Cardiac risks of testosterone, saxagliptin under investigation

This regulatory update covers an FDA review of the risk of stroke, heart attack and death in men taking testosterone products, as well as a possible increase in heart failure associated with saxagliptin.

Recalls, warnings and label changes

A recall of specific lots of insulin cartridges that are used with the t:slim Insulin Pump by Tandem Diabetes Care, because the cartridges may be at risk for leaking, which could potentially result in the device delivering too much or too little insulin.

Photo by Thinkstock
Photo by Thinkstock

A recall of Puritan Bennett 840 Series ventilators by Covidien due to a software problem which may trigger a diagnostic code that causes the ventilator to stop functioning. This issue may cause serious adverse health consequences, including death. A software update to correct the problem is available online.

A recall of calcium gluconate 10% injections by Rx Formulations due to a risk of microbial contamination, after FDA testing identified gram-positive rod bacteria in the product.

A recall of the Trufill n-BCA liquid embolic system by Codman Neuro because it carries incorrect instructions on mixing ratios, which can result in the liquid mixture solidifying too slowly in unintended areas, potentially leading to embolization or reflux into arteries and pulmonary vessels.


Tasimelteon (Hetlioz) to treat non-24-hour sleep-wake disorder in totally blind individuals. The melatonin receptor agonist is the first FDA-approved treatment for the disorder. Approval was based on 2 trials with 104 participants in which the drug increased nighttime sleep and decreased daytime sleep compared to placebo. The most common side effects were headache, elevated liver enzymes, nightmares or unusual dreams, disturbed night's sleep, upper respiratory or urinary tract infection and drowsiness.

A new indication for the Dexcom G4 Platinum Continuous Monitoring System for patients with diabetes ages 2 to 17 years. The system, which monitors blood glucose levels, had already been approved for patients ages 18 and older.

A new combined use of trametinib (Mekinist) and dabrafenib (Tafinlar) to treat advanced unresectable or metatstatic melanoma. In May 2013, the FDA approved the drugs as single agents for the same indication. Approval of the combination was based on a trial of 162 participants in which more patients had longer-lasting objective response than on single-drug treatment. The most common side effects included fever, chills, tiredness, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, joint pain, night sweats, decreased appetite, constipation and muscle pain.

A new indication for ibrutinib (Imbruvica) to treat chronic lymphocytic leukemia (CLL) in patients that have received at least 1 previous therapy. In November 2013, the FDA granted ibrutinib accelerated approval to treat mantle cell lymphoma. Accelerated approval for CLL is based on a study of 48 patients in which 58% responded. An improvement in survival or disease-related symptoms has not been established. The most common side effects include thrombocytopenia, diarrhea, bruising, neutropenia, anemia, upper respiratory tract infection, fatigue, musculoskeletal pain, rash, fever, constipation, peripheral edema, arthralgia, nausea, stomatitis, sinusitis and dizziness.

The Affymetrix CytoScan Dx Assay to detect chromosomal variations that may be responsible for a child's developmental delay or intellectual disability. Based on a blood sample, the test can analyze the entire genome and detect large and small chromosomal changes. In a comparison of 960 blood specimens, the new assay performed better karyotyping and FISH chromosomal tests. This device should not be used for stand-alone diagnostic purposes, pre-implantation or prenatal testing or screening, population screening, or for the detection of, or screening for acquired or genetic aberrations occurring after birth.

ReSure Sealant, for use in cataract surgery. It is the first gel sealant approved to stop fluid from leaking through an incision in the cornea after cataract surgery with intraocular lens placement. Previously, stitches were the only option for closing a leaking incision. Approval is based on a randomized study of 471 surgery patients, in which the sealant was more effective than use of a single suture.


The risk of stroke, heart attack, and death in men taking testosterone products is being investigated by the FDA, according to a recent announcement. The investigation is motivated by publication of 2 studies suggesting an increased risk of cardiovascular events with the drugs. The agency will communicate its final conclusions and recommendations, and in the meantime, clinicians should follow the drugs' prescribing information and consider whether the benefits of testosterone treatment are likely to exceed the potential risks.

A possible increase in heart failure associated with saxagliptin (Onglyza and Kombiglyze XR) is also being investigated by the FDA. The agency recently requested data from a manufacturer-sponsored trial which found an increased rate of hospitalization for heart failure compared to a placebo group. The manufacturer is expected to submit the data to the FDA by early March 2014, after which the agency will conduct a thorough analysis and report the findings. The analysis is part of a broader evaluation of all type 2 diabetes drug therapies and cardiovascular risk, and clinicians should continue to follow the prescribing recommendations in the drug labels, the agency advised.

The FDA recently recommended that clinicians not prescribe or dispense combination drug products containing more than 325 mg of acetaminophen per tablet, capsule or other dosage unit. No data show that taking such a dose provides additional benefit that outweighs the added risks for liver injury, the agency said. In January 2011, the FDA asked drug manufacturers to limit the acetaminophen in combination products to no more than 325 mg per dosage unit by Jan. 14, 2014, but not all have complied. A 2-tablet or 2-capsule dose, with a total dose of 650 mg, may still be prescribed, the agency noted.