Schedule H

Oral, Intravenous (select tertiary hospital/ICU settings only)

• Tablets: 100 mcg, 150 mcg, 200 mcg

• Injection: 150 mcg/mL in 1 mL ampoule (limited availability in tertiary care centres)

Note: Transdermal patch formulation is NOT AVAILABLE in India.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Essential Hypertension (Adults)

Parameter Details

Starting dose 100 mcg orally twice daily (or 50 mcg twice daily in sensitive patients)

Titration Increase by 50–100 mcg every 1–2 days based on BP response and tolerability

Usual maintenance dose 200–400 mcg/day in 2–3 divided doses

Maximum dose 900 mcg/day (in 2–3 divided doses)

Dosing by Clinical Scenario:

Clinical Scenario Starting Dose Titration Interval Maximum Dose Notes

Mild-moderate hypertension 100 mcg twice daily Every 1–2 days 600 mcg/day Not first-line; use when other agents inadequate

Resistant hypertension (add-on) 100 mcg twice daily Every 2–3 days 900 mcg/day Add to existing multidrug regimen

Elderly patients 50 mcg once or twice daily Every 5–7 days 400 mcg/day Higher sensitivity; slower titration essential

Renal impairment (CrCl <30) 50 mcg twice daily Every 3–5 days 300 mcg/day Reduce by ~50%; monitor closely

High sympathetic tone 100 mcg twice daily Every 1–2 days 600 mcg/day Useful phenotype for clonidine

Clinical Notes:

• Not a first-line antihypertensive in Indian guidelines — reserve for resistant hypertension or intolerance to preferred agents

• Last dose of the day given at bedtime may reduce daytime sedation

• MUST taper gradually over 3–7 days to avoid rebound hypertension — never stop abruptly

• Evening/bedtime dosing may help with nocturnal hypertension

1. Hypertensive Emergency — IV Use (Specialist/ICU Setting Only)

Parameter Details

Starting dose 1–2 mcg/kg IV over 10 minutes (typically 100–200 mcg for average adult)

Titration Adjust based on BP response every 5–10 minutes

Usual maintenance dose Continuous IV infusion 0.5–2 mcg/kg/hour

Maximum dose 10 mcg/kg/hour (rarely needed)

Clinical Notes:

• Use only in continuously monitored settings (ICU/CCU/HDU)

• Avoid in patients with bradyarrhythmias or AV block

• Alternative to nitroprusside or labetalol in select cases

• Not first-line for hypertensive emergency — consider labetalol, nitroprusside, or nicardipine first

• Have atropine available for bradycardia

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Specialist Required Evidence Basis

Opioid withdrawal syndrome — OFF-LABEL 100–200 mcg orally every 6–8 hours 3–7 days; taper gradually Yes (Addiction Medicine/Psychiatry) AIIMS de-addiction protocols; Indian de-addiction centre practice

Alcohol withdrawal syndrome — OFF-LABEL 100–150 mcg orally every 6–8 hours 3–5 days; taper gradually Yes (Addiction Medicine/Psychiatry) Indian de-addiction protocols; reduces autonomic hyperactivity

Vasomotor symptoms in menopause — OFF-LABEL 50–100 mcg orally twice daily Weeks to months; short courses preferred Preferable (Gynaecology) Used where HRT contraindicated; international supportive data

Migraine prophylaxis — OFF-LABEL 50–100 mcg twice daily Long-term Preferable (Neurology) Limited use; alternative when first-line agents fail

Diarrhoea in diabetic autonomic neuropathy — OFF-LABEL 100–300 mcg orally twice daily Variable; symptom-based Yes (Gastroenterology/Endocrinology) Reduces intestinal secretions; limited Indian data

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Severe/Resistant Hypertension (Paediatric Nephrology/ICU Use)

Age/Weight Starting Dose Titration Usual Maintenance Maximum Dose

Children 6–12 years 5 mcg/kg/day PO in 2–3 divided doses Increase by 5 mcg/kg/day every 3–5 days 5–25 mcg/kg/day in 2–3 divided doses 40 mcg/kg/day (rarely exceeded)

Adolescents >12 years 50–100 mcg twice daily Increase by 50 mcg every 3–5 days 100–300 mcg/day in 2–3 divided doses 600 mcg/day

Parameter Details

Starting dose 5 mcg/kg/day in 2–3 divided doses

Titration Increase by 5 mcg/kg/day every 3–5 days based on BP response

Usual maintenance dose 5–25 mcg/kg/day in 2–3 divided doses

Maximum dose 40 mcg/kg/day

Monitoring:

• Blood pressure (supine and standing)

• Heart rate

• Sedation level

• Mood and behaviour changes

Clinical Notes:

• Must taper gradually when discontinuing — same rebound risk as adults

• Use only under paediatric nephrology or cardiology supervision

• Not available as liquid formulation in India — tablets may need to be crushed for younger children (off-label manipulation)

