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Pronunciation
(kwi NYOO pris tin & dal FOE pris tin)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of complicated skin and skin structure infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes
Use: Unlabeled
Treatment of persistent MRSA bacteremia associated with vancomycin failure
Pregnancy Risk Factor
B
Pregnancy Considerations
Because adverse effects were not observed in animal reproduction studies, quinupristin/dalfopristin is classified pregnancy category B. There are no adequate and well-controlled studies of quinupristin/dalfopristin in pregnant women.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
It is not known if quinupristin/dalfopristin is excreted in human milk. The manufacturer recommends caution if administering quinupristin/dalfopristin to a nursing woman. The increased molecular weight of quinupristin/dalfopristin may minimize excretion into human milk. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to quinupristin, dalfopristin, pristinamycin, or virginiamycin, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Arthralgias/myalgias: May cause arthralgias and/or myalgias with use; reduction of dosing frequency may improve.
• Hyperbilirubinemia: May cause hyperbilirubinemia (>5 times ULN) possibly through competition for excretory pathways.
• Phlebitis: May cause pain and phlebitis when infused through a peripheral line (not relieved by hydrocortisone or diphenhydramine).
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Concurrent drug therapy issues:
• Cisapride: Concurrent therapy with cisapride (which may prolong QTc interval and lead to arrhythmias) should be avoided.
• Drugs metabolized by CYP3A4: May inhibit the metabolism of many drugs metabolized by CYP3A4.
Adverse Reactions
>10%:
Hepatic: Hyperbilirubinemia (3% to 35%)
Local: Local pain (40% to 44%), inflammation at infusion site (38% to 42%), local edema (17% to 18%), infusion site reaction (12% to 13%)
Neuromuscular & skeletal: Arthralgia (up to 47%), myalgia (up to 47%)
1% to 10%:
Central nervous system: Pain (2% to 3%), headache (2%)
Dermatologic: Rash (3%), pruritus (2%)
Endocrine & metabolic: Hyperglycemia (1%)
Gastrointestinal: Nausea (3% to 5%), vomiting (3% to 4%), diarrhea (3%)
Hematologic: Anemia (3%)
Hepatic: GGT increased (2%), LDH increased (3%)
Local: Thrombophlebitis (2%)
Neuromuscular & skeletal: CPK increased (2%)
<1%: Abdominal pain, allergic reaction, anaphylactoid reaction, anxiety, apnea, arrhythmia, bone pain, BUN increased, cardiac arrest, chest pain, coagulation disorder, confusion, constipation, creatinine increased, diaphoresis, dizziness, dysautonomia, dyspepsia, dyspnea, encephalopathy, fever, gastrointestinal hemorrhage, gout, hematuria, hemolysis, hemolytic anemia, hepatitis, hyperkalemia, hypertonia, hypoglycemia, hyponatremia, hypotension, hypoventilation, hypovolemia, infection, insomnia, leg cramps, maculopapular rash, mesenteric artery occlusion, myasthenia, neck rigidity, neuropathy, oral candidiasis, palpitation, pancreatitis, pancytopenia, paraplegia, paresthesia, pericarditis, peripheral edema, phlebitis, pleural effusion, pseudomembranous colitis, respiratory distress, seizure, shock, skin ulcer, stomatitis, syncope, thrombocytopenia, tremor, transaminases increased, urticaria, vaginitis, vasodilation
Metabolism/Transport Effects
Refer to individual components.
Drug Interactions
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
CycloSPORINE: Quinupristin may increase the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Quinupristin may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Storage
Store unopened vials under refrigeration at 2°C to 8°C (36°F to 46°F). The following stability information has also been reported: May be stored at room temperature for up to 7 days (Cohen, 2007).
Reconstitution
Reconstitute single dose vial with 5 mL of 5% dextrose in water or sterile water for injection. Swirl gentle to dissolve; do not shake (to limit foam formation). The reconstituted solution should be diluted within 30 minutes. Stability of the diluted solution prior to the infusion is established as 5 hours at room temperature or 54 hours if refrigerated at 2°C to 8°C (36°F to 46°F). Reconstituted solution should be added to at least 250 mL of 5% dextrose in water for peripheral administration (increase to 500 mL or 750 mL if necessary to limit venous irritation). An infusion volume of 100 mL may be used for central line infusions. Do not freeze solution.
