MILNACIPRAN HYDROCHLORIDE 12.5 mg Tablet, Film Coated, 60-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Serotonin and Norepinephrine Reuptake Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Great question, because it's a common source of confusion. Milnacipran belongs to a class of drugs called SNRIs, which are also used to treat depression — but milnacipran itself is...
- What exactly is milnacipran used for — is it an antidepressant?
- Yes, nausea is the most common side effect, but there's a practical tip: try taking your tablet with food. The label specifically notes that taking milnacipran with food can help i...
- Nausea seems really common with this medication — is there anything I can do about it?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII UTY7PDF93L
A plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
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A synthetic blue dye combined with aluminum to create a stable colorant. It's used in medicines and supplements to add blue color or create specific shades for product identification and appearance.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII NX76LV5T8J
A synthetic plastic polymer made from methacrylic acid and ethyl acrylate. It's used as a coating or binder to control how and where the medicine dissolves in your digestive system.
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UNII 7T9FYH5QMK
A plant-derived powder that serves as a binder and filler in tablets and capsules. It helps hold ingredients together, adds bulk, and aids in smooth tablet disintegration when swallowed.
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Polyethylene glycol 3350 is a synthetic polymer used as a solvent, humectant, and thickening agent in medicines. It helps dissolve other ingredients, retain moisture in the product, and achieve the desired consistency.
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Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 8MDF5V39QO
A white powder form of baking soda that acts as a buffer and pH regulator in medicines. It helps maintain the right acid-base balance and may aid tablet disintegration.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
12 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.441 | $26.44 / 60 tablets |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Milnacipran Hydrochloride 12.5 mgthis 31722-0846-60 | Camber | 60 tablets | $0.441 | AB | Availability likely | — |
| Milnacipran Hydrochloride 12.5 mg 51991-0034-06 | Breckenridge | 60 tablets | $0.441 | AB | Availability likely | — |
| Milnacipran Hydrochloride 12.5 mg 68462-0763-60 | Glenmark | 60 tablets | $0.441 | AB | Availability likely | — |
| Savella 12.5 mg 00456-1512-60 | Allergan, | 60 tablets | $8.166 | AB | Availability likely | +1753% |
| Milnacipran Hydrochloride 12.5 mg 33342-0369-09 | Macleods | 60 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 31722-0846-32 | 10 BLISTER PACK in 1 CARTON (31722-846-32) / 10 TABLET, FILM COATED in 1 BLISTER PACK | — | — | 2026-03-19 | Active |
| 31722-0846-60 You're viewing this | 60 TABLET, FILM COATED in 1 BOTTLE (31722-846-60) | $0.4406 / ea | $26.43 | 2026-03-19 | Active |
Pack size FAQ
What quantity is in NDC 31722-0846-60?
What NDC number is used to bill for this package of MILNACIPRAN HYDROCHLORIDE 12.5 mg Tablet, Film Coated?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS Milnacipran hydrochloride 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 milnacipran hydrochloride 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. Milnacipran hydrochloride is not approved for use in the treatment of major depressive disorder. Milnacipran hydrochloride is not approved for use in pediatric patients [see Indications and Usage (1) , Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ] .
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS See full prescribing information for complete boxed warning. • Increased risk of suicidal ideation, thinking, and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders ( 5.1 ). • Milnacipran is not approved for use in pediatric patients ( 1, 8.4 ).
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Milnacipran hydrochloride tablets are indicated for the management of fibromyalgia. Milnacipran hydrochloride tablets are not approved for use in pediatric patients [see Use in Specific Populations (8.4)] . Milnacipran hydrochloride tablets are a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the management of fibromyalgia (1) .
Milnacipran hydrochloride tablets are not approved for use in pediatric patients (1) .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Milnacipran hydrochloride tablets are given orally with or without food. Taking milnacipran hydrochloride tablets with food may improve the tolerability of the drug. • Administer milnacipran hydrochloride tablets 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 to 3: 25 mg/day (12.5 mg twice daily) Days 4 to 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) .
