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Milnacipran Hydrochloride Kit, 1 kit — NDC 31722-0880-31 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Milnacipran Hydrochloride Kit, 1 kit — NDC 31722-880-31 (Billing 31722-0880-31)

by Camber Pharmaceuticals, Inc. · 1 KIT in 1 BLISTER PACK

This is a package of 1 kit of Milnacipran Hydrochloride Kit from Camber Pharmaceuticals, Inc., marketed since Mar 2026 and currently FDA-listed. It is this product's only package size.

NDC 31722-0880-31
🏷️ FDA NDC (as labeled) 31722-880-31 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 31722-880-31
Product NDC 31722-880
11-digit billing NDC 31722088031
NCPDP billing unit EA — each (per item)
RxCUI 833135, 833141, 833144, 833147, 833150
UNII RNZ43O5WW5
UPC 0331722846608, 0331722847605, 0331722849609, 0331722848602
Application # ANDA205147
SPL Set ID 99efa59a-8458-4e04-8cb1-20abfc179228
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2026-03-19
Dosage form KIT
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 62504050106320
GCN Seq No 065091
GCN 22025
HICL code 021229
Ingredient (HICL) Milnacipran Hcl
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H0
Therapeutic class — intermediate (HIC2) Act On Non-Autonomic Nervous System
HIC3 code H0G
Therapeutic class — specific (HIC3) Fibromyalgia Agents,Serotonin-Norepineph Ru Inhib
AHFS code 28:16.04.16
AHFS class Sel.serotonin,Norepi Reuptake Inhibitor
FDB label name MILNACIPRAN HCL TITRATION PACK
FDB brand name Milnacipran Hcl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 065091
  • GCN: 22025
  • GPI-14 (Medi-Span): 62504050106320
  • HICL (First Databank): 021229
  • AHFS class code: 28:16.04.16
  • RxCUI (RxNorm): 833135
Why two NDCs? The FDA registers this code as 31722-880-31 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 31722-0880-31. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Serotonin and Norepinephrine Reuptake Inhibitor class.

Pharmacologic class Serotonin and Norepinephrine Reuptake Inhibitor
Drug family (ATC) Other antidepressants
How it works Norepinephrine Uptake Inhibitors, Serotonin Uptake Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name MILNACIPRAN HCL TITRATION PACK Ingredient Milnacipran Hcl
📗 Our plain-language guide HelloPharmacist
  • 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?
📖 Read our full Milnacipran guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
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.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
31722-0880-31 You're viewing this Main listing 1 KIT in 1 BLISTER PACK 2026-03-19 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Savella 00456-1500-55 Allergan, 1 kit $8.141 AB Availability likely —
Milnacipran Hydrochloridethis 31722-0880-31 Camber 1 kit — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2026
On the market since
Mar 2026
📍
2026
Currently FDA-listed
listed with the FDA
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color blue / white / pink
ShapeOval
ImprintH;M10
Size12 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerCamber Pharmaceuticals, Inc.
Application holderHETERO LABS LTD UNIT V
FDA applicationANDA205147 (ANDA)
Labeler code31722
First marketedMar 2026
Product typeHuman Prescription Drug
Portfolio603 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🔒 Controlled Substance 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~1 min read ▾

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 65 words ▾

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 ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 122 words ▾

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 180 words ▾

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 ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

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.

7.7Drugs that Interfere with Hemostasis Concomitant use of milnacipran hydrochlorid… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

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 47 words ▾

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 106 words ▾

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 ~1 min read ▾

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 ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 144 words ▾

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 220 words ▾

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 162 words ▾

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 ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

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 [CLcr] 50 to 80 mL/min), moderate (CLcr 30 to 49 mL/min), and severe (CLcr 5 to 29 mL/min) renal impairment and to healthy subjects (CLcr > 80 mL/min). The mean AUC 0 to ∞ increased by 16%, 52%, and 199%, and terminal elimination half-life increased by 38%, 41%, and 122% in subjects with mild, moderate, and severe renal impairment, respectively, compared with healthy subjects.

No dosage adjustment is necessary for patients with mild renal impairment. Exercise caution in patients with moderate renal impairment. Dose adjustment is necessary in severe renal impairment patients [see Dosage and Administration (2.2) ].

