Class: Antiadrenergic, Centrally acting analgesic
- Tablets 0.1 mg
- Tablets 0.2 mg
- Tablets 0.3 mg
- Transdermal system 2.5 mg
- Transdermal system 5 mg
- Transdermal System 7.5 mg
- Injection 100ߙmcg/mL
- Injection 500ߙmcg/mL
Stimulates central alpha-adrenergic receptors to inhibit sympathetic cardioaccelerator and vasoconstrictor centers.
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.
Vd is about 2.1 L/kg. Clonidine is 20% to 40% protein bound.IV
Distribution t ½ is about 11 min.
About 50% metabolized in the liver. The major metabolite is p-hydroxyclonidine.
The t ½ is 12 to 16 h. 40% to 60% is excreted unchanged in urine in 24 h.IV
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.
30 to 60 min.
2 to 4 h.
Special PopulationsRenal 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.
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.
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 AdministrationHypertension
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
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.
- 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.
- 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.
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 InteractionsAlcohol, 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.
CHF; orthostatic symptoms; palpitations; tachycardia; bradycardia.
Drowsiness; dizziness; sedation; nightmares; insomnia; nervousness or agitation; headache; fatigue; hypotension (epidural only); confusion (epidural only).
Rash; urticaria; erythema (with transdermal form); transient localized skin reactions; pruritus.
Itching, burning, or dry eyes; retinal degeneration; dry nasal polyps.
Dry mouth; constipation; anorexia; nausea; vomiting.
Impotence; decreased libido; nocturia; difficulty in micturition; urinary retention.
Weight gain; gynecomastia; transient elevations in blood glucose or serum creatinine phosphokinase.
Increased sensitivity to alcohol; pallor; muscle weakness; muscle or joint pain; cramps of lower limbs; weakly positive Coombs test.
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.
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.
Category C .
Excreted in breast milk.
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.
Reduced dosage may be required.
Labor and Delivery
Use of epidural clonidine during labor and delivery is not indicated.
Reduced dosage may be required.
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 is commonly seen in cancer patients and may be exacerbated by clonidine treatment.
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.
Continue clonidine therapy to within 4 h of surgery and resume as soon as possible thereafter.
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.
Bradycardia, hypotension, CNS depression, respiratory depression, constricted pupils, seizures, lethargy, agitation, vomiting, hypothermia, drowsiness, decreased or absent reflexes, irritability.