Levodopa (L-dopa) is an aromatic amine that is metabolized to dopamine. Levodopa is available in an oral inhalation formulation (Inbrija) that is used "as needed" up to 5 times daily for 'off' episodes in Parkinson's patients receiving levodopa/carbidopa. Oral levodopa formulas are combined with carbidopa (Sinemet, Sinemet CR, Duopa) for treating motor symptoms associated with Parkinson's disease or parkinsonism. Levodopa revolutionized the treatment of Parkinson's disease when it was introduced in the 1960s and it is still considered a first-line treatment option when combined with carbidopa. Levodopa can significantly decrease motor symptoms, thereby increasing quality of life in patients with Parkinson's disease. Due to low bioavailability of levodopa into the CNS, combined use with carbidopa is considered the standard of care due to the ability of carbidopa to increase the amount of levodopa available for transport into the CNS. Because of various central nervous system effects that may occur during levodopa administration, patients receiving levodopa should be monitored for depression, suicidality, hallucinations, psychosis, and other cognitive or behavioral changes.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Inhalation Administration
Oral inhalation powder (capsules for oral inhalation; i.e., Inbrija)
-Each carton contains capsules in foil blister strips and 1 inhaler.
-The capsules are for oral inhalation using the manufacturer supplied inhaler device only. Do NOT swallow the capsules. Always use the new inhaler in the new carton. Do not save or use inhalers from previous cartons.
-Healthcare providers should instruct the patient on proper use of the inhaler device.
-Ensure hands are clean and dry and find a clean, dry surface to gather supplies and prepare dose. Check the expiration date and discard any expired product.
-Inhaler preparation:
--Remove the blue cap by pulling it straight off of the inhaler and place the cap to the side for later use.
-Twist and pull off the mouthpiece to separate it from the handle.
-Capsule preparation:
--Just prior to use, remove 1 capsule from packaging by carefully peeling back the foil.
-Do NOT try to push the capsule through the back of the foil package. Only remove 1 capsule at a time.
-Discard any capsule that looks crushed, damaged, or wet.
-Preparation of capsule with inhaler:
--Hold the inhaler upright using the handle.
-Drop 1 capsule into the opening of the capsule chamber. Do not load 2 capsules at the same time.
-Line up the white arrows on the handle and mouthpiece.
-Firmly push the mouthpiece and handle together until you hear a "click". This punctures the capsule.
-Release the mouthpiece, which will spring back and stay attached. The inhaler is now ready to use.
-Do not push the handle and mouthpiece together more than 1 time since the capsule may become damaged and the full dose may not be received.
-If the capsule becomes damaged, discard it in the trash and begin with a new capsule.
-Ensure the mouthpiece is securely attached and will not fall off before taking the dose.
-Dose administration (patient instructions):
--Stand or sit with your head and chest upright.
-Hold the inhaler level and away from the mouth.
-Breathe out completely. Do NOT breathe into the mouthpiece.
-While keeping the inhaler level, close your lips firmly around the mouthpiece.
-Take in a deep, comfortable breath until your lungs feel full. This normally takes several seconds.
-As you breathe in, you will hear and feel the capsule "whirl" (spin). The whirl means the inhaler is working.
-If you cough or stop inhaling the dose, start again using the same capsule.
-After inhaling the dose, remove inhaler from your mouth and hold your breath for 5 seconds, then breathe out.
-Twist and pull off the mouthpiece and take out the used capsule.
-Repeat steps for second capsule, to complete the full dose.
-Capsule disposition: After each use, discard the used capsules in the trash. Do NOT store capsules in the inhaler for future use.
-Inhaler disposition: Ensure there are no capsules in the inhaler before storing for the next use. Attach the mouthpiece to the handle by pushing until you hear a "click". Attach the blue cap over the mouthpiece. Store for next use. Discard the inhaler after all of the capsules in the package have been used.
-Cleaning the inhaler: It is normal for some powder to remain on the inhaler. Cleaning the inhaler is not necessary; however, a dry cotton swab or a dry tissue may be used to wipe the inside or outside of the mouthpiece.
-Refer to the "Instructions for Use" section of the product labeling for detailed visual aids that accompany the written instructions.
Dyskinesia, a hyperkinetic movement disorder, is the most common of the serious effects of levodopa therapy and includes abnormal involuntary movements such as chorea, myoclonia, tics, akathisia, and dystonic reaction (e.g., trismus, oculogyric crisis). Involuntary movements, including chewing, bruxism, gnawing, twisting, protrusion of the tongue, opening and closing the mouth, bobbing of the head or body swaying movements (stereotypies), rhythmic movements of the feet or hands, quick movements of the shoulder, and ballismus, have been reported. Based on the temporal relation to dosing, levodopa-induced dyskinesia (LID) can be classified as peak-dose dyskinesia (occurring at times of peak levodopa plasma levels), diphasic dyskinesia (occurring when levodopa levels are increasing or decreasing), and off-period dystonia (inter-dose wearing off periods). Peak-dose dyskinesia accounts for more than 80% of cases involving LID, followed by off-period dystonia which affects 30% of patients, and diphasic dyskinesia which affects 20% of patients; combinations of these dyskinesias may occur in an individual patient. The development of peak-dose dyskinesias may require dosage reduction. The risk of dyskinesias is inversely related to the age of Parkinson's disease (PD) onset; patients with young-onset PD have the highest frequency of LID. Other factors that contribute to the risk of LID include more advanced PD, longer duration of disease and treatment with levodopa, a higher dose of levodopa, female gender, lower body weight, and weight loss. During a controlled trial of inhalational levodopa in adults with Parkinson's disease using an average of 2 doses per day, dyskinesia occurred in 4% of patients receiving levodopa and more frequently than in placebo-treated patients.
