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Amoxicillin/clavulanic acid

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Amoxicillin/clavulanic acid
Combination of
AmoxicillinPenicillin antibiotic
Clavulanic acidBeta-lactamase inhibitor
Clinical data
Trade namesAugmentin, Clavulin, Amoclan, others[1]
Other namesCo-amoxiclav; Amox-clav
AHFS/DrugsMonograph
MedlinePlusa685024
License data
Pregnancy
category
  • AU:B1
Routes of
administration		By mouth,intravenous[2]
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChemCID
ChemSpider
KEGG
ChEMBL
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC24H27KN4O10S
Molar mass602.66g·mol−1
3D model (JSmol)
  • CC1(C(N2C(S1)C(C2=O)NC(=O)C(C3=CC=C(C=C3)O)N)C(=O)O)C.C1C2N(C1=O)C(C(=CCO)O2)C(=O)[O-].[K+]
  • InChI=DWHGNUUWCJZQHO-ZVDZYBSKSA-M
  • Key:1S/C16H19N3O5S.C8H9NO5.K/c1-16(2)11(15(23)24)19-13(22)10(14(19)25-16)18-12(21)9(17)7-3-5-8(20)6-4-7;10-2-1-4-7(8(12)13)9-5(11)3-6(9)14-4;/h3-6,9-11,14,20H,17H2,1-2H3,(H,18,21)(H,23,24);1,6-7,10H,2-3H2,(H,12,13);/q;;+1/p-1/b;4-1-;/t9-,10-,11+,14-;6-,7-;/m11./s1
☒NcheckY(what is this?)(verify)

Amoxicillin/clavulanic acid,also known asco-amoxiclavoramox-clav,sold under the brand nameAugmentin,among others, is anantibioticmedication used for the treatment of a number ofbacterial infections.[5]It is a combination consisting ofamoxicillin,aβ-lactam antibiotic,andpotassium clavulanate,aβ-lactamase inhibitor.[5]It is specifically used forotitis media,streptococcal pharyngitis,pneumonia,cellulitis,urinary tract infections,andanimal bites.[5]It is takenby mouthor byinjection into a vein.[2]

Commonside effectsincludediarrhea,vomiting, andallergic reactions.[5]It also increases the risk ofyeast infections,headaches, andblood clotting problems.[2][6]It is not recommended in people with a history of apenicillin allergy.[2]It is relatively safe for use during pregnancy.[5]

Amoxicillin/clavulanic acid was approved for medical use in the United States in 1984.[5]It is on theWorld Health Organization's List of Essential Medicines.[7][8]The World Health Organization classifies amoxicillin/clavulanic-acid as critically important for human medicine.[9]It is available as a generic medication.[5]In 2022, it was the 96th most commonly prescribed medication in the United States, with more than 6million prescriptions.[10][11]

Medical uses

[edit]

Amoxicillin/clavulanic acid is widely used to treat or prevent many infections caused by susceptible bacteria, such as:

Urinary tract infections

[edit]

Amoxicillin/clavulanic acid is asecond-line therapyin the treatment of uncomplicatedurinary tract infections(UTIs).[14][15]It is active against UTIs caused byStaphylococcus saprophyticus,Enterococci(e.g.,Enterococcus faecalis),Escherichia coli,Klebsiella pneumoniae,andProteus mirabilis.[15]It is a definitive treatment against susceptibleextended-spectrum β-lactamase(ESBL)-producingGram-negative bacteria.[15]The drug is not effective againstPseudomonas aeruginosa,Morganella morganii,orProvidencia stuartii,nor againstAmpC β-lactamase- and ESBL-producing Gram-negative bacteria orcarbapenem-resistant Enterobacteriaceae(CRE).[15]It is not recommended in theempiric treatmentof acutepyelonephritisorhospital-acquiredUTIs.[15]

