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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use ISENTRESS safely and effectively. See full prescribing information for ISENTRESS.
ISENTRESS (raltegravir) Tablets
Initial U.S. Approval: 2007
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RECENT MAJOR CHANGES
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Indications And Usage (1)07/2009
Dosage And Administration (2)01/2009
Warnings And Precautions (5.2) - removal07/2009
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INDICATIONS AND USAGE
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ISENTRESS® is a human immunodeficiency virus integrase strand transfer inhibitor (HIV-1 INSTI) indicated:
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In combination with other antiretroviral agents for the treatment of HIV-1 infection in adult patients (1).
The safety and efficacy of ISENTRESS have not been established in pediatric patients (1).
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DOSAGE AND ADMINISTRATION
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400 mg administered orally, twice daily with or without food (2).
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During coadministration with rifampin, 800 mg twice daily (2).
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DOSAGE FORMS AND STRENGTHS
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Tablets: 400 mg (3).
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CONTRAINDICATIONS
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None (4)
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WARNINGS AND PRECAUTIONS
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Monitor for Immune Reconstitution Syndrome (5.1).
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ADVERSE REACTIONS
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DRUG INTERACTIONS
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Coadministration of ISENTRESS with drugs that are strong inducers of UGT1A1 may result in reduced plasma concentrations of raltegravir (7.2).
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USE IN SPECIFIC POPULATIONS
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Pregnancy:
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ISENTRESS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Physicians are encouraged to register pregnant women exposed to ISENTRESS by calling 1-800-258-4263 so that Merck can monitor maternal and fetal outcomes (8.1).
Nursing Mothers:
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Breast-feeding is not recommended while taking ISENTRESS (8.3).
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See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling |
Revised: 08/2010 |
Back to Highlights and Tabs
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Immune Reconstitution Syndrome
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Effect of Raltegravir on the Pharmacokinetics of Other Agents
7.2 Effect of Other Agents on the Pharmacokinetics of Raltegravir
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Use in Patients with Hepatic Impairment
8.7 Use in Patients with Renal Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.4 Microbiology
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
ISENTRESS1 is indicated in combination with other anti-retroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adult patients.
This indication is based on analyses of plasma HIV-1 RNA levels up through 48 weeks in three double-blind controlled studies of ISENTRESS. Two of these studies were conducted in clinically advanced, 3-class antiretroviral (NNRTI, NRTI, PI) treatment-experienced adults and one was conducted in treatment-naïve adults.
The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response [see Clinical Studies (14)].
The safety and efficacy of ISENTRESS have not been established in pediatric patients.
2 DOSAGE AND ADMINISTRATION
For the treatment of patients with HIV-1 infection, the dosage of ISENTRESS is 400 mg administered orally, twice daily with or without food. During coadministration with rifampin, the recommended dosage of ISENTRESS is 800 mg twice daily with or without food.
3 DOSAGE FORMS AND STRENGTHS
400 mg pink, oval shaped, film-coated tablets with "227" on one side.
4 CONTRAINDICATIONS
None
5 WARNINGS AND PRECAUTIONS
5.1 Immune Reconstitution Syndrome
During the initial phase of treatment, patients responding to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, Mycobacterium tuberculosis, or reactivation of varicella zoster virus), which may necessitate further eva luation and treatment.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Treatment-Naïve Studies
The following safety assessment of ISENTRESS in treatment-naïve subjects is based on the randomized double-blind active controlled study of treatment-naïve subjects, STARTMRK (Protocol 021) with ISENTRESS 400mg twice daily in combination with a fixed dose of emtricitabine 200 mg (+) tenofovir 300 mg, (N=281) versus efavirenz (EFV) 600 mg at bedtime in combination with emtricitabine (+) tenofovir, (N=282). During double-blind treatment, the total follow-up for subjects receiving ISENTRESS 400 mg twice daily + emtricitabine (+) tenofovir was 247 patient-years and 241 patient-years for subjects receiving efavirenz 600 mg at bedtime + emtricitabine (+) tenofovir.
In Protocol 021, the rate of discontinuation of therapy due to adverse reactions was 3% in subjects receiving ISENTRESS + emtricitabine (+) tenofovir and 6% in subjects receiving efavirenz + emtricitabine (+) tenofovir.
The clinical adverse drug reactions (ADRs) listed below were considered by investigators to be causally related to ISENTRESS + emtricitabine (+) tenofovir or efavirenz + emtricitabine (+) tenofovir. Clinical ADRs of moderate to severe intensity occurring in ≥2% of treatment-naïve subjects treated with ISENTRESS and occurring at a higher rate than efavirenz are presented in Table 1.
Table 1: Adverse Reactions* of Moderate to Severe Intensity† Occurring in ≥2% of Treatment-Naïve Adult Subjects Receiving ISENTRESS and at a Higher Rate Compared to Efavirenz (48 Week Analysis)
System Organ Class,
Preferred Term |
Randomized Study Protocol 021 |
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ISENTRESS 400mg
Twice Daily +
Emtricitabine (+) Tenofovir
(n = 281)‡
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Efavirenz 600 mg
At Bedtime +
Emtricitabine (+) Ten |
