Recalls, warnings, and alerts
A warning about an increased risk of ruptures or tears in the aorta when certain patients use fluoroquinolones. An FDA review found that the antibiotics, given by mouth or through an injection, can increase the occurrence of aortic aneurysm or dissection. The estimated background risk ranges from nine aortic aneurysm events per 100,000 people per year in the general population to 300 aortic aneurysm events per 100,000 people per year in individuals at the highest risk. Fluoroquinolones should not be used in patients at increased risk (e.g., those with a history of blockages or aneurysms of the aorta or other blood vessels, those with hypertension, and the elderly) unless there are no other treatment options available. A new warning about this risk will be added to the prescribing information and patient medication guide for all fluoroquinolones.
A class I recall of the CareScape R860 Inspiratory Safety Guard by GE Healthcare due to the risk of disconnection from the ventilated patient's breathing circuit. A manufacturing defect is the cause of the issue. The recall includes 307 devices manufactured and distributed from August 2017 through September 2018.
A warning that rare but serious cases of stroke and tears in the lining of arteries in the head and neck have occurred in patients with multiple sclerosis shortly after they received alemtuzumab (Lemtrada). The FDA has received 13 reports of stroke or cervicocephalic arterial dissection that occurred shortly after a patient received the drug. In response, the FDA has added a new warning about these risks to the drug label and patient medication guide and has also added the risk of stroke to the existing boxed warning. The drug is also approved under the brand name Campath to treat B-cell chronic lymphocytic leukemia, and that drug's label will also be updated to include these risks. Clinicians should advise patients at every infusion of the drug to seek immediate emergency medical attention if they experience symptoms of ischemic or hemorrhagic stroke or cervicocephalic arterial dissection. Because early symptoms such as headache and neck pain are not specific, clinicians should promptly evaluate patients who report symptoms consistent with these conditions.
An alert not to use drug products intended to be sterile that were produced and distributed by Promise Pharmacy due to lack of sterility assurance. During an FDA inspection of the company's facility, investigators observed insanitary conditions, including poor sterile production practices and inadequate design of one of its processing rooms. The FDA has recommended that the company recall all unexpired drug products intended to be sterile and cease sterile operations until adequate corrections are made. While the company agreed to cease sterile operations in the inadequately designed processing room, it did not recall drug products it compounded in that room.
A warning that signs and symptoms of differentiation syndrome are not being recognized in patients with acute myeloid leukemia who are receiving enasidenib (Idhifa). While the drug's prescribing information and patient medication guide already contain a warning about the syndrome, the FDA is aware of cases that were not recognized and patients who did not receive the necessary treatment. Clinicians should describe the symptoms of differentiation syndrome to patients when starting the drug and at follow-up visits. The syndrome has occurred as early as 10 days and up to five months after starting the medicine. Consider a diagnosis of differentiation syndrome if patients experience unexplained respiratory distress or other symptoms, and treat promptly with oral or IV corticosteroids.
An expanded recall of all lots of valsartan-containing products within expiry by Mylan Pharmaceuticals due to detected trace amounts of an impurity, N-nitrosodiethylamine (NDEA), in the active pharmaceutical ingredient. The 104 additional lots include 26 lots of amlodipine and valsartan tablets USP (5 mg/160 mg, 10 mg/160 mg, 5 mg/320 mg, and 10 mg/320 mg strengths), 51 lots of valsartan tablets USP (40 mg, 80 mg, 160 mg, and 320 mg strengths), and 27 lots of valsartan and hydrochlorothiazide tablets USP (80 mg/12.5 mg, 160 mg/12.5 mg, 160 mg/25 mg, 320 mg/12.5 mg, and 320 mg/25 mg strengths). Batches were distributed between March 2017 and November 2018.
A recall of two lots of losartan potassium tablets USP (100 mg) by Torrent Pharmaceuticals Limited due to detected trace amounts of NDEA in the active pharmaceutical ingredient, manufactured by Hetero Labs Limited. Batches were distributed nationwide and have an expiration date of April 2019.
A recall of CoaguChek XS Test Strips distributed directly to U.S. consumers by Terrific Care, LLC./Medex Supply Dist, Inc. The recalled products, which include all catalog/REF numbers that do not end in 160, were found to inaccurately report high international normalized ratio (INR) test results and were distributed from Dec. 27, 2017, through Dec. 15, 2018. While the manufacturer previously recalled the test strips, these batches were not included in the recall because they were not distributed by the manufacturer.
A recall of 20 lots of Dyural-40 and 61 lots of Dyural-80 by Asclemed USA Inc. due to a latex hazard. The convenience kits contain sodium chloride USP (0.9%) that was recalled by manufacturer Fresenius Kabi due to product labeling incorrectly stating the stoppers do not contain latex.
A class I recall of implantable bone growth and spinal fusion stimulators by Zimmer Biomet, Inc. due to lack of adequate validation and controls to ensure product cleanliness. The recall includes 1,360 units of the EBI Osteogen Implantable Bone Growth Stimulator, SpF PLUS-Mini (60 μA/W) Implantable Spinal Fusion Stimulator, and the SpF-XL IIb 2/DM Implantable Spinal Fusion Stimulator. Recalled devices were manufactured from Feb. 14, 2015, through April 11, 2017.
