Dosing Tips

• Extended release tablet should not be chewed, crushed, or broken before swallowing, as this could alter controlled release properties

• Do not substitute different clonidine products for each other on a mg-per-mg basis, because they have different pharmacokinetic profiles

• Adverse effects are dose-related and usually transient

• The last dose of the day should occur at bedtime so that blood pressure is controlled overnight

• If clonidine is terminated abruptly, rebound hypertension may occur within 2–4 days, so taper dose in decrements of no more than 0.1 mg every 3 to 7 days when discontinuing

• Using clonidine in combination with another antihypertensive agent may attenuate the development of tolerance to clonidine’s antihypertensive effects

• The likelihood of severe discontinuation reactions with CNS and cardiovascular symptoms may be greater after administration of high doses of clonidine

✽ In patients who have developed localized contact sensitization to transdermal clonidine, continuing transdermal dosing on other skin areas or substituting with oral clonidine may be associated with the development of a generalized skin rash, urticaria, or angioedema

✽ If administered with a beta blocker, stop the beta blocker first for several days before the gradual discontinuation of clonidine in cases of planned discontinuation

Overdose

• Hypotension, hypertension, miosis, respiratory depression, seizures, bradycardia, hypothermia, coma, sedation, decreased reflexes, weakness, irritability, dysrhythmia

Long-Term Use

• Patients may develop tolerance to the antihypertensive effects

✽ Studies have not established the utility of clonidine for long-term CNS uses

✽ Be aware that forgetting to take clonidine or running out of medication can lead to abrupt discontinuation and associated withdrawal reactions and complications

Habit Forming

• Reports of some abuse by opiate addicts

• Reports of some abuse by non-opioid dependent patients

How to Stop

✽ Discontinuation reactions are common and sometimes severe

• Sudden discontinuation can result in nervousness, agitation, headache, and tremor, with rapid rise in blood pressure

• Rare instances of hypertensive encephalopathy, cerebrovascular accident, and death have been reported after clonidine withdrawal

• Taper over 2–4 days or longer to avoid rebound effects (nervousness, increased blood pressure)

• If administered with a beta blocker, stop the beta blocker first for several days before the gradual discontinuation of clonidine

Pharmacokinetics

• Half-life 12–16 hours

• Metabolized by the liver

• Excreted renally

Drug Interactions

• The likelihood of severe discontinuation reactions with CNS and cardiovascular symptoms may be greater when clonidine is combined with beta blocker treatment

• Increased depressive and sedative effects when taken with other CNS depressants

• Tricyclic antidepressants may reduce the hypotensive effects of clonidine

• Corneal lesions in rats increased by use of clonidine with amitriptyline

• Use of clonidine with agents that affect sinus node function or AV nodal function (e.g., digitalis, calcium channel blockers, beta blockers) may result in bradycardia or AV block