New warnings on acetaminophen, ketoconazole

This regulatory update covers a rare but serious skin reaction for acetaminophen, as well as new limits on ketoconazole due to risks of liver injury.

Recalls, warnings and label changes

A warning on acetaminophen about risk of rare but serious skin reactions, including Stevens-Johnson Syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. The warning is based on case reports in the medical literature and the FDA's Adverse Event Reporting System. Reactions can occur with first-time use or later.


Acetaminophen should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Other drugs used to treat fever and pain/body aches (such as nonsteroidal anti-inflammatory drugs) also carry the risk of causing serious skin reactions. However, there does not appear to be cross-sensitivity between acetaminophen and these other drugs.

A warning and new limits on ketoconazole (Nizoral) oral tablets due to risks of liver injury, drug interactions and adrenal gland problems. The use of ketoconazole tablets in Candida and dermatophyte infections is no longer indicated. For other fungal infections, the tablets should be used only when alternatives are not available or tolerated by the patient. Acute or chronic liver disease is now a contraindication. Clinicians should monitor adrenal function in patients who have existing adrenal problems or are under prolonged periods of stress. All medications that a patient is currently taking should be assessed for possible interactions. The topical formulations of ketoconazole have not been associated with liver damage, adrenal problems or drug interactions.

A strengthened, boxed warning on mefloquine hydrochloride about neurologic and psychiatric side effects. Neurologic side effects may persist after stopping the drug or may become permanent and can include dizziness, loss of balance or ringing in the ears. Psychiatric side effects include feeling anxious, mistrustful, depressed or having hallucinations. If a patient develops neurologic or psychiatric symptoms, mefloquine should be stopped, and an alternative treatment should be used to prevent malaria.

A recall of two lots of Nexus Pharmaceuticals' benztropine mesylate injection, USP 2 mg/2 mL, in 2-mL single-dose vials, due to the potential presence of visible particulate matter, which poses a safety risk to patients, especially those with a preexisting condition of trauma or other medical condition that adversely affects the microvascular blood supply.

A recall of 21 lots of Nova Max glucose test strips because they may report a false, abnormally high blood glucose result, which could result in an insulin dosing error that could lead to a serious health risk requiring immediate medical attention.

A recall of Medtronic MiniMed Paradigm insulin infusion sets due to potential for over- or underdelivery of insulin. If insulin or other fluids come in contact with the inside of the tubing connector, it can temporarily block the vents that allow the pump to properly prime, which can result in too much or too little insulin being delivered.

A recall of the MedStream Programmable Infusion Pump due to malfunction in the fill level sensor, which may cause the pump's low-reservoir alarm to sound too early or too late.

A recall of all lots of certain sterile injectable products compounded by Beacon Hill Medical Pharmacy/Rxtra Solutions due to lack of sterility assurance.

A recall of LeMaitre Vascular's Albograft vascular grafts (distributed in Pennsylvania) due to blood leaking from the surface of the graft after implantation, which may cause serious adverse health consequences, including death.

A recall of some GE Healthcare nuclear medicine systems after a patient died due to injuries sustained while being scanned on an Infinia Hawkeye 4 Nuclear Medicine System. Affected products include: Infinia Nuclear Medicine Systems, VG and VG Hawkeye Nuclear Medicine Systems, Helix Nuclear Medicine Systems, Brivo NM615, Discovery NM630, Optima NM/CT640 and Discovery NM/CT670.

A recall of DePuy Orthopaedics LPS Lower-Extremity Dovetail Intercalary Component due to the potential for fracture when exposed to normal physiologic loads while walking, which may lead to additional pain, infection, loss of function, loss of limb, neurovascular injury or need for revision surgery. Patients weighing more than 200 pounds and/or those with high levels of activity are at higher risk of fracture.

A recall of Verathon, Inc., GlideScope Video Laryngoscope 3, 4, 5 and reusable blades due to the potential risk of breakage and premature failure of the blade tip. Device failure may not be readily visible during routine inspection before or after insertion of the laryngoscope, which could result in pieces of the blade breaking off in patients' mouths and being swallowed or blocking the airway.


The Xpert MTB/RIF Assay, the first U.S. test for simultaneous detection of tuberculosis (TB) bacteria and resistance to rifampin. The new test is less complex to perform than previous FDA-cleared tests for the detection of TB bacteria, and test results are available in approximately two hours.

The Neuropsychiatric EEG-Based Assessment Aid System to help assess attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years old. The 15- to 20-minute noninvasive test is based on electroencephalogram (EEG) technology and was found in a study of 275 patients to aid clinicians in making a more accurate diagnosis of ADHD when used in conjunction with a clinical assessment, compared with doing the clinical assessment alone.

Afatinib (Gilotrif) for metastatic non-small-cell lung cancer (NSCLC) tumors that express specific epidermal growth factor receptor (EGFR) gene mutations. The drug is being approved concurrently with a companion diagnostic test to determine if a patient's lung cancer cells express the EGFR mutations. Safety and effectiveness were established in a study of 345 patients, in which progression-free survival was 4.2 months longer with the drug than with chemotherapy. There was no statistically significant difference in overall survival. Common side effects include diarrhea, skin breakouts that resemble acne, dry skin, pruritus, inflammation of the mouth, paronychia, decreased appetite, decreased weight, cystitis, nose bleed, runny nose, fever, eye inflammation and hypokalemia.

The Verify Cronos Self-Contained Biological Indicator (SCBI), to speed the determination of whether steam sterilization of reusable medical devices is effective. The SCBI is used in medical device reprocessing and provides results in two hours.


The manufacturer of phentermine and topiramate extended-release capsules (Qsymia) reminds physicians about the drug's risks of teratogenicity and recommended steps to ensure safe and appropriate use. The Qsymia Healthcare Provider Training Program is available online. The drug is now available through certified retail pharmacies in addition to mail-order pharmacies, but certified pharmacies must provide a Medication Guide and the “Risk of Birth Defects with Qsymia” patient brochure with every prescription and every refill.