Clonidine - Drug Monograph

Introduction

Clonidine is a centrally-acting alpha-2 adrenergic agonist that has been used clinically since the 1960s. Originally developed as a nasal decongestant, it was subsequently discovered to have potent antihypertensive properties. Today, clonidine is FDA-approved for hypertension management and has numerous off-label uses including ADHD treatment, opioid withdrawal management, menopausal flushing, and chronic pain conditions. It remains an important therapeutic option due to its unique mechanism of action and versatile clinical applications.

Mechanism of Action

Clonidine exerts its primary effects through stimulation of presynaptic alpha-2 adrenergic receptors in the central nervous system, particularly in the rostral ventrolateral medulla. This activation reduces sympathetic outflow from the CNS, resulting in decreased peripheral vascular resistance, heart rate, and blood pressure. Additionally, clonidine stimulates peripheral alpha-2 receptors, which may contribute to its sedative effects. The drug also has some affinity for imidazoline receptors, which may contribute to its antihypertensive effects and explain some of its additional therapeutic applications.

Indications

• Hypertension (as monotherapy or in combination with other antihypertensive agents)

• Attention deficit hyperactivity disorder (ADHD)
• Opioid withdrawal symptoms
• Menopausal hot flashes
• Tourette syndrome
• Chronic pain conditions (including neuropathic pain)
• Anxiety disorders
• Diabetic diarrhea

Dosage and Administration

• Initial dose: 0.1 mg orally twice daily
• Maintenance dose: 0.2-0.6 mg daily in divided doses
• Maximum dose: 2.4 mg daily

• Starting dose: 0.05 mg daily at bedtime
• Titration: Increase by 0.05 mg weekly
• Maintenance: 0.1-0.4 mg daily in divided doses

• Renal impairment: Use with caution; consider dose reduction
• Hepatic impairment: Use with caution
• Elderly: Start with lower doses due to increased sensitivity
• Pediatric: Safety and efficacy not established for hypertension; used off-label for ADHD

• May be taken with or without food
• Do not crush or chew extended-release formulations
• Transdermal patch: Apply to clean, dry, hairless area of upper arm or torso; rotate application sites

Pharmacokinetics

Contraindications

• Hypersensitivity to clonidine or any component of the formulation
• Patients with sinus node dysfunction or conduction defects (e.g., sick sinus syndrome, AV block)
• Concurrent use with other centrally-acting alpha-2 agonists

Warnings and Precautions

• Transdermal patch contains aluminum; remove before MRI to avoid skin burns

• Rebound hypertension may occur with abrupt discontinuation
• Use with caution in patients with cardiovascular disease, renal impairment, or history of depression
• May cause sedation; caution patients about operating machinery
• Orthostatic hypotension may occur
• Withdrawal syndrome possible with abrupt cessation (tachycardia, hypertension, agitation)
• Periodic eye examinations recommended due to possible retinal degeneration with long-term use

Drug Interactions

• Beta-blockers: Increased risk of bradycardia and heart block
• CNS depressants (alcohol, benzodiazepines, opioids): Enhanced sedative effects
• Tricyclic antidepressants: May diminish antihypertensive effects
• Other antihypertensive agents: Additive hypotensive effects
• Digoxin: Possible increased AV blocking effects

• MAO inhibitors: Potential hypertensive crisis
• Vasodilators: Enhanced hypotensive effects
• Levodopa: Reduced anti-Parkinsonian effects

Adverse Effects

• Dry mouth (40%)
• Drowsiness/sedation (33%)
• Dizziness (16%)
• Constipation (10%)

• Fatigue, headache, nausea, hypotension, bradycardia

• Severe hypotension
• Heart block
• Rebound hypertension
• Depression
• Hallucinations
• Allergic reactions
• AV block

Monitoring Parameters

• Blood pressure (standing and supine) and heart rate regularly
• Renal function (BUN, creatinine) at baseline and periodically
• Mental status changes, especially in elderly patients
• Signs of withdrawal with dose reduction or discontinuation
• Ophthalmologic exams with long-term use
• Weight and growth parameters in pediatric patients
• Adherence to therapy

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• Rise slowly from sitting or lying position to prevent dizziness
• Avoid alcohol and other CNS depressants
• May cause drowsiness; use caution when driving or operating machinery
• Maintain good oral hygiene to manage dry mouth
• Report severe dizziness, fainting, extreme tiredness, or depression
• For transdermal patch: Apply to clean, dry skin; rotate sites; avoid cutting patches
• Keep regular follow-up appointments with healthcare provider
• Inform all healthcare providers about clonidine use, especially before surgery

References

1. FDA Prescribing Information: Catapres (clonidine) tablets 2. Chobanian AV, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252 3. Sica DA. Centrally acting antihypertensive agents: an update. J Clin Hypertens. 2007;9(5):399-405 4. Connor DF, et al. Clonidine extended-release tablets for pediatric patients with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010;49(2):171-179 5. Gowing L, et al. Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane Database Syst Rev. 2016;5:CD002024 6. Lexicomp Online, Clonidine: Drug Information. Wolters Kluwer Clinical Drug Information, Inc. 2023 7. Micromedex Solutions: Clonidine. Truven Health Analytics, Inc. 2023