Safety and tolerability of moxonidine in the treatment of hypertension.

Classical centrally acting antihypertensive agents lower blood pressure by reducing excessive sympathetic tone; however, their clinical use is limited by an adverse effect profile resulting from alpha2-adrenoceptor agonism. Moxonidine is a new centrally acting agent showing selective agonism of imidazoline I1 receptors, but very little alpha2-adrenoceptor agonism. The safety and tolerability of moxonidine was reviewed over an 8-year period (1989 to 1997), including 74 clinical trials and an estimated 370000 patient-years of exposure. Dry mouth and somnolence were the most frequently reported adverse events, followed by headache and dizziness. In phase II to IV controlled studies in patients with hypertension (n = 1460), the incidence of dry mouth was 8 to 9%, somnolence 5 to 8% and headache 6%, as recorded by spontaneous reporting; the percentage of patients discontinuing treatment because of adverse events did not exceed 4%. Subgroup analyses revealed no differences in adverse events related to age or gender. Moxonidine did not exacerbate concomitant conditions such as diabetes mellitus or chronic obstructive pulmonary disease, or interact pharmacokinetically with concurrent medications such as hydrochlorothiazide, digoxin and glibenclamide (glyburide). Coadministration of moxonidine with lorazepam resulted in small additional impairments in tasks requiring attention. A similar distribution of adverse events was observed in uncontrolled studies (n = 1058). The incidence and severity of dry mouth and somnolence were found to decrease with increasing exposure to moxonidine over a period of up to 2 years. Serious adverse events were rare in all trials and could not be attributed to administration of moxonidine. Post-marketing surveillance of the adverse effect profile of moxonidine detected 2 additional adverse effects: nausea and allergic skin reactions. The safety profile of moxonidine, combined with proven antihypertensive efficacy, suggests that it may have an important role to play in the management of mild-to-moderate hypertension.