2.1Recommended Dosing The recommended dose of milnacipran hydrochloride tablet 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 to 3: 25 mg/day (12.5 mg twice daily) Days 4 to 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 milnacipran hydrochloride tablets and do not abruptly discontinue after extended use [see Dosage and Administration (2.4) , Warnings and Precautions (5.7) ].
2.2Patients with Renal Insufficiency No dosage adjustment is necessary in patients with mild renal impairment. Use milnacipran hydrochloride tablets with caution in patients with moderate renal impairment. For patients with severe renal impairment (indicated by an estimated creatinine clearance of 5 to 29 mL/min), reduce the maintenance dose by 50% to 50 mg/day (25 mg twice daily).
Based on individual patient response, the dose may be increased to 100 mg/day (50 mg twice daily). Milnacipran hydrochloride tablets are not recommended for patients with end-stage renal disease.
2.3Patients with Hepatic Insufficiency No dosage adjustment is necessary for patients with hepatic impairment. As with any drug, exercise caution in patients with severe hepatic impairment.
2.4Discontinuing Milnacipran Hydrochloride Tablets Withdrawal symptoms have been observed in clinical trials following discontinuation of milnacipran, as with other serotonin and norepinephrine re-uptake inhibitors (SNRIs) and selective serotonin re-uptake inhibitors (SSRIs). Monitor patients for these symptoms when discontinuing treatment. Taper milnacipran hydrochloride tablets and do not abruptly discontinue after extended use [see Warnings and Precautions (5.7) ] .
2.5Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of a MAOI intended to treat psychiatric disorders and initiation of therapy with milnacipran hydrochloride tablets. Conversely, allow at least 5 days after stopping milnacipran hydrochloride tablets before starting a MAOI intended to treat psychiatric disorders [see Contraindications (4.1) ] .
2.6Use of Milnacipran Hydrochloride Tablets with other MAOIs such as Linezolid or Methylene Blue Do not start milnacipran hydrochloride tablets in a patient being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, consider other interventions, including hospitalization [see Contraindications (4.1) ]. In some cases, a patient already receiving milnacipran hydrochloride tablets therapy may require urgent treatment with linezolid or intravenous methylene blue.
If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, discontinue milnacipran hydrochloride tablets p…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Film-coated, immediate–release tablets in four strengths: 12.5 mg, 25 mg, 50 mg, and 100 mg of milnacipran hydrochloride. 12.5 mg tablets are blue, round, biconvex film-coated tablets debossed with ‘H’ on one side and ‘M8’ on the other side; 25 mg tablets are white to off-white, round, biconvex film-coated tablets debossed with ‘H’ on one side and ‘M9’ on the other side; 50 mg tablets are white to off-white, oval, biconvex film-coated tablets debossed with ‘H’ on one side and ‘M10’ on the other side; 100 mg tablets are pink, oval, biconvex film-coated tablets debossed with ‘H’ on one side and ‘M11’ on the other side. • Tablets: 12.5 mg, 25 mg, 50 mg, 100 mg (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with milnacipran hydrochloride or within 5 days of stopping treatment with milnacipran hydrochloride. Do not use milnacipran hydrochloride within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start milnacipran hydrochloride in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1 , 5.2 ).
4.1Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with milnacipran hydrochloride or within 5 days of stopping treatment with milnacipran hydrochloride is contraindicated because of an increased risk of serotonin syndrome. The use of milnacipran hydrochloride within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.5) , Warnings and Precautions (5.2) ] . Starting milnacipran hydrochloride in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.6) , Warnings and Precautions (5.2) ].
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • 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 milnacipran hydrochloride and any other serotonergic agents, and initiate supportive treatment (5.2) . • Elevated Blood Pressure and Heart Rate: Milnacipran hydrochloride may increase blood pressure and heart rate. Measure blood pressure and heart rate prior to initiating treatment with milnacipran hydrochloride and monitor periodically throughout treatment (5.3 , 5.4 ). • Seizures: Cases have been reported with milnacipran hydrochloride therapy.
