Milnacipran
Top: (1S,2R)-milnacipran (L-milnacipran)
Bottom: (1R,2S)-milnacipran (D-milnacipran) |
|
| Clinical data | |
|---|---|
| Pronunciation | /milnæsipræn/ |
| Trade names | Ixel, Joncia, Savella |
| AHFS/Drugs.com | Consumer Drug Information |
| MedlinePlus | a609016 |
| Pregnancy category |
|
| Routes of administration |
By mouth (tablets), capsules) |
| ATC code | N06AX17 (WHO) |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 85% |
| Protein binding | 13% |
| Metabolism | Hepatic |
| Biological half-life | 8 hours |
| Excretion | Renal |
| Identifiers | |
|
|
| CAS Number |
92623-85-3 
|
| PubChem (CID) | 65833 |
| DrugBank |
DB04896
|
| ChemSpider |
59245
|
| UNII |
G56VK1HF36
|
| KEGG |
D08222
|
| ChEMBL |
CHEMBL252923
|
| Chemical and physical data | |
| Formula | C15H22N2O |
| Molar mass | 246.348 g/mol |
| 3D model (Jmol) | Interactive image |
| Chirality | Racemic mixture |
|
|
|
|
Milnacipran (trade names Ixel, Savella, Dalcipran, Toledomin) is a serotonin–norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia. It is not approved for the clinical treatment of major depressive disorder in the USA, but it is in other countries.
In a pooled analysis of 7 comparative trials with imipramine, milnacipran and imipramine were shown to have comparable efficacy while milnacipran was significantly better tolerated. A pooled analysis of studies comparing milnacipran and SSRIs concluded a superior efficacy for milnacipran with similar tolerability for milnacipran and SSRIs. A more recent meta-analysis of 6 studies involving more than 1,000 patients showed no distinction between milnacipran and SSRIs in efficacy or discontinuation rates, including discontinuation for side effects or lack of efficacy. A meta-analysis of a total of 16 randomized controlled trials with more than 2200 patients concluded that there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressant agents. However, compared with TCAs, significantly fewer patients taking milnacipran dropped out due to adverse events. As with other antidepressants, 1 to 3 weeks may elapse before significant antidepressant action becomes clinically evident.
During its development for fibromyalgia, milnacipran was evaluated utilizing a composite responder approach. To be considered as a responder for the composite ‘treatment of fibromyalgia’ endpoint, each patient had to show concurrent and clinically meaningful improvements in pain, physical function and global impression of disease status. A systematic review in 2012 showed moderate relief for a minority of people with fibromyalgia. Milnacipran was associated with increased adverse events and discontinuing use of the drug.
The most frequently occurring adverse reactions (≥ 5% and greater than placebo) were nausea, headache, constipation, dizziness, insomnia, hot flush, hyperhidrosis, vomiting, palpitations, heart rate increase, dry mouth, and hypertension [FDA Savella prescribing information]. Milnacipran can have a significant impact on sexual functions, including both a decrease in sexual desire and ability. Milnacipran can cause pain of the testicles in men. The incidence of cardiovascular and anticholinergic side effects was significantly lower compared to TCAs as a controlled study with over 3,300 patients revealed. Elevation of liver enzymes without signs of symptomatic liver disease has been infrequent. Mood swing to mania has also been seen and dictates termination of treatment. In psychotic patients emergence of delirium has been noticed. Milnacipran has a low incidence of sedation but improves sleep (both duration and quality) in depressed patients. In agitated patients or those with suicidal thoughts additive sedative/anxiolytic treatment is usually indicated.
...
Wikipedia