Version July 2025
Parkinson disease:
Note: All strengths of Stalevo contain a carbidopa/levodopa ratio of 1:4 plus entacapone 200 mg. Carbidopa/levodopa/entacapone should be used as a substitute for patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone. However, some patients who have been stabilized on a given dose of carbidopa/levodopa may be treated with carbidopa/levodopa/entacapone if a decision has been made to add entacapone. Dose should be individualized based on therapeutic response; doses may be adjusted by changing strength or adjusting interval. Fractionated doses are not recommended and only 1 tablet should be given at each dosing interval. Maximum daily dose: tablets containing <200 mg levodopa component (eg, Stalevo 50, 75, 100, 125, or 150): 8 tablets/day; tablets containing 200 mg levodopa (eg, Stalevo 200): 6 tablets/day. Patients receiving <70 to 100 mg of the carbidopa component may experience nausea and vomiting.
Patients previously treated with carbidopa/levodopa IR tablets (ratio of 1:4):
Note: There are no data available on converting patients from controlled-release preparations or products with a 1:10 ratio of carbidopa/levodopa.
With current entacapone therapy: Oral: Patients who are currently treated with entacapone 200 mg tablet with each dose of standard-release carbidopa/levodopa may be switched directly to corresponding strength of combination tablet. Maximum daily dose: tablets containing <200 mg levodopa component (eg, Stalevo 50, 75, 100, 125, or 150): 8 tablets/day; tablets containing 200 mg levodopa (eg, Stalevo 200): 6 tablets/day.
Without current entacapone therapy:
Current levodopa dose >600 mg/day or history of moderate or severe dyskinesias: Oral: Levodopa dose reduction may be required when adding entacapone to therapy; therefore, titrate dose using individual products first (carbidopa/levodopa immediate release with a ratio of 1:4 plus entacapone 200 mg); then transfer to combination product once stabilized. Maximum daily dose: tablets containing <200 mg levodopa component (eg, Stalevo 50, 75, 100, 125, or 150): 8 tablets/day; tablets containing 200 mg levodopa (eg, Stalevo 200): 6 tablets/day.
Current levodopa dose ≤600 mg/day and without a history of dyskinesias: Oral: May transfer to corresponding dose of combination product; monitor, dose reduction of levodopa may be required. Maximum daily dose: tablets containing <200 mg levodopa component (eg, Stalevo 50, 75, 100, 125, or 150): 8 tablets/day; tablets containing 200 mg levodopa (eg, Stalevo 200): 6 tablets/day.
Patients previously treated with benserazide/levodopa IR tablets [Canadian product]:
With current entacapone therapy: Oral: Withhold previous therapy for 1 night, then initiate carbidopa/levodopa/entacapone therapy the following morning. Convert previous therapy to carbidopa/levodopa/entacapone dosage that provides either an equivalent amount or ~5% to 10% more levodopa. Maximum daily dose: tablets containing <200 mg levodopa component (eg, Stalevo 50, 75, 100, 125, or 150): 8 tablets/day; tablets containing 200 mg levodopa (eg, Stalevo 200): 6 tablets/day.
Discontinuation of therapy: Discontinuation of therapy may result in neuroleptic malignant-like syndrome (Ref). Avoid sudden discontinuation or rapid dose reduction.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution in biliary obstruction or hepatic disease.
Refer to adult dosing.
See individual agents.
Use of nonselective monoamine oxidase inhibitor therapy with or within 14 days prior to initiation of therapy; narrow-angle glaucoma.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to levodopa, carbidopa, entacapone, or any component of the formulation; clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematologic, pulmonary (including bronchial asthma), or renal disease; history of neuroleptic malignant syndrome (NMS) and/or nontraumatic rhabdomyolysis; hepatic impairment; pheochromocytoma; when administration of a sympathomimetic amine is contraindicated; suspicious, undiagnosed skin lesions or a history of melanoma.
Concerns related to adverse effects:
• Diarrhea: Has been associated with delayed development of diarrhea (onset after 4 to 12 weeks, but may appear as early as the first week); use with caution in patients with lower gastrointestinal disease or an increased risk of dehydration. Diarrhea may be a sign of drug-induced colitis. Monitor for weight loss. Discontinue use with prolonged diarrhea.
• Dyskinesias: May cause or exacerbate dyskinesias; may require dose adjustment.
• Hallucinations: May cause hallucinations.
• Impulse control disorders: Dopamine agonists used for Parkinson disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, increased sexual urges, intense urges to spend money uncontrollably, and other intense urges. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.
• Melanoma: Risk for melanoma development is increased in Parkinson disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed.
• Neuroleptic malignant syndrome: Entacapone, in conjunction with other drug therapy that alters brain biogenic amine concentrations (eg, MAO inhibitors, SSRIs), has been associated with a syndrome resembling neuroleptic malignant syndrome (hyperpyrexia and confusion) (some fatal) on abrupt withdrawal or dosage reduction. Concomitant use of entacapone and nonselective MAO inhibitors should be avoided.
• Orthostatic hypotension: Entacapone may cause orthostatic hypotension and syncope; Parkinson disease patients appear to have an impaired capacity to respond to a postural challenge; use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or in whom transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Parkinson patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and should be informed of this risk.
• Pleural/retroperitoneal fibrosis: Ergot-derived dopamine agonists have also been associated with fibrotic complications (eg, retroperitoneal fibrosis, pleural effusions, pleural thickening, and pulmonary infiltrates); monitor closely for signs and symptoms of fibrosis.
• Rhabdomyolysis: Severe cases have been reported (rare); may be related to severe, prolonged motor activity/dyskinesia.
• Somnolence: Somnolence and falling asleep while engaged in activities of daily living (including operation of motor vehicles) have been reported; some cases reported that there were no warning signs for the onset of symptoms. Some events have occurred more than 1 year after start of therapy. Prior to treatment initiation, evaluate for factors that may increase these risks such as concomitant sedating medications, and the presence of sleep disorders. Monitor for drowsiness or sleepiness. If significant daytime sleepiness or episodes of falling asleep during activities that require active participation occurs (eg, driving, conversations, eating), discontinue the medication. There is insufficient information to suggest that dose reductions will eliminate these symptoms. If therapy is continued, advise patient to avoid driving and other potentially dangerous activities.
Disease-related concerns:
• Endocrine disease: Use with caution when interpreting plasma/urine catecholamine levels; falsely diagnosed pheochromocytoma has been rarely reported.
• Glaucoma: Use with caution in patients with wide-angle glaucoma; monitor IOP carefully; use is contraindicated in patients with narrow-angle glaucoma.
• Hepatic impairment: Use with caution in patients with hepatic impairment and biliary obstruction.
• Peptic ulcer disease: Use with caution in patients with a history of peptic ulcer disease; risk of gastrointestinal hemorrhage may be increased.
• Psychotic disorders: Use with extreme caution in patients with psychotic disorders; observe patients closely for development of depression with concomitant suicidal tendencies.
• Renal impairment: Use with caution in patients with severe renal impairment.
Special populations:
• Older adult: Use with caution in elderly patients; may be more sensitive to CNS effects (eg, hallucinations) of levodopa.
Dosage form specific issues:
• Sucrose: Contains sucrose; avoid use in patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.
Other warnings/precautions:
• Body fluid discoloration: Urine, saliva, or sweat may appear dark in color (red, brown, black) during therapy.
