Clinical Studies
Savella has been extensively studied
Savella achieved positive outcomes in 4 of 4 efficacy studies involving nearly 4,000 patients
- History of widespread pain for ≥3 months
- Pain present at ≥11 of 18 specific tender points
INDICATION
SAVELLA® (milnacipran HCI) is indicated for the management of fibromyalgia. SAVELLA is not approved for use in pediatric patients.
IMPORTANT SAFETY INFORMATION
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. 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 SAVELLA 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. SAVELLA is not approved for use in the treatment of MDD. SAVELLA is not approved for use in pediatric patients.
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. 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 SAVELLA 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. SAVELLA is not approved for use in the treatment of MDD. SAVELLA is not approved for use in pediatric patients.
Contraindications
- The use of monoamine oxidase inhibitors (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
- Suicide Risk: All patients being treated with drugs inhibiting the reuptake of norepinephrine and/or serotonin for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of treatment and when increasing or decreasing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is worsening or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Families and caregivers of patients being treated with drugs that inhibit the reuptake of norepinephrine and/or serotonin should be alerted about the need to monitor patients daily. Prescriptions for SAVELLA should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
- Serotonin Syndrome: Selective-serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), including SAVELLA, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, ie, MAOIs. Serotonin syndrome can also occur when these drugs are used alone. Symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular syndrome (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If symptoms of serotonin syndrome occur, discontinue SAVELLA and any concomitant serotonergic agents immediately and initiate supportive treatment. If concomitant use of SAVELLA with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
- Elevated Blood Pressure: SAVELLA may increase blood pressure. Cases of elevated blood pressure requiring immediate treatment have been reported. Blood pressure should be measured prior to initiating treatment and periodically throughout SAVELLA treatment. Treat preexisting hypertension and other cardiovascular disease before starting therapy with SAVELLA. Use with caution in patients with preexisting hypertension or cardiovascular or cerebrovascular conditions that might be compromised by increases in blood pressure. Concomitant use of SAVELLA with drugs that increase blood pressure and heart rate has not been evaluated, and such combinations should be used with caution. For patients who experience a sustained increase in blood pressure while receiving SAVELLA, either reduce the dose or discontinue.
- Elevated Heart Rate: SAVELLA may increase heart rate. In an ambulatory blood pressure monitoring (ABPM) study, the mean increase in mean 24-hour heart rate from baseline was 13 beats per minute. Measure heart rate prior to initiating treatment, and periodically monitor the heart rate throughout SAVELLA treatment. Treat preexisting tachyarrhythmias and other cardiac disease before starting therapy with SAVELLA. For patients who experience a sustained increase in heart rate while receiving SAVELLA, either reduce the dose or discontinue treatment with SAVELLA, if clinically warranted.
- Seizures: SAVELLA should be prescribed with care in patients with a history of seizure disorder.
- Activation of Mania: SAVELLA should be used cautiously in patients with a history of mania.
- Hepatotoxicity: SAVELLA has been associated with mild elevations of ALT and AST (1 to 3 times the upper limit of normal). Rarely, serious liver injury, including fulminant hepatitis, has been reported in patients treated with SAVELLA. SAVELLA should be discontinued in patients who develop jaundice or other evidence of liver dysfunction and should not be resumed unless another cause can be established.
- Discontinuation of Treatment With SAVELLA: As with other SSRIs and SNRIs, withdrawal symptoms have been observed following discontinuation of SAVELLA. A gradual dose reduction is recommended.
- Hyponatremia: Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including SAVELLA. Elderly patients may be at greater risk. Discontinuation should be considered for patients with symptomatic hyponatremia.
- Increased Risk of Abnormal Bleeding: SSRIs and SNRIs, including SAVELLA, may increase the risk of bleeding events. Inform patients about the risk of bleeding associated with concomitant use of SAVELLA and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation.
- Patients With a History of Dysuria: SAVELLA can affect urethral resistance and micturition. Caution is advised in the use of SAVELLA in patients with a history of dysuria, notably in male patients with a history of obstructive uropathies, as these patients may experience higher rates of genitourinary adverse events.
- Sexual Dysfunction: SAVELLA may cause symptoms of sexual dysfunction. Discuss potential management strategies to support patients in making informed decisions about treatment.
- Angle-closure Glaucoma: SAVELLA, like other SNRI drugs, can cause pupillary dilation. This may trigger acute closed-angle glaucoma in a patient with anatomically narrow angles who does not have a patent iridectomy.
- Concomitant Use With Alcohol: SAVELLA should not be prescribed to patients who drink a substantial amount of alcohol or who have evidence of chronic liver disease.
Use in Specific Populations
- Pregnancy: Third trimester use of SAVELLA may increase risk for symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SAVELLA during pregnancy. Physicians are advised to recommend that pregnant patients taking SAVELLA enroll in the Savella Pregnancy Registry. Enrollment is voluntary and may be initiated by pregnant patients or their healthcare providers by contacting the registry at 1-877-643-3010 or by email at [email protected]. Data forms may also be downloaded from the registry website at www.savellapregnancyregistry.com.
- Lactation: Milnacipran is present in the milk of lactating women treated with SAVELLA. Monitor infants exposed to milnacipran for agitation, irritability, poor feeding, and poor weight gain.
Adverse Reactions
In clinical trials, the most frequently occurring adverse reaction was nausea (37% vs 20% for placebo). The most commonly occurring adverse reactions (≥5% and greater than placebo) were headache (18% vs 14%), constipation (16% vs 4%), dizziness (10% vs 6%), insomnia (12% vs 10%), hot flush (12% vs 2%), hyperhidrosis (9% vs 2%), vomiting (7% vs 2%), palpitations (7% vs 2%), increased heart rate (6% vs 1%), dry mouth (5% vs 2%), and hypertension (5% vs 2%).
