Warnings on testosterone, new antibiotic approved

Recalls, warnings and label changes

A label change on testosterone products clarifying that they are approved only for men who have low testosterone levels due to disorders of the testicles, pituitary gland, or brain, and warning about possible increased risk of heart attacks and strokes associated with the drugs.

A label change for varenicline (Chantix) warning about the drug's potential alcohol interaction, rare risk of seizures, and ongoing research into side effects on mood, behavior, or thinking. Clinicians should advise patients to reduce their consumption of alcohol when beginning the drug, and to stop taking the drug if they develop changes in mood or behavior. The risk of seizures should be weighed against the potential benefits of varenicline in patients with particular risk of seizure.

A safety communication about endoscopic retrograde cholangiopancreatography (ERCP) duodenoscopes and the risk that their design may impede effective reprocessing. Multidrug-resistant bacterial infections have been reported, even when reprocessing instructions are followed correctly. The FDA is actively monitoring the situation and working with other government agencies and manufacturers to identify the causes and risk factors for transmission and to develop solutions. In the interim, clinicians should inform patients of the benefits and risks of ERCP, and discuss symptoms of infection to watch for after a procedure.

A warning that Treanda (bendamustine hydrochloride) injections (45 mg/0.5 mL or 180 mg/2 mL solution) should not be used with closed system transfer devices, adapters, and syringes that contain polycarbonate or acrylonitrile-butadiene-styrene (ABS), which most do. Devices that contain polycarbonate or ABS dissolve when coming into contact with N, N-dimethylacetamide, an ingredient in the injections. This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in clinicians preparing and administering this product. The FDA recommends only using a polypropylene syringe with a metal needle and polypropylene hub to withdraw and transfer these injections.

A recall of certain lots of colistimethate and rifampin for injection by Heritage and 2 lots of atracurium besylate injection by Sagent due to a lack of sterility assurance based on FDA observations at the manufacturer, Emcure Pharmaceuticals.

A recall of ketorolac tromethamine injection by Hospira due to customer reports of a particulate, which was identified as calcium-ketorolac crystals.

A recall of 1 lot of 0.9% sodium chloride injection by Hospira due to a single confirmed customer report of particulate, which was found to be a human hair.

A recall of 1 lot of magnesium sulfate in 5% dextrose by Hospira due to an incorrect barcode. The barcode on the overwrap is correct and the printed name on the overwrap and container is correct. However, the primary container may be mislabeled with the barcode for heparin sodium.

A label change on multi-dose diabetes pen devices warning against sharing the devices, which are intended for single patient use only.

A recall of Maquet Servo 163 humidifiers due to connector cracks and cracks in connector tubes, which have been found when preparing patients for support with a ventilator and may lead to oxygen and other gases leaking from the ventilator.

A recall of Plum A+ and Plum A+3 infusion systems by Hospira because alarms may fail to sound in situations that should trigger them.

A recall of Trellis 6 and Trellis 8 peripheral infusion systems due to the balloon inflation ports being mislabeled, which may cause a physician using the device to deflate the balloons in the incorrect order. If this happens, there is a potential for blood clots to dislodge and move into the lungs.

A recall of magnetic resonance imaging (MRI) systems with magnet rundown unit (MRU) by GE Healthcare because some MRI units may have been modified by service personnel or by equipment users to disable the MRU, which is used to shut off the magnetic field of the MRI in case of an emergency, such as when a ferrous object is brought into the magnetic field.

A recall of older HeartWare ventricular assist system controllers because they exhibit a higher susceptibility to electrostatic discharge than newer controllers, which could result in a pump stop.

Approvals

Isavuconazonium sulfate (Cresemba), to treat invasive aspergillosis and invasive mucormycosis. This azole antifungal agent is available in oral and IV formulations. Approval for aspergillosis was based on a trial with 516 patients randomized to the new drug or voriconazole, and approval for mucormycosis was based on a trial with 37 patients comparing the drug to untreated mucormycosis, both of which showed it to be safe and effective. The most common side effects include nausea, vomiting, diarrhea, headache, abnormal liver blood tests, hypokalemia, constipation, dyspnea, coughing, and peripheral edema. The drug may also cause serious side effects including liver problems, infusion reactions, and severe allergic and skin reactions.

Ceftazidime-avibactam (Avycaz) to treat complicated intra-abdominal infections (cIAI), in combination with metronidazole, and complicated urinary tract infections (cUTI) including pyelonephritis. It is indicated for patients who have limited or no alternative treatment options. The most common adverse events are vomiting, nausea, constipation, and anxiety, and patients with poor renal function or penicillin allergies may have adverse reactions.

An expanded use for the Cepheid Xpert MTB/RIF test to determine if patients with suspected tuberculosis (TB) can be removed from airborne infection isolation. Clinicians may now use 1 or 2 negative results on the test to remove a patient from isolation. Approval was based on a study showing that a single negative MTB/RIF test predicted the absence of Mycobacterium tuberculosis on acid-fast bacilli smears 99.7% of the time, and 2 consecutive negative results predicted the absence of the bacteria 100% of the time. The decision whether 1 or 2 tests are necessary should be based on the specific patient being tested and hospital guidelines.

