New COPD treatment, warnings on insomnia and migraine drugs

This regulatory update covers approval of a combined long-term maintenance treatment for chronic obstructive pulmonary disease, warnings against driving after taking insomnia drugs and on use of migraine drugs in pregnant women, and more.

Recalls, warnings and label changes

A warning on ezogabine (Potiga) about the risk of blue skin discoloration and eye abnormalities characterized by pigment changes in the retina, which may or may not be reversible. All patients taking ezogabine should have baseline and periodic eye exams.


Recalls of all sterile products from The Compounding Shop, Balanced Solutions, ApothéCure, Inc., and Green Valley Drugs, as well as all lyophilized products from NuVision Pharmacy, due to concerns about a lack of sterility assurance.

A recall of Abbott FreeStyle Insulinx blood glucose meters because at extremely high blood glucose levels of 1,024 mg/dL and above, the meters will display and store in memory an incorrect test result that is 1,024 mg/dL below the measured result.

A labeling change on tolvaptan (Samsca) due to observation of increased risk of liver injury. Tolvaptan should not be used for longer than 30 days or in patients with underlying liver disease, including cirrhosis. It's also recommended that clinicians discontinue the drug in patients with symptoms of liver injury.

A new warning for zolpidem extended-release (Ambien CR) that patients who take either 6.25-mg or 12.5-mg doses should not drive or engage in other activities that require complete mental alertness the day after taking the drug because zolpidem levels can remain high enough to impair these activities.

A new contraindication for valproate sodium, valproic acid and divalproex sodium (Depacon, Depakote, Depakene and Stavzor) for prevention of migraine headaches in pregnant women. The drugs' pregnancy category for migraine use was changed from “D” (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to “X” (the risk of use in pregnant women clearly outweighs any possible benefit of the drug) based on evidence that they decreased IQ scores in children whose mothers took them while pregnant. Valproate products will remain in category D for treating epilepsy and manic episodes associated with bipolar disorder.

A drug safety communication about the risk of name confusion between ado-trastuzumab emtansine (Kadcyla) and trastuzumab (Herceptin). Some publications and information systems (including electronic medical records) are incorrectly using the United States Adopted Name for Kadcyla, trastuzumab emtansine, omitting the “ado” prefix and hyphen. Use of this truncated version may cause confusion with trastuzumab. The dosing and treatment schedules for the drugs are different, so confusion could lead to dosing errors and harm to patients. Clinicians should use both the FDA-approved proprietary name Kadcyla and its nonproprietary name (ado-trastuzumab emtansine) when communicating medication orders, on preprinted order sets and in computerized order entry systems.

A recall of certain Power Pac batteries for the Newport HT70 and HT70 Plus ventilators, after customer reports of ventilators alarming and going to internal backup battery sooner than expected. Users should ensure that alternate sources of power, including required power cords, are available nearby until this issue is resolved.

A class I recall of CareFusion Alaris PC Unit with software version 9.12 due to reports of a communication error when the unit is attached to the Alaris EtCO2 module or the Alaris SpO2 module. When the unit experiences a communication error, the infusion will continue as programmed. However, no further key presses have an effect on the system except for the System On key.

A recall of Cook Medical's Zilver PTX drug-eluting peripheral stent due to reports that the delivery system of the device had separated at the tip of the inner catheter.

A class I recall of Hospira's GemStar infusion system because when battery voltage level drops below 2.4 volts, an “11/004” error is displayed and the device is rendered inoperable. This failure mode results in a delay or interruption of therapy.

A recall of 15 lots of piperacillin and tazobactam for injection, USP 40.5 g, due to possibility of precipitation or crystallization in IV bags or lines upon reconstitution.

A recall of one lot of Fenwal's citrate phosphate dextrose solution, USP (CPD) BLOOD-PACK unit, due to a labeling issue with this batch in which the platelet container is incorrectly labeled as “AS-1 Red Blood Cell Adenine-Saline added.”

A class I recall of Cardinal Health's Presource Kits containing a pre-assembled anesthesia circuit and filter because of outer plastic packaging on one or more components. If the packaging is removed without dissembling the components, remnants of the plastic may become lodged in the filter, potentially causing an obstruction in airflow. This may result in serious adverse health consequences, including hypoxia, suffocation and death.

