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Flekainid

Klassificering: C

Preparat: Flecainide, Flekainid Sandoz, Flekainid STADA, Tambocor, Tambocor Meda Pharmaceuticals Ltd, Tambocor Retard

ATC kod: C01BC04

Substanser: flekainid, flekainidacetat

Sammanfattning

Den antiarytmiska effekten av flekainid är dosberoende. Män kan kräva högre doser av flekainid jämfört med kvinnor för att uppnå samma effekt. Studier på japanska patienter har visat större effekt hos kvinnor än män vid samma dosering sannolikt beroende på att kvinnor uppnår högre serumkoncentration jämfört med män vid samma dos.

Risken för QT-förlängning är högre hos kvinnor och därmed ökad risk för allvarlig kammartakykardi av typen Torsade de Pointes.

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 the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler män än kvinnor hämtade ut tabletter/kapslar innehållande flekainid (ATC-kod C01BC04) på recept i Sverige år 2018, totalt 3 769 män och 2 197 kvinnor. Det motsvarar 0,7 respektive 0,4 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-74 år hos män båda könen. I genomsnitt var tabletter/kapslar innehållande flekainid dubbelt så vanligt hos män [4].

Uppdaterat: 2019-05-27

Litteratursökningsdatum: 2019-02-11

Referenser

  1. 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
  2. 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
  3. 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
  4. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2018 [cited 2019-03-08.] länk

Författare: Linnéa Karlsson Lind

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson