Are there any interactions between Remeron (mirtazapine) and Xatral (alfuzosine)?/nThe question con

Fråga: Are there any interactions between Remeron (mirtazapine) and Xatral (alfuzosine)?

The question concerns the warning label in the Swedish Catalogue of Approved Medical Products (FASS 2001) about the combined use of alfuzosin and other alpha-adrenergic receptor blockers.

Sammanfattning: In summary, we have not found any data about possible interactions between mirtazapine and alfuzosine. One might speculate about a small risk of impaired effect by alfuzosine during treatment with mirtazapine, but there are no clinical reports available in support of this.

Svar: Despite an extensive literature search, no data on interactions between the two drugs was found.

Furthermore, the enzymes responsible for alfuzosine metabolism have not been identified, which makes pharmacokinetic interactions with mirtazapine difficult to assess. However, concerning possible pharmacodynamic interactions, there is space for hypothetical reasoning as follows:

Alfuzosine acts by blocking alpha-adrenergic receptors in the urethra (1). This antagonizes urethral constriction which otherwise is mediated by alpha1A receptor stimulation (2). Mirtazapine has alpha2 receptor-antagonistic properties (3) leading to enhanced adrenergic synaptic activity. In theory, this might also lead to enhanced adrenergic stimulation of the urethra and a challenge to the blocking properties of alfuzosin. The risk would therefore be an impaired therapeutic effect of alfuzosine during treatment with mirtazapine. However, since peripheral adrenergic effects (direct or indirect) of mirtazapine have been described as negligible (3, 4), eg on the cardiovascular system, it seems unlikely that mirtazapine has any clinically significant effect on the urethra.

Mirtazapine is a potent histamin1 receptor antagonist, which leads to sedation as a prominent side effect of the drug. However, according to the SPC the drug has been described to lack anticholinergic action (3, 4), which otherwise would have meant a significant risk of urinary retention in a patient with obstructive prostate hyperplasia.

In the Swedish adverse drug reactions register (5), there are for mirtazapine in total 2 reports on urinary retention, 2 reports about micturation problems, and 3 reports on urinary incontinence. The corresponding figures for the group of SSRI antidepressants are in total 27, 22, and 12, respectively.