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 film-coated tablets for oral administration contain 25, 75, 150, or 300 mg of maraviroc and the following inactive ingredients: dibasic calcium phosphate (anhydrous), magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. 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. SELZENTRY oral solution contains 20 mg per mL of maraviroc and the following inactive ingredients: citric acid (anhydrous), purified water, sodium benzoate, sodium citrate dihydrate, strawberry flavoring (501440T), and sucralose. Maraviroc is chemically described as 4,4-difluoro- N -{(1 S )-3 - [ exo -3-(3-isopropyl-5-methyl-4 H -1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}cyclohexanecarboxamide. The molecular formula is C 29 H 41 F 2 N 5 O and the structural formula is: Maraviroc is a white to pale-colored powder with a molecular weight of 513.67. It is highly soluble across the physiological pH range (pH 1.0 to 7.5). Maraviroc chemical structure

SELZENTRY is indicated in combination with other antiretroviral agents for the treatment of only CCR5‑tropic human immunodeficiency virus type 1 (HIV‑1) infection in adult and pediatric patients weighing at least 2 kg. Limitations of Use • SELZENTRY is not recommended in patients with dual/mixed- or CXCR4-tropic HIV-1 . SELZENTRY is a CCR5 co-receptor antagonist indicated in combination with other antiretroviral agents for the treatment of only CCR5-tropic HIV-1 infection in adults and pediatric patients weighing at least 2 kg. Limitations of Use: • Not recommended in patients with dual/mixed- or CXCR4-tropic HIV-1.

Tablets: • 25-mg blue, oval, film-coated tablets debossed with “MVC 25” on one side and plain on the other. • 75-mg blue, oval, film-coated tablets debossed with “MVC 75” on one side and plain on the other. • 150-mg blue, oval, film-coated tablets debossed with “MVC 150” on one side and plain on the other. • 300-mg blue, oval, film-coated tablets debossed with “MVC 300” on one side and plain on the other. Oral Solution: • 20 mg per mL clear, colorless, strawberry-flavored oral solution. • Tablets: 25 mg, 75 mg, 150 mg and 300 mg. • Oral Solution: 20 mg per mL

• Prior to initiation of SELZENTRY for treatment of HIV-1 infection, test all patients for CCR5 tropism using a highly sensitive tropism assay. • SELZENTRY tablets and oral solution are taken twice daily by mouth and may be taken with or without food. SELZENTRY must be given in combination with other antiretroviral medications. Recommended Dosage in Adult Patients: Concomitant Medications Dosage of SELZENTRY When given with potent cytochrome P450 (CYP)3A inhibitors (with or without potent CYP3A inducers) including PIs (except tipranavir/ritonavir) 150 mg twice daily With NRTIs, tipranavir/ritonavir, nevirapine, raltegravir, and other drugs that are not potent CYP3A inhibitors or CYP3A inducers 300 mg twice daily With potent and moderate CYP3A inducers including efavirenz (without a potent CYP3A inhibitor) 600 mg twice daily A more complete list of coadministered drugs is listed in Dosage and Administration . Recommended Dosage in Pediatric Patients Weighing at Least 2 kg: Administer twice daily. Dosage should be based on body weight (kg) and concomitant medications and should not exceed the recommended adult dose. Recommended Dosage in Patients with Renal Impairment: Dose adjustment may be necessary in adult patients with renal impairment

Testing prior to Initiation of SELZENTRY Prior to initiation of SELZENTRY for treatment of HIV-1 infection, test all patients for CCR5 tropism using a highly sensitive tropism assay. SELZENTRY is recommended for patients with only CCR5-tropic HIV-1 infection. 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 . Monitor patients for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin prior to initiation of SELZENTRY and at other time points during treatment as clinically indicated

General Dosing Recommendations • SELZENTRY tablets and oral solution are taken twice daily by mouth and may be taken with or without food. • SELZENTRY must be given in combination with other antiretroviral medications. • The recommended dosage of SELZENTRY differs based on concomitant medications due to drug interactions

