Diltiazem with digoxin

Verapamil additive cardiodepressant activity when combined with a -blocker additive impairment of AV conducton when combined with digoxin. Diltiazem as mentioned for verapamil. 

Another important indication for antiarrhythmic therapy is to reduce ventricular rate in atrial flutter or fibrillation. Rare forms of ventricular tachycardia appear to be DAD-mediated and respond to verapamil. Parenteral verapamil and diltiazem are approved for rapid conversion of PSVTs to sinus rhythm and for temporary control of rapid ventricular rate in atrial flutter or fibrillation. Oral verapamil may be used in conjunction with digoxin to control ventricular rate in chronic atrial flutter or fibrillation and for prophylaxis of repetitive PSVT Unlike adrenergic receptor antagonists, Ca + channel blockers have not been shown to reduce mortality after myocardial infarction. 

Blockers are contraindicated in patients with severe bradycardia (heart rate less than 50 beats per minute) or AV conduction defects in the absence of a pacemaker. (3-Blockers should be used with particular caution in combination with other agents that depress AV conduction (e.g., digoxin, verapamil, and diltiazem) because of increased risk for bradycardia and heart block. Relative contraindications include asthma, bronchospastic disease, severe depression, and peripheral vascular disease. (3,-Selective blockers are preferred in patients with asthma or chronic obstructive pulmonary... 

The answer is b. (Hardman, pp 816-818.) Digoxin levels rise with concomitant administration of diltiazem by an unknown mechanism that reduces renal clearance... 

Verapamil and diltiazem have negative inotropic effects. These calcium channel blockers may be harmful in asymptomatic patients with a low LVEF and in post-MI patients without HF symptoms. Digoxin will not be good to use in patients with low FF, with sinus rhythm and no history of HF symptoms, because the benefits will not exceed the risk. 

There has beeu a raudomized, double-bliud compar-isou of iutraveuous diltiazem aud digoxiu iu 40 patieuts with atrial fibrillatiou aud a veutricular rate of over 100/minute (156). Oue patieut giveu iutraveuous digoxin had a burning sensation at the site of injection. 

Halawa B, Mazurek W. Interakcje digoksyny z nifedypina i diltiazemem. [Interactions of digoxin with nifedipine and diltiazem.] Pol Tyg Lek 1990 45(23-24) 467-9. 

Mahgoub AA, El-Medany AH, Abdnlatif AS. A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure. Saudi Med J 2002 23(6) 725-31. 

Clinically important, potentially hazardous interactions with abarelix, acenocoumarol, amisulpride, amprenavir, anisindione, anticoagulants, arsenic, astemizole, carbimazole, celiprolol, ciprofloxacin, dabigatran, degarelix, dicumarol, digoxin, diltiazem, enoxacin, fentanyl, fosamprenavir, gatifloxacin, grapefruit juice, lomefloxacin, methotrexate, moxifloxacin, nilotinib, norfloxacin, ofloxacin, oxprenolol, quinidine, quinolones, rifabutin, rifampin, rifapentine, ritonavir, simvastatin, sparfloxacin, sulpiride, tacrolimus, tipranavir, verapamil, warfarin, zuclopenthixol... 

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 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 alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

PO. 50% bioavailability after oral dose. 75% protein bound, half-life=3 hrs, metabolites are active. Reduce dose in patients with renal dysfunction. AV node block, sick sinus syndrome, hypotension, pulmonary congestion. Beta-blockers and digoxin increase A-V conduction time. Diltiazem increases propranolol levels. Cimetidine and drugs metabolized by P-450 increase diltiazem levels. ... 

Andrejak M, Hary L, Andrejak M, Lesbre J. Diltiazem increases steady state digoxin serum levels in patients with cardiac disease. J Clin Pharmacol 1987 27 967-970. 

Serum digoxin ieveis are reported to be unchanged by diltiazem in a number of studies but others describe increases ranging from 20 to 8S%. Serum digitoxin levels have also been reported to rise in some patients, but only by about 20%. There is a risk of additive bradycardia when cardiac glycosides are given with diltiazem. 

Not understood. In those individuals showing a pharmacokinetic interaction, falls in total digoxin clearance of about 25% have been described. - Although several calcium-channel blockers may inhibit the P-glycoprotein-mediated renal clearance of digoxin, the results of an in vitro study suggest that this may not occur with diltiazem. 

Elkayam U, I ikh K, Trenal clearance and serum concentratic of digoxin in patients with cardiac disease AmJ... 

---