Patients with Hepatic Impairment Milnacipran pharmacokinetics were evaluated following single oral administration of 50 mg milnacipran hydrochloride to subjects with mild (Child-Pugh A), moderate (Child-Pugh B), and severe (Child-Pugh C) hepatic impairment and to healthy subjects. AUC 0 to ∞ and T ½ were similar in healthy subjects and subjects with mild and moderate hepatic impairment. However, subjects with severe hepatic impairment had a 31% higher AUC 0 to ∞ and a 55% higher T ½ than healthy subjects.

Exercise caution in patients with severe hepatic impairment. Drug Interaction Studies In Vitro Studies: In general, milnacipran, at concentrations that were at least 25 times those attained in clinical trials, did not inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 or induce human CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4/5 enzyme systems, indicating a low potential of interactions with drugs metabolized by the… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 71 words ▾

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.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES Management of Fibromyalgia The efficacy of milnacipran hydrochloride for the management of fibromyalgia was established in two double-blind, placebo-controlled, multicenter studies in adult patients (18 to 74 years of age). Enrolled patients met the American College of Rheumatology (ACR) criteria for fibromyalgia (a history of widespread pain for 3 months and pain present at 11 or more of the 18 specific tender point sites). Approximately 35% of patients had a history of depression.

Study 1 was six months in duration and Study 2 was three months in duration. A larger proportion of patients treated with milnacipran hydrochloride than with placebo experienced a simultaneous reduction in pain from baseline of at least 30% (VAS) and also rated themselves as much improved or very much improved based on the patient global assessment (PGIC). In addition, a larger proportion of patients treated with milnacipran hydrochloride met the criteria for treatment response, as measured by the composite endpoint that concurrently evaluated improvement in pain (VAS), physical function (SF-36 PCS), and patient global assessment (PGIC), in fibromyalgia as compared to placebo.

Study 1: This 6-month study compared total daily doses of milnacipran hydrochloride 100 mg and 200 mg to placebo. Patients were enrolled with a minimum mean baseline pain score of ≥ 50 mm on a 100 mm visual analog scale (VAS) ranging from 0 (“no pain”) to 100 (“worst possible pain”). The mean baseline pain score in this trial was 69.

The efficacy results for Study 1 are summarized in Figure 1. Figure 1 shows the proportion of patients achieving various degrees of improvement in pain from baseline to the 3-month time point and who concurrently rated themselves globally improved (PGIC score of 1 or 2). Patients who did not complete the 3-month assessment were assigned 0% improvement.

More patients in the milnacipran hydrochloride treatment arms experienced at least a 30% reduction in pain from baseline (VAS) and considered themselves globally improved (PGIC) than did patients in the placebo arm. Treatment with milnacipran hydrochloride 200 mg/day did not confer greater benefit than treatment with milnacipran hydrochloride 100 mg/day. Figure 1: Patients Achieving Various Levels of Pain Relief with Concurrent Ratings of Being Much or Very Much Improved on the PGIC ― Study 1 Study 2: This 3-month study compared total daily doses of milnacipran hydrochloride 100 mg and 200 mg to placebo.

Patients were enrolled with a minimum mean baseline pain score of ≥ 40 mm on a 100 mm VAS ranging from 0 (“no pain”) to 100 (“worst possible pain”). The mean baseline pain score in this trial was 65. The efficacy results for Study 2 are summarized in Figure 2.

Figure 2 shows the proportion of patients achieving various degrees of improvement in pain from baseline to the 3-month time point and who concurrently rated themselves globally improved (PGIC score of 1 or 2). Patients who did not complete the 3-month assessment were assigned 0% improvement. More patients in the milnacipran hydrochloride treatment arms experienced at least a 30% reduction in pain from baseline (VAS) and considered themselves globally improved (PGIC) than did patients in the placebo arm.

Treatment with milnacipran hydrochloride 200 mg/day did not confer greater benefit than treatment with milnacipran hydrochloride 100 mg/day. Figure 2: Patients Achieving Various Levels of Pain Relief with Concurrent Ratings of Being Much or Very Much Improved on the PGIC ― Study 2 In both studies, some patients who rated themselves as globally “much” or “very much” improved experienced a decrease in pain as early as week 1 of treatment with a stable dose of milnacipran hydrochloride that persisted throughout these studies. milnacipran-hydrochloride-tabletsfigure1 milnacipran-hydrochloride-tabletsfigure2

🔒 Drug Abuse and Dependence 78 words ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Milnacipran is not a controlled substance.

9.2Abuse Milnacipran did not produce behavioral signs indicative of abuse potential in animal or human studies.

