Drugs

, Volume 44, Issue 6, pp 993–1012

Moxonidine

A Review of its Pharmacology, and Therapeutic Use in Essential Hypertension
  • Paul Chrisp
  • Diana Faulds
Drug Evaluation

Summary

Synopsis

Interest in centrally acting antihypertensive agents has recently been renewed with the development of drugs that are associated with fewer central adverse effects (e.g. sedation, dry mouth) than the older drugs in this class. Moxonidine reduces sympathetic outflow and hence lowers blood pressure through stimulation of central imidazoline receptors.

Blood pressure is decreased by 10 to 20% during moxonidine treatment, with about 70% of patients with mild to moderate hypertension achieving a diastolic pressure of < 90mm Hg. The relatively few published comparative studies demonstrate that moxonidine has efficacy comparable with that of clonidine, prazosin, atenolol, nifedipine, captopril and hydrochlorothiazide. It is at least as well tolerated as these agents in trials and, importantly, appears to cause less sedation and dry mouth than clonidine. Compliance may be aided by the once-or twice-daily administration schedule with moxonidine, and dosage adjustment is only necessary in patients with moderate renal impairment.

While its published clinical data base needs further expanding, moxonidine thus appears to be a more attractive option than oral clonidine, and may be considered along with the other classes of drug used to treat patients with mild to moderate hypertension.

Pharmacodynamic Properties

Moxonidine is a selective high affinity imidazoline I1-receptor agonist, demonstrating up to 600-fold greater selectivity at this recently discovered receptor site compared with α2-receptors, depending on the tissue, species and ligand used. Binding at central imidazoline receptors in the rostral ventrolateral medulla correlates significantly with the degree of blood pressure reduction in vivo Pretreatment with BDF 6143 (a partial α2-antagonist with affinity for imidazoline sites) in animals abolished the moxonidine-induced decrease in blood pressure. Moxonidine is a full selective agonist at α2-adrenoceptors in vitro (up to 288-fold more potent vs α1-rèceptor binding). The hypotensive activity of moxonidine did not correlate significantly with α2-binding.

Plasma levels of noradrenaline (norepinephrine) at rest were decreased by 26 to 33.5% in hypertensive patients by moxonidine, and plasma renin activity decreased by 23 to 35.5%. Four hours after moxonidine administration, plasma adrenaline (epinephrine) levels were similar to baseline values, but after 6 to 9 hours there were significant decreases of 27 and 39%.

The result of this decreased sympathetic outflow is a 10 to 15% reduction in resting systolic blood pressure and a 10 to 18% reduction in diastolic pressure in hypertensive patients after single oral doses of moxonidine 0.25 or 0.4mg. Heart rate, cardiac output and stroke volume are unaffected, and signs of left ventricular hypertrophy improve during moxonidine administration.

Salivary flow is decreased by moxonidine in animals and humans, and the drug causes less sedation than clonidine.

Pharmacokinetic Properties

Peak plasma moxonidine concentrations (Cmax) of 1.3 to 2 μg/L occur within about an hour of single oral doses of moxonidine 0.2 to 0.3mg in healthy volunteers and hypertensive patients with normal renal function. Bioavailability is 88%, and the drug does not accumulate with repeated administration. Food has no significant effect on absorption or bioavailability of moxonidine.

The area under the plasma concentration-time curve (AUC) is 3.7 to 7.4 μg/L · h, and elimination half-life (t½β) is between 2 and 3 hours. The duration of antihypertensive effect following moxonidine administration (up to 12 hours) is greater than the t½β of the drug, perhaps signifying slower clearance from the central site of action, or possibly resulting from the delayed decrease in plasma adrenaline levels. Total plasma clearance (CL) is 43.6 to 69 L/h, with approximately 67% cleared renally. 58 to 60% of an absorbed dose is excreted unchanged in the urine. Thus, in patients with renal impairment, Cmax AUC, and t½β are increased, and CL and renal clearance are decreased.

Therapeutic Use

In noncomparative studies, blood pressure was reduced by between 10 and 20% in patients with mild to moderate essential hypertension taking moxonidine usually in daily doses of 0.2 to 0.4mg for up to 1 year. Diastolic pressure was reduced to ⩽ 90mm Hg in 60 to 70% of patients. Blood pressure gradually returned to baseline 1 to 3 days after discontinuing moxonidine, but a rebound phenomenon was not evident.

Mostly small comparative trials reveal an equivalent efficacy between moxonidine 0.2mg once or twice daily and clonidine 0.2mg once or twice daily, prazosin 1 to 7.5 mg/day, atenolol 50 or 100mg once daily, sustained release nifedipine 20mg once or twice daily, captopril 25mg once or twice daily, and hydrochlorothiazide 25 or 50 mg/day, both in terms of degree of blood pressure reduction and in the proportion of patients achieving goal blood pressure.

Clinical Tolerability

Moxonidine was well tolerated in clinical studies, but it caused dry mouth in approximately 15% of patients, usually within the first few weeks of treatment. Tiredness (5.6%), restlessness (1.9%), dizziness (1.8%), autonomic dystony (1.2%) and headache (1.1%) occurred in 155 patients during 12 months’ moxonidine therapy. Sedation was not reported.

In comparative trials, fewer patients reported dry mouth and sedation during moxonidine compared with clonidine treatment. Moxonidine was less likely to cause orthostatic hypotension than prazosin, and was at least as well tolerated as atenolol, nifedipine and captopril in these studies.

Dosage and Administration

The recommended starting dose of moxonidine in patients with mild to moderate essential hypertension is 0.2mg orally once daily with or after food, increasing to 0.4 mg/day after 3 weeks if necessary. The maximum daily dosage is 0.6mg in patients with normal renal function, and 0.4mg in those with moderate renal dysfunction.

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Copyright information

© Adis International Limited 1992

Authors and Affiliations

  • Paul Chrisp
    • 1
  • Diana Faulds
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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