The FDA is clarifying usage and dosing recommendations the agency issued last year for the antidepressant citalopram hydrobromide, which is marketed as Celexa and also is available in generic form.
The agency issued a warning in August, saying that the antidepressant should no longer be used at doses greater than 40 mg per day because higher doses of the drug cause QT interval prolongation that could lead to development of torsades de pointes, a potentially fatal abnormal heart rhythm.
In a March 28 safety communication(www.fda.gov), the FDA said it now has revised the drug label to include restated guidelines regarding QT interval prolongation and torsades de pointes issues, as well as new drug dosage and usage recommendations.
Several changes have been made to citalopram's packaging information:
- Patients with congenital long QT syndrome are at particular risk of torsades de pointes, ventricular tachycardia and sudden death when given drugs that prolong the QT interval. Nevertheless, the labeling recommendation for patients with congenital long QT syndrome has been changed from "contraindicated" to "not recommended," because it is recognized that there may be some patients with this condition who could benefit from a low dose of citalopram and who lack viable alternatives. Similarly, the drug is not recommended for those who have bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure.
- Although citalopram use should be avoided, if possible, in patients with certain conditions because of the risk of QT prolongation, ECG monitoring and electrolyte monitoring should be performed if citalopram must be used in these patients.
- The maximum recommended dose of citalopram is 20 mg per day for patients with hepatic impairment, adults older than 60, patients who are CYP2C19 poor metabolizers, and those who are taking cimetidine or another CYP2C19 inhibitor concurrently.
- Citalopram should be discontinued in patients who are found to have persistent QT measurements (corrected for heart rate) greater than 500 milliseconds.
In August, the FDA advised patients taking citalopram in doses greater than 40 mg per day to consult their physician and cautioned patients against stopping use of the drug without consulting their physician because suddenly stopping citalopram can cause withdrawal effects. Patients also were advised to read the drug's medication guide. Those cautions still stand, said the agency in this week's announcement, which also noted that patients should seek immediate care if they experience an irregular heartbeat, shortness of breath, dizziness or fainting while taking citalopram.
Physicians and patients are encouraged to report adverse events associated with citalopram use to the FDA's MedWatch program(www.accessdata.fda.gov).