Safinamide

Safinamide Instructions
Common name: Safinamide
Trade name: Xadago
All names: Safinamide, Safinamide, Xadago, Safinamide, Equfina

< p>

Indications:
Xadago is indicated for the treatment of adult patients with idiopathic Parkinson's disease (PD) as an add-on therapy to patients with moderate to advanced fluctuations in treatment with stable doses of levodopa (L-dopa) alone or in combination with other PD medicinal products.

Usage and dosage:
Safinamide treatment should start with 50 mg per day. The daily dose may be increased to 100 mg/day based on individual clinical needs.
If a dose is missed, the next dose should be taken at the usual time the next day.

Adverse reactions:
The most common adverse reactions (the incidence rate is calculated using XADAGO 100 mg/day at least 2% greater than placebo) for motor dysfunction, falls, nausea, and insomnia

Contraindications:
XADAGO is contraindicated in the following patients:
1. Concomitant use of:
Other monoamine oxidase inhibitors or other drugs that are strong inhibitors of monoamine oxidase (e.g., linezolid [ linezolid])
Opioids (e.g., tramadol, pethidine, and related derivatives); selective norepinephrine reuptake inhibitors; tri- or tetra-cyclic or triazopyridine antidepressants; cyclobenzaprine; phenylpiperdine methyl acetate, amphetamines, and their derivatives; St. John's wort, dextromethorphan
2. History of hypersensitivity to safinamide.
3. Severe liver damage (Child-Pugh C: 10-15)

Notes:
1. May cause or aggravate hypertension
2. When used with MAO inhibitors, antidepressants, or opioids, it may cause serotonin syndrome.
3. It may cause falling asleep during daytime activities.
4. May cause or aggravate motor dysfunction; consider reducing the dose of levodopa
5. May cause hallucinations and psychotic behavior
6. May cause problems with impulse control/compulsive behavior
7. May cause withdrawal symptoms such as hyperthermia and confusion

Storage:
Store at 25°C (77°F); excursions allowed between 15°C and 30°C (59°F and 86°F)

Mechanism of action:
Safinamide acts through dopaminergic and non-dopaminergic mechanisms of action. Safinamide is a highly selective and reversible MAO-B inhibitor that causes increased extracellular levels of dopamine in the striatum. Safinamide is associated with state-dependent inhibition of voltage-gated sodium (Na+) channels and modulation of stimulation of glutamate release. The extent to which non-dopaminergic effects contribute to the overall effect has not been determined.

Safety and Efficacy:
Two double-blind, placebo-controlled, multi-country, 24-week studies (Study 1 and Study 2) were conducted in PD patients with "OFF" status who were treated with carbidopa/levodopa and other PD drugs (such as dopamine agonists, COMT inhibitors, anticholinergic drugs and/or amantadine). In Study 1, patients were randomized to receive safinamide 50 mg once daily or safinamide 100 mg once daily or placebo. The trial results showed that in the three groups of patients (placebo vs. safinamide 50 mg vs. safinamide 100 mg), in the "ON" state, the change in the average number of hours from baseline to treatment period was - VS 0.5 VS 0.53. In the "OFF" state, the change in the average number of hours from baseline to treatment period in the three groups of patients (placebo vs. safinamide 50 mg vs. safinamide 100 mg) was - VS -0.55 VS -0.57, and the change in the UPDRS motor subscale score compared with baseline was - VS -1.75 VS -2.48.
In Study 2, patients were randomly divided into two groups, one group received 100 mg safinamide each time, and the other group received placebo treatment for up to 24 weeks. The trial results showed that in the two groups of patients (placebo vs. safinamide 100 mg), in the "ON" state, the change in average hours from baseline to treatment period was -- VS 0.99. In the "OFF" state, the change in mean hours from baseline to treatment in the three groups (placebo vs. safinamide 100 mg) was - vs -1.06, and the change in UPDRS motor subscale score from baseline was - vs -1.70.