Flecainide
Classification: CATC code: C01BC04
Summary
The antiarrhythmic effect of flecainide is dose dependent. Men may need higher doses of flecainide compared to women to achieve comparable effect. Studies in Japanese patients have shown a higher effect in women than men with the same doses, probably because women achieve a higher serum concentration than men at the same dose. The risk of QT prolongation and the ventricular tachycardia Torsade de Pointes is higher in women.
Additional information
Pharmacokinetics and dosing
The effect of CYP2D6 genotype on the pharmacokinetics of flecainide in Japanese patients (46 men, 12 women) with supraventricular tachyarrhythmia has been studied. Oral clearance of flecainide was higher in men than in women. Concentration-dose ratios were significantly higher in women than in men. No difference in the flecainide metabolic ratio between men and women was found, suggesting that the sex difference described did not involve CYP2D6 hepatic metabolism [1]. There is no difference between men and women in protein binding of flecainide, according to a study in healthy volunteers (11 men, 11 women) [2]. A cross-sectional trial examined the impact of patient’s sex on efficacy of flecainide in Japanese patients with supraventricular tachyarrhythmias (52 men, 20 women). The flecainide daily dose (50 mg single oral dose) did not differ between the sexes. Dose-efficacy curves showed that the effective doses for women were lower than those for men. With a daily dose of 2.9 mg/kg, clinically relevant efficacy occurred in 60% of the men compared to 95% of the women [3].
Effect
In the Japanese study mentioned above [3], clinically relevant efficacy of flecainide was achieved significantly less often in men than in women (60% vs. 95%). Although the daily dose did not differ between men and women, serum flecainide concentrations in men was significantly lower than those in women. Because the anti-arrhythmic effects of flecainide depend on its serum concentration, the sex-dependent efficacy of flecainide therapy is considered to be due to sex differences in flecainide pharmacokinetics. There was no significant sex difference in QRS duration, but QTc interval was significantly prolonged in women compared with men [3].
Adverse effects
No studies with a clinically relevant sex analysis regarding adverse effects of flecainide have been found.
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Updated: 2020-08-28
Date of litterature search: 2019-02-11
References
- Doki K, Homma M, Kuga K, Kusano K, Watanabe S, Yamaguchi I et al. Effect of CYP2D6 genotype on flecainide pharmacokinetics in Japanese patients with supraventricular tachyarrhythmia. Eur J Clin Pharmacol. 2006;62:919-26. PubMed
- Zordan R, Padrini R, Bernini V, Piovan D, Ferrari M. Influence of age and gender on the in vitro serum protein binding of flecainide. Pharmacol Res. 1993;28:259-64. PubMed
- Doki K, Homma M, Kuga K, Aonuma K, Sakai S, Yamaguchi I et al. Gender-associated differences in pharmacokinetics and anti-arrhythmic effects of flecainide in Japanese patients with supraventricular tachyarrhythmia. Eur J Clin Pharmacol. 2007;63:951-7. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-03-08.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson