Dosing & Uses
Dosage Forms & Strength
levodopa/carbidopa/entacapone
tablet
- 50mg/12.5mg/200mg
- 75mg/18.75mg/200mg
- 100mg/25mg/200mg
- 125mg/31.25mg/200mg
- 150mg/37.5mg/200mg
- 200mg/50mg/200mg
Parkinson Disease
Substitute an equal levodopa dose with Stalevo as patient's dose at transfer
Maintenance: Titrate as necessary
Carbidopa should be 70-100 mg/day; not to exceed 200 mg/day
Not to exceed 8 tablets/day divided q4-8hr while awake
Food increases levodopa absorption
Monitor hepatic, hematopoietic, cardiovascular, renal function
Safety & efficacy not established
Parkinson Disease
Substitute an equal levodopa dose with Stalevo as patient's dose at transfer
Maintenance: Titrate as necessary
Carbidopa should be 70-100 mg/day; not to exceed 200 mg/day
Not to exceed 8 tablets/day divided q4-8hr while awake
Food increases levodopa absorption
Monitor hepatic, hematopoietic, cardiovascular, renal function
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (8)
- isocarboxazid
isocarboxazid, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
entacapone, isocarboxazid. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Both nonselective MAO inhibitors and entacapone inhibit catecholamine metabolism, leading to increased levels of catecholamines. Potential for dangerously high HR or BP. - lonafarnib
entacapone will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.
- phenelzine
phenelzine, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
- phenelzine
entacapone, phenelzine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Both nonselective MAO inhibitors and entacapone inhibit catecholamine metabolism, leading to increased levels of catecholamines. Potential for dangerously high HR or BP.
- procarbazine
procarbazine, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
- selegiline
selegiline, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode. Concomitant therapy with selegiline and carbidopa-levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa-levodopa alone.
- selegiline transdermal
selegiline transdermal, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
- tranylcypromine
entacapone, tranylcypromine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Both nonselective MAO inhibitors and entacapone inhibit catecholamine metabolism, leading to increased levels of catecholamines. Potential for dangerously high HR or BP.
tranylcypromine, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
Serious - Use Alternative (34)
- amisulpride
amisulpride, levodopa. Either decreases effects of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid use of amisulpride, a dopamine receptor antagonist, with dopamine agonists.
- aripiprazole
aripiprazole decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- chlorpromazine
chlorpromazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- clozapine
clozapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- desvenlafaxine
levodopa and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.
- droperidol
droperidol decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- elacestrant
entacapone will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fluphenazine
fluphenazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- haloperidol
haloperidol decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- iloperidone
iloperidone decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- infigratinib
entacapone will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- linezolid
linezolid and levodopa both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
linezolid, levodopa. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of acute hypertensive episode. - loxapine
loxapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- loxapine inhaled
loxapine inhaled decreases effects of levodopa by pharmacodynamic antagonism. Contraindicated.
- lurbinectedin
entacapone will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- macimorelin
levodopa, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that may transiently elevate growth hormone (GH) concentrations may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin.
- methylene blue
methylene blue and levodopa both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If 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 intranasal
levodopa, 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, levodopa. dopaminergic effects. Avoid or Use Alternate Drug. Opposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (eg, parkinsonian symptoms) or decreased therapeutic effects of metoclopramide.
entacapone, 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. - olanzapine
olanzapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- olopatadine intranasal
entacapone 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.
- olopatadine intranasal
levodopa 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.
- omaveloxolone
entacapone will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 100 mg/day. Closely monitor for adverse effects. If adverse effects emerge, further reduce to 50 mg/day.
- pacritinib
entacapone will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- paliperidone
paliperidone decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- perphenazine
perphenazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- pimozide
pimozide decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- procarbazine
procarbazine and levodopa both increase serotonin levels. Avoid or Use Alternate Drug.
