Drug Interactions between Cardoxin and Scot-Tussin Original (old formulation)

MONITOR: The concomitant use of sympathomimetic agents and cardiac glycosides may increase the risk of cardiac arrhythmias. The mechanism of this interaction is not known. Increased ectopic pacemaker activity has been reported to occur in patients taking digoxin in combination with pseudoephedrine.

MANAGEMENT: Caution should be exercised if these two drugs are coadministered. Electrocardiogram monitoring (ECG) is recommended. The use of epinephrine (adrenaline) with high doses of digitalis glycosides is not recommended.

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MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

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MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase plasma digoxin concentrations and half-life. The exact mechanism is unknown, but may be related to reduced renal clearance of digoxin. Data have been conflicting. The interaction has been reported with indomethacin and ibuprofen, but data for other NSAIDs are not available.

MANAGEMENT: Patients who require concomitant therapy should be monitored for altered pharmacologic effects of digoxin and for increased plasma levels. The digoxin dosage may require adjustment. Patients should be advised to notify their physician if they experience nausea, anorexia, visual changes, slow pulse, or irregular heartbeats.

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MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

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Concurrent administration of antacids may decrease the oral bioavailability of digoxin and digitoxin. The mechanism of interaction is unknown. In ten healthy volunteers, administration of a single 0.75 mg dose of digoxin with 60 mL of antacid containing either 4% aluminum hydroxide gel, 8% magnesium hydroxide gel, or 8% magnesium trisilicate resulted in significantly reduced urinary excretion of digoxin (expressed as the percentage of original dose recovered) compared to administration without antacid. Specifically, the cumulative six-day urinary digoxin excretion was 40.1% for control, 30.7% for aluminum hydroxide, 27.1% for magnesium hydroxide, and 29.1% for magnesium trisilicate. In an in vitro study involving absorption across a physiological membrane, cumulative absorption of digoxin 0.25 mg was reduced 11.4% by aluminum hydroxide gel, 15.3% by light magnesium carbonate, and 99.5% by magnesium trisilicate. In a case report, an approximately 50% reduction in digoxin systemic exposure (AUC) was observed when digoxin was administered with 30 mL of an aluminum-magnesium hydroxide antacid and mexiletine. The interaction was attributed to the antacid, as mexiletine is not known to interact with digoxin. Some data also support a potential interaction with digitoxin. However, other studies have found no evidence of a significant interaction between digoxin and various antacids. Based on existing evidence, no special precautions appear necessary, although patients may consider separating the times of administration by 1 to 2 hours if an interaction is suspected.

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