Savella (milnacipran HCl)

Dosage of milnacipran hydrochloride is expressed in terms of the salt.

Milnacipran hydrochloride is administered orally twice daily in divided doses without regard to meals; however, taking the drug with food may improve tolerability.

The manufacturer states that at least 2 weeks must elapse between discontinuance of a monoamine oxidase (MAO) inhibitor intended to treat psychiatric disorders and initiation of milnacipran therapy and that at least 5 days must elapse between discontinuance of milnacipran and initiation of MAO inhibitor therapy intended to treat psychiatric disorders. (See Contraindications, Serotonin Syndrome under Warnings/Precautions: Other Warnings and Precautions, in Cautions, and Drug Interactions: Monoamine Oxidase Inhibitors.)

Patients receiving milnacipran for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, particularly during initial therapy or following any change (increase or decrease) in dosage. (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

No dosing information is available for this tab.

No dosing information is available for this tab.

In vitro and in vivo studies suggest that milnacipran is unlikely to be involved in clinically important pharmacokinetic drug interactions.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

Concurrent or recent (i.e., within 2 weeks) therapy with a monoamine oxidase (MAO) inhibitor intended to treat psychiatric disorders. Use of an MAO inhibitor intended to treat psychiatric disorders within 5 days of milnacipran discontinuance. (See Serotonin Syndrome under Warnings/Precautions: Other Warnings and Precautions, in Cautions and also see Drug Interactions: Monoamine Oxidase Inhibitors.)

Initiation of milnacipran therapy in patients receiving MAO inhibitors such as linezolid or IV methylene blue. (See Drug Interactions: Linezolid and also see Drug Interactions: Methylene Blue.)

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in at least 5% of patients with fibromyalgia receiving milnacipran and at an incidence greater than that reported with placebo in controlled studies include nausea, vomiting, constipation, headache, insomnia, dizziness, hot flushes, hyperhidrosis, palpitations, increased heart rate, hypertension, dry mouth, and migraine.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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The manufacturer states that safety and effectiveness of milnacipran in pediatric patients younger than 18 years of age with fibromyalgia have not been established and that the drug is not recommended for use in such patients. Fibromyalgia in children and adolescents has not been as well studied as in adults to date; however, the syndrome appeared to be characterized by diffuse pain and sleep disturbances in one pediatric patient series.

Milnacipran is an SNRI and is similar to some drugs used for the treatment of depression and other psychiatric disorders. FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients younger than 19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

These findings should be carefully considered when assessing potential benefits and risks of milnacipran in a child or adolescent for any clinical use. (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

Category C. (See Users Guide.)

The Savella Pregnancy Registry may be contacted at 877-643-3010 (for clinicians and patients); registry information also is available on the website http://www.savellapregnancyregistry.com or by e-mail at pregnancyregistries2@INCResearch.com.

Some neonates exposed to SNRIs or SSRIs late in the third trimester of pregnancy have developed complications, which have sometimes been severe and required prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in special-care nurseries. Such complications may arise immediately upon delivery and usually last several days or up to 2-4 weeks. Clinical findings reported to date in the neonates have included respiratory distress, cyanosis, apnea, seizures, temperature instability or fever, feeding difficulty, dehydration, excessive weight loss, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, reduced or lack of reaction to pain stimuli, and constant crying. These clinical features appear to be consistent with either a direct toxic effect of the SNRI or SSRI or, possibly, a drug withdrawal syndrome. In some cases, the clinical picture was consistent with serotonin syndrome (see Serotonin Syndrome under Warnings/Precautions, in Cautions).

Milnacipran is distributed into human milk. In a pharmacokinetic study in lactating women given a single, 50-mg dose of the drug, the maximum estimated daily infant dose from breast milk was 5% of the maternal dose based on peak plasma concentrations. In most patients, peak concentrations of milnacipran in breast milk occurred within 4 hours after the maternal dose. Because data regarding infant exposure to milnacipran are limited, caution should be exercised when milnacipran is administered to a nursing woman.

In controlled trials of milnacipran, 402 patients were 60 years of age or older; no overall differences in efficacy or safety were observed between these patients and younger adults.

Because milnacipran and its metabolites are eliminated principally by renal excretion and because of expected decreases in renal function with increasing age, renal function should be considered prior to using the drug in geriatric patients. (See Dosage and Administration: Special Populations.)

SSRIs and SNRIs, including milnacipran, have been associated with clinically important hyponatremia in geriatric patients, who may be at greater risk for this adverse effect. (See Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Secretion under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults 65 years of age or older with antidepressant therapy compared with placebo. (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)