- prochlorperazine
prochlorperazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- promethazine
promethazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- quetiapine
quetiapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- repotrectinib
entacapone will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.
- risperidone
risperidone decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b and entacapone both increase Other (see comment). Avoid or Use Alternate Drug. Narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity.
- thioridazine
thioridazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
Monitor Closely (189)
- abobotulinumtoxinA
abobotulinumtoxinA increases effects of levodopa by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.
- acebutolol
carbidopa increases effects of acebutolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of acebutolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - aclidinium
aclidinium, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- alfuzosin
carbidopa increases effects of alfuzosin by pharmacodynamic synergism. Use Caution/Monitor. Monitor for hypotension.
- acrivastine
acrivastine and entacapone both increase sedation. Use Caution/Monitor.
- amifostine
amifostine, levodopa. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.
- amiloride
carbidopa increases effects of amiloride by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of amiloride by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - amisulpride
amisulpride and entacapone both increase sedation. Use Caution/Monitor.
- amlodipine
carbidopa increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- amlodipine
levodopa increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- apomorphine
apomorphine and levodopa both increase dopaminergic effects. Use Caution/Monitor. Combination may enhance efficacy. Monitor for hypotension.
- asenapine
asenapine and entacapone both increase sedation. Use Caution/Monitor.
carbidopa increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Monitor for hypotension. - asenapine transdermal
asenapine transdermal and entacapone both increase sedation. Use Caution/Monitor.
- atenolol
carbidopa increases effects of atenolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- atenolol
levodopa increases effects of atenolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- atogepant
entacapone will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atropine IV/IM
atropine IV/IM, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- avapritinib
avapritinib and entacapone both increase sedation. Use Caution/Monitor.
- benazepril
levodopa increases effects of benazepril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of benazepril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
benazepril, levodopa. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects. - benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen and entacapone both increase sedation. Use Caution/Monitor.
- betaxolol
carbidopa increases effects of betaxolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- betaxolol
levodopa increases effects of betaxolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- bisoprolol
levodopa increases effects of bisoprolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of bisoprolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - bosentan
carbidopa increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of bosentan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - brexpiprazole
brexpiprazole and entacapone both increase sedation. Use Caution/Monitor.
- bumetanide
carbidopa increases effects of bumetanide by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- brimonidine
brimonidine and entacapone both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and entacapone both increase sedation. Use Caution/Monitor.
- bromocriptine
bromocriptine and levodopa both increase dopaminergic effects. Use Caution/Monitor. Combining drugs may be therapeutic in patients with Parkinsonism and may allow for reduced levodopa doses. Dosages should be carefully titrated during concomitant treatment.
- bumetanide
levodopa increases effects of bumetanide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- buprenorphine subdermal implant
buprenorphine subdermal implant and entacapone both increase sedation. Use Caution/Monitor.
- buprenorphine transdermal
buprenorphine transdermal and entacapone both increase sedation. Use Caution/Monitor.
- buprenorphine, long-acting injection
buprenorphine, long-acting injection and entacapone both increase sedation. Use Caution/Monitor.
- bupropion
bupropion increases effects of levodopa by pharmacodynamic synergism. Use Caution/Monitor. There is a higher incidence of adverse reactions with concurrent use of bupropion with levodopa. Use small initial dosages and small, gradual dosage increases of bupropion.
- candesartan
levodopa increases effects of candesartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- capivasertib
entacapone will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.
- captopril
levodopa increases effects of captopril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
captopril, levodopa. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.
carbidopa increases effects of captopril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - carbonyl iron
carbonyl iron decreases levels of levodopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Oral administration of iron salts should be separated from levodopa by at least 2 hours.