'Bradykinetic episodes' or 'on-off' phenomena, including akinesia, sudden return of effectiveness, and akinesia paradoxica, can occur during levodopa therapy and is likely due to both disease progression and excessive levodopa dosage. The bradykinetic episode, a sudden lack of effectiveness with concomitant akinesia, can last from 1 minute to an hour. Bradykinesia may be followed by a sudden return of effectiveness, and the cycle may occur many times a day. Increasing the frequency of levodopa administration can minimize this effect in some patients by providing less dose-to-dose variation in CNS levodopa levels. Akinesia paradoxica or freezing is an abrupt hypotonic reaction resulting in a short-lived interruption of motor function. Akinesia paradoxic is most problematic if it occurs when the patient is walking, and may cause a fall. The etiology of the freezing episodes is not well understood. The response to levodopa decreases over time and many patients develop 'wearing-off' fluctuations of their symptoms. Wearing-off occurs during the day and consists of a gradual onset of parkinsonian symptoms before the next levodopa dose takes effect, usually 1 to 3 hours after the last dose.
Hypersensitivity reactions to levodopa have included angioedema, urticaria, pruritus, Henoch-Schonlein purpura, and bullous rash (including pemphigus-like reactions). Other dermatologic effects that have been reported during treatment with oral levodopa alone or in combination with carbidopa include rash, alopecia, hyperhidrosis, and flushing. For increased sweating, lowering the levodopa dosage may be effective or, if medically appropriate, a beta-blocker may be used to decrease hyperhidrosis.
Adverse psychiatric effects that have been reported with oral levodopa alone or in combination with carbidopa include agitation, anxiety, depression, suicidal ideation, dementia, toxic delirium, hallucinations, psychosis, paranoia, delusions, confusion, euphoria, decreased mental acuity, memory impairment, nervousness, nightmares, abnormal dreams, restlessness, and disorientation. Other centrally-mediated effects include ataxia, dizziness, falls, headache, insomnia, paresthesias, peripheral neuropathy, abnormal gait, somnolence, tremor, extrapyramidal disorder, and activation of latent Horner's syndrome. Seizures have been reported; however, causality to the drug has not been established. Nocturnal effects may be improved by reducing or stopping the last evening dose or giving the last dose earlier in the evening. Levodopa-induced psychiatric effects tend to be progressive and frequently a compromise must be reached between psychiatric effects and control of Parkinson symptoms. During a controlled trial of inhalational levodopa in adults with Parkinson's disease using an average of 2 doses per day, the following centrally-mediated effects occurred in at least 2% of patients receiving levodopa and more frequently than in placebo-treated patients: headache (2%) and insomnia (2%).
Adverse gastrointestinal (GI) effects are common during levodopa therapy and frequently include nausea/vomiting, anorexia, and weight loss. The incidence of GI effects is much higher at the initiation of therapy. Oral levodopa should be administered with food until tolerance develops to the GI effects, then administration can be changed to 30 minutes before or one hour after meals. However, it should be noted that foods, especially high-protein or high-fat foods, may interfere with oral levodopa absorption. Serious events including GI bleeding and peptic ulcer have been reported rarely during oral levodopa therapy. Other GI effects reported during treatment with oral levodopa alone or in combination with carbidopa include diarrhea, constipation, dyspepsia, xerostomia, weight gain, GI pain, dysphagia, hypersalivation, flatulence, teeth grinding (bruxism), burning sensation of the tongue, hiccups, and dysgeusia. During a controlled trial of inhalational levodopa in adults with Parkinson's disease using an average of 2 doses per day, the following adverse GI effects occurred in at least 2% of patients receiving levodopa and more frequently than in placebo-treated patients: nausea (5%) and vomiting (3%).
Elevated hepatic enzymes (AST, ALT, alkaline phosphatase, lactic dehydrogenase), elevated bilirubin levels (hyperbilirubinemia), abnormalities in blood urea nitrogen (BUN), positive direct antibody test (Coombs test), elevated serum glucose, decreased serum potassium, increased serum creatinine, increased serum uric acid, proteinuria, and glycosuria have been reported during treatment with oral levodopa alone or in combination with carbidopa. Rarely, falsely diagnosed pheochromocytoma has been reported in patients receiving levodopa due to a laboratory test interference. Caution is recommended when interpreting the plasma and urine levels of catecholamines and catecholamine metabolites in patients on levodopa. Levodopa combinations may cause a false positive reaction for urinary ketone bodies when a test tape is used. False negative tests may result with the use of glucose oxidase methods for testing glucosuria. During a controlled trial of inhalational levodopa in adults with Parkinson's disease using an average of 2 doses per day, the following abnormal laboratory results occurred in at least 2% of patients receiving levodopa and more frequently than in placebo-treated patients: increased serum bilirubin (2%) and decreased red blood cell count (2%).
