Clonidine

Clonidine is a central alpha 2 adrenergic agonist that lowers blood pressure and sympathetic outflow. It has also been used for opioid withdrawal symptoms, menopausal flushing, attention deficit hyperactivity disorder, spinal analgesia and sedation. The key hazard is rebound hypertension after abrupt withdrawal.

Classification. Centrally acting alpha 2 agonist; imidazoline receptor agonist.

Mechanism. Stimulates presynaptic alpha 2 receptors and imidazoline receptors in the brainstem, reducing noradrenaline release, heart rate, peripheral resistance and renin release.

Pharmacodynamics. Oral onset in 30 to 60 minutes, peak 2 to 4 hours, effect 8 to 12 hours. Causes sedation, dry mouth, bradycardia and reduced blood pressure; an initial transient pressor effect can follow rapid IV injection.

Pharmacokinetics. Oral bioavailability 75 to 95%. Half life 12 to 16 hours, longer in kidney impairment. About 40 to 60% is excreted unchanged in urine; the remainder is metabolised in the liver.

Hypertension, adult (not first line).

• Start 50 to 100 micrograms orally twice or three times daily.

• Increase by 50 to 100 micrograms every 1 to 2 weeks.

• Usual maintenance 200 to 600 micrograms daily in two or three divided doses.

• Maximum 2.4 mg daily; doses over 1.2 mg daily rarely add benefit.

• Transdermal patch 100 micrograms/24 hours weekly, titrated to 300 micrograms/24 hours, where available.

Hypertensive emergency, adult (second line). 150 micrograms IV over at least 10 minutes, repeated if needed. Labetalol and nitrates are preferred and cause fewer sedative effects.

Opioid withdrawal, adult. 100 to 300 micrograms orally every 6 to 8 hours as needed, to a maximum of 1.2 mg daily, with blood pressure checked before each dose and held for pressure under 90/60 mmHg. Treat for 5 to 10 days and taper over 2 to 4 days.

Menopausal flushing, adult (off label). 50 micrograms orally twice daily, increased to 75 micrograms twice daily after 2 weeks.

Attention deficit hyperactivity disorder, children 6 to 17 years (modified release). Start 100 micrograms at night, increase by 100 micrograms weekly, usual range 200 to 400 micrograms daily in one or two doses, maximum 400 micrograms daily. Specialist use.

Epidural, cancer pain (specialist). 30 micrograms/hour infusion, adjusted by pain specialist.

Children, hypertension. 5 to 25 micrograms/kg daily in 3 or 4 divided doses, maximum 25 micrograms/kg daily; specialist.

Contraindications. Severe bradycardia; sick sinus syndrome; second or third degree atrioventricular block; hypersensitivity; for epidural use, obstetric and postpartum analgesia and obstetric haemorrhage.

Warnings. Abrupt withdrawal causes rebound hypertension, tachycardia, anxiety and sweating 18 to 72 hours after the last dose; taper over 2 to 4 days. If a beta blocker is also taken, stop the beta blocker several days before clonidine, since unopposed alpha stimulation can cause a severe pressor response. Sedation, depression, constipation, and impaired driving.

Adverse effects. Dry mouth, sedation, dizziness, constipation, bradycardia, orthostatic hypotension, depression, sexual dysfunction, fluid retention, skin reaction with patches.

Interactions. Beta blockers: bradycardia and worse rebound hypertension. Verapamil and diltiazem: bradycardia and atrioventricular block. Digoxin: bradycardia. Tricyclic antidepressants, mirtazapine and antipsychotics: reduce effect and cause hypotension. Additive sedation with alcohol, opioids and benzodiazepines.

Special groups.

• Pregnancy: has been used where methyldopa or labetalol cannot be used; limited data; avoid in labour.

• Breastfeeding: passes into milk; infant sedation and low blood pressure possible; avoid or monitor closely.

• Older adults: start at 50 micrograms; risk of hypotension, falls and confusion.

• Kidney impairment: eGFR under 30 mL/min: use half the usual dose and titrate slowly. It is not removed by dialysis.

• Liver impairment: caution; monitor tolerance.

Overdose. Coma, bradycardia, hypotension, miosis and respiratory depression, which mimic opioid poisoning; supportive care, atropine for bradycardia, and naloxone may help; seek toxicology advice.

Formulations. Tablets 25, 100 and 150 micrograms; modified release tablets 100 micrograms; injection 150 micrograms/mL; patches.

Administration. Oral, with or without food. Give the larger dose at bedtime to reduce daytime sedation. IV: dilute in 10 mL 0.9% sodium chloride and inject slowly.

Baseline. Blood pressure sitting and standing, heart rate, ECG if bradycardia, mood, renal function.

Monitoring. Pressure and pulse at each dose change; sedation; mood; for withdrawal use: pressure before each dose. After stopping, check pressure daily for 3 days.

Stopping. Taper by 100 to 200 micrograms every 2 to 3 days.

Common prescribing errors. Stopping abruptly or omitting doses in patients who are admitted or fasting; using it with a beta blocker without a withdrawal plan; confusing it with an opioid overdose.