Milnacipran Hydrochloride
Generic Name: milnacipran hydrochloride
Brand Names:
Savella
11 DESCRIPTION Milnacipran hydrochloride is a selective norepinephrine and serotonin reuptake inhibitor; it inhibits norepinephrine uptake with greater potency than serotonin. It is a racemic mixture with the chemical name: (±)-[1R(S),2S(R)]-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide hydrochloride. The structural formula is: Milnacipran hydrochloride is a white to off-white crystalline powder with a melting point of 179°C.
Overview
11 DESCRIPTION Milnacipran hydrochloride is a selective norepinephrine and serotonin reuptake inhibitor; it inhibits norepinephrine uptake with greater potency than serotonin. It is a racemic mixture with the chemical name: (±)-[1R(S),2S(R)]-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide hydrochloride. The structural formula is: Milnacipran hydrochloride is a white to off-white crystalline powder with a melting point of 179°C.
Uses
1 INDICATIONS AND USAGE SAVELLA is indicated for the management of fibromyalgia. SAVELLA is not approved for use in pediatric patients [see Use in Specific Populations ( 8.4 )] . • SAVELLA ® is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the management of fibromyalgia ( 1 ). • SAVELLA is not approved for use in pediatric patients ( 1 ).
Dosage
2 DOSAGE AND ADMINISTRATION SAVELLA is given orally with or without food. Taking SAVELLA with food may improve the tolerability of the drug. • Administer SAVELLA in two divided doses per day ( 2.1 ). • Based on efficacy and tolerability, dosing may be titrated according to the following schedule ( 2.1 ): Day 1: 12.5 mg once Days 2-3: 25 mg/day (12.5 mg twice daily) Days 4-7: 50 mg/day (25 mg twice daily) After Day 7: 100 mg/day (50 mg twice daily) • Recommended dose is 100 mg/day ( 2.1 ). • May be increased to 200 mg/day based on individual patient response ( 2.1 ). • Adjust dose in patients with severe renal impairment ( 2.2 ). 2.1 Recommended Dosing The recommended dose of SAVELLA is 100 mg/day (50 mg twice daily).
Side Effects
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 AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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.
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 SAVELLA is unlikely to be involved in clinically significant pharmacokinetic drug interactions [see Pharmacokinetics in Special Populations ( 12.3 )] . • SAVELLA is unlikely to be involved in clinically significant pharmacokinetic drug interactions ( 7 ). • Pharmacodynamic interactions of SAVELLA with other drugs can occur ( 7 ). 7.1 Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of SSRIs and SNRIs, including SAVELLA, with MAOIs increases the risk of serotonin syndrome.
Warnings
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS SAVELLA is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. 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 SAVELLA and any other serotonergic agents, and initiate supportive treatment ( 5.2 ). • Elevated Blood Pressure and Heart Rate : SAVELLA may increase blood pressure and heart rate. Measure blood pressure and heart rate prior to initiating treatment with SAVELLA and monitor periodically throughout treatment ( 5.3 , 5.4 ). • Seizures : Cases have been reported with SAVELLA therapy. Prescribe SAVELLA with care in patients with a history of seizure disorder ( 5.5 ). • Hepatotoxicity : SAVELLA may cause elevations of ALT and AST. 4 CONTRAINDICATIONS • Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with SAVELLA or within 5 days of stopping treatment with SAVELLA. Do not use SAVELLA within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start SAVELLA in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1 , 5.2 ).
Pregnancy
8.1 Pregnancy Risk Summary Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.2 )] . The available data on SAVELLA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Storage
16 HOW SUPPLIED/STORAGE AND HANDLING 50-mg tablets: White, oval-shaped, film-coated tablets, debossed with “FL” on one side and “50” on the reverse side Bottles of approximately 1920 film-coated tablets, NDC 55154-4626-8 Storage Store at 25°C (77°F); excursions permitted between 15°C and 30°C (between 59°F and 86°F) [See USP Controlled Room Temperature] .
Frequently Asked Questions
What is Milnacipran Hydrochloride used for?▼
1 INDICATIONS AND USAGE SAVELLA is indicated for the management of fibromyalgia. SAVELLA is not approved for use in pediatric patients [see Use in Specific Populations ( 8.4 )] . • SAVELLA ® is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the management of fibromyalgia ( 1 ). • SAVELLA is not approved for use in pediatric patients ( 1 ).
What are the side effects of Milnacipran Hydrochloride?▼
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 AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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.
Can I take Milnacipran Hydrochloride during pregnancy?▼
8.1 Pregnancy Risk Summary Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.2 )] . The available data on SAVELLA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
What are the important warnings for Milnacipran Hydrochloride?▼
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS SAVELLA is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. 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 SAVELLA and any other serotonergic agents, and initiate supportive treatment ( 5.2 ). • Elevated Blood Pressure and Heart Rate : SAVELLA may increase blood pressure and heart rate. Measure blood pressure and heart rate prior to initiating treatment with SAVELLA and monitor periodically throughout treatment ( 5.3 , 5.4 ). • Seizures : Cases have been reported with SAVELLA therapy. Prescribe SAVELLA with care in patients with a history of seizure disorder ( 5.5 ). • Hepatotoxicity : SAVELLA may cause elevations of ALT and AST. 4 CONTRAINDICATIONS • Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with SAVELLA or within 5 days of stopping treatment with SAVELLA. Do not use SAVELLA within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start SAVELLA in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1 , 5.2 ).
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Medical Disclaimer
This drug information is for educational purposes only and should not replace professional medical advice. Drug information is sourced from the FDA National Drug Code Directory and Structured Product Labeling. Always consult with a healthcare provider before starting, stopping, or changing any medication.