carbidopa/levodopa (Rx)

Brand and Other Names:Sinemet, Rytary, more...Duopa, Dhivy, Sinemet CR (DSC)
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

carbidopa/levodopa

tablet (Sinemet, generic)

  • 10mg/100mg
  • 25mg/100mg
  • 25mg/250mg

tablet (Dhivy)

  • 25mg/100mg (scored into 4 segments of 6.25mg/25mg each)

capsule, extended-release (Rytary)

  • 23.75mg/95mg
  • 36.25mg/145mg
  • 48.75mg/195mg
  • 61.25mg/245mg

enteral suspension, extended-release (Duopa)

  • (4.63mg/20mg)/mL in a single-use cassette
  • Each cassette contains ~100 mL

Parkinson Disease and Parkinson-like Disorders

Indicated for Parkinson disease, postencephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication

Maintain patients on the lowest dosage required to achieve symptomatic control and to minimize adverse reactions such as dyskinesia and nausea

Sinemet

  • Immediate release and oral disintegrating tablets: 25 mg/100 mg q8hr or 10 mg/100 mg PO q6-8hr initially; levodopa may be increased by 100 mg/day every 1-2 days
  • Carbidopa should be 70-100 mg/day but not to exceed 200 mg/day; levodopa not to exceed 800 mg/day
  • Sinemet CR: 50 mg/200 mg PO q12hr initially; may be increased up to 1600 mg/day of levodopa; doses must be given at least 6 hr apart

Rytary

  • Contains immediate-release and extended-release beads
  • Levodopa-naïve: 23.75 mg/95 mg PO TID initially; on treatment day 4, may increase to 36.25 mg/145 mg TID
  • Dose may be increased up to a maximum recommended dose of 97.5 mg/390 mg TID
  • Dosing frequency may be changed from 3x/day to a maximum of 5x/day if more frequent dosing is needed and if tolerated, up to a maximum recommended daily dose 612.5 mg/2450 mg

Dhivy

  • Initial dose: 1 tablet (carbidopa 25 mg/ levodopa 100mg) PO TID
  • May increase dosage by up to 1 whole tablet qDay or every other day, as needed to a maximum daily dosage to 8 whole tablets
  • Tablet scored into 4 segments of 6.25 mg/25 mg/segment to allow precise titration and dosage flexibility
  • Individualize and adjust dosing according to clinical response and tolerability

Motor Fluctuations in Advanced Parkinson Disease

Duopa only

Indicated for treatment of motor fluctuations in adults with advanced Parkinson disease

Individualize daily dose is determined by individualized patient titration and composed of a morning dose, a continuous dose, and extra doses

Maximum daily dose 2,000 mg of the levodopa component (ie, 1 cassette/day) administered over 16 hr; at the end of the daily 16-hr infusion, disconnect the pump from jejunal tubing and take their nighttime dose of oral immediate-release carbidopa-levodopa tablets

Before initiating

  • Convert from all other forms of levodopa to oral immediate-release (IR) carbidopa-levodopa tablets (1:4 ratio); patients should remain on stable on their medications for Parkinson disease
  • Ensure all oral Parkinson disease medication were taken the morning of the PEG-J procedure

Calculate and administer of starting dose for Day 1

  • Morning dose
    • Determine total amount of levodopa (mg) in the first dose of oral IR carbidopa-levodopa that was taken by the patient on the previous day
    • Convert oral levodopa dose from mg to mL by multiplying the oral dose by 0.8 and dividing by 20 mg/mL
    • Add 3 milliliters to the morning dose to fill (prime) the intestinal tube to obtain the total morning dose
  • Continuous dose
    • Determine the amount of oral IR levodopa that the patient received from oral IR carbidopa-levodopa doses throughout the previous day (16 waking hr), in mg
    • Do not include the doses of oral IR carbidopa-levodopa taken at night when calculating the levodopa amount
    • Subtract first oral levodopa dose taken by the patient on previous day from the total oral levodopa dose taken over 16 waking hours
    • Divide result by 20 mg/mL
    • If persistent or numerous “Off” periods occur during the 16-hr infusion, consider increasing the continuous dose or using the extra dose function
    • If dyskinesia or drug-related adverse reactions occur, consider decreasing the continuous dose or stopping infusion until the adverse reactions subside

