BiCNU (carmustine for injection, USP) 100 mg/vial - Risk of Myelosuppression, Pulmonary Toxicity, Renal and Hepatic Toxicity as a Result of Overfilled Vials - Notice to Hospitals

Starting date:

September 4, 2012

Posting date:

September 6, 2012

Type of communication:

Notice to Hospitals

Subcategory:

Drugs

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-14807

This is duplicated text of a letter from Bristol-Myers Squibb Canada, Medical Services. Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Notice to Hospitals - Health Canada Endorsed Important Safety Information on BiCNU (carmustine for injection, USP), 100 mg/vial

September 4, 2012

Dear Healthcare Professional:

Please distribute to relevant departments (eg. Surgery, Oncology, Cancer Clinics, Emergency Medicine, Pharmacy, Pediatrics, Geriatrics, Internal Medicine, Nursing, Intensive Care and other Departments as required) and other involved professional staff and post this Notice in your institution.

Subject: Risk of myelosuppression, pulmonary toxicity, renal and hepatic toxicity as a result of overfilled vials of BiCNU^® (carmustine for injection, USP) 100 mg/vial.

Bristol-Myers Squibb Canada has initiated a voluntary recall of the BiCNU^® (carmustine for injection USP) 100mg/vial lots listed below. This recall is being conducted as a precautionary measure due to the discovery of an overfilled vial of carmustine following routine stability testing for a specific lot of BiCNU^® which was not distributed in Canada. The investigation to date has determined that the occurrence of this identified defect (overfilled vial) is very low. No other test results either associated with the affected lot or any of the other carmustine vial lots were abnormal, and there is an absence of associated patient complaints and associated adverse events. The occurrence of overfilled vials could result in patients receiving a dose greater than prescribed and could result in significant risk to patients, including myelosuppression, susceptibility to serious infections, bleeding, pulmonary toxicity (especially in those with known risk factors) and renal toxicity as well as other serious adverse effects such as hepatic toxicity.

Product List

STRENGTH	DIN NO.	LIST NO.	LOT NO.	EXPIRY
100mg/vial	00297763	1217908	9H4208A	JA 2013
100mg/vial	00297763	1217908	9H4210A	JA 2013
100mg/vial	00297763	1217908	0B7003A	FE 2013
100mg/vial	00297763	1217908	1C7005A	AL 2014

• Patients may receive greater than prescribed doses due to overfilled vials of BiCNU^® (carmustine for injection USP), 100 mg/vial. This could lead to increased risks of myelosuppression, susceptibility to serious infection, bleeding, pulmonary toxicity and renal toxicity as well as other serious adverse effects such as hepatic toxicity.
• Bristol-Myers Squibb Canada is requesting your assistance in returning all product from the above lots. Please review your inventory, segregate any product with the affected lot numbers and return the affected product according to the directions below.
• Physicians should remain vigilant to the possibility of the above serious events in patients having received BiCNU^®.

BiCNU^® (carmustine for injection USP) is indicated as palliative therapy to surgery and radiotherapy or in combination therapy with other chemotherapeutic agents in the following: primary brain tumors, malignant lymphomas, multiple myeloma, malignant melanoma (disseminated) and gastrointestinal carcinoma (Canadian Product Monograph dated 30 June 2011).

Patients, who are appropriate candidates for carmustine, may be immunocompromised due to their underlying disease, co-morbid conditions, and administration of myelosuppressive agents such as carmustine and other chemotherapeutic agents. Myelosuppression can cause bleeding which may be serious. Since myelosuppression is a known dose-limiting toxicity for carmustine, excessive dosing could increase myelosuppression and, in turn, the susceptibility to develop serious infections.

The overfill of vials could predispose patients to pulmonary toxicity especially those patients with known risk factors such as smoking, the presence of a respiratory condition, pre-existing radiographic abnormalities, sequential or concomitant thoracic irradiation, and concomitant use of other agents that cause lung damage. Early onset pulmonary toxicity is characterized by pulmonary infiltrates and/or fibrosis, and cases of fatal pulmonary toxicity have occurred. The age of onset has been reported from 1 year and 10 months to 72 years of age. The incidence appears to be dose related with total cumulative doses of 1200-1500 mg/m² being associated with increased likelihood of lung fibrosis.

Another possible effect of administering large doses of carmustine is renal toxicity consisting of decreases in kidney size, progressive azotemia, and renal failure. Although it is typically reported in patients who have received large cumulative doses after prolonged therapy with carmustine, it has also been reported occasionally in patients receiving lower total doses.

