Drug Interactions between digoxin and methscopolamine / phenylephrine

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.

MONITOR: The pressor response to phenylephrine may be potentiated by the vagolytic effect of atropine, which inhibits the reflex bradycardia that would normally accompany any increases in blood pressure induced by phenylephrine. Other antimuscarinic agents may also participate in this interaction, although clinical data are lacking. In one report, pseudo-pheochromocytoma (i.e., significant increases in blood pressure and tachycardia) occurred in seven patients who underwent eye surgery and were given phenylephrine 10% ophthalmic solution and systemic atropine, three of whom subsequently developed left ventricular failure and pulmonary edema that required intensive care monitoring. Two patients had preexisting hypertension, while others had no known history of cardiovascular disease. All had received general anesthesia with propofol, phenoperidine, and vecuronium. Since phenylephrine use alone may be associated with cardiovascular toxicities including hypertension, arrhythmia, myocardial infarction and cardiac failure, the extent of involvement by atropine is uncertain. The authors reported no further cardiovascular events following implementation of various measures that reduced phenylephrine dosage and systemic exposure, including: use of a milder strength of phenylephrine ophthalmic solution; swabbing to minimize drainage into the nasolachrymal duct to the nasal mucosa; and use of a cannula to reduce drop size. In a study of six healthy volunteers, diastolic and systolic blood pressure increased by 4 mmHg following administration of phenylephrine (0.42 mcg/kg/min), compared to 17 mmHg when phenylephrine was given after three doses of atropine (0.02, 0.01 and 0.01 mg/kg at 30 minute intervals).

MANAGEMENT: Caution is advised if phenylephrine (systemic or ophthalmic) is used in combination with atropine or other antimuscarinic agents. Cardiovascular status, including blood pressure and heart rate, should be closely monitored. When using ophthalmic formulations, measures to minimize systemic absorption should be employed, such as digital compression of the lacrimal sac or lid closure after instillation. A milder strength (< 10%) is preferable if phenylephrine ophthalmic solution is given.

Anticholinergic agents may increase the absorption and oral bioavailability of some digoxin formulations. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents. In one study, coadministration with propantheline (15 mg three times a day for 10 days) led to a 30% mean increase in serum digoxin levels in 9 of 13 elderly women receiving a slow-dissolution formulation of digoxin. The interaction has also been reported with formulations containing large particle size digoxin. Other studies have found no significant effect of propantheline on digoxin elixir, solution in capsules, rapid-dissolution tablets, and micronized digoxin tablets. Therefore, the interaction is not expected to occur with most digoxin products used today in industrialized countries (e.g., Lanoxin). Due to the drug's narrow therapeutic index, however, clinicians may consider monitoring patients more closely for digoxin side effects and toxicity during coadministration with anticholinergic agents. Patients should be advised to notify their physician if they experience potential signs and symptoms of digoxin toxicity such as nausea, anorexia, visual disturbances, slow pulse, and irregular heartbeats.