Titration

  • Titrate dose as needed based on individual clinical response and tolerability
  • Morning dose adjustment
    • Inadequate clinical response within 1 hr of the morning dose on the preceding day, adjust the morning dose (exclude 3 mL for priming) as follows:
    • Morning dose on the preceding day ≤6 mL: Increase morning dose by 1 mL
    • Morning dose on the preceding day >6 mL: Increase morning dose by 2 mL
    • If dyskinesias or drug-related adverse reactions occur within 1 hr of the morning dose on the preceding day, decrease morning dose by 1 mL
  • Continuous dose adjustment
    • Consider increasing the continuous dose based on the number and volume of Extra doses (ie, total amount of levodopa component) that were needed for the previous day and patient’s clinical response
    • For troublesome adverse reactions (eg, dyskinesia) lasting for a period of ≥1 hr, decrease continuous dose by 0.3 mL/hr
    • For troublesome adverse reactions lasting for ≥1 periods of ≥1 hr, decrease continuous dose by 0.6 mL/hr

Dosage Modifications

Renal impairment: Safety and efficacy not established; use with caution

Hepatic impairment: Safety and efficacy not established; use with caution

Dosing Considerations

Sinemet

  • Immediate release (IR): When more carbidopa is required, substitute one 25 mg/100 mg tablet for each 10 mg/100 mg tablet; if necessary, dosage of 25 mg/250 mg tablet may be increased by one half or by 1 tablet every 1-2 days to maximum of 8 tablets daily; experience with total daily carbidopa doses higher than 200 mg is limited
  • Controlled-release (ER): Doses and dosing intervals may be increased or decreased according to response; most patients are adequately treated with regimens providing levodopa 400-1600 mg/day divided q4-8hr while awake; higher levodopa dosages (≥2400 mg/day) and shorter intervals (<4 hours) are used but not usually recommended; if interval <4 hours is used or if divided doses are not equal, give smaller doses at end of day; allow at least 3 days between dosage adjustments

Conversion from immediate-release to Sinemet CR

  • 300-400 mg/day IR = 200 mg CR q12hr
  • 500-600 mg/day IR = 300 mg CR q12hr or 200 mg ER q8hr
  • 700-800 mg/day IR = 800 mg CR divided q8hr
  • 900-1000 mg/day IR = 1000 CR divided q8hr

Converting from immediate-release (IR) to Rytary

  • Doses of other carbidopa/levodopa products are not interchangeable
  • For patients currently treated with carbidopa/levodopa plus catechol-O-methyl transferase (COMT) inhibitors (eg, entacapone), the initial total daily dose of levodopa in Rytary may need to be increased
  • The dosing frequency may be changed from 3x/day to a maximum of 5x/day if more frequent dosing is needed and if tolerated, up to a maximum recommended daily dose 612.5 mg/2450 mg
  • Dose conversion from IR
    • 400-549 mg IR: 3 caps 23.75mg/95mg TID
    • 550-749 mg IR: 4 caps 23.75mg/95mg TID
    • 750-949 mg IR: 3 caps 36.25mg/145mg TID
    • 950-1249 mg IR: 3 caps 48.75 mg/195 mg TID
    • ≥1250 mg IR: 4 caps 48.75 mg/195 mg TID, OR 3 caps 61.25 mg/245 mg TID

Monitoring parameters

  • Dhivy
    • Closely monitor patients during the dose adjustment period
    • Specifically, involuntary movements may occur, which may require dosage reduction
    • Blepharospasm may be a useful early sign of excess dosage in some patients

Discontinuation

  • Duopa
    • Avoid sudden discontinuation or rapid dose reduction
    • If discontinuing therapy, taper dose, or switch to oral IR carbidopa-levodopa tablets
    • When using a PEG-J tube, discontinue by withdrawing the tube and letting the stoma heal; only a qualified healthcare provider should remove the tube

Safety and efficacy not established

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Interactions

Interaction Checker

and carbidopa/levodopa

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            Contraindicated (6)

            • isocarboxazid

              isocarboxazid, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • phenelzine

              phenelzine, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • 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

              tranylcypromine, levodopa. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            Serious - Use Alternative (29)

            • 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.

