Heart Drug Targeted at African Americans Carries Lupus Risk
An active ingredient in a new heart failure drug tailored for African Americans can increase the risk of developing a form of lupus, a debilitating disease that strikes black women in disproportionately high numbers.
BiDil was officially launched Friday by Massachusetts-based NitroMed Inc. as the first drug intended for use by patients in a particular ethnic group. The Food and Drug Administration approved it June 23.
But one of its two key ingredients, a generic compound known as hydralazine hydrochloride, long has been known to cause lupus in some patients, according to FDA documents and interviews with doctors.
One in every 250 African American women has lupus, a painful immune system disorder. Black women are three times more likely to get lupus than white women. African Americans are also more likely than whites to develop congestive heart failure, a weakening of the heart that impairs its ability to pump blood. Heart failure death rates for black women are nearly twice as high as those for white women.
Several cardiologists and lupus specialists say that the benefits of BiDil appear to clearly outweigh its risks, since heart failure is much more serious than lupus. But some of them question why FDA-approved prescribing information for BiDil fails to recommend that patients taking the drug get routine blood tests for lupus.
Such tests are recommended for patients taking the generic form of the ingredient in BiDil, hydralazine, when it is prescribed separately.
“I would have rather the product [literature] say that people should have testing every six months,” said Dr. Jonathan Sackner-Bernstein, director of clinical research in the heart failure center at North Shore University Hospital on Long Island, N.Y. He was a member of the FDA advisory panel that voted unanimously to recommend BiDil’s approval.
An FDA spokeswoman said the agency stood by its decision. She suggested that decisions about testing were best left to individual doctors.
For some patients, a lack of regular testing could prove hazardous, another physician said.
Dr. Daniel J. Wallace, a lupus specialist at Cedars-Sinai Medical Center in Los Angeles, said it could backfire on patients who conscientiously take the BiDil but tend to shrug off joint pains, fever and other flu-like symptoms that could indicate lupus.
“The problem is going to be the patient who takes the drug as directed and doesn’t make the connection,” Wallace said. “They’ll keep taking the medicine and won’t call the doctor.” A blood test for lupus antibodies costs about $30, he said.
Doctors should tell patients in advance of the lupus risk, said Wallace, adding, “It’s probably good medicine to be tested twice a year.”
Indeed, the FDA-approved prescribing information for the generic form of hydralazine says patients should be tested for lupus antibodies before starting on the drug and “periodically” thereafter.
The prescribing information, also known as the drug label, serves as a guide for doctors on how to use a medication and prevent unwanted side effects.
However, prescribing information for BiDil calls for such testing only if a doctor suspects that a patient already has symptoms of lupus.
Sackner-Bernstein said tests recommended for patients taking generic hydralazine “should be carried over” to BiDil.
Dr. Manuel Worcel, chief medical officer for drug maker NitroMed, said BiDil patients would not be taking a high enough dose of hydralazine to pose a significant risk.
“The drug is safe and effective for the treatment of heart failure, and the benefits outweigh the potential side effects,” Worcel said. “At the recommended doses, we have not seen a meaningful incidence of lupus.”
As for routine lupus testing, “that is not what the FDA asked us to do,” Worcel added. “This is not what we proactively would do. [But] if a doctor wants to do that, I can understand that some would feel it necessary to do that.”
The key clinical trial that led to BiDil’s approval was carried out with 1,050 African American patients. About half were given BiDil, while the rest received standard treatment. Patients on BiDil had 43% fewer heart failure deaths and a 39% drop in hospitalizations.
There was one confirmed case of lupus among the BiDil patients, according to the FDA. But those who took BiDil were also four times more likely to develop joint pain, a symptom often linked with lupus.
Patients taking part in the clinical trial were not routinely tested for lupus antibodies, the company said.
The single lupus patient was a 40-year-old woman who developed moderate symptoms, the FDA said. She was treated with an arthritis drug, and her lupus cleared up after about seven weeks. She kept taking BiDil throughout the lupus treatment.
Lupus that is brought on by taking a drug can usually be reversed by stopping the medication, doctors say.
Dr. Clyde Yancy, one of the main investigators in BiDil clinical trial, said physicians had options if their patients developed lupus. For instance, they could reduce the dose of BiDil.
“If a patient has derived great benefit from [BiDil] and the complaints of lupus are modest, the doctor might elect to continue, albeit at a lower dose,” said Yancy, a professor of medicine at the University of Texas Southwestern Medical Center in Dallas.
“I don’t have any sense that there will be no cases of lupus,” Yancy added. “But to think there would be a significant number of cases -- that would be a totally unexpected circumstance.”
