Usual Adult Dose for Skin or Soft Tissue Infection

Complicated: 7.5 mg/kg IV every 12 hours, infused over 1 hour

Usual Adult Dose for Bacteremia

Vancomycin-resistant Enterococcus faecium infection: 7.5 mg/kg IV every 8 hours, infused over 1 hour

This indication is no longer approved by the FDA. The submitted data failed to confirm clinical benefit for this condition.

Usual Pediatric Dose for Skin or Soft Tissue Infection

Less than 12 years: Data not available
12 to less than 18 years: 7.5 mg/kg IV every 12 hours, infused over 1 hour

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Data from clinical trials suggest that the incidence of adverse effects in patients with chronic liver insufficiency or cirrhosis was comparable to that in patients with normal hepatic function. Pharmacokinetic data in patients with hepatic cirrhosis (Child Pugh A or B) suggest that dosage reduction may be necessary but exact recommendations cannot be made at this time.

Precautions

Clostridium difficile associated diarrhea (CDAD) has been reported with almost all antibiotics and may potentially be life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea following dalfopristin-quinupristin therapy. Mild cases generally improve with discontinuation of the drug, while severe cases may require supportive therapy and treatment with an antimicrobial agent effective against C difficile. Hypertoxin producing strains of C difficile cause increased morbidity and mortality; these infections can be resistant to antimicrobial treatment and may necessitate colectomy.

Dalfopristin-quinupristin is a major inhibitor of CYP450 3A4. If concurrently administered drugs are substrates of this isoenzyme and have narrow therapeutic windows, their levels should be monitored, and substrates that prolong the QTc interval should be avoided.

Dalfopristin-quinupristin should not be administered as a bolus due to the potential for increased toxicity. It should be infused over 60 minutes. There are no data on the safety of other infusion durations. Animal toxicity was higher with bolus administration compared to slow infusion.

To minimize venous irritation, a peripheral infusion should be followed by a flush with 5% dextrose in water. Saline and heparin are incompatible and should not be used for dilution or flushing. If moderate to severe venous irritation occurs with peripheral infusions of 250 mL, increasing the infusion volume to 500 mL or 750 mL, changing the infusion site, or infusing via a PICC line or central venous catheter should be considered.

Cases of arthralgia and myalgia, some severe, have been reported in with dalfopristin-quinupristin. Some patients showed improvement after reducing the dose frequency to every 12 hours. Symptoms resolved after treatment was discontinued in those patients available for follow-up.

Use of antibiotics may result in superinfections of nonsusceptible organisms. Appropriate measures should be taken if superinfection occurs during therapy.

To reduce the risk of development of drug-resistant organisms, antibiotics should only be used to treat or prevent proven or suspected infections caused by bacteria.

Safety and efficacy have not been established in pediatric patients less than 16 years of age.

Dialysis

No adjustment recommended.

Other Comments

The dosage is expressed in terms of combined "mg" of dalfopristin plus quinupristin.

The minimum recommended treatment duration for complicated skin and skin structure infections is 7 days.