New Safety Labeling Change: Chlorpropamide (DIABINESE) for Type-2 Diabetes

A new warning was added in May 2002 to the professional product labeling, or “package insert,” for the type-2 diabetes drug chlorpropamide (DIABINESE) concerning its use in the elderly. The new warning cites increased risks of low blood sugar (hypoglycemia), low blood sodium levels (hyponatremia), or both in patients aged 65 and over. The text of the warning reads:

Geriatric Use
The safety and effectiveness of Diabinese in patients aged 65 and over has not been properly evaluated in clinical studies. Adverse event reporting suggests that elderly patients may be more prone to developing hypoglycemia and/or hyponatremia when using Diabinese. Although the underlying mechanisms are unknown, abnormal renal [kidney] function, drug interaction, and poor nutrition appear to contribute to these events.

Chlorpropamide is a member of the sulfonylurea family of antidiabetic drugs that includes glyburide (DIABETA) and tolbutamide (ORINASE). The drug is produced by Pfizer Inc. of New York and has been on the U.S. market since 1959.

In 1978, we raised concerns about the safety of chlorpropamide and other diabetes drugs in the book titled Off Diabetes Pills published by the Health Research Group. We have listed chlorpropamide as a Do Not Use drug ever since publication of the 1988 edition of Worst Pills, Best Pills because it was more likely than other diabetic drugs to cause low blood sugar in the elderly. This recommendation was based on a 1985 World Health Organization publication.

Problems with chlorpropamide go back to the time of its original approval in this country. The Medical Letter on Drugs and Therapeutics, a publication we frequently cite because it is a consistent source of objective drug information, reviewed chlorpropamide in March 1959. Its conclusion:

Whatever the incidence, the toxicity of Diabinese is clearly much greater than that of Orinase and it seems highly inadvisable to substitute Diabinese for Orinase. The convenience of taking Diabinese only once daily is hardly worth the added risk.

In Senate hearings 40 years ago that, in part, examined the promotional practices of the pharmaceutical industry, Pfizer (in the case of chlorpropamide) was but one example of how companies downplay or omit adverse drug reaction information in advertisements to physicians. In its advertising, Pfizer told physicians that chlorpropamide was “the oral antidiabetic most likely to succeed,” that the drug had an “almost complete absence of unfavorable side effects,” and that it would “eventually prove to be the drug of choice in the sulfonylurea group.”

Pfizer’s president and chairman of the board was scheduled to testify before the committee armed with a document endorsed by 36 doctors saying that chlorpropamide had been investigated with great care. But one committee staffer received a tip that made him very dubious about Pfizer’s claims. The tip involved two in-house documents prepared by Pfizer’s associate director of clinical research. Despite repeated requests Pfizer did not make these documents available to the committee. However, in a classic example of the “Washington leak,” early on the morning of the Pfizer president’s appearance before the committee the documents appeared under this staffer’s office door. These leaked documents revealed that the incidence of adverse effects seen with chlorpropamide was 27 percent. The following are selected excerpts from the documents about adverse effects seen with the drug clinical trials:

Among the most striking evidences of toxicity associated with Diabinese are three instances of exfoliative dermatitis [extensive scaling, itching, and redness of the skin, along with loss of the hair]....There have been reported several additional cases of severe skin eruptions with edema [abnormally large amounts of fluid in the skin] and erythema multiforme [an acute skin affliction with burning papules and tubercles] in addition to the other skin lesions...

The gastrointestinal side effects of nausea, vomiting, and epigastric distress, although less frequent at the lower dosage levels...are still more frequent than generally noted with Orinase....There have been several instance of severe hypoglycemia...

In the February 2002 issue of Worst Pills, Best Pills News, we discussed research published in the Journal of the American Medical Association concerning the extent of dangerous prescribing to the elderly. This research found that in 1996, 21.3 percent of older adults living in the community received at least one drug that is potentially inappropriate. About 2.6 percent of elderly patients were receiving one of the 11 drugs that the authors of this study classified as a drug that should never be used in older adults. One of these was chlorpropamide.

One of the “great” successes of the pharmaceutical industry has been its ability over the years to persuade doctors to write prescriptions for unremarkable or even dangerous drugs. Chlorpropamide is a prime example. Of course, this facet of the industry’s success has been achieved at the cost of the public’s health and to the economic detriment of the health care system.

What You Can Do

Discuss with your doctor other treatments for type-2 diabetes if you or a family member is using chlorpropamide. There is no medical reason why this drug should be used instead of safer members of the sulfonylurea family of antidiabetes drugs.