Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
Angle Closure Glaucoma
- The pupillary dilation that occurs following use of SNRI drugs including Savella may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
Monoamine Oxidase Inhibitors (MAOIs)
- The use of MAOIs intended to treat psychiatric disorders with Savella or within 5 days of stopping treatment with Savella is contraindicated because of an increased risk of serotonin syndrome. The use of Savella within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated.
- Starting Savella 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.
WARNINGS AND PRECAUTIONS
- The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Savella, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, 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 and intravenous methylene blue).
- Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin…
Elevated Blood Pressure
- A double-blind, placebo-controlled ambulatory blood pressure monitoring (ABPM) study was conducted to evaluate the effects of milnacipran (up to 200 mg/day) on blood pressure in 321 fibromyalgia patients. Among fibromyalgia patients who were normotensive at baseline, an analysis of the blood pressure findings demonstrated a substantially higher proportion of Savellatreated patients had a hypertensive…
Elevated Heart Rate
- A double-blind, placebo-controlled ABPM study was conducted to evaluate the effects of milnacipran (up to 200 mg/day) on blood pressure in 321 fibromyalgia patients [see Warnings and Precautions (5.3)]. Information on heart rate was also collected. Following treatment with Savella 50 mg BID for three weeks in patients who…
Postmarketing Spontaneous Reports
- Anger, aggression and homicidal ideation
USE IN SPECIFIC POPULATIONS
- Milnacipran is present in the milk of lactating women treated with Savella. In a pharmacokinetic study, a single, oral dose of 50 mg milnacipran HCl tablet was administered to 8 lactating women who were at least 12 weeks postpartum and weaning their infants. The maximum estimated daily infant dose for milnacipran from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 5% of the maternal dose based on peak plasma concentrations. In most patients, peak concentrations of milnacipran in breast milk were seen within 4 hours after the maternal dose. Because of the limited data regarding infant exposure to Savella, caution should be exercised when Savella is administered to a nursing woman.
Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-Like Reactions
- The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including Savella, but particularly with concomitant use of serotonergic drugs (including triptans), with drugs which impair metabolism of serotonin (including MAOIs) or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.