ok INBRIJA 84 mg, 49% (n=56) were 65years of age and older and 51% (n=58) were under 65 years of age. Of these patients, thefollowing age-related differences in adverse reactions were reported in patients 65 years of ageand older vs. in patients under 65 years of age, respectively: cough 25% vs. 5%; upperrespiratory tract infection 11% vs. 2%; nausea 7% vs. 3%; vomiting 4% vs. 2%; pain in theextremities 4% vs. 0%; and discolored nasal discharge 4% vs. 0%.
10 OVERDOSAGE
Based on the limited available information, the acute symptoms of carbidopa/levodopaoverdosage can be expected to arise from dopaminergic overstimulation. Using more than onedose (84 mg) to treat the same OFF period may result in CNS disturbances, with an increasingrisk for cardiovascular disturbance (e.g., hypotension, tachycardia) and increased risk for new orworsening psychiatric problems at higher doses.
Reports of rhabdomyolysis and transient renal insufficiency suggest that levodopa overdosagemay give rise to systemic complications.
Monitor patients and provide supportive care. Patients should receive electrocardiographicmonitoring for the development of arrhythmias; if needed, appropriate antiarrhythmic therapyshould be given. The possibility that the patient may have taken other drugs, increasing the riskof drug interactions (especially catechol-structured drugs) should be taken into consideration.
11 DESCRIPTION
INBRIJA consists of a dry powder formulation of levodopa for oral inhalation with the INBRIJAinhaler. The inhalation powder is packaged in white hypromellose capsules.
Each capsule contains a spray-dried powder of 42 mg levodopa active ingredient with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and sodium chloride.
The active component of INBRIJA is levodopa, an aromatic amino acid. Its chemical name is(2S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid and its structural formula is:Levodopa has a molecular weight of 197.19 g/mol and molecular formula C9H11NO4. Levodopais a white to slightly off-white powder and is readily soluble in formic acid, slightly soluble inwater, and practically insoluble in ethanol and diethyl ether; it dissolves in dilute hydrochloric
acid.
The INBRIJA inhaler is a plastic device with a blue body, blue cap, and white mouthpiece usedfor inhaling INBRIJA powder.
The INBRIJA inhaler is breath-actuated by the patient. Under standardized in vitro testingconditions, the INBRIJA inhaler delivered 36.1 mg of levodopa (emitted dose) for the 42 mgcapsule from the mouthpiece. No significant difference in emitted dose was observed whenvarying the flow rate and volume from 20 liters per minute/1L up to 90 liters per minute/2L.
Peak inspiratory flow rates (PIFR) achievable through the INBRIJA inhaler were eva luated in 24adult patients with mild to moderate Parkinson’s disease. The mean PIFR was 64 L/min (range39–98 L/min) for patients in the ON state and 57 L/min (range 29–98 L/min) in the OFF state.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Levodopa, the metabolic precursor of dopamine, crosses the blood-brain barrier and presumablyis converted to dopamine in the brain. This is thought to be the mechanism whereby levodoparelieves symptoms of Parkinson’s disease.
12.2 Pharmacodynamics
There are no relevant data on the pharmacodynamic effects of INBRIJA.
12.3 Pharmacokinetics
In the presence of carbidopa, the pharmacokinetics of levodopa are dose-proportio |
