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(mil-na-sip-ran) ,


(trade name)


Therapeutic: antifibromyalgia agents
Pharmacologic: selective norepinephrine reuptake inhibitors
Pregnancy Category: C


Management of fibromyalgia.


Inhibits neuronal reuptake of norepinephrine and serotonin.

Therapeutic effects

Decreased pain associated with fibromyalgia.


Absorption: 85–90% absorbed following oral administration.
Distribution: Unknown.
Metabolism and Excretion: Mostly excreted urine as unchanged drug (55%) and inactive metabolites.
Half-life: D-isomer 8–10 hr; L-isomer 4–6 hr.

Time/action profile (↓ in pain)

PO1 wkunknownunknown


Contraindicated in: Uncontrolled narrow-angle glaucoma;Concurrent use of or in close temporal proximity to MAO inhibitors;End-stage renal disease;Significant history of alcohol use/abuse;Chronic liver disease.
Use Cautiously in: History of suicide risk or attempt;History of seizures;Moderate-to-severe renal impairment (↓ dose if CCr <30 mL/min);Severe hepatic impairment;Obstructive uropathy (↑ risk of adverse genitourinary effects); Geriatric: Consider age-related ↓ in renal function, chronic disease state and concurrent drug therapy; Obstetric: Use only if clearly required during pregnancy weighing benefit to mother versus potential harm to fetus; Lactation: Potential for serious adverse reactions in infant; discontinue drug or discontinue breast feeding; Pediatric: ↑ risk of suicidal thinking and behavior (suicidality) in adolescents and young adults up to 24 yr with Major Depressive Disorder (MDD) and other psychiatric disorders.

Adverse Reactions/Side Effects

Central nervous system

  • neuroleptic malignant syndrome (life-threatening)
  • suicidal thoughts (life-threatening)
  • dizziness
  • headache
  • insomnia


  • hypertension
  • tachycardia

Fluid and Electrolyte

  • hyponatremia


  • constipation
  • dry mouth
  • ↑ liver enzymes
  • nausea
  • vomiting


  • hot flushes
  • hyperhidrosis


  • serotonin syndrome (life-threatening)


Drug-Drug interaction

Concurrent use with MAO inhibitors may result in serious, potentially fatal reactions; wait at least 14 days following discontinuation of MAO inhibitor before initiation of milnacipran. Wait at least 5 days after discontinuing milnacipran before initiation of MAO inhibitor.Concurrent use of serotonergic drugs (including triptans, lithium, and tramadol ) may ↑ the risk of serotinin syndrome; also ↑ risk of coronary vasoconstriction and hypertension.Concurrent use of NSAIDs, aspirin, or other drugs that affect coagulation may ↑ the risk of bleeding.May ↓ antihypertensive effectiveness of clonidine.↑ risk of hypertension and arrhythmias with epinephrine or norepinephrine.↑ risk of euphoria and hypotension when switching from clomipramine.Concurrent use with digoxin may result in adverse hemodynamics, including hypotension and tachycardia; avoid concurrent use with IV digoxin.


Oral (Adults) Day 1—12.5 mg; Day 2–3—12.5 mg twice daily; Day 4–7—25 mg twice daily; After Day 7—50 mg twice daily. Some patients may require up to 100 mg twice daily depending on response.

Renal Impairment

Oral (Adults) CCr 5–29 mL/min—maintenance dose is 25 mg twice daily; some patients may require up to 50 mg twice daily depending on response.


Tablets (contain tartrazine): 12.5 mg, 25 mg, 50 mg, 100 mg

Nursing implications

Nursing assessment

  • Assess intensity, quality, and location of pain periodically during therapy. May require several weeks for effects to be seen.
  • Monitor BP and heart rate before and periodically during therapy. Treat pre-existing hypertension and cardiac disease prior to therapy. Sustained hypertension may be dose related; decrease dose or discontinue therapy if this occurs.
  • Monitor closely for changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
  • Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, convulsions, diaphoresis, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). Report symptoms immediately.
  • Lab Test Considerations: May cause ↑ ALT, AST, and bilirubin.
    • May cause hyponatremia.

