Safinamide is a novel, once-daily oral medication for the treatment of Parkinson's disease (PD). It is a highly selective and reversible inhibitor of monoamine oxidase B (MAO-B) with additional glutamate release inhibition via sodium channel blockade. This dual mechanism provides both dopaminergic and non-dopaminergic (anti-glutamatergic) activity, making it effective as add-on therapy to levodopa in mid-to-late stage fluctuating PD patients to reduce 'off' time and improve 'on' time without troublesome dyskinesia.
Adult: Initial dose: 50 mg once daily. May be increased to 100 mg once daily based on clinical response and tolerability after at least 2 weeks.
Note: Take orally once daily, at the same time each day, with or without food. Tablet should be swallowed whole with water. Do not crush or chew. Can be taken with levodopa doses.
Safinamide has a unique dual mechanism of action: 1) Highly selective, reversible inhibition of MAO-B enzyme, increasing dopamine availability in the striatum. 2) Inhibition of abnormal glutamate release via state- and use-dependent blockade of voltage-gated sodium channels and modulation of calcium channels, providing non-dopaminergic, neuroprotective potential.
Pregnancy: Category C. Animal studies have shown fetal toxicity. There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.
Driving: May cause dizziness, somnolence, syncope, and visual disturbances. Patients should be cautioned about operating machinery, including driving, until they are reasonably certain safinamide does not affect them adversely.
| Other MAO Inhibitors (Selegiline, Rasagiline, Phenelzine, Linezolid) | Risk of hypertensive crisis, serotonin syndrome. | Contraindicated |
| Pethidine (Meperidine) | Risk of serotonin syndrome, excitation, hypertension. | Contraindicated |
| SSRIs/SNRIs (e.g., Sertraline, Fluoxetine, Venlafaxine) | Increased risk of serotonin syndrome. | Major - Use with extreme caution and monitor closely. |
| Tricyclic Antidepressants (e.g., Amitriptyline) | Increased risk of serotonin syndrome, CNS toxicity. | Major |
| Tramadol, Tapentadol | Increased risk of serotonin syndrome, seizures. | Major |
| Dextromethorphan | Risk of serotonin syndrome. | Moderate |
| Sympathomimetics (e.g., Ephedrine, Pseudoephedrine) | Potential for exaggerated pressor response. | Moderate |
| Levodopa/Carbidopa | Potentiates dopaminergic effects, increasing risk of dyskinesia, hallucinations, impulse control disorders. Dose of levodopa may need reduction. | Moderate |