APX-AMOXICILLIN/CLAVULANIC ACID

What it is

APX-Amoxicillin/Clavulanic acid is a combination product containing amoxicillin trihydrate and potassium clavulanate, available in two strengths: 500/125 mg and 875/125 mg tablets. The product combines the semi-synthetic antibiotic amoxicillin with the beta-lactamase inhibitor potassium clavulanate. Clavulanic acid extends the antimicrobial spectrum of amoxicillin to include organisms normally resistant to amoxicillin due to beta-lactamase production.

Approved indications

APX-Amoxicillin/Clavulanic acid is indicated for short-term treatment of bacterial infections caused by amoxicillin/clavulanic acid sensitive, beta-lactamase producing organisms at the following sites: — Skin and skin structure infections. — Urinary tract infections (complicated and uncomplicated). — Upper respiratory tract infections, such as sinusitis, otitis media and recurrent tonsillitis. — Lower respiratory tract infections, including community acquired pneumonia and acute exacerbations of chronic bronchitis.

Dosing overview

The usual adult dose is one APX-Amoxicillin/Clavulanic acid 500/125 tablet every 12 hours. For more severe infections, the dose should be one APX-Amoxicillin/Clavulanic acid 875/125 tablet every 12 hours. Tablets should be taken immediately before or with the first mouthful of food, to minimise potential gastrointestinal intolerance and to optimise absorption. 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. Treatment should not exceed 14 days without review. APX-Amoxicillin/Clavulanic acid 875/125 tablets should not be used in patients with moderate to severe renal impairment (creatinine clearance less than or equal to 30 mL/minute). For the 500/125 formulation, in moderate renal impairment (creatinine clearance 10 to 30 mL/minute), one tablet should be given 12-hourly only. In severe impairment (creatinine clearance less than 10 mL/minute), one tablet should be given every 24 hours. Children weighing 40 kg and more should be dosed according to the adult recommendations. Children weighing less than 40 kg should not use amoxicillin/clavulanic acid tablet preparations.

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. Hypersensitivity reactions can progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction, with presenting symptoms that can include chest pain occurring in association with an allergic reaction to amoxicillin or clavulanic acid. Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including amoxicillin. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. 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. Signs and symptoms may not become apparent until several weeks after treatment has ceased. In extremely rare circumstances, deaths have been reported, which have almost always been cases associated with serious underlying disease or concomitant medications. Hepatic events subsequent to amoxicillin/clavulanic acid therapy have been reported predominantly in males and elderly patients and may be associated with prolonged treatment.

Contraindications

Hypersensitivity to the active substance or to any of the excipients. History of allergic reactions to beta-lactams, such as penicillins, cephalosporins, carbapenems or monobactams. Previous history of amoxicillin/clavulanic acid associated jaundice/hepatic dysfunction.

Regulatory history

APX-Amoxicillin/Clavulanic acid 500/125 (ARTG 351832) and 875/125 (ARTG 351833) were first listed on the Australian Register of Therapeutic Goods on 22 April 2021.