amoxicillin/clavulanate (Augmentin)
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Introduction
Tradename: Augmentin.
Indications
- treatment of mild to moderate bacterial infections due to beta-lactamase-producing organisms
- step-down coverage when using Unasyn for initial antibiotic coverage
- empiric treatment of febrile neutropenia[10]
- empiric treatment of fever of unknown origin[10]
Contraindications
Dosage
- 250-500 mg PO TID
- Pediatrics:
- 40 mg/kg/day divided TID (based on amoxicillin)
- 90 mg/kg/day divided BID for recurrent otitis media[5]
Tabs: 125, 250, 500 mg.
- 125: 125 mg amoxicillin & 31.2 mg clavulanate/ 5 mL, 75 & 150 mL
- 200: 200 mg amoxicillin & 28.5 mg clavulanate/ 5 mL, 50, 75 & 100 mL
- 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
- 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:
- creatinine clearance 10-50 mL/min: use every 12 hours dosing
- creatinine clearance < 10 mL/min: use QD dosing
Pharmacokinetics
- well absorbed orally
- not affected by food intake
- does not achieve therapeutic levels in CNS
- 1/2 life 1-1.5 hours, increased in renal failure
- both amoxicillin & clavulanate removed by hemodialysis
- amoxicillin pharmacokinetics not influenced by clavulanate
- clavulanate is metabolized by the liver
- amoxicillin is eliminated in the urine
Antimicrobial activity
- Streptococcus
- Streptococcus pneumonia
- Streptococcus viridans, milleri
- Enterococcus faecalis
- Enterococcus faecium
- Staphylococcus aureus (MSSA)
- Staphylococcus epidermidis
- Listeria monocytogenes
- Neisseria gonorrhoeae
- Neisseria meningitidis
- Moraxella catarrhalis
- Haemophilus
- Escherichia coli
- Klebsiella species
- Salmonella species
- Shigella species
- Proteus mirabilis
- Proteus vulgaris
- Providencia species
- Morganella species (+/-)
- Aeromonas species
- Yersinia enterocolitica (+/-)
- Pasteurella multocida
- Enterobacter
- Actinomyces
- Bacteroides fragilis
- Bacteroides melaninogenicus
- Clostridium difficile
- Clostridium species
- Peptostreptococcus species
Adverse effects
(uncommon < 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)
- serum sickness-like reaction
- fever, urticarial rash, arthralgia
- onset 1-2 weeks after administration
- anaphylaxis
- abdominal discomfort
- diarrhea
- incidence slightly higher than with ampicillin alone
- clavulanate causes diarrhea[5]
- nausea/vomiting
- vaginitis/superinfection
- increased risk of necrotizing enterocolitis in neonates[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
- typically cholestasis
- 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
- probenecid increases 1/2 life of amoxicillin
- allopurinol increases incidence of rash
Laboratory
- amoxicillin+clavulanate in serum/plasma
- amoxicillin+clavulanate-induced platelet IgG
- amoxicillin+clavulanate-induced platelet IgM
Mechanism of action
- amoxicillin inhibits bacterial cell wall synthesis
- clavulanate is an inhibitor of plasmid-mediated beta-lactamase
More general terms
Additional terms
Components
- amoxicillin (Amoxil, Polymox, Larotid, Trimox, DisperMox, Moxatag, A-cillin)
- clavulanate (clavulanic acid)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Sanford Guide to antimicrobial therapy 1997
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 5.0 5.1 5.2 5.3 Prescriber's Letter 8(11):63 2001
- ↑ 6.0 6.1 Prescriber's Letter 9(9):51 2002
- ↑ 7.0 7.1 Prescriber's Letter 9(10):58 2002
- ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/18955056
- ↑ 9.0 9.1 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: https://www.ncbi.nlm.nih.gov/pubmed/19941711
- ↑ 10.0 10.1 10.2 10.3 10.4 Deprecated Reference
- ↑ 11.0 11.1 Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300622&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/17006920
- ↑ NEJM Knowledge+ Gastroenterology