Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 09 October 2017

Indication(s)

INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of Synercid and other antibacterial drugs, Synercid should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. 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. (See CLINICAL STUDIES .)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Psoriasis

Psoriasis

See information on psoriasis pathophysiology, signs and symptoms, comorbidities, treatment options, and more.

+ 2 more

Atopic Dermatitis

Atopic Dermatitis

The Atopic Dermatitis Knowledge Centre is an educational resource, intended for healthcare professionals, that provides credible medical information on the epidemiology, pathophysiology and burden of atopic dermatitis, as well as diagnostic techniques, treatment regimens and guideline recommendations.

Chronic Spontaneous Urticaria (CSU)

Chronic Spontaneous Urticaria (CSU)

Use our patient case studies to discover how experts diagnose and treat chronic spontaneous urticaria.

+ 7 more

Load more

Related Content

Advisory information

contraindications
CONTRAINDICATIONS Synercid is contraindicated in patients with known hypersensitivity to Synercid, or with prior hypersensitivity to other streptogramins (e.g., pristinamycin or virginiamycin).
Special warnings and precautions
PRECAUTIONS General Prescribing Synercid in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. 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. Arthralgias/Myalgias 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. Superinfections The use of antibiotics may promote the overgrowth of nonsusceptible organisms. Should superinfection occur during therapy, appropriate measures should be taken. Hyperbilirubinemia 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. (See ADVERSE REACTIONS: Non-Comparative Trials .) 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. Information for Patients 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. Patients should be counseled that antibacterial drugs including Synercid should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Synercid is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Synercid or other antibacterial drugs in the future. Drug Interactions In vitro drug interaction studies have shown that Synercid significantly inhibits cytochrome P450 3A4. (See WARNINGS .) 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. Carcinogenesis, Mutagenesis, Impairment of Fertility 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). Pregnancy Teratogenic Effects 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. Nursing Mothers 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. Hepatic Insufficiency Following a single 1-hour infusion of Synercid (7.5 mg/kg) to patients with hepatic insufficiency, plasma concentrations were significantly increased. (See CLINICAL PHARMACOLOGY: Special Populations .) 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. Pediatric Use 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. Geriatric Use 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.
Adverse reactions
ADVERSE REACTIONS The safety of Synercid was evaluated in 1099 patients enrolled in 5 comparative clinical trials. Additionally, 4 non-comparative clinical trials (3 prospective and 1 retrospective in design) were conducted in which 1199 patients received Synercid for infections due to Gram-positive pathogens for which no other treatment option was available. In non-comparative trials, the patients were severely ill, often with multiple co-morbidities or physiological impairments, and may have been intolerant to or failed other antibacterial therapies. COMPARATIVE TRIALS ADVERSE REACTION SUMMARY – ALL COMPARATIVE STUDIES 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: Table 5: Percent (%) of Patients Discontinuing Therapy by Reaction Type Type Synercid Comparator Venous 9.2 2.0 Non-venous 9.6 4.3 -Rash 1.0 0.5 -Nausea 0.9 0.6 -Vomiting 0.5 0.5 -Pain 0.5 0.0 -Pruritus 0.5 0.3 CLINICAL REACTIONS – ALL COMPARATIVE STUDIES Adverse reactions with an incidence of ≥1% and possibly or probably related to Synercid administration include: Table 6: Adverse Reactions with an Incidence of ≥1% and Possibly or Probably Related to Synercid Administration Adverse Reactions % of patients with adverse reactions Synercid Comparator Inflammation at infusion site 42.0 25.0 Pain at infusion site 40.0 23.7 Edema at infusion site 17.3 9.5 Infusion site reaction 13.4 10.1 Nausea 4.6 7.2 Thrombophlebitis 2.4 0.3 Diarrhea 2.7 3.2 Vomiting 2.7 3.8 Rash 2.5 1.4 Headache 1.6 0.9 Pruritus 1.5 1.1 Pain 1.5 0.1 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: abdominal pain, worsening of underlying illness, allergic reaction, chest pain, fever, infection; Cardiovascular: palpitation, phlebitis; Digestive: constipation, dyspepsia, oral moniliasis, pancreatitis, pseudomembranous enterocolitis, stomatitis; Metabolic: gout, peripheral edema; Musculoskeletal: arthralgia, myalgia, myasthenia; Nervous: anxiety, confusion, dizziness, hypertonia, insomnia, leg cramps, paresthesia, vasodilation; Respiratory: dyspnea, pleural effusion; Skin and Appendages: maculopapular rash, sweating, urticaria; Urogenital: hematuria, vaginitis CLINICAL REACTIONS – SKIN AND SKIN STRUCTURE STUDIES 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: Table 7: Drug Related Events Most Frequently Leading to Discontinuation of Therapy % of patients discontinuing therapy by reaction type Type Synercid Comparator Venous 12.0 2.0 Non-venous 11.8 4.0 -Rash 2.0 0.9 -Nausea 1.1 0.0 -Vomiting 0.9 0.0 -Pain 0.9 0.0 -Pruritus 0.9 0.5 