As determined by a 2014literature reviewof antibiotics for UTIs, respective early clinical cure and early bacterial cure rates were 91% and 91% fortrimethoprim/sulfamethoxazole,92% and 87% fornitrofurantoin,91% and 83% forfosfomycin,90% and 91% forfluoroquinolones(ciprofloxacinandnorfloxacin), and 86% and 81% forβ-lactams(amoxicillin/clavulanic acid andcefpodoxime).[14]In a large high-qualityrandomized controlled trialof amoxicillin/clavulanic acid for UTI in 370women, early and late clinical cure rates were 79% and 58%, respectively.[14]Amoxicillin/clavulanic acid reaches a relatively lowurineconcentration, which might be involved in its lower effectiveness than other antibiotics.[15]

Amoxicillin/clavulanic acid is less effective in the treatment of UTI thanfirst-line therapiesused to treat UTIs.[14][16]A 2012network meta-analysisof antibiotics for uncomplicated UTIs found that it was less effective than all other assessed agents, including trimethoprim/sulfamethoxazole, nitrofurantoin, fosfomycin, fluoroquinolones (ciprofloxacin, norfloxacin, andgatifloxacin), andpivmecillinam.[16]However, selection of an empirical antibiotic should be based on local or regional susceptibility data.[15]Additionally, selection of the most appropriate and narrowest effective antibiotic is recommended to help limit increasedantibiotic resistancetobroad-spectrum antibiotics.[15]

Combining amoxicillin/clavulanic acid withaztreonamcan further enhance its activity against certain resistant UTI-causing bacteria.[15]

Tuberculosis

[edit]

It is also used fortuberculosisthat is resistant to other treatments.[5]The World Health Organization recommends giving amoxicillin-clavulanate along withmeropenemas one of the therapeutic options indrug-resistant tuberculosis.[17]However, across the spectrum of dosage of amoxicillin-clavulanate combination, the dose of clavulanate is constant at 125 mg, whereas the dose of amoxicillin varies at 250 mg, 500 mg and 875 mg. Thus the use of low-dose amoxicillin-clavulanate in combination with meropenem may be used in part of a treatment regimen for drug-resistant TB and this has been demonstrated in a clinical setting also. Its efficacy is attributed not to the amoxicillin component, but to the protective action of clavulanic acid over meropenem againstbeta-lactamaseproduced by themycobacteria.Therefore, the minimum dosage of amoxicillin (250 mg) is recommended.[18]

Adverse effects

[edit]

Possible side effects includediarrhea,vomiting,nausea,thrush,and skinrash.These do not usually require medical attention. As with all antimicrobial agents,antibiotic-associated diarrheadue toClostridioides difficileinfection—sometimes leading topseudomembranous colitis—may occur during or after treatment with amoxicillin/clavulanic acid.[13]

Rarely,cholestaticjaundice (also referred to as cholestatic hepatitis, a form ofliver toxicity) has been associated with amoxicillin/clavulanic acid. The reaction may occur up to several weeks after treatment has stopped and usually takes weeks to resolve. It is more frequent in men, older people, and those who have taken long courses of treatment; the estimated overall incidence is one in 100,000 exposures.[13]In the United Kingdom, co-amoxiclav carries a warning from theCommittee on Safety of Medicinesto this effect.[12]

As allaminopenicillins,amoxicillin has been associated withStevens–Johnson syndrome/toxic epidermal necrolysis,although these reactions are very rare.[13][19]

Pharmacology

[edit]

Amoxicillinis anantibioticwhileclavulanic acidis a non-antibioticβ-lactamase inhibitorwhich preventsmetabolismof amoxicillin by certainbacteria.

In addition to its β-lactamase inhibition, clavulanic acid showscentral nervous systemactions and effects andhas been studiedin the potential treatment of variouspsychiatricandneurological disorders.[20][21][22][23][24]

History

[edit]

British scientists working atBeecham(now part ofGlaxoSmithKline), filed for patent protection for the drug combination in 1977, which was granted in 1982.[25]

It was sold under the brand name Augmentin.[12][26]

Preparations

[edit]

Amoxicillin/clavulanic acid is theInternational Nonproprietary Name(INN) and co-amoxiclav is theBritish Approved Name(BAN).[citation needed]

