safinamide (Rx)

Brand and Other Names:Xadago
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 50mg
  • 100mg

Parkinson Disease

Indicated as add-on treatment for patients with Parkinson disease who are currently taking levodopa/carbidopa and experiencing “off” episodes

Initial: 50 mg PO qDay

After 2 weeks, may increase dose to 100 mg PO qDay, based on individual need and tolerability

Doses >100 mg/day have not shown additional benefit

Dosage Modifications

Liver impairment

  • Moderate (Child-Pugh B: 7-9): Not to exceed 50 mg/day
  • Severe (Child-Pugh C: 10-15): Contraindicated

Dosing Considerations

Limitation of use: Not shown effective as monotherapy for PD

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and safinamide

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      Serious - Use Alternative

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            Contraindicated (48)

            • amitriptyline

              amitriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • amoxapine

              amoxapine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • amphetamine polistirex

              amphetamine polistirex, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • clomipramine

              clomipramine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • cyclobenzaprine

              cyclobenzaprine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • cyproheptadine

              safinamide, cyproheptadine. Other (see comment). Contraindicated. Comment: MAO inhibitors may prolong and intensify the anticholinergic effects of antihistamines. Cyproheptadine may diminish the serotonergic effect of MAO inhibitors.

            • desipramine

              desipramine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • desvenlafaxine

              desvenlafaxine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • deutetrabenazine

              safinamide, deutetrabenazine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Contraindicated. Deutetrabenazine should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI.

            • dexmethylphenidate

              dexmethylphenidate, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • dextroamphetamine

              dextroamphetamine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • dextromethorphan

              dextromethorphan, safinamide. Other (see comment). Contraindicated. Comment: Coadministration of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or bizarre behavior.

            • diethylpropion

              diethylpropion, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • doxepin

              doxepin, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • duloxetine

              duloxetine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • fentanyl

              fentanyl, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • fentanyl intranasal

              fentanyl intranasal, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • fentanyl transdermal

              fentanyl transdermal, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • fentanyl transmucosal

              fentanyl transmucosal, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • imipramine

              imipramine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • isocarboxazid

              isocarboxazid, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration increases risk of nonselective MAO inhibition, that may lead to hypertensive crisis. At least 14 days should elapse between discontinuating safinamide and initiating MAOIs.

            • levomilnacipran

              levomilnacipran, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • linezolid

              linezolid, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration increases risk of nonselective MAO inhibition, that may lead to hypertensive crisis. At least 14 days should elapse between discontinuating safinamide and initiating MAOIs.

            • lisdexamfetamine

              lisdexamfetamine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

              safinamide, lisdexamfetamine. Either increases effects of the other by serotonin levels. Contraindicated. Do not use amphetamines during and within 14 days of discontinuation of monoamine oxidase inhibitors. .

            • maprotiline

              maprotiline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • meperidine

              meperidine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • methadone

              methadone, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • methamphetamine

              methamphetamine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • methylphenidate

              safinamide increases effects of methylphenidate by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode. Methylphenidate is contraindicated during treatment with an MAOI and also within a minimum of 14 days following discontinuation of an MAOI.

            • milnacipran

              milnacipran, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • morphine

              morphine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • nefazodone

              nefazodone, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • nortriptyline

              nortriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • ozanimod

              safinamide and ozanimod both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Contraindicated. Coadministration of ozanimod with MAO-B inhibitors may decrease exposure of the active metabolites of ozanimod, which may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis. Allow at least 14 days to elapse between discontinuing ozanimod and initiating with MAO inhibitors.

            • phendimetrazine

              phendimetrazine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • phenelzine

              phenelzine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration increases risk of nonselective MAO inhibition, that may lead to hypertensive crisis. At least 14 days should elapse between discontinuating safinamide and initiating MAOIs.

            • protriptyline

              protriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • rasagiline

              rasagiline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration increases risk of nonselective MAO inhibition, that may lead to hypertensive crisis. At least 14 days should elapse between discontinuating safinamide and initiating MAOIs.

            • selegiline

              selegiline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration increases risk of nonselective MAO inhibition, that may lead to hypertensive crisis. At least 14 days should elapse between discontinuating safinamide and initiating MAOIs.

            • selegiline transdermal

              selegiline transdermal, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration increases risk of nonselective MAO inhibition, that may lead to hypertensive crisis. At least 14 days should elapse between discontinuating safinamide and initiating MAOIs.

            • solriamfetol

              safinamide will increase the level or effect of solriamfetol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Contraindicated. Do no use solriamfetol during and/or within 14 days of discontinuing MAOI treatment. MAOIs irreversibly inhibit the enzyme monamine oxidase, an enzyme involved in the degradation of various monoamines, including dopamine and norepinephrine. Solriamfetol increases synaptic dopamine and norepinephrine.

            • St John's Wort

              St John's Wort, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • tapentadol

              tapentadol, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • tramadol

              tramadol, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • tranylcypromine

              tranylcypromine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration increases risk of nonselective MAO inhibition, that may lead to hypertensive crisis. At least 14 days should elapse between discontinuating safinamide and initiating MAOIs.

            • trazodone

              trazodone, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • trimipramine

              trimipramine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • venlafaxine

              venlafaxine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            Serious - Use Alternative (33)

            • alpelisib

              safinamide will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of alpelisib (BCRP substrate) with a BCRP inhibitor may increase alpelisib concentration, which may increase the risk of toxicities. If unable to avoid or use alternant drugs, closely monitor for increased adverse reactions.

            • aripiprazole

              aripiprazole decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • asenapine

              asenapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • cariprazine

              cariprazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • clozapine

              clozapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • deutetrabenazine

              deutetrabenazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • fluphenazine

              fluphenazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • haloperidol

              haloperidol decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • iloperidone

              iloperidone decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • iobenguane I 131

              safinamide will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

            • loxapine

              loxapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • loxapine inhaled

              loxapine inhaled decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • lurasidone

              lurasidone decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • methylene blue

              methylene blue, safinamide. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and safinamide may increase serotonin as a result of MAO-A inhibition. If IV methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • metoclopramide

              metoclopramide decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • metoclopramide intranasal

              safinamide, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

              metoclopramide intranasal increases toxicity of safinamide by Other (see comment). Avoid or Use Alternate Drug. Comment: Metoclopramide may enhance the hypertensive effect of monoamine oxidase inhibitors.

            • olanzapine

              olanzapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • ozanimod

              safinamide increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .

            • paliperidone

              paliperidone decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • perphenazine

              perphenazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • pimavanserin

              pimavanserin decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • pimozide

              pimozide decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • prochlorperazine

              prochlorperazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • quetiapine

              quetiapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • rimegepant

              safinamide will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP.

            • risperidone

              risperidone decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • talazoparib

              safinamide will increase the level or effect of talazoparib by Other (see comment). Avoid or Use Alternate Drug. BCRP inhibitors may increase systemic exposure of talazoparib (a BCRP substrate). If coadministration cannot be avoided, monitor for potential adverse reactions.

            • tetrabenazine

              tetrabenazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • thioridazine

              thioridazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • thiothixene

              thiothixene decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • trifluoperazine

              trifluoperazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • valbenazine

              safinamide, valbenazine. Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of valbenazine with MAOIs may increase monoamine neurotransmitter concentration in synapses, potentially increasing risk of serotonin syndrome or attenuating valbenazine effect.

            • ziprasidone

              ziprasidone decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            Monitor Closely (65)

            • atorvastatin

              safinamide will increase the level or effect of atorvastatin by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, safinamide. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • berotralstat

              safinamide increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

            • bretylium

              safinamide increases effects of bretylium by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Modify Therapy/Monitor Closely. Bretylium produces release of catecholamines from nerve endings. This increased catecholamine release is potentiated by MAOIs.