A warning that one lot of Covidien Endo GIA Articulating 60-3.5 surgical stapler reloads were stolen from the manufacturer before they were sterilized. Some of these stolen and unsterile products have been offered for sale. The use of these nonsterile products could increase the risk of infection in surgical patients.

A class I recall of Medtronic Deep Brain Stimulation Lead and Activa Dystonia HDE kits due to the use of the lead cap provided. Leads have been damaged at the connector end of the lead when the lead cap is used. Lead replacement may be required or optimal therapy may not be provided.

A class I recall of Maquet SERVO-i ventilator battery modules because some have been found to have a shorter battery run time than expected. This can result in unexpected ventilator shutdowns, which can have serious adverse health consequences, including death.

A class I recall of ShapeMatch cutting guides due to one software defect that results in wider cutting ranges and another that results in displayed parameters not matching the cutting guides. This may result in serious adverse health consequences, including joint instability, fracture, need for revision surgery and chronic pain and limitations of mobility.


Combined fluticasone furoate and vilanterol inhalation powder (Breo Ellipta) for the long-term maintenance treatment of chronic obstructive pulmonary disease (COPD) and to reduce exacerbations of COPD. Safety and efficacy were evaluated in a study of 7,700 patients in which those treated showed improved lung function and reduced exacerbations compared to placebo. The once-daily drug carries a boxed warning that long-acting beta2-adrenergic agonists increase asthma-related death. The drug may cause serious side effects, including pneumonia and bone fractures. The most common side effects are nasopharyngitis, upper respiratory tract infection, headache and thrush.

An alternative to plasma (prothrombin complex concentrate, human; brand name, Kcentra) for the urgent reversal of vitamin K antagonist anticoagulation in adults with acute major bleeding. Unlike plasma, Kcentra does not require blood group typing or thawing, so it can be administered more quickly, and it is administered in significantly lower volume than plasma. Kcentra is associated with the occurrence of blood clots when used as indicated and carries a boxed warning regarding this risk. The warning also explains that patients should be monitored for signs and symptoms of thromboembolic events. Kcentra is made from the pooled plasma of healthy donors, and approval was based on a study of 216 patients in which it was demonstrated to be similar to plasma in its ability to stop acute major bleeding.

A new nimodipine oral solution (Nymalize) to treat symptoms of subarachnoid hemorrhage. Nimodipine previously was available only as a liquid-filled gel capsule. The FDA had previously received reports of serious and sometimes fatal consequences from IV injection of the liquid contents of oral nimodipine capsules. The new drug is administered orally, or via nasogastric tube or gastric tube, which is expected to reduce the risk of medication errors. The most common adverse event is decreased blood pressure. Blood pressure should be carefully monitored during treatment.

Cysteamine bitartrate (Procysbi) for the management of nephropathic cystinosis in children and adults. This orphan product is a delayed-release capsule intended for patients ages 6 years and older and is taken every 12 hours.


Damaged or worn medical bed mattress covers pose risks of contamination and infection, the FDA recently warned. From January 2011 to January 2013, the agency received 458 reports associated with medical bed mattress covers failing to prevent blood and body fluids from leaking into the mattress. Some reports indicate that if blood and body fluids from one patient penetrate a mattress, they can later leak out from the mattress when another patient is placed on the bed. The FDA is concerned that fluid ingress from worn or damaged medical bed mattress covers may be widespread and largely under-recognized.

The FDA offered several recommendations for inspection and maintenance:

  • Regularly check each medical bed mattress cover for any visible signs of damage or wear such as cuts, tears, cracks, pinholes, snags or stains.
  • Routinely remove the medical bed mattress cover and check its inside surface. Once the mattress cover is removed, inspect the mattress for wet spots, staining, or signs of damage or wear. Check all sides and the bottom of the mattress.
  • Immediately replace any medical bed mattress cover with visible signs of damage or wear to reduce the risk of infection to patients.
  • Do not stick needles into a medical bed mattress through the mattress cover.