August 31, 2005

Subject: Cease Sale of Thioridazine in Canada

Dear Health Care Professional,

Health Canada wishes to inform you that all manufacturers of thioridazine products will be required to stop sale by September 30, 2005.

Thioridazine is known to be associated with QT prolongation, which predisposes to life threatening cardiac arrhythmia such as torsade de pointes, and sudden death. Novartis Pharmaceuticals Canada Inc., manufacturer of the brand name thioridazine medication, Mellaril^®, communicated this safety concern to Canadian healthcare professionals in July 2000. This communication can be viewed online at: http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2000/mellaril_hpc-cps_e.html. Mellaril^® was voluntarily withdrawn from the Canadian market in July 2001 and as of June 2005, Novartis has withdrawn Melleril^® worldwide citing the availability of new anti-psychotic treatments with more favourable risk-benefit profiles.

Several generic manufacturers have continued to market thioridazine products in Canada. Based on a lack of evidence to support the continued safe use of thioridazine as an anti-psychotic, Health Canada will require a total stop sale by all manufacturers of thioridazine by September 30, 2005.

Advice for discontinuation and possible switch to alternative medications for patients currently taking thioridazine:

Health Canada recommends that patients using thioridazine should be advised of the discontinuation of thioridazine, and if necessary switched to an alternative anti-psychotic medication at the earliest medically feasible point. To discontinue treatment with thioridazine, gradual reduction in thioridazine dosage over several weeks is recommended to prevent recurrence of symptoms of the underlying condition and cholinergic rebound.

Although no formal protocol for switching patients from one anti-psychotic medication to another is available, information is available in the scientific literature reviewing the techniques commonly employed in clinical practice and the important factors that should be considered when switching antipsychotics. Among the switching techniques commonly employed for antipsychotics, cross-tapering (gradual down-titration of the current medication while up-titrating the new medication) has been widely recognised and recommended.

The choice of switching strategy and its detailed execution must be individualized for each patient. Prescribers are advised to pay specific attention to any potentially occurring phenomena of major relevance, such as cardiac arrhythmias linked to QT prolongation, pharmacokinetic interactions via cytochrome P450 2D6 metabolism, rebound symptoms and the emergence of extrapyramidal features, especially involuntary movement disorders, when selecting and switching to an alternate anti-psychotic medication.

Access to thioridazine after September 30, 2005

While all manufacturers will be prohibited from selling thioridazine after September 30, 2005, pharmacies may continue to dispense remaining supplies to allow for a transition period to switch patients to an alternate therapy. Health Canada anticipates there will be sufficient supplies in pharmacies to allow patients time to switch over to another product. Should pharmacy supplies be inadequate and/or patients cannot be safely transitioned to marketed alternatives, prescribers should contact the Special Access Programme at Health Canada to request temporary access to the drug for individual patients. In most cases, alternative therapies are available to treat schizophrenia. Availability of thioridazine through the Special Access Programme may be an option for patients who cannot be adequately managed on alternative therapies. Information on the Special Access Programme is available at: http://www.hc-sc.gc.ca/dhp-mps/acces/drugs-drogues/sapfs_pasfd_2002_e.html

Reporting of Adverse Events

Reporting rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments. The identification, characterization, and management of marketed health product-related adverse reactions are dependent on the active participation of health care professionals in adverse reaction reporting programmes. Any occurrences of any serious and/or unexpected adverse reactions in patients receiving thioridazine should be reported to Health Canada at the following address:

Thank you for your attention to this important safety matter.