            • 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.

            • 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.

            • 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.

            • olanzapine

              olanzapine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • 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.

            • 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.

            • risperidone

              risperidone decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • thioridazine

              thioridazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • thiothixene

              thiothixene decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • trifluoperazine

              trifluoperazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • ziprasidone

              ziprasidone decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            Monitor Closely (143)

            • 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.

            • 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.

            • amlodipine

              levodopa increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

              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.

            • apomorphine

              apomorphine and levodopa both increase dopaminergic effects. Use Caution/Monitor. Combination may enhance efficacy. Monitor for hypotension.

            • asenapine

              carbidopa increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Monitor for hypotension.

            • atenolol

              levodopa increases effects of atenolol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

              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.

            • 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. .

            • benazepril

              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 increases effects of benazepril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

              benazepril, levodopa. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • 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.

              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.

            • 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

              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.

            • bumetanide

              levodopa increases effects of bumetanide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • 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.

            • 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

              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 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. .

            • 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.

            • 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.

              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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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. .

            • 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.

            • 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.

            • 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.

            • levomilnacipran

              levomilnacipran and levodopa both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

              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.

            • 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

              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.

              levodopa increases effects of minoxidil by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • 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.

              levodopa increases effects of moexipril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • 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.

              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.

              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.

              levodopa increases effects of nicardipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • 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.

              levodopa increases effects of nifedipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • 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.

              levodopa increases effects of nisoldipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • olmesartan

              levodopa increases effects of olmesartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • penbutolol

              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.

            • 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.

            • 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.

            • 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.

            • 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.

              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.

            • 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.

            • telmisartan

              levodopa increases effects of telmisartan by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • terazosin

              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. .

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            Adverse Effects

            >10%

            Duopa

            • Complication of device insertion (57%)
            • Nausea (30%)
            • Constipation (22%)
            • Incision site erythema (19%)
            • Dyskinesia (14%)
            • Depression (11%)
            • Post procedural discharge (11%)

            1-10%

            Duopa

            • Peripheral edema (8%)
            • Hypertension (8%)
            • Upper respiratory tract infection (8%)
            • Oropharyngeal pain (8%)
            • Atelectasis (8%)
            • Confusional state (8%)
            • Anxiety (8%)
            • Dizziness (8%)
            • Hiatal hernia (8%)
            • Postoperative ileus (5%)
            • Sleep disorder (5%)
            • Pyrexia (5%)
            • Excessive granulation tissue (5%)
            • Rash (5%)
            • Bacteriuria (5%)
            • White blood cells urine positive (5%)
            • Hallucination (5%)
            • Psychotic disorder (5%)
            • Diarrhea (5%)
            • Dyspepsia (5%)

            Frequency Not Defined

            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 flashes

            Increased or dark perspiration

            Skin eruptions

            Abdominal pain and 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 or dilated pupil

            Oculogyric problems

            Atelectasis

            Postmarketing Reports

            Suicide attempt, suicidal ideation

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            Warnings

            Contraindications

            Hypersensitivity

            Concurrent administration of nonselective monoamine oxidase inhibitors (MAOIs) or use within last 14 days

            Sinemet

            • Narrow-angle glaucoma (tablets)

            Cautions

            Avoid sudden discontinuation or rapid dose reduction; if discontinuing therapy, taper dose to reduce risk of hyperpyrexia and confusion

            Monitor patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmia, cardiac function in an intensive cardiac care facility during the initial dosage adjustment

            Hallucinations and psychotic-like behavior have been reported; do no treat patients with major psychotic disorder

            May experience an urge to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and inability to control these urges while taking 1 or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson disease; consider dosage reduction or stopping the medication if a patient develops such urges

            May exacerbate dyskinesia; reduce dose to control symptoms

            Treated patients with a history of peptic ulcer may increase the possibility of upper gastrointestinal hemorrhage

