Forest's Lexapro (escitalopram) label includes a statement of greater potency than its predecessor antidepressant Celexa (citalopram).

"Escitalopram is at least 100 fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate," labeling states. FDA approved Lexapro for the treatment of major depressive disorder Aug. 14.

Lexapro is the single isomer formulation of Forest's selective serotonin reuptake inhibitor Celexa. The product includes the (S)-enantiomer of Celexa, but not the (R)-enantiomer, which does not contribute to Celexa's antidepressant activity.

Celexa is a mixture of the mirror image (S)- and (R)-enantiomers. "Citalopram is a racemic mixture (50/50), and the inhibition of 5-HT reuptake by citalopram is primarily due to the (S)-enantiomer," Celexa's labeling states.

Forest hopes to build a case for switching from Celexa to Lexapro based on onset of action, potency and safety claims. The company maintains that Lexapro 10 mg was comparable to the higher titrated dose of Celexa 40 mg in a clinical trial.

While labeling states that efficacy for escitalopram was demonstrated in an eight-week study comparing Lexapro 10 mg and 20 mg, Celexa 40 mg and placebo, onset of action data versus Celexa was not included in the label.

"The 10 mg/day and 20 mg/day Lexapro treatment groups showed significantly greater mean improvement compared to placebo on the Montgomery Asberg Depression Rating Scale," labeling states. "The 10 mg and 20 mg Lexapro groups were similar in mean improvement on the MADRS score."

Efficacy for Lexapro was also partially based on extrapolation of data from racemic citalopram.

"Longer-term efficacy of escitalopram in major depressive disorder has not been systematically evaluated; however, longer-term efficacy of racemic citalopram in this population has been established," labeling says.

In two clinical studies, patients with a MADRS score #12 during an initial six to eight weeks of treatment with citalopram (either 20 mg or 40 mg daily or flexible doses of 20-60 mg/day) were randomized to continuation of citalopram or placebo for six months.

"In both studies, patients receiving continued racemic citalopram treatment experienced significantly lower relapse rates (MADRS $22 in the fixed dose study; MADRS $25 in the flexible dose study) over the subsequent six months compared to those receiving placebo," labeling says.

"In the fixed dose study, the decreased rate of depression relapse was similar in patients receiving 20 or 40 mg/day of racemic citalopram," labeling continues.

A follow-up group of patients who responded to an initial 22 to 25 weeks of therapy with flexible doses of citalopram were randomized to receive the same active dose or placebo. A significantly lower relapse rate was observed in citalopram patients for up to 72 weeks.

"Nevertheless, the physician who elects to use Lexapro for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient," labeling says.

The most common adverse events associated with Lexapro 10 mg compared to placebo were insomnia (7% vs. 4%), diarrhea (6% vs. 5%), dry mouth (4% vs. 3%) and somnolence (4% vs. 1%). The overall incidence of adverse events was 66% for Lexapro 10 mg, 86% for Lexapro 20 mg and 61% for placebo.

Forest expects to have Lexapro in pharmacies by Sept. 5 in 5 mg, 10 mg and 20 mg strength tablets. The recommended dose is 10 mg daily. "If the dose is increased to 20 mg, this should occur after a minimum of one week," labeling says.

Forest plans to cease sampling and promotion of Celexa, which is scheduled to lose exclusivity in January 2004 after a six-month pediatric exclusivity extension. The company is planning to launch Lexapro at a slight discount to Celexa (¹ Also see "Forest Escitalopram To Launch As Lexapro At Price Similar To Celexa" - Pink Sheet, 21 January, 2002., p. 31).

The NDA for Lexapro was filed March 23, 2001. The product was "approvable" at FDA Jan. 25.

Forest Lexapro Approval Includes Label Claim Of Greater Potency Than Celexa

More from Archive

More from Pink Sheet