Moxonidine

Approved Indications:

• Essential Hypertension (Stage 1–2):
  As monotherapy or adjunctive therapy to achieve target blood pressure in adults.
• Renal Hypertension:
  Effective in patients with mild to moderate hypertension associated with renal impairment.

Off-label (Clinically Accepted) Uses:

• Hypertensive diabetic nephropathy:
  When ACE inhibitors or ARBs are insufficient or contraindicated.
• Combination-resistant hypertension:
  Used with diuretics, ACE inhibitors, ARBs, beta-blockers, or calcium channel blockers when blood pressure remains uncontrolled.

Adults:

• Initial Dose: 0.2 mg orally once daily (morning).
• Maintenance Dose: Increase after 4 weeks to 0.4 mg/day if needed; maximum 0.6 mg/day in divided doses.

Elderly (>65 years):

• Same as adults but initiate with caution and use lower end of dosing range.

Renal Impairment:

• Mild to moderate impairment: no adjustment needed.
• Severe impairment (eGFR <30 mL/min): use maximum 0.4 mg/day; monitor closely.

Hepatic Impairment:

• Mild to moderate: no specific adjustment required.
• Severe hepatic dysfunction: not recommended due to insufficient data.

Pediatric Use:

• Not approved or recommended.

Administration Route:

• Oral; may be taken with or without food.

Moxonidine is a centrally acting antihypertensive agent that selectively stimulates imidazoline I₁ receptors in the brainstem, thereby reducing sympathetic nervous system outflow. This leads to decreased peripheral vascular resistance, lower heart rate, and a modest reduction in cardiac output, culminating in sustained blood pressure reduction. Its selectivity minimizes α₂-adrenergic receptor-mediated side effects often seen with older agents.

• Absorption:
  Rapid and nearly complete; peak plasma concentration ~1–2 hours after dosing.
  Bioavailability ~89%.
• Distribution:
  Volume of distribution ~1 L/kg; low (~20%) plasma protein binding.
• Metabolism:
  Minimally hepatic; majority excreted unchanged in urine.
• Elimination:
  Terminal half-life ~2.2 hours; effective duration ~24 hours due to sustained action.
  Excretion: ~90% unchanged renally, ~6% fecally.
• Onset of Action:
  Blood pressure begins to fall within 2 hours; full effect observed after 4–8 weeks.

• Pregnancy:
  No reliable human data; animal studies show no teratogenic effects but limited in scope. Use only when clearly needed—benefit must outweigh risk.
• Lactation:
  Excreted in low concentrations in breast milk. Use with caution; monitor infant for hypotension or irritability. Preferably avoid during breastfeeding with alternative antihypertensives.

• Primary Class: Centrally Acting Antihypertensive (Imidazoline Receptor Agonist)
• Subclass: Selective I₁-Receptor Agonist (Second-generation central antihypertensive)

• Known hypersensitivity to Moxonidine or any component of the formulation
• Severe bradycardia or atrioventricular block
• Hypotension
• Acute heart failure
• Pheochromocytoma
• Severe renal impairment (eGFR <15 mL/min), unless benefits justify use

• High‑Risk Patients:
  Elderly, those with coronary artery disease, cerebrovascular disease, or renal/hepatic impairment.
• Symptomatic Hypotension or Bradycardia:
  May occur, especially when used with other antihypertensives.
• Withdrawal Effects:
  Abrupt cessation can lead to rebound hypertension; taper gradually over 1–2 weeks.
• Central Nervous System Effects:
  Monitor for dizziness, fatigue, depression—especially during titration.
• Renal Function Monitoring:
  Due to high renal excretion, monitor periodically.

Common (≥5%):

• Dizziness
• Headache
• Fatigue
• Dry mouth
• Sleep disturbance

Less Common (1–5%):

• Bradycardia
• Hypotension
• Nausea
• Mild skin rash

Rare but Serious:

• Depression or mood alterations
• Exacerbation of heart block
• Hypersensitivity reactions
• Erectile dysfunction

Timing & Dose Dependence:

• CNS effects often appear during initiation or dose increases.
• Most side effects are dose-related and resolve with dose reduction.

• Additive Hypotensive Effect:
  With diuretics, ACE inhibitors, ARBs, beta-blockers—monitor blood pressure and heart rate.
• β-Blockers/Calcium Channel Blockers:
  Risk of pronounced bradycardia; monitor clinically.
• Alcohol or CNS Depressants:
  May worsen dizziness or sedation.
• Antidepressants (e.g., SSRIs, TCAs):
  Combined use may increase risk of depression or orthostatic hypotension.
• No significant interactions via CYP450 pathways due to limited hepatic metabolism.

• ESC/ESH 2021 Hypertension Guidelines:
  Moxonidine listed as useful in combination therapy, especially in patients with metabolic comorbidities due to neutral metabolic profile.
• EMA Review 2022:
  Reaffirmed favorable safety profile with updates to labeling on CNS side effects and withdrawal precaution.
• Emerging Evidence:
  Small studies show potential benefits on insulin resistance in hypertensive patients, but not yet reflected in standard guidelines.

• Temperature:
  Store at 20°C to 25°C (68°F to 77°F). Brief excursions to 15°C–30°C acceptable.
• Humidity and Light:
  Keep in original container, protect from moisture and light.
• Handling Precautions:
  Do not freeze; keep tightly sealed when not in use.
  Keep out of children’s reach.
  Discard unused portions if beyond expiry date or if tablet integrity is compromised.