Diltiazem overdose

List of overdose reactions
The oral LD50's in mice and rats range from 415 to 740 mg/kg and from 560 to 810 mg/kg, respectively. The intravenous LD50's in these species were 60 and 38 mg/kg, respectively. The oral LD50 in dogs is considered to be in excess of 50 mg/kg, while lethality was seen in monkeys at 360 mg/kg.

The toxic dose in man is not known. Due to extensive metabolism, blood levels after a standard dose of Diltiazem can vary over tenfold, limiting the usefulness of blood levels in overdose cases.

There have been 29 reports of Diltiazem overdose in doses ranging from less than 1 gram to 10.8 grams. Sixteen of these reports involved multiple drug ingestions.

Twenty-two reports indicated patients had recovered from Diltiazem overdose ranging from less than 1 gram to 10.8 grams. There were seven reports with a fatal outcome; although the amount of Diltiazem ingested was unknown, multiple drug ingestions were confirmed in six of the seven reports.

Events observed following Diltiazem overdose included bradycardia, hypotension, heart block, and cardiac failure. Most reports of overdose described some supportive medical measure and/or drug treatment. Bradycardia frequently responded favorably to atropine, as did heart block, although cardiac pacing was also frequently utilized to treat heart block. Fluids and vasopressors were used to maintain blood pressure, and in cases of cardiac failure inotropic agents were administered. In addition, some patients received treatment with ventilatory support, gastric lavage, activated charcoal, and/or intravenous calcium. Evidence of the effectiveness of intravenous calcium administration to reverse the pharmacological effects of Diltiazem overdose was conflicting.

In the event of overdose or exaggerated response, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. Diltiazem does not appear to be removed by peritoneal or hemodialysis. Limited data suggest that plasmapheresis or charcoal hemoperfusion may hasten Diltiazem elimination following overdose. Based on the known pharmacological effects of Diltiazem and/or reported clinical experiences, the following measures may be considered: Bradycardia High-Degree AV Block Cardiac Failure Hypotension ---

Bradycardia
Administer atropine (0.6 to 1 mg). If there is no response to vagal blockade, administer isoproterenol cautiously.

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High-Degree AV Block
Treat as for bradycardia above. Fixed high-degree AV block should be treated with cardiac pacing.

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Cardiac Failure
Administer inotropic agents (isoproterenol, dopamine, or dobutamine) and diuretics.

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Hypotension
Vasopressors (e.g., dopamine or norepinephrine bitartrate).

Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician.

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