Warnings on insomnia meds, pacemaker battery depletion

This column reviews details on recent recalls, warnings, and approvals.

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 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 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).


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 athroat 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)