pharmacopeia
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/api/v1/drug/milnacipran

Boxed warning

SUICIDALITY AND ANTIDEPRESSANT DRUGS SAVELLA is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of such drugs in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on SAVELLA should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. SAVELLA is not approved for use in the treatment of major depressive disorder.

Mechanism of action

Sourced from openFDA

The exact mechanism of the central pain inhibitory action of milnacipran and its ability to improve the symptoms of fibromyalgia in humans are unknown. Preclinical studies have shown that milnacipran is a potent inhibitor of neuronal norepinephrine and serotonin reuptake; milnacipran inhibits norepinephrine uptake with approximately 3-fold higher potency in vitro than serotonin without directly affecting the uptake of dopamine or other neurotransmitters.

Monoamine OxidaseNorepinephrine UptakeSerotonin Uptake

Indications

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  • SAVELLA is indicated for the management of fibromyalgia. SAVELLA is not approved for use in pediatric patients [see Use in Specific Populations ( 8.4 )] .

Contraindications

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  • Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with SAVELLA or within 5 days of stopping treatment with SAVELLA. Do not use SAVELLA within 14 days of stopping an MAOI intended to treat psychiatric disorders.contraindicated

Dosage & administration

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SAVELLA is given orally with or without food. Taking SAVELLA with food may improve the tolerability of the drug. Administer SAVELLA in two divided doses per day ( 2.1 ). Based on efficacy and tolerability, dosing may be titrated according to the following schedule ( 2.1 ): Day 1: 12.5 mg once Days 2-3: 25 mg/day (12.5 mg twice daily) Days 4-7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily) Recommended dose is 100 mg/day ( 2.1 ). May be increased to 200 mg/day based on individual patient response ( 2.1 ). Adjust dose in patients with severe renal impairment ( 2.2 ). 2.1 Recommended Dosing The recommended dose of SAVELLA is 100 mg/day (50 mg twice daily). Based on efficacy and tolerability dosing may be titrated according to the following schedule: Day 1: 12.5 mg once Days 2-3: 25 mg/day (12.5 mg twice daily) Days 4-7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily) Based on individual patient response, the dose may be increased to 200 mg/day (100 mg twice daily). Doses above 200 mg/day have not been studied. Taper SAVELLA and do not abruptly discontinue after extended use [see Dosage and Administration ( 2.4 ) , Warnings and Precautions ( 5.7 )] . 2.2 Patients with Renal Insufficiency No dosage adjustment is necessary in patients with mild renal impairment. Use SAVELLA with caution in patients with moderate renal impairment. For patients with severe renal impairment (indicated by an estimated creatinine clearance of 5-29 mL/min), reduce the maintenance dose by 50% to 50 mg/day (25 mg twice daily).

Warnings & precautions

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Suicidality : Monitor for worsening of depressive symptoms and suicide risk ( 5.1 ). Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue SAVELLA and any other serotonergic agents, and initiate supportive treatment ( 5.2 ). Elevated B lood P ressure and H eart R ate : SAVELLA may increase blood pressure and heart rate. Measure blood pressure and heart rate prior to initiating treatment with SAVELLA and monitor periodically throughout treatment ( 5.3 , 5.4 ). Seizures : Cases have been reported with SAVELLA therapy. Prescribe SAVELLA with care in patients with a history of seizure disorder ( 5.5 ). Hepatotoxicity : SAVELLA may cause elevations of ALT and AST. Avoid concomitant use of SAVELLA in patients with substantial alcohol use or chronic liver disease ( 5.6 ). Discontinuation : Withdrawal symptoms have been reported in patients when discontinuing treatment with SAVELLA. A gradual dose reduction is recommended ( 5.7 ). Increased Risk of Bleeding : SAVELLA may increase the risk of bleeding events. Caution patients about the risk of bleeding associated with the concomitant use of SAVELLA and NSAIDs, aspirin, or other drugs that affect coagulation ( 5.9 ). History of Dysuria : Male patients with a history of obstructive uropathies may experience higher rates of genitourinary adverse events ( 5.11 ). Sexual Dysfunction : SAVELLA use may cause symptoms of sexual dysfunction ( 5.12 ).

Adverse reactions

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The most frequently occurring adverse reactions (≥ 5% and greater than placebo) were nausea, headache, constipation, dizziness, insomnia, hot flush, hyperhidrosis, vomiting, palpitations, heart rate increased, dry mouth, and hypertension ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial s Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patient Exposure SAVELLA was evaluated in three double-blind placebo-controlled trials involving 2209 fibromyalgia patients (1557 patients treated with SAVELLA and 652 patients treated with placebo) for a treatment period up to 29 weeks. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Adverse Reactions Leading to Discontinuation In placebo-controlled trials in patients with fibromyalgia, 23% of patients treated with SAVELLA 100 mg/day, 26% of patients treated with SAVELLA 200 mg/day discontinued prematurely due to adverse reactions, compared to 12% of patients treated with placebo.

