An SNRI approved for major depressive disorder in adults.
Levomilnacipran (Fetzima) is an antidepressant approved in the United States in 2013 for the treatment of major depressive disorder in adults.
Acts as a serotonin–norepinephrine reuptake inhibitor (SNRI).
Pregnancy category US: C (Risk not ruled out).
Oral agent.
Bioavailability 92%.
Protein binding 22%.
Metabolism is Hepatic (primarily by CYP3A4)
Elimination half-life 12 hours
Excretion Renal
Approved for the treatment of major depressive disorder based on the results of one 10-week phase II and four 8-week phase III clinical trials.
Four of the five trials demonstrated a statistically significant superiority to placebo.
Side effects include: nausea, dizziness, sweating, constipation, insomnia, increased heart rate and blood pressure, urinary hesitancy, erectile dysfunction and delayed ejaculation in males, vomiting, tachycardia, and palpitations.
Has a much more balanced reuptake inhibitors of serotonin and norepinephrine compared to other SNRIs.
Has a high oral bioavailability of 92% and a low plasma protein binding of 22%.
Metabolized in the liver by the cytochrome P450 enzyme CYP3A4. It is susceptible to grapefruit-drug interactions.
Elimination half-life of approximately 12 hours, allowing for once-daily administration.
It is excreted in urine.
Not approved for use in children.
More potently inhibits norepinephrine uptake relative to serotonin reuptake by about two fold.
Significantly more effective than placebo in decreasing depression scale.
Initially started at 20 mg once daily for two days and then increased on day 3 to 40 mg a day: it may be increased every two days to a maximum dose of 120 mg per day.
Primarily renally excreted, and dose should be modified with renal insufficiency.
Gradually taper over several weeks is recommended for discontinuation.
Most common adverse effects are: headache, G.I. tract symptoms of nausea, vomiting, constipation, hyperhidrosis, tachycardia, urinary hesitancy, erectile dysfunction, and ejaculatory disorders in men.
Incidence of adversary effects are not dose related, with the exception of erectile dysfunction and urinary hesitancy.
Associated with small increase in both systolic and diastolic blood pressure, and mild increase in serum transaminase values.
Not associated with weight gain or prolongation of the QTc interval.
May be effective in fibromyalgia.