Savella (milnacipran hydrochloride)
Company: Forest Labs
Approval Status: Approved January 2009
Treatment for: fibromyalgia
Areas: Musculoskeletal
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Savella (milnacipran) is a selective serotonin and norepinephrine reuptake inhibitor. It affects the two neurotransmittersalmost equally (a 3:1 norepinephrine to serotonin balance). However, the exact mechanism of the central pain inhibitory action of milnacipran and its ability to improve the symptoms of fibromyalgia in humans are unknown.
Savella is specifically indicated for the management of fibromyalgia in adults.
Savella is supplied as a tablet designed for oral administration. The recommended initial dose of the drug is 100 mg/day (50 mg twice daily). Dosing should be titrated according to the following schedule:
Day 1: 12.5 mg once
Days 2-3: 25 mg/day (12.5 mg twice daily)
Days 4-7: 50 mg/day (25 mg twice daily)
After Day 7: 100 mg/day (50 mg twice daily)
Doses above 200 mg/day have not been studied.
Clinical Results
FDA ApprovalFDA approval of Savella was based on the results of two clinical trials.
Study One
This 6-month double-blind, placebo-controlled, multicenter study enrolled adult patients (18-74 years of age). The subjects received daily doses of Savella 100 mg and 200 mg or placebo. The minimum mean baseline pain score of >50 mm on a 100 mm visual analog scale (VAS) ranging from 0 (no pain) to 100 (worst possible pain). The mean baseline pain score in this trial was 69. More patients in the Savella treatment arms experienced at least a 30% reduction in pain from baseline (VAS) and considered themselves globally improved (PGIC) than did patients in the placebo arm.
Study Two
This 3-month, double-blind, placebo-controlled, multicenter study enrolled adult patients (18-74 years of age). The subjects received daily doses of Savella 100 mg and 200 mg or placebo. The minimum mean baseline pain score was >40 mm on a 100- mm VAS ranging from 0 (no pain) to 100 (worst possible pain). The mean baseline pain score in this trial was 65. improvement. More patients in the Savella treatment arms experienced at least a 30% reduction in pain from baseline (VAS) and considered themselves globally improved (PGIC) than did patients in the placebo arm.
In both studies, some patients who rated themselves as globally "much" or "very much" improved experienced a decrease in pain as early as week 1 of treatment.
Ongoing Study Commitments
- Forest Labs has agreed to a deferred pediatric study under PREA for the management of fibromyalgia in pediatric patients ages 13 through 17.
Protocol Submission: July 2009
Study Start Date: January 2010
Final Report Submission: October 2014 - Forest Labs has agreed to develop and maintain a prospective, observational pregnancy exposure registry study conducted in the United States that compares the pregnancy and fetal outcomes of women exposed to Savella (milnacipran HCl) during pregnancy to an unexposed control population. The registry will detect and record major and minor congenital anomalies, spontaneous abortions, stillbirths, elective terminations, and any serious adverse pregnancy outcomes. These events will be assessed among the enrolled women throughout the pregnancy. The events will also be assessed among infants through at least the first year of life. Annual interim reports will be submitted until FDA has acknowledged that sufficient data have been collected.
Protocol Submission: July 2009
Study Start Date: January 2010
Final Report Submission: Within six months of FDA notification that sufficient data have been collected. - Forest Labs has agreed to a single-dose, pharmacokinetic, open-label, clinical trial in healthy, lactating women. Concentrations of Savella (Milnacipran HCl) will be assessed in maternal plasma and breast mild so as to estimate potential infant exposure.
Protocol Submission: August 2009
Trial Start Date: August 2010
Final Report Submission: February 2012
Side Effects
Adverse events associated with the use of Savella may include, but are not limited to, the following:- Nausea
- Headache
- Constipation
- Hot flush
- Hyperhidrosis
- Vomiting
- Palpitations
- Heart rate increased
- Dry mouth
- Hypertension
Mechanism of Action
Savella (milnacipran) is a selective serotonin and norepinephrine reuptake inhibitor. It affects the two neurotransmittersalmost equally (a 3:1 norepinephrine to serotonin balance). However, the exact mechanism of the central pain inhibitory action of milnacipran and its ability to improve the symptoms of fibromyalgia in humans are unknown.
Literature References
Mease PJ, Clauw DJ, Gendreau RM, Rao SG, Kranzler J, Chen W, Palmer RH The Efficacy and Safety of Milnacipran for Treatment of Fibromyalgia. A Randomized, Double-blind, Placebo-controlled Trial. The Journal of Rheumatology 2008 Dec 15
Clauw DJ, Mease P, Palmer RH, Gendreau RM, Wang Y Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial. Clinical Therapeutics 2008 Nov;30(11):1988-2004
Owen RT Milnacipran hydrochloride: its efficacy, safety and tolerability profile in fibromyalgia syndrome. Drugs of Today 2008 Sep;44(9):653-60
Harris RE, Williams DA, McLean SA, Sen A, Hufford M, Gendreau RM, Gracely RH, Clauw DJ Characterization and consequences of pain variability in individuals with fibromyalgia. Arthritis and Rheumatism 2005 Nov;52(11):3670-4
Gendreau RM, Thorn MD, Gendreau JF, Kranzler JD, Ribeiro S, Gracely RH, Williams DA, Mease PJ, McLean SA, Clauw DJ Efficacy of milnacipran in patients with fibromyalgia. The Journal of Rheumatology 2005 Oct;32(10):1975-85
Additional Information
For additional information regarding Savella or fibromyalgia, please visit the Savella web page.The FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