Compatibility
Stable in D5W; incompatible with saline.
Y-site administration: Compatible: Anidulafungin, aztreonam, caspofungin, ciprofloxacin, fenoldopam, fluconazole (used as undiluted solution), haloperidol, metoclopramide (undiluted), or potassium chloride when admixed in D5W.
Mechanism of Action
Quinupristin/dalfopristin inhibits bacterial protein synthesis by binding to different sites on the 50S bacterial ribosomal subunit thereby inhibiting protein synthesis
Pharmacodynamics/Kinetics
Distribution: Quinupristin: 0.45 L/kg; Dalfopristin: 0.24 L/kg
Metabolism: To active metabolites via nonenzymatic reactions
Half-life elimination: Quinupristin: 0.85 hour; Dalfopristin: 0.7 hour (mean elimination half-lives, including metabolites: 3 and 1 hours, respectively)
Excretion: Feces (75% to 77% as unchanged drug and metabolites); urine (15% to 19%)
Dosage
I.V.: Children ≥12 years and Adults:
Complicated skin and skin structure infection: 7.5 mg/kg every 12 hours for at least 7 days
Bacteremia, MRSA (persistent, vancomycin failure) (unlabeled use): 7.5 mg/kg every 8 hours (Liu, 2011)
Dosage adjustment in renal impairment: No adjustment required in renal failure, hemodialysis, or peritoneal dialysis
Dosage adjustment in hepatic impairment: Pharmacokinetic data suggest dosage adjustment may be necessary; however, specific recommendations have not been proposed
Elderly: No dosage adjustment is required
Administration: I.V.
Line should be flushed with 5% dextrose in water prior to and following administration. Infusion should be completed over 60 minutes (toxicity may be increased with shorter infusion). If severe venous irritation occurs following peripheral administration of quinupristin/dalfopristin diluted in 250 mL 5% dextrose in water, consideration should be given to 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.
Monitoring Parameters
Culture and sensitivity
Patient Education
This drug can only be administered by intravenous infusion. Report immediately any pain, irritation, redness, burning, or swelling at infusion site. Report headache; rash; nausea; vomiting; diarrhea; pain; heat or swelling in muscle areas, especially in lower extremities; respiratory difficulty, tremors; or difficulty speaking.
Geriatric Considerations
No pharmacokinetic changes in the elderly in one study. No dose adjustment necessary.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May rarely cause anxiety, confusion, or insomnia
Mental Health: Effects on Psychiatric Treatment
May rarely produce pancytopenia; caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess allergy history prior to starting treatment. Use caution in presence of hepatic or renal impairment. Infusion site must be closely monitored (may cause venous irritation). Monitor for arthralgia, headache, rash, hyperglycemia, opportunistic infection (fever, chills, sore throat, burning urination, fatigue), pseudomembranous colitis, hyperbilirubinemia, dyspnea, and ataxia.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Synercid®: 500 mg: Quinupristin 150 mg and dalfopristin 350 mg
References
Bryson HM and Spencer CM, “Quinupristin/Dalfopristin,” Drugs, 1996, 52(3):406-15.
Chant C and Rybak MH, “Quinupristin/Dalfopristin (RP 59500): A New Streptogramin Antibiotic,” Ann Pharmacother, 1995, 29(10):1022-7.
Griswold MW, Lomaestro BM, and Briceland LL, “Quinupristin-Dalfopristin (RP 59500): An Injectable Streptogramin Combination,” Am J Health Syst Pharm, 1996, 53:2045-53.
Liu C, Bayer A, Cosgrove SE, et al, “Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children: Executive Summary,” Clin Infect Dis, 2011, 52(3):285-92.
Olsen KM, Rebuck JA, and Rupp ME, “Arthralgias and Myalgias Related to Quinupristin-Dalfopristin Administration,” Clin Infect Dis, 2001, 32(4):e83-6.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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