Bayer’s Aspirin/Phytosterols Combination May Draw FDA Warning

Bayer’s combination of aspirin and cholesterol-lowering supplement has industry stakeholders asking how FDA can avoid issuing a warning.

Bayer could receive a warning letter for its Aspirin with Heart Advantage OTC/supplement combination product if the agency maintains its historic hard line on combining nonprescription drugs with supplements.

Combinations of OTC drug actives and supplement ingredients that are not included in a monograph fall into a regulatory gray area. In the past, FDA has opposed certain combinations, issuing warning letters to manufacturers.

Launched this year, Aspirin with Heart Advantage packaging describes the product as "aspirin plus cholesterol-lowering phytosterols." Cholesterol-lowering health claims for phytosterols are FDA-approved for foods and supplement products.

Food and drug attorney Marc Ullman spotlighted the product in a May 20 entry on his NPI Center blog, wondering whether Bayer's product would receive similar attention from FDA.

He agrees with FDA's contention in previous warning letters to other firms that supplement ingredients added to monographed OTC drug products are considered unapproved active drug ingredients.

"I don't see how this is any different," the partner at New York-based Ullman, Shapiro & Ullman told "The Tan Sheet."

Natural Products Association's VP of scientific and regulatory affairs, Daniel Fabricant, agrees with Ullman, "I would think that FDA would send a letter to Bayer at some point in time," he said.

An FDA spokesperson said the agency is reviewing the product to determine whether it is legally marketed.

In 2001 warning letters, FDA stated that despite the presence of dietary supplement ingredients in B.F. Ascher's Melagesic PM and Omni Nutraceutical's Inholtra products, the presence of a drug ingredient "renders the entire product a drug." Melagesic combined melatonin and acetaminophen, while Inholtra included glucosamine and chondroitin with the analgesic.

As a result, the combination products are unapproved new drugs, "subject to regulatory action without further notice," the agency concluded.

Ullman allows the warning letters to Ascher and Omni cited health issues relating to the long-term use of acetaminophen that would not be of concern with Bayer's aspirin/phytosterol product.

However, "FDA also informed both companies in unequivocal terms that their products were unapproved new drugs," Ullman says.

Ullman also pointed out one potentially problematic aspect of the product - its packaging features both Drug Facts and Supplement Facts boxes and lists aspirin as an "other ingredient" in the Supplement Facts.

FDA has said that any part of a supplement product that is not a dietary ingredient must be generally recognized as safe for use in food, Ullman explained. Aspirin is not generally recognized as safe for use in food.

"Is Bayer going to contend that aspirin is GRAS for food use?" Ullman observed.

"To call this thinking outside the box might be putting it mildly. I don't see how they can do this," he added.

Bayer maintains it is "appropriate" to compare the aspirin/phytosterol product to the firm's Women's Aspirin Plus Calcium . The aspirin/calcium product has been marketed since 2002.

In what is probably the most significant difference between the two products, however, the aspirin/calcium combination is an established pairing under the internal analgesics monograph, which is not true for the aspirin/phytosterol product.

Bayer argues both products are "conceptually identical" because each combines "low-dose aspirin with a dietary supplement ingredient subject to an approved health claim."

"The key fact ... is that both Bayer products contain ingredients designed to be taken on a regimen or long-term basis," the firm told "The Tan Sheet."

-Jessica Lake ([email protected])