The Food and Drug Administration has added a boxed warning to the prescription oral sodium phosphate bowel preparation products Visicol and OsmoPrep concerning the risk of acute phosphate nephropathy.
The agency is also recommending consumers not use over-the-counter oral sodium phosphate product (OSPs) 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 of 2009, Dr. Charles Ganley, director of the FDA's Office of Nonprescription Products, said in a telephone press briefing.
The FDA has also directed Salix 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 associated with the use of OSP products and conduct a postmarketing clinical trial to further assess the risk of acute kidney injury associated with these products, Dr. Joyce Korvick, deputy director of the FDA's Division of Gastroenterology Products said at the briefing.
In 2006, the FDA issued a Science Paper and a 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 products available in the OTC setting, including 20 unique cases of kidney injury associated with the use of OsmoPrep. 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 OSPs 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.
▸ Use with caution in patients over age 55.
▸ Use OSPs with caution in patients with dehydration, kidney disease, delayed bowel emptying, or acute colitis.
▸ Use OSPs with caution in patients taking medicines that affect kidney function or perfusion, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and possibly nonsteroidal anti-inflammatory drugs.
▸ Obtain baseline and postprocedure labs (electrolytes, calcium, phosphate, BUN, and creatinine) in patients who may be at increased risk for acute phosphate nephropathy, 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 in patients recently exposed to OSP. Renal biopsy typically reveals acute and/or chronic renal tubular injury (depending on time to diagnosis), calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histologic injury.
Serious adverse events or product quality problems associated with these products can be reported www.fda.gov/MedWatch/