Gram-positive bacteria. In-vitro data suggests streptogramins possess activity against gram-negative upper respiratory tract pathogens and gram-negative anaerobes.
Inhibition of mRNA translation by binding to the 50S subunit of bacterial ribosomes.
Predominantly independent of concentration once above four times the MIC of common Staphylococci and Streptococci.
Cmax: 3.2 and 7.96mg/L (quinupristin and dalfopristin respectively)
Half-life: 3.07 and 1.04 hours (quinupristin and dalfopristin respectively)
Volume of distribution: 0.45 and 0.24L/kg (quinupristin and dalfopristin respectively)
Venous irritation due to quinupristin/dalfopristin is common. In comparative trials approximately 40% of patients experienced infusion site adverse reactions compared to 25% of comparator treated patients. Increasing the infusion volume or administering the drug via central line may attenuate this reaction.
In two compassionate use studies, arthralgias (9.1%) and myalgias (6.6%) were the most common adverse event related to quinupristin/dalfopristin. Hyperbilirubinemia was documented in up to 25% of quinupristin/dalfopristin treated patients in compassionate use/non-comparative studies.
Intravenous only – available as 500mg (150mg quinupristin and 350mg dalfopristin) and 600mg (180mg quinupristin and 420mg dalfopristin) powder for reconstitution vials
Serious or life-threatening infections associated with vancomycin-resistant Enterococcus faecium – 7.5mg/kg every 8 hours
Complicated skin and skin structure infection caused by methicillin-susceptible S. aureus or S. pyogenes – 7.5mg/kg every 12 hours
Hepatic failure: Although no dosage official dosage adjustment recommendations exist, pharmacokinetic data in
patients with hepatic cirrhosis (Childs-Pugh class A or B) suggest that dosage adjustments may be necessary.
Renal failure: No dosing adjustments are necessary in patients with renal impairment or patients undergoing peritoneal dialysis.
Quinupristin/dalfopristin is a potent inhibitor of the cytochrome P450 3A4 isoenzyme system. Caution should be exercised and monitoring is suggested when concomitantly administering quinupristin/dalfopristin with drugs that have narrow therapeutic windows and are substrates of the CYP3A4 substrates.
Category B: No evidence of risk in humans but studies inadequate.
Synercid/DSM pharmaceuticals (Marketed by Monarch pharmaceuticals)
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