- carvedilol
carbidopa increases effects of carvedilol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- carvedilol
levodopa increases effects of carvedilol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- chlorothiazide
levodopa increases effects of chlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of chlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - chlorthalidone
levodopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - clevidipine
levodopa increases effects of clevidipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of clevidipine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - clonidine
levodopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - cyclizine
cyclizine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- doxazosin
carbidopa increases effects of doxazosin by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- cyclopenthiazide
levodopa increases effects of cyclopenthiazide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- daridorexant
entacapone will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.
entacapone 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.
levodopa 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. - dicyclomine
dicyclomine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- difelikefalin
difelikefalin and entacapone both increase sedation. Use Caution/Monitor.
- difelikefalin
difelikefalin and levodopa both increase sedation. Use Caution/Monitor.
- dihydroergotamine intranasal
dihydroergotamine intranasal and levodopa both increase serotonin levels. Use Caution/Monitor.
- diltiazem
levodopa increases effects of diltiazem by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- diphenhydramine
diphenhydramine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- dobutamine
entacapone will increase the level or effect of dobutamine by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.
- dopamine
entacapone will increase the level or effect of dopamine by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.
- doxazosin
levodopa increases effects of doxazosin by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- droxidopa
carbidopa decreases effects of droxidopa by decreasing metabolism. Use Caution/Monitor. Carbidopa, a peripheral dopa-decarboxylase inhibitor, could prevent the conversion of droxidopa to norepinephrine; increased droxidopa dose may be required.
- enalapril
carbidopa increases effects of enalapril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of enalapril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - epinephrine
entacapone will increase the level or effect of epinephrine by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.
- eplerenone
carbidopa increases effects of eplerenone by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- epinephrine inhaled
entacapone will increase the level or effect of epinephrine inhaled by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.
- epinephrine racemic
entacapone will increase the level or effect of epinephrine racemic by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.
- eplerenone
levodopa increases effects of eplerenone by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- epoprostenol
carbidopa increases effects of epoprostenol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of epoprostenol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - eprosartan
levodopa increases effects of eprosartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- esmolol
carbidopa increases effects of esmolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- esmolol
levodopa increases effects of esmolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- ethacrynic acid
carbidopa increases effects of ethacrynic acid by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of ethacrynic acid by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - felodipine
carbidopa increases effects of felodipine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of felodipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - fenoldopam
levodopa increases effects of fenoldopam by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of fenoldopam by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - fentanyl
fentanyl and entacapone both increase sedation. Use Caution/Monitor.
- fosinopril
carbidopa increases effects of fosinopril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- fentanyl intranasal
fentanyl intranasal and entacapone both increase sedation. Use Caution/Monitor.
- fentanyl iontophoretic transdermal system
fentanyl iontophoretic transdermal system and entacapone both increase sedation. Use Caution/Monitor.
- fentanyl transdermal
fentanyl transdermal and entacapone both increase sedation. Use Caution/Monitor.
- ferric maltol
ferric maltol decreases levels of levodopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Oral administration of iron salts should be separated from levodopa by at least 2 hours.
- ferrous fumarate
ferrous fumarate decreases levels of levodopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Oral administration of iron salts should be separated from levodopa by at least 2 hours.
- ferrous gluconate
ferrous gluconate decreases levels of levodopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
- ferrous sulfate
ferrous sulfate decreases levels of levodopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Oral administration of iron salts should be separated from levodopa by at least 2 hours.
- finerenone
entacapone will increase the level or effect of finerenone by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.
entacapone will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed. - food
food decreases levels of levodopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Food with a high protein content may interfere with the absorption of levodopa.
- fosinopril
levodopa increases effects of fosinopril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- fosphenytoin
fosphenytoin decreases effects of levodopa by unknown mechanism. Use Caution/Monitor.
- furosemide
carbidopa increases effects of furosemide by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of furosemide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - ganaxolone
entacapone and ganaxolone both increase sedation. Use Caution/Monitor.
- guanfacine
carbidopa increases effects of guanfacine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- gepirone
entacapone will increase the level or effect of gepirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce gepirone dose by 50% when used concomitantly with a moderate CYP3A4 inhibitor.
