Crixivan

Crixivan - General Information

A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [PubChem]

Pharmacology of Crixivan

Crixivan is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. 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. Crixivan 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. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Crixivan for patients

A statement to patients and health care providers is included on the product’s bottle label. ALERT: Find out about medicines that should NOT be taken with CRIXIVAN. A Patient Package Insert (PPI) for CRIXIVAN is available for patient information.

CRIXIVAN is not a cure for HIV infection and patients may continue to develop opportunistic infections and other complications associated with HIV disease. The long-term effects of CRIXIVAN are unknown at this time. CRIXIVAN has not been shown to reduce the risk of transmission of HIV to others through sexual contact or blood contamination.

Patients should be advised to remain under the care of a physician when using CRIXIVAN and should not modify or discontinue treatment without first consulting the physician. Therefore, if a dose is missed, patients should take the next dose at the regularly scheduled time and should not double this dose. Therapy with CRIXIVAN should be initiated and maintained at the recommended dosage.

CRIXIVAN may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St. John’s wort.

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. Ingestion of CRIXIVAN with a meal high in calories, fat, and protein reduces the absorption of indinavir.

Patients receiving a phosphodiesterase type 5 (PDE5) inhibitor (sildenafil, tadalafil, or vardenafil) should be advised that they may be at an increased risk of PDE5 inhibitor-associated adverse events including hypotension, visual changes, and priapism, and should promptly report any symptoms to their doctors.

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

CRIXIVAN Capsules are sensitive to moisture. Patients should be informed that CRIXIVAN should be stored and used in the original container and the desiccant should remain in the bottle.

Crixivan 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.

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.

Crixivan 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:

Additional information about Crixivan

Crixivan Indication: For the treatment of HIV infection.
Mechanism Of Action: Crixivan inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Drug Interactions: Alprazolam The protease inhibitor increases the effect of the benzodiazepine
Chlordiazepoxide The protease inhibitor increases the effect of the benzodiazepine
Clonazepam The protease inhibitor increases the effect of the benzodiazepine
Clorazepate The protease inhibitor increases the effect of the benzodiazepine
Diazepam The protease inhibitor increases the effect of the benzodiazepine
Estazolam The protease inhibitor increases the effect of the benzodiazepine
Flurazepam The protease inhibitor increases the effect of the benzodiazepine
Halazepam The protease inhibitor increases the effect of the benzodiazepine
Midazolam The protease inhibitor increases the effect of the benzodiazepine
Prazepam The protease inhibitor increases the effect of the benzodiazepine
Quazepam The protease inhibitor increases the effect of the benzodiazepine
Triazolam The protease inhibitor increases the effect of the benzodiazepine
Warfarin The protease inhibitor increases the anticoagulant effect
Acenocoumarol The protease inhibitor increases the anticoagulant effect
Dicumarol The protease inhibitor increases the anticoagulant effect
Anisindione The protease inhibitor increases the anticoagulant effect
Vardenafil The protease inhibitor increases the effect and toxicity of vardenafil
Cyclosporine The protease inhibitor increases the effect of cyclosporine
Fentanyl The protease inhibitor increases the effect and toxicity of fentanyl
Pimozide The protease inhibitor increases the effect and toxicity of pimozide
Sildenafil The protease inhibitor increases the effect and toxicity of sildenafil
Vitamin C Vitamin C decreases indinavir levels
Trazodone This strong CYP3A4 inhibitor increases the effect and toxicity of trazodone
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Astemizole Increased risk of cardiotoxicity and arrhythmias
Cisapride Increased risk of cardiotoxicity and arrhythmias
Delavirdine Delavirdine increases the effect of indinavir
Clarithromycin Clarithromycin increases the effect and toxicity of indinavir
Carbamazepine Crixivan increases the effect and toxicity of carbamazepine
Atorvastatin Increases the effect and toxicity of atorvastatin
Amiodarone Crixivan increases the effect and toxicity of amiodarone
Efavirenz Efavirenz decreases the effect of indinavir
Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib
Esomeprazole Omeprazole decreases the absorption of indinavir
Omeprazole Omeprazole decreases the absorption of indinavir
Lansoprazole Omeprazole decreases the absorption of indinavir
Pantoprazole Omeprazole decreases the absorption of indinavir
Rabeprazole Omeprazole decreases the absorption of indinavir
Fusidic Acid Increases the effect and toxicity of fusidic acid
Ketoconazole Ketoconazole increases the efefct of indinavir
Ranolazine Increased levels of ranolazine - risk of toxicity
Rifabutin Rifabutin decreases the effect of indinavir
Rifampin Rifampin decreases the effect of indinavir
St. John's Wort St. John's Wort decreases the effect of indinavir
Sunitinib Possible increase in sunitinib levels
Tacrolimus Increases the effect and toxicity of tacrolimus
Saquinavir Possible antagonism of action
Risperidone Increased risk of extrapyramidal symptoms
Quinupristin This combination presents an increased risk of toxicity
Aluminium The antacid decreases the absorption of indinavir
Atazanavir Increased risk of hyperbilirubinemia with this association
Bismuth The antacid decreases the absorption of indinavir
Calcium The antacid decreases the absorption of indinavir
Magnesium oxide The antacid decreases the absorption of indinavir
Magnesium The antacid decreases the absorption of indinavir
Ergotamine Increases the effect and toxicity of the ergot derivative
Dihydroergotamine Increases the effect and toxicity of the ergot derivative
Food Interactions: Take on empty stomach: 1 hour before or 2 hours after meals.
Take with a full glass of water.
Avoid taking with grapefruit juice
Avoid excessive or chronic alcohol use.
Generic Name: Indinavir
Synonyms: Indinavir sulfate; Compound J
Drug Category: Anti-HIV Agents
Drug Type: Small Molecule; Approved

Other Brand Names containing Indinavir: Crixivan;
Absorption: Rapidly absorbed
Toxicity (Overdose): Symptoms of overdose include myocardial infarction and angina pectoris.
Protein Binding: 60%
Biotransformation: Hepatic. Seven metabolites have been identified, one glucuronide conjugate and six oxidative metabolites. In vitro studies indicate that cytochrome P-450 3A4 (CYP3A4) is the major enzyme responsible for formation of the oxidative metabolites.
Half Life: 1.8 (± 0.4) hours
Dosage Forms of Crixivan: Capsule Oral
Chemical IUPAC Name: (2S)-N-tert-butyl-1-[(2S,4R)-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxo-4-(phenylmethyl)pentyl]-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide
Chemical Formula: C36H47N5O4
Indinavir on Wikipedia: https://en.wikipedia.org/wiki/Indinavir
Organisms Affected: Human Immunodeficiency Virus