Overview
Levomilnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), although it is a more potent inhibitor of norepinephrine reuptake than serotonin reuptake. Levomilnacipran is the more active 1S,2R-enantiomer in the racemate milnacipran. Once administered, interconversion between levomilnacipran and its stereoisomer does not occur in humans. First approved by the FDA on July 25, 2013, levomilnacipran is used to treat major depressive disorder in adults. While levomilnacipran was previously investigated and proposed as a potential treatment for stroke in Europe, the EMA decided against this use.
Indication
Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor indicated for the treatment of major depressive disorder (MDD) in adults.
Associated Conditions
- Major Depressive Disorder (MDD)
Research Report
A Comprehensive Clinical and Pharmacological Monograph of Levomilnacipran (Fetzima): An SNRI with a Unique Noradrenergic Profile
Executive Summary
Levomilnacipran, marketed under the brand name Fetzima, is a serotonin-norepinephrine reuptake inhibitor (SNRI) approved for the treatment of Major Depressive Disorder (MDD) in adults. It represents a "chiral switch" from its parent compound, milnacipran, being the more pharmacologically active (1S,2R)-enantiomer. This monograph provides an exhaustive analysis of Levomilnacipran's chemical properties, pharmacological mechanisms, pharmacokinetic profile, clinical trial evidence, safety and tolerability, and global regulatory status.
Pharmacologically, Levomilnacipran is distinguished from other SNRIs by its potent and preferential inhibition of norepinephrine reuptake over serotonin reuptake, with an approximate 1:2 inhibition ratio. This unique noradrenergic-dominant profile may confer therapeutic advantages for MDD symptoms such as fatigue and amotivation, but it is also directly responsible for its characteristic adverse effect profile, which is heavily skewed towards cardiovascular and genitourinary symptoms, including increased heart rate, elevated blood pressure, and urinary hesitation. Emerging preclinical data also identifies Levomilnacipran as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), suggesting a potential, though unproven, role in modulating neurodegenerative processes associated with Alzheimer's disease.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2018/06/26 | Phase 3 | Completed | |||
2017/08/15 | Phase 4 | UNKNOWN | |||
2017/04/25 | Phase 4 | Completed | Howard Aizenstein | ||
2016/03/25 | Phase 3 | Completed | |||
2015/06/09 | Phase 4 | Completed | |||
2015/05/01 | Phase 3 | Completed | Forest Laboratories | ||
2014/11/11 | Phase 4 | Completed | Forest Laboratories | ||
2014/10/17 | Phase 1 | Completed | |||
2014/10/15 | Not Applicable | Completed | |||
2012/07/12 | Phase 3 | Completed |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Allergan, Inc. | 0456-2212 | ORAL | 120 mg in 1 1 | 10/10/2023 | |
| Amneal Pharmaceuticals LLC | 65162-960 | ORAL | 40 mg in 1 1 | 12/13/2023 | |
| Allergan, Inc. | 0456-2240 | ORAL | 40 mg in 1 1 | 10/10/2023 | |
| Amneal Pharmaceuticals LLC | 65162-437 | ORAL | 80 mg in 1 1 | 12/13/2023 | |
| Allergan, Inc. | 0456-2220 | ORAL | 20 mg in 1 1 | 10/10/2023 | |
| Allergan, Inc. | 0456-2280 | ORAL | 80 mg in 1 1 | 10/10/2023 | |
| Amneal Pharmaceuticals LLC | 65162-411 | ORAL | 20 mg in 1 1 | 12/13/2023 | |
| Amneal Pharmaceuticals LLC | 65162-455 | ORAL | 120 mg in 1 1 | 12/13/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
| No EMA approvals found for this drug. | |||
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No HSA approvals found for this drug. | |||||
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| No TGA approvals found for this drug. | |||||
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
|---|---|---|---|---|---|
| No Health Canada approvals found for this drug. | |||||
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
|---|---|---|---|---|---|
| No CIMA AEMPS (Spain) approvals found for this drug. | |||||
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
|---|---|---|---|---|---|
| No UK EMC drug information found for this drug. | |||||
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