            • buprenorphine subdermal implant

              safinamide, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • buprenorphine, long-acting injection

              safinamide, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • chlorothiazide

              safinamide will increase the level or effect of chlorothiazide by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • cimetidine

              safinamide will increase the level or effect of cimetidine by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • citalopram

              citalopram, safinamide. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Monitor patients for symptoms of serotonin syndrome if SSRIs are coadministered with safinamide.

            • daunorubicin

              safinamide will increase the level or effect of daunorubicin by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • dipyridamole

              safinamide will increase the level or effect of dipyridamole by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • doxorubicin

              safinamide will increase the level or effect of doxorubicin by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • duvelisib

              safinamide will increase the level or effect of duvelisib by Other (see comment). Use Caution/Monitor. Coadministration of duvelisib (a BCRP substrate) with a BCRP transport inhibitor may increase levels or effects of duvelisib.

            • escitalopram

              escitalopram, safinamide. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Monitor patients for symptoms of serotonin syndrome if SSRIs are coadministered with safinamide.

            • fluoxetine

              fluoxetine, safinamide. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Monitor patients for symptoms of serotonin syndrome if SSRIs are coadministered with safinamide.

            • fluvastatin

              safinamide will increase the level or effect of fluvastatin by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • fluvoxamine

              fluvoxamine, safinamide. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Monitor for serotonin syndrome.

            • glecaprevir/pibrentasvir

              safinamide will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with BCRP inhibitors.

            • glyburide

              safinamide will increase the level or effect of glyburide by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • hydrocodone

              hydrocodone, safinamide. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • imatinib

              safinamide will increase the level or effect of imatinib by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • irinotecan

              safinamide will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • isoniazid

              isoniazid, safinamide. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Monitor for hypertension and reaction to dietary tyramine in patients treated concomitantly with isoniazid and safinamide.

            • lapatinib

              safinamide will increase the level or effect of lapatinib by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • lasmiditan

              safinamide increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

            • ledipasvir/sofosbuvir

              safinamide will increase the level or effect of ledipasvir/sofosbuvir by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • leflunomide

              safinamide will increase the level or effect of leflunomide by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • lenvatinib

              safinamide will increase the level or effect of lenvatinib by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • levodopa inhaled

              levodopa inhaled increases effects of safinamide by dopaminergic effects. Use Caution/Monitor. Coadministration of selective MAO-B inhibitors with levodopa may be associated with orthostatic hypotension.

            • methotrexate

              safinamide will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • midazolam intranasal

              midazolam intranasal, safinamide. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • midodrine

              midodrine and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • mitoxantrone

              safinamide will increase the level or effect of mitoxantrone by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • naphazoline

              naphazoline and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • naphazoline ophthalmic

              naphazoline ophthalmic and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • naphazoline/glycerin ophthalmic

              naphazoline/glycerin ophthalmic and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • naphazoline/zinc sulfate/glycerin ophthalmic

              naphazoline/zinc sulfate/glycerin ophthalmic and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • nitrofurantoin

              safinamide will increase the level or effect of nitrofurantoin by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • oliceridine

              safinamide, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

            • osimertinib

              safinamide will increase the level or effect of osimertinib by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • oxymetazoline intranasal

              oxymetazoline intranasal and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • oxymetazoline ophthalmic

              oxymetazoline ophthalmic and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • pantoprazole

              safinamide will increase the level or effect of pantoprazole by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • paroxetine

              paroxetine, safinamide. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Monitor patients for symptoms of serotonin syndrome if SSRIs are coadministered with safinamide.

            • pazopanib

              safinamide will increase the level or effect of pazopanib by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • phenylephrine

              phenylephrine and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • phenylephrine nasal

              phenylephrine nasal and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • phenylephrine PO

              phenylephrine PO and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • pitavastatin

              safinamide will increase the level or effect of pitavastatin by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • pseudoephedrine

              pseudoephedrine and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • riociguat

              safinamide will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • rosuvastatin

              safinamide will increase the level or effect of rosuvastatin by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • selexipag

              safinamide will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.

            • sertraline

              sertraline, safinamide. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Monitor patients for symptoms of serotonin syndrome if SSRIs are coadministered with safinamide.

