Amoxicillin/clavulanic acid

{{Short description|Combination antibiotic medication}} {{Use dmy dates|date=October 2021}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 477162713 | type = combo | image = Amoxicillin and clavulanic acid.svg | image_class = skin-invert-image | alt =

| component1 = Amoxicillin | class1 = Penicillin antibiotic | component2 = Clavulanic acid | class2 = Beta-lactamase inhibitor

| tradename = Augmentin, Clavulin, Amoclan, others<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=978-1-284-05756-0|page=97}}</ref> | Drugs.com = {{drugs.com|monograph|amoxicillin-and-clavulanate-potassium}} | MedlinePlus = a685024 | DailyMedID = Amoxicillin clavulanate | pregnancy_AU = B1 | pregnancy_category = | routes_of_administration = By mouth, intravenous<ref name=WHO2008/> | ATC_prefix = J01 | ATC_suffix = CR02 | ATC_supplemental = {{ATCvet|J01|CR02}}

| legal_AU = S4 | legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024 | archive-date=6 July 2023 | archive-url=https://web.archive.org/web/20230706023149/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | url-status=live }}</ref> | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title=Regulatory Decision Summary - Amoxicillin Sodium And Potassium Clavulanate For Injection | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?linkID=RDS00643 | access-date=4 June 2022 | archive-date=5 June 2022 | archive-url=https://web.archive.org/web/20220605063339/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?linkID=RDS00643 | url-status=live }}</ref> | legal_UK = POM | legal_US = Rx-only

| IUPAC_name = | C = 24 | H = 27 | K = 1 | N = 4 | O = 10 | S = 1 | SMILES = 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+] | StdInChI = DWHGNUUWCJZQHO-ZVDZYBSKSA-M | StdInChI_comment = | StdInChIKey = 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

| density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Amoxicillin/clavulanic acid''', also known as '''co-amoxiclav''' or '''amox-clav''', sold under the brand names '''Augmentin''', and '''Ranclav''' among others, is an antibiotic medication used for the treatment of a number of bacterial infections.<ref name=AHFS2016/> It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor.<ref name=AHFS2016/> It is specifically used for otitis media, streptococcal pharyngitis, pneumonia, cellulitis, urinary tract infections, and animal bites.<ref name=AHFS2016/> It can be administered orally or intravenously.<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | publisher =World Health Organization | hdl-access=free |page=102}}</ref>

Common side effects include diarrhea, vomiting, and allergic reactions.<ref name=AHFS2016/> It also increases the risk of yeast infections, headaches, and blood clotting problems.<ref name=WHO2008/><ref>{{cite journal | vauthors = Gillies M, Ranakusuma A, Hoffmann T, Thorning S, McGuire T, Glasziou P, Del Mar C | title = Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication | journal = CMAJ | volume = 187 | issue = 1 | pages = E21–E31 | date = January 2015 | pmid = 25404399 | pmc = 4284189 | doi = 10.1503/cmaj.140848 }}</ref> It is not recommended in people with a history of a penicillin allergy.<ref name=WHO2008/> It is relatively safe for use during pregnancy.<ref name=AHFS2016/>

Amoxicillin/clavulanic acid was approved for medical use in the United States in 1984.<ref name=AHFS2016>{{cite web|title=Amoxicillin and Clavulanate Potassium|url=https://www.drugs.com/monograph/amoxicillin-and-clavulanate-potassium.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161129000556/https://www.drugs.com/monograph/amoxicillin-and-clavulanate-potassium.html|archive-date=29 November 2016}}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> The World Health Organization classifies amoxicillin/clavulanic-acid as critically important for human medicine.<ref>{{cite book | year=2019 | title=Critically important antimicrobials for human medicine | edition=6th revision | publisher = World Health Organization | location = Geneva | hdl=10665/312266 | isbn=978-92-4-151552-8 | hdl-access=free }}</ref> It is available as a generic medication.<ref name=AHFS2016/> In 2023, it was the 66th most commonly prescribed medication in the United States, with more than 9{{nbsp}}million prescriptions.<ref name="Top300Drugs">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Amoxicillin; Clavulanate Drug Usage Statistics, United States, 2014 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/AmoxicillinClavulanate | access-date = 18 August 2025 }}</ref>

