10 OVERDOSAGE

There is no known specific antidote for Bortezomib for Injection overdosage. In humans, fatal outcomes following the administration of more than twice the recommended therapeutic dose have been reported, which were associated with the acute onset of symptomatic hypotension (5.2) and thrombocytopenia (5.7). In the event of an overdosage, the patient's vital signs should be monitored and appropriate supportive care given.

Studies in monkeys and dogs showed that intravenous bortezomib doses as low as two times the recommended clinical dose on a mg/m2 basis were associated with increases in heart rate, decreases in contractility, hypotension, and death. In dog studies, a slight increase in the corrected QT interval was observed at doses resulting in death. In monkeys, doses of 3 mg/m2 and greater (approximately twice the recommended clinical dose) resulted in hypotension starting at one hour post-administration, with progression to death in 12 to 14 hours following drug administration.