Fetzima Tapering Guide
levomilnacipran
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Overview
Levomilnacipran is the more pharmacologically active enantiomer of milnacipran. It is an SNRI approved for major depressive disorder with approximately 2:1 selectivity for norepinephrine over serotonin reuptake inhibition.
20mg, 40mg, 80mg, 120mg
Extended-release capsules: 20mg, 40mg, 80mg, 120mg
Category C (risk cannot be ruled out)
Mechanism of Action
Potent dual reuptake inhibitor of serotonin and norepinephrine with preferential norepinephrine activity (NET > SERT, approximately 2:1 ratio). The active S-enantiomer of milnacipran.
Taper Notes
Active S-enantiomer of milnacipran with preferential norepinephrine reuptake inhibition (NET:SERT ~2:1). Once-daily ER formulation. Discontinuation syndrome similar to other SNRIs; taper gradually over weeks using available capsule strengths.
Maudsley Deprescribing Guidance
Step down by one dose level (e.g., 120 → 80 → 40 → 20 mg) every 1–2 weeks. Do not crush or open ER capsules — matrix integrity is required for controlled release.
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- MAOIs — contraindicated (risk of serotonin syndrome)
- Strong CYP3A4 inhibitors (ketoconazole) — max dose 80mg/day
- Serotonergic drugs increase serotonin syndrome risk
Food Interactions
- No significant food effect on absorption
- May be taken with or without food
Contraindications
- MAOIs within 14 days
- Uncontrolled narrow-angle glaucoma
- Known hypersensitivity to levomilnacipran or milnacipran
Toxicity
Serotonin syndrome risk. Blood pressure and heart rate increases. Urinary hesitation.
Pharmacokinetics
ADME Profile
Well absorbed, bioavailability ~92%. Tmax ~6–8 hours (extended-release). Food does not affect AUC.
387–473 L
Hepatic via CYP3A4 (major) with minor contribution from CYP2C8, CYP2C19, CYP2D6, and CYP2J2. Desethyl metabolite (inactive).
Renal (58% unchanged).
22%
~21 L/hr
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