9.3Dependence Milnacipran produces physical dependence, as evidenced by the emergence of withdrawal symptoms following drug discontinuation, similar to other SNRIs and SSRIs. These withdrawal symptoms can be severe. Thus, taper milnacipran hydrochloride and do not abruptly discontinue after extended use [see Warnings and Precautions (5.7)] .

🔒 Controlled Substance 9 words ▾

9.1Controlled Substance Milnacipran is not a controlled substance.

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Dietary administration of milnacipran to rats at doses of 50 mg/kg/day (2 times the MRHD on a mg/m 2 basis) for 2 years caused a statistically significant increase in the incidence of thyroid C-cell adenomas and combined adenomas and carcinomas in males. A carcinogenicity study was conducted in Tg.rasH2 mice for 6 months at oral gavage doses of up to 125 mg/kg/day. Milnacipran did not induce tumors in Tg.rasH2 mice at any dose tested.

Mutagenesis Milnacipran was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test) or in the L5178Y TK +/- mouse lymphoma forward mutation assay. Milnacipran was also not clastogenic in an in vitro chromosomal aberration test in human lymphocytes or in the in vivo mouse micronucleus assay. Impairment of Fertility Although administration of milnacipran to male and female rats had no statistically significant effect on mating or fertility at doses up to 80 mg/kg/day (4 times the MRHD on an mg/m 2 basis), there was an apparent dose-related decrease in the fertility index at clinically relevant doses based on body surface area.

13.2Animal Toxicology and/or Pharmacology Hepatic Effects Chronic administration (2 years) of milnacipran to rats at 15 mg/kg (0.6 times the MRHD on an mg/m 2 basis) and higher doses showed increased incidences of centrilobular vacuolation of the liver in male rats and eosinophilic foci in male and female rats in the absence of any change in hepatic enzymes. The clinical significance of the finding is not known. Chronic (1 year) administration in the primate at doses up to 25 mg/kg (2 times the MRHD on a mg/m 2 basis) did not demonstrate similar evidence of hepatic changes.

Ocular Effects Chronic (2 years) administration of milnacipran to rats at 15 mg/kg (0.6 times the MRHD on a mg/m 2 basis) and higher doses showed increased incidence of keratitis of the eye. One-year studies in the rat and primate did not show this response.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 185 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Dietary administration of milnacipran to rats at doses of 50 mg/kg/day (2 times the MRHD on a mg/m 2 basis) for 2 years caused a statistically significant increase in the incidence of thyroid C-cell adenomas and combined adenomas and carcinomas in males. A carcinogenicity study was conducted in Tg.rasH2 mice for 6 months at oral gavage doses of up to 125 mg/kg/day. Milnacipran did not induce tumors in Tg.rasH2 mice at any dose tested.

Mutagenesis Milnacipran was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test) or in the L5178Y TK +/- mouse lymphoma forward mutation assay. Milnacipran was also not clastogenic in an in vitro chromosomal aberration test in human lymphocytes or in the in vivo mouse micronucleus assay. Impairment of Fertility Although administration of milnacipran to male and female rats had no statistically significant effect on mating or fertility at doses up to 80 mg/kg/day (4 times the MRHD on an mg/m 2 basis), there was an apparent dose-related decrease in the fertility index at clinically relevant doses based on body surface area.

📄 Package Label / Principal Display Panel 24 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Milnacipran 12.5mg 60s Milnacipran 25mg 60s Milnacipran 50mg 60s Milnacipran 100mg 60s Milnacipran Tablets Titration milnacipranhydrochloridetablets125 milnacipran-hydrochloride-tablets25 milnacipran-hydrochloride-tablets50 milnacipran-hydrochloride-tablets100mg milnacipran-hydrochloride-tablets100mg

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Milnacipran hydrochloride — the ingredient across all brands.

Top reported reactions

Nausea696
Pain518
Headache487
Vomiting360
Fatigue342
Dizziness339
Insomnia325

Age at onset

Adult314
Elderly98

Reporter sex

5,982 reports
Male · 10%
Female · 89%
Unknown · 0%

Serious outcomes

Disabling179
Death152
Reports over time (by year) — tap or hover for the count & year
2020 2022 2024 2026 251 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product Kit / multi-component package

Kit / multi-component package

This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.

What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Camber Pharmaceuticals, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Camber Pharmaceuticals, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 31722-0879-01 · Camber 31722-0882-31 · Camber →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.