Prescribe milnacipran hydrochloride with care in patients with a history of seizure disorder (5.5) . • Hepatotoxicity: Milnacipran hydrochloride may cause elevations of ALT and AST. Avoid concomitant use of milnacipran hydrochloride in patients with substantial alcohol use or chronic liver disease (5.6) . • Discontinuation: Withdrawal symptoms have been reported in patients when discontinuing treatment with milnacipran hydrochloride. A gradual dose reduction is recommended (5.7) . • Increased Risk of Bleeding: Milnacipran hydrochloride may increase the risk of bleeding events.
Caution patients about the risk of bleeding associated with the concomitant use of milnacipran hydrochloride 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: Milnacipran hydrochloride use may cause symptoms of sexual dysfunction (5.12) .
5.1Suicide Risk Milnacipran hydrochloride is a selective serotonin and norepinephrine re-uptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders. Patients, both adult and pediatric, with depression or other psychiatric disorders may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking these medications, and this risk may persist until significant remission occurs.
Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants, including drugs that inhibit the reuptake of norepinephrine and/or serotonin, may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. In the placebo-controlled clinical trials of adults with fibromyalgia, among the patients who had a history of depression at treatment initiation, the incidence of suicidal ideation was 0.5% in patients treated with placebo, 0% in patients treated with milnacipran hydrochloride 100 mg/day, and 1.3% in patients treated with milnacipran hydrochloride 200 mg/day.
No suicides occurred in the short-term or longer-term (up to 1 year) fibromyalgia trials. Pooled analyses of short-term placebo-controlled trials of drugs used to treat depression (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with these drugs compared to placebo in adults beyond age 24; there was a reduction in suicidality risk with antidepressants compared to placebo in adults age 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 drugs used to treat depression in over 4400 patients. The pooled an…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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 Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials 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 Milnacipran hydrochloride was evaluated in three double-blind placebo-controlled trials involving 2209 fibromyalgia patients (1557 patients treated with milnacipran hydrochloride 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 milnacipran hydrochloride 100 mg/day, 26% of patients treated with milnacipran hydrochloride 200 mg/day discontinued prematurely due to adverse reactions, compared to 12% of patients treated with placebo.
The adverse reactions that led to withdrawal in ≥ 1% of patients in the milnacipran hydrochloride treatment group and with an incidence rate greater than that in the placebo treatment group were nausea (milnacipran 6%, placebo 1%), palpitations (milnacipran 3%, placebo 1%), headache (milnacipran 2%, placebo 0%), constipation (milnacipran 1%, placebo 0%), heart rate increased (milnacipran 1%, placebo 0%), hyperhidrosis (milnacipran 1%, placebo 0%), vomiting (milnacipran 1%, placebo 0%), and dizziness (milnacipran 1% and placebo 0.5%).
Discontinuation due to adverse reactions was generally more common among patients treated with milnacipran hydrochloride 200 mg/day compared to milnacipran hydrochloride 100 mg/day. Most Common Adverse Reactions in Placebo Controlled Trials In the placebo-controlled fibromyalgia patient trials, the most frequently occurring adverse reaction in clinical trials was nausea. The most common adverse reactions (incidence ≥ 5% and twice placebo) in patients treated with milnacipran hydrochloride were constipation, hot flush, hyperhidrosis, vomiting, palpitations, heart rate increased, dry mouth, and hypertension.
