Medicinal plants containing cardiac glycosides were known to the ancient Egyptians 3000 years ago, but these agents were used randomly and with variable success until the 18th century, when William Withering an English physician and botanist, published a monograph describing the clinical effects of an extract of the foxglove plant i.e., Digitalis purpurea in 1785, described in detail the indication for use of cardiacglycoside. Digoxin is considered as a prototype cardiac glycoside, combine a steroid nucleus with an unsaturated five membered lactone ring at the 17th position and a series of sugar linked to carbon 3 of nucleus, containing 3 molecules of digitxose linked to digitoxigenin. Digoxin is obtained from the leaves of Digitalis lanata. It makes the heart function more efficient. It increases the force of contraction of heart and slows heart rate, used to treat congestive heart failure, to control ventricular rate in the treatment of supraventricular dysrhythmias including atrial fibrillation and flutter, and to treat paroxysmal atrial tachycardia. Digoxin - specific antibody fragments are used FOR the treatment of known or strongly suspected, life - threatening digoxin or digitoxin overdosage, where measures beyond the discontinuation of digoxin or digitoxin and correction of electrolyte abnormality are felt to be necessary.
Interactions
Digoxin is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAcarboseAcebutololAcebutolol may enhance the bradycardic effect of digoxin.ModerateMonitor for increased bradycardia if these two agents are used concomitantly. Ophthalmic beta-blockers are likely of little concern. AdrenalineCoadministration increase risk of Cardiac Arrythmias Atenolol may enhance the vasopressor effect of Adrenaline.Adrenaline used as a local anesthetic for dental procedures will not likely cause clinically relevant problems.ModerateImmediateMonitor increased pressor effects of Adrenaline if used in patients receiving Atenolol. The amount of Adrenaline in dental procedures as part of local anesthetic administration is not likely to be of clinical concern. Infiltrating larger volumes of local anesthetics for other surgical procedures (eg, >0.06 mg Adrenaline) may cause clinically-relevant problems.Albuterolcoadministration of salbutamol with cardiac glycosides produce fall in plasma concentrations and decrease serum concentration of digoxinAlfacalcidolit potentiates action of alfacalcidol, cause hypercalcemiaAlprazolamAlprazolam may increase the serum concentration of digoxin. ADVICE: Avoid concomitant use.ModerateNo action required.Aluminium Hydroxide and OxideAluminium hydroxide may decrease the serum concentration of digoxin.MinorNo action required.Amiloride (HCl)Amiloride may diminish the therapeutic effect of Digoxin. Specifically, the inotropic effects. ModerateMonitor for decreased therapeutic effects of Digoxin if Amiloride is initiated/dose increased, or increased effects if Amiloride is discontinued/dose decreased.Amiodarone (HCl)Amiodarone may increase the serum concentration of Digoxin,increases intestinal transit time,reduce renal clearance and volume of distribution by displacing digoxin from protein binding sites.MajorDelayed (Sequence important)Decrease digoxin dose by 50% and monitor serum digoxin levels as necessary.Amlodipine (Besylate)Amlodipine increases plasma concentration of digoxinAmphotericin BAmphotericin B may enhance the toxic effect of digoxin.ModerateClose monitoring required.Amphotericin BAtenololAtenolol may enhance the bradycardic effect of digoxin.ModerateMonitor bradycardia if these two agents are used concomitantly.AtorvastatinAtorvastatin possibly increases plasma concentration of Digoxin.AzithromycinAzithromycin may increase the serum concentration of Digoxin.ModerateMonitor increased serum concentrations/altered response of Digoxin if Azithromycin is initiated or discontinued, or dosage is modified.BambuterolIncreased automaticity.Monitor ECG for arrhythmias.BendrofluazideBetaxolol (HCl)Betaxolol may enhance the bradycardic effect of digoxin.ModerateMonitor bradycardia if these two agents are used concomitantly. Ophthalmic beta-blockers are likely of little concern.Bisoprolol (Fumarate)Bisoprolol may potentiate bradycardia due to Digoxin.ModerateMonitor for increased bradycardia if these two agents are used concomitantly. Ophthalmic beta-blockers are likely of little concern.BumetanideBumetanide may enhance the adverse/toxic effect of Digoxin. This by increasing the risk of hypokalemia. ModerateMonitor for increased toxic effects of Digoxin if Bumetanide is initiated or the dose is increased. The use of a potassium-sparing diuretic might be considered to minimize potassium loss. Likewise, potassium supplementation, along with careful monitoring of serum potassium and possibly Digoxin concentrations, might be helpful. Buspirone (HCl)Increases plasma concentration of Digoxin.CalcitriolCalciumLarge