Desmopressin nasal sprays (including Apo-Desmopressin Spray) are associated with an increased risk of serious side effects involving water retention and decreased blood sodium levels (hyponatremia). - For Health Professionals

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Contact: Marketed Health Products Directorate (MHPD)

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The Health Products and Food Branch (HPFB) posts on the Health Canada web site safety alerts, public health advisories, press releases and other notices as a service to health professionals, consumers, and other interested parties. These advisories may be prepared with Directorates in the HPFB which includes pre-market and post-market areas as well as market authorization holders and other stakeholders. Although the HPFB grants market authorizations or licenses for therapeutic products, we 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 Apotex Inc. Contact the company for a copy of any references, attachments or enclosures.

Health Canada Endorsed Important Safety Information on Apo-Desmopressin Spray

July 31, 2008

Dear Health Care Professional,

Subject:

Association of increased risk of hyponatremia/water intoxication with all intra-nasal spray formulations of the antidiuretic drug desmopressin (including Apo-Desmopressin Spray).

Apotex Inc., in collaboration with Health Canada, wishes to advise you that all intranasal formulations of the antidiuretic drug desmopressin, including Apo-Desmopressin Spray, are now contraindicated for the treatment of Primary Nocturnal Enuresis, as international post-market data has indicated intranasal formulations of desmopressin are associated with greater risk of hyponatremia than oral formulations. Hyponatremia is a serious, potentially fatal, adverse reaction caused by water retention resulting from the potent antidiuretic effect of desmopressin. If unrecognized, hyponatremia can lead to seizures and death.

All intranasal formulations of desmopressin are now contraindicated for the treatment of Primary Nocturnal Enuresis (PNE). All patients using intranasal formulations of desmopressin should be reassessed to determine whether ongoing treatment with desmopressin is necessary. If continued desmopressin therapy is required, patients should be switched to the lowest starting dose of an oral desmopressin formulation, with the dose only increased if necessary to control symptoms. Fluid intake and desmopressin dosage should be adjusted carefully in order to reduce the possibility of water retention and hyponatremia especially in very young and elderly patients or when significant daily variables occur such as hot climate conditions, intense exercise or other situations where increased water intake can be expected. Prodromal symptoms such as headache, nausea or vomiting may herald impending hyponatremia. A patient treated with desmopressin for PNE and/or their guardian should be advised that if such symptoms occur, desmopressin should be discontinued and medical attention sought immediately.

Apotex Inc. will be updating the Indications and Clinical Use, Contraindications, Warnings and Precautions, Adverse Reactions, Drug Interaction and Dosage and Administration sections of the Canadian Product Monograph for Apo-Desmopressin Spray to include the new contraindication for the treatment of Primary Nocturnal Enuresis and other important safety information regarding the risk of hyponatremia.

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 post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious hyponatremia/water intoxication or other serious or unexpected adverse reactions in patients receiving Apo-Desmopressin intranasal spray formulation should be reported to Apotex Inc, or Health Canada at the following addresses:

Apotex Inc. 150 Signet Drive Toronto, ON M9L 1T9 Tel: 800-667-4708 Fax: 416-401-3819 E-mail: drugsafety@apotex.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 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 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 Products Directorate (MHPD) E-mail: mhpd_dpsc@hc-sc.gc.ca Tel: 613-954-6522 Fax: 613-952-7738

Sincerely,

original signed by

Dr. Bruce D. Clark, Ph.D.
Vice-President, Regulatory & Medical Affairs