Orthostatic hypotension is a frequent adverse effect of levodopa therapy, especially in the elderly. Tolerance usually develops within a few months, but some patients may require a dosage reduction. Cardiac arrhythmias or rate disturbances, usually sinus tachycardia, also can occur due to levodopa effects in the periphery, but are relatively infrequent. Beta-blockers have been effective in treating these arrhythmias, if they occur. Other cardiac effects, including hypotension, syncope, phlebitis, hypertension, palpitations, and myocardial infarction, have been reported during treatment with oral levodopa alone or in combination with carbidopa. During a controlled trial of inhalational levodopa in adults with Parkinson's disease using an average of 2 doses per day, orthostatic hypotension/decreased blood pressure occurred in 2% of patients receiving levodopa and more frequently than in placebo-treated patients.
Discoloration of body fluids, including respiratory secretions, saliva, sweat, or urine discoloration can occur during levodopa therapy. The dark color (red, brown, or black) appears to be clinically insignificant, but may stain garments and other fabrics. During a controlled trial of inhalational levodopa in adults with Parkinson's disease using an average of 2 doses per day, discolored sputum occurred in 5% of patients receiving levodopa and discolored nasal discharge occurred in 2% of patients receiving levodopa; neither of these effects occurred in placebo-treated patients.
Adverse respiratory effects that have been associated with oral levodopa alone or in combination with carbidopa include dyspnea, pharyngeal pain, cough, bizarre breathing patterns, upper respiratory infection, and hoarseness. During premarketing evaluation of inhalational levodopa in adults with Parkinson's disease using an average of 2 doses per day, the following respiratory effects occurred in at least 2% of patients receiving levodopa and more frequently than in placebo-treated patients: cough (15%), oropharyngeal pain (2%), upper respiratory tract infection (6%), naso-pharyngitis (3%), and bronchitis/pneumonia (2%). In one controlled trial of inhalational levodopa, 25 healthy adults with mild to moderate asthma on stable regimens of asthma medications received 84 mg of inhalational levodopa or placebo every 4 hours for a total of 3 doses. Cough was the most frequently reported adverse effect, occurring in 60% of patients receiving inhalational levodopa vs. 0% of those patients receiving placebo. Ten subjects in the levodopa group had reductions in FEV1 from baseline (reduction between 15% to 59%) versus four subjects in the placebo group; the FEV1 reductions remained asymptomatic and did not require rescue treatment. A choking sensation immediately following administration has been reported during postmarketing use. Because of the risk of bronchospasm, inhalational levodopa is not recommended in patients with asthma, chronic obstructive lung disease, or other chronic lung disease.
Levodopa is a pyridoxine antagonist and may lead to vitamin B6 deficiency. Administering vitamin B6 (pyridoxine) may be beneficial in preventing depletion and reducing adverse reactions.
Adverse hematological effects that have been reported during treatment with oral levodopa alone or in combination with carbidopa include agranulocytosis, leukopenia, non-hemolytic and hemolytic anemia, thrombocytopenia, decreased white blood cell count, and decreased hemoglobin or hematocrit. Development of severe hematological effects warrants discontinuation of the drug.
Adverse genitourinary (GU) effects that have been reported during treatment with oral levodopa alone or in combination with carbidopa include urinary retention, increased urinary frequency, urinary tract infection, urinary incontinence, priapism, leukocyturia, hematuria, and bacteriuria.
Sudden sleep onset has been reported in patient receiving levodopa. Some incidents have occurred while the patient was driving or performing other potentially hazardous activities. In some cases excessive drowsiness due to levodopa has resulted in auto accidents or other harmful events in the course of daily living. Sudden sleep onset has occurred more than one year after the initiation of treatment in some cases. Prior to initiating treatment with levodopa, patients should be advised of the potential to develop somnolence and specifically asked about factors that may increase the risk of experiencing such an event such as coadministration with other CNS depressants, ethanol ingestion, or the presence of sleep disorders (e.g., narcolepsy, sleep apnea). Patients should be cautioned against driving or operating machinery, or performing other tasks that require alertness, until they gauge how levodopa affects their motor performance. Reassessment for drowsiness or oversedation is necessary throughout levodopa therapy because patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), consider discontinuation of levodopa. If a decision is made to continue the drug, patients should be advised to avoid driving or other potentially dangerous activities. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
Some patients receiving medications that increase dopaminergic tone, including levodopa, have reported intense and uncontrollable urges to gamble, increased sexual urges, or other intense urges. Causality due to dopaminergic agents has not been established; however, in some cases the urges stopped after the dose was reduced or the drug was discontinued. Practitioners should inquire periodically about new or worsening impulse control symptoms in patients receiving levodopa. Likewise, patients should be instructed to report such changes while receiving levodopa. Dose reduction or discontinuation should be considered if impulse control symptoms occur.
During a controlled trial of inhalational levodopa in adults with Parkinson's disease using an average of 2 doses per day, the following general effects or complications occurred in at least 2% of patients receiving levodopa and more frequently than in placebo-treated patients: fall (3%), skin laceration (2%), skin abrasion (2%), and chest discomfort (2%). General effects reported during treatment with oral levodopa alone or in combination with carbidopa include chest pain (unspecified), fatigue, abdominal pain, abdominal distress, malaise, faintness, hot flashes, sense of stimulation, edema, and asthenia.
Adverse musculoskeletal effects that have been reported during treatment with oral levodopa alone or in combination with carbidopa include back pain, shoulder pain, muscle cramps, muscle twitching, and leg pain.
Adverse ophthalmic effects that have been reported during treatment with levodopa alone or in combination with carbidopa include diplopia, blurred vision, mydriasis, and blepharospasm (which may indicate toxicity). Levodopa may cause increased intraocular pressure (ocular hypertension) in patients with closed-angle glaucoma.
