Metformin Hydrochloride is indicated as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes mellitus. N‑Nitrosodimethylamine (NDMA) is classified as a probable human carcinogen (a substance with potential to cause cancer) based on results from laboratory tests. With the release of alert of NDMA presence in Metformin extended release (ER) formulations, U.S. Food and Drug Administration recommended the respective manufacturers of the tested lots to initiate voluntary recall.

Below pharmaceutical companies have initiated the recall procedures for this Metformin ER drug.

Amneal Pharmaceuticals– On 05-Jun-2020, Amneal Pharmaceuticals issued voluntary nationwide (from United States) recall of Metformin Hydrochloride Extended Release Tablets, USP, 500 mg and 750 mg, due to Detection of (NDMA) Impurity above the acceptable levels permitted by FDA.

FDA has recommended Amneal pharmaceuticals to recall the seven tested lots (having higher NDMA levels). However, the company decided to recall all the lots of this Metformin ER tablets. (The company’s metformin hydrochloride Immediate Release (IR) Tablets, USP are not affected by this recall.)

Amneal is recalling the product by notifying its direct customers via mail (UPS Standard Overnight) by mailing a recall notification letter. Company advised to quarantine the recalled lots immediately.

Teva Pharmaceuticals USA, Inc. On 05-Jun-2020, Company is voluntarily recalling fourteen (14) lots of Metformin Hydrochloride ER Tablets, USP 500 mg and 750 mg, 100 and 1000 count bottles, in the United States to the consumer-level due to the detection of NDMA impurity levels in excess of the Acceptable Daily Intake Limit (ADI).

The lots being recalled are packaged under the “Actavis Pharma, Inc. label” and are contained in the table below. They were distributed nationwide in the USA as retail bottles of 100 tablets and 1000 tablets to Teva’s direct customers between 08-Jan-2019 and 27-May-2020.

The affected Metformin Hydrochloride ER Tablets, USP 500 mg and 750 mg, being recalled are described as:

1. Metformin Hydrochloride Extended-Release Tablets, USP 500 mg, white to off-white capsule shaped tablets, debossed with an Andrx logo with “571” on one side and “500” on the opposite side.
2. Metformin Hydrochloride Extended-Release Tablets, USP 750 mg, light yellow capsule shaped tablets, debossed with an Andrx logo with “577” on one side and “750” on the opposite side.

Company has notified its distributors and customers affected by this recall. Patients taking Metformin Hydrochloride ER Tablets, USP 500 mg and 750 mg, are advised to continue taking their medication and contact their pharmacist, physician, or medical provider for advice regarding an alternative treatment.

USFDA stated that “it could be dangerous for patients with this serious condition to stop taking their metformin without first talking to their health care professionals.”

Apotex Corp– USFDA notified the company on presence of excess NDMA levels (greater than ADI) in one lot of metformin hydrochloride extended-release tablets, USP and recommended recall for the same. On 29th May, per USFDA announcement on NDMA impurity in metformin ER tablets, Apotex company had initiated a voluntary recall of metformin hydrochloride ER-Release tablets, USP 500mg at retail level. On 05-Jun-2020, company expanded its previously announced retail level recall to all the lots of Metformin Hydrochloride ER Tablets to consumer level.

Apotex requested consumers to not interrupt their therapy and to contact their health care provider for medical advice and should return the impacted product to their pharmacist.

The affected Metformin Hydrochloride Extended-Release Tablets were distributed nationwide in the USA to Warehousing Chains and can be identified by NDC numbers stated on the product label (60505‑0260-1)

Case reports

To date, the above listed company’s drug safety department has not received any adverse reaction reports or product quality complaints pertaining to the metformin hydrochloride ER tablets related to the recall.

Key Information for health care professionals/consumers:

• NDMA levels are not identified in Metformin immediate release (IR) formulations which are most commonly prescribed type of metformin medication compared to ER formulations. Also, NDMA is not identified in the samples of metformin active pharmaceutical ingredient
• If patients with type 2 diabetes stop taking the metformin prescribed by their physician, it could cause potential life-threatening risk to their health or Potential hospitalizations for hyperglycaemia and ketoacidosis. So, Patients should continue taking metformin tablets even after recalls occur, until they consult with their health care professional who can prescribe an alternative medication.
• The FDA recommended health care professionals to continue prescribing metformin to diabetic patients when clinically appropriate.

Voluntary Reporting:

In order to report any adverse reactions or quality complaints or issues or queries related to the product recall, consumers and health care professionals are advised to contact the respective manufacturers drug safety department with the below listed communication possibilities.

To report to Amneal Drug Safety-

• Phone: 1-877-835-5472, (Monday – Friday, 8:00 am – 6:00 pm, EST).
• E-mail: [email protected].

To report to Teva Drug Safety-

• Phone: 888-838-2872, option 3, then, option 4. Live calls are received Monday-Friday, 9:00 am to 5:00 pm Eastern Time with voicemail available 24 hours/day, 7 days/week.
• Email: [email protected].

To report to Apotex Drug Safety-

• Phone: 1-800-706-5575 (8:30am – 5:00pm, EST Monday thru Friday)
• Email: [email protected].

For Reporting to US-FDA:

Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

• Complete and submit the report via MedWatch Online Voluntary Reporting
• Regular Mail or Fax: Download form or call 1- 800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178