Are there any pharmacodynamic interactions between brimonidine (Alphagan) and sotalol?/nA woman wit

Fråga: Are there any pharmacodynamic interactions between brimonidine (Alphagan) and sotalol?

A woman with sick sinus syndrome has received a pacemaker. To eliminate tachycardia episodes, medication with sotalol 40mg every 12 hours is considered. The patient has also glaucoma and concomitant use of brimonidine eye-drops (one drop of a 2 per cent solution bid) is considered.

Sammanfattning: There are no reports of interactions between brimonidine and beta-blockers. In Swedis and Intdis, there is a small number of reported cardiovascular systemic effects during brimonidine medication. Clonidine, another alpha-2-receptor agonist has caused withdrawal hypertension, aggravated by beta-blocker co-medication. Since brimonidine is absorbed and systemic central nervous effects have been described, there is a theoretical risk of similar effects in this drug. When beta-blockers and brimonidine are used simultaneously, it is prudent to monitor blood pressure particularly upon cessation of brimonidine.

Svar: In the Swedish catalogue of approved medical products, caution is advised when using other adrenoceptor-active substances together with brimonidine (1). According to the manufacturer, this statement is due to a theoretical risk of effects on blood pressure (2). Brimonidine is absorbed to some extent and central nervous effects (headache, sedation) have been described (2). However, there are no reports of cardiovascular effects, and the fear is entirely based on comparisons to clonidine, an alpha-2-receptor agonist used systemically (2).

No information regarding interactions between brimonidine and beta-blockers was found in Medline, Drugline or standard pharmacological literature. Nor were there any reports of systemic effects of brimonidine in ophthalmological use. In Swedis, there is one case of aggravated angina pectoris and one of myocardial infarction, where a connection to brimonidine medication is assessed possible (3). The WHO adverse drug reactions database Intdis contains 16 cases of cardiovascular systemic effects during treatment with brimonidine (4). The reports include cardiac failure, hypotension and hypertension. However, these reports are not evaluated regarding causality due to the differences of the reporting systems in the participating countries. Although the number of reports is rather small, one should keep in mind that brimonidine is a relatively new drug on the market, with a limited number of patients exposed.

Brimonidine is, similar to clonidine, a selective alpha-2-receptor agonist (5-6). In patients co-medicated with clonidine and beta-blockers, severe withdrawal hypertension has been seen upon cessation of clonidine (7-8). The mechanism is unclear, but it is hypothesised that clonidine withdrawal leads to increased catecholamine levels, resulting in vasoconstriction mediated by alpha-1-receptors. Due to the effects of the beta-blocker, this constriction is unopposed by beta-2-mediated vasodilation, resulting in aggravated hypertension (8).