April 7, 2011
FDA and Bristol-Myers Squibb are informing healthcare professionals about severe immune mediated adverse reactions associated with ipilimumab (Yervoy), including death. A risk evaluation and mitigation strategy (REMS) was developed to ensure prescribers are aware of the serious and sometimes fatal risks so they may carefully weigh the benefits and risks before prescribing ipilimumab. The most common severe immune-mediated reactions include dermatitis or toxic epidermal necrolysis, endocrinopathy, enterocolitis, hepatitis, and neuropathy. These reactions typically occur during initial treatment but few may manifest weeks or months after discontinuation of ipilimumab. The approved labeling contains a boxed warning regarding these immune-mediated adverse reactions.
The ipilimumab REMS program contains a Communication Plan to educate healthcare professionals about the severe risks, early identification, and management of the immune mediated adverse reactions. Healthcare providers are advised to read the labeling, including the boxed warning, and discuss the potential risks with the patient. Healthcare providers should be familiar with the signs and symptoms including dermatitis, endocrinopathy, enterocolitis, and neuropathy. Discontinue treatment with ipilimumab if a severe immune mediated adverse reaction is identified and begin systemic high dose corticosteroids. Monitor liver and thyroid function tests at baseline and prior to each dose.
Additional information is available at the following links:
- MedWatch Alert:
- Dear Healthcare Professional Letter:
- Medication Guide:
The FDA requires the distribution of Medication Guides for drugs determined to be a serious and significant public health concern. With the exception of the erythropoiesis-stimulating agents (ESAs; eg, darbepoetin alfa, epoetin alfa) and naltrexone suspension, this requirement applies primarily to medications dispensed in the outpatient setting (refer to Code of Federal Regulations 21CFR208.1) for patient self-administration. When other prescription medications are administered to patients by healthcare professionals (eg, in the hospital, in infusion centers, dialysis centers, clinics, or offices), distributing a Medication Guide is not required, although it may be appropriate to educate patients about the potential hazards of prescription medications, at the clinician’s discretion. When ESAs are administered to patients by healthcare professionals, a Medication Guide must be distributed when the patient starts therapy, at least once monthly during therapy, and whenever the Medication Guide is substantially updated. When naltrexone suspension (Vivitrol) is administered to patients by healthcare professionals, a Medication Guide must be distributed when the patient starts therapy and before each injection. The complete list of drugs that require a Medication Guide as part of the FDA-regulated product labeling is available online at: http://www.fda.gov/cder/Offices/ODS/labeling.htm. For more information about the special requirements for ESA Medication Guide, see http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200297.htm.
April 7, 2011; University of Utah, Drug Information Service. Copyright 2011, Drug Information Service, University of Utah, Salt Lake City, UT.