Recalls and Safety Alerts from the FDA

Jennifer Kwon, PharmD BCOPJennifer Kwon, PharmD BCOP
Hematology/Oncology Clinical Pharmacy Specialist
VA Medical Center
West Palm Beach, FL

RECALLS

Fluorouracil Injection (Adrucil)
Teva Parenteral Medicines issued a voluntary recall of six lots of fluorouracil injection (5 g/100 mL) because of the potential presence of silicone rubber pieces from a filter diaphragm and fluorouracil crystals. There have been no adverse events reported. For a full list of recalled products, visit, http://www.fda.gov/ Safety/ Recalls/ucm456093.htm.

Gemcitabine and Methotrexate
Mylan has issued a voluntary recall of select lots of injectable products, including gemcitabine and methotrexate, because of the presence of visible particles observed during a routine quality test. Lots of gemcitabine for injection were distributed in the United States. between January 8, 2014, and February 10, 2015. Methotrexate lots were distributed in the United States between December 8, 2014, and December 19, 2014. There have been no adverse events reported related to this recall. http://www.fda.gov/ Safety/ Recalls/ucm450140.htm

Moses Lake Professional Pharmacy Recall in Washington
Moses Lake Professional Pharmacy of Moses Lake, WA, voluntarily recalled certain unexpired human and veterinary sterile compounded drugs. This recall was a result of the lack of sterility assurance. These products were made from July 21, 2014, through July 21, 2015, and dispensed to patients or distributed to physicians in Arizona, Idaho, Florida, Oregon, Texas, and Washington. There have been no adverse events reported from the recalled products. For a complete listing of affected drugs, visit: http://www.fda.gov/ Safety/ Recalls/ucm455925.htm

SAFETY ALERTS

Anagrelide (Agrylin)
The clinical trial subsection under the adverse reactions section has been edited to list other less frequent adverse reactions (<1%) in both cardiac disorders (ventricular tachycardia, supraventricular tachycardia) and nervous system disorders (hypothesia). http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm175918. htm

Brentuximab (Adcetris)
Due to reports of fatal outcomes related to respiratory issues with brentuximab use, updates have been made in the warning and precautions section along with the adverse reactions section to address pulmonary toxicity. Pneumonitis, interstitial lung disease, and acute respiratory distress syndrome can occur and patients receiving brentuximab should be closely monitored for signs and symptoms of pulmonary toxicity. The medication should be held in the event of new or worsening pulmonary symptoms. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm426241. htm

Cabazitaxel (Jevtana)
Cabazitaxel is now contraindicated for use in patients with severe he- patic impairment (total bilirubin >3 ULN). Recommendations for use in patients with mild and moderate hepatic impairment have been added to the warning and precautions section of the prescribing infor- mation. Dose reductions should be made in the setting of mild (total bilirubin > 1 to ≤ 1.5 x ULN or AST > 1.5 x ULN) and moderate (total bilirubin > 1.5 to ≤ 3.0 x ULN and any AST) hepatic impairment. The updated warnings and precautions section includes bone marrow sup- pression, specifically neutropenia and its clinical consequences. Blood counts should be monitored carefully to determine if dose modifi- cations or G-CSF is needed. Patients with high-risk clinical features should be considered to receive prophylaxis with G-CSF. The use of cabazitaxel should also be used with caution in patients with hemoglo- bin <10 g/dL. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm392358.htm

Ceritinib (Zykadia)
Updates have been made to the warnings and precautions section of the package insert for ceritinib. The update includes the risk of hepa- totoxicity, QT interval prolongation, hyperglycemia, and pancreatitis. The clinical trials had less than 1% of patients having concurrent el- evations in ALT greater than three times the ULN and total bilirubin greater than two times the ULN with normal alkaline phosphatase. QTc interval prolongation occurred in patients receiving ceritinib in clinical trials and should be monitored throughout treatment as it can lead to cardiac arrhythmia and sudden death. Serum glucose levels should be routinely monitored before and throughout treatment with ceritinib since hyperglycemia can occur. The clinical trials also showed pancreatitis occurring in less than 1% of patients on ceritinib, but there has been one report of a pancreatitis-related fatality. There are recom- mendations to monitor lipase and amylase prior to starting treatment with ceritinib and periodically during treatment. Depending on the se- verity of laboratory abnormalities, the medication should be held and dose reduction recommendations can be found in Table 1 of the pack- age insert. Due to the potential seriousness of pancreatitis, the patient counseling information recommends that patients starting therapy with ceritinib be counseled on the signs and symptoms of pancreatitis. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ ucm458065.htm

Darbepoetin alfa (Aranesp)
The increased possibility of mortality, myocardial infarction, stroke, and thromboembolism has been edited in the warnings and precau- tions section to specify “adult patients” in Table 2 of the package labeling. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm458055.htm