When used at high doses, BiCNU^® can also produce reversible hepatic toxicity (manifested by increased transaminase, alkaline phosphatase and bilirubin levels). Hepatotoxicity is delayed up to 60 days after dosing.

This recall is being initiated on a precautionary basis. To date, no reports of overfilled vials have been received for the lots subject to this recall.

Should any recalled product be found, please remove it from inventory and return it along with the completed Product Recall Return Form via Purolator, courier collect account no. 1-6088353 to Bristol-Myers Squibb Canada's reverse logistics provider Inmar for credit. You can reach Purolator at 1-888-744-7123. For your convenience, Bristol-Myers Squibb Canada has included a shipping address to be cut out of the form for your shipment.

Please fax the completed product recall return form to 1-866-922-7334 even if you do not have any recalled stock on hand. In this case, check the box to this effect on the form. Your response is vital to Bristol-Myers Squibb Canada's ability to monitor the effectiveness of this voluntary recall.

Managing marketed health product-related adverse reactions depends on healthcare professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-market adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any cases of serious myelosuppression, serious infection, bleeding, pulmonary renal or hepatic toxicity or other serious or unexpected adverse reactions possibly related to excessive dose in patients receiving BiCNU^® should be reported to Bristol-Myers Squibb Canada or Health Canada at the following addresses:

Bristol-Myers Squibb Canada, Medical Services
2344 Alfred-Nobel, suite 300
Montréal, Québec
H4S 0A4
Tel: 866-463-6267

To correct your mailing address or fax number, contact Bristol-Myers Squibb Canada, Medical Services.

To report suspected adverse reactions to these or other health products, please contact Health Canada's Canada Vigilance Program toll-free at 1-866-234-2345, or visit the MedEffect^™ Canada Web site for information on how to report.

The Reporting Forms, postage paid labels, and Guidelines can be found on the MedEffect^™ Canada Web site in the Adverse Reaction Reporting section. The Reporting Form is also in the Canadian Compendium of Pharmaceuticals and Specialties.

For other health product inquiries related to this communication, please contact Health Canada at:

Health Product and Food Branch Inspectorate (HPFBI)
E-mail: DCVIU_UVECM@hc-sc.gc.ca
Telephone: 1-800-267-9675
Fax: 1-613-946-5636

We do not expect this recall to impact the supply of BiCNU^®. Since October 2011, Bristol-Myers Squibb has been utilizing a different contract manufacturer to supply BiCNU^®.

We sincerely apologize for any inconvenience this may cause and appreciate your prompt attention to this matter.

If you have any questions regarding this recall, please contact Customer Services at 1-800-267-0005 (8:30 a.m. to 5:00 p.m. Eastern Standard Time). For medical queries, please call Medical Services at 1-866-463-6267.

Original signed by

Richard Briand, BPharm, PhD
Disease Area Head, Cardiovascular and Metabolism
Acting Vice-President Medical Affairs

Bristol-Myers Squibb Canada

Update

This HTML document is not a form. Its purpose is to display the information as found on the form for viewing purposes only. If you wish to use the form, you must use the alternate format below.

URGENT - PRODUCT RECALL TYPE I - RETURN FORM

BiCNU^® (carmustine for injection USP) 100mg per vial with diluent

PLEASE INDICATE BELOW ALL REMAINING INVENTORY OF THE RECALLED LOTS

STRENGTH	DIN NO.	LIST NO.	LOT NO.	EXPIRY DATE	QTY RETURNED
100mg/vial	00297763	1217908	9H4208A	JA 2013
100mg/vial	00297763	1217908	9H4210A	JA 2013
100mg/vial	00297763	1217908	0B7003A	FE 2013
100mg/vial	00297763	1217908	1C7005A	AL 2014

We do not have any stock of the above on hand

PLEASE COMPLETE THE FORM AND FAX IT TO 1-866-922-7334 WITHOUT DELAY

CUSTOMER NAME:
STREET ADDRESS:
CITY:
PROVINCE:
POSTAL CODE:

WHOLESALER

We have requested our accounts to return their stock of this merchandise

CREDIT NOTE: Please indicate your active Direct Account number with BMS or the Wholesaler you want us to use to issue your Credit Note (account number required)

BMS Active Direct Account no.

OR

Wholesaler name

Your account number at wholesaler

PLEASE CUT PORTION BELOW & TAPE TO SHIPPING CONTAINER

DRUG RECALL: BiCNU

PRODUCT RETURN

INMAR

ATTENTION: BRISTOL-MYERS SQUIBB CANADA Co.
2121 McCowan Road
Toronto,Ontario
M1S 3Y6