quinupristin and dalfopristin
Synercid

Available forms
Available by prescription only
Injection: 500 mg/10 ml (150 mg quinupristin and 350 mg dalfopristin)

Indications and dosages
 Serious or life-threatening infections related to vancomycin-resistant Enterococcus faecium bacteremia. Adults and adolescents age 16 and older: 7.5 mg/kg by I.V. infusion over 1 hour q 8 hours. Treatment duration should be determined by the site and severity of the infection.
 Complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin susceptible) or Streptococcus pyogenes. Adults and adolescents age 16 and older: 7.5 mg/kg by I.V. infusion over 1 hour q 12 hours for at least 7 days.

Pharmacodynamics
Antibiotic action: Quinupristin and dalfopristin work synergistically to inhibit or destroy susceptible bacteria by inhibiting protein synthesis in bacterial cells. Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome; quinupristin inhibits the late phase of protein synthesis. Unable to manufacture new proteins, bacterial cells are inactivated or die.

Pharmacokinetics
Absorption: Quinupristin and dalfopristin have differing profiles. Following infusion of multiple 7.5-mg/kg doses every 8 hours, peak quinupristin levels and metabolites are 3.2 mcg/ml; peak dalfopristin levels are 8.0 mcg/ml.
Distribution: Protein-binding is moderate.
Metabolism: Both drugs are converted to several active major metabolites by nonenzymatic reactions.
Excretion: Biliary excretion and fecal elimination accounts for about 75% of both drugs and their metabolites. Urinary excretion accounts for about 15% of quinupristin dose and 19% of dalfopristin dose. Elimination half-lives of quinupristin and dalfopristin are about 0.85 and 0.70 hours, respectively.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other streptogramin antibiotics.

Interactions
Drug-drug. Calcium channel blockers (such as diltiazem, nifedipine, or verapamil), carbamazepine, cyclosporine, delavirdine, diazepam, disopyramide, docetaxel, HMG-CoA reductase inhibitors, indinavir, lidocaine, methylprednisolone, nevirapine, ritonavir, midazolam, paclitaxel, tacrolimus, vinca alkaloids: Increases levels of these drugs; may increase therapeutic effects and adverse reactions. Use together cautiously. Monitor cyclosporine levels.
Drugs metabolized by cytochrome P-450 3A4 that increase the QTc interval on the ECG (quinidine and others): Decreases metabolism of these drugs, resulting in prolonged QTc interval. Avoid use together.

Adverse reactions
CNS: headache, pain.
CV: thrombophlebitis.
GI: nausea, diarrhea, vomiting, pseudomembranous colitis.
Musculoskeletal: arthralgia, myalgia.
Skin: rash, pruritus; inflammation, pain, edema at infusion site; infusion site reaction.

Effects on lab test results
• Increases AST, ALT, and bilirubin levels.

Overdose and treatment
Patients who receive an overdose should be observed and given supportive care. Drug isn’t removed by peritoneal dialysis or hemodialysis.

Special considerations
 ALERT Quinupristin-dalfopristin isn’t active against Enterococcus faecalis. Appropriate blood cultures are needed to avoid misidentifying E. faecalis as E. faecium.
• Drug may cause mild to life-threatening pseudomembranous colitis; consider this diagnosis in patients who develop diarrhea during or after therapy.
• Reconstitute powder for injection by adding 5 ml of either sterile water for injection or D₅W and gently swirling vial to ensure dissolution; avoid shaking to limit foaming. Reconstituted solutions must be further diluted within 30 minutes.
• The appropriate dose (according to patient’s weight) of reconstituted solution should be added to 250 ml of D₅W to make a final concentration of no more than 2 mg/ml. This diluted solution is stable for 5 hours at room temperature or 54 hours if refrigerated.
• Fluid-restricted patient with a central venous catheter may receive dose in 100 ml of D₅W, but this concentration isn’t recommended for peripheral venous administration.
• If patient develops moderate to severe peripheral venous irritation, consider increasing infusion volume to 500 or 750 ml, changing injection site, or infusing via central venous catheter.
• Give all doses by I.V. infusion over 1 hour. An infusion pump or device may be used to control rate of infusion.
• Quinupristin-dalfopristin is incompatible with saline and heparin solutions. Don’t dilute drug with saline solutions or infuse into lines that contain saline or heparin. Flush line with D₅W before and after each dose.
• Adverse reactions, such as arthralgia and myalgia, may be reduced by decreasing dosage interval to every 12 hours.
• Because nonsusceptible organisms may overgrow, monitor patient closely for signs and symptoms of superinfection.
• Monitor liver function test results during therapy.
Pregnant patients
• Safety hasn’t been established for use during pregnancy.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in patients younger than age 16 haven’t been established. In limited clinical trials, children received 7.5 mg/kg every 8 or 12 hours.
Geriatric patients
• No dosage adjustment is needed for elderly patients.

Patient education
• Advise patient to report irritation at I.V. site, pain in joints or muscles, and diarrhea immediately.
• Tell patient about the importance of reporting persistent or worsening symptoms of infection, such as pain or erythema.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use