Reviewed on 7/5/2022

What Is Milnacipran and How Does It Work?

Milnacipran is a  prescription medication used for the treatment of fibromyalgia.

  • Milnacipran is available under the following different brand names: Savella

What Are Side Effects Associated with Using Milnacipran?

Common side effects of Milnacipran include:

Serious side effects of Milnacipran include:

  • fast or pounding heartbeat,
  • painful or difficult urination,
  • seizures,
  • yellowing eyes or skin,
  • dark urine,
  • severe stomach or abdominal pain,
  • black or bloody stools,
  • vomit that looks like coffee grounds, or
  • easy bruising or bleeding.

Rare side effects of Milnacipran include:

  • none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Are Doses of Milnacipran?

Adult dosage


  • 12.5mg
  • 25mg
  • 50mg
  • 100mg


Adult dosage

  • 12.5 mg orally once on day 1, then 25 mg/day divided every 12 hours on days 2-3, then 50 mg/day divided every 12 hours on days 4-7, then 100 mg/day divided every 12 hours thereafter; not to exceed 200 mg/day
  • Therapy discontinuation
    • When discontinuing antidepressant therapy that has lasted for more than 3 weeks, taper dose gradually over 2-4 weeks; this will minimize withdrawal symptoms and help detect reemerging symptoms
    • If intolerable withdrawal symptoms occur, resume previously prescribed dose; may also decrease dose at a more gradual rate; patients on long-term treatment (above 6 weeks) may benefit from tapering over above 3 months
  • Switching to or from MAO inhibitors
    • Allow five or more days to elapse between milnacipran discontinuation and initiation of MAO inhibitor
    • Allow 14 days to elapse between MAO inhibitor discontinuation and initiation of milnacipran
    • Severe renal impairment: may increase to 50 mg twice daily if tolerated

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”

What Other Drugs Interact with Milnacipran?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Milnacipran?


  • Concomitant use of monoamine oxidase inhibitors (MAOIs), use of MAOIs within 5 days after discontinuance of milnacipran, or the initiation of milnacipran within 14 days after discontinuance of MAOIs
  • Patients being treated with linezolid or intravenous methylene blue

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Milnacipran?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Milnacipran?”


  • Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) similar to those used for depression and other psychiatric disorders; monitoring and close observation for clinical worsening, suicidality, and unusual changes in behavior are necessary, especially during the first few months of treatment and when the dosage is increased or decreased (see Black Box Warnings)
  • Potentially life-threatening serotonin syndrome has been reported with both SNRIs and selective serotonin reuptake inhibitors (SSRIs) when these agents are taken alone, but especially when they are coadministered with other serotonergic agents; thus, patient medications should be thoroughly reviewed for other serotonergic drugs (eg, tryptophan supplements, tramadol, serotonin agonists [triptans], MAOIs, tricyclic antidepressants [TCAs], SSRIs, methylene blue, buspirone, amphetamines, linezolid)
  • May increase blood pressure (BP) or heart rate (HR); BP should be controlled before initiation of milnacipran; BP and HR should be monitored while the patient is taking a drug; consider dose reduction or discontinuation of therapy in patients with sustained hypertension or tachycardia during therapy
  • SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs are known to affect platelet function may add to this risk
  • Neonates exposed to SNRIs or SSRIs late in the third trimester are at risk for complications such as feeding difficulties, irritability, and respiratory problems
  • The prescription should be written for the smallest amount consistent with good patient care; alert family members to monitor for the emergence of suicidality, including panic attacks, hostility, irritability, insomnia, anxiety, agitation, mania, and hypomania
  • Bone fracture reported with antidepressant treatment; consider the possibility of fracture in patients that present with unexplained bone pain, swelling, or bruising
  • Use caution in patients with a history of seizures
  • Moderate renal impairment
  • Avoid use in severe hepatic impairment; discontinue therapy with signs of hepatic dysfunction or jaundice; do not reinitiate therapy unless another source or cause identified
  • Avoid concomitant use in patients with substantial alcohol use or chronic liver disease
  • Withdrawal symptoms were reported in patients when discontinuing treatment; gradual dose reduction recommended
  • The pupillary dilation that occurs following the use of SNRI drugs including milnacipran may trigger angle closure attack in patients with anatomically narrow angles who do not have a patent iridectomy; for patients who have not had an iridectomy for narrow-angle glaucoma risk factors, consider performing evaluation
  • Patients with a history of obstructive uropathies may experience higher rates of genitourinary adverse drug reactions (ADRs)
  • ESRD: Use not recommended
  • Development of SIADH and hyponatremia reported with SSRIs and SNRIs, predominantly in the elderly; volume depletion and/or concurrent use of diuretics may increase the risk
  • May cause urinary hesitance; advise patients to report urinary symptoms or difficulties; use caution in patients with a history of lower urinary tract disorders, including benign prostatic hyperplasia or prostatitis
  • May worsen psychosis in patients with mood disorders; a shift to mania or hypomania reported with bipolar disorder; avoid monotherapy in patients with bipolar disorder; prospective screen patients for bipolar disorder when presenting with depressive symptoms

Sexual dysfunction

  • In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm
  • Important for prescribers to inquire about sexual function before initiation of therapy and to ask specifically about changes in sexual function during treatment because the sexual function may not be spontaneously reported
  • When evaluating changes in sexual function, obtaining a detailed history (including the timing of symptom onset) is essential because sexual symptoms may have other causes, including underlying psychiatric disorder
  • Discuss potential management strategies to support patients in making informed decisions about treatment

Pregnancy & Lactation

  • Use with caution if benefits outweigh risks during pregnancy


  • The drug is excreted in human milk; peak breast milk concentration is observed within 4 hours after the maternal dose, and estimated infant exposure is 5% of maternal dose; limited data are available regarding infant exposure, but caution is advised

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