Indinavir is an inhibitor of the cytochrome P450 isoform CYP3A4. Coadministration of CRIXIVAN and drugs primarily metabolized by CYP3A4 may result in increased plasma concentrations of the other drug, which could increase or prolong its therapeutic and adverse effects (see CONTRAINDICATIONS and WARNINGS). Indinavir is metabolized by CYP3A4. Drugs that induce CYP3A4 activity would be expected to increase the clearance of indinavir, resulting in lowered plasma concentrations of indinavir. Coadministration of CRIXIVAN and other drugs that inhibit CYP3A4 may decrease the clearance of indinavir and may result in increased plasma concentrations of indinavir. Table 8: Drugs That Should Not Be Coadministered with CRIXIVAN
Drug Class: Drug Name Clinical Comment Alpha 1-adrenoreceptor antagonist: alfuzosin Potentially increased alfuzosin concentrations can result in hypotension. Antiarrhythmics: amiodarone CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. Antimycobacterial: rifampin May lead to loss of virologic response and possible resistance to CRIXIVAN or to the class of protease inhibitors or other coadministered antiretroviral agents. Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. GI motility agents: cisapride CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. Herbal products: St. John’s wort (Hypericum perforatum) May lead to loss of virologic response and possible resistance to CRIXIVAN or to the class of protease inhibitors. HMG-CoA Reductase inhibitors: lovastatin, simvastatin CONTRAINDICATED due to an increased risk for serious reactions such as myopathy including rhabdomyolysis. Neuroleptic: pimozide CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. PDE5 inhibitor: Revatio (sildenafil) [for treatment of pulmonary arterial hypertension] A safe and effective dose has not been established when used with CRIXIVAN. There is increased potential for sildenafil-associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope). Protease inhibitor: atazanavir Both CRIXIVAN and atazanavir are associated with indirect (unconjugated) hyperbilirubinemia. Combinations of these drugs have not been studied and coadministration of CRIXIVAN and atazanavir is not recommended. Sedative/hypnotics: Oral midazolam, triazolam, alprazolam CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Table 9: Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction (See also CLINICAL PHARMACOLOGY for magnitude of interaction, WARNINGS and DOSAGE AND ADMINISTRATION.)
Drug Name Effect Clinical Comment HIV Antiviral Agents Delavirdine ↑ indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered when taking delavirdine 400 mg three times a day. Didanosine Indinavir and didanosine formulations containing buffer should be administered at least one hour apart on an empty stomach. Efavirenz ↓indinavir concentration The optimal dose of indinavir, when given in combination with efavirenz, is not known. Increasing the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to efavirenz. Nelfinavir ↑ indinavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Nevirapine ↓ indinavir concentration Indinavir concentrations may be decreased in the presence of nevirapine. The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Ritonavir ↑indinavir concentration
↑ritonavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Preliminary clinical data suggest that the incidence of nephrolithiasis is higher in patients receiving indinavir in combination with ritonavir than those receiving CRIXIVAN 800 mg q8h. Saquinavir ↑ saquinavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Other Agents Antiarrhythmics: bepridil, lidocaine (systemic) and quinidine ↑antiarrhythmic agents concentration Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics when coadministered with CRIXIVAN. Anticonvulsants: carbamazepine, phenobarbital, phenytoin ↓ indinavir concentration Use with caution. CRIXIVAN may not be effective due to decreased indinavir concentrations in patients taking these agents concomitantly. Antidepressant: Trazodone ↑trazodone concentration Concomitant use of trazodone and CRIXIVAN may increase plasma concentrations of trazodone. Adverse events of nausea, dizziness, hypotension and syncope have been observed following coadministration of trazodone and ritonavir. If trazodone is used with a CYP3A4 inhibitor such as CRIXIVAN, the combination should be used with caution and a lower dose of trazodone should be considered. Anti-gout: Colchicine ↑colchicine concentration Patients with renal or hepatic impairment should not be given colchicine with CRIXIVAN.
Treatment of gout flares:
Co-administration of colchicine in patients on CRIXIVAN: 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days.
Prophylaxis of gout flares:
Co-administration of colchicine in patients on CRIXIVAN:
If the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original colchicine regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.