A class I recall of the BrightMatter Guide with SurfaceTrace Registration by Synaptive Medical due to a software defect. The recall includes 36 of the brain-imaging devices, which were manufactured between Nov. 17, 2017, and April 24, 2018.
A field corrective action for the Puritan Bennett 980 ventilator series by Medtronic to address customer feedback. A software update will provide product enhancements, including external USB drive performance and graphical user interface functionality. The ventilators may continue to be used before the software update is installed.
A safety communication about higher-than-expected rates of duodenoscope contamination after reprocessing, according to preliminary data from postmarketing surveillance studies conducted by all three U.S. duodenoscope manufacturers. After reprocessing, up to 3% of properly collected samples tested positive for more than 100 colony-forming units of organisms that are unlikely to cause serious infections, an indication of a reprocessing failure. Another 3% of samples tested positive for organisms of high concern, such as Escherichia coli and Staphylococcus aureus. The manufacturers (Olympus, Fujifilm, and Pentax) are conducting root-cause analyses to better understand these preliminary culturing results.
A warning letter issued to the manufacturer of the active pharmaceutical ingredient found in valsartan. The manufacturer, China-based Zhejiang Huahai Pharmaceutical Co., Ltd., is the subject of an ongoing FDA investigation into the probable cancer-causing impurities N-nitrosodimethylamine and NDEA, which have been found in angiotensin-receptor blockers. The warning letter outlines several manufacturing violations, including impurity control, change control, and cross-contamination from one manufacturing process line to another. The FDA is still investigating the root cause of the impurity.
A mobile medical application to help increase retention in an outpatient treatment program for individuals with opioid use disorder. The reSET-O app, a prescription cognitive behavioral therapy, is intended to be used in addition to outpatient treatment under the care of a health care professional in conjunction with treatment that includes buprenorphine and contingency management. It may be downloaded directly to a patient's mobile device after he or she receives a prescription to do so from a doctor. In a 12-week clinical trial of 170 patients treated with buprenorphine and a behavior therapy program, with or without a desktop version of the app, those who used the app had a significant increase in retention in their treatment program compared to those who did not. However, the app was not shown to decrease illicit drug use or improve abstinence. It is not intended to be used as a standalone therapy, as a substitute for medication, or for patients whose primary language is not English. The app was not associated with side effects.
Gilteritinib (Xospata) tablets to treat adults who have relapsed or refractory acute myeloid leukemia with a FLT3 mutation, as detected by an FDA-approved companion diagnostic. In a trial of 138 patients, 21% of patients who received the orphan drug achieved complete remission or complete remission with partial hematologic recovery. Of 106 patients who required red blood cell or platelet transfusions at the start of treatment, 31% became transfusion-free for at least 56 days. Common side effects were myalgia, arthralgia, fatigue, and elevated liver aminotransferase levels. Clinicians should monitor patients who are taking the drug for posterior reversible encephalopathy syndrome, prolonged QT interval, and pancreatitis. Rare cases of differentiation syndrome have also been reported.
Ravulizumab (Ultomiris) injection to treat adults with paroxysmal nocturnal hemoglobinuria. The drug, a long-acting complement inhibitor that prevents hemolysis, was studied in a trial of 246 treatment-naive patients who were randomized to receive either the drug or eculizumab, the current standard of care for the disease. Patients in both groups had a similar incidence of hemolysis. A second trial of patients who were clinically stable after six or more months of treatment with eculizumab randomized 195 patients to receive either continued eculizumab or ravulizumab and found the latter noninferior. Common side effects were headache and upper respiratory infection. A boxed warning alerts clinicians about the risk of life-threatening meningococcal infections and sepsis.
First-time generic approvals
Buprenorphine transdermal system (5 µg/h, 10 µg/h, 15 µg/h, 20 µg/h) to manage pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. (Brand name: Butrans)
Oxycodone hydrochloride and acetaminophen oral solution (10 mg/300 mg per 5 mL) to manage pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. (Brand name: Roxicet)
Aminocaproic acid tablets USP (500 mg, 1,000 mg) to enhance hemostasis when fibrinolysis contributes to bleeding. (Brand name: Amicar)
Dexmedetomidine hydrochloride in 0.9% sodium chloride injection (80 µg/20 mL, 200 µg/50 mL, 400 µg/100 mL [4 µg/mL] single-dose containers) for the sedation of nonintubated patients prior to and/or during surgical and other procedures. (Brand name: Precedex)
Azelaic acid gel (15%) for the topical treatment of the inflammatory papules and pustules of mild to moderate rosacea. (Brand name: Finacea)
Dyclonine hydrochloride topical solution (0.5%, 1%) for anesthetizing accessible mucous membranes (e.g., the mouth, pharynx, larynx, trachea, esophagus, and urethra) prior to various endoscopic procedures. (Brand name: Dyclone)
Bismuth subsalicylate chewable tablets (262.4 mg), metronidazole tablets (250 mg), and tetracycline hydrochloride capsules (500 mg) to eradicate Helicobacter pylori in patients with H. pylori infection and active duodenal ulcer disease or a history of duodenal ulcer. (Brand name: Helidac)
Note: The FDA states that drugs are not always commercially available immediately after approval.