Macrolides Colchicine

COLCHICINE MACROLIDES Case reports of colchicine toxicity when macrolides were added Uncertain macrolides possibly inhibit hepatic metabolism of colchicine. Clarithromycin and erythromycin both inhibit intestinal P-gp, which may t bioavailability of colchicine Monitor FBC and renal function closely... 

The synthesis of five-, six-, and seven-membered cyclic esters or timides uses intramolecular condensations under the same reaction condifions as described for intermolecular reactions. Yields are generally excellent. An example from the colchicine synthesis of E.E. van Ta-melen (1961) is given below. The synthesis of macrocyclic lactones (macrolides) and lactams (n > 8), however, which are of considerable biochemical and pharmacological interest, poses additional problems because of competing intermolecular polymerization reactions (see p. 246ff.). Inconveniently high dilution, which would be necessary to circumvent this side-... 

Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis. 

Catharanthus roseus) [9]. Maytansine (3) is an ansa macrolyde isolated from Maytenus ovatus [10], and rhizoxin (4) is an antitumor macrolide isolated from the fungus Rhizopus chinensis [11]. Another very important tubulin interactive anti-cancer agent is colchicine (6), and this compound binds to a different binding site of tubulin but is also used in anti-cancer therapy. 

Drugs that may affect cyclosporine include allopurinol, amiodarone, androgens (eg, danazol, methyltestosterone), anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), azole antifungals (eg, fluconazole, ketoconazole), beta-blockers, bosentan, bromocriptine, calcium channel blockers, colchicine, oral contraceptives, corticosteroids, fluoroquinolones (eg, ciprofloxacin), foscarnet, HMG-CoA reductase inhibitors, imipenem-cilastatin, macrolide antibiotics, methotrexate, metoclopramide, nafcillin, nefazodone, orlistat, potassium-sparing diuretics, probucol, rifamycins (rifampin, rifabutin), serotonin reuptake inhibitors (SSRIs eg, fluoxetine, sertraline),... 

Halichondrin B (28), which is a polyether macrolide isolated from H. okadai, shows promising antitumor activity and has entered phase 1 clinical trials (2, 15). It inhibits polymerization of tubulin by binding to the colchicine domain. The macrocyclic portion seems to be essential for the activity (2). Halichondrins have been found in several species of sponges, which indicates their microbial origin (6). 

Information on this interaction is limited, but it appears that macrolide antibacterials can provoke acute colchicine toxicity, at the very least in predisposed individuals. If any patient is given colchicine and a macrolide (except probably azithromycin, which is not a notable CYP3A4 inhibitor), be aware of the potential for toxicity, especially in patients with pre-existing renal impairment. 

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