Secondary Indications — Paediatric (Off-label)

Indication Age Dose Duration Specialist Required Evidence Basis

ADHD (particularly with tics or hyperarousal) — OFF-LABEL ≥6 years Start 25–50 mcg at bedtime; increase by 25 mcg every 5–7 days to 100–200 mcg/day in divided doses; max 400 mcg/day Long-term Yes (Paediatric Psychiatry/Neurology) Not first-line; use when stimulants not tolerated or contraindicated; IAP practice

Tourette syndrome/Tic disorders — OFF-LABEL ≥6 years 50 mcg at bedtime; titrate to 100–200 mcg/day in 2–3 doses Long-term Yes (Paediatric Neurology) Alternative to typical antipsychotics; reduces tic severity

Sedation/Analgesia adjunct in PICU — OFF-LABEL All ages 1–2 mcg/kg/dose every 4–6 hours; or infusion 0.5–2 mcg/kg/hour ICU duration Yes (PICU) Reduces opioid and sedative requirements

⚠️ Not recommended below 6 years of age for outpatient use except under paediatric specialist supervision (Nephrology/Cardiology/Neurology) with documented justification. All paediatric use is essentially specialist-guided.

CrCl (mL/min) Dose Adjustment Monitoring Notes

60 No adjustment required Standard monitoring —

30–60 Reduce starting dose by 25% More frequent BP/HR monitoring Slower titration

<30 Reduce dose by 50% Close BP/HR monitoring every 2–3 days Maximum 300–400 mcg/day

Haemodialysis Reduce dose by 50%; give after dialysis Post-dialysis BP monitoring Clonidine not significantly dialysed

Peritoneal dialysis Reduce dose by 50% Regular BP monitoring Limited data

Note: Clonidine is approximately 50% renally excreted; accumulation in renal impairment leads to excessive hypotension, bradycardia, and sedation.

• Known hypersensitivity to clonidine or any excipient

• Severe bradyarrhythmia (heart rate <50 bpm)

• Sick sinus syndrome (without pacemaker)

• Second-degree or third-degree AV block (without pacemaker)

• Known history of syncope or severe hypotension with previous clonidine use

• Concurrent use with MAO inhibitors

• Active depression with suicidal ideation

• Coronary artery disease — bradycardia may precipitate ischaemia

• Cerebrovascular disease — hypotension risk

• Mild-moderate bradycardia — monitor HR closely

• First-degree AV block — may progress with clonidine

• History of depression or mood disorders — may worsen; monitor mental status

• Raynaud's phenomenon or peripheral vascular disease

• Moderate-severe renal impairment — dose adjustment required

• Concurrent use with beta-blockers — specific withdrawal sequence required (see Drug Interactions)

• Elderly or frail patients — enhanced sensitivity to CNS and cardiovascular effects

• Patients requiring high alertness (drivers, machinery operators) — significant sedation risk

• Abrupt discontinuation — MUST taper over 3–7 days to prevent rebound hypertensive crisis

• Pheochromocytoma — may have paradoxical effects

Parameter Details

Safety Category Considered relatively safe; crosses placenta; limited human data but extensive clinical experience

Preferred alternatives Labetalol, Methyldopa, Nifedipine (extended-release) — per Indian obstetric guidelines

When to use May be used in gestational hypertension or pre-eclampsia (2nd/3rd trimester) when preferred agents are contraindicated or insufficient; obstetrician supervision required

Monitoring Maternal blood pressure and heart rate; fetal heart rate monitoring; fetal growth; neonatal monitoring for withdrawal symptoms if used near term

Parameter Details

Compatibility Compatible with breastfeeding; excreted in low amounts in breastmilk

Drug levels in milk Low (milk:plasma ratio ~1.5, but absolute amounts small)

Preferred alternatives Methyldopa, Labetalol, Nifedipine — preferred for chronic hypertension during lactation

Infant monitoring Sedation, poor feeding, lethargy, bradycardia (rare)

Parameter Recommendation

Starting dose 50 mcg once or twice daily

Titration Slower titration over 5–7 days; increase by 50 mcg increments only

Maximum dose 400 mcg/day (avoid higher doses unless essential)

Special considerations Increased sensitivity to hypotensive, sedative, and bradycardic effects; higher risk of orthostatic hypotension

Additional risks Falls risk; cognitive dulling; constipation; dry mouth may worsen xerostomia

Discontinuation Must taper gradually — elderly at higher risk of rebound hypertension

Drug Mechanism Clinical Effect Recommendation

Beta-blockers (propranolol, metoprolol, atenolol) Both reduce sympathetic tone; beta-blockers prevent compensatory tachycardia during clonidine withdrawal Severe bradycardia during concurrent use; life-threatening rebound hypertension if clonidine stopped before beta-blocker Use with caution; if discontinuing, stop clonidine several days after stopping beta-blocker