Use in specific populations

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Pregnancy: Third trimester use may increase risk for symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate ( 8.1 ). 8.1 Pregnancy Risk Summary Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.2 )] . The available data on SAVELLA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks associated with exposure to serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective-serotonin reuptake inhibitors (SSRIs), including SAVELLA, during pregnancy (see Clinical Considerations). Animal reproduction studies have been performed in rats, rabbits and mice. Milnacipran was shown to increase embryofetal and perinatal lethality in rats and the incidence of a minor skeletal variation in rabbits at doses below (rat) or approximately equal to (rabbit) the maximum recommended human dose (MRHD) of 200 mg/day on a mg/m 2 basis. No effects were seen in mice when treated with milnacipran during the period of organogenesis at doses up to 3 times the MHRD on a mg/m 2 basis (see Data).

Pharmacokinetics

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Metabolism
Milnacipran is well absorbed after oral administration with an absolute bioavailability of approximately 85% to 90%. The exposure to milnacipran increased proportionally within the therapeutic dose range.

Overdosage

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Clinical Presentation There is limited clinical experience with SAVELLA overdose in humans. In clinical trials, cases of acute ingestions up to 1000 mg, alone or in combination with other drugs, were reported with none being fatal. In postmarketing experience, fatal outcomes have been reported for acute overdoses primarily involving multiple drugs but also with SAVELLA only. The most common signs and symptoms included increased blood pressure, cardio-respiratory arrest, changes in the level of consciousness (ranging from somnolence to coma), confusional state, dizziness, and increased hepatic enzymes. Management of Overdose There is no specific antidote to SAVELLA, but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. In case of acute overdose, treatment should consist of those general measures employed in the management of overdose with any drug. Ensure adequate airway, oxygenation, and ventilation and monitor cardiac rhythm and vital signs. Induction of emesis is not recommended.

Approval history

Sourced from openFDA
  • Jan 14, 2009NDANDA022256Abbvie
  • Jan 27, 2016ANDAANDA205071Breckenridge
  • Oct 3, 2024ANDAANDA205147Hetero Labs Ltd V

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
5,952 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Nausea69112%
  2. 2Pain5088.5%
  3. 3Headache4868.2%
  4. 4Drug Ineffective4687.9%
  5. 5Vomiting3535.9%
  6. 6Fatigue3385.7%
  7. 7Dizziness3345.6%
  8. 8Insomnia3235.4%
  9. 9Depression2944.9%
  10. 10Hyperhidrosis2864.8%
  11. 11Anxiety2664.5%
  12. 12Off Label Use2624.4%
  13. 13Drug Hypersensitivity2534.3%
  14. 14Rash2103.5%
  15. 15Blood Pressure Increased2083.5%

Literature

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Recent PubMed references pinned to Milnacipran as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 74 ClinicalTrials.gov registrations naming Milnacipran as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Milnacipran. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

Frequently asked questions

How does Milnacipran work?
The exact mechanism of the central pain inhibitory action of milnacipran and its ability to improve the symptoms of fibromyalgia in humans are unknown. Preclinical studies have shown that milnacipran is a potent inhibitor of neuronal norepinephrine and serotonin reuptake; milnacipran inhibits norepinephrine uptake with approximately 3-fold higher potency in vitro than serotonin without directly affecting the uptake of dopamine or other neurotransmitters.
What is Milnacipran used for?
According to FDA labeling, Milnacipran carries indications including: SAVELLA is indicated for the management of fibromyalgia. SAVELLA is not approved for use in pediatric patients [see Use in Specific Populations ( 8.4 )] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Milnacipran?
Milnacipran is classified as Other antidepressants, Serotonin and Norepinephrine Reuptake Inhibitor, Monoamine Oxidase Inhibitors, Norepinephrine Uptake Inhibitors, Serotonin Uptake Inhibitors, Increased Central Nervous System Norepinephrine Activity, Increased Central Nervous System Serotonin Activity.
What are the brand names for Milnacipran?
Milnacipran is marketed under brand names including Savella.
What are the contraindications for Milnacipran?
Milnacipran labeling lists contraindications including: Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with SAVELLA or within 5 days of stopping treatment with SAVELLA. Do not use SAVELLA within 14 days of stopping an MAOI intended to treat psychiatric disorders.. Always consult the full prescribing information and a clinician.
Note. Data for milnacipran is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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