Aminopenicillin + β-lactamase inhibitor (clavulanate)
Amoxicillin + clavulanic acid (co-amoxiclav) is an antibiotic combining amoxicillin with a beta-lactamase inhibitor, extending the spectrum to bacteria that would inactivate amoxicillin. It is used for respiratory infections, otitis, sinusitis, bites, dental and complicated urinary infections. It should be used on medical prescription; diarrhoea is the most common adverse effect.
Also known as: Amoxicilina/Ácido clavulânico, Co-amoxiclav
Amoxicillin + Clavulanate (a broad-spectrum antibiotic) may potentiate the anticoagulant effect of Warfarin, raising the INR and the bleeding risk.
Amoxicillin-clavulanate eliminates much of the gut bacterial flora that synthesises vitamin K, reducing the availability of the cofactor needed to carboxylate the vitamin K-dependent coagulation factors (II, VII, IX, X). Since warfarin acts precisely through that pathway (inhibition of vitamin K epoxide reductase), the additional reduction of endogenous vitamin K potentiates the anticoagulant effect and the INR rises. The effect is more evident in patients with marginal dietary vitamin K intake and can appear days after starting the antibiotic. INR monitoring during and after the antibiotic course is essential; in patients with a previously stable INR, consider more frequent checks and alert for bleeding signs (gingival bleeding, bruising, melaena).
Broad-spectrum antibiotics can potentiate warfarin by reducing the gut flora that produces vitamin K and, for some, by enzyme inhibition. Monitor the INR during and after the antibiotic and watch for bleeding.
Reduction of vitamin-K-producing gut flora and altered haemostasis increase the response to the anticoagulant.
INR, signs of bleeding (gums, bruising, melena).
Unexplained bleeding, haematuria, melena.
Monitor the INR when starting and stopping the antibiotic; adjust the warfarin dose as needed.
DailyMed/FDA (NIH/NLM) — approved Amoxicillin + Clavulanate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5250085e-5509-c577-e063-6294a90a9b87 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Alcohol may worsen the gastrointestinal effects of amoxicillin + clavulanate; limit intake.
Limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Amoxicillin + Clavulanate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5250085e-5509-c577-e063-6294a90a9b87
Taking with food reduces gastrointestinal discomfort and improves clavulanate absorption; taking at the start of a meal is recommended.
Take at the start of a meal to reduce gastrointestinal effects.
DailyMed/FDA (NIH/NLM) — approved Amoxicillin + Clavulanate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5250085e-5509-c577-e063-6294a90a9b87
Clavulanic acid is associated with cholestatic hepatitis; the combination is contraindicated in patients with a history of jaundice or hepatic dysfunction attributed to clavulanate.
Contraindicated in a history of jaundice with amoxicillin + clavulanate.
DailyMed/FDA (NIH/NLM) — approved Amoxicillin + Clavulanate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5250085e-5509-c577-e063-6294a90a9b87
Amoxicillin is a penicillin; the combination is contraindicated in patients with prior penicillin allergy.
Contraindicated in penicillin allergy; choose an alternative from another class.
DailyMed/FDA (NIH/NLM) — approved Amoxicillin + Clavulanate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5250085e-5509-c577-e063-6294a90a9b87
Amoxicillin + clavulanate is generally safe in pregnancy when indicated; use with caution in a history of cholestatic hepatitis (avoid).
May be used in pregnancy when indicated, except in a history of jaundice with this combination.
Excreted into breast milk in small amounts; compatible with breastfeeding.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Amoxicillin + Clavulanate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5250085e-5509-c577-e063-6294a90a9b87
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Combination of amoxicillin (bactericidal aminopenicillin) with clavulanic acid, a suicide inhibitor of beta-lactamases that protects amoxicillin from inactivation — extending the spectrum to penicillinase-producing staphylococci, Haemophilus, Klebsiella and E. coli. Risk of cholestatic hepatotoxicity (more frequent in the elderly, men and use >14 days).
Amoxicillin inhibits cell wall synthesis (PBP binding); clavulanate binds covalently to beta-lactamases (including plasmid-mediated enzymes of S. aureus, Haemophilus, Klebsiella, E. coli), inactivating them and restoring amoxicillin activity.
Peaks ~1.5 h after dosing with a light meal (amoxicillin 11.6 mcg/mL; clavulanate 2.2 mcg/mL for 875/125 mg); rapid, complete oral absorption; can be taken with or without food (less GI discomfort with food).
Amoxicillin is partially metabolised and excreted unchanged renally; clavulanate is extensively metabolised and excreted in urine and faeces. Adjust in renal impairment (both components accumulate).
Half-life ~1.3 h (amoxicillin) and ~1 h (clavulanate) in adults with normal renal function.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