Table 4 lists all adverse reactions that occurred in at least 2% of patients treated with milnacipran hydrochloride at either 100 or 200 mg/day and at an incidence greater than that of placebo. Table 4: Treatment-Emergent Adverse Reaction Incidence in Placebo Controlled Trials in Fibromyalgia Patients (Events Occurring in at Least 2% of All Milnacipran Hydrochloride-Treated Patients and Occurring More Frequently in Either Milnacipran Hydrochloride Treatment Group Than in the Placebo Treatment Group) System Organ Class– Preferred Term Milnacipran Hydrochloride 100 mg/day (n = 623) % Milnacipran Hydrochloride 200 mg/day (n = 934) % All Milnacipran Hydrochloride (n = 1557) % Placebo (n = 652) % Cardiac Disorders Palpitations 8 7 7 2 Tachycardia 3 2 2 1 Eye Disorders Vision blurred 1 2 2 1 Gastrointestinal Disorders Nausea 35 39 37 20 Constipation 16 15 16 4 Vomiting 6 7 7 2 Dry mouth 5 5 5 2 Abdominal pain 3 3 3 2 General Disorders Chest pain 3 2 2 2 Chills 1 2 2 0 Chest discomfort 2 1 1 1 Infections Upper respiratory tract infection 7 6 6 6 Investigations Heart rate increased 5 6 6 1 Blood pressure increased 3 3 3 1 Metabolism and Nutrition Disorders Decreased appetite 1 2 2 0 Nervous System Disord…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Milnacipran undergoes minimal CYP450 related metabolism, with the majority of the dose excreted unchanged in urine (55%) and has a low binding to plasma proteins (13%). In vitro and in vivo studies showed that milnacipran hydrochloride is unlikely to be involved in clinically significant pharmacokinetic drug interactions [see Pharmacokinetics in Special Populations (12.3)] . • Milnacipran hydrochloride is unlikely to be involved in clinically significant pharmacokinetic drug interactions (7) . • Pharmacodynamic interactions of milnacipran hydrochloride with other drugs can occur (7) .
7.1Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of SSRIs and SNRIs, including milnacipran hydrochloride, with MAOIs increases the risk of serotonin syndrome. The use of MAOIs intended to treat psychiatric disorders with milnacipran hydrochloride or within 5 days of stopping treatment with milnacipran hydrochloride is contraindicated. The use of milnacipran hydrochloride within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated.
In addition, do not initiate milnacipran hydrochloride in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with a MAOI such as linezolid or intravenous methylene blue in a patient taking milnacipran hydrochloride, discontinue milnacipran hydrochloride before initiating treatment with the MAOI [see Dosage and Administration (2.5, 2.6), Contraindications (4), Drug Interactions (7.1)].
7.2Serotonergic Drugs Serotonin syndrome can occur with use of milnacipran hydrochloride and other serotonergic drugs (other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort), or with drugs that impair metabolism of serotonin (i.e., monoamine oxidase inhibitors). Advise patients of the signs and symptoms associated with serotonin syndrome and to seek medical care immediately if they experience these symptoms [see Dosage and Administration (2.5, 2.6), Warnings and Precautions (5.2)].
7.3Triptans There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of milnacipran hydrochloride with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [see Warnings and Precautions (5.2)].
7.4Catecholamines Milnacipran hydrochloride inhibits the reuptake of norepinephrine. Therefore, concomitant use of milnacipran hydrochloride with epinephrine and norepinephrine may be associated with paroxysmal hypertension and possible arrhythmia [see Warnings and Precautions (5.3, 5.4)].
7.5CNS-active drugs Given the primary CNS effects of milnacipran hydrochloride, use caution when it is taken in combination with other centrally acting drugs, including those with a similar mechanism of action. Clomipramine: In a drug-drug interaction study, an increase in euphoria and postural hypotension was observed in patients who switched from clomipramine to milnacipran hydrochloride.
7.6Clinically Important Interactions with Select Cardiovascular Agents Digoxin: Use of milnacipran hydrochloride concomitantly with digoxin may be associated with potentiation of adverse hemodynamic effects. Postural hypotension and tachycardia have been reported in combination therapy with intravenously administered digoxin (1 mg). Avoid co-administration of milnacipran hydrochloride and intravenous digoxin [see Warnings and Precautions (5.3 , 5.4) ] .
Clonidine: Because milnacipran hydrochloride inhibits norepinephrine reuptake, co-administration with clonidine may inhibit clonidine’s anti-hypertensive effect.
7.7 Drugs that Interfere with Hemostasis Concomitant use of milnacipran hydrochlorid…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • 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 ).
