Levodopa/Carbidopa

Brand names: Lodosyn
Drug class: Antineoplastic Agents

Usage of Levodopa/Carbidopa

Parkinsonian Syndrome

Levodopa is used for symptomatic treatment of parkinsonian syndrome, including parkinson disease, postencephalitic parkinsonism, and symptomatic parkinsonian syndrome resulting from carbon monoxide intoxication or manganese intoxication. Available in various fixed-combination preparations with Carbidopa for this use.

Carbidopa is used to inhibit decarboxylation of peripheral levodopa and increase the amount of levodopa available for transport to the brain. Available in fixed combination with levodopa and also as a single-entity preparation for use in patients receiving levodopa-carbidopa who require additional carbidopa to reduce nausea and vomiting and/or facilitate more rapid dosage titration.

Levodopa (in combination with carbidopa) is currently the most effective drug for relieving motor symptoms of parkinson disease. However, effectiveness decreases over time and most patients develop motor fluctuations and dyskinesias (drug-induced involuntary movements) with long-term use.

Strategies to reduce risk of motor complications include adjusting dosage of levodopa, adding other antiparkinsonian agents (e.g., dopamine receptor agonist [e.g., pramipexole, ropinirole, rotigotine], selective monoamine oxidase [MAO]-B inhibitor [e.g., rasagiline, safinamide, selegiline], catechol-O-methyltransferase [COMT] inhibitor [e.g., Entacapone, tolcapone], amantadine), or initiating other agents first to delay use of levodopa.

Motor complications associated with long-term use of standard oral levodopa formulations are thought to result from fluctuating plasma concentrations due to short half-life, delayed gastric emptying, and erratic absorption. Several non-oral preparations of levodopa and carbidopa (e.g., levodopa oral inhalation powder, carbidopa-levodopa enteral suspension) are available for use in patients with advanced parkinson disease whose motor symptoms are not effectively controlled with oral therapies.

Levodopa oral inhalation powder is used for intermittent treatment of “off” episodes in patients receiving levodopa-carbidopa. Intended for use on an intermittent basis only in patients who are already receiving carbidopa-levodopa therapy. May be particularly useful in patients with severely delayed gastric emptying.

Carbidopa-levodopa enteral suspension is used for treatment of motor fluctuations in patients with advanced parkinson disease. Administered by continuous enteral infusion through a percutaneous endoscopic gastrojejunostomy (PEG-J) tube.

Relate drugs

How to use Levodopa/Carbidopa

Administration

Levodopa and carbidopa are administered orally as fixed-combination or single-entity (carbidopa only) conventional tablets, orally disintegrating tablets, extended-release tablets, or extended-release capsules. Levodopa also is available as a powder for oral inhalation. Carbidopa-levodopa enteral suspension is administered through a nasojejunal (NJ) tube or a PEG-J tube.

May continue therapy with other antiparkinsonian agents while carbidopa-levodopa is administered; however, dosage adjustments may be necessary.

If general anesthesia required, continue therapy as long as patient permitted to take oral medications. If therapy interrupted, observe patient for symptoms of neuroleptic malignant syndrome (NMS); resume as soon as patient is able to take oral medications. (See Hyperpyrexia and Confusion under Cautions.)

Oral Administration

Administer orally as fixed-combination or single-entity (carbidopa only) conventional (immediate-release) tablets, extended-release tablets, orally disintegrating tablets, or extended-release capsules.

Carbidopa-levodopa conventional tablets and orally disintegrating tablets contain a 1:4 or 1:10 ratio of carbidopa to levodopa. Carbidopa-levodopa extended-release tablets and capsules contain a 1:4 ratio of carbidopa to levodopa. Carbidopa and levodopa also are commercially available as fixed-combination tablets with entacapone (Stalevo) containing a 1:4 ratio of carbidopa to levodopa combined with 200 mg of entacapone.

Extended-release carbidopa-levodopa tablets: Administer as whole or half tablets; do not chew or crush.

Extended-release carbidopa-levodopa capsules: Swallow whole without regard to food; do not chew, divide, or crush. In patients with difficulty swallowing, may open capsules and sprinkle entire contents on a small amount (e.g., 1–2 tablespoons) of applesauce; administer mixture immediately and do not store for later use.

Orally disintegrating carbidopa-levodopa tablets: Just prior to administration, gently remove tablet from the bottle with dry hands. Place tablet on tongue to dissolve (usually within seconds) and swallow with saliva. Administration with water is not necessary.

Fixed-combination carbidopa, levodopa, and entacapone tablets (Stalevo): Do not divide tablets; administer only one tablet per dosing interval.

Oral Inhalation

Administer levodopa powder with a special oral inhalation device (Inbrija inhaler) that delivers powdered drug from capsules. A total of 2 capsules (each containing 42 mg of levodopa) is required for the recommended dose. Do not swallow capsules as the intended effect will not be obtained.

To administer a dose, load first capsule into inhaler. Before inhaling the dose, exhale completely as possible. While keeping inhaler level, place mouthpiece of inhaler between the lips and inhale deeply and slowly through the inhaler; the patient should feel or hear a whirling sound, which is an indication that the inhaler is working. After inhaling contents of capsule, hold breath for 5 seconds before exhaling. Repeat these steps with the second capsule to complete full dose.

Use a new inhaler with each new carton of drug.

Consult manufacturer's prescribing information for additional details.

Enteral Administration

Administer carbidopa-levodopa enteral suspension (Duopa) as a 16-hour continuous infusion through a PEG-J tube using a portable infusion device (i.e., CADD Legacy 1400 pump). PEG-J tube placement and removal should be performed by a gastroenterologist or other experienced healthcare provider. May temporarily administer through an NJ tube (e.g., as a trial to determine whether patient responds to therapy and can manage device) until a permanent PEG-J tube can be established.

Enteral suspension is commercially available in single-use cassettes containing 4.63 mg of carbidopa and 20 mg of levodopa per mL.

Store cassettes in freezer prior to use. (See Storage under Stability.) Prior to administration, remove cassette from refrigerator and allow to reach room temperature for 20 minutes. Failure to administer drug at room temperature may result in a subtherapeutic response. Cassettes are for single-use only; do not use for longer than 16 hours and discard cassette after this time period even if some drug remains.

At end of the daily 16-hour administration period, disconnect PEG-J tube from the pump and flush with room temperature potable water.

Consult manufacturer's prescribing information for additional details.

Dosage

Dosage expressed in terms of levodopa and carbidopa.

Adjust dosage carefully according to individual requirements, response, and tolerance.

Daily dosage of carbidopa should be at least 70–100 mg daily; patients receiving <70–100 mg daily are likely to experience nausea and vomiting.

Observe patient closely if dosage is reduced abruptly or drug is discontinued; risk of precipitating a symptom complex resembling neuroleptic malignant syndrome (NMS). Gradually reduce dosage when treatment is discontinued. (See Hyperpyrexia and Confusion under Cautions.)

Adults

Parkinsonian Syndrome Carbidopa-Levodopa Conventional Tablets or Orally Disintegrating Tablets Oral

Initially, carbidopa 25 mg/levodopa 100 mg (as 1 tablet) 3 times daily. May increase dosage by 1 tablet (carbidopa 25 mg/levodopa 100 mg) daily or every other day until a daily dosage of carbidopa 200 mg/levodopa 800 mg is reached.

Alternatively, initiate with carbidopa 10 mg/levodopa 100 mg (as 1 tablet) 3 or 4 times daily; however, this dosage will not provide an adequate dose of carbidopa for most patients. May increase dosage by 1 tablet (carbidopa 10 mg/levodopa 100 mg) daily or every other day until a daily dosage of carbidopa 80 mg/levodopa 800 mg is reached.

Individualize maintenance dosage according to desired therapeutic response. Patients should receive at least 70–100 mg of carbidopa daily during maintenance therapy.

Use of combination preparations containing a 1:10 ratio of carbidopa to levodopa may not provide an adequate amount of carbidopa. If a greater proportion of carbidopa is required, may substitute 1 tablet of carbidopa 25 mg/levodopa 100 mg for 1 tablet of carbidopa 10 mg/levodopa 100 mg. If additional carbidopa is still required, may administer a 25-mg dose of carbidopa (as the single-entity tablet preparation) with each first daily dose of carbidopa-levodopa; may give additional 12.5-mg or 25-mg doses of carbidopa with each subsequent dose of carbidopa-levodopa as needed.

If patients require higher dosages of levodopa while receiving a combination preparation containing 100 mg of levodopa, switch patients to a preparation containing 250 mg of levodopa.

Carbidopa-Levodopa Extended-release Tablets Oral

Extended-release tablets are not bioequivalent to immediate-release tablets; adjust dosage appropriately when converting patients between the formulations. (See Bioavailability under Pharmacokinetics.)

Patients currently receiving immediate-release levodopa preparations: Convert to an appropriate dosage of the extended-release tablets that provides approximately 10% more levodopa daily than dosage previously received as the immediate-release preparation; levodopa dosage may need to be increased up to 30% more daily, Depending on response.

Levodopa-naive patients: Initially, carbidopa 50 mg/levodopa 200 mg (as 1 extended-release tablet) twice daily; initial dosage should not be given at intervals <6 hours. Adjust dose or dosing frequency based on response and tolerance at intervals ≥3 days. Most patients are treated adequately with dosages that provide 400–1600 mg of levodopa, administered in divided doses at intervals ranging from 4–8 hours while awake. Higher dosages (≥2400 mg of levodopa per day) and shorter intervals (<4 hours) have been used but usually are not recommended. If the dosing interval is <4 hours and/or the divided doses are not equal, it is recommended that the smaller doses be given at the end of the day.

When additional levodopa is needed for symptomatic control, may consider adding doses of a conventional preparation of carbidopa-levodopa during brief periods of the day.

Carbidopa-Levodopa Extended-release Capsules Oral

Extended-release capsules are not bioequivalent to immediate-release preparations; adjust dosage appropriately when converting patients between the formulations. (See Bioavailability under Pharmacokinetics.)

Patients currently receiving immediate-release levodopa preparations: Calculate patient's current total daily dosage of levodopa and convert to an appropriate starting dosage of the extended-release capsules (see Table 1). Following conversion, adjust dose and/or dosing interval as necessary based on patient tolerance and clinical response. In patients currently receiving carbidopa-levodopa in combination with a COMT inhibitor (e.g., entacapone), may need to increase total initial daily dose of levodopa in the extended-release capsule.

Table 1. Conversion from Immediate-release Carbidopa-Levodopa Preparations to Extended-release Carbidopa-Levodopa Capsules (Rytary)117

Total Daily Dose of Levodopa in Immediate-release Carbidopa-Levodopa

Total Daily Dose of Levodopa in Extended-release Capsules

400–549 mg

855 mg (administered as 3 capsules [carbidopa 23.75 mg and levodopa 95 mg] 3 times daily)

550–749 mg

1140 mg (administered as 4 capsules [carbidopa 23.75 mg and levodopa 95 mg] 3 times daily)

750–949 mg

1305 mg (administered as 3 capsules [carbidopa 36.25 mg and levodopa 145 mg] 3 times daily)

950–1249 mg

1755 mg (administered as 3 capsules [carbidopa 48.75 mg and levodopa 195 mg] 3 times daily)

≥1250 mg

2340 mg (administered as 4 capsules [carbidopa 48.75 mg and levodopa 195 mg] 3 times daily) or 2205 mg (administered as 3 capsules [carbidopa 61.25 mg and levodopa 245 mg] 3 times daily)

Levodopa-naive patients: Initially, carbidopa 23.75 mg/levodopa 95 mg (as extended-release capsules) 3 times daily for the first 3 days. May increase to carbidopa 36.25 mg/levodopa 145 mg 3 times daily on the fourth day of treatment. Thereafter, may increase dosage based on patient tolerance and clinical response up to a maximum of carbidopa 97.5 mg/levodopa 390 mg 3 times daily; if needed, dosing frequency may be increased to a maximum of 5 times daily. Maintain patients on the lowest possible dosage necessary to achieve adequate symptom control while minimizing adverse effects.

Carbidopa, Levodopa, and Entacapone Fixed-combination Tablets Oral

Patients currently receiving carbidopa-levodopa conventional tablets with entacapone: May substitute with corresponding strength of the combination tablet containing same amounts of carbidopa and levodopa. No experience transitioning patients receiving carbidopa-levodopa extended-release tablets or carbidopa-levodopa preparations not containing a 1:4 ratio.

Patients not currently receiving entacapone: Initially titrate to a tolerable and effective dose using separate carbidopa-levodopa and entacapone tablets. Once optimum dosage established, may convert patients to a corresponding dosage of the carbidopa-levodopa-entacapone combination tablet.

Carbidopa Tablets Oral

Carbidopa: 25 mg with first dose of carbidopa/levodopa each day for patients who need additional carbidopa; additional 12.5- or 25-mg doses may be given during the day with each dose of carbidopa/levodopa.

Levodopa Oral Inhalation Powder (Inbrija) Oral Inhalation

Inhale contents of 2 capsules (total of 84 mg) as needed for “off” symptoms, up to 5 times daily.

Maximum recommended dose per “off” period is 84 mg and maximum daily dosage is 420 mg.

Carbidopa-Levodopa Enteral Suspension (Duopa) Enteral

Dosage of carbidopa-levodopa enteral suspension consists of 3 components: a morning dose (administered usually over 10–30 minutes), a continuous infusion (administered over 16 hours), and additional doses (i.e., extra doses) as needed for breakthrough symptoms.

Prior to initiating treatment, convert patient from all forms of levodopa to oral immediate-release carbidopa-levodopa tablets (1:4 ratio). Dosage of enteral suspension is based on amount of oral levodopa taken the previous day.

Determine initial morning dose of enteral suspension (in mL) as follows: calculate the total amount of levodopa (in mg) in the first dose of immediate-release carbidopa-levodopa taken the previous day. Convert this dose (in mg) to mL by multiplying by 0.8 and dividing by 20 mg/mL; add an additional 3 mL to account for priming volume.

Determine initial continuous dose of enteral suspension (in mL) as follows: calculate the total amount of levodopa from oral immediate-release carbidopa-levodopa doses taken throughout the previous day (over 16 waking hours); do not use doses taken at night in the calculation. Subtract the first oral levodopa dose taken the previous day (determined in morning dose calculation) from the total oral levodopa dose taken over 16 hours; divide this value by 20 mg/mL to obtain the continuous dose that should be administered over 16 hours. Calculate hourly infusion rate (in mL/hour) by dividing continuous dose by 16 hours.

After the first day of treatment, titrate daily morning dose and continuous dose based on individual response and tolerability until a stable dosage is obtained. (See Prescribing Limits.) If patient experiences persistent or numerous “off” periods during the 16-hour infusion period, may increase continuous dose or administer extra doses. In patients who require overnight treatment, an extended-release formulation of oral levodopa-carbidopa may be taken at bedtime after stopping the enteral infusion. If dyskinesias or other adverse effects occur, may decrease continuous dose or temporarily interrupt therapy until adverse effects subside. Consult manufacturer's prescribing information for recommendations on dosage adjustments.

Avoid sudden discontinuance of therapy or rapid dose reduction; when discontinuing therapy, taper dosage or switch patients to oral immediate-release carbidopa-levodopa therapy.

Prescribing Limits

Adults

Parkinsonian Syndrome Oral

Carbidopa: Experience with dosages >200 mg daily limited.

Carbidopa-levodopa extended-release capsules: Manufacturer recommends a maximum daily dose of carbidopa 612.5 mg and levodopa 2450 mg.

Carbidopa-levodopa-entacapone fixed-combination tablets: If preparations containing carbidopa 12.5–37.5 mg, levodopa 50–150 mg, and entacapone 200 mg (Stalevo 50, 75, 100, 125, and 150) are used, maximum of 8 tablets daily. If preparation containing carbidopa 50 mg, levodopa 200 mg, and entacapone 200 mg (Stalevo 200) is used, maximum of 6 tablets daily.

Levodopa oral inhalation: Maximum recommended dose per “off” period is 84 mg and maximum daily dosage is 420 mg.

Carbidopa-levodopa enteral suspension: Maximum recommended daily dose is 2000 mg of the levodopa component (i.e., one cassette per day).

Warnings

Contraindications

  • Concomitant use with a nonselective MAO inhibitor. (See Specific Drugs and Foods under Interactions.)
  • Angle-closure glaucoma.
  • Known hypersensitivity to levodopa, carbidopa, or any ingredient in the formulation.

    • Warnings/Precautions

    Warnings

    Motor Complications

    Therapy associated with dyskinesias; dosage reduction of levodopa-carbidopa or other antiparkinsonian agents may be needed.

    Motor fluctuations also may occur with long-term use. May manifest as “end-of-dose” effect, sudden loss of effectiveness with abrupt onset of akinesia followed by sudden return of effectiveness (“on-off” phenomenon), or sudden hypotonic freezing (patient falls frequently while attempting to walk).

    NeuropsyChiatric Effects

    Psychiatric disturbances reported. Observe patients carefully for depression with concomitant suicidal tendencies. Depression reported with increased frequency in patients receiving enteral carbidopa-levodopa suspension compared with oral immediate-release preparation.

    Hallucinations and abnormal thoughts or behavior (e.g., paranoia, confusion, psychotic disorder, agitation, delusions, delirium, psychotic-like behavior, disorientation, aggressive behavior) reported with dopaminergic drugs. Hallucinations generally occur soon after initiation of levodopa therapy and may be alleviated by reducing dosage.

    Generally avoid use in patients with major psychotic disorders.

    Generalized neuropathy, most often characterized as sensory or sensorimotor, reported in patients receiving carbidopa-levodopa enteral suspension. Electrodiagnostic findings most consistent with axonal polyneuropathy. Evaluate patients for neuropathy prior to and during treatment, particularly in those with preexisting neuropathy or risk of neuropathy. Vitamin B supplementation reported to decrease incidence of neuropathy.

    Cardiovascular Effects

    Risk of orthostatic hypotension; usually asymptomatic and tolerance usually develops within a few months.

    Cardiac ischemic events reported with use of some preparations.

    Use with caution in patients with a history of MI who have residual atrial, nodal, or ventricular arrhythmias; monitor cardiac function in a facility with intensive cardiac care during initial dosage adjustment.

    Use with caution in patients with severe cardiovascular disease.

    Respiratory Effects

    Use with caution in patients with severe pulmonary disease (e.g., bronchial asthma).

    Coughing is a frequent adverse effect of levodopa oral inhalation therapy. Clinically important changes in pulmonary function not observed; however, this dosage form is not recommended in patients with COPD, asthma, or other chronic lung diseases.

    GI Effects

    Use with caution in patients with a history of peptic ulcers; possibility of upper GI hemorrhage in these patients.

    Complications associated with the PEG-J procedure or device (e.g., bezoar; ileus; implant site erosion/ulcer; intestinal hemorrhage, ischemia, obstruction, or perforation; intussusception; pancreatitis; peritonitis; pneumoperitoneum; postoperative wound infection) may occur in patients receiving carbidopa-levodopa enteral suspension; may result in serious outcomes such as death or need for surgery. Instruct patients to notify a clinician immediately if they experience abdominal pain, prolonged constipation, nausea, vomiting, fever, or melanotic stool.

    Falling Asleep During Activities of Daily Living and Somnolence

    Episodes of falling asleep while engaged in activities of daily living (e.g., driving) reported, sometimes resulting in accidents.

    Some patients perceived no warning signs (e.g., excessive drowsiness) and believed they were alert immediately prior to the event.

    Monitor patients for drowsiness or sleepiness. Patients may not acknowledge drowsiness or sleepiness until directly questioned about such adverse effects during specific activities. Ask patients about any factors that may increase the risk of somnolence (e.g., concomitant sedating drugs, presence of sleep disorders).

    Consider discontinuing therapy if a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating). If the drug is continued, advise patients not to drive and to avoid other potentially dangerous activities. (See Advice to Patients.) Insufficient information to establish whether dosage reduction will eliminate this adverse event.

    Hyperpyrexia and Confusion

    Symptom complex resembling neuroleptic malignant syndrome (NMS; e.g., elevated temperature, muscular rigidity, altered consciousness, autonomic instability) reported following dosage reduction or abrupt withdrawal of levodopa.

    Observe patient closely when dosage is reduced or drug discontinued; especially important in patients receiving concomitant therapy with an antipsychotic agent.

    General Precautions

    Evaluate hepatic, hematopoietic, cardiovascular, and renal function periodically.

    Use of Fixed Combinations

    When the fixed-combination preparation containing levodopa, carbidopa, and entacapone (Stalevo) is used, observe the usual precautions and contraindications associated with all drugs in the preparation.

    Glaucoma

    May increase IOP in patients with glaucoma; use with caution in patients with well-controlled open-angle glaucoma and monitor IOP. (See Contraindications under Cautions.)

    Endocrine Disorders

    Use with caution.

    Closely monitor diabetic patients; levodopa may affect glycemic control.

    Melanoma

    Epidemiologic studies indicate patients with parkinsonian syndrome have a twofold to approximately sixfold higher risk of developing melanoma than the general population. Unclear whether increased risk is due to parkinsonian syndrome or other factors (e.g., drugs used to treat the disease).

    Monitor for melanoma on a frequent and regular basis. Manufacturer recommends periodic skin examinations performed by appropriately qualified individuals (e.g., dermatologists).

