Version July 2025
Parkinson disease: Oral: 50 mg once daily (in combination with carbidopa/levodopa); after 2 weeks may increase to 100 mg once daily (in combination with carbidopa/levodopa) based on response and tolerability.
Discontinuation of therapy: Decrease dose to 50 mg for one week before discontinuing therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Maximum dose: 50 mg once daily.
Severe impairment (Child-Pugh class C): Use is contraindicated by the manufacturer (has not been studied).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Neuromuscular & skeletal: Dyskinesia (17% to 21%)
1% to 10%:
Cardiovascular: Hypertension (including exacerbation of hypertension: 5% to 7%), orthostatic hypotension (2%)
Gastrointestinal: Dyspepsia (2%), nausea (6%)
Hepatic: Increased serum alanine aminotransferase (5% to 7%), increased serum aspartate aminotransferase (6% to 7%)
Nervous system: Anxiety (2%), falling (6%), insomnia (4%)
Respiratory: Cough (2%)
Frequency not defined: Nervous system: Impulse control disorder, sudden onset of sleep
Postmarketing:
Hypersensitivity: Hypersensitivity reaction
Nervous system: Headache
Hypersensitivity (eg, swelling of the tongue and oral mucosa, dyspnea) to safinamide or any component of the formulation; severe hepatic impairment (Child-Pugh class C); concomitant use of methylphenidate, amphetamine, and their derivatives, or dextromethorphan; concomitant use with or within 2 weeks of other monoamine oxidase inhibitors or other drugs that are potent inhibitors of monoamine oxidase (including linezolid), opioids (eg, meperidine, methadone, propoxyphene, tramadol), serotonin-norepinephrine reuptake inhibitors, tricyclic, tetracyclic, or triazolopyridine antidepressants, cyclobenzaprine, St John's wort.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Albinism, retinal degeneration, uveitis, inherited retinopathy or any active retinopathy (including severe progressive diabetic retinopathy)
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Somnolence and falling asleep while engaged in activities of daily living (including operation of motor vehicles) have been reported; some cases reported that there were no warning signs for the onset of symptoms. Monitor for drowsiness or sleepiness. If significant daytime sleepiness or episodes of falling asleep during activities that require active participation occur (eg, driving, conversations, eating), discontinue safinamide or instruct patient to avoid driving or other potentially dangerous activities.
• Dyskinesia: May cause or exacerbate preexisting dyskinesia. Reducing the dose of safinamide or other dopaminergic medications may mitigate this effect.
• Hypertension: May cause or exacerbate preexisting hypertension. Monitor for new-onset or worsening hypertension. Increasing the dose above 100 mg/day decreases specificity for the MAO-B receptor and increases the risk for hypertension.
• Impulse control disorders: Dopaminergic agents used for Parkinson disease have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), uncontrolled spending of money, binge eating, and/or other intense urges. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/substance use disorders, and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all, cases.
• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with concomitant use of serotonergic agents (eg, SSRIs, SNRIs, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with moderate hepatic impairment (Child-Pugh class B); use is contraindicated in patients with severe hepatic impairment (Child-Pugh class C).
• Ophthalmic disorder: Use with caution in patients with ophthalmic disorders, including a history of retinal/macular degeneration, uveitis, inherited retinal conditions, albinism, retinitis pigmentosa, any active retinopathy or family history of hereditary retinal disease. Monitor periodically for visual changes.
• Psychotic disorder: May exacerbate psychosis in patients with a major psychiatric disorder; consider discontinuing treatment or lowering dose in patients who develop hallucinations or psychotic behavior.
Other warnings/precautions:
• Parkinsonism-Hyperpyrexia syndrome: Abrupt discontinuation or interruption of dopaminergic antiparkinsonian therapy has been associated with a discontinuation syndrome, which may resemble neuroleptic malignant syndrome; symptoms may include elevated temperature, muscular rigidity, altered consciousness, and autonomic instability. Symptoms typically develop between 18 hours and 7 days following discontinuation. Management includes restarting the antiparkinsonian therapy and supportive measures; severe cases may require additional medication therapy. Avoid abrupt discontinuation of therapy (Newman 2009).
