Clonipres ER

Approved Indications:

• Hypertension (both monotherapy and adjunct to other antihypertensives)
• Attention-Deficit/Hyperactivity Disorder (ADHD) – extended-release formulation (children ≥6 years)
• Cancer Pain (epidural adjunct to opioids)

Clinically Accepted Off-Label Uses:

• Opioid Withdrawal Syndrome
• Alcohol Withdrawal
• Tourette Syndrome
• Hot Flashes (menopausal or related to prostate cancer therapy)
• Restless Legs Syndrome (RLS)
• Insomnia (especially in ADHD or PTSD)
• Postoperative or Procedural Sedation (ICU use)
• Tic Disorders
• Autism Spectrum Disorders (behavioral symptoms)
• Migraine Prophylaxis
• Glaucoma (topical formulations)

Route of Administration: Oral (IR/ER tablets), transdermal patch, and epidural (for cancer pain)

Adults:

• Hypertension (Oral Immediate-Release):
• Initial: 0.1 mg twice daily
• Titrate in 0.1 mg/day increments every 1–2 weeks
• Maintenance: 0.2–0.6 mg/day in 2–3 divided doses
• Max: 2.4 mg/day (rarely required)
• Hypertension (Transdermal Patch):
• Initial: 0.1 mg/24 hours patch, changed weekly
• Titrate up by 0.1 mg/week as needed (max: 0.3 mg/24 hrs)
• ADHD (Extended-Release – e.g., Kapvay®):
• Initial: 0.1 mg at bedtime
• Titrate by 0.1 mg/day weekly to 0.2–0.4 mg/day in 1–2 divided doses
• Max: 0.4 mg/day

Pediatrics (ADHD, Off-label for withdrawal or behavioral symptoms):

• 6–17 years:
• Initial: 0.05–0.1 mg/day (oral ER or IR)
• Titrate cautiously up to 0.2–0.4 mg/day
• Divide into 1–2 doses

Elderly:

• Start low (e.g., 0.05 mg/day) due to higher risk of hypotension and sedation

Hepatic/Renal Impairment:

• Use caution; adjust dose based on response and monitor BP, HR, and sedation
• Accumulation may occur in renal impairment

Clonidine is a centrally acting alpha-2 adrenergic agonist. It stimulates presynaptic alpha-2 receptors in the brainstem, particularly in the locus coeruleus and medulla, leading to decreased sympathetic outflow. This reduces peripheral vascular resistance, heart rate, and blood pressure. In ADHD, clonidine’s central action modulates noradrenergic signaling, resulting in improved attention regulation, impulsivity, and hyperactivity control. Its sedative and anxiolytic effects also arise from reduced central sympathetic activity.

• Absorption: Well absorbed orally (bioavailability ~75–95%)
• Onset: Oral – 30–60 minutes; Patch – gradual (12–24 hours)
• Peak Plasma Time: Oral – 1–3 hours; Patch – 2–3 days
• Distribution: Widely distributed; crosses blood-brain barrier; protein binding ~20–40%
• Metabolism: Hepatic (minimal metabolism)
• Half-life: 12–16 hours (oral), up to 20–41 hours (patch); prolonged in renal impairment
• Excretion: Primarily renal (~60% unchanged), small fecal excretion

• Pregnancy: Category C – Use only if benefits outweigh risks; may cause neonatal hypotension, bradycardia, or somnolence if used late in pregnancy
• Lactation: Excreted in breast milk; caution advised due to potential CNS depression in the infant, especially with high doses or long-term use

• Primary Class: Antihypertensive
• Subclasses: Centrally Acting Alpha-2 Adrenergic Agonist, Sedative, ADHD Agent

• Hypersensitivity to clonidine or any component of the formulation
• Epidural administration: Do not use with anticoagulant therapy or bleeding diathesis (relative contraindication)
• Severe bradyarrhythmia or advanced AV block without pacemaker
• Severe hypotension

• Abrupt Discontinuation: May lead to rebound hypertension, agitation, headache, tremor – taper over 2–4 days
• Bradycardia & Hypotension: Use with caution in cardiac patients
• Sedation & CNS Depression: May impair mental/physical ability; avoid operating machinery
• Depression: May worsen pre-existing depression
• Orthostatic Hypotension & Falls: Increased risk in elderly
• Patch Site Reactions: Monitor for contact dermatitis or allergic reaction
• Use with CNS Depressants or Alcohol: Enhanced sedation

Very Common (≥10%):

• Drowsiness
• Dry mouth
• Fatigue
• Headache
• Dizziness
• Constipation

Common (1–10%):

• Bradycardia
• Hypotension
• Irritability (in children)
• Nightmares
• Depression
• Insomnia
• Rash (patch site)
• Erectile dysfunction

Rare/Serious:

• Severe hypotension or bradycardia
• AV block
• Rebound hypertension (with abrupt withdrawal)
• Hepatotoxicity
• Hallucinations or mental status changes (especially in elderly)
• Allergic reactions to patch adhesives

• Beta-blockers: Additive bradycardia/hypotension; avoid abrupt discontinuation
• CNS Depressants (e.g., opioids, sedatives): Increased sedation risk
• TCAs & MAOIs: May reduce clonidine's antihypertensive effect
• Calcium Channel Blockers (e.g., verapamil): May enhance bradycardic effects
• CYP Enzymes: Clonidine is not a significant CYP substrate; minimal interactions through metabolism
• Alcohol: Potentiates CNS depression

• FDA Labeling: Emphasizes tapering to avoid withdrawal and hypertensive crises
• Updated ADHD Guidelines: Extended-release clonidine is recommended as adjunct or monotherapy for pediatric ADHD, especially with comorbid sleep issues
• Hypertension Management (JNC-8, AHA): Clonidine may be considered as adjunctive therapy in resistant hypertension, but not first-line
• Opioid Withdrawal Management (SAMHSA): Clonidine remains a non-opioid option for symptom relief, especially where methadone or buprenorphine are contraindicated

• Tablets (IR/ER): Store at 20°C to 25°C (68°F to 77°F); protect from moisture and light
• Transdermal Patch:
• Store flat at 20°C to 25°C
• Do not cut the patch
• Apply to clean, dry, hairless area
• Avoid heat exposure (e.g., heating pads, hot tubs) while using patch
• Epidural Preparation: Use preservative-free formulation; store as per manufacturer's guidance