Quinupristin/dalfopristin

From WikiProjectMed
Jump to navigation Jump to search
Quinupristin/dalfopristin
Quinupristin.png
Dalfopristin chemical structure.png
Quinupristin (top) and dalfopristin (bottom)
Combination of
QuinupristinStreptogramin antibiotic
DalfopristinStreptogramin antibiotic
Names
Pronunciationkwi NYOO pris tin / dal FOE pris tin
Trade namesSynercid
Clinical data
Drug classStreptogramin antibiotics[1]
Main usesMethicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE)[1]
Side effectsPain at the site of injection, nausea, diarrhea, joint and muscle pain, headache, rash[1]
Pregnancy
category
  • AU: B3
Routes of
use
IV
External links
AHFS/Drugs.comMonograph
US NLMQuinupristin/dalfopristin
Legal
Legal status
 ☒NcheckY (what is this?)  (verify)

Quinupristin/dalfopristin, sold under the brand name Synercid, is a combination of two antibiotics used to treat infections by staphylococci, including Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE).[1] It is not very effective against VRE.[2] It is given by gradual injection into a vein.[1]

Common side effects include pain at the site of injection, nausea, diarrhea, joint and muscle pain, headache, and rash.[1] Other side effects may include Clostridioides difficile infection and anaphylaxis.[1] Quinupristin and dalfopristin are both streptogramin antibiotics, made from from pristinamycin.[1]

The combination was approved for medical use in the United States in 1999.[1] In the United States 10 doses of 350 mg/150 mg costs about 4,900 USD as of 2021.[3] In the United Kingdom it is no longer available as of 2018.[2]

Medical uses

Dosage

Intravenous, usually 7.5 mg/kg every 8 hours (infections/life threatening VRSA); every 12 hours (skin infections).[1]

Side effects

Common:

  1. Joint aches or muscle aches
  2. Nausea, diarrhea or vomiting
  3. Rash or itching
  4. Headache
  5. Hyperbilirubinemia
  6. Anemia
  7. Thrombophlebitis

Serious:

  1. C.diff-associated diarrhea
  2. anaphylaxis
  3. angioedema[4]

Interactions

The drug inhibits P450 and enhances the effects of terfenadine, astemizole, indinavir, midazolam, calcium channel blockers, warfarin, cisapride and ciclosporin.

Mechanism of action

Quinupristin and dalfopristin are protein synthesis inhibitors in a synergistic manner. While each of the two is only a bacteriostatic agent, the combination shows bactericidal activity.

  • Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, and changes the conformation of it, enhancing the binding of quinupristin[5] by a factor of about 100. In addition, it inhibits peptidyl transfer.[5]
  • Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide,[5] as well as causing incomplete chains to be released.[5]

Pharmacokinetics

Clearance by the liver CYP450:3A4 inhibitor, half-life quinupristin 0.8 hours, dalfopristin 0.7 hours (with persistence of effects for 9–10 hours).

Excretion: Quinupristin: 85% feces, 15% urine; Dalfopristin: 81% feces, 19% urine

They are combined in a weight-to-weight ratio of 30% quinupristin to 70% dalfopristin.

Society and culture

Quinupristin is derived from pristinamycin IA; dalfopristin from pristinamycin IIA.[1]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 "Quinupristin/Dalfopristin Monograph for Professionals". Drugs.com. Retrieved 20 October 2021.
  2. 2.0 2.1 Barer, Michael R.; Irving, Will L. (13 January 2018). Medical Microbiology E-Book: A Guide to Microbial Infections. Elsevier Health Sciences. p. 53. ISBN 978-0-7020-7198-0.
  3. "Synercid Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 20 October 2021.
  4. Epocrates v 19.5
  5. 5.0 5.1 5.2 5.3 Denyer SP, Hodges N, Gorman SP, eds. (2004). Hugo and Russell's Pharmaceutical microbiology (7th ed.). Blackwell Science. p. 212. ISBN 978-0-632-06467-0.

External links

External sites:
Identifiers: