INBRIJA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INBRIJA (INBRIJA).
INBRIJA (levodopa inhalation powder) is a combination of levodopa, an aromatic amino acid, and a prodrug of dopamine, which is decarboxylated to dopamine in the brain, thereby restoring dopamine levels in the striatum and improving motor function in Parkinson disease.
| Metabolism | Levodopa is extensively metabolized by aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyltransferase (COMT); peripheral decarboxylation to dopamine is inhibited by concomitant carbidopa administration. The inhalation route bypasses first-pass metabolism. |
| Excretion | Primarily renal excretion of metabolites and unchanged drug. Approximately 80% of a dose is recovered in urine as levodopa metabolites (mainly 3-O-methyldopa and vanilpyruvic acid) and <10% as unchanged levodopa. Fecal excretion accounts for <5%. |
| Half-life | 0.75–1.5 hours (terminal elimination half-life of levodopa). Short half-life necessitates frequent dosing or continuous dopaminergic stimulation strategies. |
| Protein binding | 10–30% (primarily bound to albumin; low binding limits distribution changes due to protein displacement). |
| Volume of Distribution | 0.5–1.0 L/kg (levodopa is widely distributed into tissues, including crossing the blood-brain barrier). |
| Bioavailability | Inhalation: approximately 55–70% relative to intravenous levodopa (due to pulmonary absorption and first-pass metabolism; interpatient variability notable). |
| Onset of Action | Inhalation: 10–15 minutes (time to measurable plasma levodopa concentrations and clinical improvement in OFF episodes). |
| Duration of Action | 2–3 hours (duration of ON time following a single inhaled dose; clinical effect correlates with plasma levodopa concentrations above therapeutic threshold). |
Inhaled levodopa powder, 84 mg (two 42 mg capsules) inhaled orally via the INBRIJA inhaler as needed for OFF episodes, up to 5 times per day. Maximum daily dose: 420 mg (5 doses).
| Dosage form | POWDER |
| Renal impairment | No specific dose adjustment recommended in renal impairment; limited data in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No specific dose adjustment recommended for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment required; elderly patients may have higher risk of levodopa-related adverse effects (e.g., hallucinations, dyskinesias) and should be monitored closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INBRIJA (INBRIJA).
| Breastfeeding | Levodopa is excreted in human breast milk; M/P ratio not specifically reported for INBRIJA. Levodopa may suppress prolactin secretion, potentially reducing milk production. Caution is advised as there is a theoretical risk of adverse effects in the nursing infant, including dyskinesias and developmental effects. Consider alternative therapies or temporarily discontinue breastfeeding during treatment. |
| Teratogenic Risk | INBRIJA (levodopa inhalation powder) is classified as FDA Pregnancy Category C. No adequate well-controlled studies in pregnant women. Levodopa crosses the placenta. In animal studies, levodopa caused fetal malformations (skeletal and cardiovascular) at doses similar to human. First trimester exposure may increase risk of congenital anomalies. Second and third trimester use may be associated with fetal distress, altered fetal movements, and risk of premature labor. Use only if potential benefit justifies risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with nonselective monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuation","Narrow-angle glaucoma","History of hypersensitivity to levodopa or any component of the formulation"]
| Precautions | ["May cause somnolence and sudden sleep onset during activities of daily living","May cause hallucinations and psychosis","May cause dyskinesias","May cause impulse control disorders (e.g., compulsive behaviors)","May cause hypotension, especially orthostatic hypotension","May precipitate or worsen glaucoma","May cause bronchospasm in patients with pulmonary disease","Not for use in patients with asthma or COPD"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal motor function, blood pressure, and adverse effects (e.g., dyskinesias, orthostatic hypotension). Perform fetal ultrasound for anomaly detection if first-trimester exposure. Monitor fetal heart rate and uterine activity during labor. Assess for fetal distress (e.g., abnormal fetal heart rate tracings) and preterm labor. Postnatal neonatal monitoring for adverse effects such as rigidity or altered feeding. |
| Fertility Effects | Levodopa therapy has been associated with alterations in hormonal profiles, including hyperprolactinemia and galactorrhea in some patients, which may impact fertility. In men, levodopa may cause decreased libido and impotence. Levodopa-containing products have been reported to potentially influence menstrual cycles and ovulation. Clinical significance uncertain; consider individual assessment. |