Erythromycin with digoxin

The interaction of erythromycin with digoxin (70,71) is probably due to inhibition of its presystemic metabohsm by inhibition of the growth of Eubacterium glenum. 

Interactions Erythromycin and clarithromycin inhibit the hepatic metabolism of theophylline, warfarin, terfenadine, astemizole, carbamazepine and cyclosporine which can lead to toxic accumulations of these drugs. An interaction with digoxin may occur in some patients. In this case, the antibiotic eliminates a species of intestinal flora that ordinarily inactivates digoxin, thus leading to greater reabsorption of digoxin from the enterohepatic circulation. 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Maxwell DL, Gilmour-White SK, Hall MR. Digoxin toxicity due to interaction of digoxin with erythromycin. BMJ 1989 298(6673) 572. 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Clinically important, potentially hazardous interactions with amitriptyline, amphetamines, aprepitant, astemizole, clarithromycin, dexibuprofen, dextroamphetamine, diethylpropion, digitalis, digoxin, duloxetine, erythromycin, isocarboxazid, linezolid, MAO inhibitors, mazindol, methamphetamine, molindone, phendimetrazine, phenelzine, phentermine, phenylpropanolamine, pseudoephedrine, risperidone, selegiline, sibutramine, St John s wort, sumatriptan, sympathomimetics, tranylcypromine, trazodone, troleandomycin... 

Clinically important, potentially hazardous interactions with acebutolol, amiodarone, aspirin, atenolol, atorvastatin, betaxolol, carbamazepine, carteolol, celiprolol, donidine, dabigatran, dantrolene, digoxin, dofetilide, epirubicin, eplerenone, erythromycin, esmolol, eucalyptus, everolimus, lovastatin, metoprolol, mistletoe, nadolol, oxprenolol, penbutolol, pindolol, propranolol, quinidine, ranolazine, sibutramine, simvastatin, timolol, trabectedin... 

Clearance of quinidine depends on CyP 3A4. Induction of this system by drugs such as carbamazepine, phenytoin, and St. John s Wort leads to enhanced clearance of quinidine. Diminished organ perfusion, CyP 3A4 inhibition by grapefruit juice or erythromycin, or co-administration with protease inhibitors results in decreased clearance. Quinidine itself has been reported to dilate peripheral blood vessels, resulting in mild to moderate hypotension and reduced clearance over the short term. Quinidine affects the rate of clearance of digoxin, Quinidine is analyzed by either HPLC or immunoassay. Fluorescence techniques should be considered obsolete. 

Since erythromycin complexes and inactivates drug oxidizing systems such as cytochrome P-450, it has the potential to alter the metabolism of other drugs. The metabolism and excretion of theophylline, warfarin, carbamaz-epine, and methylprednisolone are inhibited by erythromycin [283-286]. As a potent antibiotic, it can also affect metabolism by gut micro-organisms of drugs such as digoxin. At least some of the newer derivatives may cause fewer drug interactions and thus may be better tolerated if co-administered with medications for other illnesses [287-289]. 

Clarithromycin markedly increases digoxin levels, and numerous cases of digoxin toxicity have been reported. Increases in serum digoxin levels also occur with telithromycin. Cases of rapid and marked two to fourfold increase in serum digoxin levels have also been reported for azithromycin, erythromycin, josamycin and roxithromycin. A similar case has been seen with digitoxin and azithromycin. 

In another 15-year, population-based, nested, case-control study, the association between hospitalization for digoxin toxicity and recent exposure to individual macrolide antibiotics was investigated [7 ]. Clarithromycin was associated with the highest risk of digoxin toxicity (adjusted OR = 15 95% Cl = 7.9, 28), whereas erythromycin and azithromycin were associated with much lower risks (adjusted OR = 3.7 95% CI = 1.7, 7.9 and adjusted OR = 3.7 95% Cl = 1.1, 13 respectively). There was no increased risk with a neutral comparator, cefuroxime (adjusted OR = 0.8 95% Cl = 0.2, 3.4). The combination of digoxin with clarithromycin should be avoided if possible, and digoxin concentrations should be monitored closely when the combination is used. 

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