Alerts
Bortezomib (Velcade) - Dose Adjustment in Hepatic Impairment
January 26, 2010
FDA and Takeda, the manufacturer of bortezomib (Velcade), released information to healthcare professionals about new dose adjustment recommendations in patients with moderate to severe hepatic impairment. Bortezomib is labeled for use in multiple myeloma. It is also labeled in patients with refractory or relapsed mantle cell lymphoma. Bortezomib is metabolized through liver enzymes. A pharmacokinetic analysis of 51 patients with cancer showed the area under the concentration versus time curve (AUC) increased 60% in patients with moderate to severe hepatic dysfunction compared to patients with normal hepatic function. Due to this increased drug exposure, decrease the starting dose of bortezomib in patients with hepatic dysfunction and monitor for increased toxicity.
The recommended starting doses of bortezomib in patients with hepatic impairment are listed below.
- Mild hepatic impairment (bilirubin ≤ 1.5 x upper limit of normal): no dose adjustment needed
- Moderate and severe hepatic impairment (bilirubin > 1.5 x upper limit of normal): reduce starting dose to 0.7 mg/m2 in the first cycle. Consider increasing dose to 1 mg/m2 or decreasing dose to 0.5 mg/m2 in subsequent cycles based on toxicity.
Additional information is available at the following links:
- MedWatch Alert
http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm198424.htm - Dear Healthcare Professional Letter
http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/UCM198426.pdf
Updated
January 27, 2010; University of Utah, Drug Information Service. Copyright 2010, Drug Information Service, University of Utah, Salt Lake City, UT.
