Usual Adult Dose for HIV Infection

With potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer): 150 mg orally twice a day

With noninteracting concomitant medications: 300 mg orally twice a day

With potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor): 600 mg orally twice a day

Comments:

• Potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer) including: protease inhibitors (except tipranavir/ritonavir), elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, cobicistat, nefazodone, telithromycin
• Noninteracting concomitant medications include all agents that are not potent CYP450 3A inhibitors or inducers such as: dolutegravir, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, enfuvirtide.
• Potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor) including: efavirenz, rifampin, etravirine, carbamazepine, phenobarbital, phenytoin

Use: In combination with other antiretroviral agents, for the treatment of only C-C chemokine receptor type 5 (CCR5)-tropic HIV-1 infection

Usual Pediatric Dose for HIV Infection

ORAL SOLUTION:
Weight At Least 2 kg:
With potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer):

• Weight 2 to less than 10 kg: Not recommended (insufficient data available to recommended use).
• Weight 10 to less than 20 kg: 50 mg orally twice a day
• Weight 20 to less than 30 kg: 80 mg orally twice a day
• Weight 30 to less than 40 kg: 100 mg orally twice a day
• Weight at least 40 kg: 150 mg orally twice a day

With noninteracting concomitant medications:

• Weight 2 to less than 4 kg: 30 mg orally twice a day
• Weight 4 to less than 6 kg: 40 mg orally twice a day
• Weight 6 to less than 10 kg: 100 mg orally twice a day
• Weight 10 to less than 14 kg: 150 mg orally twice a day
• Weight 14 to less than 30 kg: 200 mg orally twice a day
• Weight at least 30 kg: 300 mg orally twice a day

With potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor): Not recommended (insufficient data available to recommended use).

TABLETS:
2 Years or Older Weighing At Least 10 kg:
With potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer):

• Weight 10 to less than 20 kg: 50 mg orally twice a day
• Weight 20 to less than 30 kg: 75 mg orally twice a day
• Weight 30 to less than 40 kg: 100 mg orally twice a day
• Weight at least 40 kg: 150 mg orally twice a day

With noninteracting concomitant medications:

• Weight 10 to less than 14 kg: 150 mg orally twice a day
• Weight 14 to less than 30 kg: 200 mg orally twice a day
• Weight at least 30 kg: 300 mg orally twice a day

With potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor): Not recommended (insufficient data available to recommended use).

Comments:

• Recommended dose should be based on body weight and should not exceed the recommended adult dose.
• Potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer) including: protease inhibitors (except tipranavir/ritonavir), elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, cobicistat, nefazodone, telithromycin
• Noninteracting concomitant medications include all agents that are not potent CYP450 3A inhibitors or inducers such as: dolutegravir, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, enfuvirtide.
• Potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor) including: efavirenz, rifampin, etravirine, carbamazepine, phenobarbital, phenytoin

Use: In combination with other antiretroviral agents, for the treatment of only CCR5-tropic HIV-1 infection

Renal Dose Adjustments

Adult Patients:

• Mild to moderate renal dysfunction (CrCl 30 to 80 mL/min): No adjustment recommended.
• Severe renal dysfunction (CrCl less than 30 mL/min):
• With potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer): Contraindicated
• With noninteracting concomitant medications: No adjustment recommended.
• With potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor): Contraindicated

Pediatric Patients:

• Mild or moderate renal dysfunction (CrCl 30 to 80 mL/min): Data not available
• Severe renal dysfunction (CrCl less than 30 mL/min): Contraindicated in patients receiving potent CYP450 3A inhibitors or inducers

Comments:

• Potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer) including: protease inhibitors (except tipranavir/ritonavir), elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, cobicistat, nefazodone, telithromycin
• Noninteracting concomitant medications include all agents that are not potent CYP450 3A inhibitors or inducers such as: dolutegravir, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, enfuvirtide.
• Potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor) including: efavirenz, rifampin, etravirine, carbamazepine, phenobarbital, phenytoin

Liver Dose Adjustments

Adult Patients:

• Mild to moderate liver dysfunction: No adjustment recommended.
• Severe liver dysfunction: Data not available

Pediatric Patients: Data not available

Comments:

• Adults with moderate liver dysfunction using maraviroc 150 mg with a potent CYP450 3A inhibitor should be monitored closely for drug-related side effects.

