Recalls, warnings, and alerts
A new boxed warning for certain prescription insomnia medications due to the risk of rare but serious injuries caused by sleepwalking, sleep driving, and engaging in other activities while not fully awake. These complex sleep behaviors have also resulted in deaths and appear to be more common with eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist) than with other prescription medicines used for sleep. These sedative-hypnotics will now include a boxed warning in the prescribing information and the patient medication guides.
An alert about potential premature battery depletion of certain Medtronic implantable pacemakers. There have been at least three related events where clinicians were unable to communicate with the device due to battery depletion, and one resulted in the death of a pacemaker-dependent patient. These events occurred within a year of the device being implanted, whereas the pacemakers are designed to last between about 7.5 and 15 years or 6 and 10 years before requiring battery replacement, depending on the device and the amount of pacing. About 132,000 devices have been sold in the U.S. to date, and prophylactic removal and replacement of affected devices are not recommended. Clinicians should carefully monitor battery status using home monitoring systems. To reduce risk of this issue, the FDA approved a new step in the manufacturing process developed to better detect capacitor failures in newly manufactured devices.
A class I recall of UniCel DxH 800, DxH 600, and DxH 900 hematology analyzers by Beckman Coulter Life Sciences due to risk of inaccurate results. The analyzers sporadically produced erroneously elevated platelet count results without flags or system messages. The recall includes 3,428 devices distributed from January 2008 to present (DxH 800 and DxH 600) and from April 2018 to present (DxH 900).
A recall of all sterile compounded drugs by Pharm D Solutions dispensed from Oct. 24, 2018, to May 21, 2019. A routine FDA inspection led to concerns that practices at the pharmacy have the potential to pose a risk of contamination to products that are intended to be sterile. Recalled products were distributed nationwide.
A class I recall of the LimiTorr Volume Limiting CSF Drainage System and the MoniTorr ICP External CSF Drainage and Monitoring System by Integra LifeSciences due to device failure. Serious patient injuries related to breakage of the devices have been associated with infection and cerebrospinal fluid leakage. The recall includes 24,587 devices distributed from March 1, 2017, to March 31, 2019.
A class I recall of EV1000 Clinical Platforms by Edwards Lifesciences due to the risk of fluids leaking into the AC power outlet. Use of the EV1000A, EV1000NI, or EV1000CS models may result in electrical short circuit, potentially causing them to stop working or catch fire. The recall includes 11,000 devices distributed from Nov. 5, 2010, to March 4, 2019.
A class I recall of circular staplers by Ethicon due to insufficient firing and failure to completely form staples. The recall of the Endo-Surgery and Endo-Surgery Endoscopic Curved Intraluminal Staplers includes 92,496 devices distributed from March 15, 2018, to March 8, 2019.
A recall of three lots of eltrombopag (Promacta) for oral suspension by Novartis due to the risk of potential peanut flour contamination that occurred at a third-party contract manufacturing site. Only the 12.5-mg formulation for oral suspension is impacted by the recall.
A recall of one lot of mycophenolate mofetil for injection USP by Par Pharmaceutical, Inc., at the hospital and retail pharmacy level. A glass fragment was observed in one vial of reconstituted product. Recalled products were distributed nationwide between Jan. 23, 2019, and Feb. 11, 2019.
A recall of 19 lots of losartan potassium tablets (25 mg, 50 mg, 100 mg) by Heritage Pharmaceuticals due to the detection of an impurity, N-Nitroso-N-methyl-4-aminobutyric acid, a potential human carcinogen. The lots were manufactured by Vivimed Life Sciences in India.
A recall of one lot of ketorolac tromethamine injection USP (60 mg/2 mL [30 mg per mL]) by Sagent Pharmaceuticals due to lack of sterility assurance. Microbial growth was detected during a routine simulation of the manufacturing process. Recalled products were distributed nationwide from January through March 2019.
A warning that patients should not use unauthorized devices for diabetes management, either alone or with authorized devices. Clinicians should be aware that use of unauthorized devices could result in inaccurate glucose level readings or unsafe insulin dosing, potentially leading to death or injury requiring medical intervention. In one report, a patient used an unauthorized device that received the electronic signal from an FDA-authorized glucose sensor and converted it to a glucose value using an unauthorized algorithm. These glucose values were sent to an unauthorized automated insulin-dosing device, which gave too much insulin, resulting in an insulin overdose requiring medical intervention.
A recall of two unreleased batches of injection drugs by Heritage Pharmaceuticals due to sterility test failure. Microbial growth was detected in one sublot of amikacin sulfate injection USP (1 gm/4 mL [250 mg/mL]) and one sublot of prochlorperazine edisylate injection USP (10 mg/2 mL [5 mg/mL]).
