Macrolides Calcium-channel blockers

MACROLIDES CALCIUM CHANNEL BLOCKERS t plasma concentrations of felodipine when co-administered with erythromycin cases of adverse effects of verapamil (bradycardia and 1 BP) with both erythromycin and clarithromycin Erythromycin inhibits CYP3A4-metabolism of felodipine and verapamil. Clarithromycin and erythromycin inhibit intestinal P-gp, which may t bioavailability of verapamil Monitor PR and BP closely watch for bradycardia and 1 BP. Consider i dose of calcium channel blocker during macrolide therapy... 

Agents that may increase theophylline levels include allopurinol, beta blockers (nonselective), calcium channel blockers, cimetidine, oral contraceptives, corticosteroids, disulfiram, ephedrine, influenza virus vaccine, interferon, macrolides, mexiletine, quinolones, thiabendazole, thyroid hormones, carbamazepine, isoniazid, and loop diuretics. 

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

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),... 

In contrast, decreases in theophylline metabolism by selective inhibitors of CYP1A2, such as fluvoxamine and some quinolone antibiotics, or by selective and potent inhibitors of CYP3A4, such as the macrolide antibiotics, have resulted in serious theophylline toxicity (22). It is postulated that taken over time, the macrolide antibiotics act as mechanism-based inhibitors of CYP isoforms other than just CYP3A4. Some nonselective inhibitors of P450s, such as cimetidine, some p-blockers and calcium channel blockers, and others (19,22), also appear to inhibit the metabolism of theophylline enough to cause toxicity. 

Caleium-ehaimel bloekers are metabolised in the gut wall and liver by the eytoehrome P450 CYP3A subfamily of isoenzymes, which are inhibited by erythromycin, clarithromycin, and telithromycin, so that in their presence a normal oral dose becomes in effect an overdose with its attendant adverse effects. Verapamil, erythromycin and possibly clarithromycin are also P-glycoprotein inhibitors, which may contribute to the pharmacokinetic interaction by reducing the elimination of the calcium-channel blocker, or by increasing macrolide absorption. ... 

Information seems to be limited but the interaction would appear to be established and clinically important, although its incidence is probably low. Anticipate the need to reduce the felodipine or verapamil dosage if erythromycin or clarithromycin, or possibly also telithromycin, is added. Nifedipine may also interact. Other reports suggests that the cardiac toxicity of erythromycin may be increased by verapamil, and diltiazem, and the authors of one of these reports consider that erythromycin should not be used with CYP3A4 inhibitors (that is diltiazem and verapamil). There seem to be no reports of interactions between any of the other calcium-channel blockers and macrolides. However, because of the theoretical possibility of an interaction, many of the manufacturers of calcium-channel blockers warn of the possibility of increased plasma levels and the need to either avoid use with macrolides such as erythromycin, or troleandomycin, or to monitor and reduce doses where necessary. 

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