Itraconazole Digoxin

Angirasa AK, Koch AZ. P-glycoprotein as the mediator of itraconazole-digoxin interaction. J Am Podiatr Med Assoc (2002) 92, 471-2. 

P-gp (ABCB1) Verapamil, digoxin, mitoxantrone, vinblastine, doxorubicin, losartan, talinolol, cortisol, dexamethasone, colchicine, loperamide, domperidone, indinavir, erythromycin, tetracycline, itraconazole, cyclosporine, methotrexate, amitryptyline, phenobarbital, morphine, cimetidine, and others... 

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... 

Release-related bioavailability problems have been encountered in the pharmaceutical development of formulations for a number of quite different chemical entities, including ciclos-porin, digoxin, griseofulvin, and itraconazole, to name but a few. A thorough knowledge of hydrodynamics is useful in... 

Itraconazole is a triazole antifungal, which increases the plasma concentration of digoxin, hence increasing the risk of digoxin toxicity. 

Drugs that may be affected by proton pump inhibitors include azole antifungal agents (eg, itraconazole, ketoconazole), benzodiazepines, cilostazol, clarithromycin, digoxin, phenytoin, salicylates, sulfonylureas, and warfarin. Drugs that may affect proton pump inhibitors include sucralfate and clarithromycin. 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

Itraconazole has significant interactions with a number of commonly prescribed drugs, such as rifampin, phenytoin, and carbamazepine. Itraconazole raises serum digoxin and cyclosporine levels and may affect the metabolism of oral hypoglycemic agents and coumadin. Absorption of itraconazole is impaired by antacids, Hj blockers, proton pump inhibitors, and drugs that contain buffers, such as the antiretroviral agent didanosine. 

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. 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

Itraconazole Alfentanil, alprazolam, astemizole, atorvastatin, buspirone, cisapride, cyclosporine, delavirdine, diazepam, digoxin, felodipine, indinavir, loratadine, lovastatin, midazolam, nisoldipine, phenytoin, quinidine, ritonavir, saquinavir, sildenafil, simvastatin, sirolimus, tacrolimus, triazolam, verapamil, warfarin... 

Digoxin [NE] Increased plasma concentrations of digoxin with itraconazole, posaconazole, and ketoconazole. 

Drug Interactions Gemfibrozil Niacin Erythromycin Cholestyramine Digoxin Cimetidine/ranitidine/ omeprazole Rifampicin Warfarin Itraconazole Gemfibrozil Niacin Erythromycin Propranolol Digoxin Warfarin Antacids Colestipol Digoxin Erythromycin Oral contraceptives Fibrates Niacin Azole antifungals... 

The ratio of renal clearance of digoxin to creatinine clearance decreased with the coadministration of clarithromycin (0.64 and 0.73), and was restored (1.30) after administration of clarithromycin had stopped (326). The role of P-gp efflux in this interaction was confirmed using an in vitro kidney epithelial cell line (326). The administration of itraconazole, a P-gp inhibitor, with digoxin resulted in an increased trough concentration and a decrease in the amount of renal clearance, possibly by an inhibition of the renal tubular secretion of digoxin via P-gp (329). The P-gp modulator verapamil has also been shown to decrease the renal clearance of digoxin (330). 

Alderman CP, Allcroft PD. Digoxin-itraconazole interaction possible mechanisms. Ann Pharmacother 1997 31(4) 438 140. 

Acyclovir Erythromycin Ivermectin Itraconazole Rifampin Actinomycin D Daunorubicin Doxorubicin Docetaxel Epirubicin Etoposide Imatinib Irinotecan Paclitaxel Vinblastine Vincristine Amprenavir Indinavir Nelfinavir Ritonavir Saquinavir Cyclosporine A Tacrolimus Digoxin Quinidine Verapamil Diltiazem Aldosterone Cortisol Corticosterone Dexamethasone Hydrocortisone Cyclosporine Metkephamid Enkephalin... 

DIGOXIN ITRACONAZOLE Itraconazole may cause t plasma levels of digoxin cases reported of digoxin toxicity Itraconazole inhibits P-gp-mediated renal clearance and t intestinal absorption of digoxin Monitor digoxin levels watch for digoxin toxicity... 

A 62-year-old woman who was taking digoxin took itraconazole 400 mg/day for 3 days developed nausea, anorexia, and lethargy the symptoms improved within 48 hours after withdrawal of itraconazole (231). The serum digoxin concentrations were not reported. 

In a 75-year-old man who took itraconazole in a low dose (200 mg/day) the steady-state serum digoxin concentration only rose from 0.8 to 1.1 ng/ml after 8 days (232). 

Two renal transplant patients developed digoxin toxicity when they also took itraconazole (233). 

Alderman CP, Jersmann HP. Digoxin-itraconazole interaction. Med J Aust 1993 159(ll-12) 838-9. 

Sachs MK, Blanchard LM, Green PJ. Interaction of itraconazole and digoxin. Clin Infect Dis 1993 16(3) 400-3. 

Mathis AS, Friedman GS. Coadministration of digoxin with itraconazole in renal transplant recipients. Am J Kidney Dis 2001 37(2) E18. 

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