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
Because of the inconvenient dosing regimen and fluid requirements, indinavir is not recommended for initial therapy.108 Because of the high incidence of nephrolithiasis, ritonavir-boosted indinavir is not recommended for initial therapy.108
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 95 97 Used in conjunction with other antiretrovirals.95
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.184 Used in conjunction with other antiretrovirals.184
Indinavir Sulfate Dosage and Administration
Administration
Oral Administration
Administer orally.1
If used without low-dose ritonavir, administer with water at least 1 hour before or 2 hours after a meal.1 108 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
Some clinicians suggest the drug may be taken without regard to meals if used with low-dose ritonavir (ritonavir-boosted indinavir).108
To ensure adequate hydration, patients should drink at least 1.5 L (approximately 48 ounces) of liquids daily (i.e., every 24 hours).1 4 108 If ritonavir-boosted indinavir is used, some experts suggest patients drink 1.5–2 L of noncaffeinated liquids daily.108
Dosage
Available as indinavir sulfate; dosage expressed as indinavir.1
Must be given in conjunction with other antiretrovirals.1 If used with delavirdine, certain didanosine preparations, efavirenz, lopinavir/ritonavir, nelfinavir, nevirapine, or ritonavir, adjustment in the treatment regimen recommended.1 100 105 108 180 (See Specific Drugs and Food under Interactions.)
Pediatric Patients
Treatment of HIV Infection
Oral
Children 4–15 years of age†: 500 mg/m2 every 8 hours under investigation.147
Adults
Treatment of HIV Infection
Oral
800 mg every 8 hours.1 108 If ritonavir-boosted indinavir is used, 800 mg twice daily with low-dose ritonavir (100 or 200 mg twice daily).108
Postexposure Prophylaxis of HIV†
Occupational Exposure†
Oral
800 mg twice daily boosted with low-dose ritonavir (100 mg twice daily).95 Alternatively, 800 mg every 8 hours (without low-dose ritonavir).95
Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.95
Nonoccupational Exposure†
Oral
800 mg twice daily boosted with low-dose ritonavir (100 or 200 mg every 12 hours).184 Alternatively, 800 mg every 8 hours (without low-dose ritonavir).184
Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.184
Special Populations
Hepatic Impairment
Treatment of HIV Infection
Oral
Adults with mild to moderate hepatic impairment due to cirrhosis: 600 mg every 8 hours.1 108
Renal Impairment
Treatment of HIV Infection
Oral
Dosage adjustment not needed.108
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 CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alprazolam, amiodarone, cisapride, ergot alkaloids, oral midazolam, pimozide, triazolam).1 (See Specific Drugs and Food under Interactions.)
Warnings/Precautions
Warnings
Interactions
Concomitant use with certain drugs not recommended (e.g., lovastatin, rosuvastatin, simvastatin, St. John’s wort, fluticasone) or requires particular caution (e.g., sildenafil, tadalafil, vardenafil).1 (See Specific Drugs and Food under Interactions.)
Renal and GU Effects
Nephrolithiasis/urolithiasis,1 4 26 68 73 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.1 108 Risk of nephrolithiasis/urolithiasis may be greater with ritonavir-boosted indinavir compared with indinavir (without low-dose ritonavir).1 108
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
Hemolytic Anemia
Acute hemolytic anemia, including cases resulting in death, 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 73
Hyperglycemic Effects
Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of PIs; diabetic ketoacidosis has occurred.1 88 120 121 122 123
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.1 147 Effect of indinavir therapy on subsequent therapy with other PIs under investigation.1 147
Hemophilia A and B
Spontaneous bleeding noted with PIs; causal relationship not established.1 40 119
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
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 800-258-4263.1
Hyperbilirubinemia, generally reported as an increase in indirect bilirubin, has occurred in patients receiving indinavir; it is not known whether administration of the drug to a pregnant woman during the perinatal period can exacerbate physiologic hyperbilirubinemia in the neonate.1
Substantially decreased plasma indinavir concentrations reported during pregnancy.1 172 (See Special Populations under Pharmacokinetics.)
