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.
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 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 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 (NDMA) and NDEA, which have been found in angiotensin II 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 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.
Draft guidance on blood glucose monitors providing recommendations to industry about the types of information that should be included in premarket submissions for blood glucose monitoring test systems for prescription point-of-care use and self-monitoring blood glucose test systems for over-the-counter use. Revisions to the guidance were based on stakeholder feedback, which requested clarification on design considerations and recommended standards. When finalized, the new guidance will update two documents issued in 2016.
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 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.
Rituximab-abbs (Truxima) as the first biosimilar to rituximab (Rituxan) to treat CD20-positive, B-cell non-Hodgkin lymphoma (NHL) to be used as a single agent or in combination with chemotherapy. The drug is indicated for adults with relapsed or refractory, low-grade or follicular CD20-positive B-cell NHL as a single agent; previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy; and nonprogressing, low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy. The most common side effects are infusion reactions, fever, lymphopenia, chills, infection, and asthenia.
Trastuzumab-pkrb (Herzuma) as a biosimilar to trastuzumab (Herceptin) for HER2-overexpressing breast cancer. Like trastuzumab, the drug's labeling contains a boxed warning alerting clinicians about increased risks of cardiomyopathy, infusion reactions, pulmonary toxicity, and embryo-fetal toxicity. Common side effects include headache, diarrhea, nausea, chills, fever, infection, congestive heart failure, insomnia, cough, and rash. Serious side effects include worsening of chemotherapy-induced neutropenia.
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. In a second trial of 195 patients who were clinically stable after six or more months of treatment with eculizumab, which randomized patients to receive either continued eculizumab or ravulizumab, the latter was again found to be 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
Colchicine capsules (0.6 mg) for the prophylaxis of gout flares in adults. (Brand name: Mitigare)
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)
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)
Ganirelix acetate injection (250 µg/0.5 mL single-dose prefilled syringe) for the inhibition of premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation. (Brand name: Ganirelix Acetate Injection)
Note: The FDA states that drugs are not always commercially available immediately after approval.