right away Crixivan Generic Name: Indinavir Sulfate Class: HIV Protease Inhibitors VA Class: AM800 Chemical Name: [1S-[1α(R*),2α]]-2,3,5-trideoxy-N-(2,3-dihydro -2-hydroxy-1H-inden-1-yl)-5-[2-[[(1,1-dimethylethyl)amino]carbonyl]-4 -(3-pyridinylmethyl)-1-piperazinyl]-2-(phenylmethyl)-d-erythro-pentonamide sulfate (1:1) (salt) Molecular Formula: C 36 H 47 N 5 O 4 CAS Number: 157810-81-6 Overview Side Effects Dosage Professional Interactions More Pregnancy Warnings Breastfeeding Warnings User Reviews Drug Images Support Group Q & A Pricing & Coupons Introduction Antiretroviral; HIV protease inhibitor (PI). 1 2 3 6 7 Slideshow 10 Serious Infections That Will Make You Shudder Uses for Crixivan 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 Crixivan Dosage and Administration Administration Oral Administration Administer orally. 1 Administer with water 1 hour before or 2 hours after a meal. 1 Alternatively, administer with some other liquid (e.g., skim milk, juice, coffee, tea) or with a light meal (e.g., dry toast with jelly, apple juice, coffee with skim milk and sugar; corn flakes with skim milk and sugar). 1 Do not administer with a meal high in calories, fat, and protein. 1 To ensure adequate hydration, patients should drink at least 1.5 L (approximately 48 ounces) of liquids daily (i.e., every 24 hours). 1 4 Dosage Available as indinavir sulfate; dosage expressed as indinavir. 1 Pediatric Patients Treatment of HIV Infection Oral Optimal dosage not established. 1 (See Pediatric Use under Cautions.) Adults Treatment of HIV Infection Oral 800 mg every 8 hours. 1 If ritonavir-boosted indinavir is used, 800 mg twice daily with low-dose ritonavir (100 or 200 mg twice daily) has been recommended. 200 Special Populations Hepatic Impairment Treatment of HIV Infection Oral Mild to moderate hepatic impairment due to cirrhosis: 600 mg every 8 hours. 1 200 Renal Impairment Treatment of HIV Infection Oral Dosage adjustment not necessary. 200 Geriatric Patients Select dosage with caution. 1 Cautions for Crixivan Contraindications Known hypersensitivity to indinavir or any ingredient in the formulation. 1 Concomitant use with drugs highly dependent on CYP3A4 for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, alprazolam, amiodarone, cisapride, ergot alkaloids, oral midazolam, pimozide, sildenafil used for treatment of pulmonary arterial hypertension [PAH], triazolam, lovastatin, simvastatin). 1 (See Specific Drugs and Food under Interactions.) Warnings/Precautions Warnings Renal and GU Effects Nephrolithiasis/urolithiasis, 1 4 26 sometimes associated with substantial renal impairment, acute renal failure, or pyelonephritis with or without bacteremia, reported. 1 Adequate hydration recommended for all patients receiving indinavir. 1 Risk of nephrolithiasis/urolithiasis may be greater with ritonavir-boosted indinavir compared with indinavir (without low-dose ritonavir). 1 If signs and symptoms of nephrolithiasis/urolithiasis (flank pain, with or without hematuria or microscopic hematuria) occur, temporary interruption (e.g., for 1 3 days) or discontinuance of therapy may be considered. 1 Interstitial nephritis with medullary calcification and cortical atrophy reported in patients with asymptomatic severe leukocyturia ( 100 cells per high power field). 1 Monitor patients who have asymptomatic severe leukocyturia (i.e., perform frequent urinalysis); further diagnostic evaluation may be needed. 1 Consider discontinuing indinavir in patients with severe leukocyturia. 1 Interactions Concomitant use with certain drugs not recommended or requires particular caution. 1 (See Specific Drugs and Food under Interactions.) Hemolytic Anemia Acute hemolytic anemia, including fatalities, reported. 1 If acute hemolytic anemia occurs, take appropriate measures to treat the condition (including discontinuance of indinavir). 1 Hepatic Effects Acute hepatitis sometimes resulting in hepatic failure and death reported; causal relationship not established. 1 116 Generally has occurred in patients with confounding medical conditions and/or receiving concomitant drugs. 1 Elevated indirect bilirubin, infrequently associated with increased serum AST (SGOT) or ALT (SGPT) concentrations, reported. 1 4 17 23 Hyperglycemic Effects Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of PIs; diabetic ketoacidosis has occurred. 1 120 121 122 123 Monitor blood glucose and initiate or adjust dosage of oral hypoglycemic agent or insulin as needed. 