Recalls and warnings
A class I recall of Echelon Flex Endopath staplers by Ethicon due to failure to completely form staples. An out-of-specification component within the jaw of the device may cause malformed staples. Seven serious injuries and one death have been reported. A total of 5,733 recalled devices were distributed from Aug. 1 to Sept. 26, 2019.
A class I recall of the CentriMag circulatory support system motor by Abbott due to pump and motor issues. Due to a calibration error resulting from electromagnetic interference, the pump may slow or stop and various inaccurate alarms may sound. Forty-five injuries have been reported. A total of 381 recalled devices were distributed from Nov. 22, 2017, to Aug. 6, 2019.
A class I recall of the Forte Gamma Camera System by Philips Medical Systems due to the potential for the gamma camera detector (660 pounds) to drop in an uncontrolled manner to the end of its range of motion without a command from the clinician. While the manufacturer received one customer complaint, no serious injuries or deaths were reported. A total of 852 recalled devices were distributed from Jan. 1, 1998, to Dec. 31, 2008.
A class I recall of the ROSA Brain 3.0 Robotic Surgery System by Zimmer Biomet due to a software issue that incorrectly positions the robotic arm. The manufacturer has received five complaints, including one patient injury, related to this issue. A total of 86 recalled devices were distributed from April 8, 2016, to March 19, 2019.
A recall of 22 lots of blood administration sets by B. Braun Medical due to potential for leakage at the joint between the blood filters and tubing of the administration sets. A total of 43,026 units of the recalled sets were distributed between June 11 and Sept. 27, 2019.
A recall of one lot of alprazolam tablets USP (0.5 mg) by Mylan Pharmaceuticals due to the potential presence of a foreign substance. The batch was distributed between July and August 2019.
A recall of all lots of LETS GEL KIT convenience packs by Fagron Inc. due to potential microbial contamination. The topical anesthetic was distributed nationwide to hospitals, pharmacies, and distributors.
A recall of one lot of lactated Ringer's injection USP and one lot of 0.9% sodium chloride injection USP by ICU Medical, Inc., due to the presence of particulate matter. Products were distributed to hospitals between February and June 2018 and December 2018 and March 2019, respectively.
Recalls of several forms of over-the-counter (OTC) ranitidine due to potential contamination with N-nitrosodimethylamine (NDMA), a probable human carcinogen. An FDA investigation found that the levels of NDMA detected in ranitidine are low; however, the agency has asked manufacturers to recall ranitidine if product lots contain NDMA levels above the acceptable limits. It has also asked companies to recall nizatidine, a chemically similar histamine H2 receptor antagonist, if NDMA is detected above the acceptable level. Manufacturers that have recalled ranitidine tablets (150 mg and 300 mg) and oral solution (15 mg/mL) include Novitium Pharma LLC, Aurobindo Pharma USA, Inc., Amneal Pharmaceuticals, LLC, American Health Packaging, and Lannett Company, Inc. The FDA recommended that patients taking OTC ranitidine or nizatidine can consider using other OTC products approved for their condition. So far, FDA and industry testing of H2 blockers and proton-pump inhibitors has only identified NDMA in ranitidine and nizatidine. Alternative medicines, such as famotidine, cimetidine, esomeprazole, lansoprazole, and omeprazole, have not tested positive for NDMA impurities. Patients taking prescription ranitidine who wish to stop should speak to their clinicians about other treatment options, the FDA said.
A warning letter to Greenbrier International, Inc. (doing business as Dollar Tree), for receiving potentially unsafe drugs. The warning letter details Dollar Tree's receipt of adulterated OTC drugs from manufacturers that received FDA warning letters in 2018. The warning letters sent to the contract manufacturers show a pattern of serious violations of federal law, such as not testing raw materials or finished drugs for pathogens and quality. The FDA has requested that Dollar Tree implement a system to ensure that it does not import adulterated drugs.
A new report on the root causes of and potential solutions to recent drug shortages. At the request of Congress in 2018, the FDA formed a Drug Shortages Task Force of economists and scientists to study the problem. The task force analyzed 163 drugs that went into shortage from 2013 to 2017 and compared them to similar medicines that did not go into shortage. Shortage drugs were more likely to be relatively low-price, financially unattractive to manufacturers, and sterile injectables. Shortages often occurred as a result of disruption in supply. Prices rarely rose after shortages began, and during shortages, production typically did not increase enough to restore supply to preshortage levels. The task force's three recommendations to address the root causes of drug shortages are: 1) increasing understanding of the impacts of drug shortages and companies' contracting practices that may contribute to them, 2) developing a system to measure and rate a facility's quality management maturity, and 3) considering new contracting approaches that help ensure a reliable supply of drugs. The full report is online.
Efforts to reduce reliance on ethylene oxide in medical device sterilization techniques due to environmental and public health concerns. Through two innovation challenges, the FDA has selected 11 applications from companies to identify new, alternative sterilization methods as well as strategies or technologies that can reduce the amount of ethylene oxide used to sterilize devices. The agency is working directly with the applicants to accelerate the development and review of these technologies.
