IMPORTANT SAFETY INFORMATION

WARNING: Hepatotoxicity: See full Prescribing Information for complete Boxed Warning.
Hepatotoxicity has been reported, which may be preceded by severe rash or other features of a systemic allergic reaction (eg, fever, eosinophilia or elevated IgE). Immediately evaluate patients with signs or symptoms of hepatitis or allergic reaction.
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Tolerability Profile

Most common adverse events through Week 96

MERIT (through 96 weeks): The most common adverse events (>8% incidence) reported with SELZENTRY with frequency rates higher than efavirenz, regardless of causality1
  SELZENTRY 300 mg BID +
zidovudine/lamivudine

(N=360), %
Efavirenz
600 mg QD +
zidovudine/lamivudine

(N=361), %
Upper respiratory tract infection 32 30
Bronchitis 13 9
Flatulence, bloating, and distention 10 7
Upper respiratory tract signs and symptoms 9 5
GI atonic and hypomotility disorders NEC 9 5

BID=twice daily.
QD=once daily.
GI=gastrointestinal.
NEC=not elsewhere classified.

Discontinuations in MERIT through 96 weeks

BID=twice daily.
QD=once daily.

Discontinuations in MERIT during the open-label phase (Weeks 97 to 240)

BID=twice daily.
QD=once daily.

Long-term safety endpoints

BID=twice daily.
QD=once daily.
SAEs=serious adverse events.

Most common adverse events through 48 weeks

MOTIVATE: The most common adverse events (>8% incidence) reported with SELZENTRY with frequency rates higher than placebo, regardless of causality1
  SELZENTRY
300 mg BID* + OBT
(N=426), %
Placebo + OBT (N=209), %
Upper respiratory tract infection 23 13
Cough 14 5
Pyrexia 13 9
Rash 11 5
Dizziness 9 8

   Analysis includes all patients who received at least 1 dose of study medication. Analysis was not adjusted for the
   duration of treatment exposure or for multiple testing.

* 300-mg dose equivalent.

BID=twice daily.
OBT=optimized background therapy.

  • At 48 weeks, the rate of discontinuation due to adverse events for patients treated with SELZENTRY + OBT was 4% vs 5% for patients treated with placebo + OBT2

Long-term safety outcomes in treatment-experienced patients

  • After confirming eligibility for the observational phase, patients were assessed at 6-month intervals for selection/confirmation of OBT regimen and selected safety assessments
  • During the observational phase, selected safety endpoints were captured and were also retrospectively identified in the double-blind and open-label phases

300-mg dose equivalent.

BID=twice daily.
OBT=optimized background therapy.
SAEs=serious adverse events.
PY=patient-years.

No new safety signals for SELZENTRY were identified based on selected safety endpoints through 240 weeks.

IMPORTANT SAFETY INFORMATION

WARNING: Hepatotoxicity: See full Prescribing Information for complete Boxed Warning.

Hepatotoxicity has been reported, which may be preceded by severe rash or other features of a systemic allergic reaction (eg, fever, eosinophilia or elevated IgE). Immediately evaluate patients with signs or symptoms of hepatitis or allergic reaction.

INDICATION 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 patients and one study in treatment-naïve patients. Both studies in treatment-experienced patients 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 patients 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 patients, more patients treated with SELZENTRY experienced virologic failure and developed lamivudine resistance compared with efavirenz

IMPORTANT SAFETY INFORMATION

WARNING: Hepatotoxicity: See full Prescribing Information for complete Boxed Warning.

Hepatotoxicity has been reported, which may be preceded by severe rash or other features of a systemic allergic reaction (eg, fever, eosinophilia or elevated IgE). Immediately evaluate patients with signs or symptoms of hepatitis or allergic reaction.

CONTRAINDICATION

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 cytochrome P450 (CYP) 3A inhibitors or inducers.

ADDITIONAL WARNINGS AND PRECAUTIONS

Hepatotoxicity

Hepatotoxicity accompanied by severe rash or systemic allergic reaction including potentially life-threatening events has been reported in clinical trials and postmarketing. These events occurred approximately one month after starting treatment. Among reported cases of hepatitis, some were observed in the absence of allergic features or with no pre-existing hepatic disease.

Hepatic laboratory parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin should be obtained prior to starting SELZENTRY and at other time points during treatment as clinically indicated. If rash or symptoms or signs of hepatitis or allergic reaction develop, hepatic laboratory parameters should be monitored and discontinuation of treatment should be considered.

Caution should be used when administering SELZENTRY to patients with pre-existing liver dysfunction or who are coinfected with viral hepatitis B or C. The safety and efficacy of SELZENTRY have not been specifically studied in patients with significant underlying liver disorders.

Severe skin and hypersensitivity reactions

Severe, potentially life-threatening skin and hypersensitivity reactions have been reported in patients taking SELZENTRY, in most cases concomitantly with other drugs associated with these reactions. These include cases of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS). The cases were characterized by features including rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure. Discontinue SELZENTRY and other suspected agents immediately if signs or symptoms of severe skin or hypersensitivity reactions develop. Delay in stopping treatment with SELZENTRY or other suspect drugs after the onset of rash may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated.

