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Quinupristin-Dalfopristin is an antibiotic that is FDA approved for the treatment of complicated skin and skin structure infections caused by staphylococcus aureus (methicillin susceptible) or streptococcus pyogenes. Common adverse reactions include injection site edema, injection site inflammation, injection site pain, injection site reaction, rash, diarrhea, nausea, vomiting, thrombophlebitis, conjugated hyperbilirubinemia, hyperbilirubinemia, arthralgia, and myalgia.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Complicated Skin And Skin Structure Infections
- Synercid is indicated in adults for the treatment of the following infections when caused by susceptible strains of the designated microorganisms.
- Complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin susceptible) or Streptococcus pyogenes.
- Synercid should be administered by intravenous infusion in 5% Dextrose in Water solution over a 60-minute period. An infusion pump or device may be used to control the rate of infusion. If necessary, central venous access (e.g., PICC) can be used to administer Synercid to decrease the incidence of venous irritation. The recommended dosage for the treatment of complicated skin and skin structure infections is 7.5 mg/kg q12h. The minimum recommended treatment duration for complicated skin and skin structure infections is seven days.
Off-Label Use and Dosage (Adult)
There is limited information regarding Off-Label Guideline-Supported Use of Quinupristin-Dalfopristin in adult patients.
Bacteremia associated with intravascular line, due to ampicillin- and vancomycin-resistant Enterococcus faecium
- Quinupristin/dalfopristin 7.5 mg/kg every 8 hours.
Infective endocarditis, due to vancomycin-resistant Enterococcus faecium
- 7.5 mg/kg IV every 8 hours for a minimum of 8 weeks.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Complicated Skin And Skin Structure Infections
- The recommended dose of Synercid for pediatric patients (12 to <18 years of age) is 7.5 mg/kg q12h. No dosing recommendations are available in pediatric patients less than 12 years of age.
Off-Label Use and Dosage (Pediatric)
There is limited information regarding Off-Label Guideline-Supported Use of Quinupristin-Dalfopristin in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of Quinupristin-Dalfopristin in pediatric patients.
- Synercid is contraindicated in patients with known hypersensitivity to Synercid, or with prior hypersensitivity to other streptogramins (e.g., pristinamycin or virginiamycin).
- In vitro drug interaction studies have demonstrated that Synercid significantly inhibits cytochrome P450 3A4 metabolism of cyclosporin A, midazolam, nifedipine and terfenadine. In addition, 24 subjects given Synercid 7.5 mg/kg q8h for 2 days and 300 mg of cyclosporine on day 3 showed an increase of 63% in the AUC of cyclosporine, an increase of 30% in the Cmax of cyclosporine, a 77% increase in the t1/2 of cyclosporine, and, a decrease of 34% in the clearance of cyclosporine. Therapeutic level monitoring of cyclosporine should be performed when cyclosporine must be used concomitantly with Synercid.
- It is reasonable to expect that the concomitant administration of Synercid and other drugs primarily metabolized by the cytochrome P450 3A4 enzyme system may likely result in increased plasma concentrations of these drugs that could increase or prolong their therapeutic effect and/or increase adverse reactions. (See Table below.) Therefore, coadministration of Synercid with drugs which are cytochrome P450 3A4 substrates and possess a narrow therapeutic window requires caution and monitoring of these drugs (e.g., cyclosporine), whenever possible. Concomitant medications metabolized by the cytochrome P450 3A4 enzyme system that may prolong the QTc interval should be avoided.
- Concomitant administration of Synercid and nifedipine (repeated oral doses) and midazolam (intravenous bolus dose) in healthy volunteers led to elevated plasma concentrations of these drugs. The Cmax increased by 18% and 14% (median values) and the AUC increased by 44% and 33% for nifedipine and midazolam, respectively.
- Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Synercid, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
- C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
- If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
- Venous Irritation: Following completion of a peripheral infusion, the vein should be flushed with 5% Dextrose in Water solution to minimize venous irritation. DO NOT FLUSH with saline or heparin after Synercid administration because of incompatibility concerns.
- 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. In clinical trials, concomitant administration of hydrocortisone or diphenhydramine did not appear to alleviate venous pain or inflammation.
- Rate of Infusion
- In animal studies toxicity was higher when Synercid was administered as a bolus compared to slow infusion. However, the safety of an intravenous bolus of Synercid has not been studied in humans. Clinical trial experience has been exclusively with an intravenous duration of 60 minutes and, thus, other infusion rates cannot be recommended.
- Episodes of arthralgia and myalgia, some severe, have been reported in patients treated with Synercid. In some patients, improvement has been noted with a reduction in dose frequency to q12h. In those patients available for follow-up, treatment discontinuation has been followed by resolution of symptoms. The etiology of these myalgias and arthralgias is under investigation.
- The use of antibiotics may promote the overgrowth of nonsusceptible organisms. Should superinfection occur during therapy, appropriate measures should be taken.
- Elevations of total bilirubin greater than 5 times the upper limit of normal were noted in approximately 25% of patients in the non-comparative studies. In some patients, isolated hyperbilirubinemia (primarily conjugated) can occur during treatment, possibly resulting from competition between Synercid and bilirubin for excretion. Of note, in the comparative trials, elevations in ALT and AST occurred at a similar frequency in both the Synercid and comparator groups.
Clinical Trials Experience
- Safety data are available from five comparative clinical studies (n= 1099 Synercid; n= 1095 comparator). One of the deaths in the comparative studies was assessed as possibly related to Synercid. The most frequent reasons for discontinuation due to drug-related adverse reactions were as follows:
- Adverse reactions with an incidence of ≥1% and possibly or probably related to Synercid administration include:
- Additional adverse reactions that were possibly or probably related to Synercid with an incidence less than 1% within each body system are listed below:
Body as a Whole
Skin and Appendages
- In two of the five comparative clinical trials Synercid (n=450) and comparator regimens (e.g., oxacillin/vancomycin or cefazolin/vancomycin; n=443) were studied for safety and efficacy in the treatment of complicated skin and skin structure infections. The adverse event profile seen in the Synercid patients in these two studies differed significantly from that seen in the other comparative studies. What follows is safety data from these two studies.
- Discontinuation of therapy was most frequently due to the following drug related events:
- Venous adverse events were seen predominately in patients who had peripheral infusions. The most frequently reported venous and non-venous adverse reactions possibly or probably related to study drug were:
- There were eight (1.7%) episodes of thrombus or thrombophlebitis in the Synercid arms and none in the comparator arms.
- The following table shows the number (%) of patients exhibiting laboratory values above or below the clinically relevant "critical" values during treatment phase (with an incidence of 0.1% or greater in either treatment group).
- Approximately one-third of patients discontinued therapy in these trials due to adverse events. However, the discontinuation rate due to adverse reactions assessed by the investigator as possibly or probably related to Synercid therapy was approximately 5.0%.
- There were three prospectively designed non-comparative clinical trials in patients (n = 972) treated with Synercid. One of these studies (301), had more complete documentation than the other two (398A and 398B). The most common events probably or possibly related to therapy were:
- The percentage of patients who experienced severe related arthralgia and myalgia was 3.3% and 3.1%, respectively. The percentage of patients who discontinued treatment due to related arthralgia and myalgia was 2.3% and 1.8%, respectively.
- In addition to adverse events reported from clinical trials, reports of angioedema and anaphylactic shock have been identified during post approval use of Synercid.
- In vitro drug interaction studies have shown that Synercid significantly inhibits cytochrome P450 3A4.
- Synercid does not significantly inhibit human cytochrome P450 1A2, 2A6, 2C9, 2C19, 2D6, or 2E1. Therefore, clinical interactions with drugs metabolized by these cytochrome P450 isoenzymes are not expected.
- A drug interaction between Synercid and digoxin cannot be excluded but is unlikely to occur via CYP3A4 enzyme inhibition. Synercid has shown in vitro activity (MICs of 0.25 mcg/mL when tested on two strains) against Eubacterium lentum. Digoxin is metabolized in part by bacteria in the gut and as such, a drug interaction based on Synercid's inhibition of digoxin's gut metabolism (by Eubacterium lentum) may be possible.
- 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), β-lactams (cefepime, ampicillin, and amoxicillin), glycopeptides (vancomycin), quinolones (ciprofloxacin), tetracyclines (doxycycline) and also chloramphenicol against enterococci and staphylococci did not show antagonism.
Use in Specific Populations
- Pregnancy Category B
- Reproductive studies have been performed in mice at doses up to 40 mg/kg/day (approximately half the human dose based on body-surface area), in rats at doses up to 120 mg/kg/day (approximately 2.5 times the human dose based on body-surface area), and in rabbits at doses up to 12 mg/kg/day (approximately half the human dose based on body-surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to Synercid.
- There are, however, no adequate and well-controlled studies with Synercid in pregnant women. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed.
