Amoxicillin/clavulanic acid

Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an antibiotic medication used for the treatment of a number of bacterial infections.^[4] It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor.^[4] It is specifically used for otitis media, streptococcal pharyngitis, pneumonia, cellulitis, urinary tract infections, and animal bites.^[4] It is taken by mouth or by injection into a vein.^[2]

Amoxicillin/clavulanic acid

Combination of
Amoxicillin	Penicillin antibiotic
Clavulanic acid	Beta-lactamase inhibitor
Clinical data
Trade names	Augmentin, Clavulin, Amoclan, others^[1]
AHFS/Drugs.com	Monograph
MedlinePlus	a685024
License data	US DailyMed: Amoxicillin clavulanate US FDA: Augmentin
Pregnancy category	AU: B1
Routes of administration	By mouth, intravenous^[2]
ATC code	J01CR02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only ^[3] UK: POM (Prescription only) US: ℞-only
Identifiers
CAS Number	74469-00-4 74428-36-7
PubChem CID	6435924
ChemSpider	4940608
KEGG	D06485
ChEMBL	ChEMBL1697738
CompTox Dashboard (EPA)	DTXSID40225477
Chemical and physical data
Formula	C24H27KN4O10S
Molar mass	602.66 g·mol^−1
3D model (JSmol)	Interactive image
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+]
InChI 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
^NY (what is this?)  (verify)

Common side effects include diarrhea, vomiting, and allergic reactions.^[4] It also increases the risk of yeast infections, headaches, and blood clotting problems.^[2][5] It is not recommended in people with a history of a penicillin allergy.^[2] It is relatively safe for use during pregnancy.^[4]

Amoxicillin/clavulanic acid was approved for medical use in the United States in 1984.^[4] It is on the World Health Organization's List of Essential Medicines.^[6] The World Health Organization classifies amoxicillin/clavulanic-acid as critically important for human medicine.^[7] It is available as a generic medication.^[4] In 2020, it was the 107th most commonly prescribed medication in the United States, with more than 6 million prescriptions.^[8][9]

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)^[10][11]

It is also used for tuberculosis that is resistant to other treatments.^[4] The World Health Organisation recommends giving amoxicillin-clavulanate along with meropenem as one of the therapeutic options in drug resistant tuberculosis, where clavulanate and not amoxicillin is being relied upon for anti TB activity. 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 treatment regime for drug resistant TB and this has been demonstrated in a clinical setting also.^[12]

This combination results in an antibiotic with an increased spectrum of action and restored efficacy against amoxicillin-resistant bacteria that produce β-lactamase.^{[citation needed]}

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 Clostridium difficile infection—sometimes leading to pseudomembranous colitis—may occur during or after treatment with amoxicillin/clavulanic acid.^[11]

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.^[11] In the United Kingdom, co-amoxiclav carries a warning from the Committee on Safety of Medicines to this effect.^[10]

As all aminopenicillins, amoxicillin has been associated with Stevens–Johnson syndrome/toxic epidermal necrolysis, although these reactions are very rare.^[11][13]

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.^[14] It was sold under the brand name Augmentin.^[10][15]

Preparations

Amoxicillin/clavulanic acid is the International Nonproprietary Name (INN) and co-amoxiclav is the British 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 of clavulanic acid.^[10][16]

An intravenous preparation has been available in the UK since 1985,^[17] but no parenteral preparation is available in the US;^{[citation needed]} the nearest equivalent is ampicillin/sulbactam.^{[citation needed]}

Suspensions of amoxicillin/clavulanic acid are available for use in children.^{[citation needed]} They must be refrigerated to maintain effectiveness.^{[citation needed]}

Veterinary use

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

• Dogs: periodontitis, kennel cough^[18][19]
• Cats: urinary tract infections, skin and soft tissue infections^{[citation needed]}
• Calves: enteritis, navel ill^{[citation needed]}
• Cattle: respiratory tract infections, soft tissue infections, metritis, mastitis^{[citation needed]}
• Pigs: respiratory tract infections, colibacillosis, mastitis, metritis, agalactia^{[citation needed]}

In combination with prednisolone, it is used for intramammary infusion for the treatment of mastitis in lactating cows.^{[citation needed]} Trade names include Clavaseptin, Clavamox, and Synulox.^{[citation needed]}

Amoxicillin/clavulanic acid is banned from use in domestic-food animals (cattle, swine, etc.) in both the US and Europe;^{[citation needed]} in the UK, Synulox can be used in domestic-food animals as long as a specified withdrawal period is observed.^{[citation needed]}

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.^[20]

References

1. Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 97. ISBN 9781284057560.
2. World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 102. hdl:10665/44053. ISBN 9789241547659.
3. "Regulatory Decision Summary - Amoxicillin Sodium And Potassium Clavulanate For Injection". Health Canada. 23 October 2014. Retrieved 4 June 2022.
4. "Amoxicillin and Clavulanate Potassium". The American Society of Health-System Pharmacists. from the original on 29 November 2016. Retrieved 8 December 2016.
5. Gillies, M; Ranakusuma, A; Hoffmann, T; Thorning, S; McGuire, T; Glasziou, P; Del Mar, C (17 November 2014). "Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication". Canadian Medical Association Journal. 187 (1): E21-31. doi:10.1503/cmaj.140848. PMC 4284189. PMID 25404399.
6. 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.
7. World Health Organization (2019). Critically important antimicrobials for human medicine (6th revision ed.). Geneva: World Health Organization. hdl:10665/312266. ISBN 9789241515528.
8. "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
9. "Amoxicillin; Clavulanate - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
10. British National Formulary (57 ed.). March 2009.
11. Gordon 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. ISBN 978-0-340-92767-0.
12. Mishra, Gyanshankar; Caminero, Jose (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. Retrieved 7 May 2021.
13. Harr T, French LE (2010). "Toxic epidermal necrolysis and Stevens-Johnson syndrome". Orphanet Journal of Rare Diseases. 5: 39. doi:10.1186/1750-1172-5-39. PMC 3018455. PMID 21162721.
14. GB 2005538, Crowley, Patrick John, "Pharmaceutical compositsions", published 1982-05-26, assigned to Beecham Group Ltd. 
15. Bryan, Jenny (23 June 2011). "Still going strong at 30: co-amoxiclav". The Pharmaceutical Journal. 286: 762.
16. "Augmentin -- Prescribing Information" (PDF). December 2006. (PDF) from the original on 20 December 2013.
17. 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): 385–90. doi:10.1111/j.1365-2125.1988.tb03395.x. PMC 1386558. PMID 3190988.
18. . Archived from the original on 21 May 2006. Retrieved 30 May 2013.
19. "Kennel Cough - Symptoms and Treatment". 30 April 2013. from the original on 10 May 2013. Retrieved 30 May 2013.
20. Federation of Veterinarians in Europe Position Paper: "Antibiotic Resistance & Prudent Use of Antibiotics in Veterinary Medicine"

External links

• "Amoxicillin / clavulanic acid". Drug Information Portal. U.S. National Library of Medicine.