Yes: Tablet

Alpha₂ Agonist

Management of mild to moderate hypertension; either used alone or in combination with other antihypertensives

C

Clinical effects on the fetus: Crosses the placenta. Caution should be used with this drug due to the potential of rebound hypertension with abrupt discontinuation.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics has NO RECOMMENDATION.

Hypersensitivity to clonidine hydrochloride or any component

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.

Incidence of adverse events is not always reported.

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), weakness (10% 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)

Miscellaneous: Withdrawal syndrome (1% oral)

<1% (Limited to important or life-threatening symptoms): 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), palpitations (oral, transdermal), tachycardia (oral, transdermal), bradycardia (oral), sinus bradycardia (oral, transdermal), atrioventricular block (oral, transdermal), congestive heart failure (oral, transdermal), EKG 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), anorexia (transdermal), vomiting (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 alcohol (oral), palpitations (oral), tachycardia (oral), thrombocytopenia (oral), abdominal pain (oral), pseudo-obstruction (oral)

Symptoms of overdose include bradycardia, CNS depression, hypothermia, diarrhea, respiratory depression, apnea

Treatment is primarily supportive and symptomatic. Hypotension usually responds to I.V. fluids or Trendelenburg positioning. Naloxone may be utilized in treating CNS depression and/or apnea and should be given I.V. 0.4-2 mg, with repeated doses as needed or as an infusion.

CNS depressants: Effects may be additive.

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

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

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

TCAs antagonize hypotensive effects of clonidine; best to avoid this combination; consider an alternative agent.

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.

Narcotic analgesics may potentiate hypotensive effects of clonidine.

Alcohol and barbiturates may increase the CNS depression; epidural clonidine may prolong the sensory and motor blockade of local anesthetics.

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

Onset of effect: Oral: 0.5-1 hour; T_max: 2-4 hours

Duration: 6-10 hours

Distribution: V_d: 2.1 L/kg (adults); highly lipid soluble; distributes readily into extravascular sites; protein binding: 20% to 40%

Metabolism: Hepatic (enterohepatic recirculation); extensively metabolized to inactive metabolites

Bioavailability: 75% to 95%

Half-life: Adults: Normal renal function: 6-20 hours; Renal impairment: 18-41 hours

Elimination: 65% excreted in urine, 32% unchanged, and 22% excreted in feces; not removed significantly by hemodialysis

Oral:

Children: 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

Adults: Initial dose: 0.1 mg twice daily, usual maintenance dose: 0.2-1.2 mg/day in 2-4 divided doses; maximum recommended dose: 2.4 mg/day

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

Elderly: Initial: 0.1 mg once daily at bedtime, increase gradually as needed.

Transdermal: 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.

Epidural infusion: 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.

Dosing adjustment in renal impairment: Cl_cr <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.

Hypertensive patients may need to decrease sodium and calories in diet

Blood pressure, standing and sitting/supine, respiratory rate and depth, pain relief, mental status, heart rate (bradycardia may be treated with atropine)

Therapeutic: 1-2 ng/mL (SI: 4.4-8.7 nmol/L)

sodium (S); catecholamines (U)

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 advent of the clonidine patch has provided an important alternative to frequent daily dosing. However, it is important that overlap of therapy be maintained 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.

Drowsiness is common

Dry mouth, orthostatic hypotension, and sedation may be increased with concurrent psychotropic use; used to treat clozapine-induced sialorrhea; TCAs may antagonize clonidine's hypotensive effect

No information available to require special precautions

>10% of patients experience significant dry mouth

Take as directed, at bedtime. Do not skip doses or discontinue without consulting prescriber. If using patch, check daily for correct placement. Do not use OTC medications which may affect blood pressure (eg, cough or cold remedies, diet pills, stay-awake medications) without consulting prescriber. This medication may cause drowsiness, dizziness, or impaired judgment (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 (increase roughage, bulk in diet); or dry mouth or nausea (frequent mouth care or sucking lozenges may help). Report difficulty, pain, or burning on urination; increased nervousness or depression; 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; wet cough or respiratory difficulty; chest pain or palpitations; muscle weakness, fatigue, or pain; or other persistent side effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

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; if needed, gradually reduce dose over 2-4 days to avoid rebound hypertension; during epidural administration, monitor cardiovascular and respiratory status carefully

Injection, preservative free, as hydrochloride: 100 mcg/mL (10 mL)

Patch, transdermal, as hydrochloride: 1, 2, and 3 (0.1, 0.2, 0.3 mg/day, 7-day duration)

Tablet, as hydrochloride: 0.1 mg, 0.2 mg, 0.3 mg

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.

Corazza M, Mantovani L, Virgili A, et al, "Allergic Contact Dermatitis From a Clonidine Transdermal Delivery System," Contact Dermatitis, 1995, 32(4):246.

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.

Hart-Santora D and Hart LL, "Clonidine in Attention Deficit Hyperactivity Disorder," Ann Pharmacother, 1992, 26(1):37-9.

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.

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.

Rocchini AP, "Childhood Hypertension: Etiology, Diagnosis, and Treatment," Pediatr Clin North Am, 1984, 31(6):1259-73.

Sinaiko AR, "Pharmacologic Management of Childhood Hypertension," Pediatr Clin North Am, 1993, 40(1):195-212.