Skip to content
ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Antibiotic (Penicillin + Beta-Lactamase Inhibitor) Pregnancy: SPC 4.6 Pregnancy: animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Limited data on the use of amoxicillin/clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. 'Use should be avoided during pregnancy, unless considered essential by the physician.' Breast-feeding: both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant); diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so breast-feeding might have to be discontinued; the possibility of sensitisation should be taken into account. Amoxicillin/clavulanic acid should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

Co-Amoxiclav

Brand names: Augmentin

Used in: Pneumonia Urinary Tract Infection Cellulitis & Skin Infection Acute Appendicitis

Co-amoxiclav is a fixed combination of the penicillin amoxicillin with the beta-lactamase inhibitor clavulanic acid, used for infections caused by beta-lactamase-producing organisms resistant to amoxicillin alone.

Adult dose

Dose: Infections listed in the SPC (section 4.1): acute bacterial sinusitis; acute otitis media; acute exacerbations of chronic bronchitis; community acquired pneumonia; cystitis; pyelonephritis; skin and soft tissue infections, in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis; bone and joint infections, in particular osteomyelitis. Product: co-amoxiclav 500 mg/125 mg film-coated tablet (each tablet contains amoxicillin 500 mg as trihydrate and clavulanic acid 125 mg as potassium clavulanate). Adults and children 40 kg and over: one 500 mg/125 mg tablet taken three times a day.
Route: Oral
Frequency: Three times a day. Administer at the start of a meal to minimise potential gastrointestinal intolerance and optimise absorption of amoxicillin/clavulanic acid.
SCOPE: these figures are the UK SPC for ONE product only, co-amoxiclav 500 mg/125 mg film-coated tablets (Bristol Laboratories, PL179070483). This page also lists an intravenous route and a lower 250/125 tablet strength; neither is covered by this SPC and no intravenous or 250/125 dose is given here. The SPC says only: 'Therapy can be started parenterally according the SPC of the IV-formulation and continued with an oral preparation.' Other co-amoxiclav presentations (suspensions, sachets, higher-dose amoxicillin products) have their own SPCs and are not covered. TOTAL DAILY DOSE (printed, not a ceiling): 'For adults and children >= 40 kg, this formulation of Co-amoxiclav provides a total daily dose of 1500 mg amoxicillin /375 mg clavulanic acid, when administered as recommended below.' The SPC prints no maximum dose for adults. 'If it is considered that a higher daily dose of amoxicillin is required, it is recommended that another preparation of Co-amoxiclav is selected in order to avoid administration of unnecessarily high daily doses of clavulanic acid.' CHOICE OF DOSE (SPC 4.2): the dose selected should take into account the expected pathogens and their likely susceptibility to antibacterial agents, the severity and the site of the infection, and the age, weight and renal function of the patient; 'Consideration should be given to official guidance on the appropriate use of antibacterial agents' (4.1). DURATION: determined by the response of the patient; some infections (e.g. osteomyelitis) require longer periods of treatment; 'Treatment should not be extended beyond 14 days without review.' Doses are expressed in terms of amoxicillin/clavulanic acid content. Elderly: no dose adjustment is considered necessary. Some sections of the product information we used were incomplete — check the full SPC. The SPC side-effect table was flattened by PDF extraction, so frequency categories are not reproduced except where stated in prose.

Paediatric dose

Dose: Children under 40 kg (SPC section 4.2, this tablet formulation): 20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day of amoxicillin/clavulanic acid, given in three divided doses. This is a TOTAL DAILY figure shared across three doses, not a per-dose figure.
Route: Oral
Frequency: Three divided doses per day
Children may be treated with co-amoxiclav tablets, suspensions or paediatric sachets. 'As the tablets cannot be divided, children weighing less than 25 kg must not be treated with Co-amoxiclav tablets.' Children aged 6 years and below, or weighing less than 25 kg, should preferably be treated with co-amoxiclav suspension or paediatric sachets. For a child of 25 kg to 40 kg given a single 500/125 mg tablet the SPC table shows the dose received per tablet: at 40 kg amoxicillin 12.5 mg/kg and clavulanic acid 3.1 mg/kg; at 35 kg 14.3 and 3.6; at 30 kg 16.7 and 4.2; at 25 kg 20.0 and 5.0 (single dose recommended: amoxicillin 6.67 to 20 mg/kg, clavulanic acid 1.67 to 5 mg/kg). SPC: 'No clinical data are available on doses of Co-amoxiclav 4:1 formulations higher than 40 mg/10 mg/kg/day in children under 2 years.' No figure is given for neonates and none is written here. Children weighing 40 kg or more are dosed as adults. Renal adjustment for children under 40 kg is in renalAdjustment. Verify against a children's formulary.