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

* Urinary tract infections * Respiratory tract infections * Skin and soft tissue infections * Sinus infections * Tonsillitis * Cat scratches * Infections caused by the bacterial flora of the mouth, such as: ** Dental infections ** Infected animal bites ** Infected human bites (including uncomplicated "clenched-fist" or "reverse-bite" injuries)<ref name="BNF" /><ref name="Kucers">{{cite book |author =Gordon D |chapter=Amoxicillin–Clavulanic Acid (Co-Amoxiclav) |editor=Grayson ML |display-editors=etal |title=Kucers' the Use of Antibiotics: a Clinical Review of Antibacterial, Antifungal, Antiparasitic and Antiviral Drugs |publisher=Hodder Arnold/ASM Press |location=London |year=2010 |pages=193–4 |isbn=978-0-340-92767-0}}</ref> * Treatment-resistant tuberculosis (see below) * Diverticulitis

===Urinary tract infections=== Amoxicillin/clavulanic acid is a second-line therapy in the treatment of uncomplicated urinary tract infections (UTIs).<ref name="GrigoryanTrautnerGupta2014">{{cite journal | vauthors = Grigoryan L, Trautner BW, Gupta K | title = Diagnosis and management of urinary tract infections in the outpatient setting: a review | journal = JAMA | volume = 312 | issue = 16 | pages = 1677–1684 | date = 2014 | pmid = 25335150 | doi = 10.1001/jama.2014.12842 | url = }}</ref><ref name="BaderLoebLeto2020">{{cite journal | vauthors = Bader MS, Loeb M, Leto D, Brooks AA | title = Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents | journal = Postgrad Med | volume = 132 | issue = 3 | pages = 234–250 | date = April 2020 | pmid = 31608743 | doi = 10.1080/00325481.2019.1680052 | url = }}</ref> It is active against UTIs caused by ''Staphylococcus saprophyticus'', ''Enterococci'' (e.g., ''Enterococcus faecalis''), ''Escherichia coli'', ''Klebsiella pneumoniae'', and ''Proteus mirabilis''.<ref name="BaderLoebLeto2020" /> It is a definitive treatment against susceptible extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria.<ref name="BaderLoebLeto2020" /> The drug is not effective against ''Pseudomonas aeruginosa'', ''Morganella morganii'', or ''Providencia stuartii'', nor against AmpC β-lactamase- and ESBL-producing Gram-negative bacteria or carbapenem-resistant Enterobacteriaceae (CRE).<ref name="BaderLoebLeto2020" /> It is not recommended in the empiric treatment of acute pyelonephritis or hospital-acquired UTIs.<ref name="BaderLoebLeto2020" />

As determined by a 2014 literature review of antibiotics for UTIs, respective early clinical cure and early bacterial cure rates were 91% and 91% for trimethoprim/sulfamethoxazole, 92% and 87% for nitrofurantoin, 91% and 83% for fosfomycin, 90% and 91% for fluoroquinolones (ciprofloxacin and norfloxacin), and 86% and 81% for β-lactams (amoxicillin/clavulanic acid and cefpodoxime).<ref name="GrigoryanTrautnerGupta2014" /> In a large high-quality randomized controlled trial of amoxicillin/clavulanic acid for UTI in 370{{nbsp}}women, early and late clinical cure rates were 79% and 58%, respectively.<ref name="GrigoryanTrautnerGupta2014" /> Amoxicillin/clavulanic acid reaches a relatively low urine concentration, which might be involved in its lower effectiveness than other antibiotics.<ref name="BaderLoebLeto2020" />

