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Special Alerts
Transdermal Patches: Risk of Burns During MRI - March 2009
The U.S. Food and Drug Administration (FDA) has issued a public health advisory regarding the risk of burns associated with the use of transdermal medication patches containing aluminum or other metals during MRI screening. The package labeling for certain metal-containing patches includes a warning related to the risk of burns if the patches are not removed prior to MRI procedures. However, not all transdermal medication patches with metallic backings have this warning in the labeling. Although metal materials are present in certain patches, it may not be visible. The FDA is currently reviewing the components of all transdermal medication systems to ensure that proper warnings are present in the labeling of those patches that do contain metal materials. In the interim, the FDA recommends that healthcare professionals who refer patients to have an MRI procedure should identify patients who are wearing a transdermal medication patch prior to the scan. Those patients who are wearing a transdermal medication patch should be advised on the proper removal of the patch prior to the procedure as well as reapplication following the scan.
Additional information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm111493.htm
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.
Medication Safety Issues
Sound-alike/look-alike issues:
CloNIDine may be confused with Clomid®, clomiPHENE, clonazePAM, clozapine, Klonopin®, quiNIDine
Catapres® may be confused with Cataflam®, Cetapred®, Combipres
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (epidural administration) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Transdermal patch may contain conducting metal (eg, aluminum); remove patch prior to MRI.
Pronunciation
(KLON i deen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Tablet
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of mild-to-moderate hypertension; either used alone or in combination with other antihypertensives
Orphan drug: Duraclon®: For continuous epidural administration as adjunctive therapy with intraspinal opiates for treatment of cancer pain in patients tolerant to or unresponsive to intraspinal opiates
Use: Unlabeled/Investigational
Heroin or nicotine withdrawal; severe pain; dysmenorrhea; vasomotor symptoms associated with menopause; ethanol dependence; prophylaxis of migraines; glaucoma; diabetes-associated diarrhea; impulse control disorder, attention-deficit/hyperactivity disorder (ADHD), clozapine-induced sialorrhea
Pregnancy Risk Factor
C
Pregnancy Considerations
Clonidine crosses the placenta. Caution should be used with this drug due to the potential of rebound hypertension with abrupt discontinuation.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Enters breast milk; AAP has NO RECOMMENDATION.
Contraindications
Hypersensitivity to clonidine hydrochloride or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Epidural use: See “Dosage form specific issues” below.
Concerns related to adverse effects:
• CNS depression: May cause significant CNS depression; use with caution in patients with pre-existing CNS disease or depression.
• 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.
• Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.
• Renal impairment: Use with caution in patients with chronic renal impairment.
Special populations:
• Elderly: Use with caution in the elderly; may be at greater risk for CNS depressive effects, favoring other agents in this population.
• Pediatrics: Safety and efficacy of tablet and transdermal product have not been established in children <12 years of age. In pediatric patients, epidural clonidine should be reserved for cancer patients with severe intractable pain, unresponsive to other analgesics or epidural or spinal opiates.
• Surgical patients: Discontinue within 4 hours of surgery then restart as soon as possible after.
Dosage form specific issues:
• Epidural use: [U.S. Boxed Warning]: Epidural clonidine is not recommended for perioperative, obstetrical, or postpartum pain. It is not recommended for use in patients with severe cardiovascular disease or hemodynamic instability. In all cases, the epidural route may lead to cardiovascular instability (hypotension, bradycardia). Should be administered via a continuous epidural infusion device.
• 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.
Other warnings/precautions:
• Discontinuation of therapy: Gradual withdrawal is needed (over 1 week for oral, 2-4 days with epidural) 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. Then slowly decrease clonidine.
Adverse Reactions
Incidence of adverse events is not always reported.
>10%:
Central nervous system: Drowsiness (35% oral, 12% transdermal), dizziness (16% oral, 2% transdermal)
Dermatologic: Transient localized skin reactions characterized by pruritus, and erythema (15% to 50% transdermal)
Gastrointestinal: Dry mouth (40% oral, 25% transdermal)
1% to 10%:
Cardiovascular: Orthostatic hypotension (3% oral)
Central nervous system: Headache (1% oral, 5% transdermal), sedation (3% transdermal), fatigue (6% transdermal), lethargy (3% transdermal), insomnia (2% transdermal), nervousness (3% oral, 1% transdermal), mental depression (1% oral)
Dermatologic: Rash (1% oral), allergic contact sensitivity (5% transdermal), localized vesiculation (7%), hyperpigmentation (5% at application site), edema (3%), excoriation (3%), burning (3%), throbbing, blanching (1%), papules (1%), and generalized macular rash (1%) has occurred in patients receiving transdermal clonidine.
