Indinavir: profile and news

A different kind of prescription Mar 3, 2006
HIV patients on the protease inhibitor indinavir, for example, saw the level of the drug in their systems suppressed when they took the mild depression ... - Baltimore Sun,

CROI: Low rates of resistance seen in Staccato trial of CD4-guided ... Feb 26, 2006
...resistant virus contained two mutations in the protease gene (M36I and M46I), which would result in resistance to the protease inhibitor indinavir (Crixivan). ... - Aidsmap,

Boehringer Ingelheim Announces 48-week Results from Aptivus ... Feb 10, 2006
CPIs included lopinavir, saquinavir, amprenavir and indinavir. ... The comparator PIs were lopinavir, indinavir, saquinavir and amprenavir. ... - DG News

Gilead Sciences Welcomes Guidance From Nice On Treatment Of ... Feb 22, 2006
At doses of adefovir dipivoxil from 60 mg to 120 mg, no interactions with zidovudine, nelfinavir, nevirapine, indinavir, efavirenz, delaviridine, or lamivudine ... - Medical News Today (press release),

Schering-Plough Presents Vicriviroc Clinical Study Results at 13th ... Feb 10, 2006
...researchers. Vicriviroc was studied in combination with ritonavir-boosted atazanavir, fosamprenavir, indinavir, nelfinavir, and saquinavir. ... - DG News

Multi-component drug delivery system: An emerging trend Feb 8, 2006
Protease Inhibitors (PIs), which include amprenavir (Agenerase), nelfinavir (Viracept), saquinavir (Fortavase), indinavir (Crixivan), ritonavir (Norvir ... - Express Pharma Pulse,

Advances in First-Line and "Switch" Antiretroviral Strategies for ... Feb 2, 2006
A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic ... - Medscape (subscription)

Boehringer Ingelheim Announces 48-week Results from Aptivus(R) ... 09 Feb 2006
CPIs included lopinavir, saquinavir, amprenavir and indinavir. ... The comparator PIs were lopinavir, indinavir, saquinavir and amprenavir. ... - PR Newswire (press release),

Reduce platelet aggregation, blood clotting, inflammation, nervous ... Jan 12, 2006
It cannot be used together with the anti-Aids drug indinavir, or cyclosporine, used to treat some auto immune disease like systemic lupus erythematosis and to ... - Health24.com,

HIV Virus Emerging Drug Resistant In UK, Prompting Fear Of A ... Nov 18, 2005
The currently available drugs are Zidovudine, Stavudine, Lamivudine, Abacavir, Indinavir, Efavirenz, Nevirapine and Didanosine. ... - MedIndia,

The overuse of Tamiflu in treating avian flu Dec 2, 2005
Three or four antiretrovirals (ao zidovudine, didanosine, nefirapine, and indinavir) have been contributing modestly to the treatment of HIV-positive patients. ... - Jakarta Post,

Tipranavir continues to show benefit in treatment-experienced ... Nov 30, 2005
This consisted of the best option, based on resistance testing, from a choice of ritonavir-boosted lopinavir (Kaletra), indinavir (Crixivan), saquinavir ... - Aidsmap,

Interleukin-2 has short-lived negative impact on quality of life Dec 1, 2005
All of the patients took an anti-HIV drug combination of indinavir (Crixivan) and two nucleoside reverse transcriptase inhibitors (NRTIs) for twelve weeks. ... - Aidsmap,

Study of nucleoside-sparing regimens stopped early due to high ... Nov 22, 2005
PI) regimens. The NNRTI and PI drugs were restricted to boosted efavirenz or nevirapine plus boosted lopinavir or indinavir. All ... - Aidsmap,

APTIVUS(R) Sustains Convincing Anti-HIV Nov 21, 2005
...comparator protease inhibitors (PIs) that included lopinavir/r (Kaletra(R)), amprenavir/r (Agenerase(R)), saquinavir/r (Invirase(R)) and indinavir/r (Crixivan(R ... - APA OTS (Pressemitteilung),

Once-daily boosted saquinavir has low blood levels when used with ... Nov 11, 2005
...inhibitors, and it is known that rifampicin can reduce blood levels of â€œunboostedâ€? protease inhibitors, such as saquinavir, indinavir, nelfinavir and ... - Aidsmap,

Boehringer Ingelheim Announces 48-Week Results from Aptivus(R) ... Nov 21, 2005
...response based on resistance testing. The comparator PIs were lopinavir, indinavir, saquinavir and amprenavir. In addition, patients in ... - Yahoo! News (press release)

Aptivus Sustains Convincing Anti-HIV Effect Through 48 Weeks Nov 21, 2005
...comparator protease inhibitors (PIs) that included lopinavir/r (KaletraÂ®), amprenavir/r (AgeneraseÂ®), saquinavir/r (InviraseÂ®) and indinavir/r (Crixivan ... - PharmaLive.com (press release),

Infection with harmless hepatitis G doesn't mean that HIV ... Nov 24, 2005
...infection. The MaxCmin 1 trial was designed to compare the safety and efficacy of ritonavir-boosted saquinavir and indinavir. The ... - Aidsmap,

Lab studies show that protein in St John's wort can inhibit HIV ... 31 Oct 2005
...usually bought over the counter without medical advice, has been shown to interfere with the way the body metabolises the protease inhibitor indinavir (Crixivan ... - Aidsmap,