Some experts state use of ritonavir-boosted indinavir is an alternative HIV protease inhibitor (not a preferred PI) for use in pregnant women;172 however optimal dosage of ritonavir-boosted indinavir for use during pregnancy not known.1
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 57 172
Pediatric Use
Safety and efficacy not established in pediatric patients.1
Has been used in a limited number of HIV-infected children ≥3 months of age†.1 39 72 124 125 147 151 152 166 173 Nephrolithiasis/urolithiasis reported more frequently in pediatric patients than in adults.1
Because hyperbilirubinemia has been reported in patients receiving indinavir,1 4 17 23 73 147 the drug should not be used in neonates until further information is available.147
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 CYP3A.1
Inhibits CYP3A 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 CYP3A with possible alteration in metabolism of indinavir and/or other drug.1
Specific Drugs and Food
Drug or Food
|
Interaction
|
Comments
|
|---|
Antiarrhythmic agents (amiodarone, systemic lidocaine, quinidine)
|
Potential increased antiarrhythmic concentrations1
Potential for serious or life-threatening effects (e.g., cardiac arrhythmias) if indinavir used with amiodarone1
|
Concomitant use with amiodarone contraindicated1
Caution if indinavir used concomitantly with systemic lidocaine or quinidine; monitoring plasma antiarrhythmic concentrations recommended1
|
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)
|
Possible decreased plasma concentrations of indinavir; possible decreased antiretroviral effectiveness1
No change in plasma concentrations of carbamazepine167
|
Use concomitantly with caution;1 consider using alternative anticonvulsants, using ritonavir-boosted indinavir, and/or monitoring indinavir concentrations108
|
Antifungals, azole (itraconazole, ketoconazole, voriconazole)
|
Increased concentrations of indinavir when administered with itraconazole, ketoconazole, or fluconazole; no change in AUC of indinavir with fluconazole1 74 108 145
Voriconazole: Pharmacokinetic interactions unlikely with indinavir;108 decreased voriconazole concentrations reported with low-dose ritonavir108
|
Fluconazole: Dosage adjustment not needed145
Itraconazole: When given with itraconazole 200 mg twice daily, reduce indinavir dosage to 600 mg every 8 hours;1 108 do not use itraconazole dosage >200 mg twice daily108
Ketoconazole: When given with ketoconazole, reduce indinavir dosage to 600 mg every 8 hours1 108
Voriconazole: Dosage adjustment not needed with indinavir1 108
Voriconazole: Concomitant use with ritonavir-boosted indinavir not recommended unless potential benefits outweigh risk108
|
Antimycobacterials
|
Isoniazid: No change in AUC of indinavir and clinically unimportant increases in AUC of isoniazid1 74
Rifabutin: Decreased indinavir concentrations and increased rifabutin concentrations1 108
Rifampin: Decreased indinavir concentrations; possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance1
|
Isoniazid: Dosage adjustment not needed1
Rifabutin: Reduce rifabutin dosage to 150 mg once daily or 300 mg 3 times weekly; increase indinavir dosage to 1 g every 8 hours1 108
Rifampin: Concomitant use not recommended1 108 148
Rifapentine: Concomitant use not recommended108
|
Atazanavir
|
Potential for additive hyperbilirubinemia;108 e concomitant use has not been studiede
In vitro evidence of additive antiretroviral effectse
|
Concomitant use not recommended108 e
|
Benzodiazepines
|
Pharmacokinetic interaction with alprazolam, midazolam, or triazolam; potential for prolonged or increased sedation or respiratory depression1
|
Concomitant use with alprazolam, oral midazolam, or triazolam contraindicated;1 108 some experts state that a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation108
|
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 108
|
Corticosteroids (fluticasone)
|
Fluticasone nasal spray/oral inhalation: Increased plasma fluticasone concentrations with indinavir (with or without low-dose ritonavir) resulting in decreased cortisol concentrations1
|
Fluticasone nasal spray/oral inhalation: Consider alternative in patients receiving indinavir (without ritonavir), especially when long-term corticosteroid therapy is anticipated; concomitant use with ritonavir-boosted indinavir not recommended unless potential benefits outweigh risk of systemic corticosteroid adverse effects1
|
Co-trimoxazole
|
Interaction unlikely1
|
Dosage adjustment not needed1
|
Darunavir
|
Increased concentrations of darunavir and indinavir185
|
Appropriate dosage for concomitant use of ritonavir-boosted darunavir and indinavir not established185
|
Delavirdine
|
Increased peak plasma concentrations and AUC of indinavir; no change in pharmacokinetics of delavirdine1 108 129 144
|
When given with delavirdine 400 mg 3 times daily (usual delavirdine dosage), reduce indinavir dosage to 600 mg every 8 hours1 108 129
