Amoxicillin + clavulanic acid is a broad-spectrum antibiotic combining a penicillin with a substance that defeats the defences of many resistant bacteria. It treats ear, sinus, lung, urinary, skin and dental infections.
Also known as: Augmentin, Clavulin, Curam
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
Taking at the start of a meal improves gastric tolerability and clavulanate stability (which degrades more in an empty acid stomach).
Take at the start of meals to reduce gastric discomfort (site monograph).
Site monograph (amoxicillin-clavulanate — take at start of meals); EMC-UK co-amoxiclav SmPC 4.2.
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
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
Clavulanate causes cholestatic jaundice — contraindicated in anyone with prior jaundice/hepatic dysfunction with this combination.
Always ask about prior jaundice/hepatitis with amoxicillin-clavulanate; contraindicates re-exposure.
Site monograph (prior jaundice/hepatitis with this combination contraindicates re-exposure); EMC-UK co-amoxiclav SmPC 4.3/4.4.
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 (and ampicillin) causes a high-rate rash (almost universal) in mononucleosis — not true allergy but discourages use.
Suspect mononucleosis in pharyngitis with lymphadenopathy in the young; prefer another antibiotic.
Site monograph (mononucleosis — high rash risk); Prontuário 6.1.1.
Reduce the dose or extend the dosing interval to 8-12 hours in severe renal impairment; skin rashes more frequent.
Reduce the dose or extend the interval in severe renal impairment.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 4, Drugs and renal impairment: Reduce the dose or extend the dosing interval to 8-12 hours in severe renal impairment; skin rashes more frequent.
Amoxicillin alone is safe in pregnancy; the clavulanate combination requires caution: Annex 1 records "the association of clavulanic acid with amoxicillin increases hepatic toxicity 6-fold, so caution is recommended in pregnancy" (factor D). Use only when amoxicillin alone is not adequate.
Use if clearly indicated (infections resistant to amoxicillin alone); reserve the combination for when benefit justifies.
Amoxicillin is "safe at the usual dose" (Annex 2, l. 42225); the clavulanate combination is likewise considered compatible with monitoring of the infant for intestinal flora changes.
No specific additional contraception.
Prontuário Terapêutico INFARMED — Annex 1: Beta-lactamase inhibitors (l. 40593-94, factor D); Annex 2: "Amoxicillin — Safe at the usual dose" (l. 42225). EMC-UK (MHRA) — Co-amoxiclav SmPC.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bactericidal through cell wall synthesis inhibition; clavulanate extends the spectrum to beta-lactamase producers.
Amoxicillin binds PBPs (penicillin-binding proteins) preventing peptidoglycan cross-linking; clavulanate irreversibly inhibits bacterial beta-lactamases.
Good oral absorption (75–90%), reduced by food but without clinically relevant impact on total dose.
Partial hepatic hydrolysis; predominantly renal excretion (≥ 60% unchanged in urine). Adjust in renal failure.
Amoxicillin ~ 1–1.5 h; clavulanate ~ 1 h (reduced in renal failure).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
