Clarification of Dosing Recommendation for FRAGMIN (dalteparin sodium injection) - Pharmacia Canada Inc. - Health Professional Advisory

Date: 2003-04-01

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The Marketed Health Products Directorate (MHPD), Therapeutic Products Directorate (TPD) and Biologics and Genetic Therapies Directorate (BGTD) post safety alerts, public health advisories, press releases and other notices from industry as a service to health professionals, consumers, and other interested parties. Although MHPD, TPD and BGTD approve therapeutic products, MHPD, TPD and BGTD do not endorse either the product or the company. Any questions regarding product information should be discussed with your health professional.

This is duplicated text of a letter from Pharmacia Canada Inc. Contact the company for a copy of any references, attachments or enclosures.

April 01, 2003

Dear Healthcare Professional:

Re: Clarification of Dosing Recommendations for FRAGMIN® (dalteparin sodium injection)

The purpose of this letter is to provide important clarification concerning the dosage and administration of FRAGMIN. This letter is in follow-up to the one, some of you received December 24, 2002 regarding close proximity dosing for elective hip surgery.

Indications for FRAGMIN include thromboprophylaxis in conjunction with surgery. Pharmacia Canada Inc., in consultation with Health Canada, wishes to clarify the dosing option for thromboprophylaxis in conjunction with elective hip surgery, as outlined in the box below.

Please note the following revised wording of the Product Monograph specific to the post-operative initiated use of FRAGMIN for thromboprophylaxis in patients undergoing elective hip surgery.

The pre-operative dose may be omitted and an initial dose of 2500 IU s.c. administered 4-8 hours after the operation, provided primary hemostasis is obtained. Starting on the day after surgery, 5000 IU s.c. is given each morning, in general for 5-7 days or longer. Omission of the pre-operative dose may reduce risk of peri-operative bleeding, however increased risk of venous thromboembolic events is possible. This option is based on the results of the North American Fragmin Trial (NAFT), which excluded patients at high risk of bleeding, i.e., documented cerebral or gastrointestinal bleeding within 3 months prior to surgery, defective hemostasis, e.g., thrombocytopenia (<100 x 109/L), ongoing anticoagulant treatment.

For completeness, the recently updated dosing options for thromboprophylaxis in conjunction with surgery are presented below. Also included is the relevant Precaution related to selection of general surgery patients.

Thromboprophylaxis in Conjunction with Surgery

The dose of FRAGMIN required for adequate prophylaxis without substantially increasing bleeding risk varies depending on patient risk factors.

General surgery with associated risk of thromboembolic complications: 2500 IU s.c. administered 1-2 hours before the operation, and thereafter 2500 IU s.c. each morning until the patient is mobilized, in general 5-7 days or longer.

General surgery associated with other risk factors (see PRECAUTIONS, Selection of General Surgery Patients): 5000 IU s.c. is given the evening before the operation and then 5000 IU s.c. the following evenings. Treatment is continued until the patient is mobilized, in general for 5-7 days or longer.

As an alternative, 2500 IU s.c. is given 1-2 hours before the operation, with 2500 IU s.c. given again no sooner than 4 hours after surgery, but at least 8 hours after the previous dose, provided primary hemostasis is obtained. Starting on the day after surgery, 5000 IU s.c. is given each morning, in general for 5-7 days or longer.

Elective hip surgery: 5000 IU s.c. is given the evening before the operation and then 5000 IU s.c. the following evenings. Treatment is continued until the patient is mobilized, in general for 5-7 days or longer.

As an alternative 2500 IU s.c. is given 1-2 hours before the operation and 2500 IU s.c. 4-8 hours after surgery, provided primary hemostasis is obtained. Starting on the day after surgery, 5000 IU s.c. is given each morning, in general for 5-7 days or longer.

The pre-operative dose may be omitted and an initial dose of 2500 IU s.c. administered 4-8 hours after the operation, provided primary hemostasis is obtained. Starting on the day after surgery, 5000 IU s.c. is given each morning, in general for 5-7 days or longer. Omission of the pre-operative dose may reduce risk of peri-operative bleeding, however increased risk of venous thromboembolic events is possible. This option is based on the results of the North American Fragmin Trial (NAFT), which excluded patients at high risk of bleeding, i.e., documented cerebral or gastrointestinal bleeding within 3 months prior to surgery, defective hemostasis, e.g., thrombocytopenia (<100 x 109/L), ongoing anticoagulant treatment.

PRECAUTIONS

Selection of General Surgery Patients

Risk factors associated with post-operative venous thromboembolism following general surgery include history of venous thromboembolism, varicose veins, obesity, heart failure, malignancy, previous long bone fracture of a lower limb, bed rest for more than 5 days prior to surgery, predicted duration of surgery of more than 30 minutes, age 60 years or above.

Pharmacia Canada Inc. is committed to providing you with the most current product information available for the management of your patients requiring FRAGMIN. Please review the full Product Monograph when prescribing FRAGMIN. An updated FRAGMIN Product Monograph is available at  http://www.pharmacia.ca

The identification, characterization, and management of drug-related adverse events are dependent on the active participation of healthcare professionals in adverse drug reaction reporting programmes. Any occurrences of adverse events in patients receiving FRAGMIN should be reported to:

Pharmacia Canada Inc.
55 Standish Court, Suite 1200
Mississauga, Ontario L5R 4E3
Attention: Director, Medical Information and Drug Safety

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.

If you have any questions or require additional information on FRAGMIN, please call the Pharmacia Canada Inc. Medical Information Department at 1-800-268-7888.

Sincerely,

original signed by

David Cook, M.D.
Vice President, Medical and Scientific Affairs
Pharmacia Canada

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