A symptom complex resembling neuroleptic malignant syndrome (i.e., neuroleptic malignant syndrome-like symptoms) can develop following abrupt discontinuation or dose reduction of levodopa, especially in patients receiving antipsychotic agents concomitantly. Patients should be observed closely for manifestations of this symptom complex, which includes fever or hyperthermia. Neurological findings, including muscle rigidity, involuntary movements, altered consciousness, mental status changes; other disturbances, such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper- or hypotension; laboratory findings, such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin have been reported. Early diagnosis is important for the appropriate management of this condition.
Skin cancer (melanoma) has been reported postmarketing in patients receiving oral levodopa therapy, alone or in combination with carbidopa. Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma skin cancer than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear. Patients and providers are advised to monitor for melanomas frequently and on a regular basis when using oral levodopa for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).
Levodopa may cause or exacerbate dyskinesias. If troublesome dyskinesias occur, prescribers may need to consider stopping treatment with oral or inhalational levodopa and/or adjusting the patient's daily medications for the treatment of Parkinson's disease.
Levodopa use is contraindicated in patients currently taking nonselective monoamine oxidase (MAO) inhibitor therapy (MAOI therapy) or who have recently (within 2 weeks) taken a nonselective MAOI. Hypertension can occur if these drugs are used concurrently. Non-selective MAOIs should be discontinued at least 2 weeks before initiation of oral or inhalational levodopa therapy.
Avoid abrupt discontinuation of oral or oral inhalation levodopa therapy. A symptom complex that resembles neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy. Prior to general anesthesia and surgery, levodopa may be continued as long as the patient is permitted to take medication. If levodopa-based therapy is interrupted temporarily, the patient should be observed for discontinuation symptoms, and the usual dosage should be administered as soon as the patient is able to resume usual medications.
All patients receiving levodopa should be monitored closely for changes in thought processes, moods, or behaviors. Levodopa may cause mental status and behavioral changes, which may be severe, including psychotic-like behavior, during treatment. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies or suicidal ideation. Patients with past or current psychosis should be treated with caution. Dopaminergic therapy in patients with Parkinson's disease has been associated with hallucinations and may lead to drug withdrawal or patient hospitalization in rare instances. These reactions are thought to be due to increased brain dopamine following administration of levodopa.
Levodopa has the potential to cause drowsiness or somnolence. There have been postmarketing reports of patients who have experienced sudden sleep onset when taking dopaminergic agents. In some cases, excessive drowsiness has resulted in automobile accidents or other harmful events in the course of daily living. Patients should be advised of this effect and be instructed to use extreme caution when driving or operating machinery or performing other tasks that require alertness while receiving levodopa therapy. Reassessment for drowsiness or oversedation is necessary throughout therapy. Sleep disorders (e.g., narcolepsy, sleep apnea), coadministration with other CNS depressants, or interacting medications may increase the risk of suddenly falling asleep while on this medication. Patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Advise patients to speak with their health care prescriber before ethanol ingestion, taking sedating medications, or before taking other CNS depressant medications because of the possible additive effects in combination with levodopa. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), consider levodopa discontinuation. If a decision is made to continue treatment, patients should be advised to avoid driving or other potentially dangerous activities. There is insufficient data to establish if dose reduction will eliminate sudden episodes of falling asleep.
Some patients receiving medications that increase dopaminergic tone have reported intense and uncontrollable urges to gamble, increased sexual urges, or other intense urges. Causality due to dopaminergic agents has not been established; however, in some cases the urges stopped after the dose was reduced or the drug was discontinued. Practitioners should inquire periodically about new or worsening impulse control symptoms in patients receiving levodopa. Likewise, patients should be instructed to report such changes while receiving levodopa. Dose reduction or discontinuation should be considered in those who experience these effects.
Levodopa for oral inhalation is not recommended for use in patients with asthma, chronic obstructive pulmonary disease (COPD), or other chronic underlying pulmonary disease because of the risk of bronchospasm. Oral levodopa must also be used cautiously in those with bronchial asthma or other severe lung disease.
There is a general precaution about using oral levodopa therapy in Parkinson's patients who are prone to hypotension or orthostatic hypotension, including some patients with cardiac disease. Syncope and/or orthostatic hypotension have been reported with drugs that increase dopaminergic tone, including levodopa. Reports of syncope are generally more frequent in patients who have experienced prior episodes of documented hypotension. Cardiac monitoring in a facility with provisions for intensive cardiac care is recommended during initial titration of oral levodopa in Parkinson's patients with significant cardiac disease, including patients a history of myocardial infarction who have residual cardiac arrhythmias (i.e., atrial, nodal, or ventricular arrhythmias).
There is a very general precaution that oral levodopa therapy should be administered with caution to patients with renal disease or hepatic disease. No dosage adjustments are recommended based on renal or hepatic impairment; titration occurs to clinical response.
Use levodopa oral inhalation with caution in patients with closed-angle glaucoma; levodopa oral inhalation may cause an increase in intraocular pressure; monitor for increased intraocular pressure in such patients during treatment. Oral levodopa is contraindicated in patients with closed-angle glaucoma, but may be used in patients with open-angle glaucoma if intraocular pressure is closely monitored and controlled.
Patients with diabetes mellitus should be monitored during oral levodopa therapy. Alterations in blood glucose may occur in some individuals as a result of the sympathomimetic effects of levodopa. Levodopa may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. False-negative tests may result with use of glucose-oxidase methods of testing for glucosuria.