|
Didanosine
|
When buffered didanosine preparations administered at the same time as indinavir, decreased AUC of indinavir155
In vitro evidence of synergistic antiretroviral effects1
|
Administer indinavir and buffered didanosine (pediatric oral solution admixed with antacid) ≥1 hour apart1 4
|
Efavirenz
|
Decreased peak plasma concentrations and AUC of indinavir; no change in pharmacokinetics of efavirenz1 149
In vitro evidence of synergistic antiretroviral effects149
|
Adjustment of efavirenz dosage not needed; increase indinavir dosage to 1 g every 8 hours or consider ritonavir-boosted indinavir108
|
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 108
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 possible147
|
Estrogens/Progestins
|
Hormonal contraceptives: Increased AUC of ethinyl estradiol and norethindrone reported with oral contraceptive preparations1
|
Hormonal contraceptives: Dosage adjustment not needed1 108
|
Etravirine
|
Decreased indinavir concentrationsg
|
Concomitant use not recommended108 g
|
Fosamprenavir
|
Studies using amprenavir indicate possible increased plasma amprenavir concentrations and AUC;f concomitant use of ritonavir-boosted fosamprenavir with indinavir not evaluatedf
In vitro evidence of additive antiretroviral effectsf
|
Appropriate dosages for concomitant use with respect to safety and efficacy not establishedf
|
Grapefruit juice
|
Decreased AUC and concentrations of indinavir1 108
|
Monitor virologic response108
|
Histamine H2-receptor antagonists (cimetidine)
|
Pharmacokinetic interaction unlikely with cimetidine1
|
Dosage adjustment not needed1
|
HMG-CoA reductase inhibitors (statins)
|
Decreased clearance and increased concentrations of some HMG-CoA reductase inhibitors with potential for increased risk of myopathy (including rhabdomyolysis)1
|
Concomitant use with lovastatin, rosuvastatin, or simvastatin not recommended1
If used with atorvastatin, use lowest possible dosage of atorvastatin1
Consider using HMG-CoA reductase inhibitors with low potential for interaction (e.g., fluvastatin, pravastatin)1
|
Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)
|
Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus1
| |
Lopinavir
|
Pharmacokinetic interaction; increased indinavir AUC and concentrations108 177
|
Consider indinavir 600 mg twice daily with 400 mg of lopinavir and 100 mg of ritonavir twice daily108 177
|
Macrolides (clarithromycin)
|
Increased AUC of indinavir and clarithromycin; decreased AUC of 14-hydroxyclarithromycin1 74 108 171
|
Indinavir manufacturer states appropriate dosages for concomitant use with respect to safety and efficacy not established;1 some experts state that modification of usual clarithromycin dosage not necessary in patients with normal renal function; reduce clarithromycin dosage by 50% if Clcr 30–60 mL/minute and reduce by 75% if Clcr <30 mL/minute 108
|
Maraviroc
|
Possible increased concentrations of maraviroc108
|
Recommended dosage of maraviroc is 150 mg twice daily108
|
Methadone
|
Pharmacokinetic interactions unlikely1 108
| |
Nelfinavir
|
Increased AUC of both drugs105 126 127
|
Appropriate dosages for concomitant use with respect to safety and efficacy not established1 105
Limited data supports use of indinavir 1.2 g twice daily with nelfinavir 1.25 g twice daily108
|
Nevirapine
|
Decreased peak and trough plasma concentration and AUC of indinavir; no clinically important change in the pharmacokinetics of nevirapine100 108
In vitro evidence of additive or synergistic antiretroviral effects60
|
Manufacturers state appropriate dosages for concomitant use with respect to safety and efficacy not established1
Some experts state adjustment of nevirapine dosage not needed; consider increasing indinavir dosage to 1 g every 8 hours or using ritonavir-boosted indinavir100 108
|
Pimozide
|
Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1
|
Concomitant use contraindicated1 108
|
Quinupristin and dalfopristin
|
Possible increased indinavir plasma concentrations169
| |
Ritonavir
|
Increased indinavir concentrations and increased ritonavir concentrations;1 5 44 108 concomitant low-dose ritonavir used to therapeutic advantage (ritonavir-boosted indinavir)108
Incidence of renal effects (nephrolithiasis) may be higher when ritonavir and indinavir used concomitantly compared with usual dosage of indinavir alone1
|
Limited data supports use of indinavir 400 mg twice daily with ritonavir 400 mg twice daily 108 174 180 or indinavir 800 mg twice daily with ritonavir 100 or 200 mg twice daily108 180
|
Saquinavir
|
Increased saquinavir concentrations;1 30 no effect on indinavir concentrations108
Data not available on concomitant use with ritonavir-boosted saquinavir30
|
Appropriate dosages for concomitant use with respect to safety and efficacy not established 1 30
|
St. John’s wort (Hypericum perforatum)
|
