Synercid (150mg of quinupristin and 350mg of dalfopristin)
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Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]
|[Prescribed dose] [250ml] [60 min]
Note: if patient complains of pain at injection site add prescribed dose to 500 ml D5W.
Stability / Miscellaneous
|Stability: RT: 5hr ; REF: 54 hr.
Reconstitution: dilute vial with 5 ml sterile water or D5W (concentration = 100 mg/ml). Do not shake. // If patient has a central line, may add prescribed dose to 100 ml D5W.
Supplied: 500mg vial (150mg of quinupristin and 350mg of dalfopristin) --keep refrigerated.
Dosing: 7.5 mg/kg every 8 to 12 hours. Dosage adjustment not required in renal failure.
Microbiology: The streptogramin components of Synercid, quinupristin and dalfopristin, are present in a ratio of 30 parts quinupristin to 70 parts dalfopristin. These two components act synergistically so that Synercid's microbiologic in vitro activity is greater than that of the components individually. Quinupristin's and dalfopristin's metabolites also contribute to the antimicrobial activity of Synercid. In vitro synergism of the major metabolites with the complementary parent compound has been demonstrated.
Synercid is bacteriostatic against Enterococcus faecium and bactericidal against strains of methicillin-susceptible and methicillin-resistant staphylococci.
The site of action of quinupristin and dalfopristin is the bacterial ribosome. Dalfopristin has been shown to inhibit the early phase of protein synthesis while quinupristin inhibits the late phase of protein synthesis.
In vitro combination testing of Synercid with aztreonam, cefotaxime, ciprofloxacin, and gentamicin against Enterobacteriaceae and Pseudomonas aeruginosa did not show antagonism.
In vitro combination testing of Synercid with prototype drugs of the following classes: aminoglycosides (gentamicin), ß-lactams (cefepime, ampicillin, and amoxicillin), glycopeptides (vancomycin), quinolones (ciprofloxacin), tetracyclines (doxycycline) and also chloramphenicol against enterococci and staphylococci did not show antagonism.
The mode of action differs from that of other classes of antibacterial agents such as ß-lactams, aminoglycosides, glycopeptides, quinolones, macrolides, lincosamides and tetracyclines. There is no cross resistance between Synercid and these agents when tested by the minimum inhibitory concentration (MIC) method.
In non-comparative studies, emerging resistance to Synercid during treatment of VREF infections occurred. Resistance to Synercid is associated with resistance to both components (i.e., quinupristin and dalfopristin).
Synercid has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections, as described in the INDICATIONS AND USAGE section.
Aerobic gram-positive microorganisms
NOTE: Synercid is not active against Enterococcus faecalis. Differentiation of enterococcal species is important to avoid misidentification of Enterococcus faecalis as Enterococcus faecium.
The following in vitro data are available, but their clinical significance is unknown.
The combination of quinupristin and dalfopristin (Synercid) exhibits in vitro minimum inhibitory concentrations (MIC's) of ≤1.0 µg/mL against most (≥90%) isolates of the following microorganisms; however, the safety and effectiveness of Synercid in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Aerobic gram-positive microorganisms
Vancomycin-resistant Enterococcus faecium (VREF)
One of Synercid's approved indications is for the treatment of patients with serious or life-threatening infections associated with vancomycin-resistant Enterococcus faecium (VREF) bacteremia. Synercid has been approved for marketing in the United States for this indication under FDA's accelerated approval regulations that allow marketing of products for use in life-threatening conditions when other therapies are not available. Approval of drugs for marketing under these regulations is based upon a demonstrated effect on a surrogate endpoint that is likely to predict clinical benefit.
Approval of this indication is based upon Synercid's ability to clear VREF from the bloodstream, with clearance of bacteremia considered to be a surrogate endpoint. There are no results from well-controlled clinical studies that confirm the validity of this surrogate marker. However, a study to verify the clinical benefit of therapy with Synercid on traditional clinical endpoints (such as cure of the underlying infection) is presently underway.
Complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin susceptible) or Streptococcus pyogenes. (See PACKAGE INSERT FOR CLINICAL STUDIES)
DOSAGE AND ADMINISTRATION
The minimum recommended treatment duration for Complicated Skin and Skin Structure Infections is seven days. For Vancomycin-Resistant Enterococcus faecium infection, the treatment duration should be determined based on the site and severity of the infection.
Preparation and administration of solution:
Reconstitute the 600 mg single dose vial by slowly adding 6 mL of 5% Dextrose in Water or Sterile Water for injection.
GENTLY swirl the vial by manual rotation without shaking to ensure dissolution of contents while LIMITING FOAM FORMATION.
According to the patient's weight, the reconstituted Synercid solution should be added to 250 mL of 5% Dextrose solution. An infusion volume of 100 mL may be used for central line infusions.
If moderate to severe venous irritation occurs following peripheral administration of Synercid diluted in 250 mL of Dextrose 5% in water, consideration should be given to increasing the infusion volume to 500 or 750 mL, changing the infusion site, or infusing by a peripherally inserted central catheter (PICC) or a central venous catheter.
The desired dose should be administered by intravenous infusion over 60 minutes.
Source: [package insert]