FDA Drug Safety Communication: Abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide)

Safety Announcement
Additional Information for Patients
Additional Information for Healthcare Professionals
Data Summary

Safety Announcement

[8-24-2011] The U.S. Food and Drug Administration (FDA) is informing healthcare professionals and patients that the antidepressant Celexa (citalopram hydrobromide; also marketed as generics) should no longer be used at doses greater than 40 mg per day because it can cause abnormal changes in the electrical activity of the heart. Studies did not show a benefit in the treatment of depression at doses higher than 40 mg per day.

Facts about Celexa (citalopram hydrobromide)

Is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). Thought to work by increasing the amount of serotonin in the brain.1 Available as 10 mg, 20 mg, and 40 mg tablets. Also available as an oral solution (10 mg/5 mL).

Previously, the citalopram drug label stated that certain patients may require a dose of 60 mg per day.

Changes in the electrical activity of the heart (prolongation of the QT interval of the electrocardiogram [ECG]) - see Data Summary below - can lead to an abnormal heart rhythm (including Torsade de Pointes), which can be fatal. Patients at particular risk for developing prolongation of the QT interval include those with underlying heart conditions and those who are predisposed to low levels of potassium and magnesium in the blood.

The citalopram drug label has been revised to include the new drug dosage and usage recommendations, as well as information about the potential for QT interval prolongation and Torsade de Pointes. (See Additional Information for Healthcare Professionals)

Additional Information for Patients

Do not stop taking citalopram or change your dose without talking to your healthcare professional. Stopping citalopram suddenly can cause unwanted side effects.
If you are currently taking a citalopram dose greater than 40 mg per day, talk to your healthcare professional about changing your dose.
Seek immediate care if you experience an irregular heartbeat, shortness of breath, dizziness, or fainting while taking citalopram.
If you are taking citalopram, your healthcare professional may occasionally order an electrocardiogram (ECG, EKG) to monitor your heart rate and rhythm. An ECG is a test that checks for problems with the electrical activity of your heart.
Read the Medication Guide for citalopram carefully and discuss any questions you have with your healthcare professional.
Report any side effects you experience to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of the page.



Additional Information for Healthcare Professionals
Citalopram causes dose-dependent QT interval prolongation. Citalopram should no longer be prescribed at doses greater than 40 mg per day.
Citalopram 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 Torsade de Pointes.
Hypokalemia and hypomagnesemia should be corrected before administering citalopram. Electrolytes should be monitored as clinically indicated.
Consider more frequent electrocardiogram (ECG) monitoring in patients with congestive heart failure, bradyarrhythmias, or patients on concomitant medications that prolong the QT interval.
20 mg per day is the maximum recommended dose for patients with hepatic impairment, who are greater than 60 years of age, who are CYP 2C19 poor metabolizers, or who are taking concomitant cimetidine (Tagamet®), because these factors lead to increased blood levels of citalopram, increasing the risk of QT interval prolongation and Torsade de Pointes.
No dose adjustment is necessary for patients with mild or moderate renal impairment.
Advise patients to contact a healthcare professional immediately if they experience signs and symptoms of an abnormal heart rate or rhythm while taking citalopram.
Report adverse events involving citalopram to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.

Data Summary

FDA has received post-marketing reports of QT interval prolongation and Torsade de Pointes associated with Celexa and its generic equivalents. In addition, FDA has evaluated the results of a thorough QT study assessing the effects of 20-mg and 60-mg doses of citalopram on the QT interval in adults. In this randomized, multi-center, double-blind, placebo-controlled, crossover study, 119 subjects received citalopram 20 mg per day (Day 9), citalopram 60 mg per day (Day 22), and placebo. The overall summary of findings is presented in Table 1

Table 1: Increase in the Corrected QT Interval for Citalopram (FDA Analysis)

Citalopram Dose	Increase in QT Interval (ms)	90% Confidence Interval (ms)
20 mg/day	8.5	(6.2, 10.8)
60 mg/day	18.5	(16.0, 21.0)
40 mg/day	12.6*	(10.9, 14.3)*

*Estimate based on the relationship between citalopram blood concentration and QT interval.

Compared to placebo, maximum mean prolongations in the individually corrected QT intervals were 8.5 and 18.5 milliseconds (ms) for 20 mg and 60 mg citalopram, respectively. For 40 mg citalopram, prolongation of the corrected QT interval was estimated to be 12.6 ms.

As a result of this thorough QT study, FDA has determined that citalopram causes dose-dependent QT interval prolongation and should no longer be used at doses above 40 mg per day. Important safety information about the potential for QT interval prolongation and Torsade de Pointes with drug dosage and usage recommendations are being added to the package inserts of Celexa and its generic equivalents.

References

1. National Center for Biotechnology Information. U.S. National Library of Medicine. PubMed Drug & Supplements Monograph Citalopram. Available at: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a699001.html¹. Accessed July 20, 2011.