The FDA is informing health care professionals and patients that the antidepressant citalopram hydrobromide, which is marketed as Celexa, should no longer be used at doses greater than 40 mg per day because higher doses of the drug cause QT interval prolongation that can lead to development of torsades de pointes, a potentially fatal abnormal heart rhythm.
The FDA said in an Aug. 24 safety announcement(www.fda.gov) that patients with underlying heart conditions and those who are predisposed to hypokalemia and hypomagnesemia are at increased risk for developing torsades de pointes.
Furthermore, the agency said studies have shown no additional benefit in treating depression with doses higher than 40 mg per day. Citalopram is available in 10-mg, 20-mg and 40-mg tablets, as well as a 10-mg/5-mL oral solution.
The FDA said citalopram's drug label has been revised to include new drug dosage and usage recommendations, as well as information about the potential for QT interval prolongation and torsade de pointes. Previously, the drug's label stated that some patients may require a dose of 60 mg per day.
The agency issued the following recommendations for physicians:
- Citalopram causes dose-dependent QT interval prolongation and should no longer be prescribed at doses greater than 40 mg per day.
- The drug should not be used in patients with congenital long QT syndrome;
- Patients with congestive heart failure, bradyarrhythmias, or predisposition to hypokalemia or hypomagnesemia because of concomitant illness or drugs are at higher risk of developing torsades de pointes.
- Consider more frequent electrocardiogram monitoring in patients with congestive heart failure, bradyarrhythmias or patients on concomitant medications that prolong the QT interval.
- Hypokalemia and hypomagnesemia should be corrected before administering citalopram, and electrolytes should be monitored as clinically indicated.
- A maximum dose of 20 mg per day is recommended for patients who have hepatic impairment and those who are older than 60, are poor metabolizers of CYP 2C19 or are taking concomitant cimetidine because these factors lead to increased blood levels of citalopram, increasing the risk of QT interval prolongation and torsades de pointes.
- No dose adjustment is needed for patients with mild or moderate renal impairment.
- Advise patients to contact a health care professional immediately if they experience an irregular heartbeat, shortness of breath, dizziness or fainting while taking citalopram.
- Report adverse events to the FDA's MedWatch program(www.accessdata.fda.gov).
The FDA advised patients taking citalopram in doses greater than 40 mg per day to consult their physician. The agency also cautioned patients against stopping their use of the drug without consulting their physician because suddenly stopping citalopram can cause side effects. Patients also are advised to read the drug's medication guide.