Kapvay - Drug Monograph

Introduction

Kapvay (clonidine hydrochloride) is an alpha-2 adrenergic agonist approved by the FDA for the treatment of attention-deficit hyperactivity disorder (ADHD) as monotherapy or as adjunctive therapy to stimulant medications. Originally developed as an antihypertensive agent, Kapvay represents an extended-release formulation specifically designed for once-daily dosing in ADHD management.

Mechanism of Action

Kapvay exerts its therapeutic effects through selective stimulation of presynaptic alpha-2 adrenergic receptors in the brain. This action results in reduced norepinephrine release from locus coeruleus neurons, leading to decreased sympathetic outflow from the central nervous system. The resulting modulation of noradrenergic tone is believed to improve attention, impulse control, and hyperactivity in ADHD through effects on prefrontal cortex function.

Indications

• FDA-approved for the treatment of ADHD in children and adolescents ages 6-17 years
• May be used as monotherapy or as adjunctive therapy to stimulant medications
• Off-label uses may include treatment of Tourette syndrome, anxiety disorders, and opioid withdrawal (though these are not FDA-approved indications for this formulation)

Dosage and Administration

• Tablets should be swallowed whole and not crushed, chewed, or broken
• May be administered with or without food
• When discontinuing, taper gradually by decreasing dose by 0.1 mg every 3-7 days

• Renal impairment: Use with caution; consider dose reduction
• Hepatic impairment: Use with caution; no specific dosing recommendations
• Geriatric patients: Use with caution due to increased sensitivity
• Pediatric patients: Safety established in children ≥6 years

Pharmacokinetics

Contraindications

• Hypersensitivity to clonidine or any component of the formulation
• Patients with history of severe cardiovascular disease including:

- Severe bradycardia - Heart block greater than first degree - Sick sinus syndrome

• Concurrent use with other centrally acting alpha-2 agonists

Warnings and Precautions

• Sedation/Somnolence: May cause significant drowsiness; caution patients about operating machinery
• Rebound hypertension: Abrupt discontinuation may cause rapid BP elevation, tachycardia, and nervousness
• Cardiovascular effects: May cause bradycardia and hypotension; monitor vital signs regularly
• Depression: Use with caution in patients with history of depression
• Renal impairment: Requires dose adjustment and careful monitoring
• Pregnancy: Category C - use only if potential benefit justifies potential risk
• Suicidal ideation: Monitor for emergence or worsening of depression/suicidal thoughts

Drug Interactions

• CNS depressants: Enhanced sedative effects (alcohol, benzodiazepines, opioids)
• Beta-blockers: Potential for enhanced bradycardia and AV block
• Tricyclic antidepressants: May diminish antihypertensive effects
• CYP2D6 inhibitors: May increase clonidine levels (e.g., fluoxetine, paroxetine)
• Vasodilators/diuretics: Enhanced hypotensive effects

• Digoxin: Additive effects on AV conduction
• Levodopa: Reduced efficacy of levodopa
• NSAIDs: May reduce antihypertensive effects

Adverse Effects

• Somnolence (30-40%)
• Fatigue (15-20%)
• Upper abdominal pain (10-15%)
• Irritability (10-15%)
• Nightmares (5-10%)
• Dry mouth (5-10%)
• Headache (5-10%)
• Nausea (5-10%)

• Severe hypotension
• Symptomatic bradycardia
• Heart block
• Depression
• Hallucinations
• Allergic reactions
• Hepatitis

Monitoring Parameters

• Comprehensive medical history
• Blood pressure and heart rate (supine, sitting, standing)
• ECG if cardiac abnormalities suspected
• Renal and hepatic function tests
• ADHD rating scales

• Vital signs at each dose adjustment and periodically during maintenance
• ADHD symptom assessment using standardized scales
• Growth parameters in pediatric patients
• Mood and behavioral changes
• Signs of sedation or fatigue
• Renal function in patients with renal impairment

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• Tablets must be swallowed whole; do not crush or chew
• Medication may cause drowsiness; avoid driving or operating machinery until effects are known
• Rise slowly from sitting/lying position to prevent dizziness
• Report any signs of allergic reaction, severe dizziness, or extreme fatigue
• Keep all follow-up appointments for monitoring
• Inform all healthcare providers about Kapvay use
• Store at room temperature away from moisture and heat
• Keep medication out of reach of children

• If missed, take as soon as remembered unless close to next dose
• Do not double doses

References

1. FDA Prescribing Information: Kapvay (clonidine hydrochloride) Extended-Release Tablets. Revised 2022. 2. Connor DF, et al. Clonidine extended-release tablets for pediatric patients with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010;49(9):868-878. 3. Jain R, et al. Clonidine extended-release tablets for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Pharmacother. 2011;12(10):1569-1575. 4. Stahl SM. Stahl's Essential Psychopharmacology: Prescriber's Guide. 6th ed. Cambridge University Press; 2017. 5. Pliszka S, et al. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921. 6. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023. 7. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI; 2023.