Inbrija

6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and elsewhere in the labeling: Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.1) ] Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions (5.2) ] Hallucinations/Psychosis [see Warnings and Precautions (5.3) ] Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.4) ] Dyskinesia [see Warnings and Precautions (5.5) ] Bronchospasm in Patients with Lung Disease [see Warnings and Precautions (5.6) ] Glaucoma [see Warnings and Precautions (5.7) ] The most common adverse reactions (incidence ≥ 5% and higher than placebo) were cough, nausea, upper respiratory tract infection, and sputum discolored ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acorda Therapeutics, Inc. at 1-800-367-5109 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Study 1 Table 1 lists the adverse reactions that occurred in at least 2% of patients with Parkinson's disease who were treated with INBRIJA 84 mg and higher than placebo for OFF periods in Study 1 [see Clinical Studies (14) ]. Study 1 was a double-blind, placebo-controlled study, in which 114 patients received INBRIJA 84 mg (two 42 mg capsules) for an average of 2 doses per day, to a maximum of 5 times a day, and 112 patients received placebo. INBRIJA-treated patients were 45-82 years of age (mean 63.5 years of age) and were predominantly male (72%) and white (94%). All patients were also treated with oral carbidopa/levodopa. The most common adverse reactions (≥ 5% and higher than placebo) in Study 1 were cough, nausea, upper respiratory tract infection, and sputum discolored. Table 1: Adverse Reactions at an Incidence ≥2% and More Frequent with INBRIJA than with Placebo in Study 1 Adverse Reactions INBRIJA 84 mg N=114 % Placebo N=112 % Respiratory, thoracic and mediastinal disorders Cough 15 2 Sputum discolored 5 0 Nasal discharge discoloration 2 0 Oropharyngeal pain 2 0 Gastrointestinal disorders Nausea 5 3 Vomiting 3 0 Infections and infestations Upper respiratory tract infection 6 3 Nasopharyngitis 3 2 Bronchitis/pneumonia 2 0 Nervous system disorders Dyskinesia 4 1 Headache 2 0 Injury, poisoning and procedural complications Fall 3 2 Laceration 2 0 Skin abrasion 2 0 General disorders and administration site conditions Chest discomfort 2 0 Investigations Blood bilirubin increased 2 0 Red blood cell count decreased 2 0 Musculoskeletal and connective tissue disorders Pain in extremity 2 1 Psychiatric disorders Insomnia 2 1 Vascular disorders Orthostatic hypotension/blood pressure decreased 2 0 Adverse Reactions Leading to Discontinuation in Study 1 In Study 1, 6 of 114 patients (5%) in the INBRIJA 84 mg group and 3 of 112 patients (3%) in the placebo group discontinued because of adverse reactions. The most common of these adverse reactions was cough, which lead to discontinuation in 2% of patients in the INBRIJA 84 mg group and none in the placebo group. 6.2 Postmarketing Experience The following adverse reaction has been identified during post approval use of INBRIJA. Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: sensation of choking immediately following administration.

4 CONTRAINDICATIONS INBRIJA is contraindicated in patients currently taking a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine) or who have recently (within 2 weeks) taken a nonselective MAO inhibitor. Hypertension can occur if these drugs are used concurrently [see Drug Interactions (7.1) ]. INBRIJA is contraindicated in patients currently taking a nonselective monoamine oxidase (MAO) inhibitor or who have recently (within 2 weeks) taken a nonselective MAO inhibitor ( 4 , 7.1 )

11 DESCRIPTION INBRIJA consists of a dry powder formulation of levodopa for oral inhalation with the INBRIJA inhaler. 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 C 9 H 11 NO 4 . Levodopa is a white to slightly off-white powder and is readily soluble in formic acid, slightly soluble in water, 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 used for inhaling INBRIJA powder. The INBRIJA inhaler is breath-actuated by the patient. Under standardized in vitro testing conditions, the INBRIJA inhaler delivered 36.1 mg of levodopa (emitted dose) for the 42 mg capsule from the mouthpiece. No significant difference in emitted dose was observed when varying 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 evaluated in 24 adult patients with mild to moderate Parkinson's disease. The mean PIFR was 64 L/min (range 39–98 L/min) for patients in the ON state and 57 L/min (range 29–98 L/min) in the OFF state. Chemical Structure

