Clarithromycin - A Review

Chief editor
DR T R RAMANUJAM M.D., C.MI.Biol (Lond)

INTRODUCTION

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

ADVERSE EFFECTS & DRUG INTERACTIONS

Most of the adverse events associated with clarithromycin are in the form of drug interactions which occur via its effects (inhibitory) on CYP3A isoezymes of Cytochrome P 450 mixed function Oxidases.

Interactions of clinical significance are

Clarithromycin (Primary drug):

Interactants: X Theophylline                      

                     X    Cyclosporin           ­ Plasma concentration

                     X    Tacrolimus

                     X    Carbamazepine

Therapeutic drug monitoring  is necessary and if needed dose adjustments

                     X  Rifampicin    ­ Metabolism of clarithromycin

                     X  Rifabutin    

With Omeprazole ,Clarithromycin inhibits metabolism of omeprazole.

Omeprazole increase clarithromycin absorption resulting in increasing concentration of both clarithromycin & omeprazole (beneficial interaction viz., rapid eradication of H.pylori because of synergy).

Clarithromycin  X  Digoxin = ­ digoxin concentration. Monitor digoxin.

Clarithromycin  X  Zidovudine  =   increased plasma concentration

Clarithromycin  X  Fluoxetin, Nitrzepam   = delirium

Clarithromycin  X  oral anticoagulants  =  bleeding – monitor PT

Clarithromycin  X  Terfinadine, astemizole, cisapride, Azole antifungals  =  Cardiac arrhythmia’s like Torsde de pointes (QT prolongation syndrome).

Rapid IV injection had resulted in suddden death due to cardiac arrest when the injection  was rapid.

PHARMACOECONOMIC CONSIDERATIONS

This becomes highly essential when it comes to using an expensive agent like Clarithromycin. In various studies in US clarithromycin appeared to be cost effective especially in patients in whom IV macrolides have been switched to per oral clarithromycin formulations known as sequential or swotching therapy. Even in out patient settings, considerable cost reductions are seen with clarithromycin on comparing with cephalosporins and amoxycillins. In clinical settings clarithromycin is the drug of choice and /or alternative drug of choice, local acquisition cost, prevalent pattern of pathogens and treatment methods need to be considered in assessing the cost.