Medical Pharmacology Chapter 35  Antibacterial Drugs

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Quinuprisin/dalfopristin (Synercid)
  • Overview

    • FDA-accelerated approval for:

      •  IV treatment of bacteremia & life-threatening infection due to vancomycin (Vancocin)-resistant Enterococcus faecium (VREF)

      •  Treatment of complicated skin & skin structure infections due to Staphylococcus aureus and Streptococcus pyrogenes

  •  Quinuprisin/dalfopristin (Synercid): properties

    • Two streptogramin antibacterials (30:70 combination)

    • Target: bacterial ribosomes

    • Effect: disruption of protein synthesis

  • Antibacterial Characteristics:

    • Active: against E. faecium (not against Enterococcus faecalis)

    • Active (in vitro): against methicillin (Staphcillin)-susceptible and-resistant S. aureus and S. epidermidis

    • Active (in vitro): against penicillin-susceptible &-resistant Streptococcus pneumoniae

    • Active (in vitro): against

      • Neisseria meningitidis, Moraxella cattarrhalis, Legionella pneumophila, Mycoplasma pneumoniae, Clostridium perfringens

  • Pharmacokinetics

    • IV administration

    • Hepatic metabolism

    • Biliary excretion

  • Some clinical trial results:

    • quinuprisin/dalfopristin (Synercid) --

      • As effective as vancomycin (Vancocin) in treating catheter-related bacteremia due to S. aureus

      • Effective in treatingVREF in aortic graft

      • Effective in treating a prosthetic valve

      • Effective in treating pericarditis is associated with continuous peritoneal dialysis

  •  Adverse Effects:

    •  Infusion site pain, inflammation, edema, thrombophlebitis -- frequency: 75%

    •  Arthralgias & myalgias: common, may be severe

    •  Drug-drug interactions

      • Quinuprisin/dalfopristin (Synercid) inhibitor of CYP3A4 (cytochrome P450 3A4) -- suggests cautious use in patients taking drugs metabolized by this enzyme

        • Increased serum nifedipine (Procardia, Adalat) concentration

        • Increased midazolam (Versed) serum concentration

        • Increased cyclosporine (Sandimmune, Neoral) serum concentration

        • Co-administration of quinuprisin/dalfopristin (Snercid) and drugs metabolized by CYP3A4 which may prolong Q-T intervals should be avoided (example: cisapride (Propulsid))

  • Clinical Use:  conclusion

    •  Quinuprisin/dalfopristin (Synercid) -- modestly effective for treatment of vancomycin (Vancocin)-resistant Enterococcus faecium bacteremia-- this effect may be life-saving

    •  High incidence of side effects and adverse drug-drug interactions suggest quinuprisin/dalfopristin (Synercid) should only rarely be used to treat any other type of infection

    The Medical Letter, climbed 41 (issue 1066), November 19, 1999, The Medical Letter Inc., New Rochelle, New York.

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