Drug Class Description
Macrolides.

Generic Name
Clarithromycin

Drug Description
Klaricid Adult Sachet 250mg or Clarithromycin 250mg Granules for Oral Suspension

Presentation
Granules for oral suspension.

Indications
Clarithromycin is indicated in the treatment of infections caused by one or more susceptible organisms. Indications include:Lower respiratory tract infections for example, acute and chronic bronchitis, and pneumonia.Upper respiratory tract infections for example, sinusitus and pharyngitis.Clarithromycin is appropriate for initial therapy in community acquired respiratory infections and has been shown to be active in vitro against common and atypical respiratory pathogens as listed in the microbiology section.Clarithromycin is also indicated in skin and soft tissue infections of mild to moderate severity.Clarithromycin in the presence of acid suppression effected by lansoprazole or omeprazole is also indicated for the eradication of H. pylori in patients with duodenal ulcers. See Dosage and Administration section.Clarithromycin is usually active against the following organisms in vitro:Gram-positive Bacteria:Staphylococcus aureus (methicillin susceptible); Streptococcus pyogenes (Group A beta-hemolytic streptococci); alpha-hemolytic streptococci (viridans group); Streptococcus (Diplococcus) pneumoniae; Streptococcus agalactiae; Listeria monocytogenes.Gram-negative Bacteria: Haemophilus influenzae; Haemophilus parainfluenzae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Legionella pneumophila; Bordetella pertussis; Helicobacter pylori; Campylobacter jejuni.Mycoplasma:Mycoplasma pneumoniae; Ureaplasma urealyticum.Other Organisms:Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae.Anaerobes: Macrolide-susceptible Bacteroides fragilis; Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes.Clarithromycin has bactericidal activity against several bacterial strains. These organisms include Haemophilus influenzae; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Helicobacter pylori and Campylobacter spp.The activity of clarithromycin against H. pylori is greater at neutral pH than at acid pH.

Adult Dosage
Patients with respiratory tract/skin and soft tissue infections.Adults: The usual dose is 250 mg twice daily for 7 days although this may be increased to 500mg twice daily for up to 14 days in severe infections.Children older than 12 years: As for adults.Children younger than 12 years: Use Clarithromycin Paediatric Suspension.Eradication of H. pylori in patients with duodenal ulcers (Adults)Triple Therapy (7 - 14 days) Clarithromycin 500mg twice daily and lansoprazole 30mg twice daily should be given with amoxycillin 1000mg twice daily for 7 - 14 days.Triple Therapy (7 days)Clarithromycin (500mg) twice daily and lansoprazole 30mg twice daily should be given with metronidazole 400mg twice daily for 7 days.Triple Therapy (7 days)Clarithromycin (500mg) twice daily and omeprazole 40mg daily should be given with amoxycillin 1000mg twice daily or metronidazole 400mg twice daily for 7 days.Triple Therapy (10 days)Clarithromycin (500mg) twice daily should be given with amoxycillin 1000mg twice daily and omeprazole 20mg daily for 10 days.Dual Therapy (14 days)The usual dose of Clarithromycin is 500 mg three times daily for 14 days. Clarithromycin should be administered with oral omeprazole 40 mg once daily. The pivotal study was conducted with omeprazole 40 mg once daily for 28 days. Supportive studies have been conducted with omeprazole 40 mg once daily for 14 days.For further information on the dosage for omeprazole see the Astra data sheet.Elderly: As for adults.Renal impairment: Dosage adjustments are not usually required except in patients with severe renal impairment (creatinine clearance < 30 ml/min). If adjustment is necessary, the total daily dosage should be reduced by half, e.g. 250 mg once daily or 250 mg twice daily in more severe infections.Clarithromycin may be given without regard to meals as food does not affect the extent of bioavailability.

Child Dosage
Use Klaricid paediatric suspension.

Contra Indications
Clarithromycin is contra-indicated in patients with known hypersensitivity to macrolide antibiotic drugs.Clarithromycin and ergot derivatives should not be co-administered.Concomitant administration of clarithromycin and any of the following drugs is contraindicated: cisapride, pimozide and terfenadine. Elevated cisapride, pimozide and terfenadine levels have been reported in patients receiving either of these drugs and clarithromycin concomitantly. This may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and Torsade de Pointes. Similar effects have been observed with concomitant administration of astemizole and other macrolides

