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Clonidine Hydrochloride

Pronunciation

Pronunciation: KLOE-ni-deen HYE-droe-KLOR-ide
Class: Antiadrenergic, Centrally acting analgesic

Trade Names

Catapres
- Tablets, oral 0.1 mg
- Tablets, oral 0.2 mg
- Tablets, oral 0.3 mg

Catapres-TTS-1
- Transdermal system 2.5 mg

Catapres-TTS-2
- Transdermal system 5 mg

Catapres-TTS-3
- Transdermal system 7.5 mg

Duraclon
- Injection 100 mcg/mL
- Injection 500 mcg/mL

Jenloga
- Tablets, modified-release, oral 0.1 mg

Kapvay
- Tablets, ER, oral 0.1 mg
- Tablets, ER, oral 0.2 mg

Nexiclon XR
- Tablets, ER, oral 0.17 mg
- Suspension, ER 0.09 mg

APO-Clonidine (Canada)
Dixarit (Canada)

Pharmacology

Stimulates central alpha-adrenergic receptors to inhibit sympathetic cardioaccelerator and vasoconstrictor centers.

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Pharmacokinetics

Absorption

Epidural

C max is approximately 4.4 ng/mL. T max is approximately 19 min.

Nexiclon XR

C max is approximately 0.49 ng/mL. T max is 7.8 h.

Tablet

T max is approximately 3 to 5 h (immediate release) and 4 to 7 h (modified release).

Transdermal

Therapeutic levels are achieved in 2 to 3 days.

Distribution

Vd is approximately 2.1 L/kg. Clonidine is 20% to 40% protein bound.

IV

Distribution half-life is approximately 11 min.

Metabolism

Approximately 50% is metabolized in the liver. The major metabolite is p-hydroxyclonidine.

Elimination

Epidural

The half-life is approximately 22 h. Cl is approximately 190 min.

IV

The half-life is approximately 9 h. 72% is excreted in the urine in 96 h (40% to 50% as unchanged drug). Renal Cl is approximately 133 mL/min. Cl is approximately 219 mL/min.

Nexiclon XR

The half-life is 13.7 h. 40% to 60% is excreted unchanged in the urine in 24 h.

Tablet

The half-life is 12 to 16 h. 40% to 60% is excreted unchanged in the urine in 24 h.

Transdermal

After removal, therapeutic levels persist for approximately 8 h and decline slowly over several days.

Onset

Tablet

30 to 60 min.

Peak

Tablet

2 to 4 h (immediate release); 4 to 7 h (modified release); 6 to 8 h ( Nexiclon XR ).

Special Populations

Renal Function Impairment

The half-life increases up to 41 h in patients with severe renal impairment. Dosage adjustment is recommended.

Hepatic Function Impairment

No data available.

Indications and Usage

Management of hypertension; treatment of attention deficit hyperactivity disorder (ADHD) in children ( Kapvay only); in combination with opiates for epidural use for relief of cancer pain (injection only).

Contraindications

Hypersensitivity to clonidine or any component of adhesive layer of the transdermal system.

Injection

In the presence of an injection-site infection; patients on anticoagulant therapy; patients with a bleeding diathesis; administration above the C4 dermatome, because there are not adequate safety data to support such use.

Dosage and Administration

ADHD
Children 6 y and older

PO Initially, 0.1 mg at bedtime; adjust in increments of 0.1 mg/day at weekly intervals until desired response is achieved (max, 0.4 mg/day).

Hypertension
Adults Initial dose

PO Initially, 0.1 mg twice daily (immediate release), 0.1 mg at bedtime (modified release), or 0.17 mg at bedtime ( Nexiclon XR ); increase by increments of 0.1 mg/day (immediate-release, modified-release) or 0.09 mg ( Nexiclon XR ) at weekly intervals until desired response is achieved (max, 2.4 mg/day of immediate release, 0.6 mg/day of modified release, or 0.52 mg/day of Nexiclon XR ).

Transdermal 0.1 mg patch weekly initially; titrate to determine best response. Doses greater than two 0.3 mg patches do not improve efficacy.

Children 12 y and older

PO Initially, 0.1 mg twice daily (immediate release); increase by increments of 0.1 mg/day at weekly intervals until desired response is achieved (max, 2.4 mg/day of immediate release).

Pain Relief
Adults

Epidural infusion 30 mcg/h as starting dose. Dosage may be titrated up or down depending on pain relief and occurrence of adverse reactions. Experience with dosage rates greater than 40 mcg/h is limited.

Elderly

PO May benefit from a lower initial dose.

Renal Function Impairment

PO Adjust dose according to the degree of renal impairment and uptitrate slowly. Start at 0.09 mg/day (suspension) in patients with ESRD on dialysis and in patients with moderate to severe kidney impairment.

