The oral Lowest published toxic dose (TDLo) is 12.86 mg/kg in man MSDS. Oral LD50 ranges from 410 to 1500 mg/kg in rat MSDS, L2292. Oral LD50 in mouse and rabbit is 880 mg/kg and 700 mg/kg, respectively ^L2292. The LD50 following intravenous administration in rat was 17 mg/kg ^L2292.

In adults, the symptoms of overdosage include sedation, drowsiness (preceding excitement, convulsions, and postictal depression), dizziness, hypotension, dryness of the mouth, confusion, tachycardia, ataxia, nausea, vomiting, dyspnea, cyanosis, convulsions, coma, respiratory paralysis and CNS depression ^L2292. Antihistamine toxicity of pizotifen in children may involve excitation, hallucinations, ataxia, incoordination, convulsions, fixed dilated pupils, flushed faces, and fever, leading to coma and cardiorespiratory collapse ^L2292. The use of activated charcoal is recommended in the management of overdose. For drug recent uptake, induction of emesis or gastric lavage and diuresis should be performed ^L2292. Supportive measures should be initiated to maintain effective respiration while closely monitoring vital signs. While severe hypotension must be corrected, the use of adrenaline may produce paradoxical effects ^L2292.

As pizotifen has the potential to cause tachycardia, an ECG should be performed and attention directed at the QRS and QT intervals ^L2292. Excitatory states or convulsions induced by pizotifen may be treated with short-acting barbiturates or benzodiazepines. However analeptics should be avoided ^L2292.