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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 ?
Food and Drug Administration has approved only three medications to treat fibromyalgia: duloxetine (Cymbalta), milnacipran (Savella), and pregabalin (Lyrica).
Witkin, first-line treatment is the use of SNRI medications including duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor), anticonvulsants such as pregabalin (Lyrica) and gabapentin (Neurontin), and tricyclic antidepressants such as amitriptyline (Elavil).
A Settlement deal has been signed by Glenmark Pharmaceuticals and Glenmark Pharmaceuticals Inc with Forest Laboratories, LLC, Forest Laboratories Holdings, and Royalty Pharma Collection Trust to settle and terminate the outstanding patent litigation affiliated with Glenmarks Abbreviated New Drug Application for Milnacipran Hydrochloride 12.
The three medications approved by the Food and Drug Administration for the treatment of fibromyalgia - prega-balin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella) - received 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 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 Food and Drug Administration-approved medications for this common condition--duloxetine (Cymbalta), pregabalin (Lyrica), and milnacipran (Savella) often provide inadequate results.
placebo, statistically significant improvement was observed with Duloxetine, Milnacipran 200 mg/day, Pregabalin 300 or 450 mg/day, and Tramadol plus Paracetamol.
Milnacipran is an SNRI that is somewhat selective for norepinephrine reuptake inhibition.
Drugs approved by the Food and Drug Administration for treating fibromyalgia include pregabalin, duloxetine and milnacipran.
Milnacipran is not a new drug; it has been sold as an antidepressant in Europe for a decade under the brand name Ixel.
Forest Laboratories and Cypress Bioscience achieved positive results from a Phase III study of milnacipran for the management of fibromyalgia.