Primus Pharmaceuticals Inc., Scottsdale, AZ has voluntarily but reluctantly withdrawn its osteoarthritis capsule Limbrel from the market following a strong recommendation from the Food and Drug Administration (FDA) that the product may cause drug-induced liver injury, and a lung condition called hypersensitivity pneumonitis.

In a letter to James D. Weir, president and chief executive officer of Primus, the FDA requested that the company cease distribution and immediately institute a recall of specific Limbrel lots, including:

• Limbrel (flavocoxid) 250 mg capsules
• Limbrel250 (250 mg flavocoxid with 50 mg citrated zinc bisglycinate) capsules
• Limbrel (flavocoxid) 500 mg capsules
• Limbrel500 (500 mg flavocoxid with 50 mg citrated zinc bisglycinate) capsules

“The FDA has determined that these Limbrel products are unapproved new drugs and represent a serious health hazard,” the agency wrote in the letter to Weir. “Between January 1, 2007, and November 9, 2017, FDA received 194 adverse event reports associated with the use of Limbrel products.”

The FDA further stated in the letter that the adverse event reports “identified a close relationship between the use of Limbrel and adverse events involving the development of drug-induced liver injury (DILI), pancreatitis, and hypersensitivity pneumonitis (HP),” conditions that can present varying degrees of severity, ranging from mild to life-threatening.

“In addition, your Limbrel products are unapproved new drugs distributed in violation of sections 301(d) and 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. § 331(d) and 355(a)],” the FDA said, adding that the claims on the product labeling, such as for the “clinical dietary management of the metabolic processes of osteoarthritis,” establish that the Limbrel products are drugs because they are intended for use in the cure, mitigation, treatment, or prevention of disease.

Primus, on its Limbrel website, said the action to withdraw the products from the market was “in response to repeated aggressive press releases from the FDA” and the letter it received from the agency on December 19.

“Primus Pharmaceuticals, in response to unwarranted pressure from the FDA, has voluntarily suspended promotion and sale of Limbrel, an important and in many cases the only medical option for people suffering from osteoarthritis, pending Primus receiving requested safety data held by the FDA and meeting with the FDA as requested,” the company said in its website statement.

“For nearly 14 years, Limbrel has been marketed as a medical food dispensed by prescription and under physician supervision, with over 2 million packages sold and sampled in that time to an estimated 450,000 patients,” the company said in a formal response to the FDA through its Washington law firm Hyman, Phelps & McNamara, P.C.

The lawyers, in the response dated December 20, claimed that Limbrel does meet the statutory definition of a medical food as set forth in the Orphan Drug Act. “In fact, Limbrel has been referenced as such in many peer-reviewed nutritional, regulatory, clinical, and scientific peer-reviewed articles.”

Primus, in the response, also countered FDA’s adverse-event claim saying that  historically, “both FDA and Primus have received very low numbers of reports of acute hypersensitivity pneumonitis (AHP) and elevated liver function tests (LFTs),” adding that the reactions have been temporary and medically reversible.

Primus reportedly has requested further meetings with the FDA in an effort to convince the agency that Limbrel is safe and that it should be considered a medical food.

If that doesn’t work, the company indicated it might pursue a reclassification of the product as a nutritional supplement, according to a report today in The Arizona Republic.

The newspaper quoted Weir as saying, “We don’t understand why this product has been on the market for so long with such consistent feedback and use, and now is an issue.”

Weir said that the company is hopeful it can work with the FDA to make the product available once again, according to the report.

(Sources: FDA; Primus Pharmaceuticals Inc.; Hyman, Phelps & McNamara, P.C.)