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Clonidine: Pediatric drug information

Clonidine: Pediatric drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Clonidine: Drug information" and "Clonidine: Patient drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Epidural use:

The 500 mcg/mL strength product should be diluted prior to use in an appropriate solution.

Note: Epidural clonidine is not recommended for obstetrical, postpartum, or perioperative pain management. The risk of hemodynamic instability, especially hypotension and bradycardia, from epidural clonidine may be unacceptable in these patients. However, in a rare obstetrical, postpartum or perioperative patient, potential benefits may outweigh the possible risks.

Brand Names: US
  • Catapres [DSC];
  • Catapres-TTS-1;
  • Catapres-TTS-2;
  • Catapres-TTS-3;
  • Duraclon;
  • Kapvay [DSC];
  • Nexiclon XR
Brand Names: Canada
  • JAMP-Clonidine;
  • MAR-Clonidine;
  • MINT-CloNIDine;
  • MINT-Clonidine;
  • Sandoz Clonidine;
  • TEVA-CloNIDine
Therapeutic Category
  • Adrenergic Agonist Agent;
  • Alpha-Adrenergic Agonist;
  • Analgesic, Nonopioid;
  • Antihypertensive Agent
Dosing: Neonatal

Dosage guidance:

Safety: To avoid adverse effects (eg, rebound hypertension), do not discontinue clonidine abruptly.

Dosing: Dosing is expressed as the salt (clonidine hydrochloride) unless otherwise noted. Extemporaneously compounded oral suspensions are available in multiple concentrations (eg, 0.01 mg/mL, 0.02 mg/mL, 0.1 mg/mL); caution should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as mcg or mg as appropriate (ie, not in mL or number of tablets).

Neonatal opioid withdrawal syndrome

Neonatal opioid withdrawal syndrome: Note: In most studies, Finnegan Neonatal Abstinence Scoring tool was utilized to assess severity of withdrawal symptoms; treatment was initiated if 3 consecutive scores were ≥8 or 2 consecutive scores ≥12; doses were increased using these same criteria.

Preterm and term neonates:

GA <35 weeks: Very limited data available: Immediate release: Oral: 0.5 to 1 mcg/kg/dose every 6 hours; dosing based on a retrospective study of 14 neonates (GA: median: 26 weeks and 2 days; range: 24 to 40 weeks; PNA at time of treatment: mean: 4.1 weeks) who received clonidine to prevent (n=10) or treat (n=4) either iatrogenic opioid dependency or neonatal opioid withdrawal syndrome; clonidine was stopped or tapered by 0.25 mcg/kg every 6 hours once patients were stabilized (Ref).

GA ≥35 weeks: Limited data available; dosing regimens variable:

Initial dose and dose escalation for symptom control: Immediate release: Oral: Initial: 0.5 to 1 mcg/kg/dose every 3 to 6 hours; higher initial doses of up to 1.5 mcg/kg/dose every 3 hours have been reported; if symptoms are not controlled, may increase dose by ~25% of the initial dose; frequency of dose increases varied; see individual studies for details or refer to institutional protocols; reported maximum dose is highly variable; maximum reported dose: 24 mcg/kg/day (Ref).

Weaning dose after symptoms controlled: Note: Dose and taper schedule should be individualized based on patient response; monitor closely for withdrawal symptoms as well as signs of accumulation. Weaning of clonidine usually occurs after withdrawal symptoms are controlled; typically weaning begins after 48 hours of stable withdrawal scores (Ref).

Immediate release: Oral: A standard approach to weaning has not been published; weaning protocols are highly variable and patient specific. Decreasing dose by 10% to 20% of the effective dose every 48 hours as tolerated is one weaning approach that has been reported; weaning dose and/or frequency daily has also been reported; see individual studies for weaning details or refer to institutional protocols (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Pediatric

Dosage guidance:

Safety: To avoid adverse effects (eg, rebound hypertension), do not discontinue clonidine abruptly.

Dosing: Dosing is expressed as the salt (clonidine hydrochloride) unless otherwise noted. Extemporaneously compounded oral suspensions are available in multiple concentrations (eg, 0.01 mg/mL, 0.02 mg/mL, 0.1 mg/mL); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as mcg or mg as appropriate (ie, not in mL or number of tablets).

Dosage form information: Immediate-release (tablets) vs extended-release (Kapvay [tablets], Nexiclon XR [tablets]) formulations of clonidine are not interchangeable on a mg per mg basis due to different pharmacokinetic profiles. Extended-released formulations (Kapvay [tablets] vs Nexiclon XR [tablets]) are not interchangeable on a mg:mg basis; only Kapvay is approved for use in pediatric patients. Transdermal patch is a membrane-controlled system; do not cut the patch to deliver partial doses; if cut, rate of drug delivery, reservoir contents, and adhesion may be affected; if partial dose is needed, surface area of patch can be blocked proportionally using adhesive bandage (Ref).

Attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) (alternative or adjunctive agent):

Note: May be used as monotherapy or as an adjunct to stimulant therapy (Ref). May be optimal for patients with comorbid tics or Tourette syndrome, a history of psychosis or mania, or emotional dysregulation (Ref).

Oral:

Immediate release: Limited data available:

Children ≥6 years and Adolescents (Ref):

Weight 27 to 40.5 kg: Oral: Initial: 0.05 mg at bedtime; sequentially increase as tolerated every 2 to 3 days in 0.05 mg/day increments given as 0.05 mg twice daily, then 3 times daily, then 4 times daily; maximum daily dose: 0.2 mg/day. Note: Dosing interval of twice daily or 3 times daily preferred by some experts for ease of dosing and increased compliance. When discontinuing therapy, taper over 1 to 2 weeks.

Weight >40.5 to 45 kg: Oral: Initial: 0.05 mg at bedtime; sequentially increase as tolerated every 2 to 3 days in 0.05 mg/day increments given as 0.05 mg twice daily, then 3 times daily, then 4 times daily; maximum daily dose: 0.3 mg/day. Note: Dosing interval of twice daily or 3 times daily preferred by some experts for ease of dosing and increased compliance. When discontinuing therapy, taper over 1 to 2 weeks.

Weight >45 kg: Oral: Initial: 0.1 mg at bedtime; sequentially increase as tolerated every 2 to 3 days in 0.1 mg/day increments given as 0.1 mg twice daily, then 3 times daily, then 4 times daily; maximum daily dose: 0.4 mg/day. Note: Dosing interval of twice daily or 3 times daily preferred by some experts for ease of dosing and increased compliance. When discontinuing therapy, taper over 1 to 2 weeks.

Extended-release tablets (eg, Kapvay or associated generics): Children ≥6 years and Adolescents: Oral: Initial: 0.1 mg at bedtime; increase as tolerated in 0.1 mg/day increments every 7 days until desired response; after initial dose, doses should be administered twice daily in the morning and at bedtime (either split equally or with the higher split dosage given at bedtime); maximum daily dose: 0.4 mg/day. Note: When discontinuing therapy, taper daily dose by ≤0.1 mg every 3 to 7 days (Ref).

Topical: Transdermal patch: Limited data available: Children ≥6 years and Adolescents: May be converted to the transdermal delivery system after oral therapy is titrated to an optimal and stable dose; a transdermal dose approximately equivalent to the total oral daily dose may be used; apply transdermal patch and change every 5 to 7 days. Adjustment of transdermal patch dose may be needed; there is variation in absorption and no exact equivalence or fixed ratio exist between the oral and transdermal routes (Ref).

