Warning on IBS drug for patients without gallbladders

This column reviews details on recent recalls, warnings, and approvals.

Recalls, alerts, warnings

A warning not to prescribe eluxadoline (Viberzi) to patients without gallbladders, who have an increased risk of developing serious pancreatitis when taking the drug. The drug, which is used to treat irritable bowel syndrome with diarrhea, has been associated with at least 120 reports of severe pancreatitis since it was first approved in May 2015. Seventy-six of these cases resulted in hospitalization, and two deaths were reported (one associated with pancreatitis, the other with sphincter of Oddi spasm). Serious pancreatitis or death has occurred in this patient population after only one or two doses.

An expanded recall of epinephrine injection (EpiPen and EpiPen Jr) Auto-Injectors due to a potential defect that may result in the devices' failure to activate. The expanded recall is related to two previous reports of failure to activate devices in the single lot that was previously recalled. This recall includes 13 lots of the 0.3-mg and 0.15-mg strengths of the devices, which were distributed between December 2015 and July 2016. Patients should continue to carry recalled devices until they obtain a replacement product at no cost from a pharmacy (either another EpiPen or a generic form, which is not included in the recall).

Photo by ThinkStock
Photo by ThinkStock

A class I recall of SynchroMed II and SynchroMed EL implantable drug infusion pumps because a software issue may cause unintended drug delivery during a priming bolus procedure and reduced delivery afterward. This can result in overdose or underdose. The pumps are used to treat primary or metastatic cancer, chronic pain, and severe spasticity. The manufacturer in October 2016 began replacing software application cards with updated cards for affected consumers.

A recall of all lots of sterile products compounded and packaged by Isomeric Pharmacy Solutions due to lack of sterility assurance. The FDA made these concerns known during a recent inspection. Recalled products were distributed to patients, clinicians, hospitals, and clinics between Oct. 4, 2016, and Feb. 7, 2017. No adverse events have been reported, and the recall does not include any nonsterile compounded medications prepared by the manufacturer.

A safety alert about Transvascular Autonomic Modulation (TVAM), an experimental procedure that uses balloon angioplasty devices outside the scope of FDA-approved indications. Although at least one physician has claimed that TVAM can treat the signs and symptoms of autonomic dysfunction in multiple neurological disorders, the procedure has not been formally studied in clinical trials.


Telotristat ethyl (Xermelo) tablets, in combination with somatostatin analog (SSA) therapy, to treat adults with carcinoid syndrome diarrhea that is inadequately controlled with SSA therapy alone. The drug, which reduces the frequency of diarrhea by inhibiting the production of serotonin by carcinoid tumors, is approved to be taken orally three times daily with food. The drug received designation as an orphan drug and was granted fast-track designation and priority review. In a 12-week randomized controlled trial of 90 adults with well-differentiated metastatic neuroendocrine tumors and carcinoid syndrome diarrhea, 33% of those randomized to add the drug to their SSA regimen had an average reduction of two bowel movements per day, compared to 4% of those randomized to placebo. The most common side effects include nausea, headache, increased levels of gamma-glutamyl transferase, depression, peripheral edema, flatulence, decreased appetite, and fever. Risk of constipation may be increased in patients who have fewer than four bowel movements per day, and clinicians should monitor patients for severe constipation.

Safinamide (Xadago) tablets as an add-on treatment for patients with Parkinson's disease who are currently taking levodopa/carbidopa and experiencing an increase in symptoms (aka "off" time). In a trial of 645 participants, those who received the add-on drug versus placebo experienced a reduction in "off" time and more beneficial times of symptom control (aka "on" time). Another trial of 549 participants showed that, compared to those who received placebo, those who received the drug had more "on" time and better motor function scores during "on" time than before the treatment was added. The most common adverse reactions were uncontrolled involuntary movement, falls, nausea, and insomnia.

Odactra(Dermatophagoides farinae and D. pteronyssinus) sublingual tablets to treat house dust mite-induced allergic rhinitis, with or without conjunctivitis, in adults ages 18 through 65. The once-daily tablet is taken year-round, and it can take about eight to 14 weeks of treatment for patients to experience noticeable improvements. In placebo-controlled studies of about 2,500 people in the U.S., Canada, and Europe, those taking the drug experienced a 16% to 18% reduction in symptoms and the need for additional medications compared to those receiving placebo. The most common adverse reactions were nausea, itching in the ears and mouth, and swelling of the lips and tongue. A boxed warning cautions that severe allergic reactions may occur, and patients should be co-prescribed autoinjectable epinephrine.

