Levomilnacipran
FETZIMA
Pronunciation: lee-voe-mil-NA-si-pran (fet-ZEE-ma)
“Leave Milhouse with a Zima Fetish”
Zima was a clear malt beverage available 1993–2008
Stimulating → strong norepinephrine reuptake inhibitor
What it isNorepinephrine-dominant serotonin-norepinephrine reuptake inhibitor; major depression.
Why this oneUnlike its sibling milnacipran, it is used for depression rather than fibromyalgia.
What limits itBlood-pressure and heart-rate elevation, urinary hesitation, and discontinuation symptoms can limit use.
Levomilnacipran prescription history
Animated chart of estimated U.S. prescriptions per year, Antidepressants (1957–2026). Levomilnacipran enters in 2013 (estimated).
FDA-approved for
- depression (2013)
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilitySexual/GI effects, hyponatremia, discontinuation and serotonin toxicity; overdose danger varies substantially by agent.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Major depressive disorder | Adults | 20 mg QD ×2 days, then 40 mg QD | 40–120 mg QD | 120 mg QD |
Titration Increase by 40 mg at intervals of ≥2 days.
Renal Mild (CLcr 60–89): no adjustment; moderate (30–59): max 80 mg QD; severe (15–29): max 40 mg QD; ESRD: not recommended.
Hepatic No adjustment for mild, moderate, or severe.
With strong CYP3A4 inhibitors, max 80 mg QD.
Instructions
- Swallow capsule whole; do not open, chew, or crush.
- Take at about the same time each day, with or without food.
- Taper gradually when discontinuing (discontinuation symptoms).
- With strong CYP3A4 inhibitors: max 80 mg QD.
- Screen for bipolar disorder before starting.
- Allow 14 days after stopping an MAOI before starting; allow 7 days after stopping FETZIMA before starting an MAOI.
Available strengths
- ER cap 20, 40, 80, 120 mg
Contraindications
- MAOIs (concurrently or within 14 days of stopping MAOI); allow 7 days after stopping levomilnacipran before starting an MAOI due to risk of serotonin syndrome
Cautions
- Serotonin syndrome
- Elevated blood pressure and heart rate — control hypertension first, monitor
- Increased bleeding risk with NSAIDs/aspirin/anticoagulants
- Angle-closure glaucoma
- Urinary hesitation/retention
- Activation of mania/hypomania
- Seizures
- Discontinuation syndrome
- Hyponatremia (SIADH)
- Sexual dysfunction
Adverse reactions
- Nausea, constipation, vomiting
- Hyperhidrosis, heart rate increased, tachycardia, palpitations
- Erectile dysfunction, ejaculation disorder, urinary hesitation
Pregnancy Insufficient human data; possible increased postpartum hemorrhage and neonatal complications with third-trimester exposure.
Lactation No levomilnacipran data; racemic milnacipran present in human milk — monitor infant for agitation, poor feeding, poor weight gain.
Cost
| Strength | #/mo | generic $/mo | brand $/mo | CostPlus | |
|---|---|---|---|---|---|
| 20 mg | ER cap | 30 qd | — | $527.92 | not offered |
| 40 mg | ER cap | 30 qd | — | $528.34 | not offered |
| 80 mg | ER cap | 30 qd | — | $527.62 | not offered |
| 120 mg | ER cap | 30 qd | — | $527.61 | not offered |
Generic entry2019
Serotonin and MAOI
Provisional washout figures
Elevating mechanismSRI
Non-elevating actionNone recorded
Exposure dependenceTherapeutic exposure; severe toxicity requires meaningful MAO-A inhibition
Washout BEFORE an MAOI7 days
Evidence confidenceHigh
InterpretationClinically significant SRI. A second SRI generally represents therapeutic duplication/additive adverse effects, not the classic life-threatening interaction.
Open Levomilnacipran in the interactive console ↗
Self-check
- Which transmitter predominates in levomilnacipran’s reuptake inhibition?
Norepinephrine. - How does levomilnacipran’s use differ from milnacipran’s?
Depression rather than fibromyalgia.