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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(KLON i deen)
Generic Available (U.S.)
Yes: Excludes extended release tablets, oral suspension
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral:
Immediate release: Management of hypertension (monotherapy or as adjunctive therapy)
Extended release:
Kapvay™: Treatment of attention-deficit/hyperactivity disorder (ADHD) (monotherapy or as adjunctive therapy)
Nexiclon™ XR: Management of hypertension (monotherapy or as adjunctive therapy)
Epidural (Duraclon®): For 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
Transdermal patch: Management of hypertension (monotherapy or as adjunctive therapy)
Use: Unlabeled
Heroin or nicotine withdrawal; severe pain; dysmenorrhea; vasomotor symptoms associated with menopause; ethanol dependence; prophylaxis of migraines; glaucoma; diabetes-associated diarrhea; impulse control disorder, clozapine-induced sialorrhea; aid in the diagnosis of growth hormone deficiency; attention-deficit/hyperactivity disorder (ADHD) and associated insomnia in children; Tourette's syndrome in children; aggression associated with conduct disorder
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in some animal reproduction studies. Clonidine crosses the placenta; 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. [U.S. Boxed Warning]: Epidural clonidine is not recommended for obstetrical or postpartum pain due to risk of hemodynamic instability.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Enters breast milk with concentrations approximately twice maternal serum concentrations
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
Warnings/Precautions
Boxed warnings:
• Epidural use: See “Dosage form specific issues” below.
Concerns related to adverse effects:
• Bradycardia: May cause dose-dependent reductions in heart rate; use with caution in patients with preexisting bradycardia or those predisposed to developing bradycardia.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: Symptomatic hypotension may occur with use. In all patients, use epidural clonidine with caution due to the potential for severe hypotension, especially in women and those of low body weight. Most hypotensive episodes occur within the first 4 days of initiation; however, episodes may occur throughout the duration of therapy.
• Respiratory depression: Epidural administration may result in mild respiratory depression (usually associated with higher than recommended doses).
• Xerostomia: May cause significant xerostomia.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe coronary insufficiency, including recent MI and conduction disturbances, including sinus node dysfunction. The use of epidural clonidine frequently reduces heart rate; AV block greater than first-degree has been reported rarely. Epidural clonidine is not recommended for use in patients with severe cardiovascular disease or hemodynamic instability. May lead to cardiovascular instability (hypotension, bradycardia).
• Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
• Renal impairment: Use with caution in patients with chronic renal impairment.
Concurrent drug therapy issues:
• Agents with SA/AV nodal blocking properties: Use with caution in patients concurrently receiving agents known to reduce SA node function and/or AV nodal conduction (eg, digoxin, diltiazem, metoprolol, verapamil); may increase risk of serious bradycardia.
• CNS depressants: Sedating effects may be potentiated when used with other CNS-depressant drugs or ethanol.
Special populations:
• Elderly: Avoid use as first-line antihypertensive due to high risk of CNS adverse effects; may also cause orthostatic hypotension and bradycardia (Beers Criteria).
• Pediatrics: Since children commonly have gastrointestinal illnesses with vomiting, they are susceptible to hypertensive episodes due to abrupt inability to take oral medication. Epidural clonidine should be reserved for pediatric cancer patients with severe intractable pain, unresponsive to other analgesics or epidural or spinal opioids.
• Surgical patients: Discontinue oral immediate release formulations within 4 hours of surgery then restart as soon as possible afterwards. Discontinue oral extended release formulations up to 28 hours prior to surgery, then restart the following day.
Dosage form specific issues:
• Epidural use: [U.S. Boxed Warning]: Must dilute concentrated epidural injectable (500 mcg/mL) solution prior to use. Epidural clonidine is not recommended for perioperative, obstetrical, or postpartum pain due to risk of hemodynamic instability. Should be administered via continuous epidural infusion device. Monitor closely for catheter-related infection such as meningitis or epidural abscess.
• Product interchangeability: Oral formulations of clonidine (immediate release versus extended release) are not interchangeable on a mg:mg basis due to different pharmacokinetic profiles. This includes commercially available oral suspension (Nexiclon™ XR) which is an extended-release preparation and should not be used interchangeably with any extemporaneously prepared clonidine oral suspension.
• 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 (taper oral immediate release or epidural dose gradually over 2-4 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. In children and adolescents, extended release formulation (Kapvay™) should be tapered in decrements of no more than 0.1 mg every 3-7 days.
Adverse Reactions
Frequency not always defined.
Oral, Transdermal: Incidence of adverse events may be less with transdermal compared to oral due to the lower peak/trough ratio.
Cardiovascular: Bradycardia (≤4%), palpitation (1%), tachycardia (1%), arrhythmia, atrioventricular block, chest pain, CHF, ECG abnormalities, flushing, orthostatic hypotension, pallor, Raynaud's phenomenon, syncope
Central nervous system: Drowsiness (12% to 38%), headache (1% to 29%), fatigue (4% to 16%), dizziness (2% to 16%), sedation (3% to 10%), insomnia (≤6%), lethargy (3%), nervousness (1% to 3%), mental depression (1%), aggression, agitation, anxiety, behavioral changes, CVA, delirium, delusional perception, fever, hallucinations (visual and auditory), irritability, malaise, nightmares, restlessness, vivid dreams
Dermatologic: Transient localized skin reactions characterized by pruritus and erythema (transdermal 15% to 50%), contact dermatitis (transdermal 8% to 34%), vesiculation (transdermal 7%), allergic contact sensitization (transdermal 5%), hyperpigmentation (transdermal 5%), burning (transdermal 3%), edema (3%), excoriation (transdermal 3%) blanching (transdermal 1%), generalized macular rash (1%), papules (transdermal 1%), throbbing (transdermal 1%), alopecia, angioedema, hives, localized hypopigmentation (transdermal), rash, urticaria
Endocrine & metabolic: Sexual dysfunction (3%), gynecomastia (1%), creatine phosphokinase increased (transient; oral), hyperglycemia (transient; oral), libido decreased
Gastrointestinal: Xerostomia (≤40%), constipation (2% to 10%), anorexia (1%), taste perversion (1%), weight gain (<1%), abdominal pain (oral), diarrhea, nausea, parotid gland pain (oral), parotitis (oral), pseudo-obstruction (oral), throat pain, vomiting
Genitourinary: Erectile dysfunction (2% to 3%), nocturia (1%), dysuria, enuresis, urinary retention
Hematologic: Thrombocytopenia (oral)
Hepatic: Liver function test (mild transient abnormalities; ≤1%), hepatitis
Neuromuscular & skeletal: Weakness (10%), arthralgia (1%), myalgia (1%), leg cramps (<1%), numbness (localized, transdermal), pain in extremities, paresthesia, tremor
Ocular: Accommodation disorder, blurred vision, burning eyes, dry eyes, lacrimation decreased, lacrimation increased
Otic: Ear pain, otitis media
Renal: Pollakiuria
Respiratory: Asthma, epistaxis, nasal congestion, nasal dryness, nasopharyngitis, respiratory tract infection, rhinorrhea
Miscellaneous: Withdrawal syndrome (1%), flu-like syndrome, thirst
Epidural: Note: The following adverse events occurred more often than placebo in cancer patients with intractable pain being treated with concurrent epidural morphine.
>10%:
Cardiovascular: Hypotension (45%), postural hypotension (32%)
Central nervous system: Confusion (13%), dizziness (13%)
Gastrointestinal: Xerostomia (13%)
1% to 10%:
Cardiovascular: Chest pain (5%)
Central nervous system: Hallucinations (5%)
Gastrointestinal: Nausea/vomiting (8%)
Otic: Tinnitus (5%)
Miscellaneous: Diaphoresis (5%)
Metabolism/Transport Effects
None known.
