Ranitidine pulled from market due to contamination

Details on recalls, withdrawals, and approvals.


Recalls

A class I recall of IMAGER II 5F Angiographic Catheters by Boston Scientific Corporation due to a potential for the catheter tip to become detached during a procedure or during procedure preparation. There are nine reported injuries related to this issue. The recall includes 6,130 devices distributed from July 16, 2018, to Nov. 26, 2019.

A class I recall of Over the Wire Embolectomy Catheters by LeMaitre Vascular Inc. due to a risk of the balloon catheter failing to deflate during use. The FDA has received 26 related medical device reports, with no deaths and one injury. The recall includes 49,393 devices distributed from Nov. 7, 2014, to March 5, 2020.

Image by Getty Images
Image by Getty Images

A recall of eight lots of tetracycline hydrochloride capsules USP (250 mg and 500 mg in 100-count bottles) by Avet Pharmaceuticals Inc. due to failed dissolution specification test results. Recalled products were distributed to wholesalers and distributors nationwide between August 2019 and March 2020.

A recall of 13 lots of ketorolac tromethamine injection USP (30 mg/mL, 1-mL fill and 30 mg/mL, 2-mL fill in 2-mL amber vials) by Fresenius Kabi USA LLC due to the presence of particulate matter. The particulate matter, found in eight reserve sample vials, was composed of carbon, silicon, oxygen, and polyamides. Recalled lots were distributed nationwide between May 5, 2018, and Dec. 16, 2019. In response to the recall, QuVa Pharma Inc. recalled all lots of ropivacaine, epinephrine, clonidine, and ketorolac (50 mL in sodium chloride-60 mL BD syringes) that were prepared using sterile ketorolac being recalled by Fresenius Kabi.

Miscellaneous

Results from two postapproval studies of liquid-filled intragastric balloon devices used for weight loss. The FDA in 2017 first communicated two specific risks for the Orbera and ReShape liquid-filled intragastric balloons: spontaneous hyperinflation and acute pancreatitis. In a letter to clinicians, the agency reported that postapproval studies found a small number of these events, whereas there were none reported in the studies used in their premarket approval applications. Selling and distribution of the ReShape device were stopped on Jan. 1, 2019, but the FDA will continue to work with Apollo Endosurgery, the manufacturer of the Orbera device, to ensure that the product labeling includes the postapproval study findings.

A request that manufacturers immediately withdraw all prescription and over-the-counter (OTC) ranitidine medications from the market due to potential contamination with N-nitrosodimethylamine (NDMA). The call to action is the latest step in the FDA's ongoing investigation of NDMA in ranitidine, a histamine-2 receptor antagonist commonly known by the brand name Zantac. The impurity in some ranitidine products increases over time and when stored at higher than room temperatures, which may result in consumer exposure to unacceptable levels of NDMA. As a result of the immediate market withdrawal request, ranitidine products will not be available for new or existing prescriptions or OTC use in the U.S. FDA testing has not found NDMA in drugs approved for the same or similar uses, such as famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec).

Approvals

Coagulation factor VIIa (recombinant)-jncw (Sevenfact) to treat and control bleeding episodes occurring in patients ages 12 years and older with hemophilia A or B who have developed inhibitors. The drug is the first hemophilia treatment that contains an active ingredient obtained from rabbits genetically engineered to produce a protein necessary for blood coagulation. The active ingredient is a recombinant analog of human coagulation factor VII, which is expressed in the mammary gland of the rabbits and secreted into their milk. During purification and processing of the milk, the analog is converted into activated coagulation factor VIIa. The FDA's Center for Veterinary Medicine approved this process and determined it to be safe for the rabbits and their handlers and to have no significant impact on the environment. In a study of 27 patients with 465 mild or moderate and three severe bleeding episodes, either a low dose or higher dose of the drug successfully treated about 86% of bleeding events. The most common side effects are headache, dizziness, infusion site discomfort, infusion-related reaction, infusion-site hematoma, and fever. The drug is contraindicated in patients with known allergy or hypersensitivity to rabbits or rabbit proteins.

Tucatinib (Tukysa) in combination with chemotherapy (trastuzumab and capecitabine) to treat adults with advanced forms of unresectable or metastatic HER2-positive breast cancer. The kinase inhibitor is indicated for patients who have received one or more prior treatments and is the first new drug approved as part of Project Orbis, an international collaboration. In a trial of 612 patients, the median progression-free survival in patients who received the orphan drug in combination with chemotherapy was 7.8 months, compared to 5.6 months in those who received placebo. Median overall survival was 21.9 months in the intervention group and 17.4 months in the placebo group. Common side effects include diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. Serious side effects include severe diarrhea associated with dehydration, acute kidney injury, and death.