FDA warns on anemia-drug dosing

The Food and Drug Administration yesterday warned doctors not to excessively boost patients' red blood cell counts with anti anemia drugs, following publication of a clinical trial this week that found exceeding the FDA's dosing recommendations increased the chance of fatal heart attacks and strokes.

Dosing in excess of those recommendations is common practice in the dialysis industry, which derives much of its revenue from administration of one of the drugs, Epogen, made by Amgen Inc. An article published yesterday in the on line edition of the British medical journal The Lancet said half of all kidney dialysis patients have their red blood cell counts boosted beyond what the FDA says is safe.

Patients with kidney failure also suffer from anemia -- low red blood cell counts -- and without treatment would require blood transfusions. The Globe reported in September that half of all kidney dialysis patients had their red blood cell counts pushed higher than what the FDA recommends, and about 20 percent of all dialysis patients -- about 65,000 -- had counts in the potential danger zone revealed in the clinical trial, called CHOIR.

The FDA label for the drugs -- Epogen and Aranesp, manufactured by Amgen, and Johnson & Johnson's Procrit -- recommends red blood cell counts no higher than 12 grams per deciliter of blood. The drugs, which stimulate bone marrow to produce red blood cells, are also prescribed for cancer patients undergoing chemotherapy.

The FDA's alert, which said the 12-gram limit should be strictly followed, casts new doubt on updated Medicare reimbursement policies approved this year that allow dialysis clinics to boost red blood cell counts to 13 grams per deciliter.

Under a 1972 law, Medicare pays for most dialysis treatment in the United States, about $2 billion annually. Critics in Congress and the scientific community have faulted Medicare reimbursement policies that guarantee dialysis clinics a 6 percent profit margin on Epogen. They say that creates a financial incentive for clinics to give patients more of the drug. Medicare did not immediately respond to a request for comment yesterday. After the CHOIR study was published Thursday in the New England Journal of Medicine, Medicare said it would review the results to determine if its reimbursement guidelines needed to be modified.

The FDA alert also raises questions about new clinical prescribing guidelines issued by the National Kidney Foundation and underwritten by pharmaceutical companies, including Amgen, that suggest it is desirable to boost red blood cell counts to 13 grams per deciliter. The foundation did not immediately respond to a request for comment yesterday, but an official said Thursday that it also would review the CHOIR study findings.

The CHOIR trial was halted in 2005 by a safety review panel which found that patients receiving the larger doses of Johnson & Johnson's Procrit to boost red blood cell counts to a target of 13.5 grams per deciliter were dying at an unexpectedly high rate.

"The CHOIR study findings underscore the importance of following the currently approved prescribing information for Procrit, Epogen, and Aranesp," the FDA said in a posting on its website.

Amgen said it supports the FDA's actions.

"We believe that the advisory was a prudent measure coming out of publications of the studies," said Dr. Robert Brenner , the California company's medical director.

Amgen has never advocated exceeding FDA dosing recommendations, the company said.

Yesterday's Lancet article questioned dialysis industry practices and National Kidney Foundation guidelines.

"There is a disconnect between the prescribing information for these drugs and their use in maintaining high hemoglobin values," said the article's author, Dr. Robert Steinbrook, of Dartmouth Medical School. "It raises patient safety and public health concerns."

Christopher Rowland can be reached at crowland@globe.com.