[Note: Milnacipran (Savella®) was the third drug to receive FDA approval for prescription to fibromyalgia patients.]
Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of milnacipran and evaluate relevant clinical trial data.
Data Sources: MEDLINE, International Pharmaceutical Abstracts, and Google Scholar searches (1966-June 2010) were conducted using the key words fibromyalgia, milnacipran, and serotonin-norepinephrine reuptake inhibitor. Searches were limited to articles published in English.
Study Selection and Data Extraction: All available English-language articles of human studies were evaluated. One pharmacokinetic study reviewed included animal data. References cited in identified articles were used for additional evaluation.
Milnacipran is a serotonin-norepinephrine reuptake inhibitor with a 3-fold increased selectivity for norepinephrine compared to serotonin.
It is well absorbed with 85%-90% bioavailability.
Maximum concentrations are achieved 2-4 hours after administration.
Milnacipran does not undergo cytochrome P450 metabolism and has a half-life of 6-8 hours.
Fifty-five percent of each dose is excreted unchanged in the urine.
Dose adjustment is needed in patients with an estimated creatinine clearance of <30 mL/min.
Clinical trials indicated that twice-daily dosing at 100 mg/day or 200 mg/day was superior to single-daily dosing.
Studies further established the effectiveness of both doses in the treatment of fibromyalgia pain utilizing patient self-reported pain scores, as well as on a visual analog scale, Patient Global Impression of Change scale, and the Short-Form 36 Physical Component Summary.
A 6-month extension trial, which evaluated patients continued on milnacipran for up to 1 year, demonstrated continued pain relief.
The most common adverse drug reaction associated with milnacipran was nausea, which was reduced with slow-dose titration and administration with food.
Milnacipran is an effective treatment option for patients with fibromyalgia.
More head-to-head clinical trials are necessary to assess its ultimate place in therapy.
Source: Annals of Pharmacotherapy, Aug 17, 2010. PMID: 20716692, by Kyle JA, Dugan BD, Testerman KK. Samford University, Birmingham, Alabama, USA. [Email: firstname.lastname@example.org]