indication

For treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

pharmacology

Maraviroc is a chemokine receptor antagonist drug developed by the drug company Pfizer that is designed to act against HIV by interfering with the interaction between HIV and CCR5.

mechanism of action

Maraviroc is an entry inhibitor and works by blocking HIV from entering human cells. Specifically maraviroc is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR5 and HIV-1 gp120. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the membrane of CD4 cells (T-cells), preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.

biotransformation

In vitro studies indicate that CYP3A is the major enzyme responsible for maraviroc metabolism.

absorption

The absolute oral bioavailability of a 100 mg dose is 23% and is predicted to be 33% at 300 mg. Coadministration of a 300mg tablet with a high fat breakfast reduced maraviroc Cmax and AUC by 33% in healthy volunteers.

half life

14-18 hours

drug interactions

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. When used with a strong CYP3A4 inhibitor, the adult dose of maraviroc should be decreased to 150 mg twice daily. Maraviroc is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min) receiving a strong CYP3A4 inhibitor. Maraviroc may be administered at a dose of 300 mg twice daily with concomitant tipranavir/ritonavir but not with other ritonavir combinations.

Telithromycin: Telithromycin may reduce clearance of Maraviroc. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Maraviroc if Telithromycin is initiated, discontinued or dose changed.

Topiramate: Topiramate, a CYP3A4 inducer, may decrease the serum concentration of Maraviroc by increasing Maraviroc metabolism and clearance. A dose adjustment of Maraviroc may be required. Monitor for changes in Maraviroc therapeutic and adverse effects if Topiramate is initiated, discontinued or dose changed.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of maraviroc by decreasing its metabolism. A dose reduction in maraviroc is warranted. Monitor for changes in the therapeutic and adverse effects of maraviroc if voriconazole is initiated, discontinued or dose changed.