SAFETY AND TOLERABILITY OF MOXONIDINE IN THE TREATMENT OF HYPERTENSION

Classical centrally acting antihypertensive agents lower blood pressur e by reducing excessive sympathetic tone; however, their clinical use is limited by an adverse effect profile resulting from alpha 2-adrenoc eptor agonism. Moxonidine is a new centrally acting agent showing sele ctive agonism of imidazoline Il receptors, but very little a2-adrenoce ptor agonism. The safety and tolerability of moxonidine was reviewed o ver an 8-year period (1989 to 1997), including 74 clinical trials and an estimated 370 000 patient-years of exposure. Dry mouth and somnolen ce were the most frequently reported adverse events, followed by heada che and dizziness. In phase II to IV controlled studies in patients wi th hypertension (n = 1460), the incidence of dry mouth was 8 to 9%, so mnolence 5 to 8% and headache 6%, as recorded by spontaneous reporting ; the percentage of patients discontinuing treatment because of advers e events did not exceed 4%. Subgroup analyses revealed no differences in adverse events related to age or gender. Moxonidine did not exacerb ate concomitant conditions such as diabetes mellitus or chronic obstru ctive pulmonary disease, or interact pharmacokinetically with concurre nt 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-marketin g surveillance of the adverse effect profile of moxonidine detected 2 additional adverse effects: nausea and allergic skin reactions. The sa fety profile of moxonidine, combined with proven antihypertensive effi cacy, suggests that it may have an important role to play in the manag ement of mild-to-moderate hypertension.