Intravenous Complicated skin and skin structure infections
Adult: Available preparation:
Quinupristin 150 mg and dalfopristin 350 mg powder for solution for infusion
Treatment of cases caused by Staphylococcus aureus (methicillin-susceptible strains) or Streptococcus pyogenes: 7.5 mg/kg (equivalent to 2.25 mg/kg quinupristin and 5.25 mg/kg dalfopristin) 12 hourly via infusion over 60 minutes for at least 7 days. To reduce venous irritation, flush the vein with 5% dextrose in water after each infusion; alternatively, infusion may be administered through a central venous catheter if necessary.
Hepatic Impairment
Dosage adjustment may be needed.
Reconstitution
Initially, reconstitute a vial labelled as 500 mg with 5 mL of 5% dextrose in water or sterile water for inj to make a final concentration of 100 mg/mL. Further, dilute reconstituted solution within 30 minutes by adding to 250 mL of 5% dextrose in water (for peripheral administration) prior to infusion. If moderate or severe venous irritation occurs after peripheral administration of 250 mL diluted solution, infusion volume may be increased to 500 or 750 mL as necessary. For central line infusions, an infusion volume of 100 mL of 5% dextrose in water may be used.
Incompatibility
Incompatible with NaCl and heparin solutions.
Contraindications
Hypersensitivity to quinupristin, dalfopristin, or other streptogramins (e.g. pristinamycin, virginiamycin).
Special Precautions
Hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Phlebitis and pain (when infused via peripheral line); arthralgia, myalgia, hyperbilirubinaemia; bacterial or fungal superinfection with prolonged use including, C. difficile-associated diarrhoea (CDAD), pseudomembranous colitis. Blood and lymphatic system disorders: Anaemia. Gastrointestinal disorders: Nausea, vomiting, diarrhoea. General disorders and administration site conditions: Local pain, infusion site reactions (e.g. pain, inflammation and oedema at the infusion site). Immune system disorders: Anaphylactic shock, angioedema. Investigations: Increased AST/ALT, lactate dehydrogenase, gamma-glutamyl transferase, and creatine phosphokinase. Metabolism and nutrition disorders: Hyperglycaemia. Nervous system disorders: Headache. Skin and subcutaneous tissue disorders: Rash, pruritus. Vascular disorders: Thrombophlebitis.
Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor conjugated bilirubin as clinically indicated.
Overdosage
Symptoms: Dyspnoea, emesis, tremors, and ataxia. Management: Supportive treatment.
Drug Interactions
Increased plasma concentrations of drugs metabolised by the CYP3A4 isoenzyme (e.g. ciclosporin, tacrolimus, midazolam, carbamazepine, nifedipine, terfenadine, methylprednisolone, lovastatin, nevirapine, ritonavir, vinblastine, paclitaxel, lidocaine, quinidine). May increase the risk of arrhythmias with drugs that prolong QT intervals (e.g. astemizole, cisapride, terfenadine). May decrease the metabolism of digoxin.
Action
Description: Mechanism of Action: Quinupristin and dalfopristin is a fixed combination streptogramin antibiotic used in the ratio of 30:70 (w/w), that exhibits greater antibacterial activity due to their synergistic actions as compared to the individual components. They prevent bacterial protein synthesis by binding to the different sites on the 50S ribosomal subunit.
Quinupristin is a type B semisynthetic streptogramin derived from pristinamycin I which inhibits peptide chain elongation in the late phase of protein synthesis.
Dalfopristin is a type A semisynthetic streptogramin derived from pristinamycin IIA that inhibits peptidyl transferase in the early phase of protein synthesis. Pharmacokinetics: Distribution: Quinupristin: Volume of distribution: 0.45 L/kg. Plasma protein binding: 55-78%.
Dalfopristin: Volume of distribution: 0.24 L/kg. Plasma protein binding: 11-26%. Metabolism: Quinupristin: Undergoes conjugation with glutathione and cysteine into active metabolites.
Dalfopristin: Metabolised via hydrolysis to form an active metabolite. Excretion: Mainly via faeces (75-77% as unchanged drug and metabolites); urine (15-19%). Elimination half-life: 0.85 hour (quinupristin); 0.7 hour (dalfopristin).
Chemical Structure
Quinupristin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5388937, Quinupristin. https://pubchem.ncbi.nlm.nih.gov/compound/Quinupristin. Accessed Nov. 24, 2020.
Dalfopristin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6323289, Dalfopristin. https://pubchem.ncbi.nlm.nih.gov/compound/Dalfopristin. Accessed Nov. 24, 2020.
Storage
Store intact vials between 2-8°C. Diluted solutions prior to infusion are stable for 5 hours at room temperature or 54 hours between 2-8°C. Do not freeze.
J01FG02 - quinupristin/dalfopristin ; Belongs to the class of streptogramins. Used in the systemic treatment of infections.
References
Anon. Quinupristin and Dalfopristin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/10/2020.Anon. Quinupristin/Dalfopristin. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 19/10/2020.Buckingham R (ed). Quinupristin/Dalfopristin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/10/2020.Synercid Injection, Lyophilized Powder for Solution (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 19/10/2020.Synercid IV (Pfizer Inc). U.S. FDA. https://www.fda.gov/. Accessed 16/11/2020.
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