COMOX

What it is

COMOX is a combination product containing amoxicillin (as trihydrate) and clavulanic acid (as potassium), supplied as film-coated tablets. Two strengths are available: COMOX 500/125 tablets containing amoxicillin 500 mg and clavulanic acid 125 mg, and COMOX 875/125 tablets containing amoxicillin 875 mg and clavulanic acid 125 mg. Clavulanic acid is a β-lactamase inhibitor that extends the antimicrobial spectrum of amoxicillin to include organisms normally resistant to amoxicillin due to β-lactamase production.

Approved indications

COMOX tablets are indicated for short term treatment of bacterial infections at the following sites when caused by sensitive organisms: — Urinary tract infections (uncomplicated and complicated) — Lower respiratory tract infections, including community acquired pneumonia and acute exacerbations of chronic bronchitis — Upper respiratory tract infections, such as sinusitis, otitis media and recurrent tonsillitis — Skin and skin structure infections

Dosing overview

COMOX tablets should be taken immediately before or with the first mouthful of food, to minimise potential gastrointestinal intolerance and to optimise absorption. The usual adult dose is one COMOX 500/125 tablet every 12 hours; for more severe infections, the dose should be one COMOX 875/125 tablet every 12 hours. Treatment should usually be continued for 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained, and treatment should not exceed 14 days without review. Children weighing 40 kg and more should be dosed according to adult recommendations; it is recommended that amoxicillin and clavulanic acid suspensions should be used for children weighing less than 40 kg. COMOX 875/125 tablets should not be used in patients with moderate to severe renal impairment (creatinine clearance ≤ 30 mL/min). For COMOX 500/125 tablets in mild renal impairment (creatinine clearance > 30 mL/min), no change in dosage is required; in moderate impairment (creatinine clearance 10–30 mL/min), one tablet every 12 hours is recommended; in severe impairment (creatinine clearance < 10 mL/min), one tablet every 24 hours.

Key safety warnings

Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins, and these reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction, with presenting symptoms including chest pain occurring in association with an allergic reaction to amoxicillin and clavulanic acid. Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin/clavulanate, with the leading symptom of protracted vomiting (1–4 hours after administration) in the absence of allergic skin or respiratory symptoms. Further symptoms could comprise abdominal pain, diarrhoea, hypotension or leucocytosis with neutrophilia, and there have been severe cases including progression to shock. Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including amoxicillin, with a toxin produced by Clostridium difficile appearing to be the primary cause. The severity of the colitis may range from mild to life threatening, and it is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Cholestatic hepatitis, which may be severe but is usually reversible, has been reported rarely, with signs and symptoms that may not become apparent until several weeks after treatment has ceased. In extremely rare circumstances, deaths have been reported, occurring predominantly in males and elderly patients and associated with prolonged treatment.

Contraindications

COMOX is contraindicated in patients with a history of allergic reaction to β-lactams (e.g. penicillins or cephalosporin) and in those with a previous history of amoxicillin/clavulanic acid-associated jaundice or hepatic dysfunction.

Regulatory history

COMOX 500/125 (ARTG 236902) and COMOX 875/125 (ARTG 236898) tablets were first registered on the Australian Register of Therapeutic Goods on 7 April 2016.