Drugs that inhibit cytochrome P450IID6, such as quinidine, might increase the plasma concentrations of flecainide in patients that are on chronic flecainide therapy; especially if these patients are extensive metabolizers.

There has been little experience with the coadministration of flecainide and either disopyramide or verapamil. Because both of these drugs have negative inotropic properties and the effects of coadministration with flecainide are unknown, neither disopyramide nor verapamil should be administered concurrently with flecainide unless, in the judgment of the physician, the benefits of this combination outweigh the risks. There has been too little experience with the coadministration of flecainide with nifedipine or diltiazem to recommend concomitant use.

Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies with flecainide in rats and mice at doses up to 60 mg/kg/day have not revealed any compound-related carcinogenic effects. Mutagenicity studies (Ames test, mouse lymphoma and in vivo cytogenetics) did not reveal any mutagenic effects. A rat reproduction study at doses up to 50 mg/kg/day (seven times the usual human dose) did not reveal any adverse effect on male or female fertility.

Pregnancy

Pregnancy Category C
Flecainide has been shown to have teratogenic effects (club paws, sternebrae and vertebrae abnormalities, pale hearts with contracted ventricular septum) and an embryotoxic effect (increased resorptions) in one breed of rabbit (New Zealand White) when given doses of 30 and 35 mg/kg/day, but not in another breed of rabbit (Dutch Belted) when given doses up to 30 mg/kg/day. No teratogenic effects were observed in rats and mice given doses up to 50 and 80 mg/kg/day, respectively; however, delayed sternebral and vertebral ossification was observed at the high dose in rats. Because there are no adequate and well-controlled studies in pregnant women, flecainide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery
It is not known whether the use of flecainide during labor or delivery has immediate or delayed adverse effects on the mother or fetus, affects the duration of labor or delivery, or increases the possibility of forceps delivery or other obstetrical intervention.

Nursing Mothers
Results from a multiple dose study conducted in mothers soon after delivery indicates that flecainide is excreted in human breast milk in concentrations as high as 4 times (with average levels about 2.5 times) corresponding plasma levels; assuming a maternal plasma level at the top of the therapeutic range (1 mcg/mL), the calculated daily dose to a nursing infant (assuming about 700 mL breast milk over 24 hours) would be less than 3 mg.

Pediatric Use
The safety and efficacy of flecainide in the fetus, infant, or child have not been established in double-blind, randomized, placebo-controlled trials (see CLINICAL PHARMACOLOGY, WARNINGS, and DOSAGE AND ADMINISTRATION).

Hepatic Impairment
Since flecainide elimination from plasma can be markedly slower in patients with significant hepatic impairment, flecainide should not be used in such patients unless the potential benefits clearly outweigh the risks. If used, frequent and early plasma level monitoring is required to guide do