SGLT2 inhibitors get new warning, rosiglitazone gets off REMS

Details on the latest recalls, warnings, and approvals.

Recalls and warnings

A warning on sodium-glucose cotransporter-2 (SGLT2) inhibitors about the risks of ketoacidosis and serious urinary tract infections. These warnings will be added to the labels of medicines in this class, such as canagliflozin, dapagliflozin, and empagliflozin. In a safety review, the FDA identified 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes treated with SGLT2 inhibitors and 19 cases of life-threatening urosepsis and pyelonephritis that started as urinary tract infections. All 19 patients were hospitalized, and a few required admission to an ICU or dialysis.

Photo by Thinkstock
Photo by Thinkstock

A recall of the RotaWire Elite Guidewire and wireClip Torquer Guidewire because wires may break and separate from the Rotablator Rotational Atherectomy System. This separation can cause serious injuries, such as tamponade, myocardial infarction, and migration of wire fragments elsewhere in the body. The manufacturer has received 3 reports of this issue occurring, including 1 patient death following medical intervention to remove the broken wire.

A recall of the Chariot Guiding Sheath because of the risk of shaft separation. These devices are used to introduce interventional devices during peripheral vascular procedures. The manufacturer has received 14 reports of shaft separation during device preparation or use, and 4 of these reports involved separation of the distal shaft. The most severe outcome of the event is embolism of device fragments, which can lead to obstruction of blood flow or additional intervention to remove the fragments. No permanent injuries or deaths have been reported.

A recall of the LS, 5i, and 7i Inspiration ventilator systems because a faulty switch on the ventilator's power board may fail, causing the ventilator to shut down without sounding an alarm. If the ventilator shuts down, the patient may not receive enough oxygen. The manufacturer received 1 report of this issue occurring, with no injuries or deaths.

A recall of the G5 Ventilator because it may stop working without sounding an alarm. This may occur when the device operator presses the oxygen enrichment key to attach the ventilator mask to the patient. The manufacturer has received 1 report of device malfunction, with no injuries or deaths.

A warning of potential contamination of certain lots of baclofen active pharmaceutical ingredient (API) manufactured in China by Taizhou Xinyou Pharmaceutical & Chemical Co. The affected APIs may be at risk for contamination with particulates and should not be used to compound sterile injectable drugs. If patients use or receive injectable drug products compounded with the affected baclofen, especially when administered directly into the spinal column, serious injury may occur.

A recall of sterile products compounded and packaged by Downing Labs, LLC, because of concerns over sterility assurance. All clinicians and patients who received the affected products, distributed from April 20, 2015, to Sept. 15, 2015, should discontinue use.


A trivalent vaccine (Fluad) for the prevention of seasonal influenza in people ages 65 years and older. This is the first flu vaccine to contain an adjuvant and is produced from 3 virus strains (2 subtype A and 1 type B). In a trial of 7,082 older participants, the new vaccine and an existing one (Agriflu) induced comparable antibody levels. Safety was evaluated in about 27,000 additional older adults, and no safety concerns were identified. The most common adverse events include injection site pain and tenderness, muscle aches, headache, and fatigue.

Uridine triacetate (Vistogard) for the emergency treatment of patients who receive an overdose of the chemotherapy agents fluorouracil and capecitabine or who develop early-onset, severe toxicities after receiving these treatments. Taken orally, the drug blocks cell damage and cell death and is administered as soon as possible after overdose or within 4 days of severe or life-threatening toxicity. In 2 trials of 135 patients, 97% of overdose patients and 89% of toxicity patients were still alive at 30 days, and 33% of all patients resumed chemotherapy in less than 30 days. The most common side effects were diarrhea, vomiting, and nausea. The drug is not recommended for non-emergency adverse reactions associated with fluorouracil and capecitabine because it may lessen their efficacy.

Sugammadex (Bridion) injection to reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide used during certain types of surgery. In 3 clinical trials involving 456 patients, treatment groups recovered faster than comparator groups, with most participants recovering within 5 minutes of routine sugammadex use. The most common adverse reactions included vomiting, hypotension, pain, headache, and nausea. Clinicians should be aware of the possibility of a hypersensitivity reaction or anaphylaxis, as well as hemodynamic changes, as cases of marked bradycardia have been observed within minutes of drug administration.

Mepolizumab (Nucala) for use with other asthma medicines for the maintenance treatment of asthma in patients ages 12 and older with a history of exacerbations despite therapy. Administered by injection every 4 weeks, the drug reduces severe asthma attacks by reducing levels of blood eosinophils. In 3 placebo-controlled trials, patients taking the drug had fewer exacerbations requiring hospitalization and/or an ED visit and a longer time to first exacerbation. Treatment did not result in a significant improvement in lung function. The most common side effects include headache, injection site reactions, back pain, and fatigue.