            Monitor intraocular pressure in patients with glaucoma

            Carefully observe patients for developing depression with concomitant suicidal tendencies

            Orthostatic hypotension may occur (more common with IR formulation)

            Peripheral neuropathy reported with use; evaluate patients for history of neuropathy and known risk factors prior to initiating therapy; assess for peripheral neuropathy periodically during therapy

            Falling asleep during activities of daily living and somnolence

            • Patients taking carbidopa/levodopa alone or with other dopaminergic drugs have reported suddenly falling asleep without warning of sleepiness while engaged in activities of daily living, including the operation of motor vehicles which have resulted in accidents
            • Reassess patients for drowsiness or sleepiness
            • Be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities
            • Before initiating, advise patients about the potential to develop drowsiness and ask specifically about factors that may increase the risk for somnolence such as use of concomitant sedating medications and the presence of sleep disorders
            • Consider discontinuing carbidopa/levodopa in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e., conversations, eating, etc.)
            • If treatment continues, advise patients not to drive and to avoid other potentially dangerous activities that might result in harm if the patients become somnolent
            • There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living

            Duopa only

            • Gastrointestinal complications from PEG-J or naso-jejunal tube can occur (eg, abscess, bezoar, ileus, intussusception, implant site erosion/ulcer, intestinal hemorrhage, intestinal ischemia, intestinal obstruction, intestinal perforation, pancreatitis, peritonitis, pneumonia, including aspiration pneumonia, pneumoperitoneum, and postoperative wound infection) sepsis; these complications may result in serious outcomes (eg, need for surgery, death)

            Drug interaction overview

            • Laboratory tests
              • Exercise caution when interpreting plasma and urine levels of catecholamines and their metabolites in patients on carbidopa levodopa therapy
              • May cause a positive Coombs test or false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria
              • Cases of falsely diagnosed pheochromocytoma in patients on carbidopa-levodopa therapy have been reported
            • Monoamine oxidase (MAO) inhibitors
            • Contraindicated
              • Discontinue use of any nonselective MAO inhibitors at least 2 weeks before initiating
              • Carbidopa/levodopa may be administered concomitantly with the manufacturer's recommended dose of selective MAO-B inhibitors (eg, rasagiline or selegiline HCl)
              • Coadministration with selegiline and carbidopa/levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa/levodopa alone
            • Dopamine D2-receptor antagonists and isoniazid
              • Monitor for worsening Parkinson’s symptoms
              • Dopamine D2 receptor antagonists (eg, phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the effectiveness of levodopa
            • Iron salts
              • If iron salts or multivitamins containing iron salts are coadministered with carbidopa/levodopa, monitor for worsening Parkinson’s symptoms
              • Iron salts or multivitamins containing iron salts can form chelates with levodopa and carbidopa and may reduce the bioavailability of carbidopa/levodopa
            • Antihypertensive drugs
              • Dosage adjustment of antihypertensive therapy may be required when initiating carbidopa/levodopa
              • Symptomatic postural hypotension occurred when treated patients are concomitantly receiving antihypertensive drugs
            • Dopamine-depleting agents
              • Use is not recommended
            • Metoclopramide
              • Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also reduce effectiveness of levodopa by its dopamine receptor antagonistic properties
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            Pregnancy & Lactation

            Pregnancy

            There are no adequate data on development risk associated with use in pregnant females

            Animal data

            • Carbidopa/levodopa has been shown to be developmentally toxic (including teratogenic effects at clinically relevant doses

            Lactation

            Levodopa has been detected in human milk after administration of carbidopa-levodopa

            There are no data on the presence of carbidopa in human milk, effects of levodopa or carbidopa on breastfed infants, or the effects on milk production

            However, inhibition of lactation may occur because levodopa decreases secretion of prolactin in humans

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Carbidopa

            • Inhibits aromatic amino-acid decarboxylase in peripheral tissues; this, in turn, inhibits peripheral breakdown of levodopa, thereby increasing availability of levodopa at blood-brain barrier and allowing a lower levodopa dose
            • May also reduce nausea and vomiting and permit more rapid titration of levodopa