Dose adjustments

Renal

SPC 4.2: 'Dose adjustments are based on the maximum recommended level of amoxicillin. No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than 30 ml/min.' Adults and children 40 kg and over: CrCl 10-30 ml/min - 500 mg/125 mg twice daily; CrCl below 10 ml/min - 500 mg/125 mg once daily; haemodialysis - 500 mg/125 mg every 24 hours, plus 500 mg/125 mg during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxicillin and clavulanic acid are decreased). Children under 40 kg: CrCl 10-30 ml/min - 15 mg/3.75 mg/kg twice daily (maximum 500 mg/125 mg twice daily); CrCl below 10 ml/min - 15 mg/3.75 mg/kg as a single daily dose (maximum 500 mg/125 mg); haemodialysis - 15 mg/3.75 mg/kg per day once daily, 15 mg/3.75 mg/kg prior to haemodialysis, and, to restore circulating drug levels, 15 mg/3.75 mg per kg after haemodialysis. SPC 4.4: in renal impairment the dose should be adjusted according to the degree of impairment; convulsions may occur in patients with impaired renal function or in those receiving high doses.

Hepatic

SPC 4.2: 'Dose with caution and monitor hepatic function at regular intervals (see sections 4.3 and 4.4).' SPC 4.4: use with caution in patients with evidence of hepatic impairment; hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. No numeric adjustment is given. A history of jaundice/hepatic impairment due to amoxicillin/clavulanic acid is a contraindication (4.3).

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via MHRA Products — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients listed in section 6.1
  • History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam)
  • History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid
  • Precaution (4.4, not a formal contraindication): avoid if infectious mononucleosis is suspected, since a morbilliform rash has been associated with this condition following the use of amoxicillin
  • Precaution (4.4): this presentation should not be used to treat penicillin-insusceptible S. pneumoniae, or when there is a high risk that presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents not mediated by beta-lactamases susceptible to inhibition by clavulanic acid

Side effects

  • Most commonly reported: diarrhoea, nausea and vomiting; diarrhoea is classified as a very common undesirable effect (4.8)
  • Nausea is more often associated with higher oral doses; if gastrointestinal reactions are evident they may be reduced by taking the medicine at the start of a meal (4.8)
  • Mucocutaneous candidiasis; overgrowth of non-susceptible organisms
  • Blood: reversible leucopenia (including neutropenia); thrombocytopenia; reversible agranulocytosis; haemolytic anaemia; prolongation of bleeding and prothrombin time
  • Immune: angioneurotic oedema; anaphylaxis; serum sickness-like syndrome; hypersensitivity vasculitis
  • Cardiac: Kounis syndrome (a serious allergic reaction that can result in myocardial infarction, 4.4)
  • Nervous system: dizziness; headache; reversible hyperactivity; convulsions (may occur with impaired renal function or high doses); aseptic meningitis
  • Gastrointestinal: indigestion; antibiotic-associated colitis including pseudomembranous and haemorrhagic colitis; black hairy tongue; drug-induced enterocolitis syndrome (reported mainly in children); acute pancreatitis
  • Hepatobiliary: rises in AST and/or ALT; hepatitis; cholestatic jaundice
  • Skin: skin rash; pruritus; urticaria; erythema multiforme; Stevens-Johnson syndrome; toxic epidermal necrolysis; bullous exfoliative dermatitis; acute generalised exanthemous pustulosis (AGEP); drug reaction with eosinophilia and systemic symptoms (DRESS); symmetrical drug-related intertriginous and flexural exanthema (SDRIFE); linear IgA disease
  • Renal: interstitial nephritis; crystalluria (including acute renal injury)
  • SPC 4.8 is truncated at the source-fetch limit and its frequency table lost its column layout in PDF extraction, so this list is not guaranteed complete and frequency categories are not given

