Efexor XR Overdosage

In animal toxicology studies, the oral LD₅₀ values for venlafaxine were equivalent to 45-90 times the maximum recommended human dose.
Among the patients treated with Efexor XR in premarketing depression evaluations, there were 2 reports of acute overdosage, either alone or in combination with other drugs. One patient took a combination of Efexor XR 6 g and lorazepam 2.5 mg. This patient was hospitalized, treated symptomatically and recovered without any untoward effects. The other patient took Efexor XR 2.85 g. This patient reported paresthesia of all 4 limbs but recovered without sequelae.
There were 2 reports of acute overdose with Efexor XR in anxiety trials. One patient took a combination of Efexor XR 0.75 g, paroxetine 200 mg and zolpidem 50 mg. This patient was described as being alert, able to communicate and a little sleepy. This patient was hospitalized, treated with activated charcoal and recovered without any untoward effects. The other patient took Efexor XR 1.2 g. This patient had moderate dizziness, nausea, numb hands and feet, and hot-cold spells 5 days after the overdose. The patient recovered and no other specific problems were found.
Among the patients treated with Efexor in premarketing evaluations, there were 14 reports of acute overdose, either alone or in combination with other drugs and/or alcohol. The majority of the reports involved ingestion in which the total dose of Efexor taken was estimated to be no more than several-fold higher than the usual therapeutic dose. The 3 patients who took the highest doses were estimated to have ingested approximately 6.75, 2.75 and 2.5 g. All patients recovered without sequelae. Most patients reported no symptoms. Among the remaining patients, somnolence was the most commonly reported symptom. The patient who ingested 2.75 g of Efexor was observed to have 2 generalized convulsions and a prolongation of QTc to 500 msec, compared with 405 msec at baseline. Coma resulted and resuscitation was required. Mild sinus tachycardia was reported in 2 of the other patients.
In post-marketing experience, overdose with venlafaxine was reported predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdose include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, convulsion and vomiting. Other changes reported include electrocardiographic changes (eg, prolongation of QT interval, bundle-branch block, QRS prolongation), ventricular tachycardia, bradycardia, hypotension, vertigo and death.
Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine-treated patients have a higher burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage as opposed to some characteristics of venlafaxine-treated patients is not clear. Prescriptions for venlafaxine should be written for the smallest quantity of drug consistent with good patient management, in order to reduce the risk of overdose.
Treament: General supportive and symptomatic measures are recommended; cardiac rhythm and vital signs must be monitored. When there is a risk of aspiration, induction of emesis is not recommended. Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients.
Administration of activated charcoal may also limit drug absorption.
Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit.
No specific antidotes for venlafaxine are known.