Intraperitoneal lowest published toxic dose (TDLO) is 10 mg/kg in rats.^L47531

Acute overdosage with tapentadol is characterized by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations.^L47286

Tapentadol overdose is managed by reestablishing a patent and protected airway and using assisted or controlled ventilation if needed. Other supportive measures can manage circulatory shock and pulmonary edema. Cardiac arrest or arrhythmias will require advanced life-support measures.^L47286

Opioid antagonists, such as naloxone, are specific antidotes to respiratory depression resulting from opioid overdose. They should be administered, in multiple doses, depending on patient response. As administration of the recommended usual dosage of the opioid antagonist will precipitate an acute withdrawal syndrome in individuals with physical dependence on opioids, administration of the opioid antagonist should be initiated with care and by titration with smaller than usual doses.^L47286