Group: antimicrobial (macrolide) agent
Tablet, 250 mg, 500 mg [non-EDL]
Suspension, 125 mg/5 ml [non- EDL]
Injection, 500 mg [non-EDL]

General information

Clarithromycin is a semisynthetic macrolide antibiotic, structurally very similar to erythromycin. It inhibits protein synthesis by penetrating the cell wall and binding to the 50S ribosomal subunit. The absolute bioavailability of clarithromycin after oral administration is 50-55%, which probably underestimates its systemic activity, as it undergoes extensive first pass metabolism to its active metabolite, 14-hydroxyclarithromycin. Limited data are available on the distribution of clarithromycin in humans. It appears to be distributed into most body tissues and fluids. However, no data is available on CSF penetration of clarithromycin. Elimination of clarithromycin follows nonlinear kinetics. It is extensively metabolized in the liver and excreted as parent drug and metabolites in urine, and faeces.

Clinical information

Uses

Treatment of Mycobacterium avium complex.

Prophylaxis of Mycobacterium avium complex.

Treatment and maintenance of toxoplasmosis.

Dosage and administration

Treatment of Mycobacterium avium complex

500 mg twice a day in combination with ethambutol or ethambutol and rifabutin indefinitely.

Prophylaxis of Mycobacterium avium complex

500 mg twice a day indefinitely

Treatment and maintenance of toxoplasmosis

1 g twice a day for 6-8 weeks in combination with either pyrimethamine and calcium folinate or minocycline then reduced to 500 mg twice a day indefinitely. The oral formulations may be given with food to reduce the incidence of GI side effects.

The powder for injection is reconstituted with water for injection and administered in sodium chloride 0.9% or glucose 5% at a final concentration of 2 mg/ml at a rate of 500 mg over one hour.

Contraindications

Known hypersensitivity, to clarithromycin, erythromycin or any other macrolide.

Severe liver impairment

Concomitant administration of terfenadine, astemizole or cisapride (see under drug interactions).

Concomitant administration of ergotamine or dihydroergotamine (see under drug interactions).

Precautions

Reduce dose by 50% if renal function falls below 30 ml/min. Monitor liver function tests during therapy. If the patient develops diarrhoea during therapy, test for Clostridium difficile toxin.

Use in pregnancy

While the potential risk to the foetus has not been elucidated to date, clarithromycin should only be used in pregnancy if the benefits outweigh the risks to the foetus.

Adverse effects

Nausea, vomiting, diarrhoea and abdominal pain, headache, ototoxicity and skin rash. Taste perversion may occur. There have been reports of transient central nervous system side effects including anxiety, dizziness, insomnia, hallucinations, bad dreams and confusion, however, a cause and effect relationship has not been established.

Drug interactions

Concomitant administration of terfenadine, astemizole or cisapride should be avoided as potentially fatal cardiac irregularities including prolonged Q-T intervals and ventricular fibrillation may occur.

Concomitant administration of ergotamine or dihydroergotamine has been associated with acute ergot toxicity, characterized by severe peripheral vasospasm and dysesthesia.

Clarithromycin may produce clinically significant increases in serum levels of the following drugs: carbamazepine, corticosteroids, digoxin, rifabutin, theophylline and warfarin.

Reduced serum levels of clarithromycin have been reported with rifampicin and to a lesser extent rifabutin. The clinical significance of this is unknown, but might lead to treatment failure. The concomitant use of rifabutin and clarithromycin has been reported to cause an increased incidence of neutropenia and uveitis.

Overdosage

Reports indicate that ingestion of large amounts of clarithromycin can be expected to produce gastro-intestinal symptoms. One patient who had a history of bipolar disorder ingested 8 grams of clarithromycin and showed altered mental status, paranoid behaviour, hypokalaemia and hypoxaemia. Allergic reactions accompanying overdosage should be treated by gastric lavage and supportive measures. Clarithromycin serum levels are not expected to be appreciably affected by haemodialysis or peritoneal dialysis.

Storage

Tablets and granules for oral suspension should be stored in tight containers at 15-30°C and protected from light. Following reconstitution, oral suspensions should be stored at 15-30°C in tightly closed containers; the reconstituted solution should not be refrigerated. Any unused solution should be discarded after 14 days.