Rarely, falsely diagnosed pheochromocytoma has been reported in patients receiving oral levodopa due to a laboratory test interference. Caution should be exercised with interpreting the plasma and urine levels of catecholamines and catecholamine metabolites in patients on levodopa.
Levodopa can cause mental status changes or other adverse effects, and the geriatric adult may be more sensitive to certain side effects of Parkinson's disease medications. During clinical trials of levodopa oral inhalation, age-related increased incidences of some adverse reactions were reported in persons 65 years of age or older vs. younger adults and included cough, upper respiratory tract infection, nausea, vomiting, pain in the extremities, and discolored nasal discharge.
Levodopa should be used in pregnancy only if the potential benefit outweighs the potential risk to the fetus. There are no adequate or well-controlled studies regarding the developmental risks to the fetus from levodopa use during human pregnancy. Levodopa/carbidopa therapy has been shown to be developmentally toxic in animal studies. When administered to pregnant rabbits throughout organogenesis, the combination caused both visceral and skeletal malformations in rabbits. No teratogenic effects were observed when carbidopa/levodopa was administered to pregnant mice; there was a decrease in the number of live pups delivered by rats receiving carbidopa/levodopa during organogenesis. Levodopa crosses the placenta in humans and reaches levels in the fetus comparable to maternal blood, although pregnancy outcomes have been primarily unremarkable. Two miscarriages were reported in the first trimester during use of carbidopa/levodopa, and one infant exposed to levodopa in utero was reported to have osteomalacia. One case of neonatal seizure occurred after use of bromocriptine plus carbidopa/levodopa/entacapone during pregnancy. Maternal complications reported in three pregnancies during use of levodopa in combination with carbidopa included first trimester vaginal bleeding, third trimester nausea and vomiting, depression, and preeclampsia. The effects of levodopa in labor and delivery are unknown. One case describes a patient who became pregnant on two separate occasions while receiving levodopa and cabergoline for Parkinson's disease. The medications were continued throughout the pregnancies. There were no fetal complications; however, cesarean section was required in the second birth due to placental abruption.
Excretion of levodopa into human breast milk has been reported, and caution is advisable in breast-feeding mothers. Because levodopa can inhibit prolactin secretion, interference with proper lactation is possible; however, there are limited data about this potential in lactating women. Partial to complete suppression of lactation has been observed in female patients given levodopa for galactorrhea. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.& If levodopa must be administered during breast-feeding, the infant should be monitored for commonly encountered adverse effects associated with dopaminergic therapy including dyskinesias, insomnia, sedation, nausea, and constipation. In one case report of a breast-feeding mother with Parkinson's disease receiving sustained-release carbidopa/levodopa 50/200 mg 4 times daily, peak levels of levodopa in milk occurred 3 hours after a dose and returned to baseline after 6 hours. After receiving the same dose of the immediate-release (IR) formulation, similar results were observed, with the exception of higher milk: plasma ratios with the IR product (0.32 vs. 0.28). The infant ingested 0.127 mg and 0.181 mg of levodopa after maternal intake of the sustained-release and immediate-release products, respectively. It was estimated that the infant received an average of 0.3% of the maternal weight-adjusted dosage of the sustained release product and 0.5% of the maternal weight-adjusted dose of the immediate-release product. No adverse effects were observed in her infant, whose development was normal at 2 years of age.
Levodopa oral inhalation has not been studied in adolescents, children, and infants under 18 years of age. Oral levodopa formulas have not been adequately studied for safety and efficacy in children and adolescents less than 18 years of age, though off-label use in children is rarely described in the literature. Juvenile onset Parkinson's disease is very rare.
For use as intermittent treatment for 'off' episodes in those with Parkinson's disease treated with carbidopa and levodopa:
Oral inhalation dosage:
Adults: Inhale the contents of 2 capsules (42 mg per capsule for a total of 84 mg) via oral inhalation with the provided inhaler as needed for 'off' symptoms up to 5 times daily. The dose should be taken when symptoms of an 'off' period start to return. DO NOT swallow the capsules; only use with the inhaler provided by the manufacturer. Max: 420 mg/day via oral inhalation.
Maximum Dosage Limits:
-Adults
Generally, 8 grams/day PO; 420 mg/day via oral inhalation.
-Geriatric
Generally, 8 grams/day PO; 420 mg/day via oral inhalation.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acebutolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Alfentanil: (Major) Prior to general anesthesia, levodopa may be continued as long as the patient is permitted to take oral medication. If levodopa-based therapy is interrupted temporarily, the usual daily dosage may be reinstituted or titrated upward to the normal dosage as soon as the patient is able to take oral medications. The patient should be observed for symptoms resembling neuroleptic malignant syndrome, and the usual regimen should be administered as soon as the patient is able to take oral medication.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Amantadine: (Minor) Amantadine can increase the efficiency of levodopa by its action on central nerve terminals.
Amiloride: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Amisulpride: (Major) Avoid using these drugs together. Amisulpride is a central dopamine antagonist and can antagonize the actions of dopamine agonists such as levodopa. Amisulpride is generally used perioperatively to prevent and treat postoperative nausea and vomiting. Prior to general anesthesia, levodopa may be continued as long as the patient is permitted to take oral medication. If levodopa-based therapy is interrupted temporarily, the usual daily dosage may be reinstituted or titrated upward to the normal dosage as soon as the patient is able to take oral medications.
