What is Catapres (clonidine) used for?

What is Catapres (Clonidine) Used For?

Catapres (clonidine) is FDA-approved for the treatment of hypertension, and extended-release formulations are approved for ADHD treatment (as monotherapy or adjunctive to stimulants), though the immediate-release oral formulation is not FDA-approved for ADHD. 1

Primary FDA-Approved Indication

Hypertension

• Clonidine is indicated for the treatment of hypertension and may be used alone or with other antihypertensive agents. 1
• The drug works by stimulating alpha-2 adrenergic receptors in the brainstem, reducing sympathetic outflow from the central nervous system and decreasing peripheral resistance, heart rate, and blood pressure. 1
• Blood pressure decline occurs within 30-60 minutes after oral dosing, with maximum effect at 2-4 hours. 1
• It is effective for all grades of hypertension, including mild, moderate, severe, and refractory cases. 2, 3

ADHD Treatment (Extended-Release Formulations)

Approved Use

• Extended-release clonidine formulations are approved for ADHD treatment as monotherapy or adjunctive therapy to stimulants in various countries. 4
• The mechanism involves postsynaptic alpha-2 agonism in the prefrontal cortex, enhancing noradrenergic neurotransmission and strengthening regulatory control of attention, thought, and working memory. 4

Regional Approval Differences

• In Europe, clonidine is not approved for ADHD treatment (unlike guanfacine). 4
• Approval details vary by country regarding whether it can be used as first-line or only when stimulants are unsuitable. 4

Dosing for ADHD

• Starting dose: 0.1 mg tablet at bedtime, increased to twice-daily administration with careful uptitration. 4
• Maximum recommended dose: 0.4 mg/day. 4
• Evening dosing is often preferred due to sedative effects. 5, 6
• Full therapeutic effect may take 2-4 weeks to develop. 5, 6

Off-Label and Adjunctive Uses

Stimulant-Induced Side Effects

• Clonidine can be used to manage stimulant-induced jaw clenching by suppressing sympathetic nervous system outflow and reducing noradrenergic activity. 5
• Dosing starts at 0.05-0.1 mg at bedtime, with gradual increases up to 0.4 mg daily maximum if needed. 5

Other Historical Uses

• Hypertensive crisis management (intramuscular administration produces effects within 5 minutes, maximal at 75 minutes, persisting 5 hours). 7
• Hyperemesis gravidarum treatment during pregnancy. 4, 6

Mechanism of Action Summary

• Central effects: Stimulates alpha-2 adrenergic receptors in the brainstem (medulla oblongata and hypothalamus), reducing sympathetic outflow. 1, 2
• Cardiovascular effects: Reduces peripheral resistance, renal vascular resistance, heart rate, and blood pressure while preserving renal function. 1, 2
• Metabolic effects: Reduces plasma renin activity and excretion of aldosterone and catecholamines. 1
• ADHD-specific effects: Enhances prefrontal cortex regulation of attention and working memory through postsynaptic alpha-2 agonism. 4

Critical Safety Considerations

Discontinuation Warning

• Clonidine must never be discontinued abruptly due to risk of rebound hypertension and potential hypertensive crisis. 5, 6
• The drug must be tapered gradually when stopping treatment. 6

Common Side Effects

• Somnolence, fatigue, dry mouth, irritability, insomnia, and nightmares are most common. 4, 5, 6
• Sedation and dry mouth are dose-related and minimized by gradual dose increases and bedtime dosing. 2

Serious Adverse Effects Requiring Monitoring

• Hypotension, bradycardia, and syncope require regular blood pressure and heart rate monitoring. 4, 5, 6
• Paradoxical hypertension may occur early in overdose situations. 8

Special Populations

• Clonidine crosses the placental barrier and is found in human milk with a relative infant dose up to 7.1%. 4, 6
• Breastfed infants should be monitored for drowsiness, hypotonia, vomiting, diarrhea, jitteriness, sedation, and seizures. 4, 6
• Half-life increases to 41 hours in patients with severe renal impairment (normal: 12-16 hours). 1

Pharmacokinetics

• Oral bioavailability: 70-80%. 1
• Peak plasma levels: 1-3 hours after oral administration. 1
• Therapeutic plasma concentration range: 0.2-2.0 ng/mL in patients with normal renal function. 1
• Metabolism: Primarily hepatic via CYP2D6 (40-60% excreted unchanged in urine). 4, 1
• The drug crosses the blood-brain barrier. 1