KLACID

What it is

KLACID is a semi-synthetic macrolide antibiotic containing clarithromycin. It is available as film-coated tablets in 250 mg and 500 mg strengths. Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunits of susceptible organisms and inhibiting protein synthesis.

Approved indications

KLACID is indicated for use in adults and children older than 12 years for the treatment of mild to moderately severe infections caused by susceptible strains of designated micro-organisms in the following conditions: — Acute streptococcal pharyngitis. — Community-acquired pneumonia due to Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila and Streptococcus pneumoniae. — Uncomplicated skin and skin structure infections due to Staphylococcus aureus or Streptococcus pyogenes. — Disseminated or localised mycobacterial infections due to Mycobacterium avium or Mycobacterium intracellulare and skin and skin structure infections due to Mycobacterium chelonae; clarithromycin should be used in combination with other antimycobacterial agents. — Prevention of disseminated Mycobacterium avium complex infection in HIV-infected adults with CD4 lymphocyte counts less than 75 cells/mm³. — Acute bacterial exacerbation of chronic bronchitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae. — Combination therapy for the treatment of peptic ulcer disease associated with Helicobacter pylori infection.

Dosing overview

For non-mycobacterial infections, the usual recommended dosage in adults and children 12 years of age and older is 250 mg twice daily; in more severe infections the dosage can be increased to 500 mg twice daily, with usual duration of therapy being 7 to 14 days. For Legionella pneumophila infection, a dose of 500 mg twice daily for 4 weeks is appropriate. For peptic ulcer disease due to H. pylori infection, clarithromycin can be administered in a dose of 500 mg twice daily in combination with other appropriate antimicrobial treatments and a proton pump inhibitor for 7 to 14 days. For mycobacterial infections in adults and children 12 years and older, the recommended dosage is 500 mg twice daily, which may be increased to 1000 mg twice daily if no clinical or bacteriological response is seen after 3 to 4 weeks of therapy.

Key safety warnings

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides including clarithromycin. Clarithromycin should be used with caution in patients with coronary artery disease, severe cardiac insufficiency, conduction disturbances or clinically relevant bradycardia. Antibiotic-associated pseudomembranous colitis has been reported with many antibiotics including macrolides; a toxin produced by Clostridium difficile appears to be the primary cause, and the severity of the colitis may range from mild to life threatening. Clostridium difficile-associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents including clarithromycin, and may range in severity from mild diarrhoea to fatal colitis. Hepatic dysfunction, including increased liver enzymes and hepatocellular and/or cholestatic hepatitis with or without jaundice, has been reported with clarithromycin; this hepatic dysfunction may be severe and is usually reversible. Clarithromycin should be discontinued immediately if signs and symptoms of hepatitis occur, such as anorexia, jaundice, dark urine, pruritus or tender abdomen. Exacerbation of symptoms of myasthenia gravis has been reported in patients receiving clarithromycin therapy.

Contraindications

KLACID is contraindicated in patients with known hypersensitivity to macrolide antibiotic drugs or any of its excipients. Concurrent administration of clarithromycin and astemizole, terfenadine, cisapride, domperidone or pimozide is contraindicated, as this may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and torsades de pointes. Clarithromycin should not be given to patients with history of QT prolongation (congenital or documented acquired QT prolongation) or ventricular cardiac arrhythmia including torsades de pointes. Clarithromycin should not be given to patients with electrolyte disturbances such as hypokalaemia or hypomagnesaemia due to the risk of prolongation of QT interval. Concomitant administration of clarithromycin and ergot alkaloids (for example ergotamine or dihydroergotamine) is contraindicated, as this may result in ergot toxicity. Concomitant administration of clarithromycin and ivabradine is contraindicated as this may result in increased plasma exposure of ivabradine. Concomitant administration of clarithromycin and oral midazolam is contraindicated. Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins) that are extensively metabolised by CYP3A4 (lovastatin or simvastatin) due to the increased risk of myopathy including rhabdomyolysis. Clarithromycin should not be used concomitantly with colchicine.

PBS listing

KLACID is listed on the PBS in tablet 250 mg strength (unrestricted, ex-manufacturer price A$6.50) and powder for oral liquid 250 mg per 5 mL 50 mL strength (restricted, ex-manufacturer price A$14.98).

Regulatory history

KLACID 500 mg tablets were first registered on the ARTG on 13 June 1995, followed by the 250 mg per 5 mL powder for oral liquid on 22 August 1996 and the 250 mg tablet on 23 July 2001.