- glycopyrrolate
glycopyrrolate, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- glycopyrrolate inhaled
glycopyrrolate inhaled, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- guanfacine
levodopa increases effects of guanfacine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- hydralazine
levodopa increases effects of hydralazine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of hydralazine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - hydrochlorothiazide
levodopa increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - hyoscyamine
hyoscyamine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- iloprost
carbidopa increases effects of iloprost by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- hyoscyamine spray
hyoscyamine spray, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- iloprost
levodopa increases effects of iloprost by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- indapamide
carbidopa increases effects of indapamide by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of indapamide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - irbesartan
carbidopa increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - iron dextran complex
iron dextran complex decreases levels of levodopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Oral administration of iron salts should be separated from levodopa by at least 2 hours.
- isradipine
carbidopa increases effects of isradipine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- isavuconazonium sulfate
entacapone will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isoproterenol
entacapone will increase the level or effect of isoproterenol by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.
- isradipine
levodopa increases effects of isradipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- ketanserin
levodopa increases effects of ketanserin by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- labetalol
carbidopa increases effects of labetalol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of labetalol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - lefamulin
entacapone will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.
- lisinopril
carbidopa increases effects of lisinopril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- levomilnacipran
levomilnacipran and levodopa both increase serotonin levels. Modify Therapy/Monitor Closely.
- lisinopril
levodopa increases effects of lisinopril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- losartan
levodopa increases effects of losartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- lumateperone
entacapone will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.
- lurasidone
lurasidone decreases effects of levodopa by pharmacodynamic antagonism. Use Caution/Monitor. Antipsychotics may diminish the therapeutic effect of anti-parkinson's agents; may increase risk of hypotension.
- mavacamten
entacapone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.
entacapone will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose. - meclizine
meclizine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- methyclothiazide
carbidopa increases effects of methyclothiazide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
levodopa increases effects of methyclothiazide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - methyldopa
methyldopa, levodopa. pharmacodynamic synergism. Use Caution/Monitor. Risk of additive hypotensive effects, and risk of toxic CNS effects such as psychosis.
entacapone will increase the level or effect of methyldopa by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure. - metolazone
carbidopa increases effects of metolazone by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- methylphenidate
levodopa, methylphenidate. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive CNS stimulation.
- metoprolol
carbidopa increases effects of metoprolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- metyrosine
carbidopa increases effects of metyrosine by pharmacodynamic synergism. Use Caution/Monitor. Monitor for hypotension.
- minoxidil
carbidopa increases effects of minoxidil by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- moexipril
carbidopa increases effects of moexipril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- nadolol
carbidopa increases effects of nadolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- nebivolol
carbidopa increases effects of nebivolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- nicardipine
carbidopa increases effects of nicardipine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- nifedipine
carbidopa increases effects of nifedipine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- nisoldipine
carbidopa increases effects of nisoldipine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- norepinephrine
entacapone will increase the level or effect of norepinephrine by decreasing metabolism. Use Caution/Monitor. Entacapone is a COMT inhibitor. Caution if coadministered with drugs metabolized by COMT. If coadministered, monitor for changes in heart rate, heart rhythm, and blood pressure.
- metoclopramide
metoclopramide decreases levels of levodopa by pharmacodynamic antagonism. Use Caution/Monitor. Avoid combination if possible.
- metolazone
levodopa increases effects of metolazone by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- metoprolol
levodopa increases effects of metoprolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- midazolam intranasal
midazolam intranasal, levodopa. 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.
- minoxidil
levodopa increases effects of minoxidil by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- moexipril
levodopa increases effects of moexipril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- nadolol
levodopa increases effects of nadolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- nebivolol
levodopa increases effects of nebivolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- nicardipine
levodopa increases effects of nicardipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- nifedipine
levodopa increases effects of nifedipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- nisoldipine
levodopa increases effects of nisoldipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- norgestrel
entacapone will increase the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may increase systemic concentration of norgestrel, which may increase risk for adverse effects
- oliceridine
entacapone will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
- olmesartan
levodopa increases effects of olmesartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- onabotulinumtoxinA
onabotulinumtoxinA, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- oxybutynin transdermal
oxybutynin transdermal decreases effects of levodopa by pharmacodynamic antagonism. Use Caution/Monitor.
