To the Editor: Since Clozaril’s patent expired in 1998, three generic products have entered the market (Zenith Goldline Pharmaceuticals, Geneva Pharmaceuticals, and Mylan Pharmaceuticals). These products have been deemed by the US Food and Drug Administration (FDA) as therapeutically equivalent to the branded product. However, bioequivalency was based on pharmacokinetic studies utilizing a significantly subtherapeutic clozapine dose of 12.5 mg/day in healthy male volunteers (1). In the few studies performed in the target population, clinical differences between products have been detected.

Mr. A was a 79-year-old man with a history of paranoid schizophrenia who was treated as an outpatient with Clozaril (Novartis Pharmaceuticals), 200 mg in the morning and 300 mg at bedtime. Mr. A’s psychosis had been stable with this dose for more than 4 years. During one visit, Clozaril was switched inadvertently to generic clozapine (Mylan Pharmaceuticals). One month later, Mr. A was admitted to the hospital with increasing paranoid delusions of being poisoned as well as failure to thrive after refusing to take anything by mouth for several days. Other causes for his altered mental status were ruled out, and it was concluded that Mr. A’s symptoms were due to an exacerbation of his schizophrenia. Mr. A was discharged 3 days later with the same dose of generic clozapine. He was readmitted the following month for similar symptoms and hospitalized for 10 days. During this admission, Mr. A was switched back to name-brand Clozaril. Two months after his, his psychosis was stable without a need for further intervention.