2R)-milnacipran
2R)-milnacipran Uses, Dosage, Side Effects, Food Interaction and all others data.
2R)-milnacipran is a selective serotonin and norepinephrine reuptake inhibitor. Chemically, levomilnacipran is the 1S,2R-enantiomer of milnacipran. FDA approved on July 25, 2013.
2R)-milnacipran binds with high affinity to human serotonin (5-HT) and norepinephrine (NE) transporters (Ki = 11 and 91 nM, respectively). It potently inhibits 5-HT and NE reuptake (IC50 = 16 - 19 and 11 nM, respectively). 2R)-milnacipran does not bind to any other receptors, ion channels, or transporters, including serotonergic (5HT1-7), α- and β adrenergic, muscarinic, or histaminergic receptors and Ca2+, Na+, K+ or Cl- channels to a significant degree. 2R)-milnacipran did not inhibit monoamine oxidase (MAO). Furthermore, levomilnacipran does not prolong the QTc interval to a clinically relevant extent.
| Trade Name | 2R)-milnacipran |
| Availability | Prescription only |
| Generic | Levomilnacipran |
| Levomilnacipran Other Names | (1S,2R)-milnacipran, Levomilnacipran |
| Related Drugs | Rexulti, sertraline, trazodone, Lexapro, Zoloft, citalopram, Cymbalta, Prozac |
| Type | |
| Formula | C15H22N2O |
| Weight | Average: 246.348 Monoisotopic: 246.173213336 |
| Protein binding | 22% bound to human plasma protein over concentration range of 10 to 1000 ng/mL. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
2R)-milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used to treat major depressive disorder (MDD).
2R)-milnacipran is a serotonin and norepinephrine reuptake inhibitor and is indicated for the treatment of major depressive disorder (MDD).
2R)-milnacipran is also used to associated treatment for these conditions: Major Depressive Disorder (MDD)
How 2R)-milnacipran works
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.
Toxicity
The most common adverse reactions are nausea, constipation, hyperhidrosis, heart rate increase, erectile dysfunction, tachycardia, vomiting, and palpitations.
Food Interaction
- Avoid alcohol. Ingesting alcohol may compromise the extended-release dosage form of levomilnacipran, causing an accelerated release of the drug, increasing its serum concentration.
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Taking herbs with antiplatelet or anticoagulant activity may increase the risk of bleeding. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
- Exercise caution with grapefruit products. Grapefruit is a moderate to strong CYP3A4 inhibitor. Do not exceed a maximum levomilnacipran dose of 80mg daily when taking strong CYP3A4 inhibitors.
- Exercise caution with St. John's Wort. Administering levomilnacipran with St. John's Wort may increase the risk of serotonin syndrome.
- Take with or without food.
[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.
Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.
Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
2R)-milnacipran Hypertension interaction
[Moderate] Selective serotonin and norepinephrine reuptake inhibitor antidepressants (SNRIs) have been associated with sustained increases in blood pressure.
Therapy with SNRI antidepressants should be administered cautiously in patients with preexisting hypertension.
Blood pressure should be assessed prior to initiating treatment and monitored regularly.
The dose should be reduced or discontinued if necessary.
2R)-milnacipran Drug Interaction
Major: amphetamine / dextroamphetamine, citalopram, duloxetine, cyclobenzaprine, sumatriptan, escitalopram, fluvoxamine, paroxetine, bupropionModerate: oxymetazoline nasal, aspirin, acetaminophen / oxycodoneUnknown: fexofenadine, zolpidem, thyroid desiccated, diphenhydramine, docusate, methylphenidate, clonazepam, bifidobacterium infantis / lactobacillus acidophilus
2R)-milnacipran Disease Interaction
Major: depression, renal diseaseModerate: glaucoma, hypertension, hyponatremia, mania, seizures, urinary tract obstruction
Volume of Distribution
- 387 - 473 L [apparent volume of distribution]
Elimination Route
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.
Half Life
12 hours
Clearance
- 21 - 29 L/h [mean apparent total clearance]
Elimination Route
2R)-milnacipran 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.
Innovators Monograph
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