Recombinant von Willebrand factor (Vonvendi) to treat bleeding episodes in adults diagnosed with von Willebrand disease. Two clinical trials of 69 adult patients with the disease demonstrated that the orphan product was safe and effective for the on-demand treatment and control of bleeding episodes from various sites on the body. The most common adverse reaction was generalized pruritus.

Human coagulation factor X (Coagadex) for controlling bleeding episodes in patients ages 12 and older with hereditary factor X deficiency. Derived from human plasma, it is the first specific coagulation factor replacement therapy approved for such patients. In a multicenter, nonrandomized study of 16 participants with mild to severe factor X deficiency, the drug controlled spontaneous, traumatic, and menorrhagic bleeding episodes, and it controlled blood loss during and after surgery in 5 individuals with mild factor X deficiency. No safety concerns were identified in either study.

Alectinib (Alecensa) to treat metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer after unsuccessful crizotinib (Xalkori) therapy. The oral medication blocks the activity of the ALK protein. In 2 clinical trials, 38% and 44% of participants experienced a partial shrinkage of their lung tumors, an effect that lasted an average of 7.5 months and 11.2 months, respectively. The most common side effects were fatigue, constipation, edema, and myalgia. In the 2 trials, 61% of participants who had measurable brain metastases experienced a complete or partial reduction in their brain tumors that lasted an average of 9.1 months. Serious side effects include liver problems, severe or life-threatening inflammation of the lungs, very slow heartbeats, and severe muscle problems. Treatment may also cause sunburn when patients are exposed to sunlight.

Necitumumab (Portrazza) in combination with 2 forms of chemotherapy to treat metastatic squamous non-small-cell lung cancer. In a clinical study of 1,093 participants who received gemcitabine and cisplatin with or without necitumumab, those taking the drug lived longer on average (11.5 months) compared to those only taking the 2 chemotherapy drugs (9.9 months). The most common side effects were skin rash and hypomagnesemia. The drug has a boxed warning on its serious risks, including cardiac arrest and sudden death.

Elotuzumab (Empliciti) in combination with 2 other therapies to treat people with multiple myeloma who have received 1 to 3 prior medications. In a study of 646 participants, those taking elotuzumab plus lenalidomide and dexamethasone experienced a delay in the amount of time before their disease worsened (19.4 months) compared to those taking only the latter 2 drugs (14.9 months). In addition, 78.5% of those taking the extra drug saw a complete or partial shrinkage of their tumors, compared to 65.5% of those taking only lenalidomide and dexamethasone. The most common side effects of elotuzumab were fatigue, diarrhea, fever, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, and pneumonia.

Daratumumab (Darzalex) to treat multiple myeloma in patients who have received at least 3 prior treatments. Given as an infusion, daratumumab injection is a monoclonal antibody that helps certain cells in the immune system attack cancer cells. In a trial of 106 patients, 29% experienced complete or partial reduction in their tumor burden, lasting an average of 7.4 months. Another study showed that 36% of 42 participants receiving the drug had complete or partial reduction in tumor burden. The most common side effects were infusion-related reactions, fatigue, nausea, back pain, fever, and cough. The drug may also result in lymphopenia, neutropenia, leukopenia, anemia, and thrombocytopenia.


A notice that lubricious coatings may separate from intravascular medical devices and cause serious injuries to patients. Various factors can cause this coating separation, such as the difficulty of the procedure, patient anatomy, and improper use or preconditioning of the device. Since Jan. 1, 2010, multiple manufacturers have conducted 11 recalls associated with hydrophilic or hydrophobic coatings peeling or flaking off of medical devices. In addition, about 500 medical device reports describing coating separation have been reported to the FDA since Jan. 1, 2014. Serious adverse events were reported, including pulmonary embolism, pulmonary infarction, myocardial embolism, myocardial infarction, embolic stroke, tissue necrosis, and death. The majority of these recalls and reports were submitted for vascular guidewires. The agency recommends that clinicians be aware of these potential issues, although the overall benefits of these devices continue to outweigh the risks.

A notice that the FDA is eliminating the Risk Evaluation and Mitigation Strategy (REMS) for rosiglitazone-containing type 2 diabetes medicines. These medications are approved as Avandia, Avandamet, Avandaryl, and generics. Drug manufacturers have fulfilled FDA requirements, such as providing training to clinicians about the heart risks of rosiglitazone medications, and the agency has determined that a REMS is no longer necessary to ensure that the benefits of these medicines outweigh their risks.

A voluntary field safety notification for 15 lots of the OmniPod Insulin Management System because of reports of its needle mechanism failing to deploy or demonstrating a delay in deployment. If deployment of the needle mechanism fails, the needle is not inserted, preventing insulin delivery. Affected lots of the product have resulted in 66 medical device reports, including 3 that required medical intervention. The reported incidence of this issue in the affected lots is about 1% to 2%. The company has corrected the manufacturing process and has implemented additional inspection steps. The FDA recommends that consumers using products from the affected lots ensure that the needle mechanism deploys properly.