intravenous doses of calcium salts can precipitate arrhythmias when given with cardiac glycosides (e.g Digoxin).Monitoring of Calcium levels is required if taken with digoxinCalcium CarbonateCalcium Carbonate may enhance the arrhythmogenic effect of Digoxin.ModerateMonitor toxic effects of digoxin (especially cardiac arrhythmias) if a calcium product (especially I.V.) is initiated or the dose is increased.Calcium ChlorideCalcium Chloride may enhance the arrhythmogenic effect of Digoxin.ModerateMonitor for toxic effects of digoxin (especially cardiac arrhythmias) if a calcium product (especially I.V.) is initiated or the dose is increased.Calcium GluconateCalcium gluconate may enhance the arrhythmogenic effect of Digoxin.ModerateMonitor for toxic effects of digoxin (especially cardiac arrhythmias) if a calcium product (especially I.V.) is initiated or the dose is increased.Canagliflozinan increase in the AUC and mean peak drug concentration (Cmax) of digoxin when co administred with canagliflozinPatients taking canagliflozin with concomitant digoxin should be monitored appropriatelyCaptoprilIncrease plasma concentration of digoxin.Monitor serum digoxin levels.Carbenoxolone (Na)CarbimazoleCarteolol (HCl)Carteolol may enhance the bradycardic effect of digoxin.ModerateMonitor for increased bradycardia if these two agents are used concomitantly. Ophthalmic beta-blockers are likely of little concern. CarvedilolDiminished cardiac contractile state.ModerateMonitor ECG for arrhythmias . The interaction may be more evident in children than adults.Celiprolol (HCl)Charcoal (Activated)Charcoal may decrease the absorption of digoxin. ModerateThe simultaneous administration of charcoal and Digoxin should be avoided. Separating the doses by at least 2 hours may help to minimize the interaction. Monitor for reduced serum concentrations/therapeutic effects of Digoxin if charcoal is concomitantly administered.Chlortetracycline (HCl)CholestyramineCholestyramine may decrease the absorption of digoxin.ModerateGive digoxin 8 hours before agent or use solution or liquid-filled capsule form of digoxin.CinitaprideCinitapride can alter the absorption of digoxin as it simulates gastric emptying. ClarithromycinClarithromycin increases the plasma concentration of digoxin by altering metabolism or absorption or by inhibiting renal secretion of digoxin.ModerateClosely monitor the serum level of digoxin. Patient should notify to physician if experience nausea, anorexia, visual disturbance, slow pulse or irregular heart beats.Colestipol (HCl)Colestipol may decrease the absorption of digoxin.ModerateMonitor for decreased serum concentrations/therapeutic effects of digoxin if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. Colestipol may be less likely to interact than cholestyramine. Co-TrimoxazoleCyclophosphamideCyclophosphamide may decrease the absorption of Digoxin. This may only affect digoxin tablets. ModerateRapidMonitor for decreased therapeutic effects of digoxin tablets if Cyclophosphamide is initiated/dose increased, or increased effects if Cyclophosphamide is discontinued/dose decreased. Digoxin absorption will likely return to normal within approximately 1 week after discontinuation of chemotherapy.Cyclosporin ACycloSPORINE may decrease the metabolism of Digoxin.ModerateRapidMonitor for toxic effects of Digoxin if cyclosporine is initiated/dose increased, or decreased effects if cyclosporine is discontinued/dose decreased. Cytarabine (HCl)Demeclocycline (HCl)Demeclocycline may decrease the absorption of Digoxin.ModerateMonitor for decreased therapeutic effects of Digoxin if oral Demeclocycline is initiated/dose increased, or increased effects if oral Demeclocycline is discontinued/dose decreased. Dose spacing does not appear to help minimize this interaction. Administering I.V. formulations of digoxin will bypass this interaction.DiazepamDiazepam may increase the serum concentration of digoxin.ModerateNo action required.Diclofenac (Na)Diclofenac increases the plasma concentration of digoxin.Diltiazem (HCl)Diltiazem (HCl) [Calcium Channel Blocker (Nondihydropyridine)] may enhance the AV-blocking effect of Digoxin. Diltiazem (HCl) may decrease the metabolism of Digoxin. MajorMonitor for increased therapeutic/toxic effects of digoxin if Diltiazem (HCl) is initiated/dose increased, or decreased effects if Diltiazem (HCl) is discontinued/dose decreased.DisopyramideDoxorubicin (HCl)Edrophonium (Cl)Edrophonium may enhance the AV-blocking effect of Digoxin.MajorRapid No action required. Enalapril (Maleate)enalapril reduce clearance of digoxin leading to increase serum level of digoxin in patients with heart failureErythromycinErythromycin may increase the serum concentration of Digoxin by about 40%-100%.ModerateMonitor serum concentrations of digoxin.FelodipineFenbufenFluoxetine (HCl)Serum concentration of digoxin may increased by fluoxetine.MinorIf interaction occur dose adjustment is needed.Fosinopril (Na)FosphenytoinFrusemide or FurosemideFrusemide decreases serum and tissue patassium (K), thus increases automaticity. Frusemide also facilitates inhibition of Na-K ATPase by digoxin.ModerateMonitor for increased toxic effects of Digoxin if Frusemide is initiated or the dose is increased. The use of a potassium-sparing diuretic might be considered to minimize potassium loss. Likewise, potassium supplementation, along with careful monitoring of serum potassium and possibly Digoxin concentrations, might be helpful.GallopamilGinkgo Biloba ExtractGinkgo Biloba does not appear to affect serum concentration of Digoxin. No action required. Gonadorelin (HCl)GuanethidineHydralazine (HCl)HydroflumethiazideHydroflumethiazide may enhance the adverse/toxic effect of Digoxin. This by increasing the risk of hypokalemia. ModerateMonitor for increased toxic effects of Digoxin if Hydroflumethiazide is initiated or the dose is increased. The use of a potassium-sparing diuretic might be considered to minimize potassium loss. Likewise, potassium supplementation, along with careful monitoring of serum potassium and possibly Digoxin concentrations, might be helpful.Hydroxychloroquine (Sulphate)Hydroxychloroquine may increase the serum concentration of Digoxin.ModerateMonitor for increased serum concentrations/toxic effects of Digoxin if Hydroxychloroquine is initiated/dose increased, or decreased serum concentrations/effects if Hydroxychloroquine is discontinued/dose decreased.Severity Moderate (Sequence Important)IspaghulaItraconazoleItraconazole may increase the serum concentration of digoxin.ModerateDelayedMonitor for increased serum concentrations/toxic effects of digoxin if itraconazole is initiated or the dose is increased.KaolinKaolin may decrease the absorption of Digoxin. ModerateGive digoxin 8 hours before agent or use solution or liquid-filled capsule form of digoxin.LacidipineLevobunolol (HCl)liraglutideliraglutide decreases AUC by 16% and Cmax by 31% of digoxintake caution when both drugs are co-administeredLornoxicamDecreased renal clearance of digoxinMonitor digoxin levels and adjeust dose accordingly.Magnesium Oxides and HydroxidesMagnesium hydroxide may decrease the serum concentration of digoxin.MinorNo action required.MannitolMetaraminolMetformin (HCl)Digoxin decreases the excretion of metformin by competing the renal tubular transport.ModerateDose of metformin should be reduced.MetipranololInfrequent reports of METIPRANOLOL [EYE] increasing the NEGATIVE CHRONOTROPIC effect of DIGOXIN. ModerateMay need to avoid combinationMetoclopramide (HCl)Mibefradil (Di HCl)Minocycline (HCl)Minocycline may decrease the absorption of Digoxin.ModerateMonitor for decreased therapeutic effects of Digoxin if oral Minocycline is initiated/dose increased, or increased effects if oral Minocycline is discontinued/dose decreased. Dose spacing does not appear to help minimize this interaction. Administering I.V. formulations of digoxin will bypass this interaction.MoexiprilConcurrent use may increase the blood pressure or heart rate.Moricizine (HCl)Nebivolol (HCl)Concurrent use may decrease the extent of absorption of Nebivolol (HCl).Nefazodone (HCl)Nefazodone may increase the serum concentration of Digoxin.ModerateMonitor for increased therapeutic effects of Digoxin if nefazodone is initiated/dose increased, or decreased effects if nefazodone is discontinued/dose decreased.NeomycinNeomycin may reduce absorption of digoxin.ModerateGive digoxin 8 hours before agent or use solution or liquid-filled capsule form of digoxin.NicardipineNifedipineVariable moderate decrease in digoxin clearance and/or volume of distribution.Monitor serum digoxin level.NimodipineNisoldipineNitrendipineAt nitrendipine doses exceeding 20 mg/day, increased digoxin levels and toxicity can occur. Noradrenaline (Acid Tartrate)OmeprazoleOmeprazole may inhibit the absorption of digoxinMinorMonitor serum digoxin levels.Pancuronium (Br)Pancuronium may enhance the arrhythmogenic effect of Digoxin. ModerateMonitor for the development of cardiac arrhythmias when Pancuronium is administered to patients who are receiving Digoxin.PantoprazolePantoprazole may increase the risk of side effects of Warfarin (Na).Paromomycin (Sulphate)ParoxetinePhenytoin (Na)Potassium BicarbonatePotassium Bicarbonate may increase the risk of digoxin side effects.PrazosinPrazosin increases plasma concentration of digoxin.Propafenone (HCl)Propafenone may increase the serum concentration of Digoxin.ModerateMonitor increased serum concentrations/toxic effects of Digoxin if propafenone is initiated/dose increased, or decreased serum concentrations/effects if propafenone is discontinued/dose decreased.Propantheline (Br)Propranolol (HCl)Propranolol may enhance the bradycardic effect of digoxin.ModerateMonitor for increased bradycardia if these two agents are used concomitantly. Ophthalmic beta-blockers