Reconstitution and Administration
Quinupristin and dalfopristin is administered by IV infusion over 60 minutes. Quinupristin and dalfopristin powder for injection must be reconstituted and diluted prior to administration. The manufacturer states that only 5% dextrose injection or sterile water for injection should be used to reconstitute the powder, and further dilution should be with 5% dextrose. Strict aseptic technique must be observed since the drug contains no preservative.
Vials labeled as containing 500 mg (150 mg of quinupristin and 350 mg of dalfopristin) should be reconstituted by slowly adding 5 mL of one of these diluents to provide a solution containing 100 mg/mL. The vial should be gently swirled by manual rotation to ensure dissolution; avoiding shaking to limit foaming. The vial should then be allowed to sit for a few minutes until all the foam has disappeared; the resulting solution should be clear. Reconstituted solutions of quinupristin and dalfopristin must be further diluted within 30 minutes, and such dilution is required prior to IV infusion. The appropriate dose is diluted in 250 mL of 5% dextrose injection for peripheral infusion and should not exceed a final concentration of 2 mg/mL.
If infused via a central line, 100 mL may be used for dilution. Increasing the infusion volume to 500-750 mL, changing the infusion site, or infusing the drug via a peripherally inserted central catheter (PICC) or central venous catheter can be used if moderate-to-severe venous irritation occurs.Dilutions are stable prior to infusion for 5 or 54 hours when stored at room temperature or refrigerated at 2-8°C, respectively. Reconstituted solutions or dilutions must not be used if precipitation or foreign matter is evident.
Dosage
Dosage is expressed in terms of combined mg of quinupristin and dalfopristin (i.e., in terms of “Synercid®”).
Vancomycin-resistant Enterococcus faecium Infections
The usual dosage of quinupristin and dalfopristin in adults and adolescents 16 years of age and older for the treatment of vancomycin-resistant Enterococcus faecium (VREF) is 7.5 mg/kg every 8 hours. This dosage also has been used in younger children, but experience is limited.Duration of therapy for VREF should be determined based on the site and severity of the infection.
Skin and Skin Structure Infections
The usual dosage of quinupristin and dalfopristin in adults and adolescents 16 years of age and older for the treatment of complicated skin and skin structure infections caused by susceptible Staphylococcus aureus (methicillin-susceptible strains) or Streptococcus pyogenes (group A b-hemolytic streptococci) is 7.5 mg/kg every 12 hours. This dosage also has been used in younger children, but experience is limited.The minimum recommended duration of therapy for complicated skin and skin structure infections is 7 days.
Special Populations
Quinupristin and dalfopristin pharmacokinetic data in patients with hepatic cirrhosis suggest that dosage reduction may be necessary, but specific recommendations cannot be made because of insufficient experience. Clinical studies suggest that the incidence of adverse effects in such patients was comparable to that in patients without hepatic impairment. No dosage adjustment is necessary in patients with renal impairment nor in geriatric patients.