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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Inhalation:
Inbrija: 42 mg per inhalation
No
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.
Parkinson disease: Intermittent treatment of OFF episodes in patients with Parkinson disease treated with carbidopa/levodopa
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Respiratory: Cough (15% to 60%)
1% to 10%:
Cardiovascular: Chest discomfort (2%), decreased blood pressure (≤2%), orthostatic hypotension (≤2%)
Dermatologic: Excoriation of skin (2%)
Gastrointestinal: Nausea (5%), vomiting (3%)
Hematologic & oncologic: Decreased red blood cells (2%)
Hepatic: Increased serum bilirubin (2%)
Nervous system: Falling (3%), hallucination (<2%), headache (2%), insomnia (2%)
Neuromuscular & skeletal: Dyskinesia (4%), limb pain (2%)
Respiratory: Bronchitis (≤2%), discoloration of sputum (5%), nasopharyngitis (3%), oropharyngeal pain (2%), pneumonia (≤2%), rhinorrhea (discoloration: 2%), upper respiratory tract infection (6%)
Miscellaneous: Laceration (2%)
Frequency not defined:
Endocrine & metabolic: Abnormal BUN, increased lactate dehydrogenase
Hematologic & oncologic: Hemolytic anemia, positive direct Coombs test
Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Nervous system: Abnormal behavior, abnormality in thinking, drowsiness, impulse control disorder, sudden onset of sleep
Postmarketing: Nervous system: Choking sensation
Concurrent use or within 14 days of nonselective MAOIs (eg, phenelzine, tranylcypromine) use
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.
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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Injection): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Amisulpride (Oral): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). Amisulpride (Oral) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Antipsychotic Agents (First Generation [Typical]): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Biperiden: May enhance the adverse/toxic effect of Levodopa-Containing Products. Specifically, the risk of choreic movements or dyskinesias may be increased. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brivudine [INT]: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Specifically, the risk of chorea may be increased. Risk C: Monitor therapy
Bromopride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: May diminish the therapeutic effect of Levodopa-Containing Products. Risk C: Monitor therapy
Glycopyrrolate (Systemic): May decrease the serum concentration of Levodopa-Containing Products. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Isoniazid: May diminish the therapeutic effect of Levodopa-Containing Products. Risk C: Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Kava Kava may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Macimorelin: Levodopa-Containing Products may diminish the diagnostic effect of Macimorelin. Risk X: 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. Risk D: Consider therapy modification
Methotrimeprazine: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Methotrimeprazine. Risk X: Avoid combination
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: 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. Risk X: Avoid combination
Monoamine Oxidase Inhibitors (Type B): Levodopa-Containing Products may enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Type B). Risk C: Monitor therapy
Multivitamins/Fluoride (with ADE): May diminish the therapeutic effect of Levodopa-Containing Products. Management: Concurrent use of a multivitamin and levodopa (without carbidopa) should be avoided. Risk D: Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May diminish the therapeutic effect of Levodopa (Oral Inhalation). Management: Avoid concomitant use of a multivitamin containing pyridoxine (vitamin B6) and levodopa in the absence of a dopa decarboxylase inhibitor (DDI). Use of a DDI (eg, carbidopa) with levodopa largely eliminates the risk of interaction. Risk D: 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. Risk D: Consider therapy modification
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Papaverine: May enhance the hypotensive effect of Levodopa-Containing Products. Papaverine may diminish the therapeutic effect of Levodopa-Containing Products. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: 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. Risk D: Consider therapy modification
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Sapropterin: May enhance the adverse/toxic effect of Levodopa-Containing Products. Risk C: Monitor therapy
Solriamfetol: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk C: Monitor therapy
Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: Avoid combination
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).
Levodopa is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Hepatic function test, BUN, CBC and direct antiglobulin (as clinically indicated); intraocular pressure (as clinically indicated in patients with glaucoma)
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).
Distribution: Vz/F: 168 L
Metabolism: Extensively metabolized by decarboxylation and O-methylation
Bioavailability: ~70% relative to availability from immediate release formulation
Half-life elimination: 2.3 hours
Time to peak: Median 0.5 hours (range: 0.17 to 2 hours)
Capsules (Inbrija Inhalation)
42 mg (per each): $20.95
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