Version May 2024
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Blood Glucose Lowering Effects: Monoamine Oxidase Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Alpha-/Beta-Agonists (Indirect-Acting): Monoamine Oxidase Inhibitors may enhance the hypertensive effect 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 combination
Alpha1-Agonists: Monoamine Oxidase Inhibitors may enhance the hypertensive effect 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 combination
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Amphetamines: Monoamine Oxidase Inhibitors may enhance the hypertensive effect 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 combination
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Apraclonidine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Apraclonidine. Monoamine Oxidase Inhibitors may increase the serum concentration of Apraclonidine. Risk X: Avoid combination
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Atomoxetine: Monoamine Oxidase Inhibitors may enhance the neurotoxic (central) effect of Atomoxetine. Risk X: Avoid combination
Atropine (Ophthalmic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). Risk X: Avoid combination
Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Benzhydrocodone: May enhance the serotonergic effect 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 enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy
Betahistine: Monoamine Oxidase Inhibitors may increase the serum concentration of Betahistine. Risk C: Monitor therapy
Bezafibrate: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Risk X: Avoid combination
Blonanserin: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Brimonidine (Ophthalmic): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Risk C: Monitor therapy
Brimonidine (Topical): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Brimonidine (Topical). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Topical). Risk C: Monitor therapy
Bromperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Buprenorphine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
BuPROPion: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of BuPROPion. Risk X: Avoid combination
Butorphanol: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
CarBAMazepine: May enhance the adverse/toxic effect 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 combination
Carbinoxamine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Carbinoxamine. Specifically, the anticholinergic effects of carbinoxamine may be enhanced and prolonged. Risk X: Avoid combination
Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Cerebrolysin: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CloZAPine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Cocaine (Topical): May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy
Codeine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Codeine. Risk X: Avoid combination
Cyclobenzaprine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Cyproheptadine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Deutetrabenazine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Deutetrabenazine. Risk X: Avoid combination
Dexmethylphenidate: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Risk X: Avoid combination
Dextromethorphan: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
Diamorphine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Diamorphine. Risk X: Avoid combination
Diethylpropion: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Diethylpropion. Risk X: Avoid combination
Dihydrocodeine: May enhance the adverse/toxic effect 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 enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Domperidone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Domperidone. Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy
DOPamine: Monoamine Oxidase Inhibitors may enhance the hypertensive effect 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 enhance the hypertensive effect of Doxapram. Risk C: Monitor therapy
DroPERidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
EPINEPHrine (Nasal): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Nasal). Risk C: Monitor therapy
EPINEPHrine (Oral Inhalation): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Risk X: Avoid combination
Epinephrine (Racemic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). Risk C: Monitor therapy
EPINEPHrine (Systemic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Esketamine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy
Fenfluramine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination
FentaNYL: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination
Flupentixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Gepirone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination
Guanethidine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Haloperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
HYDROcodone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROcodone. HYDROcodone may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. 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 enhance the adverse/toxic effect 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 enhance the adverse/toxic effect of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Indoramin: Monoamine Oxidase Inhibitors may enhance the hypotensive effect of Indoramin. Risk X: Avoid combination
Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may diminish the therapeutic effect 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 combination
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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
Isometheptene: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Isometheptene. Risk X: Avoid combination
Isoniazid: Safinamide may enhance the adverse/toxic effect of Isoniazid. Specifically, there is an increased risk for hypertension. Risk C: Monitor therapy
Isoproterenol: Monoamine Oxidase Inhibitors may enhance the therapeutic effect of Isoproterenol. Risk C: Monitor therapy
Levodopa-Foslevodopa: May enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Type B). Risk C: Monitor therapy
Levomethadone: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Levonordefrin: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Levonordefrin. Risk X: Avoid combination
Linezolid: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination
Loxapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lurasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Maprotiline: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Meptazinol: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Meptazinol. Risk X: Avoid combination
Mequitazine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Mequitazine. Risk X: Avoid combination
Metaraminol: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Metaraminol. Risk C: Monitor therapy
Methadone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Methotrimeprazine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, monoamine oxidase inhibitors may enhance dopamine blockade, possible increasing the risk for neuroleptic malignant syndrome. Methotrimeprazine may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Methyldopa: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Methyldopa. Risk X: Avoid combination
Methylene Blue: Monoamine Oxidase Inhibitors (Type B) may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Methylphenidate: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Methylphenidate. Risk X: Avoid combination
Metoclopramide: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Mianserin: Monoamine Oxidase Inhibitors may enhance the neurotoxic effect of Mianserin. Risk X: Avoid combination
Mivacurium: Monoamine Oxidase Inhibitors may increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors (Antidepressant): May enhance the hypertensive effect of Monoamine Oxidase Inhibitors (Type B). Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination
Monoamine Oxidase Inhibitors (Type B): May enhance the serotonergic effect of other Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination
Morphine (Systemic): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). Risk X: Avoid combination
Nalbuphine: Monoamine Oxidase Inhibitors may enhance the CNS depressant effect of Nalbuphine. Nalbuphine may enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Nalbuphine may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. 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 enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination
Nefopam: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Nefopam. Risk X: Avoid combination
Norepinephrine: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Norepinephrine. Risk C: Monitor therapy
Normethadone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Normethadone. Risk X: Avoid combination
OLANZapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Opium: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Opium. Risk X: Avoid combination
OxyCODONE: May enhance the serotonergic effect 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 enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Ozanimod: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Paliperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pheniramine: May enhance the anticholinergic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Pholcodine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Pimozide: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pipamperone [INT]: Anti-Parkinson Agents (Monoamine Oxidase Inhibitor) may diminish the therapeutic effect of Pipamperone [INT]. Pipamperone [INT] may diminish the therapeutic effect of Anti-Parkinson Agents (Monoamine Oxidase Inhibitor). Risk C: Monitor therapy
Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pizotifen: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Pizotifen. Risk X: Avoid combination
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
QUEtiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Reboxetine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reboxetine. Risk X: Avoid combination
Remifentanil: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Remifentanil may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. 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 enhance the adverse/toxic effect 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 enhance the adverse/toxic effect of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: Safinamide may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Use the lowest effective dose of SSRIs in patients treated with safinamide and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Serotonergic Agents (High Risk, Miscellaneous): Monoamine Oxidase Inhibitors (Type B) may enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Risk X: Avoid combination
Serotonergic Agents (Moderate Risk, Miscellaneous): Monoamine Oxidase Inhibitors (Type B) may enhance the serotonergic effect 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 therapy
Serotonergic Non-Opioid CNS Depressants: Safinamide may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid combination
Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination
Serotonin/Norepinephrine Reuptake Inhibitors: Safinamide may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Sertindole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Sevoflurane: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Sevoflurane. Specifically, the risk of hemodynamic instability may be increased. Risk C: Monitor therapy
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 therapy
Solriamfetol: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Solriamfetol. Risk X: Avoid combination
St John's Wort: Monoamine Oxidase Inhibitors (Type B) may enhance the serotonergic effect of St John's Wort. This could result in serotonin syndrome. Risk X: Avoid combination
SUFentanil: May enhance the adverse/toxic effect 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 combination
Sulpiride: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Tapentadol: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Tetrabenazine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Tetrahydrozoline (Nasal): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Risk X: Avoid combination
Thioridazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Tricyclic Antidepressants: Safinamide may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Tyrosine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Valbenazine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Viloxazine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Ziprasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
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).
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