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amoxicillin/clavulanate (Augmentin)

Tradename: Augmentin. Indications: 1) treatment of mild to moderate bacterial infections due to beta-lactamase-producing organisms a) upper respiratory tract infection - sinusitis b) lower respiratory tract infection - pneumonia c) otitis media d) skin or soft tissue infection e) urinary tract infection f) intra-abdominal infection - diverticulitis [10] - cholangitis g) diabetic foot infections h) chancroid i) mammal bites [10] 2) step-down coverage when using Unasyn for initial antibiotic coverage 3) empiric treatment of febrile neutropenia [10] 4) empiric treatment of fever of unknown origin [10] Contraindications: - pregnancy-category B - safety in lactation ? Dosage: 1) 250-500 mg PO TID 2) Pediatrics: a) 40 mg/kg/day divided TID (based on amoxicillin) b) 90 mg/kg/day divided BID for recurrent otitis media [5] Tabs: 125, 250, 500 mg. Elixir: 125 250 mg/5 mL. Suspension: 1) 125: 125 mg amoxicillin & 31.2 mg clavulanate/ 5 mL, 75 & 150 mL 2) 200: 200 mg amoxicillin & 28.5 mg clavulanate/ 5 mL, 50, 75 & 100 mL 3) 400: 400 mg amoxicillin & 57 mg clavulanate/ 5 mL, 50, 75 & 100 mL ES-600: 600 mg amoxicillin/5mL [5] Augmentin XR: 1000 mg amoxicillin & 62.5 mg clavulanate [7] 1-2 tablets PO BID Generic: - enteric-coated tabs: - 500 mg amoxicillin & 125 mg clavulanate - 875 mg amoxicillin & 125 mg clavulanate - chewable tabs: - 200 mg amoxicillin & 28.5 mg clavulanate - 400 mg amoxicillin & 57 mg clavulanate - suspension: - 200 mg amoxicillin & 28.5 mg clavulanate/5 mL - 400 mg amoxicillin & 57 mg clavulanate/5 mL [6] Storage: - store in orginal container [11] Dose adjustment in renal failure: 1) creatinine clearance 10-50 mL/min: use every 12 hours dosing 2) creatinine clearance < 10 mL/min: use QD dosing Pharmacokinetics: 1) well absorbed orally 2) not affected by food intake 3) does not achieve therapeutic levels in CNS 4) 1/2 life 1-1.5 hours, increased in renal failure 5) both amoxicillin & clavulanate removed by hemodialysis 6) amoxicillin pharmacokinetics not influenced by clavulanate 7) clavulanate is metabolized by the liver 8) amoxicillin is eliminated in the urine Antimicrobial activity: Gram positive - Streptococcus - Streptococcus group A - Streptococcus group B - Streptococcus group C - Streptococcus group G - Streptococcus pneumonia - Streptococcus viridans, milleri - Enterococcus faecalis - Enterococcus faecium - Staphylococcus aureus (MSSA) - Staphylococcus epidermidis - Listeria monocytogenes Gram negative - Neisseria gonorrhoeae - Neisseria meningitidis - Moraxella catarrhalis - Haemophilus - Haemophilus influenzae - Haemophilus influenzae - Haemophilus ducreyi - Escherichia coli - Klebsiella species - Salmonella species - Shigella species - Proteus mirabilis - Proteus vulgaris - Providencia species - Morganella species (+/-) - Aeromonas species - Yersinia enterocolitica (+/-) - Pasteurella multocida - Enterobacter Anaerobes - Actinomyces - Bacteroides fragilis - Bacteroides melaninogenicus - Clostridium difficile - Clostridium species - Peptostreptococcus species Adverse effects: (uncommon < 1%) 1) skin rash may indicate hypersensitivity - urticaria: urticarial rash that appears after a few days of therapy - morbilliform drug reaction - unlikely to occur 1-2 weeks after administration - arthralgia unlikely (see type B drug reaction) 2) serum sickness-like reaction - fever, urticarial rash, arthralgia - onset 1-2 weeks after administration 3) anaphylaxis 4) abdominal discomfort 45) diarrhea a) incidence slightly higher than with ampicillin alone b) clavulanate causes diarrhea [5] 6) nausea/vomiting 7) vaginitis/superinfection 8) increased risk of necrotizing enterocolitis in neonates [9] 9) hepatotoxicity* - typically cholestasis - elevated serum alkaline phosphatase - elevated bilirubin - mild elevations in serum transaminases - jaundice typically occurs following cessation of the drug - mean: 15 days, range: 2-55 days 10) acute interstitial nephritis * most common pharmaceutical agent causing hepatotoxicity [8] * treatment of hepatotoxicity is supportive - N-acetylcysteine use is common practice for drug-induced liver injury, but is not evidence based except for acetaminphen toxicity - refer to liver transplantation center for encephalopathy or coagulopathy Drug interactions: 1) probenecid increases 1/2 life of amoxicillin 2) allopurinol increases incidence of rash Laboratory: - amoxicillin+clavulanate in serum/plasma - amoxicillin+clavulanate-induced platelet IgG - amoxicillin+clavulanate-induced platelet IgM Mechanism of action: 1) amoxicillin inhibits bacterial cell wall synthesis 2) clavulanate is an inhibitor of plasmid-mediated beta-lactamase

Related

beta lactamase

General

beta-lactam/beta-lactamase inhibitor

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Sanford Guide to antimicrobial therapy 1997
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Prescriber's Letter 8(11):63 2001
  6. Prescriber's Letter 9(9):51 2002
  7. Prescriber's Letter 9(10):58 2002
  8. Chalasani N et al. for the Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008 Dec; 135:1924. PMID: 18955056
  9. Yudin MH et al Antibiotic therapy in preterm premature rupture of the membranes. J Obstet Gynaecol Can. 2009 Sep;31(9):863-7, 868-74. PMID: 19941711
  10. Deprecated Reference
  11. Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: 300622 (subscription needed) http://www.prescribersletter.com
  12. Lucena MI, Andrade RJ, Fernandez MC et al Determinants of the clinical expression of amoxicillin- clavulanate hepatotoxicity: a prospective series from Spain. Hepatology. 2006 Oct;44(4):850-6 PMID: 17006920
  13. NEJM Knowledge+ Gastroenterology

Components

amoxicillin (Amoxil, Polymox, Larotid, Trimox, DisperMox, Moxatag, A-cillin) clavulanate (clavulanic acid)