Drug Interactions
Alfuzosin: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antidepressants (Alpha2-Antagonist): May diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding concurrent use. If these combinations cannot be avoided, monitor for decreased effects of alpha2-agonists if an alpha2-antagonist is initiated/dose increased, or increased effects if an alpha2-antagonist is discontinued/dose decreased. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Beta-Blockers: May enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Levobunolol; Metipranolol. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Iobenguane I 123: Alpha2-Agonists may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylphenidate: May enhance the adverse/toxic effect of CloNIDine. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the antihypertensive effect of Alpha2-Agonists. Risk C: Monitor therapy
Tricyclic Antidepressants: May diminish the antihypertensive effect of Alpha2-Agonists. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression). In vitro studies have shown high concentrations of alcohol may increase the rate of release of Nexiclon™ XR.
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Epidural formulation: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Preservative free; discard unused portion.
Oral suspension, tablets: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Transdermal patches: Store below 30°C (86°F).
Reconstitution
Epidural formulation: Prior to administration, the 500 mcg/mL concentration must be diluted in 0.9% sodium chloride for injection (preservative-free) to a final concentration of 100 mcg/mL.
Compatibility
Stable in NS
Note: Epidural formulation is NOT for I.V. administration.
Y-site administration: Compatible: Aminophylline, dobutamine, dopamine, epinephrine, fentanyl, labetaolol, lorazepam, magnesium sulfate, nitroglycerin, norepinephrine, potassium chloride, theophylline, verapamil. Variable (consult detailed reference): Midazolam.
Compatibility in syringe: Compatible: Bupivacaine, bupivacaine with fentanyl, bupivacaine with morphine, fentanyl, fentanyl with lidocaine, heparin, ketamine with tetracaine, lidocaine, tetracaine, ziconotide. Variable (consult detailed reference): Morphine.
Mechanism of Action
Stimulates alpha2-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 alpha2-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 alpha2-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.
Pharmacodynamics/Kinetics
Onset of action: Oral: 0.5-1 hour; Transdermal: Initial application: 2-3 days
Duration: 6-10 hours
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: Adults: 2.1 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: 75% to 85%; Extended release (Kapvay™): 89% (relative to immediate release formulation)
Half-life elimination: Adults: Normal renal function: 12-16 hours; Renal impairment: Up to 41 hours
Epidural administration: CSF half-life elimination: 0.8-1.8 hours
Time to peak: Oral: Immediate release: 3-5 hours; Extended release: 7-8 hours
Excretion: Urine (40% to 60%as unchanged drug)
Dosage
Note: Dosing is expressed as the salt (clonidine hydrochloride) unless otherwise noted. Formulations of clonidine (immediate release versus extended release) are not interchangeable on a mg:mg basis due to different pharmacokinetic profiles. This includes commercially available oral suspension (Nexiclon™ XR) which is an extended release preparation and should not be used interchangeably with any extemporaneously prepared clonidine oral suspension.
Children:
Oral:
Hypertension (unlabeled use): Children ≥12 years: Immediate release: Initial: 0.2 mg/day in 2 divided doses; increase gradually, if needed, in 0.1 mg/day increments at weekly intervals; maximum: 2.4 mg/day (rarely required) (NHBPEP, Fourth Report)
Severe hypertension (unlabeled use): Children: Immediate release: 0.05-0.1 mg/dose; may repeat up to a maximum total dose of 0.8 mg (NHBPEP, Fourth Report)
Clonidine tolerance test (test of growth hormone release from pituitary) (unlabeled use):
0.15 mg/m2 as a single dose (Lanes, 1982)
or
5 mcg/kg as a single dose; maximum dose: 250 mcg (Richmond, 2008)
ADHD: Note: May be used alone or as an adjunct to stimulants.
Immediate release (unlabeled indication; Pliszka, 2007):
Children ≤45 kg: Initial: 0.05 mg at bedtime; sequentially increase every 3-7 days by 0.05 mg increments as twice daily, then 3 times daily, then 4 times daily; maximum daily dose: 0.2 mg/day for patients weighing 27-40.5 kg; 0.3 mg/day for patients weighing 40.5-45 kg. When discontinuing therapy, taper gradually over 1-2 weeks.
Children >45 kg: Initial: 0.1 mg at bedtime; sequentially increase every 3-7 days by 0.1 mg increments as twice daily, then 3 times daily, then 4 times daily; maximum daily dose: 0.4 mg/day. When discontinuing therapy, taper gradually over 1-2 weeks.