Many branded products indicate their strengths as the quantity of amoxicillin. Augmentin 250, for example, contains 250 mg of amoxicillin and 125 mg ofclavulanic acid.[12][27]

An intravenous preparation has been available in the UK since 1985,[28]but noparenteralpreparation is available in the US;[citation needed]the nearest equivalent isampicillin/sulbactam.[citation needed]

Suspensionsof amoxicillin/clavulanic acid are available for use in children. They must be refrigerated to maintain effectiveness.[citation needed]

Veterinary use

[edit]

Amoxicillin/clavulanic acid is used in numerous animals for a variety of conditions:

  • Dogs: Skin and soft tissue infections such as wounds, abscesses, cellulitis, superficial/juvenile and deep pyoderma due to susceptible strains of the following organisms: β-lactamase-producing Staphylococcus aureus, non-β-lactamase-producingStaphylococcus aureus,Staphylococcusspp.,Streptococcusspp., andE. coli;and periodontal infections due to susceptible strains of both aerobic and anaerobic bacteria.[29]
  • Cats: Skin and soft tissue infections such as wounds, abscesses, and cellulitis/dermatitis due to susceptible strains of the following organisms: β-lactamase-producingStaphylococcus aureus,non-β-lactamase-producingStaphylococcus aureus,Staphylococcusspp.,Streptococcusspp.,E. coli,andPasteurellaspp; urinary tract infections (cystitis) due to susceptible strains ofE. coli.[29]

Bacterial resistance

[edit]

Bacterialantibiotic resistanceis a growing problem inveterinary medicine.Amoxicillin/clavulanic acid is reported to be effective against clinicalKlebsiellainfections, but is not efficacious againstPseudomonasinfections.[30]

