Nifedipine Digoxin

Kirch W, Hutt HJ, Dylewicz P, Graf KJ, Ohnhaus EE. Dose-dependence of the nifedipine-digoxin interaction Clin Pharmacol Ther 1986 39(l) 35-9. 

Kasmer RJ, Jones EM. Diltiazem-nifedipine-digoxin interaction. Drug Intell Clin Pharm (1986) 20,985-6. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

Cardiovascular Acetyldigosin, ajmaline, amiodarone, aprindine, bepridil, bezaflbrate, captopril, dinepazide, clopidogrel, coumarins, diazoxide, digoxin, dipyridamole, disopyramide, doxazosin, enalapril, flurbiprofen, fur-oxemide, hydralazine, lisinopril methyldopa, metolazone, nifedipine, phenindione, procainamide, propanolol, propafenone, quinidine, ramapril, spironolactone, thiazide diuretics, ticlopidine, vesnarinone... 

Drugs that can precipitate lactic acidosis in patients taking metformin include ACE inhibitors, thiazide diuretics, NSAIDs, and drugs such as furosemide, nifedipine, cimetidine, amiloride, triamterene, trimethoprim, and digoxin, which are all secreted in the renal tubules, compete with metformin, and can contribute to increased plasma metformin concentrations (76). 

Glyceryl trinitrate overdose should be treated with the patient s head lowered. Other measures include respiration maintenance, use of plasma expanders, and electrolyte balance. Withdrawal of heparin treatment or dose reduction should be performed with the overdose of heparin. Protamine sulfate may be used to reduce severe bleeding. Heparin should be used with caution with glyceryl trinitrate, aprotinine, alcohol, tobacco, and ACE inhibitors. Nifedipine should be used with care when coadministering with immunosuppressants, magnesium salts, tobacco, digoxin, antineoplastics, calcium channel blockers, antihistamines, antifungals, antiepileptics, antiarrhythmics, and alcohol. 

Verapamil [ver AP a mill] slows cardiac conduction directly and thus decreases heart rate and oxygen demand. Verapamil causes greater negative inotropic effects than does nifedipine, but it is a weaker vasodilator. Verapamil is contraindicated in patients with preexisting depressed cardiac function or AV conduction abnormalities. It also causes constipation. Verapamil should be used with caution in digitalized patients, since it increases digoxin levels (see p. 160). 

DILTIAZEM, NIFEDIPINE, FELODIPINE, LACIDIPINE, LERCANIDIPINE, NICARDIPINE, NISOLDIPINE DIGOXIN Possible T plasma concentrations of digoxin These calcium channel blockers are thought to -l renal excretion of digoxin Monitor digoxin levels carefully... 

Enalapril, paracetamol, sotalol, dipyrone, vancomycin, captopril, fluconazole, cefazolin, metoprolol, aspirin, ticlopidine, prednisolone, propranolol, digoxin, sildenafil, furosemide, dexamethasone, carvedilol, ketoprofen, nifedipine, terbinafine, acenocoumarol, spironolactone/urine HPLC DAD Column LiChroCART Purospher STAR, RP-18e (250 x 4 mm, 5 pm) Mobile phase MeOH ACN 0.05 % TFA in water (gradient elution) Detection DAD X = 200 50 nm Adjusted to pH 7.0, protein precipitation LOD 0.01-1.44 pg/mL LOQ 0.04-4.35 pg/mL [72]... 

The interaction of digoxin with nifedipine increases plasma digoxin concentrations by only about 15% (178,179) and is less important. 

Kleinbloesem CH, van Brummelen P, Hillers J, Moolenaar AJ, Breimer DD. Interaction between digoxin and nifedipine at steady state in patients with atrial fibrillation. Ther Drug Monit 1985 7(4) 372-6. 

Calcium channel blockers have varying effects on the disposition of digoxin. The calcium channel blockers for which varying amounts of information are available include cinnarizine, diltiazem, felodipine, fendiline, gallo-pamil, isradipine, lidoflazine, mibefradil, nicardipine, nifedipine, nitrendipine, tiapamil, and verapamil (238). 

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. 

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... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

The potential role of the calcium current in the genesis of arrhythmias was discussed above. Verapamil (M, which inhibits calcium influx, can suppress experimental arrhythmias30 Another calcium blocker, nifedipine ( 13a), inhibits irregular rhythms produced by calcium in isolated atrial preparations.31 The calcium antagonist TMB-6( lk) was reported to be as effective as lidocaine in suppressing digoxin-induced arrhythmias in dogs.32 As expected, inhibition of calcium influx leads to depression of cardiac contractility and atrioventricular conduction. 

Heart block is a contraindication for the nondihydropyridines. The most common side effects are bradycardia and heart block (for the nondihydropyridines). Peripheral edema and headache are also common. Nondihydropyridines exacerbate bradycardic effects of /S-blockers, and verapamil raises digoxin serum concentrations by 70%. Diltiazem raises cyclosporine serum concentrations. Intravenous calcium salts inhibit the pharmacologic effect of CCBs. Generic formulations or similar products, but not necessarily generic equivalents to the original brand names, are available for verapamil, nifedipine, and diltiazem. 

Drugs or pharmacological interventions (heparin (Berger and Zaret 1984), antimicrobials or antibiotics, anticonvulsants, tranquilizers, anti-inflammatory agents (Chervu et al. 1981 Hladik et al. 1982), nifedipine (Sampson 1993), prazosin, digoxin (Lee 1983), propanolol, hydralazine, methyldopa, verapamil, chlorothiazide, furosemide, ranitidine, iron therapy, etoposide-h doxontbicin (Sampson 1993, 1995), others)... 

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