    Intense Urges

    Intense urges (e.g., urge to gamble, increased sexual urges, other intense urges) and inability to control these urges reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone (including levodopa-carbidopa). Urges stopped in some cases when dosage was reduced or drug was discontinued.

    Consider reducing dosage or discontinuing therapy if a patient develops such urges.

    Phenylketonuria with Orally Disintegrating Tablets

    Levodopa-carbidopa orally disintegrating tablets contain aspartame (NutraSweet), which is metabolized in the GI tract to phenylalanine.

    Specific Populations

    Pregnancy

    No adequate and well-controlled studies in pregnant women; in animal reproductive studies, decreased pup viability and teratogenic effects (e.g., visceral and skeletal malformations) observed.

    Weigh risks versus benefits in women of childbearing potential.

    Lactation

    Levodopa is distributed into human milk; caution advised. Carbidopa is distributed into milk in rats; not known whether carbidopa is distributed into human milk.

    Use caution in nursing women. Consider known benefits of breast-feeding along with mother's clinical need for the drug and any potential adverse effects on the infant from drug or underlying maternal condition.

    Pediatric Use

    Safety and efficacy not established in children <18 years of age.

    Geriatric Use

    Oral preparations: No overall differences in safety or efficacy relative to younger adults.

    Levodopa oral inhalation: Cough, upper respiratory tract infection, nausea, vomiting, extremity pain, and discolored nasal discharge were reported with higher frequency in geriatric patients ≥65 years of age than younger adults.

    Hepatic Impairment

    Use with caution.

    Renal Impairment

    Use with caution.

    Common Adverse Effects

    Dyskinesias, nausea, vomiting, headache, insomnia, abnormal dreams, dry mouth, anxiety, constipation, orthostatic hypotension.

    Levodopa oral inhalation: Cough, nausea, upper respiratory tract infection, discolored sputum.

    Carbidopa-levodopa enteral suspension: Complications from device insertion, nausea, depression, peripheral edema, hypertension, upper respiratory tract infection, oropharyngeal pain, atelectasis, incision site erythema.

    What other drugs will affect Levodopa/Carbidopa

    Specific Drugs and Foods

    Drug or Food

    Interaction

    Comments

    Anticholinergic agents

    Potential for decreased tremor and/or exacerbation of abnormal involuntary movements

    Possible delay in levodopa absorption and increase in gastric metabolism of levodopa

    Antidepressants, tricyclic

    Potential for hypertension and dyskinesia

    Use concomitantly with caution

    Antipsychotic agents (phenothiazines, butyrophenones, risperidone)

    Possible reduction in the therapeutic effects of levodopa

    Possible increased risk of NMS (see Hyperpyrexia and Confusion under Cautions)

    Observe patient for loss of therapeutic effect

    Benzodiazepines

    Possible reduction in the therapeutic effects of levodopa with Chlordiazepoxide or Diazepam

    Use concomitantly with caution

    Dopamine-depleting agents (e.g., reserpine, tetrabenazine)

    Concomitant use not recommended

    Hypotensive agents

    Potential for symptomatic postural hypotension

    Potential for toxic CNS effects such as psychosis with methyldopa

    Dosage adjustment of the hypotensive agent may be needed

    Iron preparations

    Possible decreased absorption of levodopa and carbidopa

    Administer concomitantly with caution and monitor patients for worsening parkinsonian symptoms; some clinicians recommend that iron supplements be taken at least 2 hours before or after levodopa

    Isoniazid

    Possible reduction in the therapeutic effects of levodopa

    Observe patient for loss of therapeutic effect

    MAO inhibitors

    Potential for hypertension, headache, hyperexcitability with nonselective MAO inhibitors

    Possible severe orthostatic hypotension with selegiline

    Contraindicated with nonselective MAO inhibitors; discontinue nonselective MAO inhibitor at least 2 weeks prior to initiation of levodopa

    May be administered concomitantly with a selective MAO inhibitor (e.g., selegiline) with caution

    Metoclopramide

    Possible increase in bioavailability of levodopa

    Possible reduction in the therapeutic effects of levodopa

    Papaverine

    Possible reduction in the therapeutic effects of levodopa

    Use concomitantly with caution and observe patient for loss of therapeutic effect

    Phenytoin

    Possible reduction in the therapeutic effects of levodopa

    Use concomitantly with caution and observe patient for loss of therapeutic effect

    Protein

    High protein foods may impair absorption of levodopa

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