The FDA has approved levomilnacipran (Fetzima), a single-enantiomer version of the fibromyalgia drug milnacipran (Savella), for treating major depression, its developers said.
Forest Laboratories and Pierre Fabre Laboratories said the once-daily drug will be available to wholesalers in the fourth quarter of 2013. Forest will sell Fetzima in the U.S. under a collaborative agreement with Pierre Fabre, which initially discovered the drug and will manufacture it as an active pharmaceutical ingredient.
Levomilnacipran is believed to be the more active of milnacipran's two enantiomers, according to information from Pierre Fabre. The drug is a dual inhibitor of serotonin and norepinephrine reuptake (SNRI).
In an initial phase III study reported in 2011, of a significant change relative to the placebo group in Montgomery-Asberg Depression Rating Scale (MADRS) scores after 8 weeks of treatment.
But subsequent phase III trials also using MADRS scores for the primary endpoints did show a significant advantage, Forest and Pierre Fabre said in announcing the approval. The drug "also demonstrated superiority over placebo as measured by improvement in the Sheehan Disability Scale functional impairment total score," the firms said.
Adverse reactions seen in at least 5% of patients and at twice the rate or more seen in the placebo groups included the following:
- Nausea, vomiting, and constipation
- Tachycardia
- Hyperhidrosis
- Erectile dysfunction
- Palpitations
Rates of these events were similar across levomilnacipran doses tested (40, 80, and 120 mg/day), except for dose-related increases in incidence of erectile dysfunction, Forest and Pierre Fabre indicated. Also, the firms said the trial data indicated increasing incidence of urinary hesitation with higher doses.
Fetzima's label will carry the same label warnings and precautions as other serotonergic drugs, including the risk of suicidal ideation and action in younger patients, and risks of serotonin syndrome. The latter may occur with serotonin reuptake inhibitors taken alone but is especially common when these are taken with other drugs that activate serotonergic pathways.