Recommended Dosage in Adult Patients with Normal Renal Function Table 1 displays oral dosage of SELZENTRY based on different concomitant medications . Table 1. Recommended Dosage in Adults Concomitant Medications Dosage of SELZENTRY a Potent CYP3A inhibitors (with or without a potent CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin. b Noninteracting concomitant medications include all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir, and tipranavir/ritonavir. c Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin. Potent cytochrome P450 (CYP)3A inhibitors (with or without a potent CYP3A inducer) a 150 mg twice daily Noninteracting concomitant medications b 300 mg twice daily Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) c 600 mg twice daily 2.4 Recommended Dosage in Pediatric Patients with Normal Renal Function The recommended dosage of SELZENTRY should be based on body weight (kg) and should not exceed the recommended adult dose. The recommended dosage also differs based on concomitant medications due to drug interactions ( Table 2 and Table 3 ) . Before prescribing SELZENTRY tablets, assess children for the ability to swallow tablets. If a child is unable to reliably swallow SELZENTRY tablets, the oral solution formulation should be prescribed. The recommended oral dosage of SELZENTRY tablets in pediatric patients aged 2 years and older weighing at least 10 kg is presented in Table 2 . Table 2. Recommended Dosage in Pediatric Patients Aged 2 Years and Older Weighing at Least 10 kg (Tablets) a Potent CYP3A inhibitors (with or without a CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin. b Noninteracting concomitant medications including all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir. c Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin. d Insufficient data are available to recommend use. Concomitant Medications Dosage of SELZENTRY Based on Weight 10 kg to <14 kg 14 kg to <20 kg 20 kg to <30 kg 30 kg to <40 kg ≥40 kg Potent CYP3A inhibitors (with or without a CYP3A inducer) a 50 mg twice daily 50 mg twice daily 75 mg twice daily 100 mg twice daily 150 mg twice daily Noninteracting concomitant medications b 150 mg twice daily 200 mg twice daily 200 mg twice daily 300 mg twice daily 300 mg twice daily Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) c Not recommended d The recommended oral dosage of SELZENTRY oral solution in pediatric patients weighing at least 2 kg is presented in Table 3 . Table 3. Recommended Dosage in Pediatric Patients Weighing at Least 2 kg (Oral Solution) a Potent CYP3A inhibitors (with or without a CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin. b Insufficient data are available to recommend use. c Noninteracting concomitant medications including all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir. d Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin. Concomitant Medications Dosage (Volume of Solution) of SELZENTRY Based on Weight 2 kg to <4 kg 4 kg to <6 kg 6 kg to <10 kg 10 kg to <14 kg 14 kg to <20 kg 20 kg to <30 kg 30 kg to <40 kg ≥40 kg Potent CYP3A inhibitors (with or without a CYP3A inducer) a Not recommended b 50 mg (2.5 mL) twice daily 50 mg (2.5 mL) twice daily 80 mg (4 mL) twice daily 100 mg (5 mL) twice daily 150 mg (7.5 mL) twice daily Noninteracting concomitant medications c 30 mg (1.5 mL) twice daily 40 mg (2 mL) twice daily 100 mg (5 mL) twice daily 150 mg (7.5 mL) twice daily 200 mg (10 mL) twice daily 200 mg (10 mL) twice daily 300 mg (15 mL) twice daily 300 mg (15 mL) twice daily Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) d Not recommended b Administer the oral solution using the included press-in bottle adapter and the appropriate oral dosing syringe: for doses of 2.5 mL or less, use the 3-mL syringe; for doses greater than 2.5 mL, use the 10-mL syringe. Care should be taken when measuring neonate doses due to the small volumes of oral solution required

Recommended Dosage in Patients with Renal Impairment Adult Patients Table 4 provides dosing recommendations for patients based on renal function and concomitant medications. Table 4. Recommended Dosage in Adults Based on Renal Function CrCl = Creatinine clearance. a Potent CYP3A inhibitors (with or without a CYP3A inducer) including: clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, protease inhibitors (except tipranavir/ritonavir), telithromycin. b Noninteracting concomitant medications include all medications that are not potent CYP3A inhibitors or inducers such as: dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir. c Dosage of SELZENTRY should be reduced to 150 mg twice daily if there are any symptoms of postural hypotension . d Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin. Concomitant Medications Dosage of SELZENTRY Based on Renal Function Normal (CrCl >80 mL/min) Mild (CrCl >50 and ≤80 mL/min) Moderate (CrCl ≥30 and ≤50 mL/min) Severe (CrCl <30 mL/min) End-Stage Renal Disease on Regular Hemodialysis Potent CYP3A inhibitors (with or without a CYP3A inducer) a 150 mg twice daily 150 mg twice daily 150 mg twice daily Contra-indicated Contra-indicated Noninteracting concomitant medications b 300 mg twice daily 300 mg twice daily 300 mg twice daily 300 mg twice daily 300 mg twice daily c Potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) d 600 mg twice daily 600 mg twice daily 600 mg twice daily Contra-indicated Contra-indicated Pediatric Patients There are no data to recommend specific doses of SELZENTRY in pediatric patients with mild or moderate renal impairment . Additionally, SELZENTRY is contraindicated for pediatric patients with severe renal impairment or end-stage renal disease (ESRD) on regular hemodialysis who are receiving potent CYP3A inhibitors or inducers .