Amoxicillin/clavulanic acid is less effective in the treatment of UTI than first-line therapies used to treat UTIs.<ref name="GrigoryanTrautnerGupta2014" /><ref name="KnottnerusGrigoryanGeerlings2012">{{cite journal | vauthors = Knottnerus BJ, Grigoryan L, Geerlings SE, Moll van Charante EP, Verheij TJ, Kessels AG, ter Riet G | title = Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials | journal = Fam Pract | volume = 29 | issue = 6 | pages = 659–670 | date = December 2012 | pmid = 22516128 | doi = 10.1093/fampra/cms029 | url = }}</ref> A 2012 network meta-analysis of antibiotics for uncomplicated UTIs found that it was less effective than all other assessed agents, including trimethoprim/sulfamethoxazole, nitrofurantoin, fosfomycin, fluoroquinolones (ciprofloxacin, norfloxacin, and gatifloxacin), and pivmecillinam.<ref name="KnottnerusGrigoryanGeerlings2012" /> However, selection of an empirical antibiotic should be based on local or regional susceptibility data.<ref name="BaderLoebLeto2020" /> Additionally, selection of the most appropriate and narrowest effective antibiotic is recommended to help limit increased antibiotic resistance to broad-spectrum antibiotics.<ref name="BaderLoebLeto2020" />

Combining amoxicillin/clavulanic acid with aztreonam can further enhance its activity against certain resistant UTI-causing bacteria.<ref name="BaderLoebLeto2020" />

===Tuberculosis=== It is also used for tuberculosis that is resistant to other treatments.<ref name=AHFS2016/> The World Health Organization recommends giving amoxicillin-clavulanate along with meropenem as one of the therapeutic options in drug-resistant tuberculosis.<ref>{{cite book | year=2016 | title=WHO treatment guidelines for drug-resistant tuberculosis, 2016 update | publisher=World Health Organization | hdl=10665/250125 | hdl-access=free | isbn=978-92-4-154963-9 }}</ref> 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 against beta-lactamase produced by the mycobacteria. Therefore, the minimum dosage of amoxicillin (250 mg) is recommended.<ref>{{cite journal |vauthors=Mishra G, Caminero J |title=First Successful Use of Low Dose Amoxicillin-Clavulanic Acid in Management of Drug Resistant Tuberculosis |journal=Journal of Clinical and Diagnostic Research |year=2018 |volume=12 |issue=10 |pages=OD08–OD10 |doi=10.7860/JCDR/2018/37279.12145 |url=https://jcdr.net/article_fulltext.asp?issn=0973-709x&year=2018&volume=12&issue=10&page=OD08&issn=0973-709x&id=12145 |access-date=7 May 2021 |doi-access=free |title-link=doi |archive-date=7 May 2021 |archive-url=https://web.archive.org/web/20210507170039/https://jcdr.net/article_fulltext.asp?issn=0973-709x&year=2018&volume=12&issue=10&page=OD08&issn=0973-709x&id=12145 |url-status=live }}</ref>

==Adverse effects== Possible side effects include diarrhea, vomiting, nausea, thrush, and skin rash. These do not usually require medical attention. As with all antimicrobial agents, antibiotic-associated diarrhea due to ''Clostridioides difficile'' infection—sometimes leading to pseudomembranous colitis—may occur during or after treatment with amoxicillin/clavulanic acid.<ref name="Kucers" />

Rarely, cholestatic jaundice (also referred to as cholestatic hepatitis, a form of liver 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.<ref name="Kucers" /> In the United Kingdom, co-amoxiclav carries a warning from the Committee on Safety of Medicines to this effect.<ref name="BNF" />

