Digoxin with cyclosporine

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

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. 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Clinically important, potentially hazardous interactions with abacavir, atorvastatin, bepridil, bupropion, carbamazepine, clarithromycin, cyclosporine, dexamethasone, digoxin, felodipine, fluticasone propionate, fosamprenavir, itraconazole, ketoconazole, lovastatin, methadone, midazolam, nicardipine, nifedipine, phenobarbital, phenytoin, rifabutin, simvastatin, sirolimus, St John s wort, systemic lidocaine, tacrolimus, tenofovir, trazodone, vinblastine, vincristine, voriconazole, warfarin, zidovudine... 

Age-related variations in central nervous system (CNS) neurotransmitter production and receptor sensitivity are the most likely explanations for the pharmacodynamic differences observed between children and adults following administration of psychotropic medications [39a], Children have lower phenobarbital ratios than adults, and the ratio increases with gestational age [40,41]. Conversely, a lower therapeutic range for children has been identified for cyclosporine, phenytoin, and digoxin [42]. 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

Fig. 20.11. Substrate quality obtained by comparing basolateral-to-apical with apical-to-basolateral transport of substrates in polarized cell monolayers of MDR1-transfected cell lines [86] plotted versus (A) the log of the air/water partition coefficient, or (B) H-bond energy (arbitrary units, EUh cf. text). Units of the air/ water partition coefficient were [M ]. Compound (concentrations in Ref. [86] in brackets) were clozapine (50 nM) (1) cyclosporin A (2 tM) (2) daunorubicin (3) dexamethasone (2 tM) (4) digoxin (2 pM) (5) domperidone (2 pM) (6) etoposide (7) flunitrazepam (500 nM) (8) haloperidol (50 nM) (9) ivermectin (50 nM) (10) loperamide (2 pM) (11) morphine (2 pM) (12) ondansetron...

Drugs that may interact with sulfasalazine include digoxin, sulfonylureas, folic acid, cyclosporine, methotrexate, thiopurines, and warfarin. 

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. 

Decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon takes place when these drugs are combined with St. John s wort. 

Despite our inability to predict quantitatively the influence P-gp may have on the in vivo transport of substrates in normal tissues with respect to other processes, in vitro experiments remain the best means of demonstrating that a compound is a substrate for polarized efflux. Nearly all experiments designed to study the extent of P-gp efflux of test compounds in vivo require adequate in vitro data to support the hypothesis (48,217,226,454). In vitro studies on P-gp substrates such as vinblastine, paclitaxel, cyclosporin A, talinolol, acebutolol, and digoxin have provided a good indication of the effect of P-gp on the in vivo pharmacokinetic behavior of these compounds. These studies show that results from the in vitro studies provide a qualitative estimate of the influence of P-gp on its in vivo pharmacokinetic behavior. Findings such as these give confidence that results from in vitro experiments can be extrapolated to explain modulation of dmg disposition by P-gp efflux. 

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