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Quinupristin-Dalfopristin in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Quinupristin-Dalfopristin during labor and delivery.
- In lactating rats, Synercid was excreted in milk. It is not known whether Synercid is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when Synercid is administered to a nursing woman.
- Synercid has been used in a limited number of pediatric patients under emergency-use conditions at a dose of 7.5 mg/kg q8h or q12h. However, the safety and effectiveness of Synercid in patients under 16 years of age have not been established.
- In phase 3 comparative trials of Synercid, 37% of patients (n=404) were ≥65 years of age, of which 145 were ≥75 years of age. In the phase 3 non-comparative trials, 29% of patients (n=346) were ≥65 years of age, of which 112 were ≥75 years of age. There were no apparent differences in the frequency, type, or severity of related adverse reactions including cardiovascular events between elderly and younger individuals.
There is no FDA guidance on the use of Quinupristin-Dalfopristin with respect to specific gender populations.
There is no FDA guidance on the use of Quinupristin-Dalfopristin with respect to specific racial populations.
There is no FDA guidance on the use of Quinupristin-Dalfopristin in patients with renal impairment.
- Following a single 1-hour infusion of Synercid (7.5 mg/kg) to patients with hepatic insufficiency, plasma concentrations were significantly increased. However, the effect of dose reduction or increase in dosing interval on the pharmacokinetics of Synercid in these patients has not been studied. Therefore, no recommendations can be made at this time regarding the appropriate dose modification.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Quinupristin-Dalfopristin in women of reproductive potentials and males.
There is no FDA guidance one the use of Quinupristin-Dalfopristin in patients who are immunocompromised.
Administration and Monitoring
There is limited information regarding Monitoring of Quinupristin-Dalfopristin in the drug label.
- DO NOT DILUTE WITH SALINE SOLUTIONS BECAUSE SYNERCID IS NOT COMPATIBLE WITH THESE AGENTS. Synercid should not be mixed with, or physically added to, other drugs except for the following drugs where compatibility by Y-site injection has been established:
- If Synercid is to be given concomitantly with another drug, each drug should be given separately in accordance with the recommended dosage and route of administration for each drug.
- With intermittent infusion of Synercid and other drugs through a common intravenous line, the line should be flushed before and after administration with 5% Dextrose in Water solution.
- Stability and Storage
- Before Reconstitution: The unopened vials should be stored in a refrigerator at 2 to 8°C (36 to 46°F).
- Reconstituted and Infusions Solutions
- Because Synercid contains no antibacterial preservative, it should be reconstituted under strict aseptic conditions (e.g., Laminar Air Flow Hood). The reconstituted solution should be diluted within 30 minutes. Vials are for single use. The storage time of the diluted solution should be as short as possible to minimize the risk of microbial contamination. Stability of the diluted solution prior to the infusion is established as 5 hours at room temperature or 54 hours if stored under refrigeration 2 to 8°C (36 to 46°F). The solution should not be frozen.
- There are four reports of patients receiving Synercid doses at up to three times that recommended (7.5 mg/kg). No adverse events were considered possibly or probably related to Synercid overdose. Signs of acute overdosage may include dyspnea, emesis, tremors, and ataxia as seen in animals given extremely high doses (50 mg/kg) of Synercid. Patients who receive an overdose should be carefully observed and given supportive treatment. Synercid is not removed by peritoneal dialysis or by hemodialysis.
There is limited information regarding Chronic Overdose of Quinupristin-Dalfopristin in the drug label.
Mechanism of Action
- 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. Synercid is bactericidal against isolates of methicillin-susceptible and methicillin-resistant staphylococci. The mode of action of Synercid differs from that of other classes of antibacterial agents such as ß-lactams, aminoglycosides, glycopeptides, quinolones, macrolides, lincosamides and tetracyclines. Therefore, there is no cross resistance between Synercid and these agents when tested by the minimum inhibitory concentration (MIC) method.
- Synercid® (quinupristin and dalfopristin powder for injection) I.V., a streptogramin antibacterial agent for intravenous administration, is a sterile lyophilized formulation of two semisynthetic pristinamycin derivatives, quinupristin (derived from pristinamycin I) and dalfopristin (derived from pristinamycin IIA) in the ratio of 30:70 (w/w).
