New warnings for fluoroquinolones

Details on the latest recalls, warnings, and approvals.

Recalls, warnings

Image by Thinkstock
Image by Thinkstock

Strengthened warnings added to fluoroquinolone drug labels that the antibiotics may cause significant decreases in blood glucose levels and certain mental health side effects. Most fluoroquinolone drug labels include a warning about blood glucose disturbances, and the mental health side effects described differ by individual drug. The new label changes will add that hypoglycemia can lead to coma and make the mental health side effects more prominent and more consistent across the drug class. The mental health side effects that will be added or updated include disturbances in attention, disorientation, agitation, nervousness, memory impairment, and delirium.

A recall of several drug products containing valsartan due to an impurity, N-nitrosodimethylamine (NDMA), detected in products manufactured by Zhejiang Huahai Pharmaceuticals in China. NDMA is classified as a probable human carcinogen. Companies that have recalled valsartan-containing products include Major Pharmaceuticals, Teva Pharmaceuticals Industries Ltd., and Solco Healthcare. Some levels of the impurity may have been in affected products for as long as four years. Patients taking recalled medicines should continue taking their medicine until they obtain a replacement product. The FDA recommends using valsartan-containing medicines unaffected by the recall or considering other available treatment options.

A recall of two lots of neostigmine methylsulfate 5-mL syringes by Fagron Sterile Services due to incorrect labeling. Some syringe units labeled as neostigmine methylsulfate 1 mg/mL, 3 mg per 3 mL, actually contain neostigmine methylsulfate 1 mg/mL, 5 mg per 5 mL. Overdose of the cholinesterase inhibitor could result in adverse events from nausea and vomiting to cholinergic crisis resulting in death. Affected lots were distributed nationwide directly to hospitals and surgical clinics.

A warning not to use drug products intended to be sterile produced and distributed by Ranier's Compounding Laboratory (also doing business as Ranier's Pharmacy and Ranier's RX Laboratory) due to lack of sterility assurance. An FDA inspection of the compounding facility found insanitary conditions, including poor sterile production practices. The company has agreed to recall all products intended to be sterile and cease sterile operations.

A warning not to use any Monsel's solution (ferric subsulfate 20%) manufactured by BioDiagnostics International because the product was made under poor conditions. During an FDA inspection, investigators found insanitary conditions and manufacturing practices that could result in contamination and decreased quality of the product. While the manufacturer has recalled all lots of the solution, drug products distributed by MedGyn Products, Inc. may remain on the market and should not be used.


The Zephyr Endobronchial Valve to treat patients with breathing difficulties associated with severe emphysema. During a procedure in a hospital setting, a physician uses a flexible bronchoscope to place the valves, which are about the size of pencil erasers, into diseased areas of the lung airways. The device is designed to prevent inhaled air from entering damaged parts of the lungs and, during exhalation, allow trapped air and fluids to escape. In a multicenter study of patients with severe emphysema, 128 participants were treated with the device and guideline-concordant medical management while 62 control patients received medical management only. At one year, 47.7% of patients treated with the device had a 15% or greater improvement in pulmonary function scores, compared to 16.8% of control patients. Adverse events in the study included death, pneumothorax, pneumonia, worsening of emphysema, coughing up blood, shortness of breath, and chest pain. The device is contraindicated in patients with active lung infections, active smokers, patients unable to tolerate bronchoscopy, and those allergic to nitinol, nickel, titanium, or silicone.

Tecovirimat (TPOXX), the first drug indicated to treat smallpox. While the World Health Organization declared in 1980 that smallpox was eradicated, the approval stems from concerns that the virus that causes the disease could be used as a bioweapon. The orphan drug's effectiveness was established in studies of animals infected with viruses that are closely related to the virus that causes smallpox. More animals treated with the drug lived compared to those treated with placebo. Safety in humans was established in a study of 359 healthy human volunteers. The most common side effects were headache, nausea, and abdominal pain.

Ribociclib (Kisqali) in combination with an aromatase inhibitor as initial endocrine-based therapy to treat pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. The drug was also approved in combination with fulvestrant to treat postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, either as initial endocrine-based therapy or following disease progression on endocrine therapy. The approval is the first to be granted as part of two new pilot programs that aim to make the development and review of cancer drugs more efficient. In two placebo-controlled trials, participants who received the drug had longer progression-free survival than control patients. Common side effects are infections, neutropenia, leukopenia, headache, cough, nausea, fatigue, diarrhea, vomiting, constipation, hair loss, and rash.