SYNERCID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYNERCID (SYNERCID).
Synercid is a combination of two streptogramin antibiotics, quinupristin and dalfopristin, which bind to the 50S bacterial ribosome and inhibit protein synthesis. Quinupristin binds to the 23S rRNA near the peptidyl transferase center, while dalfopristin binds to a nearby site and enhances quinupristin's binding. The synergistic effect results in irreversible inhibition of bacterial protein synthesis.
| Metabolism | Both quinupristin and dalfopristin are metabolized in the liver via non-enzymatic reactions and possibly by cytochrome P450 enzymes. Quinupristin has two major metabolites (quinupristin sulfoxide and N-desmethyl quinupristin) and dalfopristin has one major metabolite (dalfopristin sulfoxide). Synercid and its metabolites are primarily excreted in the feces (up to 80%) and to a lesser extent in the urine (up to 20%). |
| Excretion | Primarily hepatic metabolism with biliary excretion; approximately 15% of the dalfopristin dose and 32% of the quinupristin dose are excreted unchanged in feces; renal excretion is minor (<5% for both components). |
| Half-life | The terminal elimination half-life is approximately 0.85 hours for dalfopristin and 1.3 hours for quinupristin; however, the active metabolite of quinupristin has a half-life of about 3.5 hours, supporting twice-daily dosing. |
| Protein binding | Quinupristin: 55-78% bound to human serum albumin; dalfopristin: 11-26% bound; overall binding is moderate and nonlinear. |
| Volume of Distribution | Quinupristin: approximately 0.45 L/kg; dalfopristin: approximately 0.24 L/kg; indicates distribution primarily into extracellular fluid. |
| Bioavailability | Only available as intravenous formulation; bioavailability is 100% by IV route. |
| Onset of Action | Intravenous administration: rapid bactericidal effect with clinical response often observed within 24 to 48 hours; typical steady-state achieved by second dose. |
| Duration of Action | Dosed every 8 or 12 hours; clinical effects persist throughout dosing interval; continuous monitoring recommended due to potential resistance. |
| Molecular Weight | 2073.4 |
7.5 mg/kg IV every 8 hours, administered as a 60-minute infusion.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; however, monitor renal function closely. |
| Liver impairment | Child-Pugh Class A and B: No adjustment; Child-Pugh Class C: Consider alternative therapy or monitor liver function closely. |
| Pediatric use | Safety and efficacy not established; limited data. |
| Geriatric use | No specific dose adjustment; monitor renal and hepatic function due to age-related changes. |
| 1st trimester | Avoid use; animal studies show embryotoxicity and no adequate human data. |
| 2nd trimester | Use only if benefit outweighs risk; limited data suggest potential risk. |
| 3rd trimester | Use only if benefit outweighs risk; may cause neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for SYNERCID (SYNERCID).
| Placental transfer | Unknown; molecular weight suggests possible transfer. |
| Breastfeeding | No data on excretion in human milk; potential for serious adverse effects in nursing infants, so breastfeeding not recommended during therapy. |
| Lactation Rating | L4 |
■ FDA Black Box Warning
WARNING: INFUSION-RELATED EVENTS AND HYPERSENSITIVITY Synercid can cause severe infusion-related adverse reactions, including pain, edema, phlebitis, and thrombophlebitis at the infusion site. Hypersensitivity reactions, including anaphylaxis, have been reported. To reduce the risk, Synercid should be administered via central venous catheter if possible. If administered peripherally, the infusion site should be monitored closely and changed frequently.
| Serious Effects |
Hypersensitivity to Synercid or any componentConcurrent administration with drugs contraindicated with macrolides
| Precautions | May cause severe myalgias and arthralgias, especially in patients with hepatic impairment; consider discontinuation if symptoms are severe, Hepatotoxicity: Monitor liver function tests (LFTs); discontinue if significant elevation occurs, Infusion site reactions: Use central line for administration if possible; monitor for phlebitis, pain, and edema, Hypersensitivity reactions: Discontinue and treat appropriately if anaphylaxis occurs, Clostridioides difficile-associated diarrhea: Evaluate if diarrhea occurs during or after therapy, Drug interactions: Inhibits CYP3A4; may increase levels of drugs metabolized by this enzyme (e.g., cyclosporine, midazolam, tacrolimus). Co-administration with drugs that prolong QTc interval should be avoided or monitored |
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| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies. Insufficient human data; risk cannot be excluded. Use only if clearly needed. |
| Fetal Monitoring | Monitor liver function tests, renal function, and complete blood counts. Assess for signs of superinfection. |
| Fertility Effects | No known effects on fertility based on animal studies. |
| Food/Dietary | No known food interactions. Grapefruit juice may increase drug levels due to CYP3A4 inhibition; advise avoiding grapefruit products during treatment. |
| Clinical Pearls | Synercid (quinupristin/dalfopristin) is a streptogramin antibiotic used for vancomycin-resistant Enterococcus faecium (VRE) and complicated skin infections. Administer via central line due to severe phlebitis; flushing Red Man syndrome can occur; monitor for myalgias and arthralgias, which may require dose reduction or discontinuation; CYP3A4 inhibitor; check LFTs and bilirubin. |
| Patient Advice | This medication is given through a central intravenous line to prevent vein irritation. · Report any muscle pain, joint pain, or skin flushing during infusion. · Do not stop treatment early even if you feel better. · Inform your doctor of all other medications, especially those for cholesterol (statins), seizures, or transplants. · You may experience nausea, diarrhea, or rash; contact your healthcare provider if severe. |