Endocrine & metabolic: Sodium and water retention, sexual dysfunction (3% oral, 2% transdermal), impotence (3% oral, 2% transdermal)
Gastrointestinal: Nausea (5% oral, 1% transdermal), vomiting (5% oral), anorexia and malaise (1% oral), constipation (10% oral, 1% transdermal), dry throat (2% transdermal), taste disturbance (1% transdermal), weight gain (1% oral)
Genitourinary: Nocturia (1% oral)
Hepatic: Liver function test (mild abnormalities, 1% oral)
Neuromuscular & skeletal: Weakness (10% transdermal)
Miscellaneous: Withdrawal syndrome (1% oral)
<1% (Limited to important or life-threatening): Hepatitis (oral), difficulty in micturition (oral, transdermal), urinary retention (oral), hives (oral, transdermal), angioedema (oral, transdermal), urticaria (oral, transdermal), alopecia (oral, transdermal), parotid pain (oral), gynecomastia (oral, transdermal), transient elevation of blood glucose (oral), elevation of creatine phosphokinase (oral), palpitation (oral, transdermal), tachycardia (oral, transdermal), bradycardia (oral), sinus bradycardia (oral, transdermal), atrioventricular block (oral, transdermal), CHF (oral, transdermal), ECG abnormalities (oral, transdermal), flushing, pallor, Raynaud's phenomenon (oral, transdermal), chest pain (transdermal), blood pressure increase (transdermal), weakness, muscle or joint pain (0.6% oral), leg cramps (0.3% oral), fever (oral, transdermal), malaise (transdermal), withdrawal syndrome (transdermal), vivid dreams (oral, transdermal), nightmares (oral, transdermal), insomnia (oral), behavioral changes (transdermal), restlessness (oral, transdermal), anxiety (oral, transdermal), mental depression (transdermal), visual and auditory hallucinations (oral, transdermal), delirium (transdermal), CVA (transdermal), irritability (transdermal), weight gain (transdermal), rash (transdermal), orthostatic symptoms (transdermal), syncope (oral, transdermal), agitation (transdermal), contact dermatitis (transdermal), localized hypo- or hyperpigmentation (transdermal), anorexia (transdermal), vomiting (transdermal), loss of libido (transdermal), sexual activity decreased (transdermal), blurred vision (transdermal), burning of eyes (transdermal), dryness of eyes (transdermal), weakly positive Coombs' test (oral), ethanol sensitivity increased (oral), thrombocytopenia (oral), abdominal pain (oral), pseudo-obstruction (oral)
Drug Interactions
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 hypotensive effect of Alpha2-Agonists. 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
Iobenguane I 123: Alpha2-Agonists may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis 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).
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).
Compatibility
Y-site administration: Compatible: Lorazepam.
Compatibility in syringe: Compatible: Bupivacaine with morphine, fentanyl with lidocaine, ketamine with tetracaine.
