The pacing threshold in patients with pacemakers should be determined prior to instituting therapy with flecainide acetate, again after one week of administration and at regular intervals thereafter. Generally threshold changes are within the range of multiprogrammable pacemakers and, when these occur, a doubling of either voltage or pulse width is usually sufficient to regain capture.

Electrolyte Disturbances
Hypokalemia or hyperkalemia may alter the effects of Class I antiarrhythmic drugs. Preexisting hypokalemia or hyperkalemia should be corrected before administration of flecainide acetate.

Pediatric Use
The safety and efficacy of flecainide acetate in the fetus, infant, or child have not been established in double-blind, randomized, placebo-controlled trials. The proarrhythmic effects of flecainide acetate, as described previously, apply also to children. In pediatric patients with structural heart disease, flecainide acetate has been associated with cardiac arrest and sudden death. Flecainide acetate should be started in the hospital with rhythm monitoring. Any use of flecainide acetate in children should be directly supervised by a cardiologist skilled in the treatment of arrhythmias in children.

PRECAUTIONS

Drug Interactions
Flecainide has been administered to patients receiving digitalis preparations or beta-adrenergic blocking agents without adverse effects. During administration of multiple oral doses of flecainide to healthy subjects stabilized on a maintenance dose of digoxin, a 13% to 19% increase in plasma digoxin levels occurred at six hours postdose.

In a study involving healthy subjects receiving flecainide and propranolol concurrently, plasma flecainide levels were increased about 20% and propranolol levels were increased about 30% compared to control values. In this formal interaction study, flecainide and propranolol were each found to have negative inotropic effects; when the drugs were administered together, the effects were additive. The effects of concomitant administration of flecainide and propranolol on the PR interval were less than additive. In flecainide clinical trials, patients who were receiving beta blockers concurrently did not experience an increased incidence of side effects. Nevertheless, the possibility of additive negative inotropic effects of beta blockers and flecainide should be recognized.

Flecainide is not extensively bound to plasma proteins. In vitro studies with several drugs which may be administered concomitantly showed that the extent of flecainide binding to human plasma proteins is either unchanged or only slightly less. Consequently, interactions with other drugs which are highly protein bound (e.g., anticoagulants) would not be expected. Flecainide has been used in a large number of patients receiving diuretics without apparent interaction. Limited data in patients receiving known enzyme inducers (phenytoin, phenobarbital, carbamazepine) indicate only a 30% increase in the rate of flecainide elimination. In healthy subjects receiving cimetidine (1 gm daily) for one week, plasma flecainide levels increased by about 30% and half-life increased by about 10%.

When amiodarone is added to flecainide therapy, plasma flecainide levels may in