Long-Term Indinavir Treatment Keeps HIV Under Control at 156 Weeks ... Oct 11, 2005
SAN FRANCISCO, CA -- October 11, 2005 -- Most patients who were treated with an antiretroviral regimen that included the protease inhibitor indinavir were able ... - DG News

EU commission approves AptivusÂ® for the treatment of HIV Oct 26, 2005
...other commonly used ritonavir-boosted PIs, including KaletraÂ® (lopinavir/r), InviraseÂ® (saquinavir), AgeneraseÂ® (amprenavir) and CrixivanÂ® (indinavir).1. ... - Biotech Intelligence (press release),

EU Commission Approves Aptivus (Tipranavir) for Treatment of HIV Oct 26, 2005
...commonly used ritonavir-boosted PIs, including Kaletra(R) (lopinavir/r), Invirase(R) (saquinavir), Agenerase(R) (amprenavir) and Crixivan(R) (indinavir).1. ... - DG News

HIV drugs do not cause body fat changes Sep 29, 2005
Known by names such as "Crix belly" after the drug Crixivan (indinavir; Merck), such body fat increases are often regarded as an adverse effect of anti-HIV ... - myDNA.com,

Four year treatment break does not reverse fat loss, says case ... Oct 11, 2005
HIV in 1989 and in July 1997, when her CD4 cell count was below 100 cells/mm 3 started potent anti-HIV therapy with a regimen comprising d4T, 3TC and indinavir ... - Aidsmap,

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),

Switch to Atazanavir Normalizes Aberrant Cholesterol Values ... Oct 13, 2005
...loads and mean CD4 counts greater than 550 cells/mL while on a HAART regimen that included protease inhibitors - nelfinavir, amprenavir, indinavir or lopinavir ... - DG News

Long-Term Indinavir Treatment Keeps HIV Under Control at 156 Weeks ... 11 Oct 2005
SAN FRANCISCO, CA -- October 11, 2005 -- Most patients who were treated with an antiretroviral regimen that included the protease inhibitor indinavir were able ... - DG News

Four year treatment break does not reverse fat loss, says case ... 11 Oct 2005
HIV in 1989 and in July 1997, when her CD4 cell count was below 100 cells/mm 3 started potent anti-HIV therapy with a regimen comprising d4T, 3TC and indinavir ... - Aidsmap,

Genetic test can help predict who will develop hyperbilirubinaemia Sep 13, 2005
...to develop hyperbilirubinaemia, a potential side-effect of treatment with the protease inhibitors atazanavir (Reyataz) and indinavir (Crixivan), according to a ... - Aidsmap,

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

HAART is not reducing risk of anal cancer in gay men Aug 28, 2005
Lamivudine (3TC, Epivir; 59%) was the most commonly used, currently taken antiretroviral, followed by stavudine (d4T, Zerit; 52%), indinavir (Crixivan 26%) and ... - Aidsmap,

US men's study finds cumulative NRTI use, but not PIs or NNRTIs ... Aug 24, 2005
The most commonly prescribed PI, indinavir (Crixivan) (26%), was the only PI associated with any measure of insulin resistance - increased odds of ... - Aidsmap,

Anti-HIV drugs linked with nerve damage Aug 26, 2005
Protease inhibitors attack HIV in a different way than dideoxynucleosides. Those linked to neuropathy were indinavir, saquinavir and ritonavir. ... - Macleans,

Counterfeit Medicines - No Problem Yet Aug 11, 2005
...the mechanisms that are in place was the development of Ginovir-3D, a generic medicine containing Zidovudine in combination with Lamivudine and Indinavir. ... - AllAfrica.com,

Indian Generic Drug Firm Ranbaxy Announces Seven Antiretroviral ... Aug 16, 2005
Ranbaxy in November 2004 voluntarily removed its drugs -- including indinavir, lamivudine, nevirapine, stavudine and zidovudine tablets, as well as two ... - Kaiser network.org,

Timeline: AIDS in America Aug 13, 2005
...inhibitor class. It also approves protease inhibitors Ritonavir (Norvir, by Abbott) and indinavir (Crixivan, by Merck). * FDA approves ... - Knoxville News Sentinel (subscription),

You've done it. What now? 06 Aug 2005
...days after an HIV exposure. In some circumstances, a third drug such as indinavir is added to this treatment. A person who has had ... - Health24.com

Tipranavir, a powerful treatment option for HIV-positive treatment ... Jul 31, 2005
Aptivus versus established ritonavir-boosted comparator protease inhibitors (PIs), which included lopinavir/r, amprenavir/r, saquinavir/r or indinavir/r. PIs ... - RxPG NEWS

COMUNICADO (I): Positive Opinion in Europe for Tipranavir Jul 28, 2005
APTIVUS versus established ritonavir-boosted comparator protease inhibitors (PIs), which included lopinavir/r, amprenavir/r, saquinavir/r or indinavir/r. PIs ... - Europa Press

IAS: Have we prematurely discarded triple NRTI regimens? Jul 27, 2005
He concluded that although not all triple NRTI-regimens are alike, even the most potent are only comparable to unboosted indinavir, nelfinavir and amprenavir ... - Aidsmap

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