Decreased indinavir concentrations; possible loss of virologic response and increased risk of lopinavir resistance1
|
Concomitant use not recommended1 108
|
Sildenafil
|
Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1 108 154 170
|
Use caution and reduced sildenafil dosage (25 mg repeated no more frequently than every 48 hours);1 108 closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1 108
|
Stavudine
|
Clinically important pharmacokinetic interaction unlikely1 74 108
| |
Tadalafil
|
Increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1 108
|
Use an initial tadalafil dose of 5 mg and do not exceed a single tadalafil dose of 10 mg in 72 hours108
|
Tenofovir
|
Slight alterations in indinavir and tenofovir concentrations;108 d not clinically important108
In vitro evidence of additive or synergistic antiretroviral effectsd
|
No dosage adjustment needed108
|
Theophylline
|
Pharmacokinetic interactions unlikely1
| |
Tipranavir
|
Data not available to date108
|
Concomitant use not recommended; appropriate dosage not established108
|
Trazodone
|
Possible increased trazodone concentrations; increased risk of trazodone-associated adverse effects1 182
|
Caution; consider decreased trazodone dosage1 182
|
Vardenafil
|
Increased vardenafil concentrations and AUC and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection); decreased indinavir concentrations108 183
|
When using indinavir (without ritonavir), do not exceed a single vardenafil dosage of 2.5 mg in 24 hours;1 183 some experts recommend an initial vardenafil dosage of 2.5 mg in 72 hours108
|
Venlafaxine
|
Decreased indinavir concentrations; no change in venlafaxine concentrations1
|
Clinical importance unknown1
|
Vitamin C
|
Decreased indinavir concentrations with vitamin C dosage ≥1 g daily108
|
Monitor virologic response108
|
Zidovudine
|
Clinically important pharmacokinetic interactions unlikely1 108
In vitro evidence of synergistic antiretroviral effects1
| |
Indinavir Sulfate Pharmacokinetics
Absorption
Bioavailability
Well absorbed from GI tract; peak plasma concentrations attained within 1 hour.1 37 38
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
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 132 or children.125 134
Not known whether crosses the placenta or is distributed into human milk.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
Pharmacokinetics not studied in patients with severe hepatic impairment.1 AUC may be increased and 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 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 SpectrumActions
Pharmacologically related to other PIs (e.g., atazanavir, fosamprenavir, lopinavir, nelfinavir, ritonavir, saquinavir); 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
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 16 51
Varying degrees of cross-resistance occur among PIs; only limited data available to date regarding cross-resistance between indinavir and other PIs.1 4 5 7 9 10 11 13 39 168
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.1 Importance of using indinavir in conjunction with other antiretrovirals—not for monotherapy.1
Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.1 46 HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.1
Importance of taking on an empty stomach or with a light meal.1
Importance of drinking 1.5 L of liquids daily.1
Importance of storing indinavir in the original container; the desiccant should remain in the bottle.1
Importance of reading the patient package insert from the manufacturer.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.1
Importance of women informing clinicians if they are or plan to become pregnant or plan 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
|
| |
333 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 03/2011. 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/$1414.95
Crixivan 400MG Capsules (MERCK SHARP & DOHME): 90/$239.99 or 270/$719.98
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 2009. 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 & Company Inc. Crixivan (indinavir sulfate) capsules prescribing information. Whitehouse Station, NJ; 2008 Oct.
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]
5. Abbott Laboratories. Norvir (ritonavir) soft gelatin capsules and oral solution prescribing information. North Chicago, IL; 2001 Sept.
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.
7. Chen Z, Li Y, Schock HB et al. Three-dimensional structure of a mutant HIV-1 protease displaying cross-resistance to all protease inhibitors in clinical trials. J Biol Chem. 1995; 270:21433-6. [PubMed 7665551]
8. Condra JH, Holder DJ, Schleif WA et al. Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor. J Virol. 1996; 70:8270-6. [PubMed 8970946]
9. Tisdale M, Myers RE, Maschera B et al. Cross-resistance analysis of human immunodeficiency virus type 1 variants individually select
