Important safety information on pms-Sodium Phosphates Oral Solution with kidney impairment and nephrocalcinosis - For Health Professionals - Pharmascience Inc.

Health Canada Endorsed Important Safety Information on Phosphates solution (oral sodium phosphates)

December 2, 2005

Subject: Safety Information on Phosphates solution (oral sodium phosphates) and kidney impairment.

Dear Health Care Professional:

Pharmascience Inc., following discussion with Health Canada, would like to inform you of important new safety information regarding pms-Sodium Phosphates Oral Solution (Fleet™).

PHOSPHATES SOLUTION has an action as a laxative or purgative, and is commonly used for relief of occasional constipation or for preparing the colon for x-ray or other endoscopic examination, or surgery. Caution must be exercised as electrolyte shifts may occur in patients with or without risk factors for electrolyte shifts if a dose of 45mL (contains 5,760 mg of phosphorus) in a 24-hour period is exceeded. Three papers, involving seven case reports, have been published reporting nephrocalcinosis associated with renal failure following administration of Fleet™ Phospho-Soda®, or other oral sodium phosphate preparations, when used as a bowel cleanser^{Footnote 1 Footnote 2 Footnote 3}. In some cases acute renal failure was followed by chronic renal impairment. Six of seven patients were hypertensive with five on an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and two also on diuretics. One patient had a relative contraindication (Hyperparathyroidism) to use of the product and another patient was given an overdose.

• Acute renal failure involving calcification of renal tissue has been observed in some patients following administration of oral sodium preparations.
• Do not use in patients with clinically significant impairment of renal function. Use with caution in patients with pre-existing electrolyte disturbances, patients taking drugs that may affect electrolyte levels, the elderly or in debilitated patients.
• Adequate hydration is very important to safely and effectively use sodium phosphates as a bowel cleanser.
• Medications such as diuretics may exacerbate volume depletion associated with bowel cleansing.

Pharmascience Inc. has until this date not received any spontaneous reports of renal failure associated with the use of Sodium Phosphates Oral Solution.

The prescribing Information has recently been modified to include that care should be taken to prescribe PHOSPHATES SOLUTION as a bowel cleanser by volumes, not “by the bottle,” per recommendations with a particular attention to known contraindications and adequate hydration. Patients should be encouraged to drink large amounts of clear liquids to prevent dehydration. Drinking large amounts of clear liquids also helps ensure that the patient’s bowel will be clean for the procedure.

A caution statement has been added to the prescribing information to state that nephrocalcinosis associated with transient renal insufficiency and renal failure has been very rarely reported in patients using sodium phosphates for bowel cleansing. Reporting rates determined on the basis of spontaneously reported post-market adverse events are generally presumed to underestimate the risks associated with drug treatments.

The identification, characterization, and management of marketed health product-related adverse events are directly dependent on the participation of health care professionals in adverse drug reaction reporting. Any occurrence of neprocalcinosis, renal failure or other serious and/or unexpected adverse events in patients receiving Phosphates solution (oral sodium phosphate) should be reported to Pharmascience Inc. or Health Canada at the following addresses:

Pharmascience Inc.

6111 Royalmount

Montreal, Quebec

H4P 2T4

Tel: 1-888-550-6060

Fax: 514-342-7764

email: azurek@pharmascience.com

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: 1-866-234-2345

Fax: 1-866-678-6789

cadrmp@hc-sc.gc.ca

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.

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

Your professional commitment in this regard has an important role in the well-being of your patients by contributing to early signal detection and informed drug use. Should you have any further questions or require additional information, please contact the Pharmascience Inc. Medical and Scientific Information Department at 1-888-550-6060 from 8:30 a.m. to 5 p.m. Eastern Standard Time, Monday to Friday. A copy of the letter will be posted on the www.pharmascience.com and Health Canada Web sites.

Best Regards,

original signed by

Gaetano Gallo

Associate Director, Scientific Affairs

Pharmascience Inc.