1 General Precautions HIV Resistance Possibility of HIV resistance to indinavir and possible cross-resistance to other PIs. 1 Effect of indinavir therapy on subsequent therapy with other PIs under investigation. 1 Hemophilia A and B Spontaneous bleeding noted with PIs; causal relationship not established. 1 40 119 Use caution in patients with a history of hemophilia type A or B. 1 40 119 Increased hemostatic (e.g., antihemophilic factor) therapy may be needed. 1 Immune Reconstitution Syndrome During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis , cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii ]); 1 this may necessitate further evaluation and treatment. 1 Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy. 1 Adipogenic Effects Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement ( buffalo hump ), peripheral wasting, breast enlargement, and general cushingoid appearance. 1 Specific Populations Pregnancy Category C. 1 Antiretroviral Pregnancy Registry at 800-258-4263 or . 1 202 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. 202 In addition, data insufficient to recommend appropriate dosage of ritonavir-boosted indinavir for pregnant women. 202 Experts state indinavir (without low-dose ritonavir) not recommended at any time in pregnant women. 202 Substantially decreased plasma indinavir concentrations reported during pregnancy. 1 202 (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. 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. 1 202 Pediatric Use Only limited data available regarding use in pediatric patients. 1 When other HIV PIs cannot be used, consider limited data and increased risk of nephrolithiasis before using indinavir. 1 Hyperbilirubinemia reported in patients receiving indinavir; 1 4 17 23 201 because of risk associated with hyperbilirubinemia (kernicterus), some experts state do not use in neonates. 201 Has been used in a limited number of HIV-infected children 3 months of age. 1 124 125 151 152 166 173 201 Nephrolithiasis/urolithiasis reported more frequently in pediatric patients than in adults. 1 Geriatric Use Insufficient experience in those 65 years of age to determine whether they respond differently than younger adults. 1 Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. 1 Hepatic Impairment Dosage adjustment recommended in patients with hepatic impairment due to cirrhosis. 1 (See Hepatic Impairment under Dosage and Administration.) Common Adverse Effects Nausea, abdominal pain, headache, nephrolithiasis/urolithiasis, asymptomatic hyperbilirubinemia. 1 Interactions for Crixivan 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 hypotension 1 Concomitant use contraindicated 1 Antiarrhythmic agents (amiodarone, systemic lidocaine, quinidine) Possible increased antiarrhythmic agent concentrations; potential for serious and/or life-threatening effects 1 Amiodarone: Concomitant use contraindicated 1 Systemic lidocaine, quinidine: Use concomitantly with caution; monitor plasma antiarrhythmic concentrations 1 Anticoagulants, oral Rivaroxaban: Possible increased rivaroxaban concentrations; may increase bleeding risk 200 Warfarin: Possible altered warfarin concentrations 200 Rivaroxaban: Avoid concomitant use 200 Warfarin: Monitor INR, especially when initiating or discontinuing indinavir; adjust warfarin dosage as needed 200 Anticonvulsants (carbamazepine, phenobarbital, phenytoin) Possible decreased indinavir concentrations; possible decreased antiretroviral effectiveness 1 No change in plasma concentrations of carbamazepine 167 Carbamazepine, phenobarbital, phenytoin: Use concomitantly with caution 1 Antifungals, azoles (fluconazole, itraconazole, ketoconazole, voriconazole) Fluconazole: Decreased indinavir AUC; 74 145 no effect on fluconazole AUC 74 145 Itraconazole: Possible increased concentrations of both drugs 1 128 200 Ketoconazole: Increased indinavir concentrations 1 Voriconazole: No clinically important effect on pharmacokinetics of either drug 129 Fluconazole: Dosage adjustments not needed 145 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 dosage 200 Ketoconazole: Reduce indinavir dosage to 600 mg every 8 hours 1 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 concentrations 200 Antimycobacterials (bedaquiline, isoniazid, rifabutin, rifampin, rifapentine) Bedaquiline: Possible increased bedaquiline concentrations; 200 clinical importance unknown 200 Isoniazid: No change in indinavir AUC ; no clinically unimportant increases in isoniazid AUC 1 74 Rifabutin: Decreased indinavir concentrations and AUC; substantially increased rifabutin concentrations and AUC 1 Rifampin: Decreased indinavir