FDA NewsPerspective

FDA: Limbrel linked to 'potentially life-threatening' problems

The FDA is investigating the drug Limbrel, a capsule-based product currently marketed as a medical food to manage the metabolic processes associated with osteoarthritis, for what the administration calls “serious adverse events.”

Limbrel (flavocoxid, Primus Pharmaceuticals) has been linked to a total of 194 of adverse events, including two “serious and potentially life-threatening” medical conditions — drug-induced liver injury and hypersensitivity pneumonitis — according to an FDA statement. Of the nearly 200 adverse events, 57 cases included sufficient information to determine whether there was a link to Limbrel, the administration said.

In 30 cases, there was enough information to use the Council for International Organizations of Medical Sciences’ causality assessment method to determine the likelihood of an association between Limbrel consumption and the reported adverse events.

In response to the investigation, the FDA has issued the following recommendations:

  • Health care professionals who are aware of patients taking Limbrel should advise them to immediately stop taking the product.
  • Consumers taking Limbrel should immediately stop and contract their health care provider.

If patients experience any of the aforementioned symptoms or other health problems while taking Limbrel, health care providers should work with them to provide clinical information through MedWatch, the FDA said.

Limbrel is currently available in 250 mg and 500 mg dosages. According to the FDA, the product labeling states that it contains two types of flavonoids — baicalin (from Scutellaria baicalensis) and catechin (from Acacia catechu). Both dosages also contain zinc.

According to the statement, the FDA contacted Primus Pharmaceuticals, based in Scottsdale, Arizona, regarding the adverse events, and requested information about the product’s formula, which is now under review by the administration.

“In the interim, the agency is alerting consumers and health care providers about the potential impact to health and advising consumers not to use Limbrel,” the FDA stated. “The FDA is continuing to investigate Primus Pharmaceuticals and the manufacturing process for Limbrel, and will share updates as they become available.”

 

The FDA is investigating the drug Limbrel, a capsule-based product currently marketed as a medical food to manage the metabolic processes associated with osteoarthritis, for what the administration calls “serious adverse events.”

Limbrel (flavocoxid, Primus Pharmaceuticals) has been linked to a total of 194 of adverse events, including two “serious and potentially life-threatening” medical conditions — drug-induced liver injury and hypersensitivity pneumonitis — according to an FDA statement. Of the nearly 200 adverse events, 57 cases included sufficient information to determine whether there was a link to Limbrel, the administration said.

In 30 cases, there was enough information to use the Council for International Organizations of Medical Sciences’ causality assessment method to determine the likelihood of an association between Limbrel consumption and the reported adverse events.

In response to the investigation, the FDA has issued the following recommendations:

  • Health care professionals who are aware of patients taking Limbrel should advise them to immediately stop taking the product.
  • Consumers taking Limbrel should immediately stop and contract their health care provider.

If patients experience any of the aforementioned symptoms or other health problems while taking Limbrel, health care providers should work with them to provide clinical information through MedWatch, the FDA said.

Limbrel is currently available in 250 mg and 500 mg dosages. According to the FDA, the product labeling states that it contains two types of flavonoids — baicalin (from Scutellaria baicalensis) and catechin (from Acacia catechu). Both dosages also contain zinc.

According to the statement, the FDA contacted Primus Pharmaceuticals, based in Scottsdale, Arizona, regarding the adverse events, and requested information about the product’s formula, which is now under review by the administration.

“In the interim, the agency is alerting consumers and health care providers about the potential impact to health and advising consumers not to use Limbrel,” the FDA stated. “The FDA is continuing to investigate Primus Pharmaceuticals and the manufacturing process for Limbrel, and will share updates as they become available.”

 

    Perspective
    John R. P. Tesser

    John R. P. Tesser

    Limbrel is a medical food approved and regulated by the FDA via evidence from clinical trial data. For those of us who have had experience with Limbrel and have understood and assumed it to be a safe alternative to NSAIDs in affording some symptomatic help for OA of the knees, this is a very sad notice indeed.

    Medical foods — usually plant-derived constituents that have some bioactive activity — are given the overarching designation of GRAS or Generally Recognized As Safe. Limbrel contains the flavonoids, baicalin and catechin, which have been shown to have inhibitory effects on pro-inflammatory COX-1, COX-2 and lipoxygenase 5.

    Limbrel was approved on the back of a double-blind placebo-controlled study of 220 patients over 12 weeks, as well as an open-label study of 1067 patients over 60 days; the number of combined patients studied under controlled circumstances was relatively small with no long-term follow-up of these patients.

    Reports of liver failure began to surface with a report of 4 cases in 2012 and 7 cases of hypersensitivity pneumonitis among 270,000 patients exposed as of 2010 — approximately 0.0023% or two to three cases per 100,000.

    As the MedWatch report indicates, we are all advised to cease and desist from the use of Limbrel; however, this brings up two concerns. First, are these statistical risks great enough to advise complete discontinuation of a product? Second, how safe is any product with limited controlled trial data (both double blind and extension phases) by numbers of patients and duration of exposure?

    • John R. P. Tesser, MD
    • Arizona Arthritis & Rheumatology Associates

    Disclosures: Tesser reports no relevant financial disclosures.