Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Inhalation:
Inbrija: 42 mg per inhalation
Pharmacology
Mechanism of Action
Parkinson disease symptoms are due to a lack of striatal dopamine; levodopa circulates in the plasma to the blood-brain-barrier (BBB), where it crosses, to be converted by striatal enzymes to dopamine (Lloyd 1975).
Pharmacokinetics/Pharmacodynamics
Distribution
Vz/F: 168 L
Metabolism
Extensively metabolized by decarboxylation and O-methylation
Time to Peak
Median 0.5 hours (range: 0.17 to 2 hours)
Half-Life Elimination
2.3 hours
Use: Labeled Indications
Parkinson disease: Intermittent treatment of OFF episodes in patients with Parkinson disease treated with carbidopa/levodopa
Contraindications
Concurrent use or within 14 days of nonselective MAOIs (eg, phenelzine, tranylcypromine) use
Dosage and Administration
Dosing: Adult
Parkinson disease (as an adjunct to carbidopa/levodopa): Oral inhalation: 84 mg up to 5 times daily as needed when symptoms of an OFF period return; maximum: 84 mg/dose and 420 mg/day
Dosing: Geriatric
Refer to adult dosing.
Administration
Oral inhalation: Capsules are for oral inhalation only and should only be used with the Inbrija inhaler. Use 1 capsule per inhalation; discard used capsules. Do not swallow.
Storage
Store between 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture. Store capsules in blister packaging and only remove immediately before use.
Drug Interactions
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amisulpride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride. Avoid combination
Antipsychotic Agents (First Generation [Typical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson agents. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Consider therapy modification
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Biperiden: May enhance the adverse/toxic effect of Levodopa-Containing Products. Specifically, the risk of choreic movements or dyskinesias may be increased. Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bromopride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy
Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination
BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Fosphenytoin-Phenytoin: May diminish the therapeutic effect of Levodopa-Containing Products. Monitor therapy
Glycopyrrolate (Systemic): May decrease the serum concentration of Levodopa-Containing Products. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Isoniazid: May diminish the therapeutic effect of Levodopa-Containing Products. Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Macimorelin: Levodopa-Containing Products may diminish the diagnostic effect of Macimorelin. Avoid combination
Methionine: May diminish the therapeutic effect of Levodopa-Containing Products. Management: Avoid large daily doses of methionine in patients receiving levodopa (clinical studies showing interaction used 4.5 g methionine daily). More typical doses of methionine (eg, 500 mg) may not cause a problem. Consider therapy modification
Methylphenidate: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Monoamine Oxidase Inhibitors: Levodopa-Containing Products may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Exceptions: Rasagiline; Safinamide; Selegiline. Avoid combination
Monoamine Oxidase Inhibitors (Type B): Levodopa-Containing Products may enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Type B). Monitor therapy
Multivitamins/Fluoride (with ADE): May diminish the therapeutic effect of Levodopa-Containing Products. Management: Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May diminish the therapeutic effect of Levodopa (Oral Inhalation). Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May diminish the therapeutic effect of Levodopa-Containing Products. Management: Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Consider therapy modification
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Papaverine: May enhance the hypotensive effect of Levodopa-Containing Products. Papaverine may diminish the therapeutic effect of Levodopa-Containing Products. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pyridoxine: May diminish the therapeutic effect of Levodopa-Containing Products. Management: The concomitant use of pyridoxine and levodopa (in the absence of a dopa decarboxylase inhibitor (DDI)) should be avoided. Use of a DDI (eg, carbidopa) with levodopa will essentially eliminate the risk of this interaction. Consider therapy modification
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Sapropterin: May enhance the adverse/toxic effect of Levodopa-Containing Products. Monitor therapy
Solriamfetol: Anti-Parkinson Agents (Dopamine Agonist) may enhance the hypertensive effect of Solriamfetol. Monitor therapy
Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination
Test Interactions
False diagnosis for pheochromocytoma (rare) based on plasma and urine levels of catecholamines
Adverse Reactions
>10%: Respiratory: Cough (15% to 60%)
1% to 10%:
Cardiovascular: Chest discomfort (2%), decreased blood pressure (≤2%), orthostatic hypotension (≤2%)
Central nervous system: Falling (3%), headache (2%), insomnia (2%), hallucination (<2%)
Dermatologic: Excoriation of skin (2%)
Gastrointestinal: Nausea (5%), vomiting (3%)
Hematologic & oncologic: Decreased red blood cells (2%)
Hepatic: Increased serum bilirubin (2%)
Neuromuscular & skeletal: Dyskinesia (4%), limb pain (2%)
Respiratory: Upper respiratory tract infection (6%), discoloration of sputum (5%), nasopharyngitis (3%), oropharyngeal pain (2%), rhinorrhea (discoloration: 2%), bronchitis (≤2%), pneumonia (≤2%)
Miscellaneous: Laceration (2%)
<1%, postmarketing, and/or case reports: Abnormal behavior, abnormality in thinking, drowsiness, hemolytic anemia, impulse control disorder, increased blood urea nitrogen, increased lactate dehydrogenase, increased liver enzymes, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, positive direct Coombs test, sudden onset of sleep
Warnings/Precautions
Concerns related to adverse effects:
- Abnormal thinking/behavioral changes: Abnormal thinking and behavior changes have been reported and may include aggressive behavior, agitation, confusion, delirium, delusions, disorientation, paranoid ideation, and psychotic-like behavior.
- CNS depression: May cause CNS depression (eg, somnolence and falling asleep while engaged in activities of daily living), which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Symptom onset may occur well after initiation of treatment and without any warning signs; some events have occurred more than 1 year after start of therapy. Prior to treatment initiation, evaluate for factors that may increase these risks such as concomitant sedating medications and the presence of sleep disorders. Monitor for drowsiness or sleepiness. If significant daytime sleepiness or episodes of falling asleep during activities that require active participation occurs (eg, driving, conversations, eating), discontinue the medication. There is insufficient information to suggest that dose reductions will eliminate these symptoms.
- Dyskinesias: May cause or exacerbate dyskinesias; may require dosage reduction or discontinuation.
- Hallucinations: Hallucinations may occur and be accompanied by confusion, and to a lesser extent, sleep disorder and excessive dreaming; may require dose reduction.
- Impulse control disorders: Dopamine agonists used for Parkinson disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, increased sexual urges, intense urges to spend money, binge or compulsive eating, and/or other intense urges. Dose reduction or discontinuation of therapy have been reported to reverse these behaviors in some, but not all cases.
- Neuroleptic malignant syndrome: A symptom complex resembling neuroleptic malignant syndrome (NMS) has been reported in association with rapid dose reduction or abrupt withdrawal. Identification of more severe NMS-like reactions (eg, altered consciousness, hyperthermia, involuntary movements, muscle rigidity, autonomic instability, mental status changes) can be complex; monitor patients closely for this reaction and when the dosage of levodopa is reduced abruptly or discontinued. Discontinue treatment immediately if signs/symptoms arise.
Disease-related concerns:
- Glaucoma: May cause increased IOP in patients with glaucoma; monitor IOP.
- Psychotic disorders: May exacerbate psychosis; avoid use in patients with a major psychotic disorder.
- Respiratory disease: May cause bronchospasm; use is not recommended in patients with respiratory disease.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Body fluid discoloration: Urine, saliva, or sweat may appear dark in color (red, brown, black) during therapy.
- Discontinuation of therapy: Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on abrupt withdrawal, rapid dose reduction, significant dosage reduction after long-term use, or changes in dopaminergic therapy. Avoid sudden discontinuation or rapid dose reduction; taper dose to reduce the risk of hyperpyrexia and confusion.
Monitoring Parameters
Hepatic function test, BUN, CBC and direct antiglobulin (as clinically indicated); intraocular pressure (as clinically indicated in patients with glaucoma)
Pregnancy
Pregnancy Considerations
Levodopa crosses the placenta following administration of oral tablets (Seier 2017).
Although data related to the use of levodopa in pregnancy is limited, information following maternal use of the oral tablets is available (Seier 2017).
Patient Education
What is this drug used for?
- It is used to treat "off" episodes (when a dose wears off) in people with Parkinsons disease.
Frequently reported side effects of this drug
- Cough
- Sputum discoloration
- Common cold symptoms
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Trouble breathing
- Behavioral changes
- Sensing things that seem real but are not
- Confusion
- Agitation
- Restlessness
- Trouble sleeping
- Nightmares
- Uncontrollable urges
- Abnormal movements
- Dizziness
- Passing out
- Severe nausea
- Vomiting
- Sweating a lot
- Vision changes
- Eye pain
- Severe fatigue
- Narcolepsy
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