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
Pharmacodynamics/Kinetics
Onset of action: Oral: 0.5-1 hour; Transdermal: Initial application: 2-3 days
Duration: 6-10 hours
Distribution: Vd: Adults: 2.1 L/kg; highly lipid soluble; distributes readily into extravascular sites
Protein binding: 20% to 40%
Metabolism: Extensively hepatic to inactive metabolites; undergoes enterohepatic recirculation
Bioavailability: 75% to 95%
Half-life elimination: Adults: Normal renal function: 6-20 hours; Renal impairment: 18-41 hours
Time to peak: 2-4 hours
Excretion: Urine (65%, 32% as unchanged drug); feces (22%)
Dosage
Children:
Oral:
Hypertension: Children ?12 years: Initial: 0.2 mg/day in 2 divided doses; increase gradually at 5- to 7-day intervals; usual maintenance dose: 0.2-0.6 mg/day in divided doses; maximum: 2.4 mg/day (rarely required)
Clonidine tolerance test (test of growth hormone release from pituitary): 0.15 mg/m2 or 4 mcg/kg as single dose
ADHD (unlabeled use): Initial: 0.05 mg/day; increase every 3-7 days by 0.05 mg/day to 3-5 mcg/kg/day given in divided doses 3-4 times/day (maximum dose: 0.3-0.4 mg/day)
Epidural infusion: Pain management: Reserved for patients with severe intractable pain, unresponsive to other analgesics or epidural or spinal opiates: Initial: 0.5 mcg/kg/hour; adjust with caution, based on clinical effect
Adults:
Oral:
Acute hypertension (urgency): 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 0.6 mg
Unlabeled route of administration: Sublingual clonidine 0.1-0.2 mg twice daily may be effective in patients unable to take oral medication
Hypertension: 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
Nicotine withdrawal symptoms (unlabeled use; Fiore, 2008): Initial dose: Initial: 0.1 mg twice daily; dosage range used in clinical trials: 0.15-0.75 mg/day; duration of therapy ranged from 3-10 weeks in clinical trials
Transdermal:
Hypertension: Apply once every 7 days; for initial therapy start with 0.1 mg and increase by 0.1 mg at 1- to 2-week intervals (dosages >0.6 mg do not improve efficacy); usual dose range (JNC 7): 0.1-0.3 mg once weekly
Nicotine withdrawal symptoms (unlabeled use; Fiore, 2008): Initial: 0.1 mg/24 hour patch applied once every 7 days and increase by 0.1 mg at 1- to 2-week intervals if necessary; dosage range used in clinical trials: 0.1-0.2 mg/24 hours patch applied once every 7 days; duration of therapy ranged from 3-10 weeks in clinical trials
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.
Conversion from oral to transdermal:
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.
Epidural infusion: Pain management: Starting dose: 30 mcg/hour; titrate as required for relief of pain or presence of side effects; minimal experience with doses >40 mcg/hour; should be considered an adjunct to intraspinal opiate therapy
Elderly: Initial: 0.1 mg once daily at bedtime, increase gradually as needed
Dosing adjustment in renal impairment: Bradycardia 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 (K/DOQI, 2005). 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.
Administration: Oral
Do not discontinue clonidine abruptly. If needed, gradually reduce dose over 2-4 days to avoid rebound hypertension.
Administration: Topical
Transdermal patches should be applied weekly at bedtime 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: I.V. Detail
pH: 5-7
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).
Reference Range
Therapeutic: 1-2 ng/mL (SI: 4.4-8.7 nmol/L)
Dietary Considerations
Hypertensive patients may need to decrease sodium and calories in diet.
Patient Education
Do not take any new prescription or over-the-counter medications, or herbal products (especially cough or cold remedies and sleep or stay-awake medications that might affect blood pressure) during treatment unless approved by prescriber. Take as directed, 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 (use caution when driving or engaging in tasks that require alertness until response is known); decreased libido or sexual function (will resolve when drug is discontinued); postural hypotension (use caution when rising from sitting or lying position or when climbing stairs); constipation (increased exercise, fluids, fruit, and dietary fiber may help); or dry mouth or nausea (frequent mouth care or sucking lozenges may help). Report changes in urinary pattern; persistent nervousness, depression, lethargy, insomnia or nightmares; sudden weight gain (weigh yourself in the same clothes at the same time of day once a week); unusual or persistent swelling of ankles, feet, or extremities; skin reaction to transdermal patch; or other persistent side effects. Pregnancy precautions: Inform prescriber if you are or intend to become pregnant.
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.
Additional Information
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.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Abrupt withdrawal from clonidine therapy should be avoided. Clonidine patch has provided an important alternative to frequent daily dosing; may be used in patients unable to take oral medication. Transdermal therapy takes 2-3 days for therapeutic effects.