• Tyramine-containing products: Nonselective MAO inhibition may occur with doses greater than 100 mg/day. Hypertensive crisis as a result of ingesting tyramine-rich foods is always a concern with nonselective MAO inhibition. Discontinue therapy immediately if hypertensive crisis occurs.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Xadago: 50 mg, 100 mg
No
Tablets (Xadago Oral)
50 mg (per each): $45.58
100 mg (per each): $45.58
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Onstryv: 50 mg, 100 mg
Oral: Administer without regard to meals at the same time every day. Always administer in association with carbidopa/levodopa.
Parkinson disease: Adjunctive treatment to carbidopa/levodopa in patients with Parkinson disease experiencing "off" episodes.
Substrate of CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits Monoamine Oxidase;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Blood Glucose Lowering Effects: Monoamine Oxidase Inhibitors may increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Alpha-/Beta-Agonists (Indirect-Acting): Monoamine Oxidase Inhibitors may increase hypertensive effects of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Risk X: Avoid
Alpha1-Agonists: Monoamine Oxidase Inhibitors may increase hypertensive effects of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Risk X: Avoid
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Amphetamines: Monoamine Oxidase Inhibitors may increase hypertensive effects of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Risk X: Avoid
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Apraclonidine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Apraclonidine. Monoamine Oxidase Inhibitors may increase serum concentration of Apraclonidine. Risk X: Avoid
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Atomoxetine: Monoamine Oxidase Inhibitors may increase neurotoxic (central) effects of Atomoxetine. Risk X: Avoid
Atropine (Ophthalmic): Monoamine Oxidase Inhibitors may increase hypertensive effects of Atropine (Ophthalmic). Risk X: Avoid
Avocado: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benzhydrocodone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of benzhydrocodone is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and frequent titration of small benzhydrocodone. Risk D: Consider Therapy Modification
Beta2-Agonists: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Beta2-Agonists. Risk C: Monitor
Betahistine: Monoamine Oxidase Inhibitors may increase serum concentration of Betahistine. Risk C: Monitor
Bezafibrate: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Bezafibrate. Risk X: Avoid
Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor
Bornaprine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Brimonidine (Ophthalmic): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase serum concentration of Brimonidine (Ophthalmic). Risk C: Monitor
Brimonidine (Topical): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Brimonidine (Topical). Monoamine Oxidase Inhibitors may increase serum concentration of Brimonidine (Topical). Risk C: Monitor
Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Buprenorphine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
BuPROPion: Monoamine Oxidase Inhibitors may increase hypertensive effects of BuPROPion. Risk X: Avoid
Butorphanol: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
CarBAMazepine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Do not use carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Risk X: Avoid
Carbinoxamine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Carbinoxamine. Specifically, the anticholinergic effects of carbinoxamine may be enhanced and prolonged. Risk X: Avoid
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cerebrolysin: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Chlorphenesin Carbamate: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cocaine (Topical): May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Codeine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Codeine. Risk X: Avoid
Cyclobenzaprine: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Cyproheptadine: May decrease serotonergic effects of Monoamine Oxidase Inhibitors. Monoamine Oxidase Inhibitors may increase anticholinergic effects of Cyproheptadine. Risk X: Avoid
Deutetrabenazine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Deutetrabenazine. Risk X: Avoid
Dexmethylphenidate: Monoamine Oxidase Inhibitors may increase hypertensive effects of Dexmethylphenidate. Risk X: Avoid
Dextromethorphan: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This may cause serotonin syndrome. Risk X: Avoid
Diamorphine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Diamorphine. Risk X: Avoid
Diethylpropion: Monoamine Oxidase Inhibitors may increase hypertensive effects of Diethylpropion. Risk X: Avoid
Difenoxin: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Dihydrocodeine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Consider avoiding use of dihydrocodeine while the patient is taking monoamine oxidase inhibitors (MAOIs) and for 2 weeks after MAOI discontinuation. Risk D: Consider Therapy Modification
Diphenoxylate: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Domperidone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Domperidone. Monoamine Oxidase Inhibitors may decrease therapeutic effects of Domperidone. Domperidone may decrease therapeutic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
DOPamine: Monoamine Oxidase Inhibitors may increase hypertensive effects of DOPamine. Management: Initiate dopamine at no greater than one-tenth (1/10) of the usual dose in patients who are taking (or have taken within the last 2 to 3 weeks) monoamine oxidase inhibitors. Monitor for an exaggerated hypertensive response to dopamine. Risk D: Consider Therapy Modification
