Indinavir Sulfate (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- CRIXIVAN
Indications and Usage
CRIXIVAN in combination with antiretroviral agents is indicated for the treatment of HIV infection. This indication is based on two clinical trials of approximately 1 year duration that demonstrated: 1) a reduction in the risk of AIDS-defining illnesses or death; 2) a prolonged suppression of HIV RNA.
Dosage and Administration
The recommended dosage of CRIXIVAN is 800 mg (usually two 400-mg capsules) orally every 8 hours. CRIXIVAN must be taken at intervals of 8 hours. For optimal absorption, CRIXIVAN should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, CRIXIVAN may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal, e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; or corn flakes, skim milk and sugar. (See CLINICAL PHARMACOLOGY, Effect of Food on Oral Absorption.) To ensure adequate hydration, it is recommended that adults drink at least 1.5 liters (approximately 48 ounces) of liquids during the course of 24 hours.
Contraindications
CRIXIVAN is contraindicated in patients with clinically significant hypersensitivity to any of its components. Inhibition of CYP3A4 by CRIXIVAN can result in elevated plasma concentrations of the following drugs, potentially causing serious or life-threatening reactions: Table 7: Drug Interactions With Crixivan: Contraindicated Drugs Drug Class Drugs Within Class That Are Contraindicated With CRIXIVAN Alpha 1-adrenoreceptor antagonist alfuzosin Antiarrhythmics amiodarone Ergot derivatives dihydroergotamine, ergonovine, ergotamine, methylergonovine GI motility agents cisapride HMG-CoA Reductase Inhibitors lovastatin, simvastatin Neuroleptics pimozide PDE5 Inhibitors RevatioRegistered trademark of Pfizer, Inc. (sildenafil) [for treatment of pulmonary arterial hypertension] Sedative/hypnotics oral midazolam, triazolam, alprazolam
Drug Interactions
(also see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, Drug Interactions) 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). Based on in vitro data in human liver microsomes, indinavir does not inhibit CYP1A2, CYP2C9, CYP2E1 and CYP2B6. However, indinavir may be a weak inhibitor of CYP2D6. 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. Drug interaction studies were performed with CRIXIVAN and other drugs likely to be coadministered and some drugs commonly used as probes for pharmacokinetic interactions. The effects of coadministration of CRIXIVAN on the AUC, Cmax and Cmin are summarized in Table 2 (effect of other drugs on indinavir) and Table 3 (effect of indinavir on other drugs). For information regarding clinical recommendations, see Table 9 in PRECAUTIONS. Table 2: Drug Interactions: Pharmacokinetic Parameters for Indinavir in the Presence of the Coadministered Drug (See PRECAUTIONS, Table 9 for Recommended Alterations in Dose or Regimen) Coadministered drug Dose of Coadministered drug (mg) Dose of CRIXIVAN (mg) n Ratio (with/without coadministered drug) of IndinavirPharmacokinetic Parameters (90% CI); No Effect = 1.00 Cmax AUC Cmin All interaction studies conducted in healthy, HIV-negative adult subjects, unless otherwise indicated. Cimetidine 600 twice daily, 6 days 400 single dose 12 1.07(0.77, 1.49) 0.98(0.81, 1.19) 0.82(0.69, 0.99) Clarithromycin 500 q12h, 7 days 800 three times daily, 7 days 10 1.08 (0.85,
Mechanism of Action
HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Indinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles.
Overdosage
There have been more than 60 reports of acute or chronic human overdosage (up to 23 times the recommended total daily dose of 2400 mg) with CRIXIVAN. The most commonly reported symptoms were renal (e.g., nephrolithiasis/urolithiasis, flank pain, hematuria) and gastrointestinal (e.g., nausea, vomiting, diarrhea). It is not known whether CRIXIVAN is dialyzable by peritoneal or hemodialysis.