CELSENTRI

1 Dosing Considerations • Therapy should be initiated by a healthcare professional experienced in the management of HIV infection. • CELSENTRI must be taken every day in combination with other antiretroviral agents. The recommended dose is 300 mg twice daily, but adjustments are recommended based on the patient’s concomitant medications.

CELSENTRI can be taken with or without food. 2 Recommended Dose and Dosage Adjustment Adults The recommended dose of CELSENTRI is 300 mg twice daily. A dose adjustment may be needed due to the potential for drug interactions (see Table 1 and 9 DRUG INTERACTIONS Drug-Drug Interactions, Table 8).

Table 1 Recommended Dosing Regimen Concomitant Medications Dose of CELSENTRI Potent CYP3A4 inhibitors (with or without a CYP3A4 inducer) including, but not limited to: • protease inhibitors (except tipranavir/ritonavir) • delavirdine • ketoconazole, itraconazole, clarithromycin 150 mg twice daily Potent CYP3A4 inducers (without a potent CYP3A4 inhibitor) including, but not limited to: • efavirenz • rifampin • etravirine • carbamazepine, phenobarbital, and phenytoin 600 mg twice daily Other concomitant medications, including all other antiretrovirals that are not potent CYP3A4 inhibitors or potent CYP3A4 inducers, including tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, and enfuvirtide 300 mg twice daily Geriatrics (>65 years of age) There were insufficient numbers of subjects aged 65 and over in the clinical studies to determine whether they respond differently from younger subjects.

In general, caution should be exercised when administering CELSENTRI in elderly patients, also reflecting the greater frequency of decreased hepatic and renal function, of concomitant disease and other drug therapy. Pediatrics (<18 years of age) The pharmacokinetics, safety and efficacy of maraviroc in pediatric patients have not been established.

Therefore, maraviroc should not be used in this patient population. Renal Insufficiency CELSENTRI should not be used in patients with severe renal impairment or ESRD (CLcr < 30 mL/min) who are taking potent CYP3A inhibitors or inducers (see 7 WARNINGS AND PRECAUTIONS).

No dose adjustment is necessary for renally impaired patients, including patients with ESRD, requiring dialysis, not receiving a potent CYP3A4 inhibitor in combination with CELSENTRI. Table 2 below provides dosing interval adjustment guidelines for patients based on renal function and concomitant medications.

). 1 Dosing Considerations • Therapy should be initiated by a healthcare professional experienced in the management of HIV infection. • CELSENTRI must be taken every day in combination with other antiretroviral agents. The recommended dose is 300 mg twice daily, but adjustments are recommended based on the patient’s concomitant medications.

CELSENTRI can be taken with or without food. 2 Recommended Dose and Dosage Adjustment Adults The recommended dose of CELSENTRI is 300 mg twice daily. A dose adjustment may be needed due to the potential for drug interactions (see Table 1 and

4 Geriatrics). 2 CONTRAINDICATIONS CELSENTRI is contraindicated in patients with hypersensitivity to maraviroc or any component of this medication. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING of this product monograph.

3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions Hepatotoxicity has been reported with CELSENTRI use. A systemic allergic reaction, including pruritic rash, eosinophilia or elevated IgE may occur prior to the development of hepatotoxicity.

Patients with signs or symptoms of acute hepatitis or allergic reaction should be evaluated immediately and, if required, discontinuation of CELSENTRI treatment should be strongly considered. (see 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic and

CELSENTRI is contraindicated in patients with hypersensitivity to maraviroc or any component of this medication. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING of this product monograph.