Doxapram: Monoamine Oxidase Inhibitors may increase hypertensive effects of Doxapram. Risk C: Monitor
DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
EPINEPHrine (Oral Inhalation): Monoamine Oxidase Inhibitors may increase hypertensive effects of EPINEPHrine (Oral Inhalation). Risk X: Avoid
EPINEPHrine (Systemic): Monoamine Oxidase Inhibitors may increase hypertensive effects of EPINEPHrine (Systemic). Risk C: Monitor
Esketamine (Nasal): May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Fenfluramine: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
FentaNYL: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Fluorodopa F18: Coadministration of Anti-Parkinson Agents (Monoamine Oxidase Inhibitor) and Fluorodopa F18 may alter diagnostic results. Management: Discontinue medications used to treat Parkinson disease, including MAO inhibitors, 12 hours prior to fluorodopa F 18 administration if these medications can be safely withheld. Risk D: Consider Therapy Modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Gepirone: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Guanethidine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
HYDROcodone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of HYDROcodone. Management: Consider alternatives to this combination when possible. If coadministration is required, use test doses, titrate small doses frequently, and monitor patients closely for evidence of serotonergic and opioid toxicities. Risk D: Consider Therapy Modification
HYDROmorphone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of HYDROmorphone. Management: Coadministration of hydromorphone and monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) is not recommended. If required, use test doses, titrate small doses frequently, and monitor for CNS and respitatory depression. Risk D: Consider Therapy Modification
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Indoramin: Monoamine Oxidase Inhibitors may increase hypotensive effects of Indoramin. Risk X: Avoid
Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Isoniazid: Safinamide may increase adverse/toxic effects of Isoniazid. Specifically, there is an increased risk for hypertension. Risk C: Monitor
Isoproterenol: Monoamine Oxidase Inhibitors may increase therapeutic effects of Isoproterenol. Risk C: Monitor
Levodopa-Foslevodopa: May increase orthostatic hypotensive effects of Monoamine Oxidase Inhibitors (Type B). Risk C: Monitor
Levomethadone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Levonordefrin: Monoamine Oxidase Inhibitors may increase hypertensive effects of Levonordefrin. Management: Avoid the use of levonordefrin during or within 2 weeks of treatment with a monoamine oxidase inhibitor whenever possible. If levonordefrin cannot be avoided during this period, monitor closely for enhanced or prolonged increases in blood pressure. Risk D: Consider Therapy Modification
Linezolid: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Maprotiline: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Meptazinol: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Meptazinol. Risk X: Avoid
Mequitazine: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Mequitazine. Risk X: Avoid
Metaraminol: Monoamine Oxidase Inhibitors may increase hypertensive effects of Metaraminol. Risk C: Monitor
Methadone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Methotrimeprazine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Methotrimeprazine. Specifically, monoamine oxidase inhibitors may enhance dopamine blockade, possible increasing the risk for neuroleptic malignant syndrome. Methotrimeprazine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Methyldopa: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Methyldopa. Risk X: Avoid
Methylene Blue: Monoamine Oxidase Inhibitors (Type B) may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid
Methylphenidate: Monoamine Oxidase Inhibitors may increase hypertensive effects of Methylphenidate. Risk X: Avoid
Metoclopramide: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Mianserin: Monoamine Oxidase Inhibitors may increase neurotoxic effects of Mianserin. Risk X: Avoid
Mivacurium: Monoamine Oxidase Inhibitors may increase serum concentration of Mivacurium. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): May increase hypertensive effects of Monoamine Oxidase Inhibitors (Type B). Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Monoamine Oxidase Inhibitors (Type B): May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Morphine (Systemic): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Morphine (Systemic). Risk X: Avoid
Nalbuphine: Monoamine Oxidase Inhibitors may increase CNS depressant effects of Nalbuphine. Nalbuphine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Nalbuphine may increase hypertensive effects of Monoamine Oxidase Inhibitors. Management: Use of nalbuphine is not recommended in patients taking MAOIs, or within 14 days of stopping MAOI therapy. If urgent nalbuphine use is needed, use test doses and frequent titration while monitoring blood pressure, CNS depression, and serotonergic toxicity Risk D: Consider Therapy Modification
Nefazodone: Safinamide may increase serotonergic effects of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid
Nefopam: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Nefopam. Risk X: Avoid
Norepinephrine: Monoamine Oxidase Inhibitors may increase hypertensive effects of Norepinephrine. Risk C: Monitor
Normethadone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Normethadone. Risk X: Avoid
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Opipramol: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Opium: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Opium. Risk X: Avoid