2 DOSAGE AND ADMINISTRATION INBRIJA capsules are for oral inhalation only and should be used only with the INBRIJA inhaler. For oral inhalation only. DO NOT swallow INBRIJA capsules. Only use INBRIJA capsules with the INBRIJA inhaler ( 2.1 ) Inhale the contents of two INBRIJA capsules (84 mg) as needed for OFF symptoms, up to 5 times daily ( 2.2 ) The maximum dose per OFF period is 84 mg, and the maximum recommended daily dosage of INBRIJA is 420 mg ( 2.2 ) 2.1 Important Administration Instructions INBRIJA capsules are for oral inhalation only and should be used only with the INBRIJA inhaler. INBRIJA capsules must not be swallowed as the intended effect will not be obtained. INBRIJA capsules should be stored in their blister package and only removed immediately before use [see How Supplied/Storage and Handling (16.2) ] . 2.2 Recommended Dosage INBRIJA should be taken when symptoms of an OFF period start to return. The recommended dosage of INBRIJA is oral inhalation of the contents of two 42 mg capsules (84 mg) as needed, up to 5 times a day. The maximum dose per OFF period is 84 mg, and the maximum daily dosage is 420 mg. INBRIJA has been shown to be effective only in combination with carbidopa/levodopa [see Indications and Usage (1) ].

1 INDICATIONS AND USAGE INBRIJA is indicated for the intermittent treatment of OFF episodes in patients with Parkinson's disease treated with carbidopa/levodopa. INBRIJA is an aromatic amino acid indicated for the intermittent treatment of OFF episodes in patients with Parkinson's disease treated with carbidopa/levodopa ( 1 )

10 OVERDOSAGE Based on the limited available information, the acute symptoms of carbidopa/levodopa overdosage can be expected to arise from dopaminergic overstimulation. Using more than one dose (84 mg) to treat the same OFF period may result in CNS disturbances, with an increasing risk for cardiovascular disturbance (e.g., hypotension, tachycardia) and increased risk for new or worsening psychiatric problems at higher doses. Reports of rhabdomyolysis and transient renal insufficiency suggest that levodopa overdosage may give rise to systemic complications. Monitor patients and provide supportive care. Patients should receive electrocardiographic monitoring for the development of arrhythmias; if needed, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs, increasing the risk of drug interactions (especially catechol-structured drugs) should be taken into consideration.

7 DRUG INTERACTIONS Monitor patients on MAO-B inhibitors for orthostatic hypotension ( 7.1 ) Dopamine D2 antagonists, isoniazid, and iron salts: May reduce the effectiveness of INBRIJA ( 7.2 , 7.3 ) 7.1 Monoamine Oxidase (MAO) Inhibitors The use of nonselective MAO inhibitors with INBRIJA is contraindicated [see Contraindications (4) ] . Discontinue use of any nonselective MAO inhibitors at least two weeks prior to initiating INBRIJA. The use of selective MAO-B inhibitors with INBRIJA may be associated with orthostatic hypotension. Monitor patients who are taking these drugs concurrently. 7.2 Dopamine D2 Receptor Antagonists and Isoniazid Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide) and isoniazid may reduce the effectiveness of levodopa. Monitor patients for worsening Parkinson's symptoms. 7.3 Iron Salts Iron salts or multivitamins containing iron salts can form chelates with levodopa and consequently reduce the bioavailability of levodopa.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Levodopa, the metabolic precursor of dopamine, crosses the blood-brain barrier and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves 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-proportional in healthy subjects taking up to 84 mg of INBRIJA. In the presence of carbidopa, the terminal elimination half-life (t 1/2 ) of levodopa following a single administration of INBRIJA 84 mg was 2.3 hours. Absorption After a single dose of INBRIJA 84 mg (two 42 mg capsules), the median T max for plasma levodopa was approximately 0.5 hours (range 0.17–2.00 hours). In fasted healthy volunteers the bioavailability of levodopa from INBRIJA was approximately 70% relative to immediate-release oral levodopa tablets. The dose-normalized C max of levodopa from INBRIJA is approximately 50% of that following immediate-release oral tablets. Distribution Apparent volume of distribution (Vz/F) was 168 L for INBRIJA 84 mg. Metabolism and Elimination Levodopa is extensively metabolized, and the two major metabolic pathways are decarboxylation by dopa decarboxylase and O-methylation by catechol-O-methyltransferase (COMT). Specific Populations Geriatric Population Clinical studies specifically designed to analyze the effects of age on the pharmacokinetics of levodopa were not conducted with INBRIJA. Male and Female Patients After a single dose administration of INBRIJA 84 mg, the body-weight adjusted C max and AUC 0-24 were similar between women and men. No adjustment in dosage is required based on sex. Hepatic/ Renal Impairment INBRIJA has not been studied in patients with hepatic or renal impairment. Smokers In a pharmacokinetic study following a single administration of INBRIJA 84 mg dose in the presence of carbidopa, levodopa exposure (AUC and C max ) in smokers (N=25) and non-smokers (N=31) were similar.