As all aminopenicillins, amoxicillin has been associated with Stevens–Johnson syndrome / toxic epidermal necrolysis, although these reactions are very rare.<ref name="Kucers" /><ref>{{cite journal | vauthors = Harr T, French LE | title = Toxic epidermal necrolysis and Stevens-Johnson syndrome | journal = Orphanet Journal of Rare Diseases | volume = 5 | article-number = 39 | date = December 2010 | pmid = 21162721 | pmc = 3018455 | doi = 10.1186/1750-1172-5-39 | doi-access = free }}</ref>

==Pharmacology== Amoxicillin is an antibiotic of the penicillin family, while clavulanic acid is a non-antibiotic β-lactamase inhibitor that prevents inactivation of penicillins by certain resistant bacteria.<ref>{{cite journal | vauthors = Sutherland R | title = Beta-lactamase inhibitors and reversal of antibiotic resistance | journal = Trends in Pharmacological Sciences | volume = 12 | issue = 6 | pages = 227–232 | date = June 1991 | pmid = 2048218 | doi = 10.1016/0165-6147(91)90557-9 }}</ref>

In addition to its β-lactamase inhibition, clavulanic acid shows central nervous system actions and effects and has been studied in the potential treatment of various psychiatric and neurological disorders.<ref name="Balcazar-OchoaVentura-MartínezÁngeles-López2024">{{cite journal | vauthors = Balcazar-Ochoa LG, Ventura-Martínez R, Ángeles-López GE, Gómez-Acevedo C, Carrasco OF, Sampieri-Cabrera R, Chavarría A, González-Hernández A | title = Clavulanic Acid and its Potential Therapeutic Effects on the Central Nervous System | journal = Arch Med Res | volume = 55 | issue = 1 | article-number = 102916 | date = January 2024 | pmid = 38039802 | doi = 10.1016/j.arcmed.2023.102916 | url = https://www.researchgate.net/publication/376168515}}</ref><ref name="Ochoa-AguilarVentura-MartinezSotomayor-Sobrino2016">{{cite journal | vauthors = Ochoa-Aguilar A, Ventura-Martinez R, Sotomayor-Sobrino MA, Gómez C, Morales-Espinoza MR | title = Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules | journal = Anti-Inflamm Anti-Allergy Agents Med Chem | volume = 15 | issue = 1 | pages = 3–14 | date = 2016 | pmid = 27185396 | doi = 10.2174/1871523015666160517114027 | url = }}</ref><ref name="MilenkovicCampbellRoussel2018">{{cite journal | vauthors = Milenkovic U, Campbell J, Roussel E, Albersen M | title = An update on emerging drugs for the treatment of erectile dysfunction | journal = Expert Opin Emerg Drugs | volume = 23 | issue = 4 | pages = 319–330 | date = December 2018 | pmid = 30507329 | doi = 10.1080/14728214.2018.1552938 | url = }}</ref><ref name="ConnollyThase2012">{{cite journal | vauthors = Connolly KR, Thase ME | title = Emerging drugs for major depressive disorder | journal = Expert Opin Emerg Drugs | volume = 17 | issue = 1 | pages = 105–126 | date = March 2012 | pmid = 22339643 | doi = 10.1517/14728214.2012.660146 | url = }}</ref><ref name="AdisInsight-Clavulanic-Acid">{{cite web | title=Clavulanic acid | website=AdisInsight | date=29 December 2021 | url=https://adisinsight.springer.com/drugs/800027171 | access-date=27 September 2024}}</ref>

==History== British scientists working at Beecham (now part of GlaxoSmithKline) filed for patent protection for the drug combination in 1977, which was granted in 1982.<ref>{{Cite patent|country=GB|number=2005538|pubdate=1982-05-26|title=Pharmaceutical compositsions|assign1=Beecham Group Ltd.|inventor = Crowley PJ }}</ref>