Cardiovascular Considerations
Tolerance to the blood pressure lowering effects of clonidine may develop with long-term therapy. Abrupt withdrawal from clonidine therapy should be very specifically 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
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. Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (eg, potential for additive hypotension, bradycardia, CNS depression). Monitor blood pressure and mental status, therapeutic effectiveness (according to purpose for use), and adverse response regularly during therapy. Pediatric patients being treated for ADHD should be screened/monitored for cardiovascular risk prior to and during use. 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). Teach patient proper use (eg, do not discontinue abruptly), possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride [epidural; preservative free]:
Duraclon®: 100 mcg/mL (10 mL); 500 mcg/mL (10 mL)
Tablet, as hydrochloride: 0.1 mg, 0.2 mg, 0.3 mg
Catapres®: 0.1 mg, 0.2 mg, 0.3 mg
Transdermal system, topical [once-weekly patch]:
Catapres-TTS®-1: 0.1 mg/24 hours (4s)
Catapres-TTS®-2: 0.2 mg/24 hours (4s)
Catapres-TTS®-3: 0.3 mg/24 hours (4s)
Pricing: U.S. (www.drugstore.com)
Patch weekly (Catapres-TTS-1)
0.1 mg/24 hrs (4): $128.26
Patch weekly (Catapres-TTS-2)
0.2 mg/24 hrs (4): $200.84
Patch weekly (Catapres-TTS-3)
0.3 mg/24 hrs (4): $275.84
Tablets (Catapres)
0.1 mg (60): $88.00
0.2 mg (60): $120.99
0.3 mg (60): $148.49
Tablets (CloNIDine HCl)
0.1 mg (100): $19.99
0.2 mg (100): $22.21
0.3 mg (100): $21.99
References
American Academy of Pediatrics Subcommittee on Attention-Deficit/Hyperactivity Disorder and Committee on Quality Improvement. “Clinical Practice Guidelines: Treatment of the School-Aged Child With Attention-Deficit/Hyperactivity Disorder,” Pediatrics, 2001, 108(4):1033-44.
Capogna G, Celleno D, Zangrillo A, et al, “Addition of Clonidine to Epidural Morphine Enhances Postoperative Analgesia After Cesarean Delivery,” Reg Anesth, 1995, 20(1):57-61.
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.
Fitzgibbon D, Rapp S, Butler S, et al, “Rebound Hypertension and Withdrawal Associated With Discontinuation of an Infusion of Epidural Clonidine,” Anesthesiology, 1996, 84(3):729-31.
Fiore MC, Jaen CR, Baker TB, et al, Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008. Available at http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pdf.
Fizer DH, Moss MN, and Walker W, “Critical Care for Clonidine Poisoning in Toddlers,” Crit Care Med, 1990, 18(10):1124-8.
Fowler MA, Wheeler CA, and Wasserman GS, “Case 01-1995: A Two Year Old Female With Alteration of Consciousness,” Pediatr Emerg Care, 1995, 11(1):62.
Geyskes GG, Boer P, and Dorhout Mees EJ, “Clonidine Withdrawal. Mechanism and Frequency of Rebound Hypertension,” Br J Clin Pharmacol, 1979, 7(1):55-62.
Hart-Santora D and Hart LL, “Clonidine in Attention Deficit Hyperactivity Disorder,” Ann Pharmacother, 1992, 26(1):37-9.
Henretig F, Wiley J, and Brown L, “Clonidine Patch Toxicity: The Proof's in the Poop!” Clin Toxicol, 1995, 33(5):520-1.
Hunt RD, Minderaa RB, and Cohen DJ, “The Therapeutic Effect of Clonidine in Attention Deficit Disorder With Hyperactivity: A Comparison With Placebo and Methylphenidate,” Psychopharmacol Bull, 1986, 22(1):229-35.
“K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients,” Am J Kidney Dis, 2005, 45(4 Suppl 3):46-57.
Klein MD, “An Unusual Cause of Clonidine Toxicity,” Am J Emerg Med, 1991, 9(4):409-10.
Kulig K, Duffy JP, Rumack BH, et al, “Naloxone for the Treatment of Clonidine Overdose,” JAMA, 1982, 247(12):1697.
Metz S, Klein C, and Morton N, “Rebound Hypertension After Discontinuation of Transdermal Clonidine Therapy,” Am J Med, 1987, 82(1):17-9.
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,” Pediatrics, 2004, 114(2 Suppl):555-76.
Rocchini AP, “Childhood Hypertension: Etiology, Diagnosis, and Treatment,” Pediatr Clin North Am, 1984, 31(6):1259-73.
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 August 2009
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