8.1Pregnancy 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 milnacipran hydrochloride 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 milnacipran hydrochloride, 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) .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Consideration Maternal adverse reactions Use of milnacipran hydrochloride in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.9) ]. Fetal/Neonatal adverse reactions Neonates exposed to SNRIs or SSRIs, including milnacipran hydrochloride, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery.
Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These findings are consistent with either direct toxic effect of SSRIs and SNRIs or possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.2 , 5.7 )] .
Data Animal Data Studies were conducted in rats, rabbits and mice with dosing of milnacipran during the period of organogenesis. In rats, milnacipran was shown to increase embryofetal lethality at doses of 5 mg/kg/day (0.25 times the MRHD on a mg/m 2 basis). In rabbits, dose-dependent increases in the incidence of the skeletal variation of an extra single rib were observed in several pups from multiple litters in the absence of maternal toxicity at 15 mg/kg/day (1.5 times the MRHD on a mg/m 2 basis).
The clinical significance of this finding is unknown. In mice, no embryotoxic or teratogenic effects were seen at doses up to 125 mg/kg/day (3 times the MHRD on a mg/m 2 basis). With peri- and postnatal exposure to oral milnacipran in rats, decreases in viability and body weight were observed on Postpartum Day 4 at a dose of 5 mg/kg/day (approximately 0.25 times the MRHD on a mg/m 2 basis).
The no-effect dose for maternal and offspring toxicity was 2.5 mg/kg/day (approximately 0.1 times the MRHD on a mg/m 2 basis).
8.2Lactation Risk Summary Milnacipran is present in human milk [see Data] . There are no reports on the ef…
🤰 Pregnancy ▾
8.1Pregnancy 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 milnacipran hydrochloride 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 milnacipran hydrochloride, 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) .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Consideration Maternal adverse reactions Use of milnacipran hydrochloride in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.9) ]. Fetal/Neonatal adverse reactions Neonates exposed to SNRIs or SSRIs, including milnacipran hydrochloride, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery.
Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These findings are consistent with either direct toxic effect of SSRIs and SNRIs or possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.2 , 5.7 )] .
Data Animal Data Studies were conducted in rats, rabbits and mice with dosing of milnacipran during the period of organogenesis. In rats, milnacipran was shown to increase embryofetal lethality at doses of 5 mg/kg/day (0.25 times the MRHD on a mg/m 2 basis). In rabbits, dose-dependent increases in the incidence of the skeletal variation of an extra single rib were observed in several pups from multiple litters in the absence of maternal toxicity at 15 mg/kg/day (1.5 times the MRHD on a mg/m 2 basis).
The clinical significance of this finding is unknown. In mice, no embryotoxic or teratogenic effects were seen at doses up to 125 mg/kg/day (3 times the MHRD on a mg/m 2 basis). With peri- and postnatal exposure to oral milnacipran in rats, decreases in viability and body weight were observed on Postpartum Day 4 at a dose of 5 mg/kg/day (approximately 0.25 times the MRHD on a mg/m 2 basis).
The no-effect dose for maternal and offspring toxicity was 2.5 mg/kg/day (approximately 0.1 times the MRHD on a mg/m 2 basis).
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of milnacipran hydrochloride in a fibromyalgia pediatric population below the age of 18 have not been established [see Boxed Warning, Indications and Usage (1), and Warnings and Precautions (5.1)] . The use of milnacipran hydrochloride is not recommended in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use In controlled clinical studies of milnacipran hydrochloride, 402 patients were 60 years or older, and no overall differences in safety and efficacy were observed between these patients and younger patients. In view of the predominant excretion of unchanged milnacipran via kidneys and the expected decrease in renal function with age, renal function should be considered prior to use of milnacipran hydrochloride in the elderly [see Dosage and Administration (2.2)] . SNRIs, SSRIs, and milnacipran hydrochloride, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see Warnings and Precautions (5.8)] .
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Presentation There is limited clinical experience with milnacipran hydrochloride 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 milnacipran hydrochloride 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 milnacipran hydrochloride, 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. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients.
Because there is no specific antidote for milnacipran hydrochloride, consider symptomatic care and treatment with gastric lavage and activated charcoal as soon as possible for patients who experience a milnacipran hydrochloride overdose. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be beneficial. In managing overdose, consider the possibility of multiple drug involvement.
The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR).
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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. Milnacipran has no significant affinity for serotonergic (5-HT1-7), α- and β-adrenergic, muscarinic (M1-5), histamine (H1-4), dopamine (D1-5), opiate, benzodiazepine, and γ-aminobutyric acid (GABA) receptors in vitro .
Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Milnacipran has no significant affinity for Ca++, K+, Na+ and Cl– channels and does not inhibit the activity of human monoamine oxidases (MAO-A and MAO-B) or acetylcholinesterase.
12.2Pharmacodynamics Cardiac Electrophysiology The effect of milnacipran hydrochloride on the QTcF interval was measured in a double-blind placebo- and positive-controlled parallel study in 88 healthy subjects using 600 mg/day milnacipran hydrochloride (3 to 6 times the recommended therapeutic dose for fibromyalgia). After baseline and placebo adjustment, the maximum mean QTcF change was 8 ms (2-sided 90% CI, 3 to 12 ms). This increase is not considered to be clinically significant.
12.3Pharmacokinetics 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. It is excreted predominantly unchanged in urine (55%) and has a terminal elimination half-life of about 6 to 8 hours.
Steady-state levels are reached within 36 to 48 hours and can be predicted from single-dose data. The active enantiomer, d -milnacipran, has a longer elimination half-life (8 to 10 hours) than the l -enantiomer (4 to 6 hours). There is no interconversion between the enantiomers.
Absorption Milnacipran hydrochloride is absorbed following oral administration with maximum concentrations (C max ) reached within 2 to 4 hours post dose. Absorption of milnacipran hydrochloride is not affected by food. The absolute bioavailability is approximately 85% to 90%.
Distribution The mean volume of distribution of milnacipran following a single intravenous dose to healthy subjects is approximately 400 L. Plasma protein binding is 13%. Elimination Metabolism Milnacipran and its metabolites are eliminated primarily by renal excretion.
Excretion Following oral administration of 14 C-milnacipran hydrochloride, approximately 55% of the dose was excreted in urine as unchanged milnacipran (24% as l -milnacipran and 31% as d -milnacipran). The l -milnacipran carbamoyl-O-glucuronide was the major metabolite excreted in urine and accounted for approximately 17% of the dose; approximately 2% of the dose was excreted in urine as d-milnacipran carbamoyl-O-glucuronide. Approximately 8% of the dose was excreted in urine as the N-desethyl milnacipran metabolite.
Specific Populations Geriatric Patients C max and AUC parameters of milnacipran were about 30% higher in elderly (> 65 years) subjects compared with young subjects due to age-related decreases in renal function. No dosage adjustment is necessary based on age unless renal function is severely impaired [see Dosage and Administration (2.2) ]. Male and Female Patients C max and AUC parameters of milnacipran were about 20% higher in female subjects compared with male subjects.
Dosage adjustment based on gender is not necessary. Patients with Renal Impairment Milnacipran pharmacokinetics were evaluated following single oral administration of 50 mg milnacipran hydrochloride to subjects with mild (creatinine clearance [CL…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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. Milnacipran has no significant affinity for serotonergic (5-HT1-7), α- and β-adrenergic, muscarinic (M1-5), histamine (H1-4), dopamine (D1-5), opiate, benzodiazepine, and γ-aminobutyric acid (GABA) receptors in vitro .
Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Milnacipran has no significant affinity for Ca++, K+, Na+ and Cl– channels and does not inhibit the activity of human monoamine oxidases (MAO-A and MAO-B) or acetylcholinesterase.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Milnacipran hydrochloride tablets 12.5 mg are blue, round, biconvex film-coated tablets debossed with ‘H’ on one side and ‘M8’ on the other side Bottles of 60 tablets NDC 31722-846-60 Carton of 100 (10 x 10) unit dose tablets NDC 31722-846-32 Milnacipran hydrochloride tablets 25 mg are white to off-white, round, biconvex film-coated tablets debossed with ‘H’ on one side and ‘M9’ on the other side Bottles of 60 tablets NDC 31722-847-60 Carton of 100 (10 x 10) unit dose tablets NDC 31722-847-32 Milnacipran hydrochloride tablets 50 mg are white to off-white, oval, biconvex film-coated tablets debossed with ‘H’ on one side and ‘M10’ on the other side Bottles of 60 tablets NDC 31722-848-60 Carton of 100 (10 x 10) unit dose tablets NDC 31722-848-32 Milnacipran hydrochloride tablets 100 mg are pink, oval, biconvex film-coated tablets debossed with ‘H’ on one side and ‘M11’ on the other side Bottles of 60 tablets NDC 31722-849-60 Carton of 100 (10 x 10) unit dose tablets NDC 31722-849-32 Titration Pack: 4-Week Titration Pack NDC 31722-880-31 Blister package containing 55 tablets: 5 x 12.5 mg tablets, 8 x 25 mg tablets, and 42 x 50 mg tablets.
Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Milnacipran hydrochloride is a selective norepinephrine and serotonin reuptake inhibitor; it inhibits norepinephrine uptake with greater potency than serotonin. The chemical name: (1R,2S)-rel-2- (Amino-methyl)-N,N-diethyl-1-phenylcyclo propane carboxamide hydrochloride. The structural formula is: Milnacipran hydrochloride is a white to off-white powder with a melting point of 179°C.
It is freely soluble in water, methanol and in dimethysulphoxide, soluble in dimethyl formamide. It has an empirical formula of C 15 H 22 N 2 O.HCl and a molecular weight of 282.81 g/mol. Milnacipran hydrochloride tablets are available for oral administration as film-coated tablets containing 12.5 mg, 25 mg, 50 mg, and 100 mg milnacipran hydrochloride.
Each tablet also contains carboxymethylcellulose calcium, colloidal silicon dioxide, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, povidone, sodium bicarbonate, talc and titanium dioxide as inactive ingredients. Additionally, the 12.5 mg tablets contain FD & C Blue #2/Indigo Carmine Aluminum Lake and the 100 mg tablets contain FD&C Red #40 Allura Red AC-Aluminum Lake. milnacipran-hydrochloride-tabletsformula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Advise patients of the following issues and to alert their prescriber if these occur while taking milnacipran hydrochloride tablets. Clinical Worsening and Suicide Risk Advise patients, their families, and their caregivers that patients with depression may be at increased risk for clinical worsening and/or suicidal ideation if they stop taking anti-depressant medication, change the dose, or start a new medication.
Encourage patients, their families, and their caregivers to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, or other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during treatment with milnacipran hydrochloride tablets or other drugs that inhibit the reuptake of norepinephrine and/or serotonin, and when the dose is adjusted up or down. Advise families and caregivers to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt and to report such symptoms to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms [see Boxed Warning and Warnings and Precautions (5.1) ].
Serotonin Syndrome Inform patients about the risk of serotonin syndrome with use of milnacipran hydrochloride tablets as well as the increased risk when taken concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines and St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid) [see Warnings and Precautions (5.2) , Drug Interactions (7.2) ] .
Advise patients of the signs and symptoms associated with serotonin syndrome and to seek medical care immediately if they experience these symptoms. Elevated Blood Pressure and Heart Rate Advise patients that milnacipran hydrochloride tablets may increase their blood pressure and heart rate and that they should have their blood pressure and heart rate monitored at regular intervals when receiving treatment with milnacipran hydrochloride tablets [see Warnings and Precautions (5.3 , 5.4) ]. Increased Risk of Bleeding Advise patients that the concomitant use of drugs that interfere with serotonin reuptake, including milnacipran hydrochloride tablets, and NSAIDs, aspirin, or anticoagulants has been associated with an increased risk of abnormal bleeding [see Warnings and Precautions (5.9) ] .
Angle Closure Glaucoma Advise patients that taking milnacipran hydrochloride tablets can cause mild pupillary dilation which, in susceptible individuals, can lead to an episode of angle closure glaucoma. [see Warnings and Precautions (5.13) ]. Ability to Drive and Use Machinery Advise patients not to operate machinery or drive motor vehicles until they are reasonably certain that milnacipran hydrochloride tablets treatment does not affect their ability to engage in such activities. Alcohol Inform patients of the risks associated with drinking alcohol while taking milnacipran hydrochloride tablets [see Warnings and Precautions (5.6, 5.14) ].
Sexual Dysfunction Advise patients that use of milnacipran hydrochloride tablets may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions (5.12) ]. Discontinuation Advise patients that withdrawal symptoms can occur when discontinuing treatment with milnacipran hydrochloride tablets, particularly when discontinuation is abrupt [see Warnings and Precautions (5.7)] .
Missing a Dose Advise patients t…
💬 Medication Guide ▾
MEDICATION GUIDE Milnacipran Hydrochloride (mil naʹ si pran hyeʺ droe klorʹ ide) Tablets Milnacipran hydrochloride tablets are not used to treat depression, but it acts like medicines that are used to treat depression (antidepressants) and other psychiatric disorders. Read the Medication Guide that comes with milnacipran hydrochloride tablets before you start taking it and each time you get a refill. There may be new information.
This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about. What is the most important information I should know about Milnacipran hydrochloride tablets?
Milnacipran hydrochloride tablets and antidepressant medicines may cause serious side effects, including: 1. Suicidal thoughts or actions: • Milnacipran hydrochloride tablets and antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment or when the dose is changed. • Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Watch for these changes and call your healthcare provider right away if you notice: • New or sudden changes, in mood, behavior, thoughts, or feelings, especially if severe. • Pay particular attention to such changes when milnacipran hydrochloride tablets are started or when the dose is changed. • Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms.
Call your healthcare provider right away or go to the nearest hospital emergency room if you have any of the following symptoms, especially if they are new, worse, or worry you: • attempts to commit suicide • feeling agitated, restless, angry or irritable • acting on dangerous impulses • trouble sleeping (insomnia) • acting aggressive, being angry, or violent • an increase in activity or talking more than what is normal for you • thoughts about suicide or dying • other unusual changes in behavior or mood • new or worse depression • new or worse anxiety or panic attacks Call your healthcare provider right away or go to the nearest hospital emergency room if you have any symptoms of the serious side effects listed below: 2.
Serotonin Syndrome. This condition can be life-threatening, symptoms may include: • agitation, hallucinations, coma or other changes in mental status • coordination problems or muscle twitching (overactive reflexes) • sweating or fever • diarrhea • muscle rigidity • dizziness • tremor Symptoms such as racing heartbeat, high or low blood pressure, nausea, vomiting, and flushing are common with milnacipran hydrochloride tablets. Call your healthcare provider right away if you get these symptoms and they are severe or if they happen with any of the symptoms of serotonin syndrome listed above.
3. Increase in blood pressure or heart rate: Milnacipran hydrochloride tablets may increase your blood pressure or heart rate. Check your blood pressure and heart rate before you start and during treatment with milnacipran hydrochloride tablets.
Before taking milnacipran hydrochloride tablets, tell your healthcare provider if you have high blood pressure or problems with your heart or blood vessels (cardiovascular disease). 4. Seizures or convulsions.
5. Liver problems. Symptoms of liver problems may include: • itching • right upper abdominal pain • dark urine • yellowing of your skin or eyes • enlarged liver • increased liver enzymes 6.
Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include: • headache • weakness or feeling unsteady • confusion, problems concentrating or thinking or memory problems 7.
Abnormal bleeding: Milnacipran hydrochloride tablets and other similar medicines (antidepressants) may increase your risk of bleeding or bruising, especial…