concentrations; possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance 1 148 Rifapentine: Possible decreased indinavir concentrations 200 Bedaquiline: Use concomitantly with ritonavir-boosted indinavir with caution and only if potential benefits outweigh risks; 200 monitor for corrected QT (QT c ) interval prolongation and liver dysfunction 200 Isoniazid: Dosage adjustments not needed 1 Rifabutin: Increase indinavir dosage to 1 g every 8 hours and reduce rifabutin dosage to 50% of usual dosage 1 Rifampin: Concomitant use contraindicated 1 148 Rifapentine: Concomitant use not recommended 200 Antipsychotics (pimozide, quetiapine) Pimozide: Potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias) 1 Quetiapine: Increased quetiapine concentrations expected 200 Pimozide: Concomitant use contraindicated 1 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 200 Atazanavir Potential for additive hyperbilirubinemia 1 203 Concomitant use contraindicated 1 200 Avanafil Possible increased avanafil concentrations and AUC 188 Do not use concomitantly 188 Benzodiazepines Alprazolam, midazolam, triazolam: Pharmacokinetic interaction; potential for prolonged or increased sedation or respiratory depression 1 Diazepam: Possible increased diazepam concentrations 200 Oral midazolam, triazolam: Concomitant use contraindicated 1 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 sedation 200 Diazepam: Consider alternative benzodiazepine with less potential for pharmacokinetic interaction (e.g., lorazepam, oxazepam, temazepam) 200 Bosentan Possible increased bosentan concentrations 1 In patients already receiving indinavir, initiate bosentan at dosage of 62.5 mg once daily or every other day based on individual tolerability 1 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 200 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 1 Use concomitantly with caution; clinical monitoring recommended; 1 adjust dosage of the calcium-channel blocking agent based on clinical response and toxicities 200 Cisapride Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias) 1 Concomitant use contraindicated 1 Colchicine Increased colchicine concentrations 1 Patients with renal or hepatic impairment: Avoid concomitant use 1 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 1 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 1 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 expected 200 Budesonide or fluticasone (orally inhaled, intranasal): Increased corticosteroid concentrations; 200 may result in adrenal insufficiency or Cushing's syndrome 200 Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations; 200 may result in adrenal insufficiency or Cushing's syndrome 200 Budesonide or prednisone (systemic): Increased corticosteroid concentrations; 200 may result in adrenal insufficiency or Cushing's syndrome; 200 budesonide (systemic) may decrease indinavir concentrations 200 Dexamethasone (systemic): Possible decreased indinavir concentrations 200 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 effects 200 Dexamethasone (systemic): Use concomitantly with caution; 200 consider alternative corticosteroid for long-term use 200 Co-trimoxazole Interaction unlikely 1 Dosage adjustments not needed 1 Darunavir Ritonavir-boosted darunavir: Increased concentrations and AUCs of darunavir and indinavir 204 No in vitro evidence of antagonistic antiretroviral effects 204 Ritonavir-boosted darunavir: Appropriate dosages for concomitant use with indinavir not established 204 Delavirdine Delavirdine inhibits indinavir metabolism and may increase indinavir concentrations and AUC; no effect on delavirdine pharmacokinetics 1 144 Use reduced indinavir dosage of 600 mg every 8 hours with usual delavirdine dosage of 400 mg 3 times daily 1 212 Didanosine Buffered didanosine (Videx ): Substantially decreased indinavir concentrations and AUC if administered simultaneously 147 Didanosine delayed-release capsules (Videx EC): No effect on indinavir concentrations and AUC 217 In vitro evidence of synergistic antiretroviral effects 1 Buffered didanosine (Videx ): Administer 1 hour after indinavir 147 Efavirenz Decreased indinavir AUC; no clinically important effect on efavirenz concentrations or AUC 1 213 In vitro evidence of additive antiretroviral effects 213 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 1 213 Emtricitabine No effect on pharmacokinetics of either drug 218 Enfuvirtide In vitro evidence of additive to synergistic antiretroviral effects 223 Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine) Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity) 1 Concomitant use contraindicated 1 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 201 Estrogens/Progestins Oral hormonal contraceptives: Increased AUC of ethinyl estradiol and norethindrone reported 1 Etravirine Indinavir (without low-dose ritonavir): Possible decreased indinavir concentrations 214 No in vitro evidence of antagonistic antiretroviral effects 214 Do not use concomitantly without low-dose ritonavir 214 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 205 In vitro evidence of additive antiretroviral effects 205 Fosamprenavir (with or without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established 205 Grapefruit juice Decreased indinavir AUC and concentrations 1 Histamine H 2 -receptor antagonists (cimetidine) Pharmacokinetic interaction unlikely with cimetidine 1 Dosage adjustment not needed 1 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 1 Atorvastatin: Carefully titrate atorvastatin dosage and use lowest necessary dosage 1 Lovastatin: Concomitant use contraindicated 1 Pitavastatin: Dosage adjustments not needed 200 Rosuvastatin: Carefully titrate rosuvastatin dosage and use lowest necessary dosage 1 Simvastatin: Concomitant use contraindicated 1 Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus) Cyclosporine, sirolimus, tacrolimus: Possible increased concentrations of the immunosuppressive agent 1 Monitor concentrations of the immunosuppressive agent 200 Lamivudine Concomitant use of lamivudine, zidovudine, and indinavir: Increased indinavir concentrations and AUC and decreased lamivudine concentrations and AUC 1 Lopinavir/ritonavir Increased indinavir concentrations 207 207 In vitro evidence of additive to synergistic antiretroviral effects 207 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 207 Macrolides (clarithromycin) Increased indinavir and clarithromycin AUCs 1 Appropriate dosages for concomitant use with respect to safety and efficacy not established 1 Maraviroc No in vitro evidence of antagonistic antiretroviral effects 224 Recommended maraviroc dosage is 150 mg twice daily 224 Methadone Indinavir (without low-dose ritonavir): Pharmacokinetic interactions unlikely 1 200 Ritonavir-boosted indinavir: Opiate withdrawal is unlikely, but may occur 200 Indinavir (without low-dose ritonavir): Dosage adjustments not needed 200 Ritonavir-boosted indinavir: Monitor for opioid withdrawal and increase methadone dosage as clinically indicated 200 Nelfinavir Increased AUCs of both drugs 208 In vitro evidence of antagonistic antiretroviral effects 209 Appropriate dosages for concomitant use with respect to safety and efficacy not established 1 208 Nevirapine Decreased indinavir concentrations and AUC 215 In vitro evidence of additive to synergistic antiretroviral effects 215 Appropriate dosages for concomitant use with respect to safety and efficacy not established 1 215 Quinupristin and dalfopristin Possible increased indinavir concentrations 169 Raltegravir In vitro evidence of additive to synergistic antiretroviral effects 225 Rilpivirine Possible increased rilpivirine concentrations; not expected to affect indinavir concentrations 226 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 alone 1 Ritonavir-boosted indinavir: Some experts suggest indinavir 800 mg twice daily with ritonavir 100 or 200 mg twice daily 200 St. John s wort ( Hypericum perforatum ) Decreased indinavir concentrations; possible loss of virologic response and increased risk of indinavir resistance 1 Concomitant use not recommended 1 Saquinavir Substantially increased saquinavir concentrations 1 210 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 tachycardia 1 Concomitant use not recommended 1 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 established 1 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 concentrations 187 Concomitant use not recommended 187 200 Stavudine No clinically important change in indinavir concentrations or AUC; decreased concentrations and increased AUC of stavudine 1 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 tolerability 1 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 daily 200 Tenofovir Slight increase in tenofovir concentrations and decrease in indinavir concentrations; no effect on AUC of either drug 221 In vitro evidence of additive to synergistic antiretroviral effects 221 Theophylline Pharmacokinetic interactions unlikely 1 Trazodone Possible increased trazodone concentrations; 1 nausea, dizziness, hypotension, and syncope reported when