Selzentry™ (maraviroc) Tablets

Warnings

(description)

Clinical pharmacology

Indications and usage

Contraindications

Precautions

Adverse reactions

Dosage and administration

How supplied

Reference

Warnings

WARNING: HEPATOTOXICITY

Hepatotoxicity has been reported with SELZENTRY use. Evidence of a systemic allergic reaction (e.g., pruritic rash, eosinophilia or elevated IgE) prior to the development of hepatotoxicity may occur. Patients with signs or symptoms of hepatitis or allergic reaction following use of SELZENTRY should be evaluated immediately

(description)

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use SELZENTRY safely and effectively. See full prescribing information for SELZENTRY.

SELZENTRY (maraviroc) Tablets
Initial U.S. Approval: 2007

DESCRIPTION

SELZENTRY (maraviroc) is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR5 and HIV-1 gp120. Blocking this interaction prevents CCR5-tropic HIV-1 entry into cells.

SELZENTRY is available as film-coated tablets for oral administration containing either 150 or 300 mg of maraviroc and the following inactive ingredients: microcrystalline cellulose, dibasic calcium phosphate (anhydrous), sodium starch glycolate, and magnesium stearate. The film coat [Opadry® II Blue (85G20583)] contains FD&C blue #2 aluminum lake, soya lecithin, polyethylene glycol (macrogol 3350), polyvinyl alcohol, talc and titanium dioxide.

Clinical pharmacology

CLINICAL PHARMACOLOGY

Mechanism of Action
Maraviroc is an antiviral drug.
Maraviroc is a member of a therapeutic class called CCR5 co-receptor antagonists. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the cell membrane, preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells. CXCR4-tropic and dual-tropic HIV-1 entry is not inhibited by maraviroc.

Indications and usage

INDICATIONS AND USAGE

SELZENTRY, in combination with other antiretroviral agents, is indicated for adult patients infected with only CCR5-tropic HIV-1.

This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of SELZENTRY in treatment-experienced subjects and one study in treatment-naïve subjects. Both studies in treatment-experienced subjects were conducted in clinically advanced, 3-class antiretroviral-experienced (NRTI, NNRTI, PI, or enfuvirtide) adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

The following points should be considered when initiating therapy with SELZENTRY:
--Adult patients infected with only CCR5-tropic HIV-1 should use SELZENTRY.
--Tropism testing must be conducted with a highly sensitive tropism assay that has demonstrated the ability to identify patients appropriate for SELZENTRY use. Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on SELZENTRY.
--Use of SELZENTRY is not recommended in subjects with dual/mixed or CXCR4-tropic HIV-1 as efficacy was not demonstrated in a phase 2 study of this patient group.
--The safety and efficacy of SELZENTRY have not been established in pediatric patients.
--In treatment-naïve subjects, more subjects treated with SELZENTRY experienced virologic failure and developed lamivudine resistance compared to efavirenz.

Contraindications

CONTRAINDICATIONS
SELZENTRY should not be used in patients with severe renal impairment or end-stage renal disease (ESRD) (CrCl < 30 mL/min) who are taking potent CYP3A inhibitors or inducers.

Precautions

WARNINGS AND PRECAUTIONS
--Use caution when administering SELZENTRY to patients with pre-existing liver dysfunction or who are co-infected with viral hepatitis B or C.
--More cardiovascular events including myocardial ischemia and/or infarction were observed in treatment-experienced subjects who received SELZENTRY. Use with caution in patients at increased risk of cardiovascular events .
--If patients with severe renal impairment or end-stage renal disease (ESRD) receiving SELZENTRY (without concomitant CYP3A inducers or inhibitors) experience postural hypotension the SELZENTRY dose should be reduced from 300 mg twice daily to 150 mg twice daily.

DRUG INTERACTIONS
--Coadministration with CYP3A inhibitors, including protease inhibitors (except tipranavir/ritonavir) and delavirdine, will increase the concentration of SELZENTRY.
--Coadministration with CYP3A inducers, including efavirenz, may decrease the concentration of SELZENTRY.

USE IN SPECIFIC POPULATIONS
--SELZENTRY should only be used in pregnant women if the potential benefit justifies the potential risk to the fetus.
--There are no data available in pediatric patients; therefore, SELZENTRY should not be used in patients <16 years of age.

Adverse reactions

ADVERSE REACTIONS
The most common adverse events in treatment-experienced subjects (>8% incidence) which occurred at a higher frequency compared to placebo are upper respiratory tract infections, cough, pyrexia, rash, and dizziness.

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Dosage and administration

DOSAGE AND ADMINISTRATION

Dose Recommendations for Patients with Normal Renal Function
The recommended dose of SELZENTRY differs based on concomitant medications due to drug interactions (see Table 1). SELZENTRY can be taken with or without food. SELZENTRY must be given in combination with other antiretroviral medications.

Table 1 gives the recommended dose adjustments.
Table 1 Recommended Dosing Regimen

Concomitant Medications

SELZENTRY Dose

Potent CYP3A inhibitors (with or without a potent CYP3A inducer) including:

protease inhibitors (except tipranavir/ritonavir)
delavirdine
ketoconazole, itraconazole, clarithromycin
other potent CYP3A inhibitors (e.g., nefazodone, telithromycin)

150 mg twice daily

Other concomitant medications, including tipranavir/ritonavir, nevirapine, raltegravir all NRTIs and enfuvirtide

300 mg twice daily

Potent CYP3A inducers (without a potent CYP3A inhibitor) including:

efavirenz
rifampin
etravirine
carbamazepine, phenobarbital, and phenytoin

600 mg twice daily

Dose Recommendations for Patients with Renal Impairment

Table 2 provides dosing recommendations for patients based on renal function and concomitant medications.
Table 2 Recommended Dosing Regimens Based on Renal Function

Concomitant Medications*	SELZENTRY Dose Based on Renal Function
	Normal	Mild	Moderate	Severe	End Stage Renal Disease (ESRD)
	CrCl >80 mL/min	CrCl >50 and ≤80 mL/min	CrCl ≥30 and ≤50 mL/min	CrCl <30 mL/min	On Regular Hemodialysis
Potent CYP3A inhibitors (with or without a CYP3A inducer)*	150 mg twice daily	150 mg twice daily	150 mg twice daily	NR	NR
Other concomitant medications*	300 mg twice daily	300 mg twice daily	300 mg twice daily	300 mg twice daily†	300 mg twice daily†
Potent CYP3A inducers (without a potent CYP3A inhibitor)*	600 mg twice daily	600 mg twice daily	600 mg twice daily	NR	NR
NR = not recommended
**See Table 1 for the list of concomitant medications. †The SELZENTRY dose should be reduced to 150 mg twice daily if there are any symptoms of postural hypotension

How supplied

DOSAGE FORMS AND STRENGTHS
Tablets: 150 mg and 300 mg

Reference

Package Insert data:
LAB-0358-5.0
May 2010

PRINCIPAL DISPLAY PANEL - 150 mg Tablet Bottle Label

NDC 0069-0807-60

Rx only
60 Tablets

Selzentry™
(maraviroc) tablets

150 mg

Pfizer
Distributed by
Pfizer Labs
Division of Pfizer Inc, NY, NY 10017

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates. A local search option of this data can be found here.