| Indication |
Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor and is indicated for the treatment of major depressive disorder (MDD). |
| Mechanism of action |
The exact mechanism of the antidepressant action of levomilnacipran is unknown but is thought to be related to the potentiation of serotonin and norephinephrine in the central nervous system through inhibition of reuptake at serotonin and norepinephrine transporters. |
| Absorption |
The relative bioavailability after administration of the extended-release capsule was 92% when compared to oral solution. Food does not affect the concentration of levomilnacipran. After daily dosing of levomilnacipran (extended-release capsule) the mean Cmax is 341 ng/mL, and the mean steady-state AUC value is 5196 ng?h/mL. The Tmax is 6 - 8 hours after oral administration. Interconversion of stereoisomers does not occur in humans. |
| Protein binding |
22% bound to human plasma protein over concentration range of 10 to 1000 ng/mL. |
| Biotransformation |
Hepatic. Levomilnacipran undergoes desethylation to form desethyl levomilnacipran and hydroxylation to form p-hydroxy-levomilnacipran. Desethylation is facilitated primarily by CYP3A4 and by CYP2C8, 2C19, 2D6, and 2J2 to a lesser extent. Both metabolites undergo further conjugation with glucuronide to form conjugates. |
| Route of elimination |
Levomilnacipran and its metabolites are eliminated primarily by renal excretion. 58% of the dose is excreted in urine as unchanged levomilnacipran. N-desethyl levomilnacipran is the major metabolite
excreted in the urine and accounted for approximately 18% of the dose. Other identifiable metabolites excreted in the urine are levomilnacipran glucuronide (4%), desethyl-levomilnacipran glucuronide (3%), p-hydroxy levomilnacipran glucuronide (1%), and p-hydroxylevomilnacipran (1%). The metabolites are inactive. |
| Toxicity |
The most common adverse reactions are nausea, constipation, hyperhidrosis, heart rate increase, erectile dysfunction, tachycardia, vomiting, and palpitations. |
| Affected organisms |
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