Moxonidine (Physiotens®, Moxon®, Cynt®) is an orally administered imidazoline compound with selective agonist activity at imidazoline I1 receptors and only minor activity at α2-adrenoceptors. Moxonidine acts centrally to reduce peripheral sympathetic activity, thus decreasing peripheral vascular resistance. In patients with mild to moderate hypertension, moxonidine reduces blood pressure (BP) as effectively as most first-line antihypertensives when used as monotherapy and is also an effective adjunctive therapy in combination with other antihypertensive agents. It improves the metabolic profile in patients with hypertension and diabetes mellitus or impaired glucose tolerance, is well tolerated, has a low potential for drug interactions and may be administered once daily in most patients. Thus, moxonidine is a good option in the treatment of patients with mild to moderate hypertension, particularly as adjunctive therapy in patients with the metabolic syndrome.
Moxonidine is a centrally acting selective agonist at imidazoline I1 receptors, tor which it has an affinity >30-fold that for α2-adrenoceptors. Moxonidine inhibits peripheral sympathetic activity, which decreases peripheral vascular resistance and results in significant decreases in systolic and diastolic BP (SBP and DBP). Moxonidine has minimal effect on cardiac haemodynamics and reduces left ventricular mass. Markers of endothelial dysfunction and end-organ damage, including microalbuminuria, improved in hypertensive patients who achieved BP control with moxonidine. Moxonidine also improved the metabolic profile of patients with hypertension and type 2 diabetes or impaired glucose tolerance. Oral moxonidine is rapidly absorbed, although the maximum antihypertensive effect occurs 3–4 hours after administration.
Oral bioavailability is 88% and is unaffected by food. No first-pass metabolism occurs and moxonidine is mostly excreted unchanged in the urine.
In well designed, 8-week trials, monotherapy with moxonidine 0.2–0.6 mg/day reduced sitting DBP to a significantly greater extent than placebo (mean change from baseline −10.7 to −13.2 vs −2.3 to −9mm Hg) in patients with mild to moderate essential hypertension. Sitting SBP also improved from baseline to a significantly greater extent with moxonidine than with placebo (mean −19.5 to −24.9 vs −1.2 to −13mm Hg). Reductions in sitting SBP and DBP with moxonidine 0.2–0.8 mg/day at 8 weeks were similar to those with enalapril 5–20mg once daily, atenolol 50–100 mg/day (except in postmenopausal women where atenolol reduced BP to a greater extent than moxonidine), hydrochlorothiazide 25mg once daily and rilmenidine 1–2 mg/day. At 26 weeks, reductions in sitting SBP and DBP with moxonidine 0.2–0.4 mg/day were similar to those with nifedipine sustained release 20–40 mg/day.
Once-daily adjunctive moxonidine 0.4mg was also effective in patients with mild to moderate hypertension in well designed trials. In patients who did not respond to moxonidine monotherapy, mean improvements in sitting DBP at 4 weeks were −7.3mm Hg with moxonidine 0.4mg once daily plus amlodipine 5mg once daily, −4.8mm Hg with moxonidine 0.4mg once daily plus enalapril 10mg once daily and −3.2mm Hg with moxonidine 0.4mg once daily plus hydrochlorothiazide 12.5mg once daily. In another trial, changes in sitting SBP and DBP after 8 weeks’ treatment were significantly greater with once-daily moxonidine 0.4mg plus hydrochlorothiazide 25mg than with the respective monotherapies (−27 vs −20 and −22mm Hg and −16 vs −12 and −13mm Hg).
Moxonidine was generally well tolerated in clinical trials in patients with mild to moderate hypertension. In placebo-controlled monotherapy trials, 36–43% of moxonidine recipients experienced treatment-emergent adverse events versus 22–29% of placebo recipients and ≈32% and 35% of enalapril and hydrochlorothiazide recipients, respectively. Dry mouth was the most common adverse event with moxonidine monotherapy, affecting 11–20% of patients; other all-cause adverse events included diarrhoea, headache, bronchitis, nausea, dizziness and back pain. Other than dry mouth, asthenia and fatigue, adverse events in moxonidine monotherapy recipients were not generally related to α2-adrenoceptor inhibition. No new adverse events were reported in combination therapy trials.
Moxonidine was also well tolerated in a pooled analysis of postmarketing surveillance studies in 91 170 patients, about two-thirds of whom received moxonidine as monotherapy. Adverse events affected 9.4% of patients, causing 1.8% to discontinue treatment, and were generally not related to dosage, treatment duration, sex or age; dry mouth affected 4.2% of patients aged >65 years versus 2.7% of those aged <40 years.