            • sofosbuvir

              safinamide will increase the level or effect of sofosbuvir by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • sofosbuvir/velpatasvir

              safinamide will increase the level or effect of sofosbuvir/velpatasvir by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • sufentanil SL

              sufentanil SL, safinamide. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • sulfasalazine

              safinamide will increase the level or effect of sulfasalazine by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • tenofovir AF

              safinamide will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • tenofovir DF

              safinamide will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • tetrahydrozoline, ophthalmic

              tetrahydrozoline, ophthalmic and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            • topotecan

              safinamide will increase the level or effect of topotecan by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • tyramine

              safinamide increases toxicity of tyramine by enhancing GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Advise patients to avoid foods containing large amounts of tyramine while taking recommended doses of safinamide.

            • vemurafenib

              safinamide will increase the level or effect of vemurafenib by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • xylometazoline

              xylometazoline and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

            Minor (0)

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              Adverse Effects

              >10%

              Dyskinesia (17-21%)

              1-10%

              Hypertension (5-7%)

              ALT or AST increased to >ULN (5-7%)

              Fall (4-6%)

              Nausea (3-6%)

              Insomnia (1-4%)

              Orthostatic hypotension (2%)

              Anxiety (2%)

              Cough (2%)

              Dyspepsia (2%)

              Postmarketing Reports

              Swelling of tongue and gingiva

              Dyspnea

              Rash

              Hypersensitivity

              Headache

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              Warnings

              Contraindications

              History of hypersensitivity to safinamide; reactions include swelling of the tongue and oral mucosa, and dyspnea

              Severe hepatic impairment (Child-Pugh C: 10-15)

              Coadministration with other monoamine oxidase inhibitors (MAOIs) or drugs that are potent inhibitors of MAO (eg, linezolid); combination may result in increased blood pressure, including hypertensive crisis

              Coadministration with opioids (eg, meperidine and its derivatives, methadone, tramadol); serotonin-norepinephrine reuptake inhibitors (SNRIs); tricyclic, tetracyclic, or triazolopyridine antidepressants; cyclobenzaprine; methylphenidate, amphetamine, and their derivatives; or St John’s wort; combination could result in life-threatening serotonin syndrome

              Coadministration with dextromethorphan; combination of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or abnormal behavior

              Cautions

              May cause or exacerbate hypertension; monitor patients for new onset hypertension or hypertension not adequately controlled after initiating therapy; medication adjustment may be necessary if blood pressure elevation is sustained

              May cause serotonin syndrome when used with MAOIs, antidepressants, or opioid drugs (see Contraindications)

              May cause falling asleep during activities of daily living

              May cause or exacerbate dyskinesia; consider levodopa dose reduction to mitigate dyskinesia

              May cause hallucinations and psychotic behavior; consider dosage reduction or stopping medication if patient develops hallucinations or psychotic-like behaviors while on therapy

              May cause problems with impulse control/compulsive behaviors; consider dose reduction or stopping medication if a patient develops compulsive behavior while on therapy

              May cause withdrawal-emergent hyperpyrexia and confusion

              Retinal degeneration and loss of photoreceptor cells observed in animal studies (albino and pigmented rats); periodically monitor patients for visual changes in patients with a history of retinal/macular degeneration, uveitis, inherited retinal conditions, family history of hereditary retinal disease, albinism, retinitis pigmentosa, or any active retinopathy