A final rule on over-the-counter (OTC) hand sanitizers. The rule finalized the FDA's previous determination that 28 active ingredients, including triclosan and benzethonium chloride, are ineligible to be evaluated for use in consumer antiseptic rubs. In addition, three active ingredients (benzalkonium chloride, ethyl alcohol, and isopropyl alcohol) will be deferred from further rulemaking to allow for ongoing study and data submission. Fewer than 3% of the marketplace will be affected by the issuance of this final rule, as most OTC hand sanitizers use ethyl alcohol as the active ingredient.
An update on postmarket surveillance study results for reprocessed duodenoscopes, which showed an increase in the percentage of samples that tested positive for bacteria. Up to 5.4% of all properly collected samples of the duodenoscopes tested positive for high-concern organisms. This rate is significantly higher than the 3% contamination rate reported in December 2018. In addition, up to 3.6% of properly collected samples tested positive for low- to moderate-concern organisms, which typically do not lead to dangerous infections but are indicative of a reprocessing failure. In December, this rate was reported to be up to 3%. When these sampling studies were designed, the agency expected to see a total contamination rate of less than 1% for any type of organism. The results show that improvements are necessary, and the FDA is exploring additional steps to reduce contamination rates. Final results of root-cause analyses from the manufacturers are expected later in 2019.
A safety communication regarding cybersecurity vulnerabilities affecting implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators by Medtronic. These vulnerabilities have been identified in a wireless telemetry technology used for communication among the company's implantable cardiac devices, clinic programmers, and home monitors. The FDA recommends that clinicians and patients continue to use these devices as intended and follow device labeling.
Tafamidis meglumine (Vyndaqel) and tafamidis (Vyndamax) capsules to treat adults with cardiomyopathy caused by transthyretin-mediated amyloidosis. These are the first FDA-approved treatments for this condition. In a trial of 441 patients, the survival rate was higher in those who received tafamidis meglumine than those in the placebo group. The drug was also associated with a reduction in the number of hospitalizations for cardiovascular problems. While no drug-associated side effects were identified, the orphan drug may cause fetal harm.
Marketing of two tests that can detect the presence of Chlamydia trachomatis and Neisseria gonorrhoeae through diagnostic testing of extragenital specimens. The Aptima Combo 2 Assay and the Xpert CT/NG are the first devices cleared for extragenital diagnostic testing of chlamydia and gonorrhea via the throat and rectum. The tests were previously only cleared for testing urine, vaginal, and endocervical samples.
Alpelisib (Piqray) tablets in combination with fulvestrant to treat certain types of breast cancer. The drug is the first PI3K inhibitor approved to treat breast cancer. It is indicated for postmenopausal women and men with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen. The FDA also approved a companion diagnostic test, the therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who test negative should have tumor biopsy for PIK3CA mutation testing. In a randomized trial of 572 participants, adding the drug to fulvestrant significantly prolonged progression-free survival compared to fulvestrant and placebo (median of 11 months vs. 5.7 months). Common side effects include hyperglycemia, increase in creatinine, diarrhea, rash, decrease in lymphocyte count in the blood, elevated liver enzymes, nausea, fatigue, low red blood cell count, and increase in lipase. The drug's safety has not been established in patients with type 1 or uncontrolled type 2 diabetes.
First-time generic approvals
Amoxicillin and clavulanate potassium for oral suspension USP (125 mg/31.25 mg per 5 mL, 250 mg/62.5 mg per 5 mL) to treat lower respiratory tract infections, acute bacterial otitis media, sinusitis, skin and skin structure infections, and urinary tract infections. (Brand name: Augmentin)
Bosentan tablets (62.5 mg, 125 mg) to treat pulmonary arterial hypertension. (Brand name: Tracleer)
Pentamidine isethionate for inhalation solution (300 mg/vial) for the prevention of Pneumocystis jiroveci pneumonia (PJP) in high risk, HIV-infected patients defined by one or both of the following criteria: a history of one or more episodes of PJP, or a peripheral CD4+ lymphocyte count less than 200 cells/mm3. (Brand name: NebuPent)
Loteprednol etabonate ophthalmic suspension (0.5%) to treat steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe, such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, and cyclitis. (Brand name: Lotemax)
Valrubicin intravesical solution USP (200 mg/5 mL [40 mg/mL] in single-dose vials) for the intravesical therapy of BCG-refractory carcinoma in situ of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. (Brand name: Valstar)
Rufinamide oral suspension (40 mg/mL) for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. (Brand name: Banzel)
Note: The FDA states that drugs are not always commercially available immediately after approval.