Treatment of familial Mediterranean fever (FMF):
Co-administration of colchicine in patients on CRIXIVAN: Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day). Calcium Channel Blockers, Dihydropyridine: e.g., felodipine, nifedipine, nicardipine ↑ dihydropyridine calcium channel blockers concentration Caution is warranted and clinical monitoring of patients is recommended. Clarithromycin ↑clarithromycin concentration
↑indinavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Endothelin receptor antagonist: Bosentan ↑bosentan concentration Co-administration of bosentan in patients on CRIXIVAN or coadministration of CRIXIVAN in patients on bosentan: Start at or adjust bosentan to 62.5 mg once daily or every other day based upon individual tolerability. HMG-CoA Reductase Inhibitors: atorvastatin, rosuvastatin ↑atorvastatin concentration
↑rosuvastatin concentration The atorvastatin and rosuvastatin doses should be carefully titrated; use the lowest dose necessary with careful monitoring during treatment with CRIXIVAN. Immunosuppressants: cyclosporine, tacrolimus, sirolimus ↑immunosuppressant agents concentration Plasma concentrations may be increased by CRIXIVAN. Inhaled beta agonist: Salmeterol ↑salmeterol Concurrent administration of salmeterol with CRIXIVAN is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia. Inhaled/nasal steroid: Fluticasone ↑fluticasone concentration Concomitant use of fluticasone propionate and CRIXIVAN may increase plasma concentrations of fluticasone propionate. Use with caution. Consider alternatives to fluticasone propionate, particularly for long-term use.
Fluticasone use is not recommended in situations where CRIXIVAN is coadministered with a potent CYP3A4 inhibitor such as ritonavir unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. Itraconazole ↑indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours is recommended when administering itraconazole concurrently. Ketoconazole ↑ indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered. Midazolam (parenteral administration) ↑midazolam concentration Concomitant use of parenteral midazolam with CRIXIVAN may increase plasma concentrations of midazolam. Coadministration should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. Coadministration of oral midazolam with CRIXIVAN is CONTRAINDICATED (see Table 8). Rifabutin ↓ indinavir concentration ↑rifabutin concentration Dose reduction of rifabutin to half the standard dose and a dose increase of CRIXIVAN to 1000 mg every 8 hours are recommended when rifabutin and CRIXIVAN are coadministered. Sildenafil ↑ sildenafil concentration (only the use of sildenafil at doses used for treatment of erectile dysfunction has been studied with CRIXIVAN) May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, syncope, visual disturbances, and priapism.
Use of sildenafil for pulmonary arterial hypertension (PAH):
Use of Revatio (sildenafil) is contraindicated when used for the treatment of pulmonary arterial hypertension (PAH) [see CONTRAINDICATIONS].
Use of sildenafil for erectile dysfunction:
Sildenafil dose should not exceed a maximum of 25 mg in a 48-hour period in patients receiving concomitant CRIXIVAN therapy. Use with increased monitoring for adverse events. Tadalafil ↑ tadalafil concentration May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, visual disturbances, and priapism.
Use of tadalafil for pulmonary arterial hypertension (PAH):
The following dose adjustments are recommended for use of Adcirca (tadalafil) with CRIXIVAN:
Co-administration of Adcirca in patients on CRIXIVAN or coadministration of CRIXIVAN in patients on Adcirca:
Start at or adjust Adcirca to 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
Use of tadalafil for erectile dysfunction:
Tadalafil dose should not exceed a maximum of 10 mg in a 72-hour period in patients receiving concomitant CRIXIVAN therapy. Use with increased monitoring for adverse events. Vardenafil ↑vardenafil concentration Vardenafil dose should not exceed a maximum of 2.5 mg in a 24-hour period in patients receiving concomitant indinavir therapy. Venlafaxine ↓ indinavir concentration In a study of 9 healthy volunteers, venlafaxine administered under steady-state conditions at 150 mg/day resulted in a 28% decrease in the AUC of a single 800 mg oral dose of indinavir and a 36% decrease in indinavir Cmax. Indinavir did not affect the pharmacokinetics of venlafaxine and ODV. The clinical significance of this finding is unknown. Read the Crixivan Drug Interactions Center for a complete guide to possible interactions Learn More »