Clarithromycin

Key points

• Clarithromycin strongly inhibits the liver enzyme CYP3A4, and serious adverse reactions have been reported when it is taken together with other medicines broken down by that same enzyme.
• Its elimination half-life runs from about three to seven hours, and its main active metabolite, 14-hydroxy clarithromycin, clears on a similar timescale.
• The most frequently reported side effects in adults are diarrhoea, nausea and an altered sense of taste, each reported in about 3% of patients, with indigestion, abdominal discomfort and headache reported in about 2%.

How it works

Clarithromycin works by binding to the 50S ribosomal subunit of susceptible bacteria, blocking their protein synthesis. It is active in vitro against a range of gram-positive and gram-negative organisms, including most Mycobacterium avium complex organisms. Its main metabolite, 14-hydroxy clarithromycin, also has clinically significant antimicrobial activity and is twice as active against Haemophilus influenzae as the parent compound.

Safety specific to Clarithromycin

Clarithromycin must not be taken with certain other medicines. Concomitant use of clarithromycin with astemizole, cisapride, domperidone, pimozide or terfenadine is contraindicated, because it may result in QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation and torsades de pointes, and fatalities have been reported with this type of interaction. Prolongation of the QT interval, with a risk of arrhythmia and torsades de pointes, has also been seen more broadly in patients treated with macrolides including clarithromycin. Clarithromycin is also contraindicated with ergot alkaloids such as ergotamine or dihydroergotamine, with oral midazolam, and with the statins lovastatin or simvastatin because of the risk of rhabdomyolysis.

Hepatic dysfunction, including increased liver enzymes and hepatocellular or cholestatic hepatitis with or without jaundice, has been reported with clarithromycin. Clarithromycin is principally metabolised by the liver, and caution is also advised when giving it to patients with moderate to severe renal impairment.

Clarithromycin should be prescribed in pregnancy only after carefully weighing the benefits against the risks, particularly during the first three months.

Clarithromycin can also cause Clostridium difficile associated diarrhoea. The label states this has been reported with nearly all antibacterial agents, including this one, and that it may range in severity from mild diarrhoea to fatal colitis, because treatment alters the normal flora of the colon and lets C. difficile overgrow. Diarrhoea that is severe, persistent or bloody, during or after a course, is a reason to seek medical assessment rather than to treat it at home.

When to seek urgent care

Seek prompt medical advice if you notice yellowing of the skin or eyes while taking clarithromycin, as hepatic dysfunction with jaundice has been reported with this medicine.

Further reading

• BIAXIN- clarithromycin tablet, film coated BIAXIN- clarithromycin tablet, film coated, extended release BIAXIN- clarithromycin granule, for suspension
• Clarithromycin: MedlinePlus Drug Information
• Clarithromycin 500 mg film-coated tablets