Epidural analgesia

Epidural analgesia (adjunct therapy): Note: Manufacturer suggests reserving use for severe intractable cancer pain unresponsive to opioid analgesics.

Children and Adolescents: Epidural: Continuous infusion: Initial: 0.5 mcg/kg/hour; adjust with caution based on clinical effect; do not exceed adult doses. Do not discontinue clonidine abruptly; if needed, gradually reduce dose over 2 to 4 days to avoid withdrawal symptoms.

Growth hormone deficiency test

Growth hormone deficiency test: Limited data available: Children and Adolescents: Oral: Immediate release: 5 mcg/kg or 150 mcg/m2 as a single dose; maximum dose: 250 mcg/dose (Ref).

Hypertension

Hypertension (alternative agent ):

Acute severe hypertension with significant but not life-threatening symptoms (eg, severe headache, vomiting but no seizures): Limited data available: Children and Adolescents: Oral: Immediate release: 2 to 5 mcg/kg/dose; may repeat dose every 6 to 8 hours; maximum dose: 10 mcg/kg/dose up to a maximum total dose of 0.8 mg (Ref).

Chronic hypertension: Note: Clonidine is no longer recommended for primary use in children with chronic hypertension (Ref).

Insomnia, especially with neurodevelopmental disorders

Insomnia, especially with neurodevelopmental disorders (alternative therapy): Limited data available:

Note: Most commonly used in patients with comorbid ADHD (Ref). The use of clonidine for insomnia in patients without neurodevelopmental disorders is based on expert clinical experience (limited/no published data); use should be reserved for patients who have failed nonpharmacologic interventions and in whom other underlying contributors have been identified and appropriately managed. When discontinuing, gradually reduce dose over 2 to 7 days (Ref):

Children ≥4 years and Adolescents: Immediate release:

Weight <27 kg: Oral: Initial: 25 to 50 mcg at bedtime; titrate in 25 mcg increments every 1 to 2 weeks as tolerated; usual daily dose: 5 to 10 mcg/kg/day; maximum daily dose: 10 mcg/kg/day (Ref).

Weight 27 to 40.5 kg: Oral: Initial: 25 to 50 mcg at bedtime; titrate in 25 mcg increments every 1 to 2 weeks as tolerated; maximum daily dose: 0.2 mg/day (Ref).

Weight >40.5 kg to 45 kg: Oral: Initial: 25 to 50 mcg at bedtime; titrate in 25 mcg increments every 1 to 2 weeks as tolerated; maximum daily dose: 0.3 mg/day (Ref).

Weight >45 kg: Oral: Initial: 25 to 50 mcg at bedtime; titrate in 25 mcg increments every 1 to 2 weeks as tolerated; maximum daily dose: 0.4 mg/day (Ref).

Posttraumatic stress disorder

Posttraumatic stress disorder (PTSD): Very limited data available:

Children 5 to ≤10 years: Oral: Immediate release: Initial: 0.05 mg at bedtime; may titrate in 0.05 mg increments every 3 days; reported target dose: 0.2 to 0.5 mg/day; the total daily dose should be divided into multiple doses per day due to the short half-life (Ref); 3-times-daily dosing has been reported (Ref); maximum daily dose: 0.5 mg/day (Ref).

Children >10 years and Adolescents: Oral: Immediate release: Initial: 0.1 mg at bedtime; may titrate in 0.05 to 0.1 mg increments every 3 days based on tolerability and response; Note: Dose titration based on available literature and clinical expertise adapted from use for other clinical diagnoses (eg, attention-deficit/hyperactivity disorder); reported target dose: 0.2 to 0.5 mg/day; the total daily dose should be divided into multiple doses per day due to the short half-life (Ref); 3-times-daily dosing has been reported (Ref); maximum daily dose: 0.5 mg/day (Ref).

Tourette syndrome, tic disorder

Tourette syndrome, tic disorder: Limited data available:

Note: Efficacy results variable; compared to placebo, clonidine may be more likely to reduce tic severity, with largest effects observed in patients with comorbid ADHD (Ref):

Children ≥7 years and Adolescents: Oral: Immediate release: Initial: 0.025 to 0.05 mg/day in 1 to 2 divided doses; gradual titration to a 3- to 4-times-daily schedule using small increments (0.025 mg); usual daily dose: 0.1 to 0.4 mg/day in 3 to 4 divided doses; reported maximum daily dose: 0.6 mg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children and Adolescents: Oral: Extended release (eg, Kapvay): The manufacturer recommends dosage adjustment according to degree of renal impairment; however, there are no specific dosage adjustment provided in the labeling (has not been studied). Bradycardia, sedation, and hypotension may be more likely to occur in patients with renal failure; drug is primarily eliminated unchanged in the urine; consider using doses at the lower end of the dosage range; monitor patients closely.

Hemodialysis: Not dialyzable (0 to 5%); supplemental dose is not necessary.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Adult

(For additional information see "Clonidine: Drug information")

Dosage guidance:

Safety: Do not discontinue therapy abruptly. Taper gradually to avoid withdrawal symptoms (eg, rebound hypertension).

Dosing: Oral doses are expressed as clonidine hydrochloride and transdermal patch doses are expressed as clonidine base. Oral doses cannot be converted directly to a transdermal patch due to bioavailability differences.

Dosage form information: IR tablets and ER formulations are not interchangeable due to different pharmacokinetic profiles.

Cancer pain management, severe

Cancer pain management, severe (adjunctive agent):

Note: Optimal regimen has not been established. The dosing provided is from manufacturer labeling and is based on a small study (Ref); however, it may not reflect current clinical practice. Patient should be under the care of a pain specialist qualified in the management of neuraxial analgesia for chronic pain who can carefully titrate the dose based on patient-specific response and tolerability. Reserve for patients with severe, intractable, cancer-related pain unresponsive to conventional analgesics (eg, opioid).

Epidural: Initial: 30 mcg/hour; titrate as required for relief of pain or presence of side effects; experience with doses >40 mcg/hour is limited (Ref). May be combined with another analgesic (eg, opioid, local anesthetic) for an increased analgesic effect (Ref).

Intrathecal (off-label route): Initial: 20 to 100 mcg/day; titrate as required for relief of pain or presence of side effects to a maximum of 600 mcg/day. May be combined with another analgesic (eg, opioid, local anesthetic) for an increased analgesic effect (Ref).

Hypertension, chronic

Hypertension, chronic (alternative agent):

Note: Not recommended for initial management but may be considered as additional therapy for resistant hypertension in patients who do not respond adequately to combination therapy with preferred agents (Ref). For severe asymptomatic hypertension, may consider short-term oral use for BP lowering (eg, over hours) if there is concern that severe BP elevation will precipitate an acute cardiovascular event, such as in patients with known aortic or intracranial aneurysms (Ref).

Oral:

Immediate release: Initial: 0.1 mg twice daily; increase dose in increments of 0.1 mg/day at weekly intervals based on response and tolerability; patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication adjustment within 1 week; usual dose range: 0.2 to 0.6 mg/day in 2 or 3 divided doses. The manufacturer's labeling includes a maximum daily dose of 2.4 mg; however, doses >0.6 mg/day are generally not used (Ref).

Extended release (Nexiclon): Initial: 0.17 mg once daily at bedtime; increase dose in increments of 0.09 mg/day at weekly intervals based on response and tolerability; usual dose range: 0.17 to 0.52 mg once daily; maximum dose: 0.52 mg/day.