- 4.Brookes L. New definition of hypertension proposed [online]. Available from URL: http://www.medscape.com [Accessed 2005 Jun 9]
- 5.Prichard BNC, Owens CWI, Graham BR. Pharmacology and clinical use of moxonidine, a new centrally acting sympatholytic antihypertensive agent. J Hum Hypertens 1997 Aug; 11 Suppl. 1: 29–45Google Scholar
- 6.Schaefer HG, Toublanc N, Weimann H-J. The pharmacokinetics of moxonidine. Rev Contemp Pharmacother 1998; 9(7): 481–90Google Scholar
- 9.Prichard BNC, Graham BR. The use of moxonidine in the treatment of hypertension. J Hypertens 1997 Jan; 15 Suppl. 1: 47–55Google Scholar
- 10.Schafers RF, Holzgreve H, Distler A, et al. Double blind, multicentre comparison of moxonidine and enalapril and their effects on blood pressure and left ventricular mass: results of the MOXENA study [abstract no. P1051]. J Hypertens 2002 Jun; 20 Suppl. 4: 249Google Scholar
- 11.Waters J, Ashford J, Jäger B, et al. Use of moxonidine as initial therapy and in combination in the treatment of essential hypertension: results of the TOPIC (Trial Of Physiotens In Combination) study. J Clin Basic Cardiol 1999; 2(2): 219–24Google Scholar
- 19.Farsang C, Finta E, Kerkovits L, et al. Moxonidine possibly inhibits angiotensin converting enzyme inhibitor (ACEi)-induced cough in patients with essential hypertension: a multi-centre, open pilot study [abstract no. P2.216]. J Hypertens 2003 Jun; 21 Suppl. 4: 183Google Scholar
- 20.Troussov V, Acsenov C. Moxonidine (Phisiotens) in treatment of hypertension in elderly patients with type 2 diabetes mellitus [abstract no. 2543]. Diabetes Metab 2003 Aug; 29 (4 Suppl.): 314Google Scholar
- 21.Aparina T, Britov A, Gomazkov O. Effects of enalapril and moxonidine on left ventricular hypertrophy in relation to insulin resistance in hypertensive patients [abstract no. P1.198]. J Hypertens 2003 Jun; 21 Suppl. 4: 75Google Scholar
- 22.Reznik L, Koval S, Koval D, et al. The effects of moxonidine long-term monotherapy on endothelial vasoactive factors in patients with hypertension [abstract no. 99]. J Hypertens 2003 Jun; 21 Suppl. 4: 336Google Scholar
- 23.Sanjuliani AF, Genelhu de Abreu V, Ueleres Braga J, et al. Effects of moxonidine on the sympathetic nervous system, blood pressure, plasma renin activity, plasma aldosterone, leptin, and metabolic profile in obese hypertensive patients. J Clin Basic Cardiol 2004; 7: 19–25Google Scholar
- 24.Orynchak MA, Neyko EM, Chovganyuk OS. Role of moxonidine in insulin secretion and endothelial dysfunction in the patients with insulin resistance [abstract no. P-538]. Am J Hypertens 2005 May 2; 18(5): 202–3Google Scholar
- 25.Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin. Hannover: Solvay Pharmaceuticals, 2005. (Data on file)Google Scholar
- 26.Haenni A, Lithell H. Moxonidine improves insulin sensitivity in insulin-resistant hypertensives. J Hypertens Suppl 1999; 17 Suppl. 3: S29–35Google Scholar
- 27.Kaaja R, Manhem K, Tuomilehto J. Treatment of postmenopausal hypertension with moxonidine, a selective imidazoline receptor agonist. Int J Clin Pract 2004 Mar; Suppl. 139: 26–32Google Scholar
- 28.Jacob S, Klimm HJ, Rett K, et al. Effects of moxonidine vs. metoprolol on blood pressure and metabolic control in hypertensive subjects with type 2 diabetes. Exp Clin Endocrinol Diabetes 2004 Jun; 112(6): 315–22Google Scholar
- 39.Solvay Healthcare Limited. Physiotens tablets 200, 300 & 400 micrograms: summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk [Accessed 2005 Jun 13]
- 41.Sleight P. The sympathetic nervous system in hypertension: differing effects of drug treatment. Eur Heart J 1998 Jun; 19 Suppl. F: 39–44Google Scholar
- 43.Mogensen CE. New treatment guidelines for a patient with diabetes and hypertension. J Hypertens Suppl 2003 Mar; 21 Suppl. 1: S25–30Google Scholar
- 49.Prichard BNC, Küster LJ, Hughes PR, et al. Dose relation of blood pressure reduction with moxonidine: findings from three placebo- and active-controlled randomized studies. J Clin Basic Cardiol 2003; 6: 49–51Google Scholar
- 56.Trieb G, Jäger B, Hughes PR, et al. Long-term evaluation of the antihypertensive efficacy and tolerability of the orally acting imidazoline I1 receptor agonist moxonidine in patients with mild-to-moderate essential hypertension. Eur J Clin Res 1995; 7: 227–40Google Scholar
- 57.Rayner B, Coetzer E. Moxonidine is effective for controlling blood pressure in patients with resistant hypertension [abstract]. Cardiovasc J S Afr 2005 Mar; 16 (2 Suppl. 1): 20Google Scholar
- 60.Confirmation of the effectiveness and tolerability profile of the antihypertensive moxonidine: data from 14 post-marketing surveillance studies involving >91,000 patients. Hannover: Solvay Pharmaceuticals, 2005. (Data on file)Google Scholar
- 62.Peverill RE. Hypertension guidelines, meta-analyses and clinical trials: do we assume too much? Med J Aust 2005; 182(2): 82–Google Scholar
- 67.Pater C, Bhatnagar D, Berrou J-P, et al. A novel approach to treatment of hypertension in diabetic patients: a multicenter, double-blind, randomized study comparing the efficacy of combination therapy of eprosartan versus ramipril with low-dose hydrochlorothiazide and moxonidine on blood pressure levels in patients with hypertension and associated diabetes mellitus type 2. Rationale and design [ISRCTN55725285]. Curr Control Trials Cardiovasc Med 2004 Oct 1; 5(1): 9PubMedCrossRefGoogle Scholar