WARNING: Hepatotoxicity has been reported with SELZENTRY use. Evidence of a systemic allergic reaction (eg, 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.

SELZENTRY, in combination with other antiretroviral agents, is indicated for treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

SELZENTRY should be taken as part of an antiretroviral combination regimen. As with other antiretrovirals, SELZENTRY should be optimally combined with other antiretrovirals to which the patient's virus is sensitive.

There is limited experience in patients with reduced hepatic function; therefore, SELZENTRY should be used with caution in this population.

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 such as patients co-infected with viral hepatitis B or C. Caution should be used when administering SELZENTRY to patients with pre-existing liver dysfunction or who are co-infected with viral hepatitis B or  hepatitisC.

Use with caution in patients at increased risk of cardiovascular events. More cardiovascular events, including myocardial ischemia and/or infarction, were observed in 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.

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

SELZENTRY antagonizes the CCR5 co-receptor located on some immune cells, and therefore could potentially increase the risk of developing infections. The overall incidence and severity of infection, as well as AIDS-defining Category C infections, was comparable in the treatment groups during the Phase 3 studies of SELZENTRY. Compared with patients receiving placebo, patients in the SELZENTRY arm had higher incidences of certain upper respiratory tract infections (20.0% vs 11.5%) and Herpes virus infections (6.8% vs 3.8%). However, patients taking SELZENTRY had a lower incidence of pneumonia (2.1% vs 4.8%). Patients should be monitored closely for evidence of infection while receiving SELZENTRY.

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.

The most common adverse events reported with SELZENTRY twice-daily therapy with frequency rates higher than placebo, regardless of causality, were cough (12.7% vs 4.8%), pyrexia (12.0% vs 8.1%), upper respiratory tract infections (20.0% vs 11.5%), rash (9.6% vs 4.8%), musculoskeletal symptoms (8.7% vs 7.7%), abdominal pain (8.2% vs 7.7%), and dizziness (8.2% vs 7.7%).

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

There are no data available in pediatric patients; therefore, SELZENTRY should not be used in patients <16 years old.

The safety and efficacy of SELZENTRY have not been specifically studied in patients with renal impairment; therefore, SELZENTRY should be used with caution in this population. Patients with a creatinine clearance of less than 50 mL/min should receive SELZENTRY and a CYP3A inhibitor only if the potential benefit is felt to outweigh the risk, and should be monitored because of potential increased risk of adverse effects (including dizziness and postural hypotension) due to increased concentrations of SELZENTRY.

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