- palovarotene
entacapone will increase the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of palovarotene, a CYP3A substrate, with moderate CYP3A inhibitors. If unavoidable, reduce palovarotene dose by 50%.
- papaverine
papaverine decreases effects of levodopa by unknown mechanism. Use Caution/Monitor.
- penbutolol
levodopa increases effects of penbutolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of penbutolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - perindopril
carbidopa increases effects of perindopril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of perindopril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - phenoxybenzamine
carbidopa increases effects of phenoxybenzamine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- phentolamine
levodopa increases effects of phentolamine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- phentolamine
carbidopa increases effects of phentolamine by pharmacodynamic synergism. Use Caution/Monitor. Monitor for hypotension.
- phenytoin
phenytoin decreases effects of levodopa by unknown mechanism. Use Caution/Monitor.
- pindolol
carbidopa increases effects of pindolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of pindolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - polysaccharide iron
polysaccharide iron decreases levels of levodopa by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Oral administration of iron salts should be separated from levodopa by at least 2 hours.
- prazosin
carbidopa increases effects of prazosin by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- pramipexole
levodopa and pramipexole both increase dopaminergic effects. Use Caution/Monitor.
- prazosin
levodopa increases effects of prazosin by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- propantheline
propantheline, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- propranolol
levodopa increases effects of propranolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of propranolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - pyridoxine
pyridoxine decreases levels of levodopa by increasing metabolism. Use Caution/Monitor.
- quinapril
carbidopa increases effects of quinapril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- pyridoxine (Antidote)
pyridoxine (Antidote) decreases levels of levodopa by increasing metabolism. Use Caution/Monitor. Interaction does not occur if carbidopa taken concurrently.
- quinapril
levodopa increases effects of quinapril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- ramipril
carbidopa increases effects of ramipril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of ramipril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - rasagiline
rasagiline, levodopa. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
- sacubitril/valsartan
carbidopa increases effects of sacubitril/valsartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- ropinirole
levodopa and ropinirole both increase dopaminergic effects. Use Caution/Monitor.
- sacubitril/valsartan
levodopa increases effects of sacubitril/valsartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- sapropterin
sapropterin, levodopa. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Case reports of combination causing convulsions, over-stimulation, or irritability.
- selegiline transdermal
selegiline transdermal and levodopa both increase serotonin levels. Modify Therapy/Monitor Closely.
- silodosin
carbidopa increases effects of silodosin by pharmacodynamic synergism. Use Caution/Monitor. Monitor for hypotension.
- solriamfetol
levodopa and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
- sotalol
carbidopa increases effects of sotalol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of sotalol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - sparsentan
entacapone will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.
- spironolactone
carbidopa increases effects of spironolactone by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- spironolactone
levodopa increases effects of spironolactone by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- sumatriptan intranasal
sumatriptan intranasal and levodopa both increase serotonin levels. Use Caution/Monitor.