General Advice

  • Epidural
  • Dilute the 500 mcg/mL product in sodium chloride 0.9% injection to a final concentration of 100 mcg/mL.
  • Must not be used with a preservative.
  • When discontinuing therapy with epidural clonidine, gradually reduce the dose over 2 to 4 days to avoid withdrawal symptoms. If therapy is to be discontinued in patients receiving a beta-blocker and clonidine concurrently, discontinue the beta-blocker several days before the gradual discontinuation of epidural clonidine.
  • Tablets
  • May be used alone or with other antihypertensives in the treatment of hypertension.
  • May be used alone or as adjunctive therapy to a psychostimulant for treatment of ADHD.
  • Dosages above 0.1 mg/day should be divided and taken in the morning and at bedtime. The larger portion of the daily dose should be taken at bedtime.
  • Modified-release clonidine is not to be used interchangeably with the immediate-release formulation. Clonidine ER is not to be used interchangeably with the immediate-release formulation.
  • Reduce the dose gradually over 2 to 4 days to avoid withdrawal symptoms. When discontinuing Kapvay , the total daily dose should be tapered in decrements of no more than 0.1 mg every 3 to 7 days.
  • If therapy is to be discontinued in patients receiving a beta-blocker and clonidine concurrently, the beta-blocker should be withdrawn several days before the gradual discontinuation of clonidine.
  • ER tablets should be swallowed whole and not crushed, cut, or chewed.
  • Transdermal
  • Each transdermal system has 2 parts: (1) patch containing active drug, and (2) adhesive overlay. Apply the patch to a hairless area of intact skin on the upper arm or torso, as directed. Then apply the adhesive overlay to ensure good adhesion of patch.
  • Do not alter or trim the patch.
  • Change patch every 7 days.
  • Alternate sites of patch application to prevent skin irritation.
  • Before discarding the old patch, fold adhesive edges together.

Storage/Stability

Epidural

Store between 50° and 86°F. Discard any unused portion.

Tablets

Store immediate-release tablets and Nexiclon XR between 59° and 86°F. Store modified-release and Kapvay between 68° and 77°F.

Transdermal

Store below 86°F.

Drug Interactions

Alcohol, CNS depressants

Clonidine may enhance depressant effects. Monitor the response and adjust the sedating drug dose as needed.

Beta-adrenergic blocking agents

Attenuation or reversal of antihypertensive effect and potentially life-threatening increases in BP may occur. Because of a potential for additive effects, such as bradycardia and AV block, caution is warranted in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction (eg, beta-blockers). If clonidine therapy is discontinued in patients receiving a beta-blocker, withdraw the beta-blocker several days before gradual discontinuation of clonidine.

Calcium channel blockers (eg, verapamil)

Because of a potential for additive effects, such as bradycardia and AV block, caution is warranted in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction (eg, calcium channel blockers).

Cyclosporine

The pharmacologic and toxic effects of cyclosporine may be increased by clonidine. Monitor cyclosporine concentrations and observe the clinical response of the patient. If an interaction is suspected, decrease the cyclosporine dose or stop clonidine.

Digitalis

Because of a potential for additive effects, such as bradycardia and AV block, caution is warranted in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction (eg, digitalis).

Mirtazapine

The pharmacologic effects of clonidine may be decreased by mirtazapine. Closely monitor BP when mirtazapine is started or stopped. If an interaction is suspected, adjust the clonidine dose as needed.

Prazosin

The antihypertensive effectiveness of clonidine may be decreased. Monitor BP when prazosin is started or stopped. Adjust the clonidine dose as needed.

Tizanidine

Possible additive hypotensive effects when clonidine and tizanidine are coadministered. Avoid coadministration. If both drugs must be given, closely monitor for signs of hypotension during dose increases.

Tricyclic antidepressants (eg, amitriptyline)

Tricyclic antidepressants may block antihypertensive effects of clonidine and possibly life-threatening elevations in BP may occur. The hypotensive effect of clonidine may be reduced, necessitating an increase in the clonidine dose.

Adverse Reactions

Cardiovascular

Bradycardia (4%); heart rate increased (3%); CHF, ECG abnormalities (eg, arrhythmias, AV block, functional bradycardia, sinus node arrest), hypotension (epidural only), orthostatic symptoms, palpitations, Raynaud phenomenon, sinus bradycardia, tachycardia.

CNS

Somnolence (38%); drowsiness (33%); headache (29%); fatigue (27%); dizziness (20%); insomnia (13%); sedation (10%); irritability, nightmare (9%); emotional disorder (5%); abnormal sleep-related event, aggression, sleep terror, tremor (3%); agitation, anxiety, behavioral changes, confusion (epidural only), delirium, delusional perception, depression, malaise, nervousness, nightmares, paresthesia, restlessness, sleep disorder, syncope, visual and auditory hallucinations.

Dermatologic

Alopecia, angioneurotic edema, erythema (transdermal only), hives, pruritus, rash, transient localized skin reactions, urticaria.

EENT

Throat pain (8%); ear pain, nasal congestion (5%); acute otitis media, epistaxis, nasopharyngitis, tearfulness (3%); accommodation disorder, blurred vision, burning or dry eyes, decreased lacrimation, dryness of the nasal mucosa.

GI

Dry mouth (53%); upper abdominal pain (20%); constipation (10%); anorexia, nausea (8%); GI viral (7%); diarrhea (4%); thirst (3%); abdominal pain, hepatitis, mild transient abnormalities in LFTs, parotitis, pseudo-obstruction (including colonic pseudo-obstruction), salivary gland pain, vomiting.