Transdermal: Initial: 0.1 mg per 24-hour patch applied once every 7 days; increase by 0.1 mg at 1- to 2-week intervals; usual dose range: 0.1 to 0.3 mg per 24-hour patch applied once every 7 days. Onset of effect is delayed for 2 to 3 days following initial application.

Note: In patients undergoing surgery, maintenance dose is generally continued perioperatively to avoid rebound hypertension associated with abrupt withdrawal. ER tablets (Nexiclon) may be administered up to 28 hours prior to surgery and resumed the following day. It may be appropriate to transition to a transdermal patch ≥3 days before surgery in select patients who are not expected to resume enteral medication ≤12 hours after surgery. See "Transitioning Between Dosage Forms" below (Ref).

ICU sedation, transition from dexmedetomidine to clonidine

ICU sedation, transition from dexmedetomidine to clonidine (off-label use):

Note: Consider use in patients who are hemodynamically stable and able to receive medications enterally. Monitor blood pressure and heart rate during initiation and transition (Ref).

Oral: Immediate release:

Initial: Note: Decrease dexmedetomidine dose by 25% within 6 hours of each clonidine dose. Dexmedetomidine can usually be stopped within 48 hours.

Dexmedetomidine dose <0.7 mcg/kg/hour: 0.1 to 0.2 mg every 6 to 8 hours (Ref).

Dexmedetomidine dose ≥0.7 mcg/kg/hour: 0.3 mg every 6 to 8 hours (Ref).

Maintenance: Titrate to achieve target sedation levels to a usual dosage range of 0.2 to 0.5 mg every 6 hours (Ref). Gradually taper clonidine by extending the dosing interval every 24 to 48 hours (Ref).

Opioid withdrawal, medically supervised

Opioid withdrawal, medically supervised (adjunctive or alternative agent) (off-label use):

Note: Adjunct to opioid agonist for relief of withdrawal symptoms. May also be used as primary treatment when opioid agonist therapy is not indicated or not available. May be combined with other adjunctive medications as needed. To assess severity of withdrawal symptoms and adjust therapy, the use of a standard instrument for scoring of clinical observations (eg, Clinical Opioid Withdrawal Scale) is suggested (Ref).

Oral: Immediate release:

Initial: 0.1 to 0.2 mg (patients >90 kg may receive up to 0.3 mg); may repeat every 45 to 60 minutes if needed, up to a total of 4 doses until symptoms resolve, provided blood pressure and heart rate remain stable; maximum dose: typically, 0.8 mg/day or up to 1.2 mg/day for patients >90 kg (Ref).

Maintenance: 0.1 to 0.3 mg every 6 to 8 hours determined by symptom severity; maximum dose: 1.2 mg/day in divided doses (Ref).

Note: After a stable oral dose is established, may transition to an equivalent dose of a transdermal patch (see "Transitioning between dosage forms" below); according to some institutional protocols, may initiate therapy with a transdermal patch in select patients (Ref).

Vasomotor symptoms associated with menopause

Vasomotor symptoms associated with menopause (alternative agent):

Note: May consider use when menopausal hormonal therapy is contraindicated and when other nonhormonal therapies are ineffective or not tolerated. Side effects (eg, dry mouth, dizziness, constipation, hypotension, sedation) may limit use. Transdermal administration may provide more stable serum concentrations to help limit side effects (Ref).

Oral : Immediate release: 0.05 mg twice daily; discontinue treatment if no improvement after 2 to 4 weeks (Canadian manufacturer's labeling). Some experts recommend upward titration based on response and tolerability to a dosage range of 0.1 to 1 mg/day in divided doses (Ref).

Transdermal (off label): Initial: 0.1 mg/24-hour patch applied once every 7 days; increase to 0.2 mg/24-hour patch then 0.3 mg/24-hour patch based on response and tolerability (Ref).

Transitioning between dosage forms:

Transition from IR tablets to ER (Nexiclon) tablets:

0.05 mg twice daily of immediate release is equivalent to 0.09 mg once daily of extended release (Nexiclon).

0.1 mg twice daily of immediate release is equivalent to 0.17 mg once daily of extended release (Nexiclon).

0.2 mg twice daily of immediate release is equivalent to 0.34 mg once daily of extended release (Nexiclon).

0.3 mg twice daily of immediate release is equivalent to 0.52 mg once daily of extended release (Nexiclon).

Transition from oral to transdermal: Note: If transitioning from oral to transdermal therapy, overlap oral regimen for 1 to 3 days; transdermal route takes 2 to 3 days to achieve therapeutic effect.

An example transition is below:

Day 1: Place transdermal patch; administer 100% of oral dose.

Day 2: Patch remains; administer 50% of oral dose.

Day 3: Patch remains; administer 25% of oral dose.

Day 4: Patch remains; no further oral dosing.

Transition from transdermal to oral: After transdermal patch removal, therapeutic clonidine levels persist for ~8 hours and then slowly decrease over several days, with a potential for continued effect for 24 to 48 hours after removal. A persistent effect on blood pressure should be considered when restarting oral clonidine. Consider starting oral clonidine no sooner than 8 hours after patch removal (Ref).

Discontinuation of therapy: Do not stop oral therapy abruptly to decrease risk of acute and potentially severe rebound hypertension and withdrawal symptoms (eg, nervousness, agitation, headache, tremor); discontinue slowly over at least 6 to 10 days by reducing the dose by one-third to one-half every 2 to 3 days. For patients on both a beta-blocker and clonidine, withdraw the beta-blocker several days before clonidine, then slowly taper clonidine. Rebound hypertension and withdrawal symptoms are less likely with a transdermal patch compared to oral therapy (Ref). Note: Clonidine administration is generally not interrupted during the perioperative period (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Clonidine is excreted primarily through the kidneys as unchanged drug (40% to 60%). For this reason, dose initiation and titration should be done cautiously with monitoring of response in patients with significant kidney impairment (Ref). Additionally, patients with advanced kidney impairment may have impaired alpha-adrenergic responsiveness (Ref); individualize dose according to patient response.

Altered kidney function:

Oral, transdermal:

eGFR >30 mL/minute/1.73 m2: No dosage adjustment necessary.

eGFR <30 mL/minute/1.73 m2: Start with a low dose and titrate upward cautiously according to patient response, no more frequently than for patients with normal kidney function; monitor BP and heart rate closely (Ref).

Hemodialysis, intermittent (thrice weekly): Minimally dialyzable (0% to 5%):

ER tablet (Kapvay), IR tablet, transdermal: Start with a low dose and titrate upward cautiously according to patient response, no more frequently than for patients with normal kidney function; monitor BP and heart rate closely (Ref); no supplemental dose postdialysis is necessary (Ref).

ER tablet (Nexiclon): Initiate at 0.09 mg once daily at bedtime; titrate upward cautiously.

Peritoneal dialysis: Unlikely to be significantly dialyzable (highly lipid soluble) (Ref):

Oral, transdermal: Start with a low dose and titrate upward cautiously according to patient response, no more frequently than for patients with normal kidney function; monitor BP and heart rate closely (Ref).

CRRT:

Oral: Initial: Start with a low dose and titrate upward cautiously according to patient response, no more frequently than for patients with normal kidney function; monitor BP and heart rate closely (Ref).

Transdermal: Avoid use (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration):

Oral: Initial: Start with a low dose and titrate upward cautiously according to patient response, no more frequently than for patients with normal kidney function; monitor BP and heart rate closely (Ref).