- telmisartan
levodopa increases effects of telmisartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- terazosin
carbidopa increases effects of terazosin by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
levodopa increases effects of terazosin by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent. - timolol
levodopa increases effects of timolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of timolol by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - tiotropium
tiotropium, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- torsemide
carbidopa increases effects of torsemide by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- torsemide
levodopa increases effects of torsemide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- trandolapril
levodopa increases effects of trandolapril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of trandolapril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - treprostinil
levodopa increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - triamterene
levodopa increases effects of triamterene by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
carbidopa increases effects of triamterene by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required. - valsartan
levodopa increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- verapamil
carbidopa increases effects of verapamil by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
Minor (21)
- anticholinergic/sedative combos
anticholinergic/sedative combos, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- atropine
atropine, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- belladonna alkaloids
belladonna alkaloids, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- belladonna and opium
belladonna and opium, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- benztropine
benztropine, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- darifenacin
darifenacin, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- ferric maltol
ferric maltol decreases levels of carbidopa by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- ferrous fumarate
ferrous fumarate decreases levels of carbidopa by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- ferrous gluconate
ferrous gluconate decreases levels of carbidopa by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- ferrous sulfate
ferrous sulfate decreases levels of carbidopa by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- fesoterodine
fesoterodine, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- flavoxate
flavoxate, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- homatropine
homatropine, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- ipratropium
ipratropium, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- iron dextran complex
iron dextran complex decreases levels of carbidopa by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- methscopolamine
methscopolamine, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- oxybutynin
oxybutynin, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- oxybutynin topical
oxybutynin topical, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- oxybutynin transdermal
oxybutynin transdermal, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- polysaccharide iron
polysaccharide iron decreases levels of carbidopa by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- scopolamine
scopolamine, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
Adverse Effects
>10%
Entacapone
- Dyskinesia (25%)
- Nausea (14%)
- Diarrhea (10%)
- Hyperkinesia (10%)
- Urine discoloration (10%)
1-10%
Entacapone
- Hypokinesia (9%), dizziness (8%), Fatigue (6%), hallucinations (1-4%), anxiety (2%), somnolence (2%), asthenia (2%), agitation (1%)
- Increased sweating (2%)
- Purpura (2%)
- Abdominal pain (8%), constipation (6%), vomiting (4%), dry mouth (3%), dyspepsia (2%), flatulence (2%), taste perversion (1%), gastritis (1%)
- Back pain (4%)
- Dyspnea (3%)
- Bacterial infection (1%)
Frequency Not Defined
Levodopa/Carbodopa
- Edema
- Agitation, anxiety, ataxia, bruxism, confusion, daytime somnolence decreased attention span, dyskinesia, dystonia, euphoria, insomnia, fainting, fatigue, increased trembling of hands, insouciance, malaise, memory loss, nightmares, nervousness, restlessness, trismus, vivid dreams
- Alopecia, hot flushes, increased &/or dark perspiration, skin eruptions
- Abdominal pain & discomfort, burning feeling in tongue, constipation, diarrhea, dysgeusia, dry mouth, dysphagia, hiccups, meteorism, sialorrhea, nausea, weight loss
- Muscular spasms, muscular cramp
- Hematuria, dark urine, incontinence, priapism, urine retention
- Blurred vision, diplopia, dilated pupil, oculogyric problems
Entacapone
- Postural hypotension
- Insomnia
- Confusion
Warnings
Contradindications
Hypersensitivity
Concurrency with nonselective MAOIs (discontinue 2 weeks before starting treatment)
Narrow-angle glaucoma
Cautions
Dopaminergic therapy in patients with Parkinson’s disease has been associated with hallucinations
As with levodopa, treatment with this drug combination may increase possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer
All patients should be observed carefully for development of depression with concomitant suicidal tendencies; patients with past or current psychoses should be treated with caution
Patients with hepatic impairment should be treated with caution; as with levodopa, periodic evaluation of hepatic function is recommended during extended therapy
Cases of severe rhabdomyolysis reported with entacapone when used in combination with carbidopa and levodopa; severe prolonged motor activity including dyskinesia may possibly account for rhabdomyolysis; most cases were manifested by myalgia and increased values of creatine phosphokinase (CPK) and myoglobin; some of the reactions also included fever and/or alteration of consciousness; it is also possible that rhabdomyolysis may be a result of syndrome related to withdrawal-emergent hyperpyrexia and confusion
Drugs known to be metabolized by COMT, such as isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine, isoetherine, and bitolterol should be administered with caution in patients receiving entacapone regardless of route of administration (including inhalation), as their interaction may result in increased heart rate, arrhythmia, and/or increased blood pressure
Somnolence
- Patients with Parkinson’s disease have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (including the operation of motor vehicles); some of these episodes resulted in accidents; although many of these patients reported somnolence while taking entacapone, some did not perceive warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event; some of these events reported to occur up to one year after initiation of therapy
- Falling asleep while engaged in activities of daily living reported to always occur in a setting of pre-existing somnolence, although patients may not give such a history; prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after start of treatment; prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities; patients who have already experienced somnolence and/or an episode of sudden sleep onset should not participate in these activities during treatment
- Before initiating treatment, advise patients of potential to develop drowsiness and specifically ask about factors that may increase risk such as use of concomitant sedating medications and presence of sleep disorders; if a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (eg, conversations, eating, etc.), therapy should ordinarily be discontinued; If decision is made to continue therapy, patients should be advised not to drive and to avoid other potentially dangerous activities; there is insufficient information to establish whether dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living
Hypotension, orthostatic hypotension, and syncope
- Reports of syncope were generally more frequent in patients in both treatment groups who had had a prior episode of documented hypotension (although episodes of syncope, obtained by history, were themselves not documented with vital sign measurement); hypotension, orthostatic hypotension, and syncope are observed in patients treated with drugs that increase central dopaminergic tone including this drug
Dyskinesia
- Dyskinesia (involuntary movements) may occur or be exacerbated at lower dosages and sooner with this drug than with preparations containing only carbidopa and levodopa; occurrence of dyskinesias may require dosage reduction
- Although decreasing the dose of levodopa may ameliorate dyskinesia, many patients in controlled trials continued to experience frequent dyskinesias despite a reduction in their dose of levodopa
Compulsive behaviors
- Postmarketing reports suggest that patients treated with anti-Parkinson medications can experience intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, and other intense urges; patients may be unable to control these urges while taking one or more of the medications generally used for the treatment of Parkinson’s disease and which increase central dopaminergic tone, including entacapone taken with levodopa and carbidopa
- In some cases, although not all, these urges were reported to have stopped when dose of anti-Parkinson medications was reduced or discontinued; because patients may not recognize these behaviors as abnormal it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with entacapone; physicians should consider dose reduction or stopping therapy if patient develops such urges while taking this medication
Withdrawal-emergent hyperpyrexia and confusion
- Cases of hyperpyrexia and confusion resembling neuroleptic malignant syndrome (NMS) reported in association with dose reduction or withdrawal of therapy with carbidopa, levodopa, and entacapone; however, in some cases, hyperpyrexia and confusion were reported after initiation of treatment with entacapone
- Hyperpyrexia and confusion are uncommon but they may be life-threatening with a variety of features, including hyperpyrexia/fever/hyperthermia, muscle rigidity, involuntary movements, altered consciousness/mental status changes, delirium, autonomic dysfunction, tachycardia, tachypnea, sweating, hyper- or hypotension, and abnormal laboratory findings (eg, creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin)
