Pharmacodynamics: Maraviroc binds specifically and selectively to the host protein CCR5, one of two chemokine receptors necessary for entrance of HIV into CD4+ cells.
Indications: Maraviroc is approved for adults with CCR5-tropic (also known as R5) HIV-1 infection who are experiencing virologic failure due to resistance to other antiretroviral agents. Since maraviroc is active against HIV that uses the CCR5 co-receptor exclusively, and not against HIV strains with CXCR4, dual, or mixed tropism, tropism testing should be performed before initiating treatment with maraviroc.
Pharmacokinetics: The absorption of maraviroc is rapid but variable, with the
time to maximum absorption generally being 1–4 hours after ingestion of the
drug. Most of the drug (≥ 75%) is excreted in the feces, whereas approximately
20% is excreted in urine. The recommended dose of maraviroc varies according to
renal function and the concomitant use of CYP3A inducers or inhibitors. Maraviroc has been shown to have excellent
penetration into the cervicovaginal fluid, with levels almost four times higher
than the corresponding concentrations in blood plasma.
Contraindications: Maraviroc is contraindicated in patients with severe or
end-stage renal impairment who are taking concurrent CYP3A inhibitors or
inducers, and caution is advised when used in patients with preexisting hepatic
impairment and in those co-infected with HBV or HCV.
Drug-drug interactions: Maraviroc is a substrate for CYP3A4 and therefore requires
adjustment in the presence of drugs that interact with these enzymes. It is
also a substrate for P-glycoprotein, which limits intracellular concentrations
of the drug. The dosage of maraviroc must be decreased if it is co-administered
with strong CYP3A inhibitors (eg, delavirdine, ketoconazole, itraconazole,
clarithromycin, or any protease inhibitor other than tipranavir) and must be
increased if co-administered with CYP3A inducers (eg, efavirenz, etravirine,
rifampin, carbamazepine, phenytoin, or St. John’s wort).
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