Special Alerts:

[Posted 12/17/2010] ISSUE: FDA notified healthcare professionals that a contraindication is being added to the prescribing information advising that the injection form of dolasetron mesylate (Anzemet) should no longer be used to prevent nausea and vomiting associated with cancer chemotherapy (CINV) in pediatric and adult patients. New data demonstrate that dolasetron injection can increase the risk of developing torsade de pointes, an abnormal heart rhythm, which in some cases can be fatal. Patients at particular risk are those with underlying heart conditions or those who have existing heart rate or rhythm problems. Dolasetron causes a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram.

BACKGROUND: FDA previously noted cardiovascular safety concerns which suggested dolasetron could cause QT prolongation. However, limitations of the previous data did not clearly establish the degree to which dolasetron may cause QT prolongation. FDA recommended that the drug sponsor conduct a thorough QT study in adults in order to determine the degree of the prolongation. A pediatric study was not recommended due to the wide variability in heart rate and, thus, QTc interval in the pediatric population. See the Data Summary section of the Drug Safety Communication (DSC) for information that supports this change in the prescribing information.

RECOMMENDATION: Dolasetron should not be used in patients with congenital long-QT syndrome. Hypokalemia and hypomagnesemia should be corrected before administering dolasetron. These electrolytes should be monitored after administration as clinically indicated. Use electrocardiogram monitoring in patients with congestive heart failure, patients with bradycardia, patients with underlying heart disease, the elderly and in patients who are renally impaired who are taking dolasetron. Dolasetron injection may still be used for the prevention and treatment of postoperative nausea and vomiting because the lower doses used are less likely to affect the electrical activity of the heart and result in abnormal heart rhythms.

Dolasetron tablets may still be used to prevent CINV because the risk of developing an abnormal heart rhythm with the oral form of this drug is less than that seen with the injection form. However, a stronger warning about this potential risk is being added to the Warnings and Precautions sections of the dolasetron tablet label. For more information visit the FDA website at: [Web] and [Web].