FDA Safety Changes: Visicol, OsmoPrep, DiaBeta, Raptiva

Yael Waknine

May 07, 2009

This activity is part of an ongoing CME/CE initiative to provide information on labeling changes reported by the FDA. Activities of this nature will be posted on Medscape on a weekly basis.

May 27, 2009 — Editor's Note: Revisions were made to indicate that the recommended dosing schedule for sodium phosphate should be a PM/AM split dose to reduce potential for acute kidney injury.

May 7, 2009 (UPDATED May 27, 2009) — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise clinicians of the risk for acute kidney injury in patients receiving oral sodium phosphate products, drug interactions with glyburide, and the potential for progressive multifocal leukoencephalopathy in patients receiving efalizumab monotherapy.

Oral Sodium Phosphate Products Linked to Risk for Acute Nephropathy

The FDA approved class labeling changes for sodium phosphate monobasic monohydrate and sodium phosphate dibasic anhydrous tablets to include a boxed warning regarding the risk for acute kidney injury associated with use of this and other oral sodium phosphate products for bowel cleansing. On March 25, the boxed warning was added to the labels for Visicol and OsmoPrep (Salix Pharmaceuticals, Inc).

There have been rare, but serious, reports of acute phosphate nephropathy in patients who received oral sodium phosphate products, the FDA warned. Some cases have resulted in permanent impairment of renal function severe enough to require long-term dialysis.

Potential risk factors for injury include increased age; hypovolemia; increased bowel transit time (eg, bowel obstruction); active colitis; baseline kidney disease; and use of medications that affect renal perfusion or function such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and possibly nonsteriodal anti-inflammatory drugs.

To reduce the potential for acute kidney injury, doses of sodium phosphate should be taken according to the recommended schedule (PM/AM split dose) with adequate fluid intake before, during, and after use.

Patients should not repeat a course of sodium phosphate within 7 days of original dosing. No additional enema or laxative is required, and patients should be advised not to take additional agents, particularly those containing sodium phosphate.

The FDA notes that use of electrolyte rehydration solutions may decrease the risk for electrolyte abnormalities and hypovolemia associated with bowel cleansing.

Patients at increased risk for acute phosphate nephropathy and those with vomiting and/or signs of dehydration should be monitored using baseline and postprocedure laboratory tests, including those that measure electrolyte, calcium, phosphate, serum urea nitrogen, and creatinine levels.

For frail patients who may be unable to consume appropriate quantities of fluids or lack assistance at home, hospitalization and supportive intravenous hydration should be considered.

Sodium phosphate monobasic monohydrate plus sodium phosphate dibasic anhydrous tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years and older.

Glyburide (DiaBeta) Linked to Drug Interactions With Protein-Bound Drugs

On March 5, the FDA approved safety labeling revisions for glyburide (DiaBeta tablets; sanofi-aventis US) to advise of drug interactions.

The hypoglycemic action of sulfonylureas may be potentiated by certain medications such as nonsteroidal anti-inflammatory drugs and agents that are highly protein bound, the FDA warned, noting that the latter category includes salicylates, sulfonamides, chloramphenicol, probenecid, monoamine oxidase inhibitors, beta-adrenergic blocking agents, and also clarithromycin. Patients receiving any of these products in conjunction with glyburide therapy should be observed closely for hypoglycemia and also for loss of glycemic control when such drugs are withdrawn.

The FDA also warned of glyburide drug interactions with cyclosporine and bosentan.

Concomitant use of glyburide can increase cyclosporine plasma concentrations and the risk for toxicity. Patients receiving combination therapy may require cyclosporine dose adjustments.

In a clinical trial of glyburide in patients with chronic heart failure, an increased incidence of elevated levels of liver transaminases was observed during concomitant treatment with bosentan, a dual endothelin receptor antagonist (28.6% vs placebo, 17.6%). The mechanism of action is unknown but in part may be the result of additive inhibition of the hepatocellular bile salt export pump, resulting in increased hepatocyte concentrations of toxic bile salts. Concomitant use of glyburide and bosentan is therefore contraindicated.

Glyburide is a second-generation sulfonylurea drug indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Efalizumab (Raptiva) to Be Discontinued Because of PML Risk

On March 13, the FDA approved safety labeling revisions for efalizumab subcutaneous injection (Raptiva; Genentech, Inc) to provide strengthened warnings regarding the risk for progressive multifocal leukoencephalopathy (PML) that has resulted in the product's withdrawal from the market as of June 8, 2009.

PML is a rapidly progressive virus infection of the central nervous system that has no known treatment and leads to death or severe disability. It is caused by activation resulting from unknown factors of a polyomavirus known as the John Cunningham virus (JC virus), which is latent in 80% of healthy adults.

The risk for PML may markedly increase with the duration of efalizumab exposure, the FDA warned, noting that the time-dependent threshold for the increase remains unknown. Patients receiving efalizumab therapy should be monitored frequently for continued clinical benefit and advised to report potential PML signs and symptoms to their clinician.

Efalizumab should be withheld immediately at the first sign or symptom suggestive of PML and discontinued on positive diagnosis, which may be made on magnetic resonance imaging and cerebrospinal fluid analysis for JC viral DNA.

Healthcare professionals are advised to maintain an index of suspicion for PML in efalizumab-treated patients who present with new neurologic symptoms and to consider consultation with a neurologist as clinically indicated.

Efalizumab is a recombinant humanized monoclonal antibody indicated for the treatment of adults with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

OsmoPrep Prescribing Information

Visicol Prescribing Information

DiaBeta Prescribing Information

Raptiva Prescribing Information

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