Warnings on long-term dual antiplatelet therapy, more

This update covers the recall of rapid gram-negative combo panels, approval of an extended-release opioid analgesic, and a new rule about labeling prescription drugs related to pregnancy and lactation.

Recalls and warnings

A safety announcement on long-term dual antiplatelet therapy, after a study found a decrease in the risk of heart attacks and clot formation but increased overall risk of death with treatment for 30 months after stent implantation compared to 12 months. The FDA is continuing to evaluate available data and will communicate final conclusions and recommendations in the future. In the interim, clinicians should not change the way they prescribe these drugs, the agency said.

Photo by Thinkstock
Photo by Thinkstock

A recall of rapid gram-negative combo panels by Siemens Healthcare Diagnostics because they may produce incorrect results for certain antibiotics. The test may report certain bacteria as sensitive to aztreonam, cefotaxime, ceftazidime, and ceftriaxone when the bacteria are actually resistant.

A safety announcement about generic methylphenidate hydrochloride extended-release tablets, made by Mallinckrodt and KUDCo, because the drugs may not be therapeutically equivalent to the brand-name drug. Based on adverse event reports, a re-examination of previously submitted data, and laboratory tests, the FDA has found that the generics may deliver medication more slowly 7 to 12 hours after a dose. The therapeutic equivalence rating has been changed from AB to BX, meaning that they are still approved and can be prescribed but are no longer recommended as automatically substitutable.

A warning against using laparoscopic power morcellators to treat uterine fibroids. The devices are now contraindicated for removal of uterine tissue containing suspected fibroids in patients who are peri- or postmenopausal or candidates for en bloc tissue removal through the vagina or mini-laparotomy incision, as well as for gynecologic surgery in which the tissue to be morcellated is known or suspected to be cancerous. The warning is motivated by the risk that the procedure could spread cancerous tissue within the abdomen and pelvis.


HeartFlow FFR-CT software to non-invasively evaluate blood flow in the coronary arteries. The software can provide an estimate of fractional flow reserve (FFR) using data from a CT scan of the patient's heart. Clinicians can use the estimate, along with other patient data, to determine the likelihood that the actual FFR is below accepted limits and whether cardiac catheterization is necessary. To develop the estimate, a clinician electronically sends CT scan data to the software company, where a case analyst creates 3D computer models of different sections of the patient's heart and runs a blood flow simulator program on the models before returning a report with the estimated FFR values displayed as color images of the patient's heart. In trials comparing it to cardiac catheterization, the software was able to correctly identify 84% of the significant blockages requiring intervention and 86% of blockages not requiring intervention.

Hydrocodone bitartrate (Hysingla ER), an extended-release opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The formulation has properties that are expected to reduce, but not totally prevent, abuse. It is difficult to crush, break or dissolve and forms a viscous hydrogel and cannot be easily prepared for injection. Strengths contain 20, 30, 40, 60, 80, 100, and 120 mg of hydrocodone to be taken every 24 hours. Doses of 80 mg per day and higher should not be prescribed to opioid non-tolerant patients. The most common side effects are constipation, nausea, fatigue, upper respiratory tract infection, dizziness, headache, and somnolence. The FDA is requiring postmarketing studies to assess the effects of the abuse-deterrent features.

Blinatumomab (Blincyto) to treat Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia. Safety and effectiveness were based on a study of 185 adults in which all were treated with the drug for at least 4 weeks via infusion, after which 32% had complete remission for approximately 6.7 months. The drug carries a boxed warning about the risk for cytokine-release syndrome seen at the start of the first treatment, as well as encephalopathy or other nervous system side effects. The most common side effects were pyrexia, headache, peripheral edema, febrile neutropenia, nausea, hypokalemia, fatigue, constipation, diarrhea, and tremor. The drug is approved with a Risk Evaluation and Mitigation Strategy about the risks and the potential for preparation and administration errors.


A new rule about the labeling of prescription drugs related to pregnancy and lactation. The letter categories (A, B, C, D, and X) are being removed and drug labels will now have a pregnancy subsection, which includes information for a pregnancy exposure registry, a lactation subsection about using the drug while breastfeeding, and a new subsection with information about the need for pregnancy testing, contraception recommendations, and infertility.