Transdermal: Avoid use (Ref).

Dosing: Hepatic Impairment: Adult

No dosage adjustment provided in manufacturer's labeling.

Adverse Reactions (Significant): Considerations
Bradycardia and hypotension

Bradycardia and hypotension may occur with therapeutic or supratherapeutic dosing of clonidine in all ages. These adverse reactions may require intervention, and they are generally reversible with discontinuation.

Mechanism: Dose-related (consistently with bradycardia; more variable with hypotension); related to the pharmacologic action (ie, central alpha-2 adrenergic receptor agonist-mediated reduction in sympathetic outflow) (Ref).

Onset: Varied; may occur at any time during therapy. Varies based on dosage form (Ref). May occur within 30 minutes of oral administration (most significant effects within 1 to 4 hours) (Ref). There is a 2- to 3-day delay in onset for transdermal administration (Ref). Most hypotensive episodes occur within the first 4 days with epidural administration (Ref).

Risk factors:

Hypotension:

• Concurrent antihypertensives or antipsychotics

• History of bradycardia, dehydration, hypotension, or syncope

• Perioperative use (Ref)

• Transdermal preparations in the setting of a degraded skin barrier and excessive dosing (Ref)

• Epidural administration

- Concurrent narcotic analgesics

- Females

- Hemodynamic instability

- Low body weight

- Severe cardiovascular disease

- Use in obstetrical or postpartum patients

Bradycardia:

• Cardiac conduction abnormalities

• Clinical sinus node dysfunction (Ref)

• Concurrent administration of medications that impact sinus node function or AV node conduction (eg, beta-blockers, digoxin, diltiazem, verapamil)

• History of bradycardia, or dehydration, hypotension, or syncope

• Kidney impairment (Ref)

• Patients who develop bradycardia while taking other sympatholytic medications or who are concurrently taking another sympatholytic medication (Ref)

• Perioperative use (Ref)

• Transdermal preparations in the setting of a degraded skin barrier and excessive dosing (Ref)

• Epidural administration

- Use in obstetrical or postpartum patients

Withdrawal syndrome/rebound hypertension

A withdrawal syndrome, primarily characterized by a rapid increase in blood pressure (rebound hypertension), may occur upon abrupt discontinuation of clonidine, regardless of administration route. Additional symptoms may include diaphoresis, flushing, headache, and insomnia (Ref). Risk may be lower with transdermal clonidine administration due to a more gradual reduction in drug concentrations (Ref). Blood pressure may exceed pretreatment levels in some cases (Ref).

Mechanism: Withdrawal; result of excessive plasma catecholamine levels, “catecholamine surge” (Ref).

Onset: Rapid; typically occurs within 4 to 24 hours of drug discontinuation but may occur up to 72 hours after drug discontinuation (Ref).

Risk factors:

• Cardiovascular disease

• Concurrent cardioselective beta-blocker therapy

• Duration of use (>1 to 2 months) (Ref)

• Higher doses (>1 mg/day) (Ref)

• Hypertension

• Medication nonadherence

• Vomiting (abrupt inability to absorb oral dosage forms)

• Empty infusion pump drug reservoir (neuraxial administration)

• Infusion pump malfunction (neuraxial administration) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Oral, Transdermal: Incidence of adverse reactions may be less with transdermal compared to oral due to the lower peak/trough ratio.

>10%:

Dermatologic: Contact dermatitis (transdermal: 8% to 34%), transient skin rash (localized; characterized by pruritus and erythema; transdermal: 50%)

Gastrointestinal: Upper abdominal pain (15%), xerostomia (0% to 40%) (table 1)

Clonidine: Adverse Reaction: Xerostomia (Oral, Transdermal)

Drug (Clonidine)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

5%

1%

Children and adolescents

0.4 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

78

76

0%

1%

Children and adolescents

0.2 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

76

76

40%

N/A

Adults

N/A

Immediate-release oral tablets

Hypertension

100

N/A

25%

N/A

Adults

N/A

Transdermal patch

Hypertension

101

N/A

Nervous system: Dizziness (2% to 16%) (table 2), drowsiness (12% to 38%) (table 3), fatigue (6% to 16%) (table 4), headache (5% to 20%) (table 5)

Clonidine: Adverse Reaction: Dizziness (Oral, Transdermal)

Drug (Clonidine)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

7%

5%

Children and adolescents

0.2 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

76

76

3%

5%

Children and adolescents

0.4 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

78

76

16%

N/A

Adults

N/A

Immediate-release oral tablets

Hypertension

100

N/A

2%

N/A

Adults

N/A

Transdermal patch

Hypertension

101

N/A

Clonidine: Adverse Reaction: Drowsiness (Oral, Transdermal)

Drug (Clonidine)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

38%

4%

Children and adolescents

0.2 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

76

76

31%

4%

Children and adolescents

0.4 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

78

76

33%

N/A

Adults

N/A

Immediate-release oral tablets

Hypertension

100

N/A

12%

N/A

Adults

N/A

Transdermal patch

Hypertension

101

N/A

Clonidine: Adverse Reaction: Fatigue (Oral, Transdermal)

Drug (Clonidine)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

16%

1%

Children and adolescents

0.2 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

76

76

13%

1%

Children and adolescents

0.4 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

78

76

6%

N/A

Adults

N/A

Transdermal patch

Hypertension

101

N/A

Clonidine: Adverse Reaction: Headache (Oral, Transdermal)

Drug (Clonidine)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

20%

16%

Children and adolescents

0.2 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

76

76

13%

16%

Children and adolescents

0.4 mg//day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

78

76

5%

N/A

Adults

N/A

Transdermal patch

Hypertension

101

N/A

1% to 10%:

Cardiovascular: Bradycardia (4%) (table 6)

Clonidine: Adverse Reaction: Bradycardia (Oral, Transdermal)

Drug (Clonidine)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

4%

0%

Children and adolescents

0.4 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

78

76

Dermatologic: Burning sensation of skin (transdermal: 3%), contact hypersensitivity (transdermal: 5%), excoriation of skin (transdermal: 3%), hyperpigmentation (transdermal: 5%), macular eruption (transdermal: 1%), papule of skin (transdermal: 1%)

Gastrointestinal: Constipation (1% to 10%), dysgeusia (transdermal: 1%), nausea (1% to 5%), viral gastrointestinal infection (5%)

Genitourinary: Impotence (transdermal: ≤2%), sexual disorder (transdermal: ≤2%), urinary incontinence (4%)

Local: Localized blanching (transdermal: 1%), localized edema (transdermal: 3%), localized vesiculation (transdermal: 7%)

Nervous system: Aggressive behavior (1% to 3%), emotional disturbance (4%), insomnia (2% to 6%) (table 7), irritability (5% to 9%), lethargy (3%), nervousness (1%), night terrors (3%), nightmares (4% to 9%), restless sleep (3%), sedated state (3% to 10%), sleep disorder (1% to 3%), throbbing (transdermal: 1%), tremor (1% to 4%)

Clonidine: Adverse Reaction: Insomnia (Oral, Transdermal)

Drug (Clonidine)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

6%

1%

Children and adolescents

0.4 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

78

76

5%

1%

Children and adolescents

0.2 mg/day

Extended-release tablet

Attention-deficit/hyperactivity disorder (ADHD)

76

76

2%

N/A

Adults

N/A

Transdermal patch

Hypertension

101

N/A

Otic: Otitis media (3%; acute)

Respiratory: Dry throat (transdermal: 2%)