Cardiovascular events

Use with caution in patients at increased risk of cardiovascular events, because cardiovascular events, including myocardial ischemia and/or infarction, were observed in treatment-experienced and treatment-naïve patients who received SELZENTRY.

Caution should be used when administering SELZENTRY in patients with a history of postural hypotension or who receive concomitant medication known to lower blood pressure. Patients should be advised that if they experience dizziness while receiving SELZENTRY, they should avoid driving or operating machinery.

Postural hypotension in patients with renal impairment

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 due to an increased risk of postural hypotension as a result of increased SELZENTRY 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 and no alternative treatment options are available. If patients with severe renal impairment or ESRD not receiving a concomitant potent CYP3A inhibitor or inducer experience any symptoms of postural hypotension while taking SELZENTRY 300 mg twice daily, the dose should be reduced to 150 mg twice daily.

Immune reconstitution syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including SELZENTRY.

Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment.

Potential risk of infection

SELZENTRY antagonizes the CCR5 coreceptor located on some immune cells, and therefore, could potentially increase the risk of developing infections. Patients should be monitored closely for evidence of infection while receiving SELZENTRY.

Potential risk of malignancy

While no increase in malignancy has been observed with SELZENTRY, due to this drug's mechanism of action, it could affect immune surveillance and lead to an increased risk of malignancy. Long-term follow-up is needed to more fully assess this risk.

MOST COMMON ADVERSE EVENTS

Treatment-experienced patients through 48 weeks

The most common adverse events (>8%) reported with SELZENTRY twice-daily therapy with frequency rates higher than placebo, regardless of causality, were upper respiratory tract infections (23% vs 13%), cough (14% vs 5%), pyrexia (13% vs 9%), rash (11% vs 5%), and dizziness (9% vs 8%).

Treatment-naïve patients through 96 weeks

The most common adverse events (>8%) reported with SELZENTRY twice-daily therapy with frequency rates higher than efavirenz, regardless of causality, were upper respiratory tract infection (32% vs 30%), bronchitis (13% vs 9%), flatulence, bloating, and distention (10% vs 7%), upper respiratory tract signs and symptoms (9% vs 5%), and GI atonic and hypomotility disorders not elsewhere classified (9% vs 5%).

USE IN SPECIFIC PATIENT POPULATIONS

Pediatric Patients: There are no data available in pediatric patients; therefore, SELZENTRY should not be used in patients <16 years of age.

Hepatic Impairment: SELZENTRY is principally metabolized by the liver; therefore, caution should be exercised when administering this drug to patients with hepatic impairment, because SELZENTRY concentrations may be increased.

CONCOMITANT USE

SELZENTRY is a substrate of CYP3A and P-glycoprotein (P-gp). Coadministration with potent CYP3A inhibitors, including protease inhibitors (except tipranavir/ritonavir) or delavirdine, will increase the concentration of SELZENTRY. Coadministration with potent CYP3A inducers, including efavirenz, may decrease the concentration of SELZENTRY. Healthcare providers should ensure that an appropriate dose adjustment of SELZENTRY is made when SELZENTRY is coadministered with potent CYP3A inhibitors and/or potent CYP3A inducers since concentrations, therapeutic effects, and the safety of SELZENTRY may be affected.

Concomitant use of SELZENTRY and St. John's Wort (Hypericum perforatum) or products containing St. John's Wort is not recommended.

HOW SUPPLIED

SELZENTRY is available in 150-mg and 300-mg tablets.

References

1. SELZENTRY [prescribing information]. Research Triangle Park, NC; ViiV Healthcare Group of Companies; 2013.
2. Sierra-Madero J, Di Perri G, Wood R, et al. Efficacy and safety of maraviroc versus efavirenz, both with zidovudine/lamivudine. 96-week results from the MERIT study. HIV Clin Trials. 2010;11(3):125-132. 3. Cooper DA, Heera J, Ive P, et al. 5-year efficacy and safety of maraviroc versus efavirenz, each in conjunction with zidovudine/lamivudine in treatment-naïve HIV-1-infected patients: open-label extension of the randomized, double-blind MERIT study. Poster presented at: 19th International AIDS Conference; July 22-27, 2012; Washington, DC. TUPE026.

References

1. SELZENTRY [prescribing information]. Research Triangle Park, NC: ViiV Healthcare Group of Companies; 2013.
2. Gulick RM, Lalezari J, Goodrich J, et al. MOTIVATE Study Teams. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008;359(14):1429-1441. 3. Gulick R, Fätkenheuer G, Burnside R, et al. 5-year safety evaluation of maraviroc in HIV-1-infected, treatment-experienced patients. Poster presented at: 19th International AIDS Conference; July 22-27, 2012. Washington, DC. TUPE029.