Clinical Guidelines Portal
Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Entry and Fusion Inhibitors
(Last updated:11/1/2012; last reviewed:11/1/2012)
Maraviroc (MVC, Selzentry)
|Maraviroc (MVC, Selzentry)
For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
Tablets: 150 mg and 300 mg
- Not approved for use in neonates/infants.
Adolescent (aged >16 years)/adult dose:
- Not approved for use in children aged <16 years.
- A pediatric clinical trial is under way.
|When given with potent CYP3A inhibitors (with or without CYP3A inducers) including protease inhibitors (PIs) (except tipranavir/ritonavir [TPV/r])
||150 mg twice daily
|When given with nucleoside reverse transcriptase inhibitors (NRTIs), enfuvirtide (ENF), TPV/r, nevirapine (NVP), raltegravir (RAL), and drugs that are not potent CYP3A inhibitors or inducers
||300 mg twice daily
|When given with potent CYP3A inducers including efavirenz (EFV) and etravirine (ETR) (without a potent CYP3A inhibitor)
||600 mg twice daily
||Selected Adverse Events
- Abdominal pain
- Musculoskeletal symptoms
- Upper respiratory tract infections
- Hepatotoxicity (which may be preceded by severe rash and/or other signs of systemic allergic reaction)
- Orthostatic hypotension (especially in patients with severe renal insufficiency)
- Conduct testing with HIV tropism assay (see Antiretroviral Drug-Resistance Testing in the main body of the guidelines) before using MVC to exclude the presence of CXCR4-using or mixed/dual-tropic HIV. Use MVC in patients with only CCR5-tropic virus. Do not use if CXCR4 or mixed/dual-tropic HIV is present.
- MVC can be given without regard to food.
- Instruct patients on how to recognize symptoms of allergic reactions or hepatitis.
- Use caution when administering MVC to patients with underlying cardiac disease.
- Cytochrome P450 3A4 (CYP3A4) substrate
- Dosing of MVC in patients with hepatic impairment:
Use caution when administering MVC to patients with hepatic impairment. Because MVC is metabolized by the liver, concentrations in patients with hepatic impairment may be increased.
- Do not use MVC in patients with creatinine clearance (CrCl) <30 mL/min who are receiving potent CYP3A4 inhibitors or inducers.
- Dosing of MVC in patients with renal impairment:
Refer to the manufacturer’s prescribing information.
Drug Interactions (see also the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents):
- Absorption: Absorption of maraviroc is somewhat reduced with ingestion of a high-fat meal; however, maraviroc can be given with or without food.
- Metabolism: Maraviroc is a CYP3A4 and p-glycoprotein (Pgp) substrate and requires dosage adjustments when administered with CYP- or Pgp-modulating medications.
- Before administration, a patient’s medication profile should be carefully reviewed for potential drug interactions with maraviroc.
- More common: Cough, fever, upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain, and dizziness.
- Less common (more severe): Hepatotoxicity that may be preceded by evidence of a systemic allergic reaction (such as pruritic rash, eosinophilia or elevated immunoglobulin [IgE]) has been reported. Serious adverse events occurred in less than 2% of maraviroc-treated adult patients and included cardiovascular abnormalities (such as angina, heart failure, myocardial infarction), hepatic cirrhosis or failure, cholestatic jaundice, viral meningitis, pneumonia, myositis, osteonecrosis, and rhabdomyolysis.
Resistance: The International AIDS Society-USA (IAS-USA) maintains a list of updated resistance mutations (see http://www.iasusa.org/resistance_mutations/index.html). Clinical failure may also represent the outgrowth of CXCR4-using (naturally resistant) HIV variants.
Pediatric Use: The pharmacokinetics (PK), safety, and efficacy of maraviroc in patients aged <16 years have not been established. A dose-finding study is under way in children aged 2 to 17 years.1 In this trial, maraviroc dose is based upon body surface area and the presence or absence of a potent CYP3A4 inhibitor in the background regimen. Preliminary PK data are encouraging in those on a potent CYP3A4 inhibitor, but exposures are very low in those not on a potent CYP3A4 inhibitor.
- Vouvahis M, McFadyen, L., Duncan, B., et al. Maraviroc pharmacokinetics in CCR5-tropic HIV-1-infected children aged 2-<18 years: Preliminary results from study A4001031. 3rd International Workshop on HIV Pediatrics, Jul 15-16, 2011.