CLARITHROMYCIN

• INTRODUCTION
• ANTOMICROBIAL ACTIVITY
• CLINICAL PHARMACOKINETICS
• CLINICAL EFFICACY
• OTHER INFECTIONS
• TOLERABILITY PROFILE
• ADVERSE EFFECTS & DRUG INTERACTIONS
• PHARMACOECONOMIC CONSIDERATIONS
• CHOOSING MACROLIDES
• CONCLUDING SUMMARY
• BRIGHTER SIDE OF CLARITHROMYCIN
• DARKER SIDE OF CLARITHROMYCIN
• CURRENT TRENDS IN MACROLIDE USE

BRIGHTER SIDE OF CLARITHROMYCIN:

1. Clarithromycin exhibits BACTERICIDAL activity against H.influenzae, S.pneumoniae, S.pyogenes,S.agalactia etc.,
2. It has good activity against many respiratory pathogens causing atypical pneumonia specifically very effective against L.pneumophiliae etc.,
3. In addition to its antibacterial activity, clarithromycin exhibits  
   a. mprovement in immune function
   b. reduced the visco-elastic property of the mucus and sputum
   
4. Claritheomycin has consistent p.o absorption with good oral bioavailability exhibiting high concentrations in lung, tonsils, nasal tissue, middle ear, and WBCs etc.,
5. No need for adjustment of dosage in older patients and with mild hepatic impairment and renal impairment (except in Creatinine < 30ml/mt)
6. Clarithromycin has greater activity against opportunistic infections associated with AIDS like MAC, T.gondii, and Cryptosporidiosis with very little or no interaction with new Anti HIV proteases used in AIDS.
7. Clarithromycin has greater activity against T.gondii when combined with pyrimethammine although secondary to cotrimoxazole
8. Clarithromycin has excellent activity against M.chelonae as mono-therapy in this refractory disseminated infection
9. Recent studies have clearly shown that clarithromycin is highly effective against B.burgdorferi the tick borne Lyme disease and associated arthritis.
10. Clarithromycin produced better clinical success and bacteriological eradication rate in chest infections like Acute bronchitis, Acute Exacerbation of Chronic Bronchitis (AECB), Community acquired pneumonia, otitis media etc.,
11. Clarithromycin is an important second line drug in leprosy and given in combination with minocycline.

DARKER SIDE OF CLARITHROMYCIN:

Clarithromycin is potent inhibitor of CYP3A isoenzymes and therefore involves drug interactions with; Theophylline, cyclosporin, tacrolimus, carbamazepine, digoxin, Rifamycins necesitasting therapeutic drug monitoring and dose adjustments.

Clarithromycin X Oral anticoagulants = serious bleeding diathesis

Clarithromycin X Zidovudine, Loratidine, Fluoxetin, Nitrazepam ergot derivatives all lead to increased plasma levels of interactants and toxic effects.

Clarithromycin X Terfinadine,astemizole,Cisapride = cardia arrhythmias leading to torsade de pointes etc.,

CURRENT TRENDS IN MACROLIDE USE:

Recently Macrolides are emerging as important agents in the treatment of disorders like ;

sRheumatoid arthritis, Myocardial infarction (Acute coronary syndrome) both of which have infectious origin where infection act as a precipitating factor for inflammatory changes. Recently Azithromycin and Doxycycline combination are being tried by NIH for rheumatoid arthritis . The role of antibiotics in MI is based on the fact that patholgoical examination of coronary plaque have revealed infection associated with C.pneumoniae, H.pylori, Herpes viridae etc., and CMV associated transplant vasculopathy.

Recent pilot studies and controlled trials have demonstrated that macrolide anti microbial treatment against M.pneumoniae reduced the risk of recurrent coronary events.

Recently ROXI trials are underway in Acute Coronary Syndrome associated with QT syndrome.

By- Dr.Sunil Shroff, Dr.Rashmi