Special Precautions
Clarithromycin is principally excreted by the liver and kidney. Caution should be exercised in administering this antibiotic to patients with impaired hepatic or renal function.Prolonged or repeated use of clarithromycin may result in an overgrowth of non-susceptable bacteria or fungi. If super-infection occurs, clarithromycin should be discontinued and appropriate therapy instituted.H. pylori organisms may develop resistance to clarithromycin in a small number of patients.There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported ins ome such patients.Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Interactions
Clarithromycin has been shown not to interact with oral contraceptives.As with other macrolide antibiotics the use of clarithromycin in patients concurrently taking drugs metabolised by the cytochrome P450 system (eg. cilostazol, methylprednisolone, oral anticoagulants (eg warfarin), quinidine, ergot alkaloids, alprazolam, triazolam, midazolam, disopyramide, lovastatin, rifabutin, phenytoin, cyclosporin, vinblastine valproate and tacrolimus) may be associated with elevations in serum levels of these other drugs. Rhabdomyolysis, co-incident with the co- administration of clarithromycin, and HMG-CoA reductase inhibitors, such as lovastatin and simvastatin has been reported.The administration of clarithromycin to patients who are receiving theophylline has been associated with an increase in serum theophylline levels and potential theophylline toxicity.The use of clarithromycin in patients receiving warfarin may result in potentiation of the effects of warfarin. Prothrombin time should be frequently monitored in these patients. The effects of digoxin may be potentiated with concomitant administration of Clarithromycin. Monitoring of serum digoxin levels should be considered.Clarithromycin may potentiate the effects of carbamazepine due to a reduction in the rate of excretion.Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV infected adult patients may result in decreased steady-state zidovudine levels. This can be largely avoided by staggering the doses of Clarithromycin and zidovudine by 1 -2 hours. No such reaction has been reported in children.Ritonavir increases the area under the curve (AUC), Cmax and Cmin of clarithromycin when administered concurrently. Because of the large therapeutic window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. However, for patients with renal impairment, the following dosage adjustments should be considered: For patients with CLCR 30 to 60 ml/min the dose of clarithromycin should be reduced by 50%. For patients with CLCR <30ml/min the dose of clarithromycin should be decreased by 75%. Doses of clarithromycin greater than 1g/day should not be coadministered with ritonavir.Although the plasma concentrations of clarithromycin and omeprazole may be increased when they are administered concurrently, no adjustment to the dosage is necessary. At the dosages recommended, there is no clinically significant interaction between clarithromycin and lansoprazole. Increased plasma concentrations of clarithromycin may also occur when it is co-administered with Maalox or ranitidine. No adjustment to the dosage is necessary.There have been post-marketed reports of Torsade de Pointes occurring with the concurrent use of clarithromycin and quinidine or disopyramide. Levels of these medications should be monitored during clarithromycin therapy.Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (Pgp). Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. When clarithromycin and colchicine are administered together, inhibition of Pgp and/or CYP3A by clarithromycin may lead to increased exposure to colchicine. Patients should be monitored for clinical symptoms of colchicine toxicity.Post-marketing reports indicate that co-administration of clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischaemia of the extremities and other tissues including the central nervous system.

Adverse Reactions
Clarithromycin is generally well tolerated. Side effects include nausea, dyspepsia, diarrhoea, vomiting, abdominal pain and paraesthesia. Stomatitis, glossitis, oral monilia and tongue discolouration have been reported. Other side-effects include headache, arthralgia, myalgia and allergic reactions ranging from urticaria, mild skin eruptions and angioedema to anaphylaxis have been reported. There have been reports of Stevens-Johnson syndrome / toxic epidermal necrolysis with orally administered clarithromycin.Reports of alteration of the sense of smell, usually in conjunction with taste perversion have also been received. There have been reports of tooth discolouration in patients treated with clarithromycin. Tooth discolouration is usually reversible with professional dental cleaning.There have been reports of transient central nervous system side-effects including dizziness, vertigo, anxiety, insomnia, bad dreams, tinnitus, confusion, disorientation, hallucinations, psychosis and depersonalisation.There have been reports of hearing loss with clarithromycin which is usually reversible on withdrawal of therapy. Pseudomembranous colitis has been reported rarely with clarithromycin, and may range in severity from mild to life threatening. There have been rare reports of hypoglycaemia, some of which have occurred in patients on concomitant oral hypoglycaemic agents or insulin. There have been very rare reports of uveitis mainly in patients treated with concomitant rifabutin, most of these were reversible. Isolated cases of leukopenia and thrombocytopenia have been reported.As with other macrolides, hepatic dysfunction (which is usually reversible) including altered liver function tests, hepatitis and cholestasis with or without jaundice, has been reported. Dysfunction may be severe and very rarely fatal hepatic failure has been reported.Cases of increased serum creatinine, interstitial nephritis and renal failure, pancreatitis and convulsions have been reported rarely.As with other macrolides, QT prolongation, ventricular tachycardia and Torsade de Pointes have been rarely reported with clarithromycin.There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported in some such patients.

Manufacturer
Abbott

Drug Availability
(POM)

Updated
15 May 2009