Desmopressin acetate (Noctiva) nasal spray for adults who wake at least two times per night to urinate due to nocturnal polyuria. The drug is the first treatment approved for the condition, which causes overproduction of urine during the night. Clinicians should confirm overproduction of urine at night with a 24-hour urine collection, if not previously obtained. Patients take the drug daily, about 30 minutes before going to bed, and the medication works by increasing absorption of water through the kidneys, leading to less urine production. The drug's efficacy was established in two 12-week randomized trials in 1,045 patients ages 50 and older, which showed a small reduction in the average number of nighttime urinations with the drug compared to placebo. Compared to those who received placebo, more patients who received the drug were able to at least halve their number of nighttime urinations and report more nights with one or fewer nighttime urinations. The most common side effects were nasal discomfort, cold symptoms, nasal congestion, sneezing, high or increased blood pressure, back pain, nosebleeds, bronchitis, and dizziness. The drug includes a boxed warning because it can cause hyponatremia.

Avelumab (Bavencio) to treat patients ages 12 and older with metastatic Merkel cell carcinoma. The drug, the first to be approved for the rare, aggressive form of skin cancer, targets the PD-1/PD-L1 pathway and may help the immune system attack cancer cells. Accelerated approval was based on a single-arm trial of 88 patients, which showed that 33% experienced complete or partial shrinkage of their tumors. Of the responding patients, the response lasted for more than six months in 86% and more than 12 months in 45%. Further clinical trials are underway and are required to confirm clinical benefit. Common side effects include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reactions, rash, decreased appetite, and peripheral edema. The most common serious risks are immune-mediated.


Approved marketing of 23andMe Personal Genome Service Genetic Health Risk tests. The direct-to-consumer tests are the first to be authorized by the FDA to provide information on a person's genetic predisposition to certain medical diseases and conditions. The tests calculate genetic risk by isolating DNA from a saliva sample and testing the sample for more than 500,000 genetic variants. In scientific studies that the FDA reviewed, the tests correctly and consistently identified variants associated with the indicated diseases and conditions. In addition, a user study found that consumers understood more than 90% of the information in their reports. Risks include false-positive and false-negative findings, and test results should not be used for diagnosis or to inform treatment decisions. The 10 indicated diseases and conditions include: Parkinson's disease, late-onset Alzheimer's disease, celiac disease, alpha-1 antitrypsin deficiency, early onset primary dystonia, factor XI deficiency, Gaucher disease type 1, glucose-6-phosphate dehydrogenase deficiency, hereditary hemochromatosis, and hereditary thrombophilia.

A notice that the FDA is investigating the increased rate of major adverse cardiac events in patients with the Absorb GT1 Bioresorbable Vascular Scaffold (BVS). The FDA's initial review of two-year clinical trial data showed an 11% rate of major adverse cardiac events in patients treated with the BVS, compared to 7.9% in patients treated with the approved metallic XIENCE drug-eluting stent. Adverse cardiac events were more likely when the device was placed in small heart vessels.

An update on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) that reflects the FDA's agreement with the World Health Organization's designation of BIA-ALCL as a rare T-cell lymphoma that can develop after breast implantation. Most available data suggest that the rare condition occurs more frequently following implantation of breast implants with textured rather than smooth surfaces. It has been seen most frequently in patients undergoing implant revision operations for late-onset, persistent seroma, and prophylactic implant removal in asymptomatic patients is not recommended.

First-time generic approvals

Melphalan tablets USP (2 mg) for palliative treatment of multiple myeloma and for the palliation of nonresectable epithelial carcinoma of the ovary. (Brand name: Alkeran)

Sodium sulfate, potassium sulfate, and magnesium sulfate oral solution (17.5 g/3.13 g/1.6 g per 6 ounces) for cleansing of the colon in preparation for colonoscopy in adults. (Brand name: Suprep Bowel Prep Kit)

Venlafaxine hydrochloride extended-release tablets (225 mg base) to treat major depressive disorder and social anxiety disorder. (Brand name: Effexor XR)

Zileuton extended-release tablets (600 mg) for the prophylaxis and chronic treatment of asthma. (Brand name: Zyflo CR)

Note: The FDA states that drugs are not always commercially available immediately after approval.