              Drug interaction overview

              • Safinamide is contraindicated with other drugs in the MAOI class or other drugs that are potent inhibitors of MAO (see Contraindications)
              • Opioids combined with safinamide has caused serious and sometimes fatal reactions and is contraindicated; at least 14 days should elapse between use of safinamide and these drugs to avoid serotonin syndrome (see Contraindications)
              • Dextromethorphan and MAOIs is contraindicated, owing to reports of psychosis or bizarre behavior (see Contraindications)
              • Isoniazid has some monoamine oxidase inhibiting activity; monitor for hypertension and reaction to dietary tyramine in patients treated concomitantly with isoniazid
              • Safinamide and its major metabolite may inhibit intestinal breast cancer resistance protein (BCRP), and therefore could increase plasma concentrations of BCRP substrates (eg, methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan)
              • Dopamine antagonists, such as antipsychotics or metoclopramide, may decrease the effectiveness therapy and exacerbate the symptoms of Parkinson disease
              • Sympathomimetics
                • Severe hypertensive reactions have followed administration of sympathomimetics and nonselective MAOIs
                • Hypertensive crisis has been reported in patients taking recommended doses of selective MAO-B inhibitors and sympathomimetic medications
                • Concomitant use with methylphenidate, amphetamine, and their derivatives is contraindicated; monitor patients for hypertension if therapy is prescribed concomitantly with prescription or nonprescription sympathomimetic medications, including nasal, oral, or ophthalmic decongestants and cold remedies
              • Serotonergic drugs
                • SNRIs; triazolopyridine, tricyclic, or tetracyclic antidepressants; cyclobenzaprine; or St John’s wort are contraindicated with safinamide; at least 14 days should elapse between use of safinamide and these drugs to avoid serotonin syndrome (see Contraindications)
                • Coadministration with SSRIs: Monitor for symptoms of serotonin syndrome
              • Tyramine
                • MAO in the GI tract and liver (primarily type A) provides protection from exogenous amines (eg, tyramine)
                • If tyramine were absorbed intact, it could lead to severe hypertension, including hypertensive crisis
                • Aged, fermented, cured, smoked, and pickled foods containing large amounts of exogenous amines (eg, aged cheese, pickled herring) may cause release of norepinephrine, resulting in a rise in blood pressure (tyramine reaction)
                • Advise patients to avoid foods containing large amounts of tyramine
                • Selectivity for inhibiting MAO-B decreases in a dose-related manner above the highest recommended daily dosage, which may increase the risk for hypertension
                • In addition, isoniazid has some MAO inhibiting activity; monitor for hypertension and reaction to dietary tyramine in patients treated with isoniazid and safinamide
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              Pregnancy

              Pregnancy

              There are no adequate and well-controlled studies of safinamide in pregnant women

              Animal studies

              • Developmental toxicity, including teratogenic effects, was observed when safinamide was administered during pregnancy at clinically relevant doses
              • Developmental toxicity was observed at safinamide doses lower than those used clinically when safinamide was administered during pregnancy in combination with levodopa/carbidopa

              Lactation

              Unknown if distributed in human breast milk

              Rats: Skin discoloration, presumed to be caused by hyperbilirubinemia resulting from hepatobiliary toxicity, was observed in rat pups indirectly exposed to safinamide through the milk during the lactation period

              Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              The precise mechanism by which safinamide exerts its effect in PD is unknown

              Inhibition of MAO-B activity, by blocking the catabolism of dopamine, is thought to result in an increase in dopamine levels and a subsequent increase in dopaminergic activity in the brain

              Absorption

              Peak plasma time: 2-3 hr

              Bioavailability: 95%

              Steady-state: 3-5 days

              Distribution

              Protein bound: Not highly protein bound

              Vd: 165 L

              Metabolism

              Hydrolytic oxidation of the amide moiety leading to the primary metabolite safinamide acid

              Oxidative cleavage of the ether bond forming O-debenzylated safinamide

              Oxidative cleavage of the amine bond of either safinamide or safinamide acid to form N-dealkylated acid; this is further conjugated with glucuronic acid to yield its acyl glucuronide

              Elimination

              Half-life: 20-26 hr

              Total clearance: 4.6 L/hr

              Excretion: Primarily in urine (~5% unchanged; 76% as inactive metabolites)

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              Administration

              Oral Administration

              May take with or without food

              Take one daily dose at approximately the same time each day

              Missed dose: Take the next dose at the same time the next day

              Discontinuing: If taking 100 mg/day, taper by decreasing dose to 50 mg/day for 1 week before stopping

              Storage

              Store at 25°C (77°F); excursions permitted between 15-30°C (59-86°F)

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              Xadago oral
              -
              100 mg tablet
              Xadago oral
              -
              50 mg tablet

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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              NC NOT COVERED – Drugs that are not covered by the plan.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.