Introduction
Inbrija (levodopa inhalation powder) is an innovative Parkinson's disease medication developed by Acorda Therapeutics. It represents the first and only FDA-approved inhaled levodopa therapy for intermittent treatment of "off" episodes in patients with Parkinson's disease treated with carbidopa/levodopa. This formulation provides a novel delivery system that offers rapid onset of action for patients experiencing unpredictable motor fluctuations.
Mechanism of Action
Inbrija contains levodopa, which is converted to dopamine in the brain through decarboxylation by aromatic L-amino acid decarboxylase. Dopamine replacement addresses the fundamental dopamine deficiency in the nigrostriatal pathway that characterizes Parkinson's disease. The inhalation delivery system allows for rapid pulmonary absorption, bypassing first-pass metabolism and providing more predictable plasma concentrations compared to oral levodopa formulations during "off" episodes.
Indications
Inbrija is indicated for the intermittent treatment of "off" episodes in patients with Parkinson's disease currently treated with carbidopa/levodopa. It is specifically designed for use as needed when patients experience the return of Parkinson's symptoms between scheduled doses of their regular carbidopa/levodopa regimen.
Dosage and Administration
- Recommended dose: 84 mg (2 capsules) inhaled as needed for "off" episodes
- Maximum dosage: No more than 2 doses in any 24-hour period, with minimum 2 hours between doses
- Administration: Use only with the Inbrija inhaler device
- Special populations: Not recommended in patients with asthma, COPD, or other chronic lung diseases
- Renal/hepatic impairment: No dosage adjustment recommended
Pharmacokinetics
- Absorption: Rapid pulmonary absorption with peak plasma concentrations achieved within 10-20 minutes
- Distribution: Volume of distribution approximately 57 L; minimal protein binding
- Metabolism: Extensively metabolized peripherally by aromatic L-amino acid decoxylase and catechol-O-methyltransferase
- Elimination: Half-life approximately 1.5-2 hours; primarily excreted in urine as metabolites
- Bioavailability: Approximately 70% relative to oral levodopa/carbidopa
Contraindications
- Hypersensitivity to levodopa or any component of the formulation
- Patients with asthma, COPD, or other chronic lung diseases
- Use with non-selective monoamine oxidase (MAO) inhibitors (concurrent or within 2 weeks)
- Patients with narrow-angle glaucoma
- Patients with suspicious, undiagnosed skin lesions or history of melanoma
Warnings and Precautions
- Fall risk: Dopaminergic therapy may cause orthostatic hypotension and syncope
- Hallucinations/psychosis: May occur with dopaminergic medications
- Impulse control disorders: Pathological gambling, hypersexuality, binge eating
- Dyskinesia: May exacerbate or cause new dyskinesias
- Withdrawal symptoms: Neuroleptic malignant syndrome-like symptoms with rapid dose reduction
- Pulmonary risk: Contraindicated in patients with chronic lung diseases; monitor for respiratory symptoms
- Cardiovascular effects: May cause orthostatic hypotension, hypertension, and arrhythmias
Drug Interactions
- MAO inhibitors: Contraindicated with non-selective MAO inhibitors
- Dopamine D2 receptor antagonists: May diminish effectiveness (phenothiazines, butyrophenones)
- Iron salts: May reduce bioavailability of levodopa
- Antihypertensives: May potentiate hypotensive effects
- Protein-rich meals: May interfere with absorption and effectiveness
Adverse Effects
Most common (≥5% incidence):- Cough (15%)
- Upper respiratory tract infection (6%)
- Nausea (5%)
- Discolored sputum (5%)
- Hallucinations and psychosis
- Impulse control disorders
- Orthostatic hypotension
- Dyskinesia
- Bronchospasm and respiratory complications
- Withdrawal emergent hyperpyrexia and confusion
Monitoring Parameters
- Efficacy: "On"/"Off" time diaries, Unified Parkinson's Disease Rating Scale (UPDRS)
- Safety: Blood pressure (standing and supine), respiratory function
- Psychiatric: Regular assessment for hallucinations, psychosis, impulse control disorders
- Neurological: Monitoring for dyskinesias and motor fluctuations
- Pulmonary: Respiratory symptoms, especially in patients with risk factors
- Dermatologic: Regular skin examinations for melanoma
Patient Education
- Use only during "off" episodes, not as replacement for regular carbidopa/levodopa therapy
- Maximum of 2 doses per day, separated by at least 2 hours
- Proper inhaler technique training is essential
- Report any respiratory symptoms (wheezing, shortness of breath) immediately
- Be aware of potential for dizziness and orthostatic hypotension
- Report any new or increased impulsive behaviors
- Regular skin examinations recommended
- Do not use with non-selective MAO inhibitors
- Storage: Keep capsules in blister pack until use; protect from moisture
References
1. FDA prescribing information: Inbrija (levodopa inhalation powder). 2018. 2. LeWitt PA, et al. Inhaled levodopa (CVT-301) for early morning off periods in Parkinson's disease. Mov Disord. 2019;34(6):976-984. 3. Grosset DG, et al. Inhaled levodopa in Parkinson's disease patients with OFF periods: A randomized 12-month study. Parkinsonism Relat Disord. 2020;81:57-64. 4. Hauser RA, et al. Efficacy and safety of inhaled levodopa (CVT-301) for the treatment of OFF periods in patients with Parkinson's disease. Lancet Neurol. 2019;18(2):145-154. 5. Olanow CW, et al. Continuous dopaminergic stimulation in the treatment of Parkinson's disease. J Neural Transm. 2021;128(7):977-987.