Safinamide

The precise mechanism by which XADAGO exerts its therapeutic effects in PD is unknown. XADAGO is an inhibitor of monoamine oxidase B (MAO-B).

• XADAGO is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease (PD) experiencing "off" episodes.ICD-10: G20

• XADAGO is contraindicated in patients with: Concomitant use of other drugs in the monoamine oxidase inhibitor (MAOI) class or other drugs that are potent inhibitors of monoamine oxidase, including linezolid. The combination may result in increased blood pressure, including hypertensive crisis [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ] .contraindicated

Start with 50 mg administered orally once daily at the same time of day; after two weeks, the dose may be increased to 100 mg once daily, based on individual need and tolerability ( 2.1 ) Hepatic Impairment: Do not exceed 50 mg once daily in patients with moderate hepatic impairment; contraindicated in patients with severe hepatic impairment ( 2.2 , 4 ) 2.1 Dosing Information The recommended starting dosage of XADAGO is 50 mg administered orally once daily (at the same time of day), without regard to meals. After two weeks, the dosage may be increased to 100 mg once daily, based on individual need and tolerability. Daily dosages of XADAGO above 100 mg have not been shown to provide additional benefit, and higher dosages increase the risk for adverse reactions. XADAGO has been shown to be effective only in combination with levodopa/carbidopa [see Indications and Usage (1) ] . If a dose is missed, the next dose should be taken at the same time the next day. XADAGO 100 mg should be tapered by decreasing the dose to 50 mg for one week before stopping [see Warnings and Precautions (5.7) ] . 2.2 Dosing in Patients with Hepatic Impairment In patients with moderate hepatic impairment (Child-Pugh B: 7-9), the maximum recommended dosage of XADAGO is 50 mg orally once daily. XADAGO is contraindicated in patients with severe hepatic impairment (Child-Pugh C: 10-15) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . If a patient taking 50 mg XADAGO progresses from moderate to severe hepatic impairment, discontinue XADAGO.

May cause or exacerbate hypertension ( 5.1 ) May cause serotonin syndrome when used with MAO inhibitors, antidepressants, or opioid drugs ( 5.2 ) May cause falling asleep during activities of daily living ( 5.3 ) May cause or exacerbate dyskinesia; consider levodopa dose reduction ( 5.4 ) May cause hallucinations and psychotic behavior ( 5.5 ) May cause problems with impulse control/compulsive behaviors ( 5.6 ) May cause withdrawal-emergent hyperpyrexia and confusion ( 5.7 ) 5.1 Hypertension XADAGO may cause hypertension or exacerbate existing hypertension. In clinical trials, the incidence of hypertension was 7% for XADAGO 50 mg, 5% for XADAGO 100 mg, and 4% for placebo. Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting XADAGO. Medication adjustment may be necessary if elevation of blood pressure is sustained. Monitor for hypertension if XADAGO is prescribed concomitantly with sympathomimetic medications, including prescription or nonprescription nasal, oral, and ophthalmic decongestants and cold remedies [see Drug Interactions (7.5) ] . XADAGO is a selective inhibitor of MAO-B at the recommended dosages of 50 mg or 100 mg daily. Selectivity for inhibiting MAO-B decreases above the recommended daily dosages [see Clinical Pharmacology (12.2) ] . Therefore, XADAGO should not be used at daily dosages exceeding those recommended because of the risks of hypertension, exacerbation of existing hypertension, or hypertensive crisis.

The following serious adverse reactions are discussed in greater detail in other sections of labeling: Hypertension [see Warnings and Precautions (5.1) ] Serotonin Syndrome [see Warnings and Precautions (5.2) ] Falling Asleep During Activities of Daily Living [see Warnings and Precautions (5.3) ] Dyskinesia [see Warnings and Precautions (5.4) ] Hallucinations / Psychotic Behavior [see Warnings and Precautions (5.5) ] Impulse Control / Compulsive Behaviors [see Warnings and Precautions (5.6) ] Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions (5.7) ] Retinal Pathology [see Warnings and Precautions (5.8) ] Most common adverse reactions (incidence on XADAGO 100 mg/day at least 2% greater than placebo) were dyskinesia, fall, nausea, and insomnia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact MDD US Operations, LLC, at 1-888-492-3246 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Clinical trials are conducted under widely varying conditions; therefore, adverse reactions observed in the clinical trials of a drug cannot be directly compared to the incidence in the clinical trials of another drug and may not reflect the incidence observed in clinical practice. Common Adverse Reactions in Placebo-Controlled PD Studies Table 1 shows the incidence of adverse reactions with an incidence of at least 2% on XADAGO 100 mg/day and greater than placebo in controlled studies in PD (Study 1 and Study 2).

Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ). 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of XADAGO in pregnant women. In animals, developmental toxicity, including teratogenic effects, was observed when safinamide was administered during pregnancy at clinically relevant doses. Developmental toxicity was observed at doses lower than those used clinically when safinamide was administered during pregnancy in combination with levodopa/carbidopa. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study in rats, oral administration of safinamide (0, 50, 100, or 150 mg/kg/day) throughout organogenesis resulted in dose-related increases in fetal abnormalities (primarily urogenital malformations) at all doses. A no-effect dose for adverse effects on embryofetal development was not established. The lowest dose tested (50 mg/kg/day) is approximately 5 times the maximum recommended human dose (MRHD) of 100 mg on a body surface area (mg/m 2 ) basis.

