Clarithromycin - A Review
DR T R RAMANUJAM M.D., C.MI.Biol (Lond)
ANTIMICROBIAL ACTIVITY
CLINICAL PHARMACOKINETICS
CLINICAL EFFICACY
TOLERABILITY PROFILE
ADVERSE EFFECTS & DRUG INTERACTIONS
CHOOSING HOOSING MACROLIDES
CONCLUDING SUMMARY
BRIIGHTER SIDE OF CLARITHROMYCIN
DARKER SIDE OF CLARITHROMYCIN
CURRENT TRENDS IN MICROLIDE USE
INTRODUCTION
Macrolides are a large group of anti microbials derived from Streptomyces spp. With low toxicity exhibiting bacteriostatic and bactericidal(against some) effects through inhibition of bacterial RNA dependent protein synthesis by binding to 50S ribosomal subunit and some times manifesting cross resistance among them. The antimicrobial spectrum is similar to benzyl penicillin but in addition active against Mycoplasmae, Chlamydiae, Legionellae, gram positive anaerobes etc.. The newer agents like clarithromycin, Azithromycin, Dirithromycin are found to be effective against pathogens implicated in opportunistic infections associated with AIDS like MAC infection, Toxoplasmosis, Cryptosporidiosis etc., and also in the eradication of H.pylori infection and in Lyme disease caused by B.burgedorferi. Macrolides like Spiramycin, Kitasamycin, Josamycin and Medicamycin, Miocamycin and Rokitamycin are widely used in Japan & Europe. Erythromycin, Azithromycin and Spiramycin can safely be used in PREGNANCY. Among the Macrolides Azithromycin, Dirithromycin and Spiramycin does not interfere with CYP3A isoenzyme and therefore NO drug interactions as seen with clarithromycin.
Macrolides have additional pharmacological actions not connected with their antimicrobial actions on the following receptors:
Motility receptors in GIT, Which forms the basis for their use as prokinetic agents in diabetic gastroparesis. Efforts are underway to isolate a preparation without antimicrobial effect.
CYP Receptor in the liver – By this effect with the exception of Azithromycin, Dirithromycin and spiramycin other Macrolides inhibit CYP3A isoenzyme and therefore involved in many clinically significant drug interactions and adverse effects. Ex: Interactions with theophylline, Digoxin, Oral anticoagulants, Terfinadine, Azole antifungals, Cisapride etc.,
Auditory Receptors _ as evidenced by the production of reversible hearing loss in AIDS patients receiving high doses. IV Erythromycin has the potential for causing hearing impairment.
Agents like Rosamycin (micromonospora spp), and Flurithomycin are under investigation appear promising.
Clarithromycin is a semi synthetic broad spectrum macrolide antimicrobial agent having not only bactericidal activity against some organisms by virtue of its synergism with its microbiologically active 14 OH metabolite but also by its Post Antibiotic Effect (PAE).
Current Review focuses antimicrobial activity, Clinical pharmacokinetics, efficacy, tolerability & safety profiles, and pharmacoeconomic considerations of clarithromycin. The concluding topic of “Choosing Macrolides” has been added for the benefit of readers.