Extended release (Kapvay™): Children ≥6 years: Initial: 0.1 mg at bedtime; increase in 0.1 mg/day increments every 7 days until desired response, doses should be administered twice daily (either split equally or with the higher split dosage given at bedtime); maximum: 0.4 mg/day. Note: Maintenance treatment for >5 weeks has not been evaluated. When discontinuing therapy, taper daily dose by ≤0.1 mg every 3-7 days.
Epidural infusion: Pain management: Reserved for cancer patients with severe intractable pain, unresponsive to other opioid analgesics: Initial: 0.5 mcg/kg/hour; adjust with caution, based on clinical effect
Adults:
Oral:
Hypertension:
Immediate release: Initial dose: 0.1 mg twice daily (maximum recommended dose: 2.4 mg/day); usual dose range (JNC 7): 0.1-0.8 mg/day in 2 divided doses
Extended release (Nexiclon™ XR): Initial: 0.17 mg clonidine base once daily at bedtime; may increase increments of 0.09 mg/day every 7 days; maintenance: usual dose range: 0.17-0.52 mg clonidine base once daily; maximum: 0.52 mg/day clonidine base
Conversion between immediate release clonidine hydrochloride and extended release (Nexiclon™ XR) clonidine base:
Current dose immediate release tablets 0.05 mg twice daily: Convert to extended release tablet of 0.09 mg clonidine base once daily
Current dose immediate release tablets 0.1 mg twice daily: Convert to extended release tablet of 0.17 mg clonidine base once daily
Current dose immediate release tablets 0.2 mg twice daily: Convert to extended release tablet of 0.34 mg clonidine base once daily
Current dose immediate release tablets 0.3 mg twice daily: convert to extended release tablets of 0.52 mg clonidine base once daily
Acute hypertension (urgency) (unlabeled use): Initial 0.1-0.2 mg; may be followed by additional doses of 0.1 mg every hour, if necessary, to a maximum total dose of 0.7 mg (Atkin, 1992; Jaker, 1989)
Unlabeled route of administration: Sublingual: Initial: 0.1-0.2 mg; followed by 0.05-0.1 mg every hour until blood pressure controlled or a cumulative dose of 0.7 mg is reached (Cunningham, 1994; Matuschka, 1999)
Nicotine withdrawal symptoms (unlabeled use): Initial: 0.1 mg twice daily; titrate by 0.1 mg/day every 7 days if needed; dosage range used in clinical trials: 0.15-0.75 mg/day; duration of therapy ranged from 3-10 weeks in clinical trials (Fiore, 2008)
Transdermal:
Hypertension: Initial: 0.1 mg/24 hour patch applied once every 7 days and increase by 0.1 mg at 1- to 2-week intervals (dosages >0.6 mg/24 hours do not improve efficacy); usual dose range (JNC 7): 0.1-0.3 mg/24 hour patch applied once every 7 days
Nicotine withdrawal symptoms (unlabeled use): Initial: 0.1 mg/24 hour patch applied once every 7 days and increase by 0.1 mg at 1-week intervals if necessary; dosage range used in clinical trials: 0.1-0.2 mg/24 hour patch applied once every 7 days; duration of therapy ranged from 3-10 weeks in clinical trials (Fiore, 2008)
Epidural infusion: Pain management: Reserved for cancer patients with severe intractable pain, unresponsive to other opioid analgesics: Starting dose: 30 mcg/hour; titrate as required for relief of pain or presence of side effects; experience with doses >40 mcg/hour is limited; should be considered an adjunct to opioid therapy
Conversion from oral to transdermal: Note: If transitioning from oral to transdermal therapy, overlap oral regimen for 1-2 days; transdermal route takes 2-3 days to achieve therapeutic effects. An example transition is below:
Day 1: Place Catapres-TTS® 1; administer 100% of oral dose.
Day 2: Administer 50% of oral dose.
Day 3: Administer 25% of oral dose.
Day 4: Patch remains, no further oral supplement necessary.
