Clozapine Toxicology Clozapine is an atypical antipsychotic most often reserved for use in patients who have treatment-resistant schizophrenia. It has a greater effect on negative symptoms and in patients with suicidal ideation than other antipsychotic drugs. Clozapine Pharmacokinetics - Absorption – Well absorbed with an oral bioavailability of 50% following first-pass metabolism - Distribution – Highly variable volume of distribution (1.6 – 7 L/kg). - Metabolism - Clozapine is extensively metabolized in the liver by CYP1A2 (major), CYP2D6 and CYP3A4. Most metabolites are inactive, although one (N-desmethylclozapine) has some limited activity at dopamine receptors. - Elimination – elimination half-life of 12-14 hours, with a mix of renal (50%) and fecal (30%) elimination routes for metabolites. Clozapine is associated with common adverse effects, such as: - hypersalivation - urinary incontinence - constipation - sedation. - cholinergic rebound upon its cessation (should be tapered off if possible) Clozapine is known to cause rare but serious adverse effects including: - severe neutropenia - seizures - myocarditis - increased mortality in elderly patients with dementia-related psychosis - increased risk of orthostatic hypotension, bradycardia, and syncope By Dr. Kathryn Watson @Kat_Watson #Clozapine #Toxicology #Toxicity #Diagnosis #Pharmacology
