Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Entry and Fusion Inhibitors
Last Updated: April 27, 2017; Last Reviewed: April 27, 2017
|Maraviroc (MVC, Selzentry)
For additional information see Drugs@FDA: http://www.accessdata.fda.gov/scripts/cder/daf/
|Tablets: 25 mg, 75mg, 150 mg and 300 mg
Oral Solution: 20 mg/mL
|Dosing Recommendations||Selected Adverse Events|
Drug Interactions (see also the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and http://www.hiv-druginteractions.org/)
Absorption of maraviroc is slightly reduced with ingestion of a high-fat meal. There were no food restrictions in the adult trials (using the tablet formulation) or in the pediatric trial (using both tablet and oral solution formulations) that demonstrated the efficacy/antiviral activity and safety of maraviroc. Therefore, maraviroc can be given with or without food.
Maraviroc is a cytochrome P (CYP)3A 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; recommended maraviroc dosages are based on concomitant medications and their anticipated effect on maraviroc metabolism.
- 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) has been reported. Serious adverse events (AEs) occurred in fewer than 2% of maraviroc-treated adult patients and included cardiovascular abnormalities (e.g., angina, heart failure, myocardial infarction), hepatic cirrhosis or failure, cholestatic jaundice, viral meningitis, pneumonia, myositis, osteonecrosis, and rhabdomyolysis.
HIV tropism assay should be performed before use. The International AIDS Society-USA (IAS-USA) maintains a list of updated resistance mutations (see http://iasusa.org/sites/default/files/tam/october_november_2015.pdf#page=10). Clinical failure may also represent the outgrowth of CXCR4-using (naturally resistant) HIV variants.
Maraviroc is approved by the Food and Drug Administration in children aged ≥2 years and weighing ≥10 kg who have CCR5-tropic HIV-1.1
Pharmacokinetics and Efficacy
The pharmacokinetics, safety, and efficacy of maraviroc have been examined in a dose-finding and efficacy study involving treatment experienced children aged 2 to 17 years weighing at least 10 kg and having HIV-1 plasma RNA >1000 copies/mL. In this trial, maraviroc dose was based upon body surface area and the composition of the optimized background therapy: most (90/103; 87%) received maraviroc in combination with potent CYP3A inhibitors, and only 3 participants received maraviroc with CYP3A inducers. The key pharmacologic target (geometric mean Caverage of >100 ng/mL) was achieved with both the tablet and oral solution formulations of maraviroc. From a mean baseline plasma HIV-1 RNA of 4.4 log10 copies/mL, a decrease of >1 log10 occurred in all 4 age-based cohorts. Overall, 48% of participants achieved a decrease to <48 copies/mL at Study Week 48 and 65% of subjects achieved plasma HIV-1 RNA <400 copies/mL. The most common maraviroc-related AEs through 48 weeks were diarrhea (16.5%), vomiting (16.5%), and upper respiratory infections (13.6%).2
- Maravirioc (Selezentry) [package insert]. Food and Drug Administration. 2016. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208984_022128s017lbl.pdf.
- Giaquinto C, Mawela MP, Chokephaibulkit C, et al. Pharmacokinetics, safety and efficacy of maraviroc in pediatric patients with R5 HIV. Presented at: Conference on Retroviruses and Opportunistic Infections. 2016.Boston, MA.