trazodone and ritonavir were used concomitantly 1 Use concomitantly with caution; consider decreased trazodone dosage 1 Tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline) Increased concentrations of tricyclic antidepressant expected 200 Use lowest possible antidepressant dosage in patients receiving ritonavir-boosted indinavir; 200 titrate antidepressant dosage based on clinical assessment and/or antidepressant concentrations 200 Vardenafil Increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection); decreased indinavir concentrations 1 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 concentrations 1 Clinical importance unknown 1 Zidovudine Slightly increased indinavir concentrations and AUC; slightly increased zidovudine AUC and decreased zidovudine peak concentrations 1 In vitro evidence of synergistic antiretroviral effects 1 Crixivan Pharmacokinetics Absorption Bioavailability Well absorbed from GI tract; peak plasma concentrations attained within 1 hour. 37 38 1 Food Presence of food in the GI tract can substantially decrease the extent of absorption of oral indinavir. 1 38 Administration with a substantial meal (48.6 g fat, 31.3 g protein; 784 kcal) decreases AUC and peak plasma concentrations by 77 and 84%, respectively; administration with a light meal (e.g., dry toast with jelly, apple juice, coffee with skim milk and sugar; corn flakes with skim milk and sugar) is not associated with clinically important changes in AUC or peak or trough plasma concentrations. 1 135 Special Populations Pediatric patients: Limited data indicate pharmacokinetic profile not comparable to that reported in adults. 1 Hepatic impairment: AUC 60% higher in adults with cirrhosis and mild to moderate hepatic impairment compared with adults with normal hepatic function. 1 Pregnant women: AUC 74% lower in pregnant women receiving indinavir (without low-dose ritonavir) compared with nonpregnant patients. 1 Distribution Extent Not fully characterized. 65 Distributed into CSF in low concentration in adults 21 or children. 125 132 134 When used without low-dose ritonavir in pregnant women, only minimal amounts of indinavir crossed the placenta. 202 Not known whether distributed into human milk; 1 202 distributed into milk in rats. 1 202 Plasma Protein Binding 60%. 1 Elimination Metabolism Metabolized by CYP3A4. 1 Elimination Route Excreted principally in the feces (83%) as unabsorbed drug or metabolites. 1 Half-life 1.8 hours. 1 37 38 Special Populations Half-life prolonged in patients with hepatic impairment. 1 Half-life of 2.8 hours reported in adults with cirrhosis and mild to moderate hepatic impairment. 1 Pharmacokinetics not studied in patients with severe hepatic impairment. 1 Pharmacokinetics not studied in renal impairment. 1 Stability Storage Oral Capsules 15 30 C in tightly closed containers. 1 Protect from moisture. 1 Dispense and store in original container; the desiccant should remain in the original bottle. 1 Actions and Spectrum 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 antiretrovirals not for monotherapy. 1 Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur. 1 Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others. 200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles. 1 200 Importance of reading patient information provided by the manufacturer. 1 Importance of taking on an empty stomach or with a light meal. 1 Importance of drinking 1.5 L of liquids daily. 1 Advise patients that if a dose is missed, take the next dose at regularly scheduled time. 1 Do not take a double dose to make up for the missed dose. 1 Importance of storing indinavir in the original container; the desiccant should remain in the bottle. 1 Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products (e.g., St. John s wort), and any concomitant illnesses. 1 Advise patients receiving selective phosphodiesterase type 5 (PDE5) inhibitors (e.g., avanafil, sildenafil, tadalafil, vardenafil) that they may be at increased risk of PDE5 inhibitor-associated adverse effects (e.g., hypotension, syncope, visual disturbances, priapism) and that any symptoms should be promptly reported to their clinician. 1 188 Indinavir should not be used in patients receiving avanafil for treatment of erectile dysfunction 188 or sildenafil for treatment of PAH. 1 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Advise HIV-infected women not to breast-feed. 1 Importance of advising patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the AS most recent
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