Conversion from transdermal to oral: After transdermal patch removal, therapeutic clonidine levels persist for ~8 hours and then slowly decrease over several days. Consider starting oral clonidine no sooner than 8 hours after patch removal.
Elderly: Oral: Hypertension:
Immediate release: Initial: 0.1 mg once daily at bedtime, increase gradually as needed
Extended release (Nexiclon™ XR): No specific recommendations are provided by the manufacturer although a lower initial dose is recommended.
Dosing adjustment in renal impairment: Bradycardia, sedation, and hypotension may be more likely to occur in patients with renal failure; may consider using doses at the lower end of the dosing range and monitor closely
Not dialyzable (0% to 5%) via hemodialysis; supplemental dose is not necessary; unclear how much is removed via peritoneal dialysis. Oral antihypertensive drugs given preferentially at night may reduce the nocturnal surge of blood pressure and minimize the intradialytic hypotension that may occur when taken the morning before a dialysis session (K/DOQI, 2005).
Oral: Extended release (Nexiclon™ XR):
Moderate-to-severe impairment (not on dialysis): No dosage adjustment recommended; titrate slowly
End-stage kidney disease (on maintenance dialysis): Initial: 0.09 mg clonidine base/day; titrate slowly
Administration: Oral
May be taken with or without food. Do not discontinue clonidine abruptly. If needed, gradually reduce dose over 2-4 days to avoid rebound hypertension.
Extended release products:
Kapvay™: Swallow whole; do not crush, split, or chew.
Nexiclon™ XR: Tablets may be split. Shake suspension well before use.
Administration: Topical
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.
Administration: Other
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 2-4 days to avoid withdrawal symptoms.
Monitoring Parameters
Blood pressure, standing and sitting/supine, mental status, heart rate
When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure (when started and weaned), and consider obtaining ECG prior to initiation (Vetter, 2008).
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 withdrawal of infusion. Monitor closely for catheter-related infection (eg, meningitis or epidural abscess).
Test Interactions
Positive Coombs' test
Patient Education
Take at bedtime. If using patch, check daily for correct placement; rotate patch sites weekly. Remove patch while having MRI scan; can cause burns. Do not skip doses or discontinue without consulting prescriber (this drug must be discontinued on a specific schedule to prevent serious adverse effects). This medication may cause drowsiness, dizziness, fatigue, insomnia, decreased libido or sexual function (will resolve when drug is discontinued), postural hypotension, constipation, dry mouth, or nausea. Report chest pain, palpitations, or change in heartbeat; changes in urinary pattern; persistent nervousness, depression, lethargy, insomnia, or nightmares; sudden weight gain; unusual or persistent swelling of ankles, feet, or extremities; or skin reaction to transdermal patch.
Geriatric Considerations
Because of its potential CNS adverse effects, clonidine may not be considered a drug of choice in the elderly. If the decision is to use clonidine, adjust dose based on response and adverse reactions. In patients on the transdermal system, monitor for appropriate placement of the patch.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria: Quality of evidence - low; Strength of recommendation - strong).
Additional Information
Each 0.1 mg of clonidine hydrochloride (salt form) is equivalent to 0.087 mg of the free base.
Transdermal clonidine should only be used in patients unable to take oral medication. The transdermal product is much more expensive than oral clonidine and produces no better therapeutic effects.
When used for ADHD treatment, clonidine is recommended to be used as part of a comprehensive treatment program (eg, psychological, educational, and social) for attention-deficit disorder.
Cardiovascular Considerations
Tolerance to the blood pressure lowering effects of clonidine may develop with long-term therapy. Abrupt withdrawal from clonidine therapy should be avoided. The clonidine withdrawal syndrome is more pronounced after abrupt cessation of long-term therapy than after short-term therapy (1-2 months). It has usually been associated with previous administration of high oral doses (>1.2 mg daily) and/or continuation of beta-blocker therapy. The danger of abrupt discontinuation may be increased in patients with hypertension and/or other cardiovascular considerations. Blood pressure may increase 8-24 hours after last dose, but has occurred 60 hours after the last clonidine dose. Rebound hypertension has occurred with discontinuation of transdermal and epidural clonidine.