are likely of little concern. PropylthiouracilSerum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid.A reduced dosage of digitalis glycosides may be required.QuinidineSerum digoxin levels are increased by quinidine due to reduced renal and biliary clearance.ModerateRapidUpon initiation of quinidine, an empiric reduction (25% to 50%) in the digoxin dose seems warranted, with continued monitoring of digoxin serum concentrations until the quinidine reaches steady state (5-10 days). Monitor for toxic effects of digoxin if quinidine is initiated or the dose is increased.Onset Rapid (Sequence Important)QuinineQuinine may increase the serum concentration of Digoxin by decreasing its biliary clearance.ModerateRapidMonitor for increased serum concentrations/toxic effects of Digoxin if quinine is initiated or the dose is increased.RanolazineRanolazine (1000 mg twice daily) causes a 1.5-fold elevation of digoxin plasma concentrations. The dose of digoxin may have to be adjusted.Rauwolfia ReserpineRhubarbStimulant laxatives can decrease potassium levels in the body. Low potassium levels can increase the risk of side effects of digoxin.ModerateRifampicinRitonavirRitonavir may increase the serum concentration of Digoxin. ModerateMonitor for increased effects of digoxin if Ritonavir is initiated/dose increased, and for decreased effects if Ritonavir is discontinued/dose decreased. RoxithromycinSimvastatinConcomitant administerationn can slightly increase in digoxin levelSitagliptinThere was a slight increase in the area under the curve (AUC, 11%) and mean peak drug concentration (Cmax, 18%) of digoxin with the co-administration of 100 mg sitagliptin for 10 days.N/ADelayedPatients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or sitagliptin is recommended.Sodium NitroprussideSodium Polystyrene SulphonateSodium Polystyrene SulphonateSorafenibsorafenib has been shown to inhibit the transport protein p-glycoprotein (P-gp). Increased plasma concentrationsSpironolactoneSpironolactone may inhibit the tubular secretion of Digoxin by about 25% and thus increase the plasma digoxin concentrations. ModerateThe change is generally not enough to warrant changes in digoxin dosages.SucralfateSulphasalazineAbsorption of digoxin possibly reduced by sulphasalazine.ModerateRapidMonitor for decreased serum concentrations/therapeutic effects of digoxin if sulphasalazine is initiated/dose increased, or increased serum concentrations/effects if a sulphasalazine is discontinued/dose decreased.Suxamethonium (Cl)TegaserodTegaserod slightly decreased digoxin plasma concentrations and AUC in a clinical study (n=12). However the changes were considered clinically insignificant. The mechanism is unknown. No action is necessary.MinorTelithromycinMonitoring of digoxin side effects or serum levels should be considered during concomitant administration of digoxin and Teicoplanin.TelmisartanTelmisartan may increase the serum concentration of Digoxin.ModerateMonitor for increased serum concentrations and/or toxic effects of Digoxin if telmisartan is initiated/dose increased, or decreased serum concentrations/effects if telmisartan is discontinued/dose decreased. Tetracycline (HCl)Tetracycline may decrease the absorption of Digoxin.ModerateMonitor for decreased therapeutic effects of Digoxin if oral tetracycline is initiated/dose increased, or increased effects if oral tetracycline is discontinued/dose decreased. Dose spacing does not appear to help minimize this interaction. Administering I.V. formulations of digoxin will bypass this interaction.Ticagrelordigoxin is P-glycoprotein substrate (other e.g; Cyclosporin) and ticagrelor may increase cmax of digoxin by 75%, AUC 28%clinical monitoring is requiredTizanidineTocainide (HCl)TopiramateTrazodone (HCl)TriamtereneTriamterene may diminish the therapeutic effect of Digoxin. Specifically, the inotropic effects. ModerateMonitor for decreased therapeutic effects of Digoxin if Triamterene is initiated/dose increased, or increased effects if Triamterene is discontinued/dose decreased.TrimethoprimVerapamil (HCl)Verapamil [Calcium Channel Blocker (Nondihydropyridine)] may enhance the AV-blocking effect of Digoxin. Verapamil may decrease the metabolism of Digoxin by decreasing its renal and extra renal clearance and hence increases digoxin levels. MajorIf Verapamil and Digoxin are used together to control the supraventricular tachyarrhythmia, the dosage of each drug may have to be reduced. patients should be closely monitored for clinical and laboratory evidence of digoxin safety while taking verapamil and evaluated for under digitialisation when verapamil is discontinued.VORICONAZOLEVoriconazole may increase the serum concentration of digoxin. Monitor for increased serum concentrations and toxic effects of digoxin if voriconazole is initiated or dose increased.Xamoterol (Fumarate) These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.