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Milnacipran

SAVELLA

Pronunciation: mil-NA-si-pran

Milnacipran ballicule: receptor binding, kinetics and half-life diagram
Mechanism of action: Milnacipran ballicule
Milnacipran SAVELLA mascot mnemonic cartoon
Visual mnemonic: Milnacipran mascot
“Milhouse ran to Save Ella”

What it isSNRI licensed in the US only for fibromyalgia.

Why this oneMore noradrenergic than serotonergic, which suits the pain indication.

What limits itRaises blood pressure and heart rate. Nausea; discontinuation syndrome.

Milnacipran molecular structure (skeletal formula)
Molecular structure: Milnacipran

FDA-approved for

FDA label

BOXED WARNING Increased risk of suicidal thinking/behavior in children, adolescents, and young adults; not approved for MDD or for pediatric use
FDA dosingPopulationStartTargetMax
FibromyalgiaAdult12.5 mg QD (Day 1)50 mg BID (100 mg/day)100 mg BID (200 mg/day)
FibromyalgiaSevere renal impairment (CrCl 5–29)25 mg BID (50 mg/day)50 mg BID (100 mg/day)

Titration Per schedule: 12.5 mg Day 1 → 25 mg/day Days 2–3 → 50 mg/day Days 4–7 → 100 mg/day after Day 7

Renal Mild: none; moderate: caution; severe (CrCl 5–29): reduce maintenance 50% to 50 mg/day (may ↑ to 100 mg/day); not recommended in ESRD

Hepatic No adjustment; caution in severe impairment

Doses >200 mg/day have not been studied

Instructions

Available strengths

Contraindications

Cautions

Adverse reactions

Pregnancy SNRI exposure (esp. month before delivery) associated with <2-fold ↑postpartum hemorrhage; third-trimester exposure linked to neonatal complications; insufficient data on birth defects

Lactation Present in human milk (~5% weight-adjusted maternal dose); monitor infant for agitation, irritability, poor feeding, poor weight gain

Cost

Milnacipran (SAVELLA)
What pharmacies pay · NADAC 9/30/26
Strength#/mogeneric $/moCostPlus
12.5 mgtab30 qd$23.47offered
25 mgtab30 qd$75.78offered
50 mgtab30 qd$84.05offered
100 mgtab30 qd$84.57offered

Generic entry2016

⚠ BOXED WARNING

Classes and tags

Clinical profile

Therapeutic safety burden2 / 4
Overdose danger2 / 4
Weight-gain liability1 / 4
Sedation liability1 / 4
QT / Torsades0 / 4
Direct muscarinic antagonism0 / 4
Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilitySexual/GI effects, hyponatremia, discontinuation and serotonin toxicity; overdose danger varies substantially by agent.

Serotonin and MAOI

Provisional washout figures

SRI significance3 / 4
MAO-A inhibition0 / 4
Serotonin release0 / 4

Elevating mechanismSRI

Non-elevating actionNone recorded

Exposure dependenceTherapeutic exposure; severe toxicity requires meaningful MAO-A inhibition

Washout BEFORE an MAOI5 days

Evidence confidenceHigh

InterpretationClinically significant SRI. A second SRI generally represents therapeutic duplication/additive adverse effects, not the classic life-threatening interaction.

Open Milnacipran in the interactive console ↗

Memory aids: interaction avatars

Milnacipran Box: minimal PK interactions avatar mnemonic
Box: minimal PK interactions

Open Milnacipran in the interactive console ↗