- If a patient needs to discontinue or reduce daily dose, the dose should be decreased slowly, with supervision from a healthcare provider; specific methods for tapering entacapone have not been systematically evaluated
Diarrhea and colitis
- Typically, diarrhea presents within 4 to 12 weeks after entacapone is started, but may appear as early as first week and as late as many months after initiation of treatment; diarrhea may be associated with weight loss, dehydration, and hypokalemia
- Postmarketing experience has shown that diarrhea may be sign of drug-induced microscopic colitis, primarily lymphocytic colitis; in these cases diarrhea has usually been moderate to severe, watery and non-bloody, at times associated with dehydration, abdominal pain, weight loss, and hypokalemia
- In the majority of cases, diarrhea and other colitis-related symptoms resolved or significantly improved when entacapone treatment was stopped; in some patients with biopsy confirmed colitis, diarrhea had resolved or significantly improved after discontinuation of entacapone but recurred after retreatment with entacapone
- If prolonged diarrhea suspected to be related to Stalevo, the drug should be discontinued and appropriate medical therapy considered; if cause of prolonged diarrhea remains unclear or continues after stopping entacapone, further diagnostic investigations including colonoscopy and biopsies should be considered
Fibrotic complications
- Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening reported in patients treated with ergot-derived dopaminergic agents; these complications may resolve when drug is discontinued, but complete resolution does not always occur
- Although these adverse reactions may be related to ergoline structure of these compounds, a possible causal role of nonergot-derived drugs (eg, entacapone, levodopa), which increase dopaminergic activity, has also been considered
- The expected incidence of fibrotic complications is so low that even if entacapone caused these complications at rates similar to those attributable to other dopaminergic therapies, it is unlikely that it would have been detected in a cohort of the size exposed to entacapone during its clinical development; four cases of pulmonary fibrosis have been reported during clinical development of entacapone; 3 of these patients were also treated with pergolide and 1 with bromocriptine; the duration of treatment with entacapone ranged from 7 months to 17 months
Drug interaction overview
- Use caution with drugs metabolized by COMT
- Dose adjustment may be required when coadministered with anti-hypertensive agents
- Risk of hypertension and dyskinesia reported during concomitant use tricyclic antidepressants with carbidopa/levodopa
- Efficacy of therapy reduced when coadministered with dopamine D2 receptor antagonists, isoniazid, phenytoin, papaverine and iron salts
- Dose adjustment may be required with drugs that interfere with biliary excretion, glucuronidation and intestinal beta-glucuronidase
- Dose adjustment may be required with drugs metabolized by CYP2C9 (eg, coumadin); monitor INR when initiating therapy in patients on coumadin
Pregnancy & Lactation
Pregnancy
There are no adequate data on developmental risk associated with use of drug in pregnant women
Animal data
- In animals, administration of carbidopa-levodopa or entacapone during pregnancy was associated with developmental toxicity, including increased incidences of fetal malformations; estimated background risk of major birth defects and miscarriage in indicated population is unknown
Lactation
Levodopa has been detected in human milk after administration of carbidopa-levodopa; there are no data on presence of entacapone or carbidopa in human milk, effects of levodopa, carbidopa, or entacapone on breastfed infant, or on milk production; however, inhibition of lactation may occur because levodopa decreases secretion of prolactin; carbidopa and entacapone are excreted in rat milk; in lactating rat, oral administration of radiolabeled entacapone resulted in levels of entacapone and/or metabolites in milk up to 2 to 3 times that in plasma;
Consider developmental and health benefits of breastfeeding along with mother’s clinical need for drug and any potential adverse effects on breastfed infant or from 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
Levodopa: Crosses blood-brain barrier & converts to dopamine
Carbidopa: Inhibits decarboxylation or breakdown of peripheral levodopa
Entacapone: Selective & reversible inhibitor of COMT
Pharmacokinetics
Absorption
- levodopa: rapid
- carbidopa: slightly slower than levodopa/entacapone
- entacapone: rapid
Peak plasma time
- levodopa: 0.6-2.4 hr
- carbidopa: 2.5-3.4 hr
- entacapone: 1-1.2 hr
Half Life
- levodopa: 1.7 hr
- carbidopa: 1.6-2 hr
- entacapone: 0.8-1 hr
Protein Bound
- levodopa: 10-30%
- carbidopa: 36%
- entacapone: 98%
Metabolites
- levodopa: dopamine, homovanillic acid
- carbidopa: alpha-methyl-3-methoxy-4-hydroxyphenyl propionic acid & alpha-methyl-3,4-dihydroxyphenylpropionic acid
- entacapone: cis-isomer
Elimination
- levodopa: urine: 80-85%
- carbidopa: 30% unchanged in urine
- entacapone: Urine (10%); feces (90%)
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Formulary
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