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 with caution in patients with severe coronary insufficiency; conduction disturbances; recent MI, CVA, or chronic renal insufficiency. Caution in sinus node dysfunction. Discontinue within 4 hours of surgery then restart as soon as possible after. Clonidine injection should be administered via a continuous epidural infusion device. 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 may lead to cardiovascular instability (hypotension, bradycardia). Transdermal patch may contain conducting metal (eg, aluminum); remove patch prior to MRI. Clonidine cause significant CNS depression and xerostomia. Caution in patients with pre-existing CNS disease or depression. Elderly may be at greater risk for CNS depressive effects, favoring other agents in this population.

>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 creatinine 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), increase in blood pressure (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), decreased sexual activity (transdermal), blurred vision (transdermal), burning of the eyes (transdermal), dryness of the eyes (transdermal), weakly positive Coombs' test (oral), increased sensitivity to ethanol (oral), thrombocytopenia (oral), abdominal pain (oral), pseudo-obstruction (oral)

Antipsychotics: Concurrent use with antipsychotics (especially low potency) or nitroprusside may produce additive hypotensive effects

Beta-blockers: May potentiate bradycardia in patients receiving clonidine and may increase the rebound hypertension of withdrawal; discontinue beta-blocker several days before clonidine is tapered

CNS depressants: Sedative effects may be additive; monitor for increased effect; includes barbiturates, benzodiazepines, narcotic analgesics, ethanol, and other sedative agents

Cyclosporine: Clonidine may increase cyclosporine (and perhaps tacrolimus) serum concentrations; cyclosporine dosage adjustment may be needed

Hypoglycemic agents: Clonidine may decrease the symptoms of hypoglycemia; monitor patients receiving antidiabetic agents

Levodopa: Effects may be reduced by clonidine in some patients with Parkinson's disease (limited documentation); monitor

Local anesthetics: Epidural clonidine may prolong the sensory and motor blockade of local anesthetics

Mirtazapine: Antihypertensive effects of clonidine may be antagonized by mirtazapine (hypertensive urgency has been reported following addition of mirtazapine to clonidine); in addition, mirtazapine may potentially enhance the hypertensive response associated with abrupt clonidine withdrawal. Avoid this combination; consider an alternative agent.

Narcotic analgesics: May potentiate hypotensive effects of clonidine

Tricyclic antidepressants: Antihypertensive effects of clonidine may be antagonized by tricyclic antidepressants; in addition, tricyclic antidepressants may enhance the hypertensive response associated with abrupt clonidine withdrawal; avoid this combination; consider an alternative agent

Verapamil: Concurrent administration may be associated with hypotension and AV block in some patients (limited documentation); monitor

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).

Y-site administration: Compatible: Lorazepam

Compatibility in syringe: Compatible: Bupivacaine with morphine, fentanyl with lidocaine, ketamine with tetracaine

Onset of action: Oral: 0.5-1 hour

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%)

Children:

Oral:

Hypertension: Initial: 5-10 mcg/kg/day in divided doses every 8-12 hours; increase gradually at 5- to 7-day intervals to 25 mcg/kg/day in divided doses every 6 hours; maximum: 0.9 mg/day

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: 0.1 mg twice daily to maximum of 0.4 mg/day for 3-4 weeks

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

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: Clcr<10 mL/minute: Administer 50% to 75% of normal dose initially

Dialysis: Not dialyzable (0% to 5%) via hemo- or peritoneal dialysis; supplemental dose not necessary

Oral: Do not discontinue clonidine abruptly. if needed, gradually reduce dose over 2-4 days to avoid rebound hypertension

Transdermal patch: 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.

Note that the use of moxonidine to lower sympathetic activation in patients with heart failure was associated with increased mortality.

Injection, epidural solution, as hydrochloride [preservative free] (Duraclon™): 100 mcg/mL (10 mL); 500 mcg/mL (10 mL)

Patch, transdermal [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)

Tablet, as hydrochloride (Catapres®): 0.1 mg, 0.2 mg, 0.3 mg

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