Quinupristin/dalfopristin

Intravenous, usually 7.5 mg/kg every 8 hours (infections/life threatening VRSA); every 12 hours (skin infections). No renal dosing adjustments, hepatic dosing adjustments are not defined, consider reducing dose. ==Mechanism of action==

Quinupristin and dalfopristin are protein synthesis inhibitors in a synergistic manner. While each of the two is only a bacteriostatic agent, the combination shows bactericidal activity. • Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, and changes the conformation of it, enhancing the binding of quinupristin by a factor of about 100. In addition, it inhibits peptidyl transfer. • Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide, as well as causing incomplete chains to be released. ==Pharmacokinetics==

Clearance by the liver CYP450:3A4 inhibitor, half-life quinupristin 0.8 hours, dalfopristin 0.7 hours (with persistence of effects for 9–10 hours). ==Side effects==

Serious: • C.diff-associated diarrhea • superinfection • anaphylactoid reactions • angioedema Common: • Joint aches (arthralgia) or muscle aches (myalgia) • Nausea, diarrhea (C. diff associated) or vomiting • Rash or itching • Headache • Hyperbilirubinemia • Anemia • Thrombophlebitis ==Drug interactions==

The drug inhibits P450 and enhances the effects of terfenadine, astemizole, indinavir, midazolam, calcium channel blockers, warfarin, cisapride and ciclosporin. == References ==