Miscellaneous: Crying (1% to 3%)

Frequency not defined:

Cardiovascular: Atrioventricular block, chest pain, heart failure, orthostatic hypotension, palpitations, prolonged QT interval on ECG, Raynaud disease, syncope, tachycardia

Dermatologic: Alopecia, hypopigmentation (localized), pallor, skin rash, urticaria

Endocrine & metabolic: Gynecomastia, increased serum glucose (transient), loss of libido, weight gain

Gastrointestinal: Abdominal pain, anorexia, gastrointestinal pseudo-obstruction, parotitis, salivary gland pain, vomiting

Genitourinary: Breast hypertrophy, difficulty in micturition, erectile dysfunction, nocturia, urinary retention

Hematologic & oncologic: Positive direct Coombs’ test, thrombocytopenia

Hepatic: Abnormal hepatic function tests (mild; transient), hepatitis

Hypersensitivity: Angioedema

Nervous system: Agitation, anxiety, asthenia, behavioral changes, cerebrovascular accident, decreased sexual activity, delirium, delusion, depression, hallucination (visual and auditory), malaise, numbness (localized), paresthesia, restlessness, vivid dream, withdrawal syndrome

Neuromuscular & skeletal: Arthralgia, increased creatine phosphokinase in blood specimen (transient), lower limb cramp, myalgia

Ophthalmic: Accommodation disturbance, blurred vision, burning sensation of eyes, decreased lacrimation, dry eye syndrome

Respiratory: Dry nose

Miscellaneous: Fever

Epidural: The following adverse reactions occurred more often than placebo in cancer patients with intractable pain being treated with concurrent epidural morphine.

>10%:

Cardiovascular: Hypotension (45%) (table 8), orthostatic hypotension (32%) (table 9)

Clonidine: Adverse Reaction: Hypotension (Epidural)

Drug (Clonidine)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

45%

11%

30 mcg/hour

Epidural infusion

Analgesia

38

47

Clonidine: Adverse Reaction: Orthostatic hypotension (Epidural)

Drug (Clonidine)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

32%

0%

30 mcg/hour

Epidural infusion

Analgesia

38

47

Gastrointestinal: Xerostomia (13%) (table 10)

Clonidine: Adverse Reaction: Xerostomia (Epidural)

Drug (Clonidine)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

13%

9%

30 mcg/hour

Epidural infusion

Analgesia

38

47

Nervous system: Confusion (13%), dizziness (13%) (table 11)

Clonidine: Adverse Reaction: Dizziness (Epidural)

Drug (Clonidine)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

13%

4%

30 mcg/hour

Epidural infusion

Analgesia

38

47

1% to 10%:

Cardiovascular: Chest pain (5%)

Dermatologic: Diaphoresis (5%) (table 12)

Clonidine: Adverse Reaction: Diaphoresis (Epidural)

Drug (Clonidine)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Clonidine)

Number of Patients (Placebo)

5%

0%

30 mcg/hour

Epidural infusion

Analgesia

38

47

Gastrointestinal: Nausea and vomiting (8%)

Nervous system: Hallucination (5%)

Otic: Tinnitus (5%)

Contraindications

Hypersensitivity to clonidine hydrochloride or any component of the formulation.

Epidural administration: Injection site infection; concurrent anticoagulant therapy; bleeding diathesis; administration above the C4 dermatome.

Canadian labeling: Additional contraindications (not in US labeling): Severe bradyarrhythmia from second- or third-degree atrioventricular block or sick sinus syndrome; sinus node dysfunction; hereditary problems of galactose intolerance (eg, galactosemia).

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression (including sedation and somnolence), which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with severe coronary insufficiency, including recent MI. Epidural clonidine is not recommended for use in patients with severe cardiovascular disease or hemodynamic instability.

• Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.

• Renal impairment: Use with caution in patients with chronic renal impairment. The hemodynamic effects may be prolonged in those with renal impairment; elimination half-life significantly prolonged (up to 41 hours) in patients with severe renal impairment.

Dosage form specific issues:

• Epidural use: Should be administered via continuous epidural infusion device.

• Product interchangeability: Oral formulations of clonidine (immediate release versus extended release) are not interchangeable on a mg:mg basis due to different pharmacokinetic profiles. Oral extended-release formulations of clonidine (Kapvay [indicated for attention-deficit/hyperactivity disorder in pediatric patients] vs Nexiclon XR [indicated for hypertension in adults]) are not interchangeable on a mg:mg basis due to different pharmacokinetic profiles.

• Transdermal patch: May contain conducting metal (eg, aluminum); remove patch prior to MRI. Due to the potential for altered electrical conductivity, remove transdermal patch before cardioversion or defibrillation. Localized contact sensitization to the transdermal system has been reported; in these patients, allergic reactions (eg, generalized rash, urticaria, angioedema) have also occurred following subsequent substitution of oral therapy.

Other warnings/precautions:

• Contact lens wearers: Clonidine may cause eye dryness in patients who wear contact lenses.

• Discontinuation of therapy: Gradual withdrawal is needed (discontinue oral immediate release or epidural dose gradually over 6 to 10 days to avoid rebound hypertension) if drug needs to be stopped. Patients should be instructed about abrupt discontinuation (causes rapid increase in BP and symptoms of sympathetic overactivity). In patients on both a beta-blocker and clonidine where withdrawal of clonidine is necessary, withdraw the beta-blocker first and several days before clonidine withdrawal, then slowly decrease clonidine.

Warnings: Additional Pediatric Considerations

Prior to treatment with medications for attention-deficit/hyperactivity disorder (ADHD), the American Heart Association and the American Academy of Pediatrics recommend that all children and adolescents diagnosed with ADHD have a thorough cardiovascular assessment, including patient and family health histories, determination of all medications used (prescribed and over-the-counter), and a physical examination focused on cardiovascular disease risk factors. An ECG is not mandatory but is reasonable to consider prior to stimulant medication therapy. Prompt evaluation and appropriate referral and testing, if warranted, should occur if any cardiac symptoms present (Vetter 2008). These recommendations are based upon reports of serious cardiovascular adverse events (including sudden death) in patients (both children and adults) taking usual doses of stimulant medications. Most of these patients were found to have underlying structural heart disease (eg, hypertrophic obstructive cardiomyopathy). ECG abnormalities and 4 cases of sudden cardiac death have been reported in children receiving clonidine with methylphenidate; a dose reduction of methylphenidate when used concurrently with clonidine has been suggested; consider ECG monitoring. In patients with ADHD, clonidine may cause hypotension and bradycardia; use with caution in patients with history of hypotension, heart block, bradycardia, cardiovascular disease, syncope, conditions predisposing to syncope (including orthostatic hypotension, dehydration), or receiving concomitant antihypertensive therapy. Patients should be advised to avoid becoming dehydrated or overheated. Heart rate and blood pressure should be monitored at initiation of therapy, with any dose increase, and periodically during therapy.

Product Availability

Onyda XR (0.1 mg/mL extended-release oral suspension): FDA approved May 2024; availability anticipated in the second half of 2024. Information pertaining to this product within the monograph is pending revision. Onyda XR is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) as monotherapy and as adjunctive therapy to CNS stimulant medications in pediatric patients ≥6 years of age. Consult the prescribing information for additional information.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Patch Weekly, Transdermal:

Catapres-TTS-1: 0.1 mg/24 hr (4 ea)

Catapres-TTS-2: 0.2 mg/24 hr (4 ea)

Catapres-TTS-3: 0.3 mg/24 hr (4 ea)

Generic: 0.1 mg/24 hr (1 ea, 4 ea); 0.2 mg/24 hr (1 ea, 4 ea); 0.3 mg/24 hr (1 ea, 4 ea)

Solution, Epidural, as hydrochloride [preservative free]:

Duraclon: 100 mcg/mL (10 mL)

Generic: 100 mcg/mL (10 mL); 500 mcg/mL (10 mL)

Tablet, Oral, as hydrochloride:

Catapres: 0.1 mg [DSC] [contains corn starch, fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]

Catapres: 0.2 mg [DSC], 0.3 mg [DSC] [contains corn starch, fd&c yellow #6 (sunset yellow)]

Generic: 0.1 mg, 0.2 mg, 0.3 mg

Tablet Extended Release 12 Hour, Oral, as hydrochloride:

Kapvay: 0.1 mg [DSC]

Generic: 0.1 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Nexiclon XR: 0.17 mg [scored]

Generic: 0.17 mg

Generic Equivalent Available: US

Yes

Pricing: US

Patch weekly (Catapres-TTS-1 Transdermal)

0.1 mg/24 hrs (per each): $87.07

Patch weekly (Catapres-TTS-2 Transdermal)

0.2 mg/24 hrs (per each): $146.61

Patch weekly (Catapres-TTS-3 Transdermal)

0.3 mg/24 hrs (per each): $203.38

Patch weekly (cloNIDine Transdermal)

0.1 mg/24 hrs (per each): $33.12 - $78.28

0.2 mg/24 hrs (per each): $55.77 - $131.80

0.3 mg/24 hrs (per each): $77.36 - $182.84

Solution (cloNIDine HCl (Analgesia) Epidural)

100 mcg/mL (per mL): $3.13 - $5.04

500 mcg/mL (per mL): $12.25 - $19.50

Solution (Duraclon Epidural)

100 mcg/mL (per mL): $5.28

Tablet, 12-hour (cloNIDine HCl ER Oral)

0.1 mg (per each): $4.50

Tablet, 24-hour (cloNIDine HCl ER Oral)

0.17 mg (per each): $19.74

Tablet, 24-hour (Nexiclon XR Oral)

0.17 mg (per each): $21.96

Tablets (cloNIDine HCl Oral)

0.1 mg (per each): $0.05 - $0.26

0.2 mg (per each): $0.08 - $0.45

0.3 mg (per each): $0.13 - $0.63

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 0.025 mg

Tablet, Oral, as hydrochloride:

Generic: 0.1 mg, 0.2 mg

Extemporaneous Preparations

Note: Compounded oral suspension may be available in multiple concentrations (eg, up to 10 times more concentrated); use caution to avoid confusion; verify concentration.

0.02 mg/mL (20 mcg/mL) Oral Liquid (ASHP Standard Concentration) (ASHP 2017)

A 0.02 mg/mL (20 mcg/mL) oral liquid may be made from tablets. Crush six 0.1 mg tablets in a glass mortar and levigate with 1 to 2 mL Simple Syrup, NF. Add additional Simple Syrup, NF and transfer to a calibrated amber bottle. Rinse the mortar and pestle with the vehicle and add quantity of vehicle sufficient to make 30 mL. Label “refrigerate.” Stable for 35 days when stored in an ambler plastic bottle and refrigerated.

Sauberan JB, Phuong P, Ilog ND, Rossi SS. Stability and osmolality of extemporaneously prepared clonidine oral liquid for neonates. Ann Pharmacother. 2016;50(3):243-244. doi: 10.1177/1060028015620625.26728366

0.01 mg/mL (10 mcg/mL) Oral Suspension

A 0.01 mg/mL (10 mcg/mL) oral suspension may be made from tablets. Crush twenty 0.1 mg tablets in a glass mortar and reduce to a fine powder. Slowly add Ora-Blend in ~15 mL increments while mixing to form a uniform paste until approximately half of the total volume (~100 mL) is added. Transfer the suspension to a graduated cylinder. Rinse the mortar and pestle with the remaining vehicle and add quantity to fill the volume within the graduated cylinder to 200 mL. Transfer this amount to a calibrated bottle. Label “shake well.” When stored in clear plastic syringes, the suspension is stable for at least 91 days at room temperature (25°C) or refrigerated (4°C).

Ma C, Decarie D, Ensom MHH. Stability of clonidine oral suspension in oral plastic syringes. Am J Health-Syst Pharm. 2014;71:657-661.24688040

0.1 mg/mL (100 mcg/mL) Oral Suspension

A 0.1 mg/mL (100 mcg/mL) oral suspension may be made from tablets. Crush thirty 0.2 mg tablets in a glass mortar and reduce to a fine powder. Slowly add 2 mL Purified Water USP and mix to a uniform paste. Slowly add Simple Syrup, NF in 15 mL increments; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label "shake well" and "refrigerate". Stable for 28 days when stored in amber glass bottles and refrigerated.

Levinson ML and Johnson CE. Stability of an extemporaneously compounded clonidine hydrochloride oral liquid. Am J Hosp Pharm. 1992;49(1):122-125.1570852
Additional Information

Clonidine hydrochloride 0.1 mg is equal to 0.087 mg of the free base.

Administration: Pediatric

Oral: May be administered without regard to meals. Do not discontinue clonidine abruptly.

Extended-release (Kapvay): Swallow whole; do not crush, chew, or split.

Transdermal: Patches should be applied at bedtime to a clean, hairless area of the upper arm or chest. In adults, patches are applied every 7 days, rotating patch sites weekly; in children, the patch may need to be changed more frequently (eg, every 5 days) (Ref); in adults, redness under patch may be reduced if a topical corticosteroid spray is applied to the area before placement of the patch (Ref); Note: Transdermal patch is a membrane-controlled system; do not cut the patch to deliver partial doses; rate of drug delivery, reservoir contents, and adhesion may be affected if cut; if partial dose is needed, surface area of patch can be blocked proportionally using adhesive bandage (Ref).

Epidural: Not for IV use. Visually inspect for particulate matter and discoloration prior to administration (whenever permitted by container and solution). Specialized techniques are required for continuous epidural administration; administration via this route should only be performed by qualified individuals familiar with the techniques of epidural administration and patient management problems associated with this route. Familiarization of the epidural infusion device is essential. Do not discontinue clonidine abruptly; if needed, gradually reduce dose over 2 to 4 days to avoid withdrawal symptoms.

Administration: Adult

Epidural: Specialized techniques are required for continuous epidural administration; administration via this route should only be performed by qualified individuals familiar with the techniques of epidural administration and patient management problems associated with this route. Familiarization of the epidural infusion device is essential. Do not discontinue clonidine abruptly; if needed, gradually reduce dose over 2 to 3 days to avoid withdrawal symptoms.

Oral: May be taken with or without food. Swallow whole with water (0.025 mg tablet [Canadian product]). Swallow ER tablets (Kapvay) whole; do not crush, chew, or split. ER tablets (Nexiclon) are scored tablets and may be split in half. Administer ER tablets (Nexiclon) preferably at bedtime.

Transdermal patch: Patches should be applied weekly at a consistent time to a clean, hairless area of the upper outer arm or chest. Rotate patch sites weekly. Redness under patch may be reduced if a topical corticosteroid spray is applied to the area before placement of the patch (Ref). Dispose of any used or unused patches by folding adhesive ends together, replace in pouch or sealed container, and discard properly in trash away from children and pets.

Storage/Stability

Epidural formulation: Store at 20°C to 25°C (68°F to 77°F). Preservative free; discard unused portion.

Tablets: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

ER tablets (Kapvay): Store at 20°C to 25°C (68°F to 77°F). Protect from light.

ER tablets (Nexiclon): Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F and 86°F).

Transdermal patches: Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F and 86°F).

Use

Oral:

Immediate release: Management of hypertension (monotherapy or as adjunctive therapy) (FDA approved in adults); has also been used for the treatment of attention-deficit/hyperactivity disorder (ADHD), Tourette syndrome and tic disorders, neonatal abstinence syndrome, insomnia, posttraumatic stress disorder, and as an aid in the diagnosis of growth hormone deficiency.

Extended release: Treatment of ADHD (monotherapy or as adjunctive therapy) (Kapvay: FDA approved in ages 6 to 17 years); treatment of hypertension (Nexiclon XR: FDA approved in adults).

Parenteral: Epidural: Duraclon: For epidural administration as adjunctive therapy with opioids for treatment of severe cancer pain in patients unresponsive to opioids alone (FDA approved in pediatric patients [age not specified] and adults). Note : Although included as an FDA-approved use in the manufacturer's prescribing information, use of epidural clonidine in combination with opioids for the treatment of severe cancer pain in patients unresponsive to opioids alone is not considered standard of care.

Topical: Transdermal patch: Management of hypertension (monotherapy or as adjunctive therapy) (FDA approved in adults); has also been used for the treatment of ADHD.

Medication Safety Issues
Sound-alike/look-alike issues:

CloNIDine may be confused with Clomid, clomiPHENE, clonazePAM, cloZAPine, KlonoPIN, quiNIDine

Catapres may be confused with Cataflam, Combipres

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (epidural and intrathecal medications) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).

Older Adult: High-Risk Medication:

Beers Criteria: Clonidine is identified in the Beers Criteria as a potentially inappropriate medication in patients 65 years and older for hypertension treatment due to high risk of CNS adverse effects and risk of bradycardia and orthostatic hypotension associated with central alpha agonists. Avoid clonidine as a first-line antihypertensive (Beers Criteria [AGS 2023]).

Clonidine is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) due to an increased risk of falls and decreased tolerance compared to other antihypertensive classes. Use with caution in patients with severe aortic stenosis (O’Mahony 2023).

Administration issues:

Use caution when interpreting dosing information. Pediatric dose for epidural infusion expressed as mcg/kg/hour.

Other safety concerns:

Transdermal patch may contain conducting metal (eg, aluminum); remove patch prior to MRI. Errors have occurred when the inactive, optional adhesive cover has been applied instead of the active clonidine-containing patch.

Metabolism/Transport Effects

None known.

Reproductive Considerations

Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be continued in patients trying to conceive. Consider transitioning from clonidine to an agent preferred for use during pregnancy in patients planning to become pregnant (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019); clonidine is considered an alternative option due to possible side effects (SOGC [Magee 2022]).

Pregnancy Considerations

Clonidine crosses the placenta.

Clonidine concentrations in the umbilical cord plasma are similar to those in the maternal serum and concentrations in the amniotic fluid may be 4 times those in the maternal serum.

The pharmacokinetics of clonidine may be altered during pregnancy due to an increase in nonrenal clearance, possibly regulated by maternal CYP2D6 genotype (Buchanan 2009; Claessens 2010).

Chronic maternal hypertension is associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).

Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). When treatment of chronic hypertension is initiated during pregnancy, agents other than clonidine may be preferred (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]). Clonidine is considered an alternative option due to possible side effects (SOGC [Magee 2022]); use should be considered in consult with subspecialists (ACOG 2019).

Based on outcome data following use for hypertension during pregnancy, clonidine may be used in pregnant patients with attention-deficit/hyperactivity disorder (ADHD) when needed (Ornoy 2021). Data collection to monitor pregnancy and infant outcomes following exposure to ADHD medications is ongoing. Health care providers are encouraged to enroll patients exposed to Kapvay during pregnancy in the National Pregnancy Registry for ADHD Medications (866-961-2388).

Clonidine has been evaluated for use as an adjunctive agent for epidural labor analgesia (Allen 2018; Cavens 2022; Kumari 2018; Xia 2022; Zhang 2015), including patients who are opioid dependent (Hoyt 2018); however, the manufacturer does not recommend epidural clonidine for obstetrical or postpartum pain due to the risk of hemodynamic instability. Severe maternal hypotension may occur following epidural use, which may result in decreased placental perfusion. Potential benefits may outweigh the possible risks in some obstetrical or postpartum patients.

Clonidine has been evaluated for the management of opioid withdrawal; however, withdrawal management using clonidine is not preferred for patients who are pregnant (ASAM 2020).

Monitoring Parameters

Blood pressure, heart rate; consider ECG monitoring in patients with history of heart disease or concurrent use of medications affecting cardiac conduction.

Attention-deficit/hyperactivity disorder (ADHD): Prior to initiation of therapy, assess medical history and family history of sudden death or ventricular arrhythmia, and perform physical exam to assess for cardiac disease; patients should receive further evaluation if findings suggest cardiac disease, such as ECG and echocardiogram; promptly conduct cardiac evaluation in patients who develop exertional chest pain, unexplained syncope, or any other symptom of cardiac disease during treatment. For children already taking a stimulant, it is reasonable to evaluate medical and family history, review physical examination, and order ECG if not done prior to initiation (Vetter 2008).

Neonatal opioid withdrawal syndrome: Abstinence scoring system.

Clonidine tolerance test: In addition to growth hormone concentrations, monitor blood pressure and blood glucose (Huang 2001).

Epidural: Carefully monitor infusion pump; inspect catheter tubing for obstruction or dislodgement to reduce risk of inadvertent abrupt discontinuation of infusion. Monitor closely for catheter-related infection (eg, meningitis, epidural abscess).

Mechanism of Action

Stimulates alpha-2 adrenoceptors in the brain stem, thus activating an inhibitory neuron, resulting in reduced sympathetic outflow from the CNS, producing a decrease in peripheral resistance, renal vascular resistance, heart rate, and blood pressure; epidural clonidine may produce pain relief at spinal presynaptic and postjunctional alpha-2 adrenoceptors by preventing pain signal transmission; pain relief occurs only for the body regions innervated by the spinal segments where analgesic concentrations of clonidine exist. For the treatment of ADHD, the mechanism of action is unknown; it has been proposed that postsynaptic alpha-2 agonist stimulation regulates subcortical activity in the prefrontal cortex, the area of the brain responsible for emotions, attentions, and behaviors and causes reduced hyperactivity, impulsiveness, and distractibility. Epidurally administered clonidine produces dose-dependent analgesia not antagonized by opiate antagonists. The analgesia is limited to the body regions innervated by the spinal segments where analgesic concentrations of clonidine are present. Clonidine is thought to produce analgesia at presynaptic and postjunctional alpha-2 adrenoceptors in the spinal cord by preventing pain signal transmission to the brain.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action:

Antihypertensive effect: Oral: Immediate release: 0.5 to 1 hour (maximum reduction in blood pressure: 2 to 4 hours); Transdermal: Initial application: 2 to 3 days; Transdermal: Steady state reached in ~3 days.

Attention-deficit/hyperactivity disorder: Oral: Extended release (Kapvay): Onset of action: 1 to 2 weeks (AAP [Wolraich 2011]).