OxyCODONE: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Use of oxycodone is not recommended for patients taking MAOIs or within 14 days of MAOI discontinuation. If combined, use test doses and frequent titration of small doses while monitoring blood pressure, CNS depression, and signs of serotonin syndrome. Risk D: Consider Therapy Modification
OxyMORphone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Ozanimod: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pheniramine: May increase anticholinergic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Pholcodine: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Pizotifen: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Pizotifen. Risk X: Avoid
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Reboxetine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Reboxetine. Risk X: Avoid
Remifentanil: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Management: The use of remifentanil is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and titrate small doses of remifentanil frequently. Risk D: Consider Therapy Modification
Reserpine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Monitor closely for paradoxical effects of reserpine (eg, excitation, hypertension). Risk D: Consider Therapy Modification
RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: Safinamide may increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Serotonergic Agents (High Risk, Miscellaneous): Monoamine Oxidase Inhibitors (Type B) may increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Risk X: Avoid
Serotonergic Agents (Moderate Risk, Miscellaneous): Monoamine Oxidase Inhibitors (Type B) may increase serotonergic effects of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonergic Non-Opioid CNS Depressants: Safinamide may increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid
Serotonergic Opioids (High Risk): May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Serotonin/Norepinephrine Reuptake Inhibitor: Safinamide may increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sevoflurane: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Sevoflurane. Specifically, the risk of hemodynamic instability may be increased. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Solriamfetol: Monoamine Oxidase Inhibitors may increase hypertensive effects of Solriamfetol. Risk X: Avoid
St John's Wort: Monoamine Oxidase Inhibitors (Type B) may increase serotonergic effects of St John's Wort. This could result in serotonin syndrome. Risk X: Avoid
SUFentanil: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Specifically, the risk for serotonin syndrome or opioid toxicities (eg, respiratory depression, coma) may be increased. Management: Sufentanil should not be used with monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) due to the potential for serotonin syndrome and/or excessive CNS depression. Risk X: Avoid
Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tapentadol: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Tetrabenazine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tricyclic Antidepressants: Safinamide may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tyrosine: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Valbenazine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Viloxazine: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Ziprasidone: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
At doses ≤100 mg/day, interaction with tyramine-containing foods and beverages is unlikely, however concurrent ingestion of foods and beverages rich in tyramine (>150 mg) may cause hypertensive crisis. Management: Avoid foods and beverages that are very high in tyramine. Food's freshness is also an important concern; improperly stored or spoiled food can create an environment in which tyramine concentrations may increase (Walker 1996).
Adverse events were observed in animal reproduction studies.
The incidence of Parkinson disease in pregnancy is relatively rare. When treatment for Parkinson disease is needed, agents other than safinamide may be preferred in pregnant women (Seier 2017).
It is not known if safinamide is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
At doses ≤100 mg/day, interaction with tyramine-containing foods and beverages is unlikely, however patients should avoid foods and beverages with very high (>150 mg) tyramine concentrations. Food's freshness is also an important concern; improperly stored or spoiled food can create an environment where tyramine concentrations may increase (Walker 1996).
BP (baseline, periodic intervals, and as clinically indicated); hepatic function (baseline and as clinically indicated); visual changes (periodically) in patients with albinism, inherited retinal conditions, family history of hereditary retinal disease, history of retinal/macular degeneration, retinitis pigmentosa, uveitis, or any active retinopathy (eg, diabetic retinopathy).
Inhibitor of MAO-B. Plasma concentrations achieved via administration in recommended doses (≤100 mg/day) confer selective inhibition of MAO-B activity, blocking the catabolism of dopamine, resulting in an increase in dopamine levels and a subsequent increase in dopaminergic activity in the brain. The precise mechanism by which safinamide exerts its effect in Parkinson disease is unknown.
Distribution: Vdss: ~165 L
Protein binding: ~88%
Metabolism: Predominantly metabolized to inactive metabolites by non-microsomal enzymes (cytosolic amidases/MAOA); CYP3A4 and other CYP iso-enzymes play only a minor role in its overall biotransformation.
Bioavailability: 95%
Half-life elimination: 20 to 26 hours
Time to peak: 2 to 3 hours
Excretion: Urine (76%, primarily in the form of inactive metabolites; ~5% unchanged)
Hepatic function impairment: An approximately 30% increase in AUC was observed in mild hepatic impairment (Child-Pugh A). Exposure to safinamide was increased by about 80% in moderate hepatic impairment (Child-Pugh B).
