Safinamide (Xadago): Approved as Add-On for Parkinson’s

June 13, 2017

Xadago has been approved as a supplementary medication for patients with Parkinson's disease who are having "off" episodes or whose disease is progressing.

Parkinson’s disease affects an estimated one million Americans: 50,000 new cases are diagnosed annually.1 This disorder is characterized by tremors and difficulty ambulating due to decreased production of dopamine, which helps transmit signals that produce purposeful movements. Dopamine replacement therapies, such as levodopa, are the mainstay of treatment. As the disease progresses, patients experience “off” episodes during which symptoms worsen, and “on” times when symptoms are reduced without troublesome dyskinesia.


The FDA approved safinamide (Xadago) by Newron Pharmaceuticals in March 2017 as an add-on treatment for patients taking levodopa/carbidopa who experience “off” episodes.1 Safinamide is a monoamine oxidase (MAO) B inhibitor: it decreases the breakdown of dopamine and leads to increased dopamine levels and subsequently increased dopaminergic activity.2 Safinamide has greater selectivity for MAO-B versus MAO-A than selegiline and rasagiline.3

Efficacy
The effectiveness of safinamide was demonstrated in two randomized clinical trials in patients who were also taking levodopa and experiencing “off” episodes. In the first trial, 645 patients were randomized to safinamide 50 mg, safinamide 100 mg, or placebo for up to 24 weeks.4 The “on” time was significantly increased for safinamide 50 mg and 100 mg compared to placebo.4 The effect of safinamide 100 mg was numerically greater than safinamide 50 mg, but no statistical comparison was completed. Improvements in “on” time were not associated with any increases in dyskinesia.4


In the second trial, 549 patients were randomized to safinamide 100 mg daily or placebo for up to 24 weeks.5 This trial demonstrated an effect similar to that seen in the previous trial: there was significantly increased “on” time for safinamide 100 mg relative to placebo.5 Patients in the safinamide group also had less “off” time and improved motor function during “on” time.5

 

Safety
Common adverse effects associated with safinamide identified in pre-approval studies include uncontrolled   involuntary movement, falls, nausea, and insomnia.2 Less common but serious side effects include hypertension, serotonin syndrome with concomitant use of serotonergic agents, falling asleep during activities of daily living, hallucinations, and problems with impulse control behaviors.2


Safinamide is contraindicated in patients with severe hepatic impairment2 and it has several significant drug interactions. Concomitant use of other medications in the MAO-inhibitor class or other medications that inhibit monoamine oxidase, including linezolid, is contraindicated because of increased risk of hypertensive crisis.2 Concomitant use of opioids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, cyclobenzaprine, methylphenidate, amphetamine and their derivatives, or St. John’s wort is also contraindicated due to increased risk of serotonin syndrome.2 Finally, concomitant use of dextromethorphan is contraindicated due to reported risk of psychosis.2


Safinamide use by pregnant woman has not been studied.2 The potential for transmission of safinamide in human milk during lactation has not been studied. In animal models, however, indirect exposure to safinamide through milk has been observed.2

Dosing
Safinamide is stored at room temperature and is available as 50-mg and 100-mg tablets.2


The recommended dosing of safinamide is 50 mg by mouth once daily at the same time each day without regard to meals.2 After 2 weeks, the dose can be increased to 100 mg once daily based on individual need and tolerability. Doses exceeding 100 mg have not been shown to provide additional benefit and increase the risk for adverse reactions.2 If a dose is missed, the next dose should be taken at the same time the next day.2 If safinamide is discontinued, doses of 100 mg daily should be tapered by decreasing the dose to 50 mg daily for one week before full discontinuation.2


In patients with moderate hepatic impairment, the maximum recommended dose of safinamide is 50 mg once daily.2 If patients currently taking safinamide 50 mg once daily progress from moderate to severe hepatic dysfunction, safinamide should be discontinued.  


References
1. U.S. Food and Drug Administration. FDA approves drug to treat Parkinson’s disease [internet]. Silver Spring, MD: U.S. Food and Drug Administration; 2017 March 21. http://bit.ly/2rvIcQ7 . Accessed May 18, 2017.
2. Xadago [package insert] Louisville, Kentucky: Newron Pharmaceuticals; 2017
3. Kulisevsky J. Emerging role of safinamide in Parkinson’s disease therapy. Eur NeurolRev. 2014;9:108-112.
4. Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s Disease with motor fluctuations. Mov Disord. 2014; Feb;29:229-237.
5. Schapira A, Fox S, Hauser R, et al. Assessment of safety and efficacy of safinamide as a levodopa adjunct in patients with Parkinson disease and motor fluctuations. JAMA Neurology. 2017;74:216-224.