CLONIDINE HYDROCHLORIDE

Clinical safety rating: safe

CNS depressants may enhance sedative effects Abrupt discontinuation can cause rebound hypertension and nervousness.

How it works

Alpha-2 adrenergic agonist; centrally acting antihypertensive that reduces sympathetic outflow from the CNS, decreasing peripheral resistance, heart rate, and blood pressure.

What the body does with it

Metabolism	Hepatic metabolism via CYP2D6 (minor), with ~50% of drug metabolized; renally excreted as unchanged drug and metabolites.
Excretion	Renal: 40-60% unchanged; hepatic metabolism to inactive metabolites (about 50%); fecal: minimal (<5%).
Half-life	Terminal half-life: 12-16 hours (range 6-20 hours); prolonged in renal impairment (up to 40 hours).
Protein binding	20-40% bound to albumin and alpha-1 acid glycoprotein.
Volume of Distribution	2.1-3.5 L/kg; distributes widely into tissues including CNS.
Bioavailability	Oral: 70-90% (immediate-release); transdermal: 60-70% relative to oral; epidural: near 100% (systemic absorption).
Onset of Action	Oral: 30-60 minutes; transdermal: 2-3 days; epidural: 30 minutes.
Duration of Action	Oral: 6-8 hours (single dose); transdermal: 7 days (patch application); epidural: 4-6 hours.

Classification & Brands

Dosing & administration

Initial 0.1 mg orally twice daily; maintenance 0.2-0.6 mg/day in divided doses; maximum 2.4 mg/day. Also available as transdermal patch: 0.1-0.3 mg/day applied every 7 days.

Dosage form	TABLET
Renal impairment	CrCl 10-50 mL/min: reduce dose by 25-50%; CrCl <10 mL/min: reduce dose by 50-75% and monitor closely. Not significantly removed by hemodialysis.
Liver impairment	Child-Pugh Class B: reduce dose by 25-50%; Class C: reduce dose by 50-75% or avoid use. Reduced hepatic metabolism may lead to accumulation.
Pediatric use	Initial 5-10 mcg/kg/day orally in divided doses every 8-12 hours; titrate gradually to 25 mcg/kg/day max. For ADHD: 0.05-0.1 mg at bedtime, increase weekly to 0.3-0.4 mg/day.
Geriatric use	Start with lowest dose (0.05 mg orally twice daily) due to increased sensitivity and risk of bradycardia, hypotension, and sedation. Titrate slowly. Transdermal patch preferred for stable levels and reduced adverse effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants may enhance sedative effects Abrupt discontinuation can cause rebound hypertension and nervousness.

FDA category	Animal
Breastfeeding	Clonidine is excreted in human breast milk; M/P ratio approximately 2.0. Limited data suggest low risk at maternal doses ≤0.3 mg/day; monitor infant for hypotension, bradycardia, sedation, and poor feeding.
Teratogenic Risk	First trimester: No increased risk of major malformations observed in human studies; animal studies show delayed ossification at high doses. Second/third trimester: Risk of neonatal bradycardia, irritability, and blood pressure instability due to placental transfer; avoid prolonged use near term.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	ADHD
Serious Effects

Absolute Contraindications

["Hypersensitivity to clonidine or components","Severe bradycardia or sick sinus syndrome (if not paced)","Severe hypotension","Concurrent use of other central alpha-2 agonists"]

Clinical Precautions

Precautions

["Rebound hypertension upon abrupt discontinuation (monitor tapering)","CNS depression (sedation, dizziness)","Bradycardia and hypotension","Sinus node dysfunction/conduction abnormalities","Renal impairment (dose adjustment recommended)","Risk of severe allergic reactions"]

Clinical Tips & Counseling

Drug interactions

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CLONIDINE HYDROCHLORIDE

Clinical safety rating: safe

CNS depressants may enhance sedative effects Abrupt discontinuation can cause rebound hypertension and nervousness.

How it works

Alpha-2 adrenergic agonist; centrally acting antihypertensive that reduces sympathetic outflow from the CNS, decreasing peripheral resistance, heart rate, and blood pressure.

What the body does with it

Metabolism	Hepatic metabolism via CYP2D6 (minor), with ~50% of drug metabolized; renally excreted as unchanged drug and metabolites.
Excretion	Renal: 40-60% unchanged; hepatic metabolism to inactive metabolites (about 50%); fecal: minimal (<5%).
Half-life	Terminal half-life: 12-16 hours (range 6-20 hours); prolonged in renal impairment (up to 40 hours).
Protein binding	20-40% bound to albumin and alpha-1 acid glycoprotein.
Volume of Distribution	2.1-3.5 L/kg; distributes widely into tissues including CNS.
Bioavailability	Oral: 70-90% (immediate-release); transdermal: 60-70% relative to oral; epidural: near 100% (systemic absorption).
Onset of Action	Oral: 30-60 minutes; transdermal: 2-3 days; epidural: 30 minutes.
Duration of Action	Oral: 6-8 hours (single dose); transdermal: 7 days (patch application); epidural: 4-6 hours.

Classification & Brands

Dosing & administration

Initial 0.1 mg orally twice daily; maintenance 0.2-0.6 mg/day in divided doses; maximum 2.4 mg/day. Also available as transdermal patch: 0.1-0.3 mg/day applied every 7 days.

Dosage form	TABLET
Renal impairment	CrCl 10-50 mL/min: reduce dose by 25-50%; CrCl <10 mL/min: reduce dose by 50-75% and monitor closely. Not significantly removed by hemodialysis.
Liver impairment	Child-Pugh Class B: reduce dose by 25-50%; Class C: reduce dose by 50-75% or avoid use. Reduced hepatic metabolism may lead to accumulation.
Pediatric use	Initial 5-10 mcg/kg/day orally in divided doses every 8-12 hours; titrate gradually to 25 mcg/kg/day max. For ADHD: 0.05-0.1 mg at bedtime, increase weekly to 0.3-0.4 mg/day.
Geriatric use	Start with lowest dose (0.05 mg orally twice daily) due to increased sensitivity and risk of bradycardia, hypotension, and sedation. Titrate slowly. Transdermal patch preferred for stable levels and reduced adverse effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants may enhance sedative effects Abrupt discontinuation can cause rebound hypertension and nervousness.

FDA category	Animal
Breastfeeding	Clonidine is excreted in human breast milk; M/P ratio approximately 2.0. Limited data suggest low risk at maternal doses ≤0.3 mg/day; monitor infant for hypotension, bradycardia, sedation, and poor feeding.
Teratogenic Risk	First trimester: No increased risk of major malformations observed in human studies; animal studies show delayed ossification at high doses. Second/third trimester: Risk of neonatal bradycardia, irritability, and blood pressure instability due to placental transfer; avoid prolonged use near term.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	ADHD
Serious Effects

Absolute Contraindications

["Hypersensitivity to clonidine or components","Severe bradycardia or sick sinus syndrome (if not paced)","Severe hypotension","Concurrent use of other central alpha-2 agonists"]