Recalls and Safety Alerts from the FDA

Exemestane (Aromasin)
The “Warnings and Precautions” section for exemestane now recommends that women with osteoporosis or those at risk of osteoporosis undergo a formal assessment of their bone mineral density by bone densitometry when initiating therapy. Patients should be monitored for bone mineral density loss and treated as indicated. Additionally, postmarketing reports of paresthesia and acute generalized exanthematous pustulosis have been added to the prescribing information.
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm250607.htm

 Crizotinib (Xalkori)
The “Clinical Pharmacology Drug Interactions” section of the package insert has been revised to include information regarding the potential for crizotinib to inhibit uridine diphosphate glucuronosyl-transferase (UGT) enzymes, as well as other hepatic and renal transporters. Additionally, updated safety margins for pregnant and pediatric patient populations have been included within the “Use in Specific Populations” section of the package insert.
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm295722.htm

 Docetaxel Intoxication
The U.S. Food and Drug Administration (FDA) has issued a safety announcement to warn that docetaxel contains ethanol and may cause patients to feel intoxicated or drunk during and after treatment. Product label revisions are being made to warn about the risk. Healthcare professionals (HCPs) should take this into consideration when prescribing and administering docetaxel, especially in patients in whom alcohol intake should be avoided or minimized, and when used in combination with certain drugs. Patients should be monitored for signs of alcohol intoxication during and after treatment. Alcohol content may vary between formulations. In patients who experience this adverse reaction, HCPs may consider using a docetaxel formulation with the lowest alcohol content and slowing the infusion rate during administration. Patients should be notified about the alcohol content in docetaxel and the potential for this to affect the central nervous system. Patients should be advised to avoid driving, operating machinery, and performing activities that are dangerous or require skill for 1 to 2 hours after the infusion.
http://www.fda.gov/ Drugs/ DrugSafety/ucm401752.htm

Gemcitabine (Gemzar)
The “Warnings and Precautions,” “Adverse Reactions,” and “Dose Modifications” sections of gemcitabine’s prescribing information have been updated to include information on the risk for posterior reversible encephalopathy syndrome (PRES). PRES has been reported with single-agent gemcitabine, as well as in combination with other chemotherapy agents. If PRES develops during therapy with gemcitabine, it is recommended to permanently discontinue the agent.
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm356107.htm

Denosumab (Xgeva) Hypocalcemia with Renal Dysfunction
The prescribing information for denosumab (Xgeva) has been revised to update information on the risk for hypocalcemia in the “Warnings and Precautions” and “Use in Specific Populations” sections. There is an increased risk for the development of hypocalcemia in patients with renal dysfunction, most commonly in patients with severe impairment—defined as those with a creatinine clearance less than 30 mL/min and/or those on dialysis—and with inadequate or no calcium supplementation. Calcium levels should be monitored and supplemented with calcium and vitamin D as needed.
http://www.fda.gov/safety/medwatch/safetyinformation/ucm343116. htm

Denosumab (Prolia) Musculoskeletal Pain
The “Warnings and Precautions” section of the prescribinginformation for denosumab (Prolia) has been revised to include postmarketing reports of severe and possibly incapacitating bone, joint, and muscle pain. Severe symptoms may warrant therapy discontinuation. http://www.fda.gov/safety/medwatch/safetyinformation/safety-relateddruglabelingchanges/ucm307218.htm

Eculizumab (Soliris) Recall
Alexion Pharmaceuticals, Inc., has issued a voluntary recall of certain lots of eculizumab distributed in the United States. This was due to the use of a process component during vial filling that resulted in the presence of visible particles. The company has identified the problem and is implementing a process change. There have been no safety risks identified in patients who have received eculizumab. There are no anticipated interruptions in patient supply.
http://www.fda.gov/safety/recalls/ucm399527.htm

Sunitinib (Sutent) Proteinuria and Dermatologic Toxicities
Proteinuria and dermatologic toxicities, including Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis,and necrotizing fasciitis, have been added to the “Warnings and Precautions and Medication Guide” of sunitinib’s package insert.
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm224050.htm

