Recognizing & Managing Clozaril Toxicity: How Much is Too Much?

Clozaril (clozapine) has the potential to cause a number of toxic effects, especially at high doses. Symptoms of Clozaril toxicity include:

  • Sedation and drowsiness: Excessive sedation is a sign of elevated Clozaril levels and risk of toxicity. Patients may seem overly lethargic, drowsy or even in a stupor. Dose reduction usually reverses this effect.
  • Dizziness or confusion: Feeling lightheaded, unsteady or confused can indicate toxicity and require medical review. May lead to falls if severe.
  • Tachycardia: A rapid heart rate, often above 120 beats per minute. Can usually be managed by temporarily withholding Clozaril and may necessitate dose reduction or beta-blockers.
  • Hypersalivation: Although common even within the therapeutic range, excessive salivation may be a symptom of toxicity in some patients, especially if of sudden onset or severity. Anticholinergics can provide relief but toxicity may still need to be addressed.
  • Nausea or diarrhea: Sometimes transient, but can be severe in toxicity and lead to dehydration or electrolyte imbalance if prolonged. May require IV fluids or hospitalization.
  • Agitation or delirium: Although less likely at higher doses, some patients may become increasingly agitated, restless, irritable or even delirious when Clozaril levels are too high. Often resolves within 24-48 hours of stopping Clozaril.
  • Seizures: Clozaril lowers the seizure threshold and at very high levels seizures become more likely, especially in susceptible individuals or if combined with other seizure risk factors. Requires immediate medical help and discontinuation of Clozaril.
  • Neuroleptic malignant syndrome: A rare but life-threatening reaction seen with excessive dopaminergic blockade. Manifests as severe rigidity, fever, delirium and autonomic instability. Discontinue Clozaril and other antipsychotics immediately. IV fluids and medications may be needed to manage symptoms.
  • Loss of consciousness: High Clozaril levels that produce stupor, confusion or delirium can progress to a loss of consciousness in some cases. Patients will require hospitalization for close monitoring and supportive management until drug levels decrease and symptoms improve.
  • Other effects: Constipation, changes in blood pressure or temperature, blurred vision, tremor or headache may also indicate toxicity for some individuals. Seek medical review, especially if multiple symptoms are present or a sudden change from baseline.

In summary, symptoms of Clozaril toxicity span sedation through to potential loss of consciousness in severe cases. However, not all patients will demonstrate the full range or same number of symptoms. Close monitoring, especially when changing doses or if side effects seem disproportionate, is key to early detection and intervention to limit risks. Prompt review and, where indicated, temporary cessation or reduction of Clozaril will usually reverse symptoms and prevent progression, although some may require hospital support until stabilized. Ongoing vigilance and individual risk management remain essential due to inter-patient variability in sensitivity and manifestations of toxicity.

There are various forms of drugs available, such as tablets or liquids, and each may have a separate patient information leaflet (PIL) for different doses. It is important to refer to the PIL for the specific form and dose of the drug that you have been prescribed.

You can search for further information and PILs on websites such as: