On January 14, 2009, the FDA approved Savella (milnacipran HCl) for the management of fibromyalgia. Savella is classified as a selective serotonin and norepinephrine dual reuptake inhibitor. The drug has been used for several years in Europe and Asia to treat depression.
What Is a Selective Serotonin and Norepinephrine Dual Reuptake Inhibitor?
As a selective serotonin and norepinephrine dual reuptake inhibitor, also known as SSNRI, Savella increases norepinephrine and serotonin activity in the brain. In the test tube, Savella seems to have more effect on norepinephrine activity. This is important for fibromyalgia patients because low brain norepinephrine levels are thought to be related to increased pain and cognitive difficulties (“brain fog”).
How Is Savella Given?
Savella is administered in two divided doses per day. The dosage is gradually increased over the course of the first week to get to the recommended dose of 100 mg/day.
Savella is available as 12.5 mg, 25 mg, 50 mg, and 100 mg tablets. On day 1, you take 12.5 mg once. On days 2 to 3, you take 12.5 mg/twice daily. On days 4 to 7, you take 25 mg/twice daily. After day 7, the usual dose is 50 mg/twice daily. Some patients may require 200 mg/day—and some may require a lower dose if they have renal (kidney) impairment.
How Has Savella Performed in Clinical Trials?
The safety and efficacy of Savella was determined from the results of two phase III clinical trials in the U.S. There were more than 2,000 patients with fibromyalgia involved in the studies.
Contraindications for Savella
Savella is contraindicated (should not be used) in patients with uncontrolled narrow-angle glaucoma. Savella should also not be used by patients taking MAOIs (monoamine oxidase inhibitors), typically used for depression. Savella is not approved for use in children.
Warnings Associated With Savella
Patients prescribed Savella should be aware of the following warnings and precautions:
- Worsening depressive symptoms and suicide risk are possible with Savella.
- Serotonin syndrome (a life-threatening drug reaction that causes the body to have too much serotonin) is possible.
- Elevated blood pressure and heart rate may occur with Savella.
- Seizures have been reported in patients taking Savella.
- Hepatotoxicity has been reported (patients with excessive alcohol use or chronic liver disease should avoid Savella).
- Withdrawal symptoms may occur if Savella is not discontinued gradually.
- Savella may increase the risk of bleeding especially in patients taking NSAIDs, aspirin, or other drugs that affect bleeding.
- There may be higher rates of genitourinary adverse events with Savella use.
- The manufacturer of Savella states that no adequate or well-controlled studies have been reported for pregnant women, though animal studies show there may be fetal risks. Therefore it should be used during pregnancy only if potential benefits justify potential risks to the fetus.
- Controlled studies of Savella have not been conducted on nursing mothers.
Common Side Effects and Adverse Events
Nausea, headache, constipation, dizziness, insomnia, flushing, increased perspiration, vomiting, palpitations, and dry mouth are adverse reactions associated with Savella.