Overdose : מינון יתר

4.9   Overdose

The symptoms of overdose with Anafranil are similar to those reported with other tricyclic antidepressants.
Cardiac abnormalities and neurological disturbances are the main complications.
In children, accidental ingestion of any amount should be regarded as serious and potentially fatal.
Symptoms
The first signs and symptoms generally appear within 4 hours of ingestion and reach maximum severity after 24 hours. Owing to delayed absorption (anticholinergic effect), long half-life, and enterohepatic recycling of the drug, the patient may be at risk for up to 4-6 days.

The following symptoms may be seen:
Central nervous system
Somnolence, stupor, coma, ataxia, restlessness, agitation, hyperreflexia, muscler rigidity and choreoathetosis, convulsions. In addition, symptoms consistent with serotonin syndrome (hyperpyrexia, myoclonus, delirium and coma) may be observed.

Cardiovascular system
Hypotension, tachycardia, arrhythmias, QTc prolongation and arrhythmias including torsades de pointes, conduction disorders, shock, heart failure; in very rare cases cardiac arrest.
Respiratory depression, cyanosis, vomiting, fever, mydriasis, sweating, and oliguria or anuria may also occur.

Treatment
There is no specific antidote, and treatment is essentially symptomatic and supportive.
Anyone suspected of receiving an overdose of Anafranil, particularly children, should be hospitalised and kept under close surveillance for at least 72 hours.

Perform gastric lavage or induce vomiting as soon as possible if the patient is alert. If the patient is not alert, secure the airway with a cuffed endotracheal tube before beginning lavage, and do not induce vomiting.
These measures are recommended for up to 12 hours or even longer after the overdose since the anticholinergic effect of the drug may delay gastric emptying. Administration of activated charcoal may help to reduce drug absorption.

Since it has been reported that physostigmine may cause severe bradycardia, asystole, and seizures, its use is not recommended in cases of overdosage with Anafranil.
Peritoneal dialyses or haemodialyses are ineffective because of the low plasma concentrations of clomipramine.

Rare cases of pharmacobezoar, (masses of undigested or indigestible material) of varying severity, including fatal outcome, have been reported in association with overdose of prolonged release Anafranil. The pharmacobezoar may be radiopaque, facilitating radiological (X-ray or CT scan) confirmation; but cannot exclude the diagnosis. The formation of a pharmcobezoar may cause a slow but continual release and absorption of clomipramine, which may lead to overdose complications, including death, hours after drug ingestion and initial treatment with gastric lavage and activated charcoal. Since gastric lavage may be ineffective and could further increase systemic drug levels, considerationshould be given to physical removal of the pharmacobezoar by endoscopy or surgery in selected patients. Since these cases are very rare, there is insufficient clinical data regarding optimal treatment, which should also take into account the size and location of the pharmacobezoar, patient symptoms and condition and drug levels.