• Discontinuation of therapy: Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on abrupt withdrawal or significant dosage reduction after long-term use.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Stalevo 50: Levodopa 50 mg, carbidopa 12.5 mg, and entacapone 200 mg [DSC]
Stalevo 75: Levodopa 75 mg, carbidopa 18.75 mg, and entacapone 200 mg [DSC]
Stalevo 100: Levodopa 100 mg, carbidopa 25 mg, and entacapone 200 mg [DSC]
Stalevo 125: Levodopa 125 mg, carbidopa 31.25 mg, and entacapone 200 mg [DSC]
Stalevo 150: Levodopa 150 mg, carbidopa 37.5 mg, and entacapone 200 mg [DSC]
Stalevo 200: Levodopa 200 mg, carbidopa 50 mg, and entacapone 200 mg [DSC]
Generic: Levodopa 50 mg, carbidopa 12.5 mg, and entacapone 200 mg; Levodopa 75 mg, carbidopa 18.75 mg, and entacapone 200 mg; Levodopa 100 mg, carbidopa 25 mg, and entacapone 200 mg; Levodopa 125 mg, carbidopa 31.25 mg, and entacapone 200 mg; Levodopa 150 mg, carbidopa 37.5 mg, and entacapone 200 mg; Levodopa 200 mg, carbidopa 50 mg, and entacapone 200 mg
Yes
Tablets (Carbidopa-Levodopa-Entacapone Oral)
12.5-50-200 mg (per each): $3.75
18.75-75-200 mg (per each): $3.75
25-100-200 mg (per each): $3.75
31.25-125-200 mg (per each): $3.75
37.5-150-200 mg (per each): $3.75
50-200-200 mg (per each): $3.75
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Stalevo: Levodopa 50 mg, carbidopa 12.5 mg, and entacapone 200 mg (10s, 30s, 100s); levodopa 75 mg, carbidopa 18.75 mg, and entacapone 200 mg (10s, 30s, 100s); levodopa 100 mg, carbidopa 25 mg, and entacapone 200 mg (10s, 30s, 100s); levodopa 125 mg, carbidopa 31.25 mg, and entacapone 200 mg (10s, 30s, 100s); levodopa 150 mg, carbidopa 37.5 mg, and entacapone 200 mg (10s, 30s, 100s)
Oral: Swallow tablet whole; do not crush, break, or chew. Only 1 tablet should be administered at each dosing interval. May be administered without regard to meals; absorption may be delayed 2 hours if given with a high-fat, high-calorie meal.
Parkinson disease: Treatment of Parkinson disease.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (anti-Parkinson agent) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Long-Term Care Settings).
Strengths listed in Stalevo brand names correspond to the levodopa component of the formulation only. All strengths of Stalevo contain a levodopa/carbidopa ratio of 4:1 plus entacapone 200 mg.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May increase serum concentration of Levodopa. Risk X: Avoid
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Alizapride: May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amisulpride (Injection): May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid
Amisulpride (Oral): Anti-Parkinson Agents (Dopamine Agonist) may decrease therapeutic effects of Amisulpride (Oral). Amisulpride (Oral) may decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid
Antipsychotic Agents (First Generation [Typical]): May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider Therapy Modification
Antipsychotic Agents (Second Generation [Atypical]): May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider Therapy Modification
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Biperiden: May increase adverse/toxic effects of Levodopa-Foslevodopa. Specifically, the risk of choreic movements or dyskinesias may be increased. Risk C: Monitor
Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Blood Pressure Lowering Agents: May increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Bornaprine: May increase adverse/toxic effects of Levodopa-Foslevodopa. Specifically, dyskinesia may be increased. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Anti-Parkinson Agents (Dopamine Agonist). Specifically, the risk of chorea may be increased. Risk C: Monitor
Bromopride: May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may increase adverse/toxic effects of BuPROPion. Risk C: Monitor
CNS Depressants: Entacapone may increase CNS depressant effects of CNS Depressants. Risk C: Monitor
COMT Substrates: COMT Inhibitors may increase serum concentration of COMT Substrates. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Droxidopa: Carbidopa may decrease therapeutic effects of Droxidopa. Carbidopa may decrease active metabolite exposure of Droxidopa. Carbidopa may increase serum concentration of Droxidopa. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Fluorodopa F18: Coadministration of Anti-Parkinson Agents (Dopamine Agonist) and Fluorodopa F18 may alter diagnostic results. Management: Discontinue medications used to treat Parkinson disease, including dopamine agonists, 12 hours prior to fluorodopa F 18 administration if these medications can be safely withheld. Risk D: Consider Therapy Modification
Fluorodopa F18: Coadministration of COMT Inhibitors and Fluorodopa F18 may alter diagnostic results. Management: Discontinue medications used to treat Parkinson disease, including peripheral COMT inhibitors, 12 hours prior to fluorodopa F 18 administration if these medications can be safely withheld. Risk D: Consider Therapy Modification
Fosphenytoin-Phenytoin: May decrease therapeutic effects of Levodopa-Foslevodopa. Risk C: Monitor