The Eclipse System, a fecal incontinence (FI) device for women. It is intended to treat women 18 to 75 years old who have had 4 or more FI episodes in a 2-week period. The device includes an inflatable balloon, which is placed in the vagina and exerts pressure through the vaginal wall onto the rectal area. Approval was based on a trial with 61 women, of whom almost 80% experienced a 50% decrease in FI episodes during a month of device use. Adverse events included pelvic cramping and discomfort; pelvic pain; vaginal abrasion, redness, or discharge; and urinary incontinence.

The VenaSeal system to permanently treat superficial varicose veins of the legs that cause symptoms. The sterile kit is made up of an adhesive and delivery system components that include a catheter, guidewire, dispenser gun, dispenser tips, and syringes. A clinician inserts the catheter through the skin into the diseased vein to allow injection of the adhesive. Approval was based on a trial comparing the system to radio-frequency ablation, which showed it to be safe and effective. It should not be used in patients who have a known hypersensitivity to the adhesive, acute inflammation of the veins due to blood clots, or acute whole-body infection. Adverse events included phlebitis and paresthesia in the treatment zone.

ResQCPR System, 2 devices for out-of-hospital, non-traumatic cardiac arrest. The first device, the ResQPump Active Compression Decompression CPR Device, attaches to the patient's chest with a suction cup, allowing the rescuer to push to deliver compressions and lift for decompressions. It also has a pressure gauge and timing mechanism. The second device, the ResQPod 16.0 Impedance Threshold Device, impedes airflow into the chest during chest decompression, reducing the pressure inside the patient's chest and drawing more blood back to the heart. Approval was based on a clinical trial showing that patients who received CPR with the devices were more likely to survive than those getting standard CPR, although there was a higher rate of pulmonary edema.

Lenvatinib (Lenvima) to treat progressive, differentiated thyroid cancer that is radioactive iodine refractory. Approval is based on a trial of 392 patients in which those on the drug had a median progression-free survival of 18.3 months and 65% had a reduction in tumor size, compared to 3.6 months and 2%, respectively, on placebo. The most common side effects were hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, and dysphonia. The drug may also cause serious side effects, including cardiac failure, arterial thromboembolic events, hepatotoxicity, renal failure and impairment, gastrointestinal perforation or fistula formation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, and hemorrhage.

Panobinostat (Farydak) to treat multiple myeloma. It is a histone deacetylase inhibitor and is intended for patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent. It is to be used in combination with bortezomib and dexamethasone. Approval was based on a trial of 193 patients, which found that those who took panobinostat with bortezomib and dexamethasone had 10.6 months progression-free survival and 59% response rate compared to 5.8 months and 41%, respectively, on bortezomib and dexamethasone. The drug carries a boxed warning about severe diarrhea and cardiac risks. The most common side effects were diarrhea, tiredness, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting and weakness.

Filgrastim-sndz (Zarxio), a biosimilar product to filgrastim (Neupogen). This is the first FDA approval of a biosimilar product and it is approved to treat the same indications as filgrastim, which was licensed in 1991. Approval is based on a review that found structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data demonstrated biosimilarity to filgrastim. Filgrastim-sndz was designated by the FDA as a placeholder nonproprietary name for the drug.

An expanded indication for nivolumab (Opdivo) to treat metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy. Approval is based on a trial of 272 patients in which those taking the drug lived 3.2 months longer than those on docetaxel. The most common side effects are fatigue, shortness of breath, musculoskeletal pain, decreased appetite, cough, nausea, and constipation. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands. The drug was previously approved to treat unresectable or metastatic melanoma.

A direct-to-consumer test from 23andMe to determine if someone is a genetic carrier for Bloom syndrome. The FDA also announced it will be exempting carrier tests from premarket review. The agency is requiring that the manufacturer explain to the consumer in the product labeling what the results might mean for prospective parents, and if the test is sold over-the-counter, to provide information about how to obtain access to a board-certified clinical molecular geneticist or equivalent to assist in pre- and post-test counseling.

Lixelle Beta 2-microglobulin Apheresis Column, a device to treat dialysis-related amyloidosis. The device removes beta 2-microglobin from the blood during hemodialysis. Approval is based on data from 300 patients in Japan, which generally showed improvement in symptoms with use of the device. The most common adverse events are temporary hypotension and a decrease in hematocrit.

Miscellaneous

The FDA recently launched a mobile app to provide information about drug shortages. The app identifies current drug shortages, resolved shortages, and discontinuations of drug products. App users can search or browse by a drug's generic name or active ingredient, and browse by therapeutic category. The app can also be used to report a suspected drug shortage or supply issue to the FDA. The app is available for free via iTunes or the Google Play store by searching “FDA Drug Shortages.”