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MELLARIL (THIORIDAZINE HCL): OVERDOSAGE

Many of the symptoms observed are extensions of the side effects described under Adverse Reactions. Thioridazine Hydrochloride (Mellaril) can be toxic in overdose, with cardiac toxicity being of particular concern. Frequent ECG and vital sign monitoring of overdosed patients is recommended. Observation for several days may be required because of the risk of delayed effects.

Signs and Symptoms

Effects and clinical complications of acute overdose involving phenothiazines may include:

Cardiovascular: Hypotension, cardiac arrhythmias, shock, increased QT and PR intervals, ECG changes, non-specific ST and T wave changes, bradycardia, atrioventricular block, sinus tachycardia, ventricular tachycardia, Torsade de pointes, ventricular fibrillation, myocardial depression.

Central Nervous System: Extrapyramidal effects, sedation, confusion, hypothermia, agitation, hyperthermia, seizures, restlessness, areflexia, coma.

Autonomic Nervous System: Miosis, mydriasis, dry skin, nasal congestion, dry mouth, urinary retention, blurred vision.

Respiratory: Apnea, respiratory depression, pulmonary edema.

Gastrointestinal: Constipation, hypomotility, ileus.

Renal: Oliguria, uremia.

Toxic dose and blood concentration ranges for the phenothiazines have not been firmly established. It has been suggested that the toxic blood concentration range for thioridazine begins at 1.0 mg/dL, and 2-8 mg/dL is the lethal concentration range.

Treatment

An airway must be established and maintained. Adequate oxygenation and ventilation must be ensured.

Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. Treatment may include one or more of the following therapeutic interventions: correction of electrolyte abnormalities and acid-base balance, lidocaine, phenytoin, isoproterenol, ventricular pacing, and defibrillation. Disopyramide, procainamide, and quinidine may produce additive QTprolonging effects when administered to patients with acute overdosage of Mellaril and should be avoided. Caution must be exercised when administering lidocaine, as it may increase the risk of developing seizures.

Treatment of hypotension may require intravenous fluids and vasopressors. Phenylephrine, levarterenol, or metaraminol are the appropriate pressor agents for use in the management of refractory hypotension. The potent a adrenergic blocking properties of the phenothiazines makes the use of vasopressors with mixed alpha- and beta-adrenergic agonist properties inappropriate, including epinephrine and dopamine. Paradoxical vasodilation may result. In addition, it is reasonable to expect that the a adrenergic-blocking properties of bretylium might be additive to those of Mellaril (Thioridazine), resulting in problematic hypotension.

In managing overdosage, the physician should always consider the possibility of multiple drug involvement. Gastric lavage and repeated doses of activated charcoal should be considered. Induction of emesis is less preferable to gastric lavage because of the risk of dystonia and the potential for aspiration of vomitus. Emesis should not be induced in patients expected to deteriorate rapidly, or those with impaired consciousness.

Acute extrapyramidal symptoms may be treated with diphenhydramine hydrochloride or benztropine mesylate.

Avoid the use of barbiturates when treating seizures, as they may potentiate phenothiazine-induced respiratory depression.

Forced diuresis, hemoperfusion, hemodialysis and manipulation of urine pH are of unlikely benefit in the treatment of phenothiazine overdose due to their large volume of distribution and extensive plasma protein binding.

Up-to-date information about the treatment of overdose can often be obtained from a certified Regional Poison Control Center. Telephone numbers of certified Regional Poison Control Centers are listed in the Physicians' Desk Reference.

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