Archived – Serious Adverse Reactions in Pediatric Patients Treated with ORTHOCLONE OKT*3 (muromonab-CD3) – Notice to Hospitals

Starting date:

May 13, 2004

Posting date:

May 13, 2004

Type of communication:

Notice to Hospitals

Subcategory:

Biologic/vaccine

Source of recall:

Health Canada

Issue:

Important Safety Information

Audience:

Hospitals

Identification number:

RA-17000765

This is duplicated text of a letter from Janssen-Ortho Inc.

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 ORTHOCLONE OKT*3 (muromonab-CD3)

May 13, 2004

To: Hospital Chief of Medical Staff

Please distribute to the relevant Departments of Surgery, Medicine, Pediatrics, Intensive Care, Anesthesiology, Emergency, Nursing, Pharmacy, Laboratory Services, and other involved professional staff and post this NOTICE in your institution.

Subject: Serious adverse reactions in pediatric patients treated with ORTHOCLONE OKT*3 (muromonab-CD3)

ORTHOCLONE OKT*3 (muromonab-CD3) is a murine monoclonal antibody indicated for the treatment of acute renal, cardiac, and hepatic allograft rejection refractory to conventional anti-rejection therapy or when conventional therapy is contraindicated in adult patients.

Cerebral Edema

Pediatric patients may be at increased risk of developing neurological complications, including cerebral edema and cerebral herniation. Since 1986, nine cases of cerebral edema were reported worldwide in pediatric patients (age up to 17 years), with subsequent cerebral herniation and death in 6 of the 9 cases. The majority of the cases of cerebral herniation in pediatric patients occurred within a few hours to 1 day after the first injection.

In Canada, two (2) pediatric cases describing cerebral edema have been reported following treatment with ORTHOCLONE OKT*3. However, there have been no Canadian cases of fatal cerebral herniation in either children or adults.

All patients, regardless of age, must be carefully evaluated for fluid retention and hypertension before the initiation of ORTHOCLONE OKT*3 therapy and closely monitored for neurological deficits within the first days of therapy. ORTHOCLONE OKT*3 should not be administered to patients with a history of seizures or fluid overload. Treatment should be stopped if symptoms compatible with cerebral edema are observed.

Infections

Pediatric patients may be at increase risk of infectious complications due to immunosuppression induced by ORTHOCLONE OKT*3. For example, meningitis is a frequent infection encountered in pediatric allograft recipients. Viral infections often include pathogens uncommon in adults, such as varicella zoster virus (VZV), adenovirus, and respiratory syncytial virus (RSV). A large proportion of children have not been infected by herpes viruses (e.g., Epstein-Barr [EBV], Cytomegalovirus [CMV], Herpes simplex virus [HSV]) prior to transplantation and, therefore, are more susceptible to developing primary infections from the grafted organ and/or blood products.

Post-Transplant Lymphoproliferative Disorders (PTLD)

Patients with primary EBV infection may be at a higher risk for the development of EBV-associated lymphoproliferative disorders (LPD), a source of significant concern in the pediatric population. There may be an association between the development of LPD at the time of active EBV infection and ORTHOCLONE OKT*3 administration in pediatric allograft recipients.

Patient exposure to ORTHOCLONE OKT*3 has declined, with approximately 25 patients receiving the product in Canada in 2003.

Janssen-Ortho Inc. is currently working with Health Canada to update the Canadian Product Monograph to include the information contained in this letter.

The identification, characterization, and management of marketed health product-related adverse reactions are dependent on the active participation of health care professionals in adverse drug reaction reporting programmes. Any occurrences of serious and/or unexpected adverse reactions in patients receiving ORTHOCLONE OKT*3 should be reported to Janssen-Ortho Inc. or the Marketed Health Products Directorate at the following addresses:

Janssen-Ortho Inc.

19 Green Belt Drive

Toronto, Ontario

M3C 1L9

or call toll free at 1-800-567-3331

or email to dsscan@joica.jnj.com

or fax to 416-449-2658

Any suspected adverse reaction can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Marketed Health Products Directorate

HEALTH CANADA

Address Locator: 0701C

OTTAWA, Ontario, K1A 0K9

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

To report an Adverse Reaction, consumers and health professionals may call toll free:

Tel: 866 234-2345

Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

For other inquiries: please refer to contact information.

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

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.

Health Canada asks that you share these recommendations with your staff or membership and encourage their implementation in the interest of patient safety.

Should you have any questions or require additional information, please contact Janssen-Ortho Inc. Medical Information Department at 1-800-567-3331 from 9:00 am to 5:00 pm Monday to Friday Eastern Standard Time (EST) or by Facsimile at 416-449-2658.

Sincerely,

original signed by

Wendy Arnott, Pharm.D.

Vice President

Regulatory, Safety and Quality

* All trademark rights used under license