Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (50)
- 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.
- methylphenidate transdermal
methylphenidate transdermal and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Contraindicated. Coadministration of MAOIs and CNS stimulants can cause hypertensive crisis.
- 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.
- serdexmethylphenidate/dexmethylphenidate
serdexmethylphenidate/dexmethylphenidate, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.
- 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 (34)
- 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.
- olopatadine intranasal
safinamide and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- 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 (67)
- 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.
- daridorexant
safinamide and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- 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.
- difelikefalin
difelikefalin and safinamide both increase sedation. Use Caution/Monitor.
- 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)
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
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
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.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)
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)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Xadago oral - | 100 mg tablet |  | |
| Xadago oral - | 50 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Formulary
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