Bowel preps linked to phosphate nephropathy

The Food and Drug Administration has added a boxed warning to the prescription oral sodium phosphate bowel preparation products concerning the risk of acute phosphate nephropathy.

The agency is also recommending consumers not to use over-the-counter oral sodium phosphate (OSP) products for bowel cleansing. Although available data do not show a risk of acute kidney injury when the OTC products are taken at the lower doses for laxative use, when used at higher doses for bowel cleansing they are associated with the same risks as the prescription OSP products. Boxed warnings are not used for OTC products, but the agency plans to issue an amended label for OTC OSP products by May 2009, the director of the FDA’s Office of Nonpescription Products said.

The FDA has also directed Pharmaceuticals, maker of both products, to develop a risk evaluation and mitigation strategy, distribute a medication guide to alert patients to the risk of acute kidney injury, and conduct a postmarketing clinical trial to further assess the risk of acute kidney injury associated with these products, the deputy director of FDA’s Division of Gastroenterology Products said.

In 2006, the FDA issued a Science Paper and Healthcare Professional sheet on the risks associated with the use of OSP products for bowel cleansing. Since then, the agency has received reports of acute phosphate nephropathy with both prescription and OTC products, including 20 unique cases kidney injury associated with the use of the reported cases, three were biopsy-proven acute phosphate nephropathy. The onset of kidney injury in these cases varied, occurring in some cases within several hours of OSP use and in other cases up to 21 days after use.

Health care providers are advised to consider the following when prescribing OSP for bowel preparation:

• Provide easy-to-understand instructions to the patient about preparing for the procedure. Tell them what symptoms to be aware of so they can recognize and possibly mitigate the risk of acute kidney injury.

• Instruct patients to drink sufficient quantities of clear fluids before, during and after bowel cleansing. An electrolyte or carbohydrate-electrolyte replacement solution may help decrease the electrolyte abnormalities and hypovolemia associated with OSP bowel cleansing.

• Avoid exceeding the maximum recommended OSP doses.

• Avoid concomitant use of laxatives containing sodium phosphate.

• Avoid use in patients under age 18, and use with caution to patients over age 55.

• Use OSP with caution in patients with dehydration, kidney disease, delayed bowel emptying, or acute colitis.

• Use OSP with caution in patients taking medicines that affect kidney function or perfusion, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and NSAIDs.

• Obtain baseline and postprocedure labs (electrolytes, calcium, phosphate, BUN, and creatinine) in patients who may be at increased risk, including those with vomiting and/or signs of dehydration. For smaller, frail individuals, also monitor glomerular filtration rate.

• Consider hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or have no assistance at home.

Acute phosphate nephropathy presents as acute kidney injury with minimal proteinuria and a bland urine sediment. Renal biopsy typically reveals renal tubular injury and calcium-phosphate crystal deposition.