A safety communication reminding clinicians that biotin, or vitamin B7, can significantly interfere with certain lab tests. High levels of the water-soluble vitamin are often found in multivitamins, prenatal vitamins, and dietary supplements marketed for hair, skin, and nail growth. Since first communicating about this issue in 2017, the FDA has continued to receive adverse event reports related to biotin interference, including with troponin tests. The agency recommends that patients and clinicians discuss all supplement use.
Cefiderocol (Fetroja) to treat adults with complicated urinary tract infections, including kidney infections caused by susceptible gram-negative microorganisms. The antibacterial drug is indicated for patients who have limited or no alternative treatment options. In a study of 448 patients with complicated urinary tract infections, 72.6% of those who received the drug had resolution of symptoms and eradication of the bacteria approximately seven days after completing treatment, compared with 54.6% of patients who received an alternative antibiotic. Clinical response rates were similar between the two groups. The drug's labeling includes a warning with regard to the higher all-cause mortality rate observed in critically ill patients with multidrug-resistant gram-negative bacterial infections who received the drug compared to those treated with other antibiotics. While the cause of the increase in mortality has not been established, the higher all-cause mortality rate was observed in patients treated for nosocomial pneumonia, bloodstream infections, or sepsis. Common adverse reactions included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion site reactions, candidiasis, cough, headache, and low potassium levels. The drug should not be used in individuals with a known history of severe hypersensitivity to beta-lactams.
Cenobamate tablets (XCOPRI) to treat partial-onset seizures in adults. In two trials of 655 patients, doses of 100 mg, 200 mg, and 400 mg daily reduced the percent of seizures per 28 days compared with the placebo group. The recommended maintenance dose, following a titration period, is 200 mg/d; however, some patients may need additional titration to 400 mg/d, the maximum recommended dose. The most common side effects were somnolence, dizziness, fatigue, diplopia, and headaches. Some patients experienced drug reaction with eosinophilia and systemic symptoms, and one patient died, when the drug was titrated rapidly (weekly or faster titration). In addition, a higher percentage of patients who received the drug had a shortening of the QT interval of greater than 20 ms compared to those who received placebo.
Voxelotor (Oxbryta) to treat sickle cell disease in patients ages 12 years and older. In a trial of 274 patients, those who received 1,500 mg/d had a 51.1% increase in hemoglobin response rate at 24 weeks, compared to 6.5% in the placebo group. Common side effects of the orphan drug were headache, diarrhea, abdominal pain, nausea, fatigue, rash, and fever.
Crizanlizumab-tmca (Adakveo) to reduce the frequency of vaso-occlusive crisis in patients ages 16 years and older. In a trial of 198 patients with sickle cell disease and a history of vaso-occlusive crisis, patients who received the drug had fewer health care visits for vaso-occlusive crisis (median annual rate of 1.63 visits) than patients who received placebo (median annual rate of 2.98 visits). In addition, 36% of patients who received the orphan drug did not experience vaso-occlusive crisis during the study, and treatment delayed the time that patients first experienced vaso-occlusive crisis after starting treatment from 1.4 months to 4.1 months. Common side effects were back pain, nausea, fever, and arthralgia. Clinicians should monitor patients for infusion-related reactions and discontinue the drug in the case of severe reactions. Patients who receive the drug should also be monitored for interference with automated platelet counts or platelet clumping. Clinicians are advised to run blood tests as soon as possible after samples are collected or to use tubes containing citrate.
Marketing of a test to detect HIV-1 drug resistance mutations using next-generation sequencing technology. The Sentosa SQ HIV Genotyping Assay is the first HIV drug-resistance assay using this technology to be authorized for marketing in the U.S. In performance studies, the assay demonstrated a greater than 95% sensitivity and specificity in detecting 342 HIV drug-resistant mutations. It is indicated for use only in patients with HIV-1 who are about to start or are already taking antiviral therapy and is not intended for diagnosing HIV infection. Test results are intended to be used in conjunction with clinical observations, patient history, and other laboratory evidence to make patient management decisions.
Marketing of the first duodenoscope with a sterile, disposable elevator component. While the FDA has previously cleared duodenoscopes with removable endcap components, the Pentax Medical Video ED34-i10T2 model duodenoscope is the first device with a disposable elevator component, a part that has been traditionally difficult to clean and reprocess. The disposable elevator component will reduce the number of device parts that need to be cleaned and disinfected between uses. The device is intended to be used with endoscopic devices, and its risks include burns, electric shock, perforation, infection, and bleeding.
Supplemental approval of acalabrutinib (Calquence) to treat adults with chronic lymphocytic leukemia or small lymphocytic lymphoma. In two trials, patients receiving the drug had a longer progression-free survival than those receiving other standard treatments. The most common side effects were anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain. Patients may experience atrial fibrillation and flutter and should be monitored for symptoms of arrhythmias. They should also be monitored for serious infections, bleeding, and low blood counts.
Adalimumab–afzb (Abrilada), a biosimilar to Humira. The approval is one of nine new biosimilar products the FDA has taken action on in 2019, bringing the overall total of biosimilar approvals to 25.
First-time generic approvals
Digoxin oral solution USP (0.05 mg/mL) for the treatment of atrial fibrillation in adults and heart failure in adult and pediatric patients. (No brand name provided.)
Note: The FDA states that drugs are not always commercially available immediately after approval.