The Food and Drug Administration has clarified its warning and dosing recommendations regarding the potential risk of QT prolongation with the antidepressant citalopram, the agency announced March 28.
In a MedWatch alert issued in August 2011, the agency recommended that citalopram should no longer be used at doses greater than 40 mg a day because of the potential for prolongation of the QT interval, which can lead to torsades de pointes, a potentially fatal cardiac arrhythmia. The 2011 warning also stated that citalopram should not be used in patients with congenital long QT syndrome, and that patients who have congestive heart failure or bradyarrhythmias, or are predisposed to hypokalemia or hypomagnesemia because of concomitant illness or drugs, are at higher risk of developing the arrhythmia.
There have been postmarketing reports of torsades de pointes associated with citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for treating depression in 1998 and marketed as Celexa by Forest Laboratories. It also is available in generic formulations.
In the March 28 statement posted on the MedWatch site, the FDA said the citalopram label is being revised to include information on the lower doses that should be used in people over age 60 years. In addition, while the use of citalopram "at any dose is discouraged in patients with certain conditions because of the risk of QT prolongation," the statement adds, "because it may be important for some of those patients to use citalopram, the drug label has been changed to describe the particular caution that needs to be taken when citalopram is used in such patients."
The FDA’s revised recommendations are as follows:
• Citalopram is not recommended at doses greater than 40 mg per day "because such doses cause too large an effect on the QT interval and confer no additional benefit."
• Citalopram is not recommended for patients with congenital long QT syndrome, bradycardia, hypokalemia, or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure.
• Citalopram is not recommended for patients treated with other drugs that prolong the QT interval.
• The maximum recommended dose of citalopram is 20 mg per day for patients who have hepatic impairment, are older than age 60, are CYP 2C19 poor metabolizers, or are taking cimetidine (Tagamet) or another CYP2C19 inhibitor. These factors result in increased blood levels of citalopram, and increase the risk of QT prolongation and torsades de pointes.
Serious adverse events associated with citalopram should be reported to the FDA’s MedWatch program at 800-332-1088.