1 de julio de 2016

Reports of QT interval prolongation and Torsade de Pointes associated with Celexa (citalopram)

Fuente:  http://www.fda.gov/Drugs/DrugSafety/ucm297391.htm
Data Summary
FDA has received post-marketing reports of QT interval prolongation and Torsade de Pointes associated with Celexa (citalopram) and its generic equivalents. FDA evaluated the results of thorough QT studies assessing the effects of doses of citalopram and its active S-isomer escitalopram (Lexapro) on the QT interval in adults.  Both studies are randomized, double-blind, placebo-controlled, crossover studies. In the citalopram study, 119 subjects received citalopram 20 mg/day and 60 mg/day, moxifloxacin 400 mg/day, and placebo. In the escitalopram study, 113 subjects received escitalopram 10 mg/day and 30 mg/day, moxifloxacin 400 mg/day, and placebo.
The summary of findings is presented in Table 1. As of March 27, 2012, this table has been updated to provide comparative information for escitalopram.  Citalopram is a racemic mixture of S- and R-isomers. Escitalopram is the S-isomer of citalopram. The antidepressant activity of citalopram is limited to the S-isomer; therefore, each row of Table 1 shows equally effective doses of citalopram and escitalopram.  The maximum recommended dose of escitalopram is 20 mg once daily.
Table 1:  Citalopram and Escitalopram: Dose-dependent Change in Corrected QT Interval (QTc) [revised 3/27/2012 to include escitalopram]
Citalopram
Escitalopram
Dose
Change in QTc 
(90% Confidence Interval)
(ms)
Dose
Change in QTc 
(90% Confidence Interval)
(ms)
20 mg
40 mg*
60 mg
Moxifloxacin 400 mg
8.5 (6.2, 10.8)
12.6 (10.9, 14.3)
18.5 (16.0, 21.0)
13.4 (10.9, 15.9)
10 mg
20 mg*
30 mg
Moxifloxacin 400 mg
4.5 (2.5, 6.4)
6.6 (5.3, 7.9)
10.7 (8.7, 12.7)
9.0 (7.3, 10.8)
* Estimate based on the relationship between citalopram (and escitalopram) blood concentrations and QT interval
Although the antidepressant effects of the drugs are known to be limited to the S-isomer, the difference between the effects of citalopram racemate and escitalopram on the QT interval presumably means that the QT effects are not specific to the S-isomer. 
These studies show that citalopram causes dose-dependent QT interval prolongation that is clinically significant with the 60 mg daily dose. In addition, clinical trials do not show any added effectiveness of citalopram at 60 mg/day compared to 40 mg/day. Therefore, citalopram should not be used at doses above 40 mg per day. Important safety information about the potential for QT interval prolongation and Torsade de Pointes with updated drug dosage and usage recommendations have been added to the citalopram drug label. Given that these findings were not observed with escitalopram, there are no changes planned for escitalopram at this time.