References

[edit]
  1. ^Hamilton R (2015).Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition.Jones & Bartlett Learning. p. 97.ISBN9781284057560.
  2. ^abcdWorld Health Organization(2009). Stuart MC, Kouimtzi M, Hill SR (eds.).WHO Model Formulary 2008.World Health Organization. p. 102.hdl:10665/44053.ISBN9789241547659.
  3. ^"Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017".Therapeutic Goods Administration (TGA).21 June 2022.Archivedfrom the original on 6 July 2023.Retrieved30 March2024.
  4. ^"Regulatory Decision Summary - Amoxicillin Sodium And Potassium Clavulanate For Injection".Health Canada.23 October 2014.Archivedfrom the original on 5 June 2022.Retrieved4 June2022.
  5. ^abcdefgh"Amoxicillin and Clavulanate Potassium".The American Society of Health-System Pharmacists.Archivedfrom the original on 29 November 2016.Retrieved8 December2016.
  6. ^Gillies M, Ranakusuma A, Hoffmann T, Thorning S, McGuire T, Glasziou P, et al. (January 2015)."Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication".CMAJ.187(1): E21–E31.doi:10.1503/cmaj.140848.PMC4284189.PMID25404399.
  7. ^World Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  8. ^World Health Organization(2021).World Health Organization model list of essential medicines: 22nd list (2021).Geneva: World Health Organization.hdl:10665/345533.WHO/MHP/HPS/EML/2021.02.
  9. ^World Health Organization(2019).Critically important antimicrobials for human medicine(6th revision ed.). Geneva: World Health Organization.hdl:10665/312266.ISBN9789241515528.
  10. ^"The Top 300 of 2022".ClinCalc.Archivedfrom the original on 30 August 2024.Retrieved30 August2024.
  11. ^"Amoxicillin; Clavulanate Drug Usage Statistics, United States, 2013 - 2022".ClinCalc.Retrieved30 August2024.
  12. ^abcdBritish National Formulary(57th ed.). March 2009.
  13. ^abcdGordon D (2010). "Amoxicillin–Clavulanic Acid (Co-Amoxiclav)". In Grayson ML, et al. (eds.).Kucers' the Use of Antibiotics: a Clinical Review of Antibacterial, Antifungal, Antiparasitic and Antiviral Drugs.London: Hodder Arnold/ASM Press. pp. 193–4.ISBN978-0-340-92767-0.
  14. ^abcdGrigoryan L, Trautner BW, Gupta K (2014). "Diagnosis and management of urinary tract infections in the outpatient setting: a review".JAMA.312(16): 1677–1684.doi:10.1001/jama.2014.12842.PMID25335150.
  15. ^abcdefghiBader MS, Loeb M, Leto D, Brooks AA (April 2020). "Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents".Postgrad Med.132(3): 234–250.doi:10.1080/00325481.2019.1680052.PMID31608743.
  16. ^abKnottnerus BJ, Grigoryan L, Geerlings SE, Moll van Charante EP, Verheij TJ, Kessels AG, et al. (December 2012). "Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials".Fam Pract.29(6): 659–670.doi:10.1093/fampra/cms029.PMID22516128.
  17. ^World Health Organization (2016).WHO treatment guidelines for drug-resistant tuberculosis, 2016 update.World Health Organization.hdl:10665/250125.ISBN9789241549639.
  18. ^Mishra G, Caminero J (2018)."First Successful Use of Low Dose Amoxicillin-Clavulanic Acid in Management of Drug Resistant Tuberculosis".Journal of Clinical and Diagnostic Research.12(10): OD08–OD10.doi:10.7860/JCDR/2018/37279.12145.Archivedfrom the original on 7 May 2021.Retrieved7 May2021.
  19. ^Harr T, French LE (December 2010)."Toxic epidermal necrolysis and Stevens-Johnson syndrome".Orphanet Journal of Rare Diseases.5:39.doi:10.1186/1750-1172-5-39.PMC3018455.PMID21162721.
  20. ^Balcazar-Ochoa LG, Ventura-Martínez R, Ángeles-López GE, Gómez-Acevedo C, Carrasco OF, Sampieri-Cabrera R, et al. (January 2024)."Clavulanic Acid and its Potential Therapeutic Effects on the Central Nervous System".Arch Med Res.55(1): 102916.doi:10.1016/j.arcmed.2023.102916.PMID38039802.
  21. ^Ochoa-Aguilar A, Ventura-Martinez R, Sotomayor-Sobrino MA, Gómez C, Morales-Espinoza MR (2016). "Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules".Anti-Inflamm Anti-Allergy Agents Med Chem.15(1): 3–14.doi:10.2174/1871523015666160517114027.PMID27185396.
  22. ^Milenkovic U, Campbell J, Roussel E, Albersen M (December 2018). "An update on emerging drugs for the treatment of erectile dysfunction".Expert Opin Emerg Drugs.23(4): 319–330.doi:10.1080/14728214.2018.1552938.PMID30507329.
  23. ^Connolly KR, Thase ME (March 2012). "Emerging drugs for major depressive disorder".Expert Opin Emerg Drugs.17(1): 105–126.doi:10.1517/14728214.2012.660146.PMID22339643.
  24. ^"Clavulanic acid".AdisInsight.29 December 2021.Retrieved27 September2024.
  25. ^GB 2005538,Crowley PJ, "Pharmaceutical compositsions", published 1982-05-26, assigned toBeecham Group Ltd.
  26. ^Bryan J (23 June 2011)."Still going strong at 30: co-amoxiclav".The Pharmaceutical Journal.286:762. Archived fromthe originalon 22 August 2017.Retrieved20 December2020.
  27. ^"Augmentin -- Prescribing Information"(PDF).December 2006.Archived(PDF)from the original on 20 December 2013.
  28. ^Davies BE, Boon R, Horton R, Reubi FC, Descoeudres CE (October 1988)."Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin".British Journal of Clinical Pharmacology.26(4): 385–390.doi:10.1111/j.1365-2125.1988.tb03395.x.PMC1386558.PMID3190988.
  29. ^ab"Recent Animal Drug Approvals".U.S. Food and Drug Administration.15 March 2024.Archivedfrom the original on 5 April 2024.Retrieved5 April2024.Public DomainThis article incorporates text from this source, which is in thepublic domain.
  30. ^Federation of Veterinarians in Europe Position Paper: "Antibiotic Resistance & Prudent Use of Antibiotics in Veterinary Medicine"
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