Genitourinary

Enuresis (4%); pollakiuria (3%); decreased sexual activity, difficulty in micturition, erectile dysfunction, loss of libido, nocturia, urinary retention.

Metabolic

Gynecomastia, transient elevations in blood glucose or serum CPK, weight gain.

Respiratory

Upper respiratory tract infection (11%); asthma, lower respiratory tract infection (3%).

Miscellaneous

Increased body temperature (5%); influenza-like illness (3%); fever, increased sensitivity to alcohol, leg cramps, muscle or joint pain, pallor, thrombocytopenia, weakly positive Coombs test, weakness, withdrawal syndrome.

Precautions

Warnings

Injection

Not recommended for obstetrical, postpartum, or perioperative pain management because the risk of hemodynamic instability (eg, hypotension, bradycardia) may be unacceptable in this population. Dilute the 500 mcg/mL strength prior to use.


Monitor

Assess BP and apical pulse before administering the drug, following dose increases, and periodically while on therapy. If systolic BP is less than 90 mm Hg or pulse is less than 60 bpm, withhold drug. Monitor patients with renal impairment carefully to prevent excessive hypotension, bradycardia, or sedation. Implantable epidural catheters are associated with a risk of catheter-related infections. Evaluation of fever in a patient receiving epidural clonidine should include the possibility of a catheter-related infection, such as meningitis or epidural abscess. Note any rash or skin irritation when removing patch.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Restrict the use of clonidine to children with severe intractable pain from malignancy that is unresponsive to epidural or spinal opiates or other more conventional analgesia techniques. Select the starting dose on a per kilogram basis (0.5 mcg/kg/h) and cautiously adjust based on clinical response. Safety and efficacy in children (modified-release tablets) or in children younger than 12 y (immediate-release tablets and transdermal) have not been established. Safety and efficacy of Kapvay in children with ADHD younger than 6 y have not been established. Safety and efficacy of Nexiclon XR has not been established.

Elderly

Per the Beers list, clonidine has the potential for orthostatic hypotension and CNS adverse effects in elderly patients.

Labor and Delivery

Use of epidural clonidine during labor and delivery is not indicated.

Renal Function

Monitor patients carefully to prevent excessive BP lowering or bradycardia. Uptitrate slowly in patients with chronic renal failure.

Special Risk Patients

Uptitrate slowly and use with caution in patients with severe coronary insufficiency, conduction disturbances, recent MI, or cerebrovascular disease.

Cardiac effects

Clonidine frequently causes decreases in heart rate. Rarely, AV block greater than first degree has been reported. Clonidine does not alter the hemodynamic response to exercise, but may mask the increase in heart-associated hypovolemia.

Debilitated patients

Reduced dosage may be required.

Depression

Depression is commonly seen in cancer patients and may be exacerbated by clonidine treatment.

Hypotension

Because severe hypotension may follow clonidine administration, use with caution in all patients. It is not recommended in most patients with severe CV disease or in those who are otherwise hemodynamically unstable. Balance the benefit of administration in these patients against the potential risks resulting from hypotension. Monitor vital signs frequently, especially during the first few days of epidural administration. When clonidine is infused into the upper thoracic spinal segments, more pronounced decreases in BP may be seen.

Perioperative considerations

Continue clonidine therapy to within 4 h of surgery and resume as soon as possible thereafter. Nexiclon XR may be administered up to 28 h prior to surgery and resumed the following day.

Respiratory depression and sedation

Clonidine administration may result in sedation and somnolence. High clonidine doses cause sedation and ventilatory abnormalities that are usually mild. Tolerance to these effects can develop with long-term administration.

Sensitization to transdermal clonidine

Generalized skin rash, urticaria, or angioedema may develop in patients with localized reaction to the patch if they are switched to oral clonidine.

Overdosage

Symptoms

Agitation, apnea, bradycardia, CNS depression, coma, constricted pupils, decreased or absent reflexes, drowsiness, hypotension, hypothermia, irritability, lethargy, respiratory depression, reversible cardiac conduction defects or dysrhythmias, seizures, vomiting, weakness.

Patient Information

  • ER tablets may be taken with or without food and should be swallowed whole and never crushed, cut, or chewed.
  • Inform patients that if the total daily dose of clonidine does not result in equal doses in the morning and at bedtime, the higher of the 2 doses should be taken at bedtime.
  • Instruct patients not to discontinue therapy without consulting their health care provider. Sudden cessation of clonidine treatment has, in some cases, resulted in symptoms such as nervousness, agitation, headache, and tremor.
  • Caution patients who wear contact lenses that treatment with clonidine may cause dryness of the eyes.
  • Advise patients who engage in potentially hazardous activities, such as operating machinery or driving, of a possible sedative effect of clonidine. Also inform them that this sedative effect may be increased by concomitant use of alcohol, barbiturates, or other sedating drugs.
  • Advise breast-feeding women taking modified-release tablets not to breast-feed.

Copyright © 2009 Wolters Kluwer Health.

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