Wednesday, September 18, 2013

so you know!


Important Drug Warning
SUBJECT: Risks associated with the use of XGEVA® (denosumab 120 mg)
  • Severe symptomatic hypocalcemia, including fatal cases
  • Hypersensitivity, including anaphylactic reactions
August 27, 2013
Dear Health Care Professional,
This letter is issued to notify healthcare providers about risks associated with
 the use of Xgeva; severe symptomatic hypocalcemia, including fatal cases,
and hypersensitivity, including anaphylactic reactions. Xgeva is indicated for
the prevention of skeletal-related events in patients with bone metastases
from solid tumors and for the treatment of adults and skeletally mature
adolescents with giant cell tumor of bone that is unresectable or where
surgical resection is likely to result in severe morbidity. Xgeva is not indicated
 for the prevention of skeletal-related events in patients with multiple myeloma.
Severe symptomatic hypocalcemia, including fatal cases
In the postmarketing setting, in patients with cancer receiving Xgeva for
prevention of skeletal-related events, severe symptomatic hypocalcemia,
 including fatal cases, has been reported. Signs and symptoms of these
 cases include altered mental status, tetany, seizures and QTc prolongation,
which were temporally associated with Xgeva use and decreased serum calcium levels.
 The calculated reporting rate of severe symptomatic hypocalcemia suggests
that the incidence in the postmarketing setting is similar to the rate observed
in clinical trials. During clinical trials, severe hypocalcemia (corrected
serum calcium < 7 mg/dL or < 1.75 mmol/L) occurred in 3.1% of patients
receiving treatment with Xgeva and 1.4% of patients had hypocalcemia reported
 as a serious adverse event.
Action being taken by Amgen
To communicate this important safety information, changes have been made
 to the US prescribing information (USPI) as described below:
  • The Contraindications section has been updated to reflect that pre-existing
  •  hypocalcemia must be corrected prior to initiating therapy with Xgeva.
  • The Warnings and Precautions section has been updated to reflect that 
  • Xgeva can cause severe symptomatic hypocalcemia, and fatal cases have 
  • been reported.
  • The Adverse Reactions section has been updated to include “severe symptomatic
  •  hypocalcemia, including fatal cases” as a postmarketing adverse drug reaction.
Summary of Recommendations for Health Care Professional
The risk of severe symptomatic hypocalcemia among patients receiving Xgeva can be
minimized by the following:
  • Correction of pre-existing hypocalcemia prior to Xgeva treatment.
  • Administration of calcium and vitamin D as necessary to treat or prevent 
  • hypocalcemia. Monitor calcium levels and administer calcium, magnesium, 
  • and vitamin D as necessary. Monitor levels more frequently when Xgeva is 
  • administered with other drugs that can also lower calcium levels. Advise 
  • patients to contact a healthcare professional for symptoms of hypocalcemia.
  • Identification of risk factors for hypocalcemia in patients receiving Xgeva. 
  •  Based on clinical trials using a lower dose of denosumab (single dose of 
  • 60 mg denosumab), patients without cancer and with severe renal impairment 
  • (creatinine clearance less than 30 mL/min) or receiving dialysis were at greater
  •  risk of severe hypocalcemia compared to patients with normal renal function.
Hypersensitivity, including anaphylactic reactions
In the postmarketing setting, two spontaneously reported cases of anaphylactic
reactions were identified and were considered causally related to Xgeva. The calculated
reporting rate of anaphylactic reaction is 5.4 per 100,000 patient-years, which classifies
 anaphylactic reaction as a very rare event.
Action being taken by Amgen
To communicate this important safety information, changes have been made to the
 US prescribing information (USPI) as described below:
  • The Contraindications section has been updated to reflect that Xgeva is 
  • contraindicated in
    patients with known clinically significant hypersensitivity to Xgeva.
  • The Warnings and Precautions section and the Adverse Reactions section 
  • have been updated to indicate that clinically significant hypersensitivity 
  •  including anaphylactic reactions has been reported with use of Xgeva.
Summary of Recommendations for Health Care Professional
Patients with clinically significant hypersensitivity to Xgeva should not receive Xgeva.
Further Information
These are not the only risks associated with the use of this product. Please see
 the full prescribing information for more information about the risks associated
with the use of this product. This information is also available at www.xgeva.com.
Contact details for adverse event reporting or to request further information
Any suspected adverse reactions should be reported to FDA’s MedWatch
Adverse Event Reporting Program:
  • by phone (1-800-FDA-1088), by facsimile (1-800-FDA-0178),
  • online (www.fda.gov/medwatch), or
  • by mail using the MedWatch Form FDA 3500 postage paid form,
  •  to the FDA Medical Products Reporting Program, 5600 Fishers Lane,
  •  Rockville, MD 20852-9787.
Should you have any questions or require additional information regarding the
use of Xgeva, please contact Amgen’s Medical Information Department at
1-800-77-AMGEN.
Sincerely,

Michael Severino, MD
Senior Vice President, Global Development, and Chief Medical Officer
Amgen
Amgen, Inc. | PO Box 681308 | Indianapolis, IN 46268

74864-R1-V1
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