Important safety information on Fleet Phospho-Soda (sodium phosphates oral solution) with kidney impairment and nephrocalcinosis - For Health Professionals - MERCK Consumer Pharmaceuticals

Health Canada Endorsed Important Safety Information on Fleet^® Phospho-Soda^® (Sodium Phosphates Oral Solution)

December 2, 2005

Subject: Reports of renal impairment and nephrocalcinosis with Fleet® Phospho-Soda® (Sodium Phosphates Oral Solution)

Dear Health Care Professional:

Johnson and Johnson MERCK Consumer Pharmaceuticals, following discussions with Health Canada, would like to inform you of important new safety information for Fleet^® Phospho-Soda^® (Sodium Phosphates Oral Solution).

Sodium phosphates oral solution is commonly used as a purgative for bowel cleansing prior to patients going to surgery or for preparing the colon for x-ray or endoscopic examination. Appropriate patient screening and adequate hydration are important considerations in using this product as electrolyte shifts and volume depletion may occur. Three papers, involving seven cases 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 the 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 also been identified in an additional thirty spontaneous reports, of which nine cases were received from a non-medical source. Two Canadian cases have been identified, one published case and one spontaneous report. Based upon the information available to date, some of the cases appear to have involved inappropriate patient selection, as well as overdosing and use in patients at higher risk for dehydration (e.g. elderly, debilitated).

• Acute renal failure involving calcification of renal tissue has been observed in some patients following administration of oral sodium phosphate 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.

Appropriate hydration is necessary to help prevent electrolyte disturbances and also to achieve effective bowel cleansing. When using the product for bowel cleansing the 45 mL dose should be consumed after dilution in clear liquid. This can be accomplished by diluting 15 mL of the sodium phosphates oral solution in a glass (240 mL) of clear liquid and then repeating this twice to give a total dose of 45 mL within three glasses (720 mL) of clear liquids. The patient should then drink at least three additional glasses (720 mL) of clear liquids. Patients should be encouraged to drink as much liquid as possible to help prevent dehydration and increase bowel-cleansing effectiveness.

The prescribing information is being updated to highlight that nephrocalcinosis has been very rarely reported in patients using sodium phosphates for bowel cleansing. In addition, the labeling will further emphasize the importance of appropriate patient screening as well as adequate fluid ingestion both with the sodium phosphates and in follow-up to sodium phosphates dosing.

Further research studies are currently underway to more extensively examine this issue. Additional insights gained through these efforts will be incorporated into the prescribing information.

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 dependent on the active participation of health care professionals in adverse drug reaction reporting programmes. Any occurrences of neprocalcinosis, renal failure or other serious and/or unexpected adverse events in patients receiving Fleet^® Phospho-Soda^® (Sodium Phosphates Oral Solution) should be reported to Johnson and Johnson MERCK Consumer Pharmaceuticals or Health Canada at the following addresses:

Johnson and Johnson MERCK Consumer Pharmaceuticals

890 Woodlawn Road West

Guelph, Ontario

N1K 1A5

Telephone: 1-888-730-4636

Fax: (519) 826-6205

e-mail: fleet@mcneilcanada.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: 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 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

email: 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 questions or require additional information concerning the use of Fleet^® Phospho-Soda^®, please contact Johnson and Johnson MERCK Consumer Pharmaceuticals Health Information Centre at 1-888-730-4636 from 8:00 am to 8:00 pm, Eastern Standard Time, Monday to Friday.

Sincerely,

original signed by

James H. Swann, M.D., F.R.C.P.(C)

Vice-President, Medical