It was sold under the brand name Augmentin.<ref name="BNF">{{cite book |title=British National Formulary |edition=57th |date=March 2009}}</ref><ref name=Bryan2011>{{Cite journal|vauthors=Bryan J|date=23 June 2011|title=Still going strong at 30: co-amoxiclav|url=https://www.pharmaceutical-journal.com/opinion/comment/still-going-strong-at-30-co-amoxiclav/11079379.article|journal=The Pharmaceutical Journal|volume=286|page=762|access-date=20 December 2020|archive-date=22 August 2017|archive-url=https://web.archive.org/web/20170822100525/http://www.pharmaceutical-journal.com/opinion/comment/still-going-strong-at-30-co-amoxiclav/11079379.article}}</ref>

==Preparations== Amoxicillin/clavulanic acid is the International Nonproprietary Name (INN) and co-amoxiclav is the British Approved Name (BAN).{{cn|date=April 2021}}

Many branded products indicate their strengths as the quantity of amoxicillin. Augmentin 250, for example, contains 250 mg of amoxicillin and 125 mg of clavulanic acid.<ref name="BNF"/><ref name="GSK">{{cite web |title=Augmentin -- Prescribing Information |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050575s037550597s044050725s025050726s019lbl.pdf |date=December 2006 |url-status=live |archive-url=https://web.archive.org/web/20131220172200/http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050575s037550597s044050725s025050726s019lbl.pdf |archive-date=20 December 2013 }}</ref>

An intravenous preparation has been available in the UK since 1985,<ref name="pmid3190988">{{cite journal | vauthors = Davies BE, Boon R, Horton R, Reubi FC, Descoeudres CE | title = Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin | journal = British Journal of Clinical Pharmacology | volume = 26 | issue = 4 | pages = 385–390 | date = October 1988 | pmid = 3190988 | pmc = 1386558 | doi = 10.1111/j.1365-2125.1988.tb03395.x }}</ref> but no parenteral preparation is available in the US;{{cn|date=April 2021}} the nearest equivalent is ampicillin/sulbactam.{{cn|date=April 2021}}

Suspensions of amoxicillin/clavulanic acid are available for use in children. They must be refrigerated to maintain effectiveness.{{cn|date=April 2021}}

==Veterinary use== 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-producing ''Staphylococcus aureus'', ''Staphylococcus'' spp., ''Streptococcus'' spp., and ''E. coli''; and periodontal infections due to susceptible strains of both aerobic and anaerobic bacteria.<ref name="FDA approvals">{{cite web | title=Recent Animal Drug Approvals | website=U.S. Food and Drug Administration | date=15 March 2024 | url=https://www.fda.gov/animal-veterinary/approved-animal-drug-products-green-book/recent-animal-drug-approvals | access-date=5 April 2024 | archive-date=5 April 2024 | archive-url=https://web.archive.org/web/20240405052111/https://www.fda.gov/animal-veterinary/approved-animal-drug-products-green-book/recent-animal-drug-approvals | url-status=live }} {{PD-notice}}</ref>

* Cats: Skin and soft tissue infections such as wounds, abscesses, and cellulitis/dermatitis due to susceptible strains of the following organisms: β-lactamase-producing ''Staphylococcus aureus'', non-β-lactamase-producing ''Staphylococcus aureus'', ''Staphylococcus'' spp., ''Streptococcus'' spp., ''E. coli'', and ''Pasteurella'' spp; urinary tract infections (cystitis) due to susceptible strains of ''E. coli.''<ref name="FDA approvals" />

===Bacterial resistance=== Bacterial antibiotic resistance is a growing problem in veterinary medicine. Amoxicillin/clavulanic acid is reported to be effective against clinical ''Klebsiella'' infections, but is not efficacious against ''Pseudomonas'' infections.<ref>Federation of Veterinarians in Europe Position Paper: "Antibiotic Resistance & Prudent Use of Antibiotics in Veterinary Medicine"</ref>

==References== {{Reflist}}

Category:Cat medications Category:Combination antibiotics Category:Dog medications Category:Drugs developed by GSK plc Category:Hepatotoxins Category:Penicillins Category:Veterinary drugs Category:World Health Organization essential medicines Category:Wikipedia medicine articles ready to translate