What is moxonidine?

Moxonidine: A Centrally Acting Antihypertensive Agent

Moxonidine is a centrally acting antihypertensive medication that selectively activates imidazoline I1 receptors with only minor activity at alpha2-adrenoceptors, but it is NOT recommended for patients with heart failure with reduced ejection fraction (HFrEF) due to increased mortality risk. 1

Mechanism of Action and Pharmacology

• Moxonidine acts centrally to reduce peripheral sympathetic activity by selectively binding to imidazoline I1 receptors in the rostral ventro-lateral medulla, resulting in decreased peripheral vascular resistance 2, 3
• It has 33 times higher affinity for imidazoline I1 receptors compared to alpha2-adrenoceptors, distinguishing it from older centrally acting agents like clonidine 3
• After oral administration, it has high bioavailability (approximately 90%), with a half-life of about 2.5 hours, though its antihypertensive effect lasts longer 3
• It is primarily excreted unchanged in the urine, with minimal biotransformation 3

Clinical Use

• Moxonidine is indicated for the treatment of essential hypertension, typically administered once daily 4, 5
• The usual dosage is 0.4 mg daily, with an initial dose of 0.2 mg/day 4
• It can be used as monotherapy in mild to moderate hypertension or as adjunctive therapy in combination with other antihypertensive agents 2, 5
• It may be particularly beneficial in patients with metabolic syndrome or diabetes mellitus, as it improves metabolic profile in these populations 2, 5

Safety and Adverse Effects

• The most common adverse effects include dry mouth (8-9%), somnolence (5-8%), headache (6%), and dizziness 6
• The incidence and severity of dry mouth and somnolence tend to decrease with continued use over time 6
• It may precipitate or exacerbate depression, bradycardia, and orthostatic hypotension 1
• Sudden cessation of treatment can produce a withdrawal syndrome 1

Important Contraindications and Warnings

• Moxonidine is contraindicated in patients with heart failure with reduced ejection fraction (HFrEF) due to increased mortality risk 1
• European Society of Cardiology guidelines explicitly recommend against using moxonidine to reduce blood pressure in HFrEF patients (Class III recommendation, Level of Evidence B) 1
• It should not be used as a first-line antihypertensive agent and is recommended only when there is intolerance or lack of efficacy of other antihypertensive medications 1

Place in Therapy

• Moxonidine is generally considered a second or third-line antihypertensive agent 1
• It may be particularly useful in patients with:
  • Metabolic syndrome or diabetes mellitus due to favorable metabolic effects 2, 5
  • Hypertension associated with mental stress 5
  • Need for combination therapy in resistant hypertension 4, 5
• It has low potential for drug interactions, making it suitable for patients on multiple medications 2, 6

Monitoring

• Blood pressure should be regularly monitored during treatment 1
• Patients should be assessed for signs of depression, bradycardia, and orthostatic hypotension 1
• Caution is advised when discontinuing therapy to avoid withdrawal symptoms 1