Indinavir_Sulfate: profile and news

Merck Announces New Unisured Discount Program Targeted to More ... Oct 7, 2005
...programs for a number of other prescription medicines, including CANCIDAS(R) (caspofungin acetate) for Injection, CRIXIVAN(R) (indinavir sulfate) Capsules, and ... - Hispanic PR Wire (press release),

FDA Approvals: Naglazyme, Trizivir, Levaquin Aug 11, 2005
...from a multicenter, double-blind study in which 562 therapy-naive adults were randomized to receive either abacavir sulfate or indinavir sulfate in addition to ... - Medscape (subscription)

Merck Announces New Unisured Discount Program Targeted to More ... Apr 19, 2005
...programs for a number of other prescription medicines, including CANCIDAS(R) (caspofungin acetate) for Injection, CRIXIVAN(R) (indinavir sulfate) Capsules, and ... - Hispanic PR Wire

Governor Tom Vilsack Supports New Merck Uninsured Discount Program ... Apr 20, 2005
...for a number of other prescription medicines, including CANCIDAS(R) (caspofungin acetate) for Injection, CRIXIVAN(R) (indinavir sulfate) Capsules, EMEND(R ... - PR Newswire

American Pharmaceutical Group Welcomes Framework for Industry ... Mar 30, 2005
Merck has provided its antiretrovirals, CRIXIVAN (indinavir sulfate) and STOCRIN (efavirenz), to the poorest countries and those hardest hit by the HIV ... - mysan.de (Pressemitteilung),

Other information

Indication
For the treatment of HIV infection

Pharmacology
Indinavir 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. 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. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Mechanism Of Action
Indinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

Drug Category
Anti-HIV Agents; ATC:J05AE02

Brand Names/Synonyms
Compound J; Crixivan; Indinavir; Indinavir Sulfate; Indinavir [Usan]

Dosage Forms
Oral capsules

Absorption
Rapidly absorbed

Interactions
-->Interactions for Indinavir:

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.

Table 8
Drugs That Should Not Be Coadministered with CRIXIVAN
Drug Class:	Drug Name Clinical Comment
Antiarrhythmics: amiodarone	CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
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.
Sedative/hypnotics: midazolam, triazolam	CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression.
GI motility agents: cisapride	CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Neuroleptic: pimozide	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.
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.
HMG-CoA Reductase inhibitors: lovastatin, simvastatin	Potential for serious reactions such as risk of myopathy including rhabdomyolysis.
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.

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
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.
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.
HMG-CoA Reductase Inhibitor: atorvastatin	↑ atorvastatin concentration	Use lowest possible dose of atorvastatin with careful monitoring, or consider HMG-CoA reductase inhibitors that are not primarily metabolized by CYP3A4, such as pravastatin, fluvastatin, or rosuvastatin in combination with CRIXIVAN.
Immunosuppressants: cyclosporine, tacrolimus, sirolimus	↑ immunosuppressant agents concentration	Plasma concentrations may be increased by CRIXIVAN.
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.
Rifabutin	¯ indinavir concentration ↑ rifabutin concentration	Dose reduction of rifabutin to half the standard dose and a dose increase of CRIXIVAN to 1000 mg (three 333-mg capsules) every 8 hours are recommended when rifabutin and CRIXIVAN are coadministered.
Sildenafil	↑ sildenafil concentration	Sildenafil dose should not exceed a maximum of 25 mg in a 48- hour period in patients receiving concomitant indinavir therapy.
Tadalafil	↑ tadalafil concentration	Tadalafil dose should not exceed a maximum of 10 mg in a 72- hour period in patients receiving concomitant indinavir therapy.
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.
Note: ↑ = increase; ¯ = decrease

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Chemical IUPAC Name
1-[2-hydroxy-4-[(2-hydroxy-2,3-dihydro-1H-inden-1-yl)carbamoyl]-5-phenyl-pentyl]-4-(pyridin-3-ylmethyl)-N-tert-butyl-piperazine-2-carboxamide

Chemical Formula
C36H47N5O4

Half Life
1.8 (+/- 0.4) hours

Drug Type
Approved Drug

# Accession No
APRD00069

CAS Registry Number
150378-17-9