Signs and Symptoms: Vildagliptin: In healthy subjects (7-14 subjects/treatment group), vildagliptin was administered in once-daily doses of 25 mg, 50 mg, 100 mg, 200 mg, 400 mg and 600 mg for up to 10 consecutive days. Doses up to 200 mg were well tolerated. At 400 mg, there were 3 cases of muscle pain, and individual cases of mild and transient paresthesia, fever, edema and transient increase in lipase levels (2 x ULN). At 600 mg, 1 subject experienced edema of the feet and hands, and an excessive increase in creatine phosphokinase (CPK) levels, accompanied by elevations of AST, C-reactive protein and myoglobin. Three additional subjects in this dose group presented with edema of both feet, accompanied by paresthesia in 2 cases. All symptoms and laboratory abnormalities resolved after study drug discontinuation.
Vildagliptin is not dialyzable, however, the major hydrolysis metabolite (LAY151) can be removed by haemodialysis.
Metformin HCl: Overdose of metformin HCl has occurred, including ingestion of amounts >50 g. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin HCl has been established. Lactic acidosis has been reported in approximately 32% of metformin HCl overdose cases. Metformin HCl is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin HCl overdosage is suspected.
Treatment: In the event of overdosage, appropriate supportive treatment should be initiated according to patient's clinical signs and symptoms.