Glycopyrrolate (Systemic): May decrease serum concentration of Levodopa-Foslevodopa. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iron Preparations: May decrease serum concentration of Entacapone. Management: Consider separating doses of the agents by 2 or more hours to minimize the effects of this interaction. Monitor for decreased therapeutic effects of levodopa during concomitant therapy, particularly if doses cannot be separated. Risk D: Consider Therapy Modification
Iron Preparations: May decrease serum concentration of Levodopa. Only applies to oral iron preparations. Management: Consider separating doses of the agents by 2 or more hours to minimize the effects of this interaction. Monitor for decreased therapeutic effects of levodopa during concomitant therapy, particularly if doses cannot be separated. Risk D: Consider Therapy Modification
Isoniazid: May decrease therapeutic effects of Levodopa-Foslevodopa. Risk C: Monitor
Kava Kava: May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Kava Kava may increase adverse/toxic effects of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lofepramine: Entacapone may increase adverse/toxic effects of Lofepramine. Risk X: Avoid
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Macimorelin: Coadministration of Levodopa-Foslevodopa and Macimorelin may alter diagnostic results. Risk X: Avoid
Metergoline: May increase adverse/toxic effects of Levodopa-Foslevodopa. Management: Consider the need for possible reductions in levodopa dose with initiation of or increasing doses of metergoline. Monitor for evidence of increased levodopa adverse effects with use of the combination. Risk D: Consider Therapy Modification
Methotrimeprazine: May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may decrease therapeutic effects of Methotrimeprazine. Risk X: Avoid
Metoclopramide: May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Monoamine Oxidase Inhibitors (Type B): Levodopa-Foslevodopa may increase orthostatic hypotensive effects of Monoamine Oxidase Inhibitors (Type B). Risk C: Monitor
Monoamine Oxidase Inhibitors: Levodopa-Foslevodopa may increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Risk X: Avoid
Multivitamins/Fluoride (with ADE): May decrease therapeutic effects of Levodopa-Foslevodopa. Management: Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Risk D: Consider Therapy Modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease therapeutic effects of Levodopa. Multivitamins/Minerals (with ADEK, Folate, Iron) may decrease serum concentration of Levodopa. Only applies to oral iron-containing preparations. Management: Separate doses of these agents by 2 or more hours. Monitor for decreased levodopa effects, particularly if doses cannot be separated. Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Risk D: Consider Therapy Modification
Multivitamins/Minerals (with AE, No Iron): May decrease therapeutic effects of Levodopa-Foslevodopa. Management: Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Risk D: Consider Therapy Modification
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
Papaverine: May decrease therapeutic effects of Levodopa-Foslevodopa. Papaverine may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pyridoxine: May decrease therapeutic effects of Levodopa-Foslevodopa. Management: The concomitant use of pyridoxine and levodopa (in the absence of a dopa decarboxylase inhibitor (DDI)) should be avoided. Use of a DDI (eg, carbidopa) with levodopa will essentially eliminate the risk of this interaction. Risk D: Consider Therapy Modification
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Reserpine: Levodopa-Foslevodopa may increase hypotensive effects of Reserpine. Reserpine may decrease therapeutic effects of Levodopa-Foslevodopa. Management: Consider alternatives to the coadministration of levodopa and reserpine. If combined, monitor for reduced levodopa efficacy and hypotension. Risk D: Consider Therapy Modification
Sapropterin: May increase adverse/toxic effects of Levodopa-Foslevodopa. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Solriamfetol: May increase adverse/toxic effects of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor
Spiramycin: May decrease serum concentration of Carbidopa. And thus may decrease the effectiveness of levodopa. Risk C: Monitor
Sulpiride: May decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid
Tiapride: Levodopa-Foslevodopa may decrease therapeutic effects of Tiapride. Tiapride may decrease therapeutic effects of Levodopa-Foslevodopa. Risk X: Avoid
Vesicular Monoamine Transporter 2 (VMAT2) Inhibitors: May decrease therapeutic effects of Levodopa-Foslevodopa. Management: Consider alternatives to the coadministration of levodopa and vesicular monoamine transporter 2 (VMAT2) inhibitors. If combined, monitor for reduced levodopa efficacy. Risk D: Consider Therapy Modification
Warfarin: Entacapone may increase serum concentration of Warfarin. Specifically, entacapone may increase levels of the less potent R-enantiomer of warfarin Risk C: Monitor
High-protein diets and increased stomach acid may delay absorption of levodopa. Management: Avoid high-protein diets during therapy.
