Version May 2024
Note: Use of quinupristin/dalfopristin is limited by poor tolerance and frequent need for administration via central line (Kullar 2016; O’Driscoll 2015; Reissier 2021).
Bloodstream infection (alternative agent) (off-label use):
Note: Reserve use for patients who cannot receive other agents due to intolerance or resistance (IDSA [Mermel 2009]).
Pathogen-directed therapy for ampicillin- and vancomycin-resistant E. faecium: IV: 7.5 mg/kg every 8 hours; maximum dose is not established. Treat uncomplicated bacteremia for 7 to 14 days from day of first negative blood culture (IDSA [Mermel 2009]). Some experts recommend a duration of 5 to 7 days for uncomplicated infection with rapid blood culture clearance (within 24 hours) and in the absence of metastatic infection (Murray 2021).
CNS infection, health care–associated (eg, cerebrospinal fluid shunt infection) (alternative agent) (off-label use):
Note: Reserve use for patients who cannot receive other agents due to intolerance or resistance (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
Pathogen-directed therapy for ampicillin- and vancomycin-resistant E. faecium:
IV: 7.5 mg/kg every 8 hours for ≥10 days; maximum dose is not established (IDSA [Tunkel 2017]; Knoll 2013; Tush 1998; Williamson 2002).
Intraventricular (adjunct to systemic therapy; use a preservative-free preparation) (off-label): Note: Reserve use for when parenteral therapy fails or for cerebrospinal fluid (CSF) shunt infections when the shunt cannot be removed (Baddour 2021).
2 to 5 mg daily (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]; Tan 2000). When administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF). Duration is individualized according to clinical and microbiologic response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
Skin and soft tissue infection, complicated:
Note: Reserve for patients who cannot receive other agents due to intolerance or resistance (IDSA [Stevens 2014]).
IV: 7.5 mg/kg every 12 hours for at least 7 days.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal impairment: No dosage adjustment necessary.
Hemodialysis: There are no dosage adjustments provided in the manufacturer’s labeling; however, the high molecular weights of quinupristin and dalfopristin suggest that they are unlikely to be removed by hemodialysis.
Peritoneal dialysis: No dosage adjustment necessary.
There are no dosage adjustments provided in the manufacturer’s labeling. However, pharmacokinetic data suggest dosage adjustment may be necessary.
Refer to adult dosing.
(For additional information see "Quinupristin and dalfopristin: Pediatric drug information")
Dosage is expressed in terms of combined “mg” of quinupristin plus dalfopristin:
General dosing, susceptible infection: Severe infection: Infants, Children, and Adolescents: Limited data available in infants and children <12 years: IV: 7.5 mg/kg every 8 to 12 hours (Liu 2011; Loeffler 2002; Red Book [AAP 2018])
Enterococcus faecium, vancomycin resistant (VREF): Limited data available: Infants, Children, and Adolescents: IV: 7.5 mg/kg/dose every 8 hours; dosing based on an Emergency-Use Program (n=127, mean age: 7.3 years [range: 1.2 months to 17 years]) (Loeffler 2002) and two case series (total n=17, range: 10 months to 18 years) (Gray 2000; Verma 2001)
MRSA infection, vancomycin failure salvage therapy: Limited data available: Infants, Children, and Adolescents: IV: 7.5 mg/kg/dose every 8 hours (Liu 2011; Loeffler 2002)
Skin and skin structure infection, complicated, treatment: Infants, Children, and Adolescents: Limited data available in infants and children <12 years: IV: 7.5 mg/kg/dose every 12 hours for at least 7 days (Red Book [AAP 2018])
VP-shunt infection, ventriculitis; multidrug resistant: Limited data available: Infants, Children, and Adolescents: Intraventricular/intrathecal (use a preservative-free preparation): Usual dose: 1 to 2 mg/day; reported range: 1 to 5 mg; in adults, the usual range is 2 to 5 mg/day; use in combination with IV quinupristin/dalfopristin therapy (IDSA [Tunkel 2017]; Nachman 1995; Tush 1998)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment is required for use in patients with renal impairment or patients undergoing peritoneal dialysis. Not removed by peritoneal dialysis or hemodialysis
There are no dosage adjustments provided in the manufacturer labeling; not studied; pharmacokinetic data suggest adjustment may be necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Local: Infusion-site pain (40% to 45%), infusion-site reaction (12% to 13%), local inflammation (infusion site: 38% to 42%), localized edema (infusion site: 17% to 18%)
1% to 10%:
Cardiovascular: Thrombophlebitis (≤2%), thrombosis (≤2%)
Dermatologic: Pruritus (2%), skin rash (3%)
Endocrine & metabolic: Hyperglycemia (1%), increased lactate dehydrogenase (3%), increased serum glucose (1%)
Gastrointestinal: Diarrhea (3%), nausea (4% to 5%), vomiting (3% to 4%)
Hematologic & oncologic: Anemia (3%)
Hepatic: Increased gamma-glutamyl transferase (2%), increased serum bilirubin (<1%; increased direct serum bilirubin: 3%)
Nervous system: Headache (2%), pain (2% to 3%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (2%)
<1%:
Cardiovascular: Chest pain, palpitations, peripheral edema, phlebitis, vasodilation
Dermatologic: Diaphoresis, maculopapular rash, urticaria
Endocrine & metabolic: Decreased serum bicarbonate, hyperkalemia, hypoglycemia, hyponatremia, increased serum bicarbonate
Gastrointestinal: Abdominal pain, Clostridioides difficile colitis, constipation, dyspepsia, oral candidiasis, pancreatitis, stomatitis
Genitourinary: Hematuria, vaginitis
Hematologic & oncologic: Increased hematocrit, thrombocythemia, thrombocytopenia
Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Hypersensitivity: Hypersensitivity reaction
Nervous system: Anxiety, confusion, dizziness, hypertonia, insomnia, myasthenia, paresthesia
Neuromuscular & skeletal: Arthralgia, gout, lower limb cramp, myalgia
Renal: Increased blood urea nitrogen, increased serum creatinine
Respiratory: Dyspnea, low blood pCO2, pleural effusion
Miscellaneous: Fever
Postmarketing:
Dermatologic: Sweet syndrome (Choi 2003)
Gastrointestinal: Clostridioides difficile-associated diarrhea
Hypersensitivity: Anaphylactic shock, angioedema
Hypersensitivity to quinupristin, dalfopristin, other streptogramins (eg, pristinamycin, virginiamycin), or any component of the formulation
Concerns related to adverse effects:
• Arthralgias/myalgias: May cause arthralgias and/or myalgias, sometimes severe; reversible with treatment discontinuation. Reduction of dosing frequency has led to improvement in some patients.
• Hyperbilirubinemia: May cause hyperbilirubinemia (>5 times ULN; primarily conjugated bilirubin) 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.
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 [DSC]
No
Solution (reconstituted) (Synercid Intravenous)
150-350 mg (per each): $559.21
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IV: Line should be flushed with D5W 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, quinupristin/dalfopristin may be further diluted (to 500 mL or 750 mL), infusion site changed, or infused by a peripherally inserted central catheter or a central venous catheter. In general, administration by central venous catheter is required to avoid phlebitis (Kullar 2016; O'Driscoll 2015).
Intrathecal/Intraventricular (off-label route): Use preservative-free preparations only. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow quinupristin-dalfopristin solution to equilibrate in the CSF (IDSA [Tunkel 2017]).
Parenteral: IV: Administer IV infusion over 60 minutes (toxicity may be increased with shorter infusion); prior to and following administration, the infusion line should be flushed with D5W to minimize venous irritation; DO NOT FLUSH with saline or heparin solutions due to incompatibility. If severe venous irritation occurs following peripheral administration, quinupristin/dalfopristin may be further diluted, infusion site changed, or infused by a peripherally inserted central catheter (PICC) or a central venous catheter.
Skin and soft tissue infections, complicated: Treatment of complicated skin and skin structure infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes. Note: Use of quinupristin/dalfopristin is limited by poor tolerance and frequent need for administration via central line (Kullar 2016; O’Driscoll 2015; Reissier 2021).
Bloodstream infection; CNS infection, health care–associated (eg, cerebrospinal fluid shunt infection)
The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Inhibits CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Cisapride: Quinupristin and Dalfopristin may increase the serum concentration of Cisapride. Risk X: Avoid combination
CycloSPORINE (Systemic): Quinupristin and Dalfopristin may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Adverse events have not been observed in animal reproduction studies.
It is not known if quinupristin/dalfopristin is excreted in breast milk. The manufacturer recommends that caution be exercised when 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.
Culture and sensitivity, conjugated bilirubin if clinically indicated
Quinupristin/dalfopristin inhibits bacterial protein synthesis by binding to different sites on the 50S bacterial ribosomal subunit thereby inhibiting protein synthesis
Distribution: Quinupristin: 0.45 L/kg; Dalfopristin: 0.24 L/kg
Metabolism: Quinupristin is conjugated with glutathione and cysteine to active metabolites; dalfopristin is hydrolyzed to an active metabolite
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%)
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