Metabolism

Pharmacokinetics of safinamide is linear over a range of 50 mg to 300 mg (3 times the maximum recommended daily dose). Steady state is reached within 5 to 6 days.

There is no human experience with XADAGO overdose. There is no known antidote to XADAGO nor any specific treatment for XADAGO overdose. If an overdose occurs, XADAGO treatment should be discontinued and supportive treatment should be administered as clinically indicated. In cases of overdose with XADAGO, dietary tyramine restriction should be observed for several weeks. The Poison Control Center should be called at 1-800-222-1222 for the most current treatment guidelines.

• Mar 21, 2017NDANDA207145Mdd Us

1. 1Fall16013%
2. 2Hallucination14512%
3. 3Dyskinesia14011%
4. 4Death967.6%
5. 5Gait Disturbance967.6%
6. 6Parkinson^s Disease947.5%
7. 7Drug Ineffective907.2%
8. 8Tremor846.7%
9. 9Fatigue776.1%
10. 10Freezing Phenomenon766.0%
11. 11On And Off Phenomenon756.0%
12. 12Somnolence675.3%
13. 13Anxiety635.0%
14. 14Nausea614.9%
15. 15Dizziness584.6%

The 10 most recently updated of 28 ClinicalTrials.gov registrations naming Safinamide as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Effect of Safinamide on Sleep Quality in Patients With Parkinson's Disease
  Terminated · Phase 4 · Interventional · 11 enrolled · Alain Kaelin
  NCT03968744updated 2026-03-13
• Fall Risk Assessment in Parkinson's Disease Using Kinetikos Health
  Not yet recruiting · Observational · 100 enrolled · Taipei Medical University Shuang Ho Hospital
  NCT07257393updated 2025-12-04
• A Study to Evaluate the Efficacy and Safety of Safinamide Mesilate as Add-on Therapy to Levodopa in Parkinson's Disease Participants With Motor Fluctuation in South Korea
  Completed · Phase 4 · Interventional · 201 enrolled · Eisai Korea Inc.
  NCT05312632updated 2024-09-23
• An Observational Study on Safinamide, Rasagiline and Other Standard of Care in PD
  Completed · Observational · 1,235 enrolled · Zambon SpA
  NCT03994328updated 2024-04-11
• Overnight Switch From Rasagiline To Safinamide
  Completed · Phase 4 · Interventional · 20 enrolled · IRCCS San Raffaele Roma
  NCT03843944updated 2024-04-10
• A Study to Evaluate the Efficacy and Safety of Safinamide, as add-on Therapy, in Idiopathic Chinese Parkinson's Disease (PD) Patients With Motor Fluctuations Treated With Stable Doses of Levodopa
  Completed · Phase 3 · Interventional · 307 enrolled · Zambon SpA
  NCT03881371updated 2024-03-20
• Clinical Outcome Assessment of Parkinson's Disease Patients Treated With XADAGO (Safinamide)
  Completed · Observational · 164 enrolled · Supernus Pharmaceuticals, Inc.
  NCT03944785updated 2023-06-07
• Effect of Safinamide on Parkinson's Disease Related Chronic Pain
  Completed · Phase 4 · Interventional · 94 enrolled · Zambon SpA
  NCT03841604updated 2023-05-22
• A Single and Multiple Dose Study to Assess How the Drug Enters, Moves Through and Exits the Body, Safety and Tolerability of Safinamide in Healthy Adult Chinese Volunteers
  Completed · Phase 1 · Interventional · 24 enrolled · Zambon SpA
  NCT03887221updated 2023-03-17
• Safinamide for Multiple System Atrophy (MSA)
  Completed · Phase 2 · Interventional · 49 enrolled · Zambon SpA
  NCT03753763updated 2021-10-13

Frequently asked questions

How does Safinamide work?

The precise mechanism by which XADAGO exerts its therapeutic effects in PD is unknown. XADAGO is an inhibitor of monoamine oxidase B (MAO-B).

What is Safinamide used for?

According to FDA labeling, Safinamide carries indications including: XADAGO is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease (PD) experiencing "off" episodes.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Safinamide?

Safinamide is classified as Monoamine oxidase B inhibitors, Monoamine Oxidase Type B Inhibitor, Breast Cancer Resistance Protein Inhibitors, Chloride Channel Antagonists, Cytochrome P450 1A2 Inhibitors, Cytochrome P450 2B6 Inhibitors, Cytochrome P450 2C19 Inhibitors, Cytochrome P450 2C9 Inhibitors, Cytochrome P450 2D6 Inhibitors, Cytochrome P450 3A5 Inhibitors, Monoamine Oxidase-A Inhibitors, Monoamine Oxidase-B Inhibitors, Monoamine Oxidase Inhibitors, Potassium Channel Antagonists, Decreased Glutamate Activity.

What are the brand names for Safinamide?

Safinamide is marketed under brand names including Xadago.

What are the contraindications for Safinamide?

Safinamide labeling lists contraindications including: XADAGO is contraindicated in patients with: Concomitant use of other drugs in the monoamine oxidase inhibitor (MAOI) class or other drugs that are potent inhibitors of monoamine oxidase, including linezolid. The combination may result in increased blood pressure, including hypertensive crisis [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ] .. Always consult the full prescribing information and a clinician.