Pharmacological Class:
Serotonin and norepinephrine reuptake inhibitor (SNRI).

Active Ingredient(s):
Levomilnacipran 20mg, 40mg, 80mg, 120mg; ext-rel caps.

Company
Forest Laboratories

Indication(s):
Treatment of major depressive disorder (MDD) in adults. Limitations of use: not approved for the management of fibromyalgia. The efficacy and safety for the management of fibromyalgia have not been established.

Pharmacology:
Although the exact mechanism of the antidepressant action of levomilnacipran is unknown, it is thought to be related to the potentiation of serotonin and norepinephrine in the CNS, through inhibition of reuptake at serotonin and norepinephrine transporters.

Clinical Trials:
The efficacy of Fetzima was established in three 8-week, randomized, double-blind, placebo-controlled studies at doses 40–120mg once daily in adult outpatients with MDD. Two of these studies were fixed dose (Study 1 and Study 2), and one study was flexible dose (Study 3).

In Study 1 (N=713), patients received Fetzima 40mg, 80mg, or 120mg once daily or placebo. In Study 2 (N=562), patients received either Fetzima 40mg or 80mg once daily or placebo. In Study 3 (N=434), patients received Fetzima 40–120mg once daily or placebo.

In all three studies, Fetzima demonstrated superiority over placebo in the improvement of depressive symptoms, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Fetzima also demonstrated superiority over ­placebo as measured by ­improvement in the Sheehan Disability Scale functional impairment total score.

For more clinical trial results, see full labeling.

Legal Classification:
Rx

Adults:
Swallow whole. Initially 20mg once daily for 2 days, and then increase to 40mg once daily; may increase dose in 40mg increments at intervals of ≥2 days; max 120mg once daily. Renal impairment: moderate (CrCl 30–59mL/min): max 80mg once daily; severe (CrCl 15–29mL/min): max 40mg once daily. ESRD: not recommended. Concomitant strong CYP3A4 inhibitors: max 80mg once daily.

Children:
<18years: not established.

Contraindication(s):
During or within 14 days of MAOIs. Concomitant linezolid or IV methylene blue (see full labeling). Uncontrolled narrow-angle glaucoma.

Warnings/Precautions:
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; monitor closely for clinical worsening and unusual changes. Monitor for serotonin syndrome; discontinue if develops. History of bipolar disorder, mania, or hypomania. Pre-existing hypertension, cardio- or cerebrovascular disease, or tachyarrhythmias. Monitor BP and heart rate; reduce dose or discontinue if elevation persists. Risk of bleeding. Controlled narrow-angle glaucoma. Obstructive urinary disorders. Seizure disorder. Volume depleted. Hyponatremia risk (esp. in elderly). Reeva luate periodically. Write Rx for smallest practical amount. Avoid abrupt cessation. Pregnancy (Category C). Nursing mothers: not studied.

Interaction(s)
See Contraindications. Allow at least 14 days after MAOI discontinuation before starting levomilnacipran; allow at least 7 days after discontinuing levomilnacipran before starting an MAOI. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Increased risk of bleeding with concomitant NSAIDs, aspirin, anticoagulants; monitor. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir): adjust dose. Avoid alcohol. Caution with other CNS-active drugs, or drugs that can increase BP or heart rate.

Adverse Reaction(s)
Nausea, constipation, vomiting, hyperhidrosis, increased heart rate, erectile dysfunction, tachycardia, palpitations; hypertension, urinary hesitation.

How Supplied:
Caps 20mg—30; 40mg, 80mg, 120mg—30, 90
Titration Pack—1 (2 x 20mg + 26 x 40mg)

LAST UPDATED:
11/8/2013