12.1 Mechanism of Action Levodopa, the metabolic precursor of dopamine, crosses the blood-brain barrier and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves 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-proportional in healthy subjects taking up to 84 mg of INBRIJA. In the presence of carbidopa, the terminal elimination half-life (t 1/2 ) of levodopa following a single administration of INBRIJA 84 mg was 2.3 hours. Absorption After a single dose of INBRIJA 84 mg (two 42 mg capsules), the median T max for plasma levodopa was approximately 0.5 hours (range 0.17–2.00 hours). In fasted healthy volunteers the bioavailability of levodopa from INBRIJA was approximately 70% relative to immediate-release oral levodopa tablets. The dose-normalized C max of levodopa from INBRIJA is approximately 50% of that following immediate-release oral tablets. Distribution Apparent volume of distribution (Vz/F) was 168 L for INBRIJA 84 mg. Metabolism and Elimination Levodopa is extensively metabolized, and the two major metabolic pathways are decarboxylation by dopa decarboxylase and O-methylation by catechol-O-methyltransferase (COMT). Specific Populations Geriatric Population Clinical studies specifically designed to analyze the effects of age on the pharmacokinetics of levodopa were not conducted with INBRIJA. Male and Female Patients After a single dose administration of INBRIJA 84 mg, the body-weight adjusted C max and AUC 0-24 were similar between women and men. No adjustment in dosage is required based on sex. Hepatic/ Renal Impairment INBRIJA has not been studied in patients with hepatic or renal impairment. Smokers In a pharmacokinetic study following a single administration of INBRIJA 84 mg dose in the presence of carbidopa, levodopa exposure (AUC and C max ) in smokers (N=25) and non-smokers (N=31) were similar.

20230119

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3 DOSAGE FORMS AND STRENGTHS INBRIJA (levodopa inhalation powder) consists of INBRIJA capsules and the INBRIJA inhaler. INBRIJA capsules contain 42 mg dry powder formulation of levodopa in a white capsule with two black color bands, and "A42" printed on one side. Inhalation powder: INBRIJA capsules contain 42 mg levodopa for use with the INBRIJA inhaler ( 3 )

Inbrija levodopa DIPALMITOYLPHOSPHATIDYLCHOLINE, DL- SODIUM CHLORIDE LEVODOPA LEVODOPA A42

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In rats, oral administration of carbidopa/levodopa for two years resulted in no evidence of carcinogenicity. Mutagenesis Studies to assess the potential mutagenic or clastogenic effects of levodopa have not been conducted. Impairment of Fertility In reproduction studies in rats, oral administration of carbidopa/levodopa resulted in no effects on fertility.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In rats, oral administration of carbidopa/levodopa for two years resulted in no evidence of carcinogenicity. Mutagenesis Studies to assess the potential mutagenic or clastogenic effects of levodopa have not been conducted. Impairment of Fertility In reproduction studies in rats, oral administration of carbidopa/levodopa resulted in no effects on fertility.