Tricyclic antidepressants (amitriptyline, imipramine) TCAs antagonise alpha-2 receptors Reduced antihypertensive effect of clonidine Avoid combination; consider alternative antidepressant or antihypertensive

MAO inhibitors Unpredictable catecholamine effects Hypertensive crisis or severe hypotension Contraindicated — avoid concurrent use

Moxonidine Both centrally acting antihypertensives Additive hypotension; risk of severe rebound if either discontinued Avoid concurrent use

Verapamil, Diltiazem Additive AV nodal depression and bradycardia Severe bradycardia; AV block Use with caution; monitor ECG and HR closely

Drug Interaction Recommendation

Other antihypertensives (ACE inhibitors, ARBs, CCBs, diuretics) Additive hypotensive effect Monitor BP closely; adjust doses accordingly

Digoxin Additive bradycardia and AV nodal depression Monitor HR and ECG; use with caution

CNS depressants (benzodiazepines, opioids, alcohol, sedating antihistamines) Additive sedation and CNS depression Monitor for excessive sedation; reduce doses if needed

Antipsychotics (haloperidol, risperidone) Additive hypotension and sedation Monitor BP and mental status

Methylphenidate May reduce clonidine efficacy; also additive cardiovascular effects Monitor BP and HR if used together (e.g., in ADHD)

Levodopa Clonidine may reduce levodopa efficacy Monitor Parkinson's symptom control

NSAIDs May attenuate antihypertensive effect Monitor BP; consider dose adjustment

• Dry mouth (most common; dose-related)

• Sedation and drowsiness

• Dizziness

• Constipation

• Fatigue and weakness

• Headache

• Orthostatic hypotension

• Bradycardia

• Nausea

• Insomnia (paradoxical)

• Erectile dysfunction

• Rebound hypertensive crisis — occurs 18–72 hours after abrupt discontinuation; may present with severe headache, tachycardia, sweating, tremor, anxiety; can lead to stroke or MI; always taper over 3–7 days

• Severe bradycardia — may require dose reduction, atropine, or discontinuation

• AV block — dose-related; monitor ECG in at-risk patients

• Syncope — especially with rapid titration, orthostatic stress, or drug interactions

• Severe CNS depression — particularly in overdose or elderly; may require supportive care

• Depression worsening — monitor mood; discontinue if significant

• Allergic reactions — rare; discontinue if occurs

⚠️ Overdose management: Supportive care; atropine for bradycardia; IV fluids for hypotension; tolazoline (alpha-blocker) may be used in severe cases but is rarely available in India.

Phase Parameters

Baseline Blood pressure (supine and standing); heart rate; ECG (in patients with cardiac disease, elderly, or on other nodal-blocking agents); renal function; mood/depression screening

During titration BP and HR daily until stable; orthostatic symptoms; sedation level; dry mouth assessment

Long-term BP and HR at each visit; periodic ECG if on high doses or with conduction concerns; mood assessment; renal function annually

Discontinuation Taper over 3–7 days with daily BP monitoring; watch for rebound symptoms (headache, tachycardia, sweating, anxiety, severe hypertension)

• Arkamin® (Unichem)

• Catapres® (Boehringer — limited availability)

• Cloneon® (Sun Pharma)

• Clonotril® (Torrent)

• Clonipress® (Ipca)

• Clonidine Intas®

Note: Injectable formulation available only in select tertiary care centres.

Note: Not included in NLEM 2022; not NPPA price-controlled; widely available in private market.

• Never stop abruptly: Rebound hypertension can be life-threatening — always taper over 3–7 days; risk increases with higher doses and longer duration of use

• Beta-blocker withdrawal sequence: If patient is on both clonidine and beta-blocker, stop clonidine LAST (several days after beta-blocker) — stopping clonidine first removes sympathetic suppression while beta-blockade prevents compensatory tachycardia, precipitating severe hypertensive crisis

• Not first-line: Reserve clonidine for resistant hypertension, intolerance to first-line agents, or specific indications (opioid withdrawal, ADHD) — more sedating and more dangerous than modern antihypertensives

• Useful in high sympathetic states: Particularly effective in patients with tachycardia, anxiety, or autonomic hyperactivity (e.g., withdrawal syndromes)

• Transdermal patch NOT available in India: Despite Western literature references, only oral tablets are available in Indian market

• Dry mouth management: Counsel patients; sugar-free lozenges and adequate hydration help compliance

clonidine; hypertension; centrally acting antihypertensive; alpha-2 agonist; opioid withdrawal; resistant hypertension; paediatric hypertension; ADHD (off-label); rebound hypertension; bradycardia risk; sedation; Schedule H; India

RxIndia v1.0 — 08 Jun 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Hypertension and De-addiction Protocols

• ICMR Guidelines on Hypertension

• Indian Society of Hypertension Guidelines (ISH-India)

• Indian Paediatric Nephrology practice standards

• IAP Guidelines — Paediatric Hypertension, ADHD

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine