Version July 2025
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.
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 (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 (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 (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 (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 (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.
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).
No dosage adjustment provided in manufacturer's labeling.
Hypertension: Note: Avoid as first-line treatment due to risk of CNS effects, bradycardia, and orthostatic hypotension.
Oral:
Extended release: Consider initiating at a lower dose.
Immediate release: Initial: 0.1 mg once daily at bedtime, increase gradually as needed.
(For additional information see "Clonidine: Pediatric drug information")
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], Onyda XR [oral suspension]) formulations of clonidine are not interchangeable on a mg per mg basis due to different pharmacokinetic profiles. Extended-released formulations (Kapvay [tablets], Onyda XR [oral suspension], Nexiclon XR [tablets]) are not interchangeable on a mg:mg basis; Kapvay and Onyda XR are 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 (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:
Oral suspension (eg, Onyda XR): 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; maximum daily dose: 0.4 mg/day once daily at bedtime. Note: When switching from other clonidine products, discontinue that product and titrate using the dosing schedule above. When discontinuing therapy, taper daily dose by ≤0.1 mg every 3 to 7 days (Ref).
Tablets, twice-daily formulation (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 (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; gradually reduce dose over 2 to 4 days to avoid withdrawal symptoms.
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 (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 (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 (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: 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.
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.
There are no dosage adjustments provided in the manufacturer's labeling.
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
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)
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)
|
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)
|
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 |
|
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 |
|
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 |
|
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)
|
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: Erectile dysfunction (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%)
|
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)
|
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 |
|
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)
|
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)
|
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)
|
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%)
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).
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, Onyda XR, Nexiclon XR) 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.
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.
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)
Suspension Extended Release, Oral, as hydrochloride:
Onyda XR: 0.1 mg/mL (7 mL, 30 mL, 60 mL [DSC]) [contains edetate (edta) disodium, methylparaben, polysorbate 80, propylparaben]
Tablet, Oral, as hydrochloride:
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:
Nexiclon XR: 0.17 mg [scored]
Generic: 0.17 mg
May be product dependent
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): $19.50
Solution (Duraclon Epidural)
100 mcg/mL (per mL): $5.28
Suspension Extended Release (Onyda XR Oral)
0.1 mg/mL (per mL): $16.12
Tablet, 12-hour (cloNIDine HCl ER Oral)
0.1 mg (per each): $4.50
Tablet, 24-hour (cloNIDine 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 - $0.43
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.
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
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. 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).
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Oral tablet, immediate-release:
Gastric (eg, NG, G-tube) or post-pyloric (eg, J-tube) tubes (≥8 French): Crush tablet(s) into a fine powder and disperse in 10 to 20 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated clonidine tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are dispersed sufficiently with an adequate amount of purified water prior to administration (Ref).
General guidance: Hold enteral nutrition (EN) during clonidine administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 20 mL) and restart EN (Ref).
Oral tablet, extended-release 24-hour:
Enteral feeding tube administration of clonidine ER 24-hour tablets is not recommended. Crushing modified release dosage forms (eg, ER tablets) may result in release of excessive doses, variable serum concentrations, and increased risk of severe adverse effects (Ref).
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
The following feeding tube recommendations are based upon the best available evidence and clinical expertise. Senior editor panel: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties that may vary among products from different manufacturers.
Oral: May be administered without regard to meals. Do not discontinue clonidine abruptly.
Oral suspension, extended-release (commercially available): Onyda XR: Administer at bedtime. With first use, insert bottle adapter and keep in place. Gently shake using a smooth up and down motion (to avoid foaming) for 10 seconds prior to measuring the dose; attach provided oral syringe and measure dose. While patient is seated, insert syringe in patient's mouth against cheek, depress plunger and administer dose. Clean oral syringe by rinsing out with tap water and letting air dry.
Administration via feeding tube: Enteral feeding tube administration of clonidine extended-release oral suspension has not been evaluated.
Tablets, immediate-release:
Administration via feeding tube:
Gastric (eg, NG, G-tube) or post-pyloric tubes (eg, J-tube) (≥8 French): Crush tablet(s) into a fine powder and disperse in 10 to 20 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some formulations may be film-coated; administration of film-coated clonidine tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are sufficiently dispersed prior to administration (Ref).
General guidance: Hold enteral nutrition during clonidine administration (Ref). Flush feeding tube with the lowest volume of purified water necessary to clear the tube prior to administration based on size of patient and/or feeding tube (eg, neonates: 1 to 3 mL; infants and children: 2 to 5 mL; adolescents: 15 mL); refer to institutional policies and procedures (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Tablets, extended-release twice-daily formulation (eg, Kapvay): Swallow whole; do not crush, chew, or split.
Administration via feeding tube: Enteral feeding tube administration of clonidine extended-release twice-daily formulation is not recommended. Crushing modified-release dosage forms (eg, extended-release tablets) may result in release of excessive doses, variable serum concentrations, and increased risk of severe adverse effects (Ref).
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.
Attention-deficit/hyperactivity disorder (ER tablet [Kapvay], ER suspension [Onyda]): Treatment of attention-deficit/hyperactivity disorder (monotherapy or as adjunctive therapy) in pediatric patients ≥6 years of age.
Cancer pain management, severe (epidural): Continuous epidural administration as adjunctive therapy with opioids for treatment of severe cancer pain in patients tolerant to or unresponsive to opioids alone; epidural clonidine is generally more effective for neuropathic pain and less effective (or possibly ineffective) for somatic or visceral pain.
Hypertension, chronic (ER tablet [Nexiclon], IR tablet, and transdermal patch): Management of hypertension.
Vasomotor symptoms associated with menopause (0. 025 mg tablet [ Canadian product]): Relief of menopausal flushing in patients for whom hormonal replacement therapy is unnecessary or not desirable.
ICU sedation, transition from dexmedetomidine to clonidine; Opioid withdrawal, medically supervised; Vasomotor symptoms associated with menopause
CloNIDine may be confused with Clomid, clomiPHENE, clonazePAM, cloZAPine, KlonoPIN, quiNIDine
Catapres may be confused with Cataflam, Combipres
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).
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).
Use caution when interpreting dosing information. Pediatric dose for epidural infusion expressed as mcg/kg/hour.
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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): May increase CNS depressant effects of CloNIDine. Alcohol (Ethyl) may increase serum concentration of CloNIDine. Specifically, the rate of dissolution from the clonidine extended-release tablet may be enhanced in the presence of alcohol. Risk C: Monitor
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Beta-Blockers: May increase rebound hypertensive effects of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Alpha2-Agonists may increase AV-blocking effects of Beta-Blockers. Sinus node dysfunction may also be enhanced. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Risk D: Consider Therapy Modification
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider Therapy Modification
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
EPHEDrine (Systemic): CloNIDine may increase therapeutic effects of EPHEDrine (Systemic). Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid
Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider Therapy Modification
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor
Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Macimorelin: Coadministration of CloNIDine and Macimorelin may alter diagnostic results. Risk X: Avoid
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mirtazapine: May decrease antihypertensive effects of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Risk D: Consider Therapy Modification
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider Therapy Modification
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: May decrease therapeutic effects of Alpha2-Agonists. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Siponimod: Bradycardia-Causing Agents may increase bradycardic effects of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider Therapy Modification
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
TiZANidine: Alpha2-Agonists may increase hypotensive effects of TiZANidine. Risk X: Avoid
Tricyclic Antidepressants: May decrease antihypertensive effects of Alpha2-Agonists. Management: Consider avoiding this combination. If used, monitor for decreased effects of the alpha2-agonist. Exercise great caution if discontinuing an alpha2-agonist in a patient receiving a TCA. Risk D: Consider Therapy Modification
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
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]).
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).
Clonidine is present in breast milk.
Data related to the presence of clonidine in breast milk are available.
• Breast milk samples were obtained on the first 3 days postpartum from 3 women administered oral clonidine 0.3 mg/day. Treatment was initiated 1 to 23 days prior to delivery. Clonidine concentrations were 0.8 to 2.8 ng/mL in breast milk and 0.4 to 1.5 ng/mL in the maternal plasma (Boutroy 1988).
• Data are available from a lactating patient, 4 weeks postpartum, taking oral clonidine 0.0.375 mg twice daily. Clonidine concentrations were 0.33 ng/mL in the maternal plasma (1 hour after the dose), 0.6 ng/mL in breast milk (2.5 hours after the dose), and undetectable (<0.096 ng/mL) in the infant plasma, 1 hour after breastfeeding (Bunjes 1993).
• Clonidine concentrations in breast milk were approximately twice those of the maternal serum in 9 patients treated with clonidine during pregnancy and postpartum. Breast milk and maternal serum were sampled 1 to 5 days, 10 to 14 days, and 45 to 60 days after delivery. Clonidine was also measurable in the breastfed infant serum at each time point (Hartikainen-Sorri 1987).
• Based on available lactation studies, one manufacturer reports the relative infant dose of clonidine to be 4.1% to 8.4% of the weight adjusted maternal dose (maternal dose and milk concentrations not presented).
Adverse events observed in some breastfed infants also exposed in utero include apathy syndrome, hypoglycemia, hypotonia, drowsiness, feeding difficulties, and hyperexcitability (Hartikainen-Sorri 1987; Sevrez 2014).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. When treatment for hypertension is needed in a breastfeeding patient, clonidine may be acceptable for use (ESC [Cífková 2020]); however, due to adverse events observed in breastfeeding infants, other sources do not recommend use in patients who are breastfeeding (Ornoy 2021) or recommend avoiding use when breastfeeding infants born <34 weeks' gestation or when large maternal doses are needed (Atkinson 1988).
Infants exposed to clonidine via breast milk should be monitored for symptoms of hypotension and/or bradycardia (eg, sedation, lethargy, tachypnea, poor feeding).
BP, heart rate, mental status.
Epidural: Carefully monitor infusion pump; inspect catheter tubing for obstruction or dislodgement to reduce risk of inadvertent abrupt withdrawal of infusion. Monitor closely for catheter-related infection (eg, meningitis or epidural abscess).
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.
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) and oral suspension (Onyda XR) 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); Extended release (Onyda XR): 96.6% to 97.1% (relative to extended-release tablets); 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; Extended release (Onyda XR): Median: 7.5 hours (4 to 17 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).
Altered kidney function: The half-life increases up to 41 hours in patients with severe renal impairment.
