Indications: infections due to beta-lactamase-producing strains (where amoxicillin alone not appropriate) including:

respiratory-tract infections, bone and joint infections genito-urinary and abdominal infections. Cellulitis, animal bites severe dental infection with spreading cellulitis or dental infection not responding to first-line antibacterial.

Cautions: maintain adequate hydration with high doses (particularly during parenteral therapy).

Cholestatic jaundice: can occur either during or shortly after the use of co-amoxiclav.

An epidemiological study has shown that the risk of acute liver toxicity was about 6 times greater with co- amoxiclav than with amoxicillin. Cholestatic jaundice is more common in patients above the age of 65 years and in men (these reactions have only rarely been reported in children).

Jaundice is usually self-limiting and very rarely fatal. The duration of treatment should be appropriate to the indication and should not usually exceed 14 days.

Contra-indications: penicillin hypersensitivity, history of co-amoxiclav-associated or penicillin-associated jaundice or hepatic dysfunction.

Hepatic impairment: monitor liver function in liver disease.

Renal impairment: CrCl <30 ml/minute: Do not use 875 mg tablet or extended release tablets. CrCl 10-30 ml/minute: 250-500 mg every 12 hours CrCl <10 ml/minute:

250-500 mg every 24 hours Hemodialysis: Moderately dialyzable, 250-500 mg every 24 hours; administer dose during and after dialysis. Do not use extended release tablets.

Peritoneal dialysis: Moderately dialyzable, Amoxicillin: Administer 250 mg every 12 hours Clavulanic acid: Dose for CrCl <10 ml/minute Continuous arteriovenous or venovenous hemofiltration effects: Amoxicillin: ~50 mg of amoxicillin/L of filtrate is removed Clavulanic acid: Dose for CrCl <10 ml/minute

Pregnancy: not known to be harmful

Breast-feeding: trace amounts in milk, but appropriate to use.

Side Effects: Commonly: hepatitis, cholestatic jaundice Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, vasculitis reported. Rarely: prolongation of bleeding time, dizziness, headache, convulsions (particularly with high doses or in renal impairment); superficial staining of teeth with suspension, phlebitis at injection site.

Dose: one 250/125 strength tablet every 8 hours; increased in severe infection to one 500/125 strength tablet every 8 hours. neonate: ml/kg of 125/31 suspension every 8 hours child 1 month–1 year 0.25 ml/kg of125/31 suspension every 8 hours, dose doubled in severe infection 1–6 years 5 ml of 125/31 suspension every 8 hours or 0.25 ml/kg of 125/31 suspension every 8 hours, dose doubled in severe infection 6–12 years 5 ml of 250/62 suspension every 8 hours or 0.15 ml/kg of 250/62 suspension every 8 hours, dose doubled in severe infection. Severe dental infections (but not generally first- line expressed as co-amoxiclav. adult and child over 12 years one 250/125 strength tablet every 8 hours for 5 days.