LEVOMILNACIPRAN HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVOMILNACIPRAN HYDROCHLORIDE (LEVOMILNACIPRAN HYDROCHLORIDE).
SNRI; inhibits reuptake of norepinephrine and serotonin, increasing their concentrations in the synaptic cleft.
| Metabolism | Primarily via CYP3A4; also involves CYP2C8 and CYP2D6 to a lesser extent. |
| Excretion | Primarily renal excretion: approximately 58% of the dose is excreted unchanged in urine. Fecal excretion accounts for about 5%. |
| Half-life | Terminal elimination half-life is approximately 12 hours (range 10-14 hours). This supports once-daily dosing in major depressive disorder. |
| Protein binding | Approximately 92% bound to serum proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Mean volume of distribution is approximately 1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 92%, indicating high systemic exposure after oral administration. |
| Onset of Action | Oral: Therapeutic effects may be observed within 1-2 weeks, but full antidepressant response typically requires 4-8 weeks. |
| Duration of Action | Duration of action supports once-daily dosing. Steady-state is achieved in approximately 2-3 days. |
20 mg orally twice daily, with or without food.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | eGFR 30-44 mL/min: 20 mg once daily; eGFR 15-29 mL/min: 20 mg every other day; eGFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class B: 20 mg once daily; Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | Maximum dose 40 mg daily; start at 20 mg once daily due to decreased renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVOMILNACIPRAN HYDROCHLORIDE (LEVOMILNACIPRAN HYDROCHLORIDE).
| Breastfeeding | Excreted into breast milk in low amounts; M/P ratio not established. Infant exposure estimated <5% of maternal weight-adjusted dose. Monitor for irritability, poor feeding, and sedation in the breastfed infant. |
| Teratogenic Risk | First trimester: Limited data; potential risk of persistent pulmonary hypertension of the newborn (PPHN) from late pregnancy exposure. Third trimester: Risk of neonatal adaptation syndrome (respiratory distress, feeding difficulties, jitteriness). Not associated with major congenital malformations in available studies. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.
| Common Effects | Nausea Vomiting Constipation Decreased appetite Anxiety Insomnia difficulty in sleeping Increased sweating Dizziness Sexual dysfunction |
| Serious Effects |
["Concomitant use with MAOIs","Concomitant use with linezolid or methylene blue","Known hypersensitivity","Use within 14 days of MAOI discontinuation"]
| Precautions | ["Suicidality","Serotonin syndrome","Elevated blood pressure","Angle-closure glaucoma","Urinary hesitancy/retention","Activation of mania/hypomania","Seizures","Discontinuation syndrome"] |
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| Fetal Monitoring | Monitor maternal blood pressure (risk of hypertension), heart rate, and electrocardiogram (QT interval). Fetal monitoring during third trimester for signs of distress. Observe neonate for serotonin withdrawal syndrome and PPHN. |
| Fertility Effects | Animal studies show no significant impairment of fertility. Human data not available; theoretical risk of hyperprolactinemia and sexual dysfunction affecting conception. |