"The cystic fibrosis (CF) drug Orkambi (Vertex Pharmaceuticals) has received a green light from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP).
Orkambi is a fixed-dose oral combination "...
The signs and symptoms of clonidine hydrochloride overdosage include hypotension, bradycardia, lethargy, irritability, weakness, somnolence, diminished or absent reflexes, miosis, vomiting and hypoventilation. With large overdoses, reversible cardiac conduction defects or arrhythmias, apnea, seizures and transient hypertension have been reported. The oral LD50 of clonidine in rats was 465 mg/ kg, and in mice 206 mg/kg.
The general treatment of clonidine hydrochloride overdosage may include intravenous fluids as indicated. Bradycardia can be treated with intravenous atropine sulfate and hypotension with dopamine infusion in addition to intravenous fluids. Hypertension, associated with overdosage, has been treated with intravenous furosemide or diazoxide or alpha-blocking agents such as phentolamine.
Tolazoline, an alpha-blocker, in intravenous doses of 10 mg at 30-minute intervals, may reverse clonidine's effects if other efforts fail. Routine hemodialysis is of limited benefit, since a maximum of 5% of circulating clonidine is removed.
In a patient who ingested 100 mg clonidine hydrochloride, plasma clonidine levels were 60 ng/mL (one hour), 190 ng/mL (1.5 hours), 370 ng/mL (two hours) and 120 ng/mL (5.5 and 6.5 hours). This patient developed hypertension followed by hypotension, bradycardia, apnea, hallucinations, semicoma, and premature ventricular contractions. The patient fully recovered after intensive treatment.
Symptoms of acute overdosage include nausea, weakness, dizziness and disturbances of electrolyte balance. The oral LD50 of the drug in the mouse and the rat is more than 25,000 mg/kg body weight. The minimum lethal dose (MLD) in humans has not been established. There is no specific antidote but gastric lavage is recommended, followed by supportive treatment. Where necessary, this may include intravenous dextrose-saline with potassium, administered with caution.
CLORPRES (clonidine hydrochloride and chlorthalidone) ® is contraindicated in patients with known hypersensitivity to chlorthalidone or other sulfonamide-derived drugs.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/28/2009
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