Flecainide warnings and precautions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
Warnings and Precautions
PRECAUTIONS
Drug Interactions. Flecainide acetatehas been administered to patients receiving digitalis preparations or beta-adrenergic blocking agents without adverse effects. During administration of multiple oral doses of flecainide acetate to healthy subjects stabilized on a maintenance dose of digoxin, a 13% to 19% increase in plasma digoxinlevels occurred at six hours postdose.
In a study involving healthy subjects receiving flecainide acetate 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 acetate 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 acetate and propranolol on the PR interval were less than additive. In flecainide acetate 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 acetatehas been used in a large number of patients receiving diuretics ithout 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 gram 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 increase two-fold or more in some patients, if flecainide dosage is not reduced. (SeeDOSAGE AND ADMINISTRATION)
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 acetate and either disopyramide or verapamil Because both of these drugs have negative inotropic properties and the effects of coadministration with flecainide acetate are unknown, neither disopyramide or verapamil should be administered concurrently with flecainide acetate 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 acetate 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 acetate 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 acetate 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 acetate in the fetus, infant, or child have not been established in double-blind, randomized, placebo-controlled trials (seeCLINICAL PHARMACOLOGY,WARNINGS, and DOSAGE AND ADMINISTRATION).
Hepatic Impairment. Since flecainide elimination from plasma can be markedly slower in patients with significant hepatic impairment, flecainide acetate 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 dosage (see DOSAGE AND ADMINISTRATION, Plasma Level Monitoring); dosage increases should be made very cautiously when plasma levels have plateaued (after more than four days). [1]
References
- ↑ "FLECAINIDE ACETATE TABLET [APOTEX CORP.]". Retrieved 11 March 2014.
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