Interactions

  • Oral anticoagulants (acenocoumarol, warfarin): increased INR reported with amoxicillin; if co-administration is necessary, monitor prothrombin time or INR carefully when amoxicillin is added or withdrawn; anticoagulant dose adjustment may be necessary
  • Methotrexate: penicillins may reduce the excretion of methotrexate, causing a potential increase in toxicity
  • Probenecid: concomitant use not recommended; it decreases renal tubular secretion of amoxicillin and may increase and prolong blood levels of amoxicillin but not of clavulanic acid
  • Mycophenolate mofetil: approximately 50% reduction in pre-dose concentration of the active metabolite mycophenolic acid after starting oral amoxicillin plus clavulanic acid; a change in mycophenolate dose should not normally be necessary without clinical evidence of graft dysfunction, but close clinical monitoring is advised during the combination and shortly after antibiotic treatment
  • Allopurinol: concomitant use with amoxicillin can increase the likelihood of allergic skin reactions (4.4)

Monitoring

  • Before starting, make careful enquiry about previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents; stop the drug and institute alternative therapy if an allergic reaction occurs
  • Hepatic function at regular intervals in hepatic impairment (4.2); signs and symptoms of hepatic events may appear during treatment, shortly afterwards, or occasionally not until several weeks after treatment has ceased
  • Periodic assessment of renal, hepatic and haematopoietic function is advisable during prolonged therapy (4.4)
  • Prothrombin time/INR if anticoagulants are prescribed concomitantly (4.4, 4.5)
  • Review before extending treatment beyond 14 days (4.2); some infections such as osteomyelitis require longer courses
  • Consider antibiotic-associated colitis in patients with diarrhoea during or after antibiotics; if it occurs stop the drug immediately and consult a physician (anti-peristaltic medicinal products are contra-indicated in this situation)
  • Maintain adequate fluid intake and urinary output during high doses to reduce the possibility of amoxicillin crystalluria; check bladder catheter patency regularly
  • Use enzymatic glucose oxidase methods when testing urine for glucose during amoxicillin treatment (false positives with non-enzymatic methods); clavulanic acid may cause a false positive Coombs test
  • SPC 4.4 is truncated at the source-fetch limit (it stops partway through a paragraph on the Bio-Rad Platelia Aspergillus EIA test), so further monitoring requirements may exist that were not retrieved

Clinical monograph

How it works

Amoxicillin inhibits bacterial cell-wall synthesis by binding penicillin-binding proteins, while clavulanic acid irreversibly inhibits beta-lactamase enzymes, protecting amoxicillin from degradation.

Prescribing in practice

  • Cholestatic jaundice and hepatitis can occur, sometimes weeks after stopping, and are more common with prolonged treatment and in older men; it is contraindicated where there is a history of co-amoxiclav- or penicillin-associated jaundice.
  • It is contraindicated in penicillin hypersensitivity and shares cross-reactivity with cephalosporins.
  • Reserve for infections likely to be caused by resistant organisms because broad-spectrum use promotes resistance and Clostridioides difficile infection.

Monitoring

Monitor hepatic function in prolonged courses and remain alert for diarrhoea suggesting C. difficile infection.

Counselling the patient

  • Report yellowing of the skin or eyes, dark urine or pale stools.
  • Seek advice for severe or bloody diarrhoea.
  • Complete the prescribed course and report any rash or breathing difficulty.

Evidence & guidelines

NICE antimicrobial guidance positions co-amoxiclav as a reserve agent for specific indications rather than routine first-line empirical use.

Reference: PHE/UKHSA Antibiotic Guidelines; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways