Synercid

Synercid

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Questions & Answers

Side Effects & Adverse Reactions

Drug Interactions

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.


Table of Selected Drugs That Are Predicted to Have Plasma Concentrations Increased by Synercid +

Antihistamines: astemizole, terfenadine

Anti-HIV (NNRTIs and Protease inhibitors): delavirdine, nevirapine, indinavir, ritonavir

Antineoplastic agents: vinca alkaloids (e.g., vinblastine), docetaxel, paclitaxel

Benzodiazepines: midazolam, diazepam

Calcium channel blockers: dihydropyridines (e.g., nifedipine), verapamil, diltiazem

Cholesterol-lowering agents: HMG-CoA reductase inhibitors (e.g., lovastatin)

GI motility agents: cisapride

Immunosuppressive agents: cyclosporine, tacrolimus

Steroids: methylprednisolone

Other: carbamazepine, quinidine, lidocaine, disopyramide

+ This list of drugs is not all inclusive.

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.

Legal Issues

There is currently no legal information available for this drug.

FDA Safety Alerts

There are currently no FDA safety alerts available for this drug.

Manufacturer Warnings

There is currently no manufacturer warning information available for this drug.

FDA Labeling Changes

There are currently no FDA labeling changes available for this drug.

Uses

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.)

History

There is currently no drug history available for this drug.

Other Information

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:

ChemStructure 1

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:

ChemStructure2

Synercid Manufacturers


  • Pfizer Laboratories Div Pfizer Inc
    Synercid (Quinupristin And Dalfopristin) Injection, Powder, Lyophilized, For Solution [Pfizer Laboratories Div Pfizer Inc]

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