Absorption: Oral: Extended-release tablets (Kapvay) are not bioequivalent with immediate-release formulations; peak plasma concentrations are 50% lower compared to immediate-release formulations.

Distribution: Vd: ~2.9 L/kg; highly lipid soluble; distributes readily into extravascular sites.

Note: Epidurally administered clonidine readily distributes into plasma via the epidural veins and attains clinically significant systemic concentrations.

Protein binding: 20% to 40%.

Metabolism: Extensively hepatic to inactive metabolites; undergoes enterohepatic recirculation.

Bioavailability: Oral: Immediate release: 70% to 80%; Extended release (Kapvay): ~89% (relative to immediate-release formulation); Transdermal: ~60%.

Half-life elimination:

Children: 6.13 ± 1.33 hours (Lonnqvist 1993).

Adults: Normal renal function: 12 to 16 hours; Renal impairment: ≤41 hours.

Epidural administration: CSF half-life elimination: 1.3 ± 0.5 hours; plasma half-life elimination: 22 ± 15 hours.

Transdermal: Half-life elimination (after patch removal): ~20 hours (due to skin depot effect; increase in plasma clonidine concentrations may occur after patch removal [MacGregor 1985]).

Time to peak, plasma: Oral: Immediate release: 1 to 3 hours; Extended release (Kapvay): 7 to 8 hours; Extended release (Nexiclon): 7.8 ± 1.7 hours.

Excretion: Urine (40% to 60% as unchanged drug).

Clearance:

Oral:

Neonates: 0.16 L/kg/hour (Xie 2011).

Infants and Children ≤4 years: ~0.3 L/kg/hour (Xie 2011).

Children 5 to 10 years: ~0.26 L/kg/hour (Xie 2011).

Adults: Single dose: ~0.25 L/kg/hour; Multiple dose: ~0.4 L/kg/hour (Frisk-Holmberg 1981).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: The half-life increases up to 41 hours in patients with severe renal impairment.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Arkamin | Catapres;
  • (AR) Argentina: Catapresan | Clonidina gray;
  • (AT) Austria: Catapresan;
  • (AU) Australia: Apo-clonidine | Catapres | Catapres clonidine hydrochloride | Clonidine | Clonidine scp;
  • (BD) Bangladesh: Catapres | Clonipres;
  • (BE) Belgium: Catapressan | Dixarit;
  • (BG) Bulgaria: Chlophazolin | Clonidon;
  • (BR) Brazil: Atensina | Clonesina | Neo clodil;
  • (CH) Switzerland: Catapresan;
  • (CL) Chile: Catapresan;
  • (CN) China: Clonidine;
  • (CO) Colombia: Catapresan | Clonidin | Clonidina | Clonidina E-cardio | Clonidina winthrop;
  • (CZ) Czech Republic: Catapresan | Haemiton;
  • (DE) Germany: Catapresan | Clonidin | Clonidin ratiopharm | Clonistada | Haemiton | Paracefan;
  • (DO) Dominican Republic: Cataperten | Catapresan | Clonidina mamey | Cloniperten | Coasin | Iclotan | Karpatil | Presonal;
  • (EC) Ecuador: Catapresan | Clonidina;
  • (EE) Estonia: Catapresan | Chlophazolin | Clophelin | Haemiton;
  • (EG) Egypt: Catapres;
  • (ES) Spain: Catapresan;
  • (FI) Finland: Caprysin | Catapresan | Clonisin;
  • (FR) France: Catapressan | Clonidine Dci | Clonidine rpg;
  • (GB) United Kingdom: Catapres | Catapres tts | Clonidine | Clonidine sandoz | Clonidine teva | Dixarit;
  • (GR) Greece: Catapres | Catapresan | Catapressan;
  • (HK) Hong Kong: Apo-clonidine | Catapres | Dixarit;
  • (HU) Hungary: Clonidin;
  • (ID) Indonesia: Catapres | Clonidine;
  • (IE) Ireland: Catapres | Clonidine | Dixarit;
  • (IL) Israel: Clonnirit | Normopresan;
  • (IN) India: Arkamin | Arkapres | Catapres | Clodict | Clonithem | Clonomide | Clopresyn | Nefropres c | Nefropress c;
  • (IT) Italy: Adesipress | Catapresan | Clonidina provvisoria;
  • (JP) Japan: Catapres;
  • (KR) Korea, Republic of: Catapres | Clonidine | Kapvay | Senidine;
  • (LB) Lebanon: Catapres | Catapressan;
  • (LT) Lithuania: Apo clonidin | Catapresan | Chlophazolin | Clophelin | Haemiton | Iporel;
  • (LU) Luxembourg: Catapressan | Dixarit;
  • (LV) Latvia: Catapresan | Chlophazolin | Clophelin | Haemiton;
  • (MA) Morocco: Catapressan;
  • (MX) Mexico: Bomath | Catapresan | Clonidina | Epiclodina;
  • (MY) Malaysia: Clonidine bnm | Dixarit;
  • (NL) Netherlands: Catapresan | Clonidine HCL | Clonidine Hcl Actavis | Clonidine hcl PCH | Clonidine hcl sandoz | Dixarit;
  • (NO) Norway: Carexarit | Catapresan | Catapresan glenwood | Catapresan tts-2 | Catapresan unimedic | Catapress TTS | Catapressan | Clonidin ratiopharm | Clonidine | Clonidine hcl aurobindo | Clonidine hcl cf | Iporel | Kapvay | Mar clonidine | Teva Clonidine;
  • (NZ) New Zealand: Catapres | Clonidine | Clonidine teva | Dixarit;
  • (PE) Peru: Catapresan | Clonidina;
  • (PH) Philippines: Alphapres | Catamed | Catapin | Catapres | Clodin | Clonidine | Clonigen | Clonimed | Clonipress;
  • (PL) Poland: Haemiton | Iporel | Paracefan;
  • (PR) Puerto Rico: Catapres | Clonidine | Clonidine extended release | Clonidine HCL | Clonidine hcl er | Clonidine hydrochloride er | Clonidine hydrochloride extended release | Kapvay | Nexiclon xr;
  • (PT) Portugal: Catapresan;
  • (QA) Qatar: Catapres | Catapresan | Clonistada;
  • (RO) Romania: Clonidina | Clonidine | Haemiton;
  • (RU) Russian Federation: Clofelin | Clophelin | Haemiton;
  • (SA) Saudi Arabia: Catapres;
  • (SE) Sweden: Catapresan;
  • (SG) Singapore: Dixarit;
  • (SI) Slovenia: Catapresan | Catapress | Catapressan | Clonidin ratiopharm | Clonistada;
  • (SK) Slovakia: Catapresan;
  • (TH) Thailand: Capril | Catapres | Coropress | Hypodine;
  • (TN) Tunisia: Catapressan;
  • (TR) Turkey: Catapres;
  • (TW) Taiwan: Catapren | Catapres | Chianda | Clodin | Clonidine | Dixarit | Hypolax | Kochaniin | Pinsanidine | Winpress;
  • (UA) Ukraine: Catapresan | Clophelin | Clophelinum | Clophelinum ic | Haemiton;
  • (UY) Uruguay: Catapresan | Epyclon | Normopresin;
  • (VE) Venezuela, Bolivarian Republic of: Catapresan | Clonidina | Clonipres | Naclodin | Velaril;
  • (VN) Viet Nam: Tepirace;
  • (ZA) South Africa: Catapres | Dixarit | Menograine
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