidovudine plus Lamivudine Percent
(n=571)		 Zidovudine plus Lamivudine Percent
(n=575)
Hematology
Decreased hemoglobin < 7.0 g/dL 0.6 0.9 3.3 2.4 3.5
Decreased platelet count < 50 THS/mm³ 0.9 0.9 1.8 0.2 0.9
Decreased neutrophils < 0.75 THS/mm³ 2.4 2.2 6.7 5.1 14.6
Blood chemistry
Increased ALT > 500% ULN* 4.9 4.1 3.0 2.6 2.6
Increased AST > 500% ULN 3.7 2.8 2.7 3.3 2.8
Total serum bilirubin > 250% ULN 11.9 9.7 0.6 6.1 1.4
Increased serum amylase > 200% ULN 2.1 1.9 1.8 0.9 0.3
Increased glucose > 250 mg/dL 0.9 0.9 0.6 1.6 1.9
Increased creatinine > 300% ULN 0 0 0.6 0.2 0
*Upper limit of the normal range.

Post-Marketing Experience

Body As A Whole: redistribution/accumulation of body fat (see PRECAUTIONS, Fat Redistribution).

Cardiovascular System: cardiovascular disorders including myocardial infarction and angina pectoris; cerebrovascular disorder.

Digestive System: liver function abnormalities; hepatitis including reports of hepatic failure (see WARNINGS); pancreatitis; jaundice; abdominal distention; dyspepsia.

Hematologic: increased spontaneous bleeding in patients with hemophilia (see PRECAUTIONS); acute hemolytic anemia (see WARNINGS).

Endocrine/Metabolic: new onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, hyperglycemia (see WARNINGS).

Hypersensitivity: anaphylactoid reactions; urticaria; vasculitis.

Musculoskeletal System: arthralgia, periarthritis.

Nervous System/Psychiatric: oral paresthesia; depression.

Skin and Skin Appendage: rash including erythema multiforme and Stevens-Johnson syndrome; hyperpigmentation; alopecia; ingrown toenails and/or paronychia; pruritus.

Urogenital System: nephrolithiasis/urolithiasis, in some cases resulting in renal insufficiency or acute renal failure, pyelonephritis with or without bacteremia (see WARNINGS); interstitial nephritis sometimes with indinavir crystal deposits; in some patients, the interstitial nephritis did not resolve following discontinuation of CRIXIVAN; renal insufficiency; renal failure; leukocyturia (see PRECAUTIONS), crystalluria; dysuria.

Laboratory Abnormalities

Increased serum triglycerides; increased serum cholesterol.

What is indinavir (crixivan)?

Indinavir is an antiviral medication in a group of HIV medicines called protease (PRO-tee-ayz) inhibitors. Indinavir prevents human immunodeficiency virus (HIV) cells from multiplying in your body.

Indinavir is used to treat HIV, which causes acquired immunodeficiency syndrome (AIDS). Indinavir is not a cure for HIV or AIDS.

Indinavir may also be used for purposes not listed in this medication guide.

What should i discuss with my healthcare provider before taking indinavir (crixivan)?

You should not take this medication if you are allergic to indinavir.

Life-threatening side effects may occur if you take indinavir with alfuzosin (Uroxatral), amiodarone (Cordarone, Pacerone), cisapride (Propulsid), pimozide (Orap), alprazolam (Xanax), oral midazolam (Versed), triazolam (Halcion), lovastatin (Mevacor, Altoprev, Advicor), simvastatin (Zocor, Simcor, Vytorin, Juvisync), sildenafil (Revatio, for treating pulmonary arterial hypertension), or ergot medicines such as ergotamine (Ergomar, Cafergot), dihydroergotamine (D.H.E. 45, Migranal Nasal Spray), ergonovine (Ergotrate), or methylergonovine (Methergine).

To make sure you can safely take indinavir, tell your doctor if you have any of these other conditions:

  • liver disease;
  • kidney disease, or a history of kidney stones;
  • diabetes;
  • a bleeding disorder such as hemophilia; or
  • high cholesterol or triglycerides.

FDA pregnancy category C. It is not known whether indinavir will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. HIV can be passed to the baby if the mother is not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection while you are pregnant.

Your name may need to be listed on an antiviral pregnancy registry when you start using this medication.

Women with HIV or AIDS should not breast feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

Introduction

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

Uses for Indinavir Sulfate

Treatment of HIV Infection

Treatment of HIV infection in adults, adolescents, and pediatric patients;1 used in conjunction with other antiretrovirals.1

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).200

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).200

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.201

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

Anticoagulants, oral

Rivaroxaban: Possible increased rivaroxaban concentrations; may increase bleeding risk200

Warfarin: Possible altered warfarin concentrations200

Rivaroxaban: Avoid concomitant use200

Warfarin: Monitor INR, especially when initiating or discontinuing indinavir; adjust warfarin dosage as needed200

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 128 200

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 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 dosage200

Ketoconazole: Reduce indinavir dosage to 600 mg every 8 hours1

Voriconazole: Dosage adjustments not needed;129 concomitant use with ritonavir-boosted indinavir not recommended unless potential benefits outweigh risks;200 if used with ritonavir-boosted indinavir, consider monitoring voriconazole plasma concentrations200

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

Bedaquiline: Possible increased bedaquiline concentrations;200 clinical importance unknown200

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

Bedaquiline: Use concomitantly with ritonavir-boosted indinavir with caution and only if potential benefits outweigh risks;200 monitor for corrected QT (QTc) interval prolongation and liver dysfunction200

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

Antipsychotics (pimozide, quetiapine)

Pimozide: Potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1

Quetiapine: Increased quetiapine concentrations expected200

Pimozide: Concomitant use contraindicated1

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 quetiapine200

Atazanavir

Potential for additive hyperbilirubinemia1 203

Concomitant use contraindicated1 200

Avanafil

Possible increased avanafil concentrations and AUC188

Do not use concomitantly188

Benzodiazepines

Alprazolam, midazolam, triazolam: Pharmacokinetic interaction; potential for prolonged or increased sedation or respiratory depression1

Diazepam: Possible increased diazepam concentrations200

Oral midazolam, triazolam: Concomitant use contraindicated1

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;1 experts state a single parenteral midazolam dose can be used with caution in a monitored situation for procedural sedation200

Diazepam: Consider alternative benzodiazepine with less potential for pharmacokinetic interaction (e.g., lorazepam, oxazepam, temazepam)200

Bosentan

Possible increased bosentan concentrations1

In patients already receiving indinavir, initiate bosentan at dosage of 62.5 mg once daily or every other day based on individual tolerability1

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 tolerability200

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 recommended;1 adjust dosage of the calcium-channel blocking agent based on clinical response and toxicities200

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

Beclomethasone (orally inhaled, intranasal): Clinically important pharmacokinetic interactions not expected200

Budesonide or fluticasone (orally inhaled, intranasal): Increased corticosteroid concentrations;200 may result in adrenal insufficiency or Cushing's syndrome200

Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations;200 may result in adrenal insufficiency or Cushing's syndrome200

Budesonide or prednisone (systemic): Increased corticosteroid concentrations;200 may result in adrenal insufficiency or Cushing's syndrome;200 budesonide (systemic) may decrease indinavir concentrations200

Dexamethasone (systemic): Possible decreased indinavir concentrations200

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;200 consider alternative (e.g., beclomethasone)200

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)200

Budesonide or prednisone (systemic): Do not use concomitantly unless potential benefits outweigh risks of systemic corticosteroid adverse effects200

Dexamethasone (systemic): Use concomitantly with caution;200 consider alternative corticosteroid for long-term use200

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 and AUC; 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, 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

Pitavastatin: Dosage adjustments not needed200

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

Monitor concentrations of the immunosuppressive agent200

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

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;1 200 209 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

St. John’s wort (Hypericum perforatum)

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

Concomitant use not recommended1

Saquinavir

Substantially increased saquinavir concentrations1 210

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

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

Simeprevir

Possible altered (increased or decreased) simeprevir concentrations187

Concomitant use not recommended187 200

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

Tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline)

Increased concentrations of tricyclic antidepressant expected200

Use lowest possible antidepressant dosage in patients receiving ritonavir-boosted indinavir;200 titrate antidepressant dosage based on clinical assessment and/or antidepressant concentrations200

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

Actions and Spectrum

  • 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

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 antiretroviralsnot 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.)

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