Dosing and uses of Synercid (quinupristin/dalfopristin)
Adult dosage forms and strengths
quinupristin/dalfopristin
lyophilized powder for solution
- 500mg (150mg/350mg) per vial
Skin & Skin Structure Infection
Indicated for complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin susceptible) or Streptococcus pyogenes
7.5 mg/kg IV q12hr for at least 7 days
Also see Administration for IV preparation and infusion rate
Bacteremia (Off-label
IDSA guidelines recommend for methicillin-resistant S aureus
7.5 mg/kg IV q8hr
Intravascular Catheter-associated Bacteremia (Off-label)
IDSA guidelines recommend for methicillin-resistant coagulase negative staphylococci or ampicilin0 and vancomycin-resistant E Faecium)
7.5 mg/kg IV q8hr
Pediatric dosage forms and strengths
quinupristin/dalfopristin
lyophilized powder for solution
- 500mg (150mg/350mg) per vial
Skin & Skin Structure Infection
Indicated for complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin susceptible) or Streptococcus pyogenes
<16 years: Safety and efficacy not established
≥16 years: 7.5 mg/kg IV q12hr for at least 7 days
Also see Administration for IV preparation and infusion rate
Synercid (quinupristin/dalfopristin) adverse (side) effects
>10%
Local pain (40-44%)
Inflammation at infusion site (38-42%)
Hyperbilirubinemia (3-35%)
Local edema (17-18%)
Infusion site reaction (12-13%)
1-10%
Arthralgia (<1-8%)
Nausea (3-5%)
Myalgia (<1-5%)
Vomiting (3% to 4%)
Anemia (3%)
Diarrhea (3%)
incr LDH (3%)
Rash (3%)
Pain (2-3%)
Headache (2%)
Increased CPK (2%)
Increased GGT (2%)
Pruritus (2%)
Thrombophlebitis (2%)
Hyperglycemia (1%)
Warnings
Contraindications
Hypersensitivity to drug, or other streptogramins (eg, pristinamycin, virginiamycin)
Cautions
Not active against E. faecalis
Caution in hepatic impairment
May cause arthralgias/myalgias, hyperbilirubinemia and phlebitis
Prolonged use may result in fungal or bacterial superinfection
Inhibits metabolism of drugs metabolized by CYP3A4
May prolong QTc when administered concurrently with cisapride
Pregnancy and lactation
Pregnancy category: B
Lactation: unknown
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Synercid (quinupristin/dalfopristin)
Mechanism of action
Inhibits early and late phase protein synthesis at bacterial ribosome by binding at different sites on the 50S bacterial ribosomal unit
Quinupristin and dalfopristin act synergistically
Absorption
Peak plasma concentration: 3.2 mcg/mL (quinupristin and metabolites); 7.96 mcg/mL (dalfopristin and metabolite)
AUC: 7.2 mcg·h/mL (quinupristin and metabolites); 10.57 mcg·h/mL (dalfopristin and metabolite)
Distribution
Vd: 0.45 L/kg (quinupristin); 0.24 L/kg (dalfopristin)
Protein bound: Moderate
Metabolism
Quinupristin and dalfopristin are the main active components circulating in plasma
Quinupristin and dalfopristin are converted to several active major metabolites: 2 conjugated metabolites for quinupristin (1 with glutathione and 1 with cysteine) and 1 nonconjugated metabolite for dalfopristin (formed by drug hydrolysis)
Shown to be a major inhibitor; in vitro inhibits 70% cyclosporine biotransformation at 10 mcg/mL
Elimination
Half-life: 0.85 hr (quinupristin); 0.7 hr (dalfopristin); mean elimination half-lives, including metabolites: 3 and 1 hr, respectively
Clearance: 0.72 L/hr/kg (similar for both drugs)
Excretion: Feces (75-77% as unchanged drug and metabolites); urine (15-19%)
Administration
IV Incompatibilities
Solution: NaCl-containing diluents
IV Compatibilities
Y-site: aztreonam, ciprofloxacin, fenoldopam, fluconazole, haloperidol, metoclopramide, KCL
IV Preparation
Reconstitute 500 mg-containing vial with 5 mL of D5W or SWI to obtain 100 mg/mL solution
Do not shake; swirl gently to dissolve while limiting foam formation
Dilute reconstituted solution within 30 min
Reconstituted solution should be added to at least 250 mL of D5W for peripheral administration (increase to 500 mL or 750 mL if necessary to limit venous irritation). Final conc NMT 2 mg/mL
An infusion volume of 100 mL may be used for central line infusions
Do not freeze solution
IV Administration
Flush with D5W before and after administration; incompatible with saline
Complete infusion over 1 hr (toxicity may be increased with shorter infusion)
If severe venous irritation occurs following peripheral administration of quinupristin/dalfopristin diluted in 250 mL D5W, consider increasing the infusion volume to 500 mL or 750 mL, changing the infusion site, or infusing by a peripherally inserted central catheter (PICC) or a central venous catheter
Storage
Refrigerate unopened vials