The incidence of Parkinson disease in pregnancy is relatively rare and information related to the use of carbidopa/levodopa/entacapone in pregnant women is limited (Seier 2017; Tüfekçioglu 2018).
Refer to the entacapone and the carbidopa/levodopa monographs for additional information.
Levodopa is present in breast milk (Thulin 1998); excretion of carbidopa and entacapone are not known.
Lactation may be inhibited by levodopa. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Refer to the entacapone monograph and the carbidopa/levodopa monographs for additional information.
Distribute protein intake throughout the day to avoid fluctuations in levodopa absorption. Separate dosing of iron supplements and multivitamins with minerals.
Signs and symptoms of Parkinson's disease; CBC, liver function tests, renal function; blood pressure, mental status; signs and symptoms of neuroleptic malignant syndrome if abrupt discontinuation required (as with surgery); serum iron (if signs of anemia); IOP (in patients with wide-angle glaucoma); dermatologic examination (regularly while on therapy); weight loss (patients with diarrhea); cardiac function with initial dose adjustments and periodically during prolonged therapy (patients with history of MI, arrhythmia); fibrotic complications (eg, retroperitoneal fibrosis, pulmonary infiltrates or effusions, pleural thickening); signs of excessive drowsiness or sleepiness during treatment; signs of depression (including suicidal thoughts); signs and symptoms of impulse control/compulsive behaviors.
Levodopa: The metabolic precursor of dopamine, a chemical depleted in Parkinson's disease. Levodopa is able to circulate in the plasma and cross the blood-brain-barrier (BBB), where it is converted by striatal enzymes to dopamine.
Carbidopa: Inhibits the peripheral plasma breakdown of levodopa by inhibiting its decarboxylation; increases available levodopa at the BBB
Entacapone: A reversible and selective inhibitor of catechol-O-methyltransferase (COMT). Alters the pharmacokinetics of levodopa, resulting in more sustained levodopa serum levels and increased concentrations available for absorption across the BBB.
Also see individual agents.
Protein binding: Levodopa: ~10% to 30%; Carbidopa: ~36%; Entacapone: 98% (primarily to albumin)
Time to peak: Levodopa: ~1 to 2 hours; Carbidopa: 2.5 to 3.4 hours; Entacapone: ~1 hour
Half-life: Levodopa: 1.7 hours (range: 1.1 to 3.2 hours); Carbidopa: 1.6-2 hours (range ~1 to 4 hours); Entacapone: ~1 hour (range: 0.3 to 4.5 hours)
Metabolism: Levodopa: Two major pathways (decarboxylation and O-methylation) of metabolism; Carbidopa inhibits the decarboxylation of levodopa to dopamine in the peripheral tissue to allow greater levodopa distribution into the CNS; Entacapone: Isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer
Excretion: Levodopa: Urine (as metabolites); Carbidopa: Urine (30% as unchanged drug; also as metabolites); Entacapone: Feces (90%); urine (10%; <1% as unchanged drug)