The advent of the clonidine patch has provided an important alternative to frequent daily dosing. However, it is important that overlap of therapy be maintained for 2-3 days when switching from oral medications to the patch. Important side effects of clonidine include drowsiness. It has also been suggested that clonidine may be useful in promoting smoking cessation.
Note that the use of moxonidine to lower sympathetic activation in patients with heart failure was associated with increased mortality.
ADHD: Cardiovascular Evaluation: In an effort to reduce the rate of sudden cardiac death especially in pediatric patients receiving stimulant medications for the treatment of attention-deficit/hyperactivity disorder (ADHD), the American Heart Association (AHA) issued a statement in April 2008 (Vetter, 2008) recommending that all children diagnosed with ADHD who may be candidates for stimulant medications have a thorough cardiovascular assessment (including a combination of a thorough medical history, family history, and physical examination with the intent to identify risk factors for sudden death) prior to initiation of drug therapy. Although not mandatory, physicians should consider obtaining an ECG. These recommendations are based on the Food and Drug Administration (FDA) 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). Stimulant medications theoretically increase cardiovascular risk due to potential effects on blood pressure elevation and increased heart rate. These effects have generally been considered clinically insignificant in most children, however, may be detrimental in certain patients with underlying cardiovascular disease. None of the medications have been shown to cause heart conditions or proven to have caused sudden cardiac death.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes upon discontinuation), orthostatic hypotension, and abnormal taste.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness is common
Mental Health: Effects on Psychiatric Treatment
Dry mouth, orthostatic hypotension, and sedation may be increased with concurrent psychotropic use; used to treat clozapine-induced sialorrhea (unlabeled use); TCAs may antagonize clonidine's hypotensive effect
Mental Health: Child/Adolescent Considerations
One retrospective review looked specifically at insomnia associated with ADHD in 42 children and 20 adolescents. Improvement in insomnia was documented in 85% of cases with immediate-release clonidine 50-800 mcg per night over ~35 months (Prince, 1996).
Cinnamon Bidwell L, Dew RE, and Kollins SH, "Alpha-2 Adrenergic Receptors and Attention-Deficit/Hyperactivity Disorder," Curr Psychiatry Rep, 2010, 12(5):366-73.
Palumbo DR, Sallee FR, Pelham WE Jr, "Clonidine for Attention-Deficit/Hyperactivity Disorder: I. Efficacy and Tolerability Outcomes," J Am Acad Child Adolesc Psychiatry, 2008, 47(2):180-8.
Prince JB, Wilens TE, Biederman J, "Clonidine for Sleep Disturbances Associated With Attention-Deficit Hyperactivity Disorder: A Systematic Chart Review of 62 Cases," J Am Acad Child Adolesc Psychiatry, 1996, 35(5):599-605.
Nursing: Physical Assessment/Monitoring
Use with caution and monitor closely in presence of pre-existing renal impairment, cardiovascular disease, hemodynamic instability, CNS disease or depression. Monitor blood pressure and mental status throughout. Advise patients using oral hypoglycemic agents or insulin to check glucose levels closely; clonidine may decrease the symptoms of hypoglycemia. When discontinuing, monitor blood pressure and taper dose gradually (over 1 week for oral, 2-4 days for epidural).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride [epidural, preservative free]: 100 mcg/mL (10 mL); 500 mcg/mL (10 mL)
Duraclon®: 100 mcg/mL (10 mL); 500 mcg/mL (10 mL)
Patch, transdermal: 0.1 mg/24 hours (4s); 0.2 mg/24 hours (4s); 0.3 mg/24 hours (4s)
Catapres-TTS®-1: 0.1 mg/24 hours (4s) [contains metal]
Catapres-TTS®-2: 0.2 mg/24 hours (4s) [contains metal]
