Important Information About the Risk of Dosing Error for Tamiflu (oseltamivir phosphate) Powder for Oral Suspension (12 mg/mL) - For Health Professionals

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Contact: Marketed Health Products Directorate (MHPD)

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This is duplicated text of a letter from Hoffmann-La Roche Limited.
Contact the company for a copy of any references, attachments or enclosures.

Health Canada Endorsed Important Safety Information on TAMIFLU (oseltamivir phosphate) Suspension

October 13, 2009

Subject: Important information about risk of dosing error for TAMIFLU^® (oseltamivir phosphate) Powder for Oral Suspension (12 mg/mL).

Dear Health Care Professional,

Hoffmann-La Roche Limited, in consultation with Health Canada, would like to inform you of important dosing and administration information regarding the use of TAMIFLU^® (oseltamivir phosphate) Powder for Oral Suspension.

TAMIFLU is a viral neuraminidase inhibitor authorized for sale in Canada for use in the treatment and prevention of uncomplicated acute illness due to influenza infection in adults and children above the age of 1 who have been symptomatic for no more than 2 days or have come in close contact with an infected individual (the index case). Health Canada has also issued an Interim Order (1) in July 2009 expanding use of TAMIFLU as a treatment or prophylaxis for children less than 1 year of age for infection caused by the pandemic H1N1 2009 virus.

There have been reported cases, in the US, where the units of measure in the instructions on the pharmacy prescription label were provided in milliliters (mL) or teaspoons, while the dosing device provided with the prescription was graduated in milligrams (mg). This has led to patient or caregiver confusion and dosing errors.

There have been no reports in Canada suggesting dosing errors associated with the use of TAMIFLU Powder for Oral Suspension.

When dispensing commercially manufactured TAMIFLU Powder for Oral Suspension (12 mg/mL), pharmacists should ensure the units of measure on the prescription instructions match the dosing device.

• If prescription instructions specify administration using milligrams (mg), as per the approved dosing recommendations, then the oral dosing dispenser included in the TAMIFLU product package should be provided to patients and the pharmacy prescription label should provide dosing instructions in milligrams (mg).
• If prescription instructions specify administration using milliliters (mL) or teaspoons (tsp), then the oral dosing dispenser included in the TAMIFLU product package should be removed and replaced with an appropriate measuring device, such as an oral syringe.

Currently, the supply of TAMIFLU Powder for Oral Suspension is very limited and will continue to be so throughout this year. We would like to remind you that should the oral suspension not be readily available, the package insert provides guidance for emergency compounding of capsules to produce liquid suspensions (15 mg/mL) for administration to children or adults with difficulty swallowing capsules. Note: This compounding procedure results in a 15 mg/mL suspension, which is different from the commercially available TAMIFLU for Oral Suspension, which has a concentration of 12 mg/mL.

Dose recommendations according to the TAMIFLU Canadian product monograph (2) for patients greater than 1 year of age and the Health Canada Interim Order (1,3) dosing instructions for patients less than 1 year of age are summarized in the tables below. Please note that the last column in the tables refers to the commercially available oral suspension, and not the one obtained after compounding. A compounded suspension will have a different concentration and a different final volume.

Table 1: Treatment of influenza - Each dose is given twice daily for 5 days

In patients 1 year of age or older
Body Weight in kg	Body Weight in bs	Recommended Dose for 5 days	Quantity of TAMIFLU for Oral Suspension to Withdraw for Each Dose
≤15 kg	≤33 lbs	30 mg twice daily	2.5 mL
> 15 kg to 23 kg	> 33 lbs to 51 bs	45 mg twice daily	3.8 mL
> 23 kg to 40 kg	> 51 lbs to 88 bs	60 mg twice daily	5.0 mL
> 40 kg	> 88 lbs	75 mg twice daily	6.2 mL
In patients less than 1 year of age
Based on weight (recommended): 2 mg / kg BID x 5 days
If weight is not available: 0 - < 3      months 12 mg twice daily for 5 days 3 - < 6      months 20 mg twice daily for 5 days 6 - < 12      months 25 mg twice daily for 5 days

Table 2: Prophylaxis of influenza - Each dose is given once a day for 10 days

In patients 1 year of age or older
Body Weight in kg	Body Weight in bs	Recommended Dose for at least 10 days	Quantity of TAMIFLU for Oral Suspension to Withdraw for Each Dose
≤15 kg	≤33 lbs	30 mg once daily	2.5 mL
> 15 kg to 23 kg	> 33 lbs to 51 bs	45 mg once daily	3.8 mL
> 23 kg to 40 kg	> 51 lbs to 88 bs	60 mg once daily	5.0 mL
> 40 kg	> 88 l bs	75 mg once daily	6.2 mL
In patients less than 1 year of age
Based on weight (recommended): 2 mg / kg once a day x 10 days
If weight is not available: 0 - < 3      months Not recommended for use at this time 3 - < 6      months 20 mg once a day x 10 days 6 - < 12      months 25 mg once a day x 10 days

We encourage you to become familiar with these dosing instructions. For additional information regarding compounding from capsules as well as emergency compounding, please refer to the product monograph (2). Should you have any questions or require additional information regarding the use of TAMIFLU, please contact the Drug Information Department at Hoffman-La Roche Limited at 1-888-762-4388 from 8:30 a.m. to 4:30 p.m. Monday to Friday Eastern Standard Time.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported postmarketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious or unexpected adverse reactions in patients receiving TAMIFLU^® Tablets and Oral Solution should be reported to Hoffmann-La Roche Limited or Health Canada at the following addresses:

Hoffmann-La Roche Limited
Drug Safety Department
2455 Meadowpine Boulevard
Mississauga, Ontario, L5N 6L7
or call toll free at: 1-888-762-4388
or Fax at: 905-542-5864
or Email: mississauga.drug_safety@roche.com

Any suspected adverse reaction can also be reported to:
Canada Vigilance Program
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
Ottawa, Ontario, K1A 0K9
Telephone: 613-957-0337 or Fax: 613-957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Telephone: 866-234-2345
Fax: 866-678-6789
CanadaVigilance@hc-sc.gc.ca

The Adverse Reaction Reporting Form and the Adverse Reaction Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

For other inquiries related to this communication, please contact Health Canada at:
Marketed Health Product Directorate (MHPD)
E-mail: mhpd_dpsc@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

Sincerely,

original signed by

Lorenzo Biondi,
Vice President, Medical and Regulatory Affairs
Hoffmann-La Roche Limited

References:

1. Interim Order Respecting the Sale of Oseltamivir Phosphate - Expanded use for Children under One Year of Age. Parliament of Canada. July 20, 2009. Accessed: 2009-09-29.
2. Tamiflu, Approved Product Monograph. Hoffmann-La Roche Limited, Mississauga, Ontario. Revised July 10, 2009.
3.  Interim Guidance for emergency use of oseltamivir (Tamiflu^®) In children under one year of age in the context of 2009 (H1N1) pandemic. Public Health Agency of Canada. Modified: 2009-07-20. Accessed: 2009-09-29.