Archived – Important Safety Information Regarding Medication Errors Resulting from Confusion Between Seroquel® and Serzone-5HT2® – AstraZeneca and Bristol-Myers Squibb

IMPORTANT SAFETY INFORMATION REGARDING MEDICATION ERRORS RESULTING FROM CONFUSION BETWEEN SEROQUEL® AND SERZONE-5HT2®

October 31, 2002

Dear Health Care Professional:

Please be aware of the following:

Potential for medication error resulting from confusion between Seroquel® and Serzone-5HT2® (sound-alike medications).

AstraZeneca Canada Inc. has received one report of a medication error in Canada involving confusion between its atypical antipsychotic Seroquel® (quetiapine fumarate) indicated for the management of the manifestations of schizophrenia, and Serzone-5HT2® (nefazodone hydrochloride), manufactured by Bristol-Myers Squibb, indicated for the symptomatic relief of depressive illness. This report resulted from a dispensing error. Serzone-5HT2® was prescribed, however Seroquel® was received by the patient. No other reports of medication errors between these two drugs have been received by AstraZeneca Canada Inc. or Bristol-Myers Squibb Canada Inc., at the time of writing this letter.

This letter is being issued to health care professionals and all Canadian hospitals, and relevant professional associations advising them of the possibility and potential seriousness of confusing Seroquel® and Serzone-5HT2®.

A similar letter was sent to healthcare professionals in the U.S.A. and a safety alert letter was also posted on the FDA website (on May 20, 2002).

The URL is: http://www.fda.gov/medwatch/SAFETY/2002/seroquel.htm.

The letter on the FDA website contained the following information. Several reports of medication errors were received by AstraZeneca in the U.S., where Seroquel® was incorrectly administered to patients instead of Serzone®, and visa-versa, leading to various adverse events. The primary events noted in these reports included mental status deterioration, hallucination, paranoia, nausea, diarrhea, vomiting, muscle weakness, lethargy, dizziness and complications associated with these disorders. Three patients were hospitalized and four patients required emergency room visits. A 25 year-old female experienced fever and respiratory arrest after taking Seroquel® for 3 days instead of Serzone®, and eventually died, although a causal relationship has not been established.

According to the medication error reports, verbal and written prescriptions were incorrectly interpreted, labelled, and/or filled due to the similarity in names between Seroquel® and Serzone®. Furthermore, the overlapping strengths (100 mg and 200 mg), the dosage forms (tablets), the dosing interval (BID), and the fact that these two products were stocked close together in pharmacies were also critical in causing these errors.

Seroquel® is supplied for oral administration as 25 mg (peach), 100 mg (yellow), 150 mg (pale yellow), 200 mg (round, white) tablets and 300 mg (capsule shaped tablets) intagliated with the name "Seroquel". Serzone-5HT2® tablets are available in 50, 100, 150, and 200 hexagonal color-coded tablets, and are imprinted "BMS".

In clinical trials of Seroquel®, the adverse events with an incidence of 5% or greater and twice that of placebo were dizziness, postural hypotension, dry mouth, and dyspepsia. In clinical trials of Serzone-5HT2®, the adverse events with an incidence of 5% or greater and significantly greater than placebo patients were somnolence, dry mouth, nausea, dizziness, constipation, asthenia, lightheadedness, blurred vision, confusion and abnormal vision.

Although both medications have short half-lives (6 hours for quetiapine, 4 hours for nefazodone and its major active metabolite), an abrupt accidental switch may result in a brief period where the medications may interact. While co-administration of these medications is not specifically contraindicated, concurrent usage has not been studied. Because quetiapine is metabolized by the cytochrome P450 3A isoenzyme system, caution is indicated when Seroquel® is administered with inhibitors of this system. Serzone-5HT2® is an inhibitor of the cytochrome P450 3A4 isoenzyme system.

Please note that reporting rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments.

Physicians are reminded to print clearly on prescriptions and ensure that patients know the name and the purpose of their medication. Pharmacists are reminded that the two medications should not be stored in close proximity to each other, and pharmacists need to confirm with both the physician and patient that the correct medication is being dispensed. Your assistance is requested in clearly communicating both verbal and written prescriptions for these products to help avoid future dispensing errors.

The identification, characterization, and management of drug-related adverse events is dependent on the active participation of health care professionals in adverse drug reaction reporting programmes. Health care professionals are asked to report any suspected adverse reactions in patients receiving Seroquel® or Serzone-5HT2® in error, to the appropriate manufacturer (AstraZeneca 1-800-668-6000; Bristol-Myers Squibb 1-800-267-1088); or to the Marketed Health Products Directorate at the following addresses:

AstraZeneca Canada Inc.

1004 Middlegate Road

Mississauga, ON L4Y 1M4

http://www.astrazeneca.com

Bristol-Myers Squibb

2365 Cote-de-Liesse Road

Montreal, QC H4N 2M7

http://www.bms.com

Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use. Thank you for your attention.

Sincerely,

original signed by

Kazimierz R. Borkowski, Ph.D.

Vice-President, Medical Affairs

AstraZeneca Canada Inc.

original signed by

Nacia Faure, M.D.

Medical Director

Bristol-Myers Squibb Canada Inc.

Please consult the complete prescribing information for Seroquel® and Serzone-5HT2®.

Any suspected adverse drug reactions can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Marketed Health Products Directorate

HEALTH CANADA

Address Locator: 0201C2

OTTAWA, Ontario, K1A 1B9

Tel: (613) 957-0337 or Fax: (613) 957-0335

Toll free for consumers and health professionals:

Tel: 866 234-2345, Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

The ADR Reporting Form and the ADR Guidelines can be found on the TPD web site or in The Canadian Compendium of Pharmaceuticals and Specialties.