Azithromycin gets warning, incretin mimetics investigated

This regulatory update covers a new warning on azithromycin about abnormal changes in the electrical activity of the heart, and a possible increased risk of pancreatitis and precancerous findings from incretin mimetic drugs.

Recalls, warnings and label changes

A new warning on azithromycin (Zithromax or Zmax) about abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm. Patients are at particular risk if they have existing QT-interval prolongation, low blood levels of potassium or magnesium, a slower than normal heart rate or take certain drugs used to treat arrhythmias. Clinicians should consider the risk of torsades de pointes and fatal heart rhythms when choosing treatments for patients who are already at risk for cardiovascular events but should recall that alternative drugs in the macrolide class, or non-macrolides such as the fluoroquinolones, also have the potential for QT prolongation or other significant side effects.


A recall of all lots of peginesatide (Omontys) injection due to postmarketing reports of serious hypersensitivity reactions, including anaphylaxis. Fatal reactions have been reported in approximately 0.02% of patients following the first intravenous dose, and all serious hypersensitivity reactions occurred within 30 minutes of administration.

A class I recall of the St. Jude Medical Amplatzer TorqVue FX Delivery System because the distal end of the core wire could potentially fracture when exposed to a combination of certain cardiac anatomies and usage conditions.

A recall of one lot of cidofovir (Vistide) injection due to the presence of particulate matter in some vials. Before injecting the drug, clinicians should inspect the product and any product with lot number B120217A should not be injected.

A class I recall of certain models of Lumenis VersaCut Tissue Morcellator due to potential for air embolisms to occur if the aspiration tubing is hooked up backward to the aspiration control box housing. This may cause serious adverse health consequences, including death.

A class I recall of Ad-Tech Macro Micro Subdural Electrodes because the microelectrodes may be defective. There is the potential for abrasion of brain tissue and for broken pieces to remain in the brain tissue when the electrode is removed. This may lead to hemorrhaging or a seizure, as well as death. One serious injury has been reported.


Ospemifene (Osphena) to treat women experiencing moderate to severe dyspareunia. A pill taken with food once daily, it acts like estrogen to make vaginal tissues thicker and less fragile. Safety and effectiveness were established in three clinical studies of 1,889 postmenopausal women. After 12 weeks of treatment, women had statistically significant improvement of dyspareunia with the drug compared to placebo. The drug carries a boxed warning about the risk of endometrium thickening and the incidence rates of

thrombotic and hemorrhagic strokes and deep venous thrombosis (0.72, 1.45 and 1.45 per thousand women, respectively). It should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman.

Ado-trastuzumab emtansine (Kadcyla) to treat HER2-positive, metastatic breast cancer. The drug is intended for patients who were previously treated with trastuzumab and taxanes. Safety and effectiveness were evaluated in a study of 991 patients randomized to ado-trastuzumab emtansine (median progression-free survival of 9.6 months) or lapatinib plus capecitabine (6.4 months). The drug is being approved with a boxed warning about liver toxicity, heart toxicity and death.

Regorafenib (Stivarga) to treat advanced gastrointestinal stromal tumors that cannot be surgically removed and that no longer respond to other FDA-approved treatments for this disease. Safety and effectiveness were evaluated in study of 199 patients in which patients taking the drug had 3.9 months more progression-free survival than patients who were given placebo. The drug was approved to treat colorectal cancer in September 2012.

Technetium Tc 99m tilmanocept (Lymphoseek) injection, a radioactive diagnostic imaging agent to locate lymph nodes in patients with breast cancer or melanoma who are undergoing surgery to remove tumor-draining lymph nodes. It is the first drug approved for lymph node mapping in more than 30 years. Safety and effectiveness were established in two trials of 332 patients, in which Lymphoseek and blue dye localized most lymph nodes but a notable number were localized only by Lymphoseek.

The Argus II Retinal Prosthesis System, the first implanted device to treat advanced retinitis pigmentosa. The device, which includes a small video camera, a transmitter mounted on a pair of eyeglasses, a video processing unit and an implanted retinal prosthesis, replaces the function of degenerated cells in the retina and may improve a patient's ability to perceive images and movement. Of 30 patients who received the device in a trial, most were better able to perform basic activities and 19 experienced no adverse events. Eleven study subjects experienced a total of 23 serious adverse events, including erosion of the conjunctiva, dehiscence, retinal detachment, inflammation and hypotony.

A new silicone breast implant, the Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Gel Filled Breast Implant, for augmentation in women at least 22 years old and for reconstruction in women of any age. Approval was based on seven years of data from 941 women, which showed complications and outcomes similar to previous breast implant studies, including capsular contracture, re-operation, implant removal, asymmetry and infection. In addition, investigators observed fissures in the gel of some Natrelle 410 implants.


The FDA has stopped all pediatric clinical trials of cinacalcet hydrochloride (Sensipar) after the recent death of a 14-year-old patient in a trial. The drug is currently approved for use in adults but not in children. The FDA reminds clinicians that patients should be monitored for the development of hypocalcemia. Serum calcium levels should be measured within one week after initiation or dose adjustment of the drug. Once a maintenance dose has been established, serum calcium should be measured monthly. If serum calcium levels decrease below the normal range, appropriate steps should be taken to increase calcium levels, such as providing supplemental calcium, initiating or increasing the dose of a calcium-based phosphate binder, initiating or increasing the dose of vitamin D sterols, or temporarily withholding the drug.

The FDA is investigating reports of possible increased risk of pancreatitis and precancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. The investigation is based on unpublished new findings based on examination of a small number of pancreatic tissue specimens taken from patients after they died of unspecified causes. The FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the agency can further investigate potential pancreatic toxicity associated with the incretin mimetics. Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto). The FDA has not reached any new conclusions about safety risks with incretin mimetic drugs and will communicate its final conclusions and recommendations when the review is complete or when additional information is available to report.