FDA Announces Irbesartan Recall, After Cancer-Causing Chemical Turns Up in More Generic ARBs

Published on January 22, 2019 by Sandy Liebhard

The U.S. Food & Drug Administration (FDA) has announced another irbesartan recall, after unacceptable amounts of N-Nitrosodiethylamine (NDEA) were detected in the active ingredient used to make the medication.

Irbesartan Recall Third Involving Contaminated ARBs this Month

According to the agency, the recall involves one lot of irbesartan and seven lots of irbesartan HCTZ combination tablets distributed by Solco Healthcare LLC, a subsidiary of Prinston Pharmaceutical Inc.

Patients taking medications included in the irbesartan recall should contact their pharmacist for a replacement. However, they should not stop using their medication until they have obtained a replacement, as doing so could lead to serious adverse events.

This is the third time in a month that the FDA has recalled a generic angiotensin II receptor blockers (ARB) contaminated with a potentially cancer-causing chemical.

Earlier this month, Torrent Pharmaceuticals expanded its recall of generic losartan tablets to include two additional lots. The company’s initial losartan recall was announced last month and included 8 lots.

On December 31^st, Aurobindo Pharma USA recalled 80 lots of amlodipine valsartan, valsartan HCTZ, and single-ingredient valsartan tablets after NDEA was detected in those medications.

Valsartan, Losartan, and Irbesartan Recall Announcements Began Last June

ARBs are indicated to treat patients suffering from:

• Hypertension (high blood pressure)
• Hypertensive patients with Left Ventricular Hypertrophy
• Nephropathy associates with Type 2 diabetes

Since June, numerous generic drug makers around the world have recalled ARBs contaminated with NDEA or N-nitrosodimethylamine (NDMA), including:

• Single-ingredient valsartan
• Amlodipine in combination with valsartan
• Valsartan HCTZ
• Single-ingredient irbesartan
• Irbesartan HCTZ
• Single-ingredient losartan
• Amlodipine in combination with losartan
• Losartan HCTZ

The FDA has posted updated lists of  valsartan products under recall, losartan medications under recall, and irbesartan products under recall at its website.

NDEA and NDMA belong to a class of chemical compounds called nitrosamines. Animals tests involving rats and mice suggest exposure to high levels of NDEA or NDMA can cause liver cancer, kidney cancer, colorectal cancer, respiratory, stomach cancer, and bladder cancer.

In addition to Torrent, Aurobindo, and Prinston, other generic drug makers forced to recall ARBs include Teva Pharmaceuticals, Mylan Pharmaceuticals, Sandoz, ScieGen Pharmaceuticals, Camber Pharmaceuticals, and Major Pharmaceuticals.

Contaminated ARBs Traced to Two Overseas Suppliers

The contaminated active ingredients used in recalled valsartan, irbesartan, and losartan products have been traced to two overseas suppliers: China-based Zhejiang Huahai Pharmaceuticals and Hetero Labs of India.

According to the FDA, NDEA and NDMA may have occurred as byproducts of the manufacturing process used by these two companies. That production method has been in use since 2014, so it’s likely that contaminated IRBs have been in circulation for over four years.

In November, the FDA issued a Warning Letter to Zhejiang Huahai Pharmaceuticals, after an agency inspection turned up numerous problems at its manufacturing plant in China. The company is also subject to an import alert that prohibits its products from entering the United States.

The FDA is now testing all ARBs for the presence of NDEA or NDMA. Since the recalls began, the agency has also updated its testing methods and established acceptable intake levels for nitrosamine impurities in ARBs.

More than a dozen plaintiffs throughout the United States have since filed lawsuits for cancer and other injuries allegedly caused by recalled valsartan. On January 31^st, the U.S. Judicial Panel on Multidistrict Litigation will hold oral arguments on a proposal to centralize all federally-filed valsartan lawsuits in a single U.S. District Court for coordinated discovery and other pretrial proceedings.