Precautions

US BOXED WARNING:

• HEPATOTOXICITY: Hepatotoxicity reported. Severe rash or evidence of systemic allergic reaction (e.g., fever, eosinophilia, elevated immunoglobulin E [IgE]) may precede hepatotoxicity. Patients with signs/symptoms of hepatitis or allergic reaction after use of this drug should be evaluated at once.

CONTRAINDICATIONS:

• Severe renal dysfunction or ESRD (CrCl less than 30 mL/min) when concurrently taking potent CYP450 3A inhibitors or inducers

This drug is not recommended for use in preterm neonates or pediatric patients weighing less than 2 kg.

Consult WARNINGS section for additional precautions.

Dialysis

ESRD on Regular Hemodialysis:
Adult patients:

• With potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer): Contraindicated
• With noninteracting concomitant medications: No adjustment recommended; however, if any symptoms of postural hypotension develop, dose should be reduced to 150 mg orally twice a day.
• With potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor): Contraindicated

Pediatric patients: Contraindicated in patients receiving potent CYP450 3A inhibitors or inducers

Comments:

• Potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer) including: protease inhibitors (except tipranavir/ritonavir), elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, cobicistat, nefazodone, telithromycin
• Noninteracting concomitant medications include all agents that are not potent CYP450 3A inhibitors or inducers such as: dolutegravir, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, enfuvirtide.
• Potent and moderate CYP450 3A inducers (without a potent CYP450 3A inhibitor) including: efavirenz, rifampin, etravirine, carbamazepine, phenobarbital, phenytoin

Other Comments

Administration advice:

• Before starting this drug for treatment of HIV-1 infection, test all patients for CCR5 tropism using a highly sensitive tropism assay.
• Before starting this drug and periodically during therapy as clinically indicated, monitor patients for ALT, AST, and bilirubin.
• Administer with other antiretroviral agents.
• Administer with or without food.
• Do not chew the tablets; swallow whole.
• Before prescribing the tablets, assess children for ability to swallow tablets; if child is unable to reliably swallow the tablets, use the oral solution formulation.
• Administer the oral solution with the included press-in bottle adapter and the appropriate oral dosing syringe: for doses up to 2.5 mL, use the 3-mL syringe; for doses greater than 2.5 mL, use the 10-mL syringe. Take care when measuring neonate doses due to the small volume of oral solution needed.
• Discard any unused oral solution 60 days after first opening the bottle.
• Consult the manufacturer product information regarding missed doses.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted between 15C and 30C (59F and 86F).

General:

• Limitations of Use: This drug is not recommended for patients with C-X-C chemokine receptor type 4 (CXCR4)-tropic or dual/mixed-tropic HIV-1.
• This drug is recommended for patients with only CCR5-tropic HIV-1 infection; outgrowth of preexisting low-level CXCR4-tropic or dual/mixed-tropic HIV-1 not identified by tropism testing at screening has been associated with virologic failure on this drug.
• Recommended dosage differs based on coadministered agents (due to drug interactions).

Monitoring:

• General: For CCR5 tropism (before therapy); for infections (during therapy)
• Hepatic: ALT, AST, and bilirubin (before starting and periodically during therapy as clinically indicated)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Stop this drug and seek medical evaluation at once if signs/symptoms of hepatitis or allergic reaction develop after using this drug.
• Avoid potentially hazardous activities (e.g., driving, operating machinery) if dizziness occurs during therapy.
• It is important to take this drug with other antiretroviral agents on a regular dosing schedule; avoid missing doses as it can lead to development of resistance.