Overdosing signs were observed in a toxicity study conducted in healthy adult Beagle dogs treated with 2 mg/kg, 4 mg/kg or 6 mg toceranib/kg once every other day for 13 consecutive weeks without dose interruption. Toceranib was well tolerated at 2 mg/kg dose level whereas adverse reactions were noted in some dogs treated with 4 mg/kg and thus a NOAEL could not be established.
Dogs in the 6 mg/kg every other day group exhibited the most adverse effects which included decreased food consumption and weight loss. Sporadic dose related lameness, stiffness, weakness and pain in limbs resolved without treatment. Anaemia and neutropenia and eosinopenia were dose-related. Two dogs (6 mg/kg) were euthanased at approximately 3 weeks for treatment-related clinical toxicities initiated by decreased feed intake and melaena culminating in anorexia, weight loss and haematochezia.
The main target organs of toxicity include the gastrointestinal tract, bone marrow, gonads and musculoskeletal system.
In case of adverse events following overdose, treatment should be discontinued until resolution and then resumed at the recommended therapeutic dose level.