            Levodopa

            • Metabolic precursor of dopamine, a neurotransmitter depleted in Parkinson disease; crosses blood-brain barrier to be converted by striatal enzymes to dopamine

            Absorption

            Peak plasma time

            • Dhivy: 3 hr (carbidopa); 1 hr (levodopa)
            • Duopa: 2.5 hr

            Bioavailability

            • Duopa: 97%

            Effect of food

            • High-fat, high-calorie meal: Reduced levodopa Cmax by ~25% while the AUC remained unchanged; peak concentration of both carbidopa/levodopa were observed approximately 30 minutes later
            • High protein diet: Absorption of levodopa may be impaired, since levodopa competes with certain amino acids for transport across the gut wall

            Distribution

            Both drugs widely distributed; carbidopa does not cross blood-brain barrier; <1% of levodopa enters CNS

            Protein bound: Carbidopa, 36%; levodopa, 10-30%

            Vd: Levodopa, 0.9-1.6 L/kg in presence of carbidopa

            Metabolism

            Carbidopa not extensively metabolized; levodopa metabolized in small amounts in GI tract and undergoes first-pass hepatic metabolism

            Metabolites: Dopamine, homovanillic acid

            Elimination

            Half-life

            • Carbidopa: 2 hr
            • Levodopa: 3.5 hr; 1.5 hr (administer with carbidopa)

            Excretion

            • Simultaneous administration of carbidopa and levodopa produced greater urinary excretion of levodopa in proportion to the excretion of dopamine than administration of the 2 drugs at separate times
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            Administration

            Oral Administration

            Dhivy

            • Take with or without food
            • Advise patients that changes in diet (eg, high-protein diets) may delay absorption of levodopa and reduce its plasma concentration
            • Excess acidity also delays stomach emptying, thus delaying absorption of levodopa
            • Patients who have difficulty swallowing tablets: May cut tablets at the score lines
            • Tablet scored into 4 segments of 6.25 mg/25 mg/segment to allow precise titration and dosage flexibility

            Rytary

            • Swallow capsule whole with or without food
            • A high-fat, high-calorie meal may delay the absorption of levodopa by about 2 hr
            • Do not chew, divide, or crush capsules
            • Difficulty swallowing: May open capsule and sprinkle entire contents on a small amount of applesauce and consume immediately

            Enteral feed administration (Duopa)

            Remove 1 cassette and carton out of refrigerator 20 minutes before use; inaccurate infusion rate if too cold

            Administered as a 16-hr intrajejunal infusion via a nasojejunal tube for short-term administration or through a PEG-J for long-term administration

            Cassettes are for single-use only; do not use for longer than 16 hr, even if some drug product remains; do not reuse an opened cassette

            Administer morning dose over 10-30 minutes; continuous dose is over 16 hr

            Disconnect PEG-J from the pump once 16-hr infusion is completed and flush line with room temperature potable water with a syringe

            Long-term administration requires placement of a PEG-J outer transabdominal tube and inner jejunal tube by percutaneous endoscopic gastrostomy

            Cassettes are specifically designed to be connected to the CADD-Legacy 1400 pump

            See prescribing information for appropriate tubing sets for long-term and short-term administration

            Storage

            Tablets

            • Store at 20-25ºC (68-77ºF); excursions permitted between 15-30ºC (59-86ºF)
            • Store in a tightly closed container, protect from light and moisture
            • Dispense in a light-resistant container

            Duopa

            • Freeze at -20ºC (-40ºF); thaw in refrigerator at 2-80ºC (36-460ºF) before dispensing
            • Cassettes should be protected from light and kept in the carton before use
            • Thawing instructions for pharmacies
              • Assign a 12 week “Use By” date based on the time the cartons are put into the refrigerator to thaw
              • Fully thaw in the refrigerator before dispensing
              • To ensure controlled thawing, take cartons containing the seven individual cassettes out of the transport box and separate the cartons from each other
              • Thawing may take up to 96 hr when cartons are taken out of the transport box
              • Once thawed, pack the individual cartons in a closer configuration within the refrigerator
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            Images

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            Patient Handout

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

            FormularyPatient Discounts

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

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.