- Quinupristin is a white to very slightly yellow, hygroscopic powder. It is a combination of three peptide macrolactones. The main component of quinupristin (>88.0%) has the following chemical name: N-[(6R,9S,10R,13S,15aS,18R,22S,24aS )-22-[p-(dimethylamino)benzyl]-6-ethyldocosahydro-10,23-dimethyl-5,8,12,15,17,21,24-heptaoxo-13-phenyl-18-[(3S )-3-quinuclidinylthio] methyl]-12H-pyrido[2,1-f ]pyrrolo-[2,1-l ][1,4,7,10,13,16] oxapentaazacyclononadecin-9-yl]-3-hydroxypicolinamide.
- The main component of quinupristin has an empirical formula of C53H67N9O10S, a molecular weight of 1022.24 and the following structural formula:
- Dalfopristin is a slightly yellow to yellow, hygroscopic, powder. The chemical name for dalfopristin is: (3R,4R,5E,10E,12E,14S,26R,26aS )-26-[2-(diethylamino)ethyl]sulfonyl]-8,9,14,15,24,25,26,26a-octahydro-14-hydroxy-3-isopropyl-4,12-dimethyl-3H-21,18-nitrilo-1H,22H-pyrrolo[2,1-c ][1,8,4,19]-dioxadiazacyclotetracosine-1,7,16,22(4H,17H )-tetrone.
- Dalfopristin has an empirical formula of C34H50N4O9S, a molecular weight of 690.85 and the following structural formula:
There is limited information regarding Pharmacodynamics of Quinupristin-Dalfopristin in the drug label.
- Quinupristin and dalfopristin are the main active components circulating in plasma in human subjects. Quinupristin and dalfopristin are converted to several active major metabolites: two conjugated metabolites for quinupristin (one with glutathione and one with cysteine) and one non-conjugated metabolite for dalfopristin (formed by drug hydrolysis).
- Pharmacokinetic profiles of quinupristin and dalfopristin in combination with their metabolites were determined using a bioassay following multiple 60-minute infusions of Synercid in two groups of healthy young adult male volunteers. Each group received 7.5 mg/kg of Synercid intravenously q12h or q8h for a total of 9 or 10 doses, respectively. The pharmacokinetic parameters were proportional with q12h and q8h dosing; those of the q8h regimen are shown in the following table:
- The clearances of unchanged quinupristin and dalfopristin are similar (0.72 L/h/kg), and the steady-state volume of distribution for quinupristin is 0.45 L/kg and for dalfopristin is 0.24 L/kg. The elimination half-life of quinupristin and dalfopristin is approximately 0.85 and 0.70 hours, respectively.
- The total protein binding of quinupristin is higher than that of dalfopristin. Synercid does not alter the in vitro binding of warfarin to proteins in human serum.
- Penetration of unchanged quinupristin and dalfopristin in noninflammatory blister fluid corresponds to about 19% and 11% of that estimated in plasma, respectively. The penetration into blister fluid of quinupristin and dalfopristin in combination with their major metabolites was in total approximately 40% compared to that in plasma.
- In vitro, the transformation of the parent drugs into their major active metabolites occurs by non-enzymatic reactions and is not dependent on cytochrome-P450 or glutathione-transferase enzyme activities.
- Synercid has been shown to be a major inhibitor (in vitro inhibits 70% cyclosporin A biotransformation at 10 μg/mL of Synercid) of the activity of cytochrome P450 3A4 isoenzyme.
- Synercid can interfere with the metabolism of other drug products that are associated with QTc prolongation. However, electrophysiologic studies confirm that Synercid does not itself induce QTc prolongation.
- Fecal excretion constitutes the main elimination route for both parent drugs and their metabolites (75 to 77% of dose). Urinary excretion accounts for approximately 15% of the quinupristin and 19% of the dalfopristin dose. Preclinical data in rats have demonstrated that approximately 80% of the dose is excreted in the bile and suggest that in man, biliary excretion is probably the principal route for fecal elimination.
- Special Populations
- Elderly: The pharmacokinetics of quinupristin and dalfopristin were studied in a population of elderly individuals (range 69 to 74 years). The pharmacokinetics of the drug products were not modified in these subjects.
- Gender: The pharmacokinetics of quinupristin and dalfopristin are not modified by gender.
- Renal Insufficiency: In patients with creatinine clearance 6 to 28 mL/min, the AUC of quinupristin and dalfopristin in combination with their major metabolites increased about 40% and 30%, respectively.
- In patients undergoing Continuous Ambulatory Peritoneal Dialysis, dialysis clearance for quinupristin, dalfopristin and their metabolites is negligible. The plasma AUC of unchanged quinupristin and dalfopristin increased about 20% and 30%, respectively. The high molecular weight of both components of Synercid suggests that it is unlikely to be removed by hemodialysis.
- Hepatic Insufficiency: In patients with hepatic dysfunction (Child-Pugh scores A and B), the terminal half-life of quinupristin and dalfopristin was not modified. However, the AUC of quinupristin and dalfopristin in combination with their major metabolites increased about 180% and 50%, respectively.
- Obesity (body mass index ≥30): In obese patients the Cmax and AUC of quinupristin increased about 30% and those of dalfopristin about 40%.
- Pediatric Patients: The pharmacokinetics of Synercid in patients less than 16 years of age have not been studied.
- Long-term carcinogenicity studies in animals have not been conducted with Synercid. Five genetic toxicity tests were performed. Synercid, dalfopristin, and quinupristin were tested in the bacterial reverse mutation assay, the Chinese hamster ovary cell HGPRT gene mutation assay, the unscheduled DNA synthesis assay in rat hepatocytes, the Chinese hamster ovary cell chromosome aberration assay, and the mouse micronucleus assay in bone marrow. Dalfopristin was associated with the production of structural chromosome aberrations when tested in the Chinese hamster ovary cell chromosome aberration assay. Synercid and quinupristin were negative in this assay. Synercid, dalfopristin, and quinupristin were all negative in the other four genetic toxicity assays.
- No impairment of fertility or perinatal/postnatal development was observed in rats at doses up to 12 to 18 mg/kg (approximately 0.3 to 0.4 times the human dose based on body-surface area).
Complicated Skin and Skin Structure Infections
- Two randomized, open-label, controlled clinical trials of Synercid (7.5 mg/kg q12h intravenously [iv]) in the treatment of complicated skin and skin structure infections were performed. The comparator drug was oxacillin (2g q6h iv) in the first study (JRV 304) and cefazolin (1g q8h iv) in the second study (JRV 305); however, in both studies vancomycin (1g q12h iv) could be substituted for the specified comparator if the causative pathogen was suspected or confirmed methicillin-resistant staphylococcus or if the patient was allergic to penicillins, cephalosporins or carbapenems. Study JRV 304 enrolled 450 patients (n = 229 Synercid; n= 221 Comparator) and Study JRV 305 enrolled 443 patients (n = 221 Synercid; n = 222 Comparator).
- In the first study, 105 patients (45.9%) and 106 patients (48.0%) in the Synercid and Comparator arms, respectively, were found to be clinically evaluable. For the second study, these values were 113 (51.1%) and 120 (54.1%) patients in the Synercid and Comparator arms, respectively. Patients were found not to be clinically evaluable for reasons such as: wrong diagnosis, lower extremity infection in patients with diabetes or peripheral vascular disease since these infections were assumed to include aerobic gram-negative and anaerobic organisms, no specimen for culture obtained, insufficient therapy, no test of cure assessment, etc.
- For the patients found to be clinically evaluable, in Study JRV 304 the success rate was 49.5% in the Synercid arm and 51.9% in the Comparator arm. In Study JRV 305, the success rates were 66.4% and 64.2% in the Synercid and Comparator arms, respectively.
- The following table shows the clinical success rate (combined results from two clinical trials) in the clinically evaluable population. Due to the small numbers of patients in the subsets, statistical conclusions could not be reached.
- Synercid is supplied as a sterile lyophilized pyrogen-free preparation in single-dose 10 mL type I glass vials with gray elastomeric closure, and aluminum seal with a dark blue flip-off cap for the 500 mg vial.
- NDC 61570-260-10 Synercid IV 500 mg 150 mg quinupristin and 350 mg dalfopristin 10 vials
There is limited information regarding Quinupristin-Dalfopristin Storage in the drug label.
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Patient Counseling Information
- Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
Precautions with Alcohol
- Alcohol-Quinupristin-Dalfopristin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Look-Alike Drug Names
There is limited information regarding Quinupristin-Dalfopristin Look-Alike Drug Names in the drug label.
The contents of this FDA label are provided by the National Library of Medicine.
- Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP; et al. (2009). "Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America". Clin Infect Dis. 49 (1): 1–45. doi:10.1086/599376. PMC 4039170. PMID 19489710.
- Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME; et al. (2005). "Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America". Circulation. 111 (23): e394–434. doi:10.1161/CIRCULATIONAHA.105.165564. PMID 15956145.
- "SYNERCID quinupristin and dalfopristin injection, powder, lyophilized, for solution".