Mood disorders:

Indications for: FETZIMA

Major depressive disorder (MDD).

Limitations of Use:

Not approved for the management of fibromyalgia; efficacy and safety have not been established.

Adult Dosage:

Swallow whole. Initially 20mg once daily for 2 days, and then increase to 40mg once daily; may increase dose in 40mg increments at intervals of ≥2 days; max 120mg once daily. Renal impairment: moderate (CrCl 30–59mL/min): max 80mg once daily; severe (CrCl 15–29mL/min): max 40mg once daily. ESRD: not recommended. Concomitant strong CYP3A4 inhibitors: max 80mg once daily.

Children Dosage:

<18yrs: not established.

FETZIMA Contraindications:

During or within 14 days of MAOIs. Initiating MAOIs during or within 7 days of levomilnacipran. Concomitant linezolid or IV methylene blue.

Boxed Warning:

Suicidal thoughts and behaviors.

FETZIMA Warnings/Precautions:

Increased risk of suicidal thoughts and behavior in children and young adults; monitor for clinical worsening and unusual changes. Suicidal ideation. Screen for bipolar disorder, mania, or hypomania prior to initiation. Monitor for serotonin syndrome; discontinue if occurs. Pre-existing hypertension, cardio- or cerebrovascular disease, or tachyarrhythmias. Monitor BP, HR prior to and during therapy; consider discontinuation or other treatment if elevation persists. Risk of bleeding. Avoid in those with anatomically narrow angles. Obstructive urinary disorders. History of mania/hypomania. Seizure disorder. Renal impairment. Volume depleted. Hyponatremia (esp. elderly). Sexual dysfunction. Avoid abrupt cessation. Reevaluate periodically. Write ℞ for smallest practical amount. Pregnancy: see full labeling for effects on neonates in 3rd trimester. Nursing mothers: monitor infants.

FETZIMA Classification:


FETZIMA Interactions:

See Contraindications. Allow at least 14 days after MAOI discontinuation before starting levomilnacipran; allow at least 7 days after discontinuing levomilnacipran before starting an MAOI. Increased risk of serotonin syndrome with other serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs, linezolid, IV methylene blue). Increased risk of bleeding with concomitant NSAIDs, aspirin, warfarin, and others that affect coagulation. Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, itraconazole, ritonavir); see Adult. Avoid alcohol. Caution with other CNS-active drugs, or drugs that can increase BP or HR.

Adverse Reactions:

Nausea, constipation, vomiting, hyperhidrosis, heart rate increase, erectile dysfunction, tachycardia, palpitations; hypertension, urinary hesitation/retention (consider discontinuing if occurs).


Levomilnacipran undergoes desethylation which is catalyzed primarily by CYP3A4 with minor contribution by CYP2C8, 2C19, 2D6, and 2J2.

Drug Elimination:

Renal (58%).

Mean apparent total clearance: 21–29 L/h.

Half-life: ~12 hours.

Generic Drug Availability:


How Supplied:

Caps 20mg—30; 40mg, 80mg, 120mg—30, 90; Titration Pack—1 (2 x 20mg + 26 x 40mg)