Is there a clinically significant interaction between flecainide and escitalopram. If there is, wil

Fråga: Is there a clinically significant interaction between flecainide and escitalopram. If there is, will a dose adjustment of flecainide be a way to avoid consequences of the interaction?

The question relates to a patient being treated with flecainide and bisoprolol. Due to depression the patient´s physician wants to start treatment with escitalopram.

Sammanfattning: In conclusion there is a possibility for an interaction between flecainide and escitalopram, but the clinical relevance of this is uncertain. Mesurements of flecainide concentrations are recommended.

Svar: Flecainide is an antiarrhytmic agent with a narrow therapeutic range that in a large extent is metabolized by CYP2D6. Approximately 50-70% is being metabolized by CYP2D6 and 30-50% is excreted unchanged in the urine (1).

In an extensive search in relevant databases and literature we have found no data concerning a possible interaction between flecainide and escitalopram. However, we have found data regarding a mechanistically similar interaction between escitalopram and metoprolol (2). Escitalopram has been shown to inhibit CYP2D6 in a concentration-dependent manner (2). In one study the single-dose pharmacokinetics of metoprolol was used as a marker for CYP2D6 activity. The exposition for metoprolol (n=16) was measured before and after 17 days of treatment with escitalopram (20 mg/day) and it increased by 41% (from 1217 +/- 293 to 1721 +/- 339 h*ng/mL) when the AUC:s were compared (3). In the same study the effects of sertraline on metoprolol pharmacokinetics where studied (n=16) and the exposition increased by approximately 39% (AUC from 1120 +/- 136 to 1559 +/- 150 h*ng/mL) after 17 days of sertraline treatment (100 mg/day) (3).

As flecainide to some extent is excreted unchanged in the urine it is possible that the interaction with escitalopram will have less clinical effects than for metoprolol (in a patient with normal renal function). However, the effect is probably not negligible and measurements of flecainide concentrations before and during treatment with escitalopram are recommended.

There is also a possible interaction between bisoprolol and escitalopram, as bisoprolol to some extent (50%) is metabolized by CYP2D6. However, as 50% is excreted unchanged in the urine and the therapeutic range for bisoprolol is wide this interaction should have minor clinical relevance. Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999 Cipralex. Summary of product characteristics (SPC) (Lundbeck) Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS et al. Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. J Clin Psychopharmacol 2007;27(1):28-34.