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: Table 8: The Most Frequently Reported Venous and Non-Venous Adverse Reactions Possibly or Probably Related to Study Drug % of patients with adverse reactions Synercid Comparator Venous 68.0 32.7 -Pain at infusion site 44.7 17.8 -Inflammation at infusion site 38.2 14.7 -Edema at infusion site 18.0 7.2 -Infusion site reaction 11.6 3.6 Non-venous 24.7 13.1 -Nausea 4.0 2.0 -Vomiting 3.7 1.0 -Rash 3.1 1.3 -Pain 3.1 0.2 There were eight (1.7%) episodes of thrombus or thrombophlebitis in the Synercid arms and none in the comparator arms. LABORATORY EVENTS-ALL COMPARATIVE STUDIES Table 9 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). Table 9: Laboratory Events Parameter Critically High or Low Value Synercid Critically High or Low Comparator Critically High or Low AST > 10 × ULN 9 (0.9) 2 (0.2) ALT > 10 × ULN 4 (0.4) 4 (0.4) Total Bilirubin > 5 × ULN 9 (0.9) 2 (0.2) Conjugated Bilirubin > 5 × ULN 29 (3.1) 12 (1.3) LDH > 5 × ULN 10 (2.6) 8 (2.1) Alk Phosphatase > 5 × ULN 3 (0.3) 7 (0.7) Gamma-GT > 10 × ULN 19 (1.9) 10 (1.0) CPK > 10 × ULN 6 (1.6) 5 (1.4) Creatinine ≥ 440 μmoL/L 1 (0.1) 1 (0.1) BUN ≥ 35.5 mmoL/L 2 (0.3) 9 (1.2) Blood Glucose > 22.2 mmoL/L 11 (1.3) 11 (1.3) < 2.2 mmoL/L 1 (0.1) 1 (0.1) Bicarbonates > 40 mmoL/L 2 (0.3) 3 (0.5) < 10 mmoL/L 3 (0.5) 3 (0.5) CO2 > 50 mmoL/L 0 (0.0) 0 (0.0) < 15 mmoL/L 1 (0.2) 0 (0.0) Sodium > 160 mmoL/L 0 (0.0) 0 (0.0) < 120 mmoL/L 5 (0.5) 3 (0.3) Potassium > 6.0 mmoL/L 3 (0.3) 6 (0.6) < 2.0 mmoL/L 0 (0.0) 1 (0.1) Hemoglobin < 8 g/dL 25 (2.6) 16 (1.6) Hematocrit > 60% 2 (0.2) 0 (0.0) Platelets > 1,000,000/mm3 2 (0.2) 2 (0.2) < 50,000/mm3 6 (0.6) 7 (0.7) NON-COMPARATIVE TRIALS CLINICAL ADVERSE REACTIONS 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 are presented in Table 10: Table 10: The Most Common Events Probably or Possibly Related to Therapy Adverse Reactions % of patients with adverse reaction Study 301 Study 398A Study 398B Arthralgia 7.8 5.2 4.3 Myalgia 5.1 0.95 3.1 Arthralgia and Myalgia 7.4 3.3 6.8 Nausea 3.8 2.8 4.9 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. LABORATORY EVENTS The most frequently observed abnormalities in laboratory studies were in total and conjugated bilirubin, with increases greater than 5 times upper limit of normal, irrespective of relationship to Synercid, reported in 25.0% and 34.6% of patients, respectively. The percentage of patients who discontinued treatment due to increased total and conjugated bilirubin was 2.7% and 2.3%, respectively. Of note, 46.5% and 59.0% of patients had high baseline total and conjugated bilirubin levels before study entry. OTHER Serious adverse reactions in clinical trials, including non-comparative studies, considered possibly or probably related to Synercid administration with an incidence < 0.1% include: acidosis, anaphylactoid reaction, apnea, arrhythmia, bone pain, cerebral hemorrhage, cerebrovascular accident, coagulation disorder, convulsion, dysautonomia, encephalopathy, grand mal convulsion, hemolysis, hemolytic anemia, heart arrest, hepatitis, hypoglycemia, hyponatremia, hypoplastic anemia, hypoventilation, hypovolemia, hypoxia, jaundice, mesenteric arterial occlusion, neck rigidity, neuropathy, pancytopenia, paraplegia, pericardial effusion, pericarditis, respiratory distress syndrome, shock, skin ulcer, supraventricular tachycardia, syncope, tremor, ventricular extrasystoles and ventricular fibrillation. Cases of hypotension and gastrointestinal hemorrhage were reported in less than 0.2% of patients. Post-marketing Experiences In addition to adverse events reported from clinical trials, reports of angioedema and anaphylactic shock have been identified during post approval use of Synercid.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION Synercid should be administered by intravenous infusion in 5% Dextrose in Water solution over a 60-minute period. (See WARNINGS .) 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. Special Populations Elderly No dosage adjustment of Synercid is required for use in the elderly. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and PRECAUTIONS: Geriatric Use .) Renal Insufficiency No dosage adjustment of Synercid is required for use in patients with renal impairment or patients undergoing peritoneal dialysis. (See CLINICAL PHARMACOLOGY: Pharmacokinetics .) Hepatic Insufficiency Data from clinical trials of Synercid suggest that the incidence of adverse effects in patients with chronic liver insufficiency or cirrhosis was comparable to that in patients with normal hepatic function. Pharmacokinetic data in patients with hepatic cirrhosis (Child Pugh A or B) suggest that dosage reduction may be necessary but exact recommendations cannot be made at this time. (See CLINICAL PHARMACOLOGY: Special Populations and PRECAUTIONS: General: Hepatic Insufficiency sections.) Pediatric Patients 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. (See PRECAUTIONS: Pediatric Use .)
Pregnancy and lactation
Nursing Mothers 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.

Interactions

Drug Interactions In vitro drug interaction studies have shown that Synercid significantly inhibits cytochrome P450 3A4. (See WARNINGS .) 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.

More information

Category Value
Authorisation number NDA050748
Agency product number R9M4FJE48E
Orphan designation No
Product NDC 61570-260
Date Last Revised 08-08-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 261306
Storage and handling Stability and Storage Before Reconstitution: The unopened vials should be stored in a refrigerator at 2 to 8°C (36 to 46°F).
Marketing authorisation holder Pfizer Laboratories Div Pfizer Inc