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.
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.
Macrolides are important alternatives to betalactams in the treatment of number of infections. Major advantages of macrolides are that even though the spectrum covers the organisms amenable to benzyl penicillin, they are highly effectives against many intracellular pathogens by attaining high I.C concentration and high tissue fluid concentrations when compared with plasma concentrations..
Erythromycin, Azithromycin and Clarithromycin are equally effective against gram-positive infections.
Clarithromycin and azithromycin have better activity against H.influenzae, M.catarhalis, especially in the treatment of community acquired pneumonia and acute exacerbations of chronic bronchitis.
Clarithromycin is highly effective for treatment and prophylaxis of MAC (disseminated) infection in AIDS patients while Azithromycin is effective in prophylaxis alone.
Clarithromycin exhibits good activity against Gram Positive anaerobes, C.trachomatis, M.catarrhalis, L.pneumophiliae, H.influenzae and H.parainfluenzae, B.bdgedorferi, H.pylori, MAC, M.chelonae.
Clarithromycin is the drug of choice in H.pylori along with omeprazole in rapid eradication either in 3 or 4-drug regimen.
Azithromycin is the drug of choice in C.trachomatis, and gi en as single dose 1 G curative (Long plasma half life for azithromycin viz., 245-96 hrs). Unlike clarithromycin azithromycin does not affect CYP isoenzymes and there is no drug interaction.
Dirithromytcin is similar to Erythromycin in antibacterial activity Poor against H.influenzae but exhibit good activity against several strains of H.pylori.
Clarithromycin demonstrated activity against M.chelonae (disseminated cutaneous infection), disseminated MAC in AIIDS and in M.leprae.
Recent trials have demonstrated activity of clarithromycin against B>burgdorferi.
Azithromycin has increased activity against gram-negative organisms including H.influenzae, Enterobactericiae, Salmonellae, Shigellae, and E.coli, aerobic and anaerobic gram-negative organisms.
Roxithromycin is less effective than erythromycin well absorbed but food decreases absorption - usual dose is 150mg bd or 300mg/day.
Spiramycin (16membered macrolide from Str. aumbofauceus) is similar to erythromycin. A combination preparation with metronidazole is available for amebiasis. Spiramycin has no embryo toxicity, no teratogenecity, no mutagenecity and found to be active against Legionellirs, Toxoplasmosi, Chlamydiae and certain anaerobes (except B.fragilis and fusobacterium).
Spirmaycin exhibits very poor or no penetration into CNS.Major indications of spiramycin include;
Recent trials have proved that clarithromycin is a beter agent among macrolides in producing better clinical cure and bacteriological eradication when compared with other macrolides. The major drawbacks include its adverse effects in the form of drug interactions and the next one is cost.By therapeutic monitoring adverse drug effect can be minimised .Despite the above limitations CLARITHROMYCIN occupies an important in the place of therapeutic armamentarium of physicians dealing with infectious diseases.