Docetaxel Respiratory Adverse Reactions
There have been additional respiratory adverse reactions reported in postmarketing surveillance of docetaxel. The package insert has been updated and now includes the following statement: “Dyspnea, acute pulmonary edema, acute respiratory distress syndrome/pneumonitis, interstitial lung disease, interstitial pneumonia, respiratory failure, and pulmonary fibrosis have rarely been reported and may be associated with fatal outcome. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.”
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ ucm396551.htm

Temozolomide (Temodar) Hepatotoxicity
The “Warnings and Precautions” section for temozolomide’s package insert has been updated to include the risk of fatal and severe hepatotoxicity reported in patients receiving this agent. Recommended monitoring includes liver function tests at baseline, midway through the first cycle, prior to each subsequent cycle, and approximately 2 to 4 weeks after the last dose of temozolomide. A case control study is being conducted to determine the correlation between temozolomide and severe acute liver injury.
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm211909.htm

Thalidomide Venous and Arterial Thromboembolism Update
Updates have been made to the “Warnings and Precautions—Venous and Arterial Thromboembolism” section of the package insert for thalidomide. The update includes the following information: “Ischemic heart disease (11.1%), including myocardial infarction (1.3%) and stroke (cerebrovascular accident, 2.6%) have also occurred in patients with previously untreated mutliple myeloma treated with Thalomid and dexamethasone compared to placebo and dexamethasone (4.7%,1.7%, and 0.9%, respectively) in one clinical trial.”
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm402899.htm

Topotecan (Hycamtin) Renal Impairment
Revisions to the dosing recommendations in renal impairment for oral topotecan have been made in the package insert.
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm279915.htm

Pazopanib (Votrient) Drug Interactions
The solubility of pazopanib is pH dependent. Concomitant administration of pazopanib with drugs that raise gastric pH should be avoided. A drug interaction trial demonstrated a decrease in the exposure of pazopanib by approximately 40% (AUC and Cmax) when administered with esomeprazole. If therapy with these agents is necessary, short-acting antacids instead of PPIs and H2 receptor antagonists should be used whenever possible. The administration of antacids and pazopanib should be separated by several hours.
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm303649.htm

Obinutuzumab (Gazyva) Thrombocytopenia and Hemorrhagic Events
Updated safety data include reports of fatal hemorrhagic events during cycle 1 in patients treated with obinutuzumab. It is recommended to monitor all patients frequently, especially during the first cycle, for thrombocytopenia and hemorrhagic events. Dose delays of obinutuzumab and chlorambucil or dose reductions of chlorambucil can be considered in patients with grade 3 or 4 thrombocytopenia. Consideration should be made to withholding concomitant agents that increase bleeding risk, especially during the first cycle of therapy.
http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm404996.htm

ISMP Medication Safety Alerts (March–June)

May8,2014 (Volume19,Issue9)
The Institute for Safe Medication Practices (ISMP) has asked the FDA and Teva to investigate commas that have replaced decimals on tbo-filgrastim (Granix) syringes. The outer carton and peel-away prefilled syringe wrappers list the syringe volume using a decimal point (e.g., 300 mcg per 0.5 mL). However, the barrel of the syringe uses commas for volume increments (e.g., 0,5 mL). The use of a comma rather than a decimal has caused problems in the past. Toprevent inadvertent errors from occurring, ISMP has requested further investigation.

May22,2014 (Volume19,Issue10)
The ISMP reported a dosing error that occurred with nilotinib (Tasigna). A patient was instructed to take once-daily dosing because of previous intolerance to twice-daily dosing. The pharmacy filledthe prescription with instructions to take once daily. However, the preprinted dosing instructions on the manufacturer’s blister packaging provide instructions to take the medication every morning and evening. This led to confusion; the patient took nilotinb twice daily instead of once daily. The ISMP has notified the FDA and Novartis about the incident.