Keep it inside the locker room: FDA drug safety reviews

Congressional investigators and the New York Times have identified at least five reviewers at the Food and Drug Administration (FDA) who have recently been disciplined for uncovering evidence about the dangers of certain popular drugs. They include: Dr. Rosemary Johann-Liang, for her investigation of the diabetes drug Avandia; Dr. Andrew Mosholder over anti-depressants; Dr. David Ross over the antibiotic Ketek; and Dr. Victoria Hampshire over her review of heartworm medicines with fatal effects on more than 500 dogs.

Dr. Hampshire describes a "feeling of fear" among reviewers at the FDA. The FDA Commissioner, Andrew C. von Eschenbach, has urged the safety officials to keep disagreements "inside the locker room," and said those who discussed findings with outsiders would be "traded from the team." Indeed, Dr. Hampshire’s work in uncovering the dangers of heartworm medicine led to her being disciplined and being made the subject of a criminal investigation.

Secrecy by the FDA blocks patients from empowering themselves. And if the FDA does not adequately guard us from dangerous drugs, we have to be more vigilant.

Advice: If you’re prescribed Ketek or Avandia, ask your doctor about adverse reactions. Ask your vet about adverse drug reactions from your dog’s heartworm medicine.

Read another of our Avandia stories, or read Gardiner Harris’ source story in today’s New York Times, "Potentially Incompatible Goals at FDA."

Three days later, he was fine: Adverse Drug Reaction - Avandia

[Translation appears below]
A 70-year-old man with hypertension and chronic renal insufficiency presented with dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Metformin had been replaced with rosiglitazone, 4 mg/d, 1 month previously. The patient had no history of congestive heart failure. Physical examination revealed tachypnea and bilateral lower extremity edema. Chest radiography showed cardiomegaly with bilateral basilar infiltrates. Transthoracic echocardiography revealed left ventricular hypertrophy and diastolic dysfunction but normal LVEF. The serum digoxin level was slightly increased at 2.3 ng/mL. Serum creatinine values did not change. Rosiglitazone was discontinued, and intravenous furosemide was administered. Metoprolol, digoxin, minoxidil, and verapamil were replaced with losartan and felodipine. After 3 days, the patient was asymptomatic.

Translation: A 70-year-old man with high blood pressure and bad kidneys came to the hospital because he had a distinctive kind of rapid and labored breathing. Examination and test results showed he had an enlarged heart, and feet swollen with fluid. He had started taking Avandia a month earlier. Though he had no congestive heart failure before the Avandia, it looked like he was getting it, or another serious heart problem. In the hospital, doctors took him off Avandia. Three days later, he was fine.

He was one of millions of patients taking the highly profitable drug.

Two days ago, researchers published an article in the prestigious New England Journal of Medicine that reviewed 40 earlier studies on the subject, and discovered that users of Avandia (thiazolidinedione) got 40% more heart attacks than other diabetic patients who were not taking it.

In one of these studies, quoted above, Dr. Asra Kermani and his co-authors “conclude that thiazolidinediones can cause pulmonary edema or exacerbate heart failure. Thiazolidinediones should be used with caution or avoided in patients with left ventricular dysfunction or chronic renal insufficiency.”

Advice to people with diabetes: Discuss with your doctor what to do. There may well be alternative drugs, not to mention other alternatives like exercise, diet, etc.

Read another of our adverse drug reaction stories, or read Stephanie Saul’s story in Tuesday’s New York Times.