Potential Nursing Diagnoses

Chronic pain (Indications)
Risk for suicide (Adverse Reactions)


  • Oral: May be administered without regard to meals; may be more tolerable if taken with food.

Patient/Family Teaching

  • Instruct patient to take milnacipran as directed at the same time each day. Take missed doses as soon as possible unless time for next dose. Do not stop abruptly; must be decreased gradually. Advise patient to read the Medication Guide prior to therapy and with each Rx refill.
  • Encourage patient and family to be alert for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, worsening of depression and suicidal ideation, especially during early antidepressant therapy. Assess symptoms on a day-to-day basis as changes may be abrupt. If these symptoms occur, notify health care professional.
  • May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications. Avoid use of aspirin, NSAIDs, and warfarin due to increased risk for bleeding.
  • Instruct patient to notify health care professional if signs of liver damage (pruritus, dark urine, jaundice, right upper quadrant tenderness, unexplained "flu-like" symptoms) or hyponatremia (headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness), hyponatremia (headache, difficulty concentrating, memory impairment, confusion, weakness, unsteadiness, falls), rash, or serotonin syndrome (mental status changes: agitation, hallucinations, coma; autonomic instability: tachycardia, labile BP, hyperthermia; neuromuscular aberrations: hyperreflexia, incoordination; and/or gastrointestinal symptoms: nausea, vomiting, diarrhea) occur.
  • Advise patient to avoid taking alcohol during milnacipran therapy.
  • Instruct patient to notify health care professional if pregnancy is planned or suspected or if breast feeding. Encourage patients who become pregnant while taking milnacipran to enroll in the pregnancy registry by calling 1–800–643–3010 or by e-mail at
  • Encourage patient to maintain routine follow-up visits with health care provider to determine effectiveness.

Evaluation/Desired Outcomes

  • Reduction in pain and soreness associated with fibromyalgia.
References in periodicals archive ?
The three medications approved by the Food and Drug Administration for the treatment of fibromyalgia--pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella)--received only a weak grade C recommendation in the German guidelines (Schmerz 2012;26:287-90) because all three failed to achieve their primary endpoints in pivotal European clinical trials.
The strongest evidence of efficacy exists for the Food and Drug Administration--approved drugs duloxetine, milnacipran, and pregabalin, along with the off-label agents venlafaxine, gabapentin, cyclobenzaprine, and the tricyclic antidepressants.
The Therapeutic Goods Administration (TGA), Australia's regulatory body for therapeutic products, granted Pierre Fabre Medicament's milnacipran market authorisation for the treatment of fibromyalgia ("for the management of fibromyalgia").
Milnacipran is an SNRI that is somewhat selective for norepinephrine reuptake inhibition.
Therapeutic use: Milnacipran (27-29) is a dual norepinephrine and serotonin reuptake inhibitor indicated for the treatment of fibromyalgia.
Milnacipran is not a new drug; it has been sold as an antidepressant in Europe for a decade under the brand name Ixel.
Two yet to be launched products, Forest Laboratories/Cypress Biosciences's antidepressant milnacipran and Schwarz Pharma's sodium ion channel antagonist/CRMP2 modulator lacosamide (Vimpat), will compete for market share as well as provide the benefit of an additional mechanism of action.
Effects of diazepam, desipramine, fluvoxamine and milnacipran on the duration of immobility of depression-like model mice in the FST
Nasdaq:CYPB), San Diego, has announced that, as part of its commitment to be the innovator and commercial leader in providing products for the diagnosis and treatment of patients with Functional Somatic Syndromes, such as the Fibromyalgia Syndrome (FMS), it plans to expand its clinical program for milnacipran to study its efficacy in depressed mood associated with chronic pain states.
Cypress' experience with the invivodata(TM) system in this pilot trial convinced the company to use it in the current Phase II trial of the drug Milnacipran, an NSRI (norepinephrine and serotonin reuptake inhibitor), which is being evaluated as a potential treatment for FMS.
The other drugs approved by the FDA for treating fibromyalgia are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).
Patients with fibromyalgia often respond to aerobic exercise with a dramatic decrease in pain, and the use of Lyrica, Cymbalta, or milnacipran should be instituted prior to resorting to opioids in these patients.