• Hepatotoxicity accompanied by severe rash or systemic allergic reaction, including potentially life-threatening events, has been reported. 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. When administering SELZENTRY to patients with pre-existing liver dysfunction or who are co-infected with hepatitis B and/or C virus, additional monitoring may be warranted. • Severe and potentially life-threatening skin and hypersensitivity reactions have been reported in patients taking SELZENTRY. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction, and toxic epidermal necrolysis. Immediately discontinue SELZENTRY and other suspected agents if signs or symptoms of severe skin or hypersensitivity reactions develop and monitor clinical status, including liver aminotransferases, closely. • More cardiovascular events, including myocardial ischemia and/or infarction, were observed in treatment-experienced subjects who received SELZENTRY. Additional monitoring may be warranted. • If patients with severe renal impairment or ESRD receiving SELZENTRY (without concomitant CYP3A inducers or inhibitors) experience postural hypotension, the dose of SELZENTRY should be reduced from 300 mg twice daily to 150 mg twice daily. 5.1 Hepatotoxicity Hepatotoxicity with allergic features including life-threatening events has been reported in clinical trials and postmarketing. Severe rash or evidence of systemic allergic reaction including drug-related rash with fever, eosinophilia, elevated IgE, or other systemic symptoms have been reported in conjunction with hepatotoxicity . These events occurred approximately 1 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. Appropriate laboratory testing including ALT, AST, and bilirubin should be conducted prior to initiating therapy with SELZENTRY and at other time points during treatment as clinically indicated. Hepatic laboratory parameters should be obtained in any patient who develops rash, or signs or symptoms of hepatitis, or allergic reaction. 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. When administering SELZENTRY to patients with pre-existing liver dysfunction or who are co-infected with hepatitis B and/or C virus, additional monitoring may be warranted. 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 (including, but not limited to, severe rash or rash accompanied by fever, malaise, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, lip swelling, eosinophilia). 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 Eleven subjects (1.3%) who received SELZENTRY had cardiovascular events, including myocardial ischemia and/or infarction, during the Phase 3 trials in treatment‑experienced subjects (total exposure 609 patient‑years [300 on SELZENTRY once daily + 309 on SELZENTRY twice daily]), 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 use of SELZENTRY, and the relative contribution of SELZENTRY to these events is not known. In the Phase 2b/3 trial in treatment‑naive adult subjects, 3 subjects (0.8%) who received SELZENTRY had events related to ischemic heart disease 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-1–infected adult subjects in Phase 3 trials, postural hypotension was seen at a rate similar to placebo (approximately 0.5%). Patients with cardiovascular comorbidities, risk factors for postural hypotension, or receiving concomitant medication known to lower blood pressure, could be at increased risk of cardiovascular adverse events triggered by postural hypotension. Additional monitoring may be warranted. Postural Hypotension in Patients with Renal Impairment An increased risk of postural hypotension may occur in patients with severe renal insufficiency or in those with 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 adult 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

Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including SELZENTRY. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as infection with Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], tuberculosis, or reactivation of Herpes simplex and Herpes zoster ), which may necessitate further evaluation and treatment. 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 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, were comparable in the treatment groups during the Phase 3 adult treatment‑experienced trials of SELZENTRY. While there was a higher rate of certain upper respiratory tract infections reported in the treatment arm receiving SELZENTRY compared with placebo (23% versus 13%), there was a lower rate of pneumonia (2% versus 5%) reported in subjects receiving SELZENTRY. A higher incidence of Herpes virus infections (11 per 100 patient‑years) was also reported in the treatment arm receiving SELZENTRY when adjusted for exposure compared with placebo (8 per 100 patient‑years). In the Phase 2b/3 trial in treatment‑naive adult subjects, the incidence of AIDS-defining Category C events when adjusted for exposure was 1.8 for SELZENTRY compared with 2.4 for efavirenz per 100 patient‑years of exposure. Patients should be monitored closely for evidence of infections 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. The exposure-adjusted rate for malignancies per 100 patient‑years of exposure in adult treatment‑experienced trials was 4.6 for SELZENTRY compared with 9.3 on placebo. In treatment‑naive adult subjects, the rates were 1.0 and 2.4 per 100 patient‑years of exposure for SELZENTRY and efavirenz, respectively. Long-term follow-up is needed to more fully assess this risk.

• Coadministration with CYP3A inhibitors, including protease inhibitors (except tipranavir/ritonavir), will increase the concentration of SELZENTRY. • Coadministration with CYP3A inducers, including efavirenz, may decrease the concentration of SELZENTRY. • Coadministration with St. John’s wort is not recommended

Effect of Concomitant Drugs on the Pharmacokinetics of Maraviroc Maraviroc is metabolized by CYP3A and is also a substrate for P-glycoprotein (P-gp), organic anion-transporting polypeptide (OATP)1B1, and multidrug resistance-associated protein (MRP)2. The pharmacokinetics of maraviroc are likely to be modulated by inhibitors and inducers of CYP3A and P-gp and may be modulated by inhibitors of OATP1B1 and MRP2. Therefore, a dosage adjustment may be required when maraviroc is coadministered with those drugs . Concomitant use of maraviroc and St. John's wort ( Hypericum perforatum ) or products containing St. John's wort is not recommended. Coadministration of maraviroc with St. John's wort is expected to substantially decrease maraviroc concentrations and may result in suboptimal levels of maraviroc and lead to loss of virologic response and possible resistance to maraviroc. Additional drug interaction information is available .