Amitriptyline: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Amlodipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Amlodipine; Atorvastatin: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Amlodipine; Benazepril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Amlodipine; Celecoxib: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Amlodipine; Olmesartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Amlodipine; Valsartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Amoxapine: (Moderate) Amoxapine exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Angiotensin II receptor antagonists: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Angiotensin-converting enzyme inhibitors: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Aripiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Asenapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Atenolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Atenolol; Chlorthalidone: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Atropine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Atropine; Difenoxin: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
atypical antipsychotic: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Azilsartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Azilsartan; Chlorthalidone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Belladonna; Opium: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Benazepril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Benzphetamine: (Major) Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions or discontinuation of benzphetamine is recommended if the two agents are used concurrently.
Benztropine: (Minor) Through its central antimuscarinic actions, antimuscarinics such as benztropine can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if benztropine is added.
Beta-blockers: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Betaxolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Bisoprolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Brexpiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Brimonidine; Timolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Bumetanide: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Bupropion: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Bupropion; Naltrexone: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Calcium-channel blockers: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Candesartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Captopril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Cariprazine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Carteolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Carvedilol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Central-acting adrenergic agents: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Chlorothiazide: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Chlorpromazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Chlorthalidone: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Clevidipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Clomipramine: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Clonidine: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Clozapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Cocaine: (Major) Concomitant use of cocaine with levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) can result in an increase in the risk of developing cardiac arrhythmias. Levodopa should be used cautiously in patients who are known users of cocaine. Conversely, electrocardiographic monitoring should be considered when using cocaine in patients receiving levodopa.
Codeine; Phenylephrine; Promethazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Codeine; Promethazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Dacarbazine, DTIC: (Moderate) Levodopa response may be decreased during chemotherapy with dacarbazine, DTIC. If dacarbazine is used in a patient stabilized on levodopa therapy, practitioners may wish to be alert for needed adjustments in the levodopa regimen to maintain patient status.
Darifenacin: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
Desipramine: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Dextromethorphan; Bupropion: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Diazoxide: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Dicyclomine: (Minor) Anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diltiazem: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Diphenoxylate; Atropine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Dorzolamide; Timolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Doxazosin: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Doxepin: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Droperidol: (Major) Droperidol, a butyrophenone derivative, is a dopamine D2 receptor antagonist and thus, may reduce the therapeutic effects of levodopa, which is an agonist at dopamine D2 receptors. Avoidance of droperidol use in a patient with Parkinson's disease may be advisable unless the benefit of droperidol outweighs the risk of CNS depressive effects and decreased therapeutic response to dopamine agonists.
Enalapril, Enalaprilat: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Eplerenone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Epoprostenol: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Eprosartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Esketamine: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as levodopa, and CNS depressants, such as esketamine. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
Esmolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Ethacrynic Acid: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Felodipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fenoldopam: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Ferric Maltol: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Fluphenazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions. (Major) Many levodopa products may be taken with or without food. Follow the directions of the product prescribed. However, foods with a high protein content may delay or impair the oral absorption of levodopa and may reduce efficacy. The Parkinson's Foundation states that most patients have no problem taking levodopa-containing products with meals, but some experience less benefit if they take such products with a stomach full of protein (including meats, cheeses and other dairy products). When this occurs, it is recommended to only take carbidopa/levodopa along with non-protein foods. For patients with more advanced PD, it is best to take levodopa-containing medications 30 to 60 minutes before eating a meal to limit food interference. If nausea occurs, the products may be taken with a small non-protein snack, such as fruit or a cracker, to help. (Major) Patients with Parkinson's disease should avoid foods high in fat around the time of taking carbidopa; levodopa. These foods may delay gastric emptying, which can decrease and delay the absorption of levodopa. (Major) Patients with Parkinson's disease should avoid foods high in fiber around the time of taking carbidopa; levodopa. These foods may delay gastric emptying, which can decrease and delay the absorption of levodopa.
Fosinopril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Fosphenytoin: (Moderate) Monitor for loss of efficacy in during concomitant use of levodopa and fosphenytoin. The beneficial effects of levodopa in Parkinson disease have been reported to be revered by phenytoin.
Furosemide: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and levodopa. Concomitant use of gabapentin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Glycopyrrolate; Formoterol: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Guanfacine: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Hydralazine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Hyoscyamine: (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Iloperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Iloprost: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Imipramine: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Indacaterol; Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Irbesartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Iron Salts: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Iron: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Isocarboxazid: (Contraindicated) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as isocarboxazid. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertensive crisis and other adverse cardiovascular effects can occur. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
Isoflurane: (Major) If administered before halogenated anesthetics, levodopa without a concurrent decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthesia is required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Isoniazid, INH: (Major) Concurrent use of levodopa with drugs that have MAOI-type activity, such as isoniazid, INH should be avoided if possible. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertension and other adverse cardiovascular effects can occur.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Concurrent use of levodopa with drugs that have MAOI-type activity, such as isoniazid, INH should be avoided if possible. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertension and other adverse cardiovascular effects can occur.
Isoniazid, INH; Rifampin: (Major) Concurrent use of levodopa with drugs that have MAOI-type activity, such as isoniazid, INH should be avoided if possible. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertension and other adverse cardiovascular effects can occur.
Isoproterenol: (Major) Levodopa is the metabolic precursor to dopamine. Since a portion of administered levodopa is converted to dopamine peripherally, concomitant administration with isoproterenol should be used with caution as the risk of cardiovascular toxicity is increased.
Isradipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Labetalol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and levodopa. Dosage adjustments of lemborexant and levodopa may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levamlodipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Levobunolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Linezolid: (Major) Concomitant use of levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) and drugs with monoamine oxidase inhibitor (MAOI) activity, such as linezolid, can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
Lisinopril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Loop diuretics: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Losartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Loxapine: (Major) Due to opposing effects on central dopaminergic activity, loxapine and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to loxapine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Lumateperone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Lurasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may transiently elevate growth hormone concentrations, such as levodopa. Healthcare providers are advised to discontinue levodopa therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Maprotiline: (Moderate) Maprotiline exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Mecamylamine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Methamphetamine: (Major) Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions of amphetamines are recommended if the two agents are used concurrently.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Methscopolamine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Methyldopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Metoclopramide: (Major) Metoclopramide is a central dopamine antagonist. Metoclopramide can antagonize the actions of dopamine agonists such as levodopa. In addition, metoclopramide may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Dyskinesias and other extrapyramidal effects have been reported during treatment with various anti-parkinson's medications, particularly levodopa. A symptom complex resembling neuroleptic malignant syndrome in association with rapid dose reduction, withdrawal of, or changes in anti-parkinsonian therapy has also been observed. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and dopamine agonists; however, coadministration should be avoided if possible.
Metolazone: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Metoprolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Metyrosine: (Major) The extrapyramidal effects of metyrosine can antagonize the effects of levodopa. Dosage adjustments of either of these medications may be required.
Minoxidil: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Moexipril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Molindone: (Major) Due to opposing effects on central dopaminergic activity, molindone and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Animal studies have not shown increased toxicity when molindone is given concurrently with representative members of the antiparkinson drugs class.
Nabilone: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as levodopa, and CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Nadolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Nebivolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Nebivolol; Valsartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Neostigmine; Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Nicardipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
NIFEdipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Nimodipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Nisoldipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Nitroprusside: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Nortriptyline: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Olanzapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Olanzapine; Fluoxetine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Olanzapine; Samidorphan: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Oliceridine: (Major) Concomitant use of oliceridine with levodopa may cause excessive sedation and somnolence. Limit the use of oliceridine with levodopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Olmesartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Oxybutynin: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
Paliperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Papaverine: (Major) The beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by coadministration of papaverine; avoid concurrent use in these patients. Papaverine may block dopamine receptors in the striatum and result in loss of control of Parkinson's disease in patients who are taking levodopa.
Perindopril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Perindopril; Amlodipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Perphenazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Perphenazine; Amitriptyline: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other. (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Phenelzine: (Contraindicated) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as phenelzine, due to increased risk of hypertensive crisis. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added. (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Phenothiazines: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Phenoxybenzamine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Phenytoin: (Moderate) Monitor for loss of efficacy in during concomitant use of levodopa and phenytoin. The beneficial effects of levodopa in Parkinson disease have been reported to be revered by phenytoin.
Pimozide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Pindolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Polysaccharide-Iron Complex: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Pramipexole: (Minor) Pramipexole increases the Cmax of levodopa and decreases Tmax from 2.5 to 0.5 hrs.
Prazosin: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and levodopa. Concomitant use of pregabalin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Procarbazine: (Major) Concomitant use of levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity (e.g., procarbazine) can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
Prochlorperazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Promethazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Promethazine; Dextromethorphan: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Promethazine; Phenylephrine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Propantheline: (Moderate) Anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Propofol: (Major) If administered before halogenated anesthetics, levodopa without concomitant use of a decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthetics are required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Propranolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Protriptyline: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Pyridoxine, Vitamin B6: (Moderate) Monitor for reduced levodopa efficacy during concomitant use of pyridoxine (vitamin B6). Pyridoxine, in doses as low as 10 mg/day, may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine.
Quetiapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Quinapril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Ramipril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Rasagiline: (Moderate) There may be some increase in rasagiline blood levels in the presence of levodopa, the effect is modest and rasagiline dosing need not be modified in the presence of carbidopa; levodopa. Rasagiline and carbidopa; levodopa are frequently used together; however, there is the possibility of increased dyskinesia and postural hypotension when combined.
Risperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Rotigotine: (Moderate) In clinical studies, concurrent use of L-dopa/carbidopa with rotigotine had no effect on the pharmacokinetics of either agent. However, rotigotine may potentiate the dopaminergic side effects of levodopa via a pharmacodynamic interaction. Subsequent worsening of pre-existing dyskinesias may occur.
Sacubitril; Valsartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Safinamide: (Moderate) Safinamide and carbidopa; levodopa are indicated for use in combination; however, there is the possibility of new onset dyskinesias or exacerbation of pre-existing dyskinesias. Patients should be advised to contact their health care provider if they notice new or worsening dyskinesias while taking these medicines together.
Sapropterin: (Major) Coadministration of sapropterin and levodopa has been associated with seizures. Post-marketing safety surveillance showed 3 patients (all with underlying neurologic disorder) develop convulsions, exacerbation of convulsions, over-stimulation, or irritability while receiving concomitant levodopa and sapropterin.
Scopolamine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Selegiline: (Moderate) Monitor blood pressure during concomitant use of levodopa and selegiline. Concomitant use of levodopa with selective MAO-B inhibitors may be associated with orthostatic hypotension.
Sevoflurane: (Major) If administered before halogenated anesthetics, levodopa without a concurrent decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthesia is required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Solifenacin: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as levodopa. Caution is recommended since this combination has not been evaluated.
