Savella

Suicide Risk

• Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18­-24) with major depressive disorder (MDD) and other psychiatric disorders.

• No suicides occurred in any of the pediatric studies.

• The risk of suicidal thoughts and behaviors is unknown with long-term use.

• Monitor all patients for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months and at times of dosage changes.

• In patients whose depression persistently worsens, consider changing the therapeutic regimen by tapering gradually if possible.

• Families/caregivers: Monitor patients for emergence of agitation, irritability, unusual changes in behavior and report to health care provider.

• Prescriptions for Savella should be written for the smallest quantity of capsules consistent with good patient management in order to reduce overdose risk.

Serotonin Syndrome

• See Interactions.

• Serotonin syndrome: Mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia),  neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), and GI symptoms (eg, nausea, vomiting, diarrhea).

• Has been reported with SSRIs and SNRIs, including Savella, and with concomitant use of serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John’s Wort) and with drugs that impair serotonin metabolism (eg, MOAIs, linezolid, IV methylene blue).

• Monitor patients for the emergence of serotonin syndrome.

• Concomitant use of MAOIs and Savella is contraindicated; discontinue Savella before initiating treatment with an MAOI.

• Patients should be made aware of the potential for serotonin syndrome if concomitant use of Savella and other serotonergic drugs is clinically warranted.

Elevated Blood Pressure

• Monitor blood pressure prior to initiation and regularly during treatment. Treat pre-existing hypertension and other cardiovascular disease prior to starting therapy with Savella.

• Consider reducing dose or discontinuing treatment if sustained increase in blood pressure occurs.

Elevated Heart Rate

• Monitor HR prior to initiation and periodically during treatment. Treat pre-existing tachyarrhythmias and other cardiac disease prior to starting therapy with Savella.

• Consider reducing dose or discontinuing treatment if sustained increase in heart rate occurs.

Seizures

• Use caution in patients with a seizure disorder.

Hepatotoxicity

• There have been cases of increased liver enzymes and reports of severe liver injury, including fulminant hepatitis with milnacipran from foreign postmarketing experience.

• Discontinue Savella if jaundice or other evidence of liver dysfunction occurs. Do not resume treatment with Savella unless another cause can be established.

• In general, do not prescribe Savella to patients with substantial alcohol use or evidence of chronic liver disease.

Discontinuation of Treatment with Savella

• Withdrawal symptoms have been observed in clinical trials after Savella was discontinued.

• Monitor for withdrawal symptoms when discontinuing treatment with Savella.

• A gradual dosage reduction is recommended. Do not abruptly discontinue Savella. Consider resuming previously prescribed dose of Savella if intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment.

Hyponatremia

• Greater risk of developing hyponatremia with SNRIs, SSRIs, or Savella in elderly patients, patients taking diuretics, or those who are otherwise volume-depleted.

• Consider discontinuing treatment with Savella in patients with symptomatic hyponatremia.

Increased Risk of Bleeding  

• See Interactions.

• Concomitant use with aspirin, NSAIDs, warfarin, other anticoagulants or other drugs known to affect platelet function may increase the risk of bleeding.

• Advise patients about the increased risk of bleeding when Savella is coadministered with NSAIDs, aspirin, or other drugs. 

Activation of Mania 

• Treatment with Savella may precipitate a mixed/manic episode. 

• Use caution in patients with a history of mania.

Patients with a History of Dysuria

• Use caution in patients with a history of dysuria, notably in male patients with prostatic hypertrophy, prostatitis, and other lower urinary tract obstructive disorders.

Sexual Dysfunction

• SNRIs, including Savella, may cause symptoms of sexual dysfunction.

• Prescribers should inquire about sexual function prior to initiation and about changes in sexual function during treatment.

Angle-Closure Glaucoma 

• Savella may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Concomitant Use with Alcohol

• Do not prescribe Savella to patients with substantial alcohol use or evidence of chronic liver disease because it may aggravate pre-existing liver disease.