Prescription Drug Information: SELZENTRY

SELZENTRY — maraviroc tablet, film coated
Physicians Total Care, Inc.

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 [see Warnings and Precautions (5.1) ].

1 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. [see Microbiology (12.4) Clinical Studies (14.3)] .
  • 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. [see Microbiology (12.4) Clinical Studies (14.3)]

2 DOSAGE AND ADMINISTRATION

2.1 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 [see Drug Interactions (7.1) ].

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

2.2 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
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 [see Warnings and Precautions (5.2)].
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

3 DOSAGE FORMS AND STRENGTHS

  • 150 mg blue, oval film-coated tablets debossed with “Pfizer” on one side and “MVC 150” on the other
  • 300 mg blue, oval film-coated tablets debossed with “Pfizer” on one side and “MVC 300” on the other

4 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.

5 WARNINGS AND PRECAUTIONS

5.1 Hepatotoxicity

A case of possible SELZENTRY-induced hepatotoxicity with allergic features has been reported in a study of healthy volunteers. Discontinuation of SELZENTRY should be considered in any patient with signs or symptoms of hepatitis, or with increased liver transaminases combined with rash or other systemic symptoms.

The safety and efficacy of SELZENTRY have not been specifically studied in patients with significant underlying liver disorders. In studies of treatment-experienced HIV-infected subjects, approximately 6% of subjects were co-infected with hepatitis B and approximately 6% were co-infected with hepatitis C. Due to the small number of co-infected subjects studied, no conclusions can be drawn regarding whether they are at an increased risk for hepatic adverse events with SELZENTRY administration. However, caution should be used when administering SELZENTRY to patients with pre-existing liver dysfunction or who are co-infected with viral hepatitis B or C.

5.2 Cardiovascular Events

Use with caution in patients at increased risk for cardiovascular events. Eleven subjects (1.3%) who received SELZENTRY had cardiovascular events including myocardial ischemia and/or infarction during the Phase 3 studies in treatment-experienced studies [total exposure 609 patient-years (300 on once daily + 309 on twice daily SELZENTRY)], while no subjects who received placebo had such events (total exposure 111 patient-years). These subjects generally had cardiac disease or cardiac risk factors prior to SELZENTRY use, and the relative contribution of SELZENTRY to these events is not known.

In the Phase 2b/3 study in treatment-naïve subjects, 3 subjects (0.8%) who received SELZENTRY had events related to ischemic heart diseases and 5 subjects (1.4%) who received efavirenz had such events (total exposure 506 and 508 patient-years for SELZENTRY and efavirenz, respectively).

When SELZENTRY was administered to healthy volunteers at doses higher than the recommended dose, symptomatic postural hypotension was seen at a greater frequency than in placebo. However, when SELZENTRY was given at the recommended dose in HIV subjects in Phase 3 studies, postural hypotension was seen at a rate similar to placebo (approximately 0.5%). Caution should be used when administering SELZENTRY in patients with a history of postural hypotension or on concomitant medication known to lower blood pressure.

Postural Hypotension in Patients with Renal Impairment

Patients with impaired renal function may have cardiovascular co-morbidities and could be at increased risk of cardiovascular adverse events triggered by postural hypotension. An increased risk of postural hypotension may occur in patients with severe renal insufficiency or in those with end-stage renal disease (ESRD) due to increased maraviroc exposure in some patients. SELZENTRY should be used in patients with severe renal impairment or ESRD only if they are not receiving a concomitant potent CYP3A inhibitor or inducer. However, the use of SELZENTRY in these patients should only be considered when no alternative treatment options are available. If patients with severe renal impairment or ESRD experience any symptoms of postural hypotension while taking 300 mg twice daily the dose should be reduced to 150 mg twice daily [see Dosage and Administration (2.2)].

5.3 Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including maraviroc. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as infection with Mycobacterium avium, cytomegalovirus, Pneumocystis jirovecii, Mycobacterium tuberculosis, or reactivation of Herpes simplex and Herpes zoster), which may necessitate further evaluation and treatment.

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