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Cardiovascular safety pharmacology studies in monkeys and dogs show that IV doses approximately two to three times the recommended clinical dose on a mg/m2 basis are associated with increases in heart rate, decreases in contractility, hypotension and death. The decreased cardiac contractility and hypotension responded to acute intervention with positive inotropic or pressor agents. In dog studies, a slight increase in the corrected QT interval was observed at a lethal dose.
Overdosage more than twice the recommended dose in patients has been associated in patients with the acute onset of symptomatic hypotension and thrombocytopenia with fatal outcomes.
There is no known specific antidote for VELCADE overdosage. In the event of an overdosage, the patient's vital signs should be monitored and appropriate supportive care given to maintain blood pressure (such as fluids, pressors, and/or inotropic agents) and body temperature (see Precautions and Dosage & Administration).
