Version May 2024
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
Stalevo 75: Levodopa 75 mg, carbidopa 18.75 mg, and entacapone 200 mg
Stalevo 100: Levodopa 100 mg, carbidopa 25 mg, and entacapone 200 mg
Stalevo 125: Levodopa 125 mg, carbidopa 31.25 mg, and entacapone 200 mg
Stalevo 150: Levodopa 150 mg, carbidopa 37.5 mg, and entacapone 200 mg
Stalevo 200: Levodopa 200 mg, carbidopa 50 mg, and entacapone 200 mg
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
Tablets (Stalevo 100 Oral)
25-100-200 mg (per each): $9.18
Tablets (Stalevo 125 Oral)
31.25-125-200 mg (per each): $9.18
Tablets (Stalevo 150 Oral)
37.5-150-200 mg (per each): $9.18
Tablets (Stalevo 200 Oral)
50-200-200 mg (per each): $9.18
Tablets (Stalevo 50 Oral)
12.5-50-200 mg (per each): $9.18
Tablets (Stalevo 75 Oral)
18.75-75-200 mg (per each): $9.18
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 drugs that have a heightened risk of causing significant patient harm when used in error.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect 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 diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Amisulpride (Oral): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). Amisulpride (Oral) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Antipsychotic Agents (First Generation [Typical]): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect 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 diminish the therapeutic effect 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 enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Biperiden: May enhance the adverse/toxic effect of Levodopa-Foslevodopa. Specifically, the risk of choreic movements or dyskinesias may be increased. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Specifically, the risk of chorea may be increased. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
COMT Substrates: COMT Inhibitors may increase the serum concentration of COMT Substrates. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Droxidopa: Carbidopa may diminish the therapeutic effect of Droxidopa. Carbidopa may decrease serum concentrations of the active metabolite(s) of Droxidopa. Carbidopa may increase the serum concentration of Droxidopa. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fosphenytoin-Phenytoin: May diminish the therapeutic effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Glycopyrrolate (Systemic): May decrease the serum concentration of Levodopa-Foslevodopa. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Iron Preparations: May decrease the 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
Iron Preparations: May decrease the 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
Isoniazid: May diminish the therapeutic effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Kava Kava may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofepramine: Entacapone may enhance the adverse/toxic effect of Lofepramine. Risk X: Avoid combination
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Macimorelin: Levodopa-Foslevodopa may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methionine: May diminish the therapeutic effect of Levodopa-Foslevodopa. Management: Avoid large daily doses of methionine in patients receiving levodopa (clinical studies showing interaction used 4.5 g methionine daily). More typical doses of methionine (eg, 500 mg) may not cause a problem. Risk D: Consider therapy modification
Methotrimeprazine: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Methotrimeprazine. Risk X: Avoid combination
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: Levodopa-Foslevodopa may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Risk X: Avoid combination
Monoamine Oxidase Inhibitors (Type B): Levodopa-Foslevodopa may enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Type B). Risk C: Monitor therapy
Multivitamins/Fluoride (with ADE): May diminish the therapeutic effect 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 diminish the therapeutic effect of Levodopa. Multivitamins/Minerals (with ADEK, Folate, Iron) may decrease the 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 diminish the therapeutic effect of Levodopa-Foslevodopa. Management: Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Risk D: Consider therapy modification
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect 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
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Papaverine: May enhance the hypotensive effect of Levodopa-Foslevodopa. Papaverine may diminish the therapeutic effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pyridoxine: May diminish the therapeutic effect 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 enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Reserpine: Levodopa-Foslevodopa may enhance the hypotensive effect of Reserpine. Reserpine may diminish the therapeutic effect 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
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Sapropterin: May enhance the adverse/toxic effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Solriamfetol: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy
Spiramycin: May decrease the serum concentration of Carbidopa. And thus may decrease the effectiveness of levodopa. Risk C: Monitor therapy
Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Vesicular Monoamine Transporter 2 (VMAT2) Inhibitors: May diminish the therapeutic effect 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
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
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)
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