Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. If a patient receiving clonidine is also taking tricyclic antidepressants, the hypotensive effect of clonidine may be reduced, necessitating an increase in the clonidine dose. If a patient receiving clonidine is also taking neuroleptics, orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue) may be induced or exacerbated.
Monitor heart rate in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction e.g., digitalis, calcium channel blockers, and beta-blockers. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil.
Amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats (see
Hypertension may develop early and may be followed by hypotension, bradycardia, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, weakness, irritability and miosis. The frequency of CNS depression may be higher in children than adults. Large overdoses may result in reversible cardiac conduction defects or dysrhythmias, apnea, coma and seizures. Signs and symptoms of overdose generally occur within 30 minutes to two hours after exposure. As little as 0.1 mg of clonidine has produced signs of toxicity in children.
If symptoms of poisoning occur following dermal exposure, remove all Catapres-TTS® (clonidine) transdermal therapeutic systems. After their removal, the plasma clonidine levels will persist for about 8 hours, then decline slowly over a period of several days. Rare cases of CATAPRES-TTS poisoning due to accidental or deliberate mouthing or ingestion of the patch have been reported, many of them involving children.
There is no specific antidote for clonidine overdosage. Ipecac syrup-induced vomiting and gastric lavage would not be expected to remove significant amounts of clonidine following dermal exposure. If the patch is ingested, whole bowel irrigation may be considered and the administration of activated charcoal and/or cathartic may be beneficial. Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension and vasodilators for hypertension. Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension and/or coma; blood pressure should be monitored since the administration of naloxone has occasionally resulted in paradoxical hypertension. Dialysis is not likely to significantly enhance the elimination of clonidine.
The largest overdose reported to date, involved a 28-year old male who ingested 100 mg of clonidine hydrochloride powder. This patient developed hypertension followed by hypotension, bradycardia, apnea, hallucinations, semicoma, and premature ventricular contractions. The patient fully recovered after intensive treatment. Plasma clonidine levels were 60 ng/mL after 1 hour, 190 ng/mL after 1.5 hours, 370 ng/mL after 2 hours, and 120 ng/mL after 5.5 and 6.5 hours. In mice and rats, the oral LD50 of clonidine is 206 and 465 mg/kg, respectively.