Catapres-TTS®-3: 0.3 mg/24 hours (4s) [contains metal]
Suspension, extended release, oral, as base:
Nexiclon™ XR: 0.09 mg/mL (118 mL)
Tablet, oral, as hydrochloride: 0.1 mg, 0.2 mg, 0.3 mg
Catapres®: 0.1 mg, 0.2 mg, 0.3 mg [scored]
Tablet, extended release, oral, as base:
Nexiclon™ XR: 0.17 mg [scored]
Tablet, extended release, oral, as hydrochloride:
Kapvay™: 0.1 mg
Pricing: U.S. (www.drugstore.com)
Patch weekly (Catapres-TTS-1)
0.1 mg/24 hrs (4): $165.98
Patch weekly (Catapres-TTS-2)
0.2 mg/24 hrs (4): $260.99
Patch weekly (Catapres-TTS-3)
0.3 mg/24 hrs (4): $359.01
Patch weekly (CloNIDine HCl)
0.1 mg/24 hrs (4): $109.99
0.2 mg/24 hrs (4): $179.99
0.3 mg/24 hrs (4): $245.97
Tablets (Catapres)
0.1 mg (60): $99.99
0.2 mg (60): $154.98
0.3 mg (60): $165.98
Tablets (CloNIDine HCl)
0.1 mg (100): $19.99
0.2 mg (100): $21.99
0.3 mg (100): $21.99
Extemporaneously Prepared
Note: Extended-release oral suspension commercially available (0.09 mg/mL as clonidine base). The commercially available oral suspension (Nexiclon™ XR) is an extended-release preparation and should not be in used interchangeably with any extemporaneously prepared clonidine oral suspension.
A 0.1 mg/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):122-5.
References
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Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Corazza M, Mantovani L, Virgil A, et al, “Allergic Contact Dermatitis From a Clonidine Transdermal Delivery System,” Contact Dermatitis, 1995, 32(4):246.
Cunningham FE, Baughman VL, Peters J, et al, “Comparative Pharmacokinetics of Oral versus Sublingual Clonidine,” J Clin Anesth, 1994, 6(5):430-3.
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Huang C, Banergee K, Sochett E, et al, “Hypoglycemia Associated With Clonidine Testing for Growth Hormone Deficiency,” J Pediatr, 2001, 139(2):323-4.
Jaker M, Atkin S, Soto M, et al, “Oral Nifedipine vs Oral Clonidine in the Treatment of Urgent Hypertension,” Arch Intern Med, 1989, 149(2):260-5.
“K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients,” Am J Kidney Dis, 2005, 45(4 Suppl 3):46-57. Available at http://www.kidney.org/professionals/KDOQI/guidelines_cvd/index.htm
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National Institute for Health and Clinical Excellence (NICE), National Collaborating Centre for Mental Health , “Attention Deficit Hyperactivity Disorder, The NICE Guideline on Diagnosis and Management of ADHD in Children, Young People and Adults,” National Clinical Practice Guideline Number 72, 2008:1-664. Available at www.nice.org.uk/cg072
NHBPEP (National High Blood Pressure Education Program) Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Available at http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf
Pliszka S, “Practice Parameter for the Assessment and Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder,” J Am Acad Child Adolesc Psychiatry, 2007, 46(7):894-921.
“Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain,” 6th ed, Glenview, IL: American Pain Society, 2008.
Richmond EJ and Rogol AD, “Growth Hormone Deficiency in Children,” Pituitary, 2008, 11(2):115-20.
Rocchini AP, “Childhood Hypertension: Etiology, Diagnosis, and Treatment,” Pediatr Clin North Am, 1984, 31(6):1259-73.
Scahill L, "Alpha-2 Adrenergic Agonists in Attention Deficit Hyperactivity Disorder," J Pediatr, 2009, 154(5 Suppl):32-7.
Schmidt GR and Schuna AA, “Rebound Hypertension After Discontinuation of Transdermal Clonidine,” Clin Pharm, 1988, 7(10):772-4.
Sinaiko AR, “Pharmacologic Management of Childhood Hypertension,” Pediatr Clin North Am, 1993, 40(1):195-212.
Vetter VL, Elia J, Erickson CH, et al, “Cardiovascular Monitoring of Children and Adolescents With Heart Disease Receiving Stimulant Drugs. A Scientific Statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing,” Circulation, 2008, 117:2407-23.
International Brand Names
Lexi-Comp.com
Last full review/revision April 2012
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