Professional Information

Clonidine Hydrochloride

Pronouncation: (KLOE-nih-DEEN HIGH-droe-KLOR-ide)
Class: Antiadrenergic, Centrally acting analgesic

Trade Names:
Catapres
- Tablets 0.1 mg
- Tablets 0.2 mg
- Tablets 0.3 mg

Trade Names:
Catapres-TTS-1
- Transdermal system 2.5 mg

Trade Names:
Catapres-TTS-2
- Transdermal system 5 mg

Trade Names:
Catapres-TTS-3
- Transdermal System 7.5 mg

Trade Names:
Duraclon
- Injection 100ߙmcg/mL
- Injection 500ߙmcg/mL

APO-Clonidine (Canada)
Dixarit (Canada)
Novo-Clonidine (Canada)
Nu-Clonidine (Canada)

Pharmacology

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

Pharmacokinetics

Absorption

Oral

T _max is about 3 to 5 h.

Epidural

C _max is about 4.4 ng/mL. T _max is about 19 min.

Transdermal

Therapeutic levels are achieved in 2 to 3 days.

Distribution

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

Distribution t _½ is about 11 min.

Metabolism

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

Elimination

Oral

The t _½ is 12 to 16 h. 40% to 60% is excreted unchanged in urine in 24 h.

The t _½ is about 9 h. 72% is excreted in urine in 96 h (40% to 50% as unchanged drug). Renal Cl is about 133 mL/min. Cl is about 219 mL/min.

Epidural

The t _½ is about 22 h. Cl is about 190ߙmin.

Transdermal

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

Onset

Oral

30 to 60 min.

Peak

Oral

2 to 4 h.

Special Populations

Renal Function Impairment

The t _½ increases up to 41ߙh in those with severe renal impairment. Dosage adjustment is recommended.

Indications and Usage

Management of hypertension. Used in combination with opiates for epidural use for relief of cancer pain.

Unlabeled Uses

Treatment of constitutional growth delay in children; diabetic diarrhea; Tourette syndrome; hypertensive urgencies; menopausal flushing; postherpetic neuralgia; diagnosis of pheochromocytoma; ulcerative colitis; reduction of allergen-induced inflammatory reactions in patients with extrinsic asthma; facilitation of smoking cessation; alcohol withdrawal; methadone/opiate detoxification.

Contraindications

Hypersensitivity to clonidine or any component of adhesive layer of 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

Hypertension
Adults Initial dose

PO 0.1 mg twice daily; maintenance dose: increase by increments of 0.1 to 0.2 mg/day until desired response is achieved (max, 2.4ߙmg/day in divided doses). SL 0.2 to 0.4ߙmg/day. Transdermal 0.1 mg patch weekly initially; titrate to determine best response. Dosage greater than two 0.3 mg patches does not improve efficacy.

Children

PO 5 to 25 mcg/kg/day in divided doses given every 6 h; increase dose as necessary at 5- to 7-day intervals.

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 40ߙmcg/h is limited.

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.

Transdermal
Each transdermal system has 2 parts: (1) patch containing active drug, and (2) adhesive overlay. Apply patch to hairless area of intact skin on upper arm or torso as directed. Then apply adhesive overlay to ensure good adhesion of patch.
Do not alter or trim patch.
Change patch every 7 days.
Alternate sites of patch application to prevent skin irritation.
Before discarding old patch, fold adhesive edges together.

Storage/Stability

Epidural

Store at controlled room temperature 15° to 30°C (50° to 86°F). Discard any unused portion.

Oral

Store tablets in tightly closed light-resistant container at room temperature.

Drug Interactions

Alcohol, CNS depressants

Clonidine may enhance depressant effects.

Beta-adrenergic blocking agents

May increase potential for rebound hypertension when clonidine therapy is discontinued.

Local anesthetics

Epidural clonidine may prolong the duration of pharmacologic effects of epidural local anesthetics, including sensory and motor blockade.

Narcotic analgesics

May potentiate the hypotensive effects of clonidine.

Tricyclic antidepressants

May reduce effect of clonidine.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

CHF; orthostatic symptoms; palpitations; tachycardia; bradycardia.

CNS

Drowsiness; dizziness; sedation; nightmares; insomnia; nervousness or agitation; headache; fatigue; hypotension (epidural only); confusion (epidural only).

Dermatologic

Rash; urticaria; erythema (with transdermal form); transient localized skin reactions; pruritus.

EENT

Itching, burning, or dry eyes; retinal degeneration; dry nasal polyps.

GI

Dry mouth; constipation; anorexia; nausea; vomiting.

Genitourinary

Impotence; decreased libido; nocturia; difficulty in micturition; urinary retention.

Metabolic

Weight gain; gynecomastia; transient elevations in blood glucose or serum creatinine phosphokinase.

Miscellaneous

Increased sensitivity to alcohol; pallor; muscle weakness; muscle or joint pain; cramps of lower limbs; weakly positive Coombs test.

Precautions

Warnings

Not recommended for obstetrical, postpartum, or perioperative pain management as 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 drug. If systolic BP is less than 90ߙmmߙHg or pulse is less than 60 bpm, withhold drug and notify health care provider.

Epidural

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.

Rash/Skin irritation

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.

Elderly

Reduced dosage may be required.

Labor and Delivery

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

Debilitated patients

Reduced dosage may be required.

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.

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.

Rebound hypertension

Discontinue therapy by reducing dose gradually over 2 to 4 days to avoid rapid increase in BP.

Respiratory depression and sedation

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

Sensitization to transdermal clonidine

Generalized skin rash may develop in patients with localized reaction to patch if they are switched to oral clonidine.

Overdosage

Symptoms

Bradycardia, hypotension, CNS depression, respiratory depression, constricted pupils, seizures, lethargy, agitation, vomiting, hypothermia, drowsiness, decreased or absent reflexes, irritability.