Sotalol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Spironolactone: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Tedizolid: (Major) Concomitant use of levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity (e.g., tedizolid) can result in hypertensive crisis or unstable blood pressure changes. Simultaneous use of these agents should be avoided if possible.
Telmisartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Telmisartan; Amlodipine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Tetrabenazine: (Moderate) Monitor for a decrease in levodopa efficacy during concomitant tetrabenazine use. Levodopa and tetrabenazine may antagonize each other's effects: levodopa is metabolized to dopamine while tetrabenazine depletes dopamine stores and acts as a dopamine receptor blocker. While concomitant use is generally not recommended for this reason, combination therapy may be beneficial in the management of some levodopa-related dyskinesias.
Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Thioridazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Timolol: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Torsemide: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Trandolapril: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Trandolapril; Verapamil: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Tranylcypromine: (Contraindicated) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as tranylcypromine, due to the increased risk of hypertensive crisis. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
Treprostinil: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Triamterene: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Tricyclic antidepressants: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Trifluoperazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Trihexyphenidyl: (Minor) The doses of trihexyphenidyl and levodopa may need to be adjusted when the drugs are given simultaneously. Trihexyphenidyl can potentiate the dopaminergic effects of levodopa.
Trimipramine: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Valsartan: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects. (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Vasodilators: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Verapamil: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Vitamin B Complex Supplements: (Moderate) Monitor for reduced levodopa efficacy during concomitant use of pyridoxine (vitamin B6). Pyridoxine, in doses as low as 10 mg/day, may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine.
Ziprasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Levodopa is the amino acid precursor of dopamine. Unlike dopamine, levodopa crosses the blood-brain barrier, although the method of administration is important for the effectiveness of the drug in disorders of central degeneration of dopaminergic neurons such as Parkinson's disease.
When levodopa is administered orally, it is rapidly decarboxylated to dopamine in the periphery leaving only a small portion of levodopa for diffusion into the central nervous system (CNS). Carbidopa is required in combination with levodopa for optimal oral therapy since carbidopa inhibits the peripheral breakdown of levodopa, making more levodopa available for delivery into the CNS.
Levodopa oral inhalation diffuses directly into the CNS where it is converted to dopamine. Disease progression is associated with 'off' episodes, which occur between routine doses of carbidopa; levodopa when the medication benefits wear off and motor symptoms re-emerge. Intermittent use of levodopa treats these episodes, which are thought to result from loss of ability to store dopamine, and possibly from changes in peripheral levodopa pharmacokinetics or postsynaptic dopamine functioning.
Levodopa is administered orally and by oral inhalation. When levodopa is administered orally, it is rapidly decarboxylated in extracerebral tissues to dopamine, leaving only a small portion of a dose to be transported unchanged into the central nervous system. The plasma half-life of oral levodopa is about 50 minutes. When levodopa is administered with carbidopa, the half-life is increased to 1.5 hours. The half-life of levodopa following a single orally inhaled dose (84 mg) is 2.3 hours. The two major metabolic pathways are decarboxylation by dopa decarboxylase and O-methylation by catechol-O-methyltransferase (COMT). Levodopa is excreted in the urine primarily as metabolites, including dopamine and homovanillic acid (HVA). Carbidopa reduces the amount of levodopa required for a given response by about 75% and decreases plasma and urinary dopamine and HVA.
Affected Cytochrome P450 isoenzymes and drug transporters: None
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration, amino acid transport mechanisms carry levodopa across the membrane of the gastrointestinal tract. Levodopa competes with certain amino acids for transport across the gut wall; therefore, the absorption of levodopa may be impaired in those on a high protein diet. Any food (i.e., high fat or high protein) or drug that delays gastric emptying may decrease the absorption of levodopa. Iron salts or multivitamins containing iron salts can form chelates with levodopa and reduce the bioavailability of levodopa.
Inhalation Route
Following oral inhalation of one 84-mg dose of levodopa, the median time to maximum plasma concentrations of levodopa is about 0.5 hours (range: 0.17 to 2 hours). In fasting healthy volunteers, the bioavailability of levodopa is about 70% relative to immediate-release oral levodopa tablets. The dose-normalized maximum concentration from orally inhaled levodopa is about 50% of that following immediate-release oral tablets.
-Special Populations
Hepatic Impairment
Levodopa has not been evaluated in patients with hepatic impairment.
Renal Impairment
Levodopa has not been evaluated in patients with renal impairment.
Pediatrics
Safety and efficacy of levodopa have not been established in pediatric patients; pharmacokinetic data in this population are not available.
Geriatric
Clinical studies specifically designed to evaluate the kinetics of orally inhaled levodopa in the elderly were not conducted. There are no specific dosing recommendations for oral levodopa based upon age since the drug is titrated to tolerability and clinical effect.
Gender Differences
After administration of a single dose (84 mg) of orally inhaled levodopa, the body-weight adjusted maximum concentration and AUC were similar between men and women; therefore, no dosage adjustment of orally inhaled levodopa is required based upon gender. In a separate study of an oral carbidopa; levodopa formulation, females had higher levodopa peak concentrations (approximately 23% to 33%) and systemic exposure (approximately 33% to 37%) than males while the median time to peak concentration and terminal half-life were comparable between males and females.
Other
Smoking
After administration of a single dose (84 mg) of orally inhaled levodopa in the presence of carbidopa, levodopa exposure in smokers and non-smokers was similar; therefore, no dosage adjustment of orally inhaled levodopa is required based upon smoking status.