NDA209184

Inbrija

levodopa

10144-342

HUMAN PRESCRIPTION DRUG

RESPIRATORY (INHALATION)

PRINCIPAL DISPLAY PANEL - 42 mg Capsule Blister Pack Carton NDC 10144-342-60 Rx ONLY Inbrija® (levodopa inhalation powder) For Oral Inhalation Only 42 mg capsules CONTENTS: 60 capsules (15 blister strips of 4 capsules each) 1 inhaler Prescribing Information Patient Information Instructions for Use Do not swallow Inbrija® capsules Inbrija® capsules are for use with Inbrija® inhaler only. 60-count carton

Marketed by: Acorda Therapeutics, Inc. Pearl River, NY 10965 USA 2212342MFPI-0

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Instructions for Administering INBRIJA It is important for patients to understand how to correctly administer INBRIJA. It is recommended that patients be instructed in the proper administration of INBRIJA prior to use [see Dosage and Administration (2.1) ] . Patients should be counseled to take a dose of INBRIJA when the return of their Parkinson's symptoms (OFF periods) first occur [see Dosage and Administration (2.2) ] . Instruct patients to read the Instructions for Use before using INBRIJA. Remind patients that INBRIJA capsules should only be administered via the INBRIJA inhaler and the INBRIJA inhaler should not be used for administering other medications. Remind patients that the contents of INBRIJA capsules are for oral inhalation only and must not be swallowed. Instruct patients to keep INBRIJA capsules in their sealed blister packaging and to remove each INBRIJA capsule immediately before using [see Dosage and Administration (2.1) ] . Remind patients they need to orally inhale the contents of two capsules to take a full dose. They should not take more than 5 doses of INBRIJA in one day. Instruct patients they should not take more than one dose (2 capsules) per OFF period [see Dosage and Administration (2.2) ] . Lung Disease Ask patients to report whether they develop asthma, COPD, or other chronic lung diseases, since INBRIJA is not recommended in patients with these conditions [see Warnings and Precautions (5.6) ] . Cough/Sensation of Choking Inhalation of INBRIJA can lead to coughing or a sensation of choking at the time of administration [see Warnings and Precautions (5.6) , and Adverse Reactions (6.1 , 6.2) ] . Discoloration of Body Fluids Patients should be advised that dark color may appear in bodily fluids (saliva, sputum, urine, or sweat) when using INBRIJA [see Adverse Reactions (6.1) ] . Falling Asleep Advise patients that certain side effects such as sleepiness and dizziness may affect some patients' ability to drive and operate machinery safely. Advise patients of the possible additive sedative effects when taking other CNS depressants in combination with INBRIJA [see Warnings and Precautions (5.1) ] . Impulse Control Disorder Inform patients of the potential for experiencing Impulse Control Disorder: patients may experience intense urges to gamble, increased sexual urges, and other intense urges and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone, that are generally used for the treatment of Parkinson's disease [see Warnings and Precautions (5.4) ] . Dyskinesia Instruct patients to notify their healthcare provider if abnormal involuntary movements appear or get worse during treatment with INBRIJA [see Warnings and Precautions (5.5) ] . Hypotension and Syncope Advise patients that while they are on levodopa therapy, including INBRIJA, that they may develop orthostatic hypotension with or without symptoms such as dizziness, nausea, syncope, and sweating [see Adverse Reactions (6.1) ] . Advise patients to rise slowly after sitting or lying down, especially if they have been doing so for a prolonged period. Iron Salts Inform patients that iron salts or multivitamins containing iron salts can reduce the bioavailability of levodopa [see Drug Interactions (7.3) ]. Pregnancy and Breastfeeding Instruct patients to notify their physicians if they become pregnant or intend to become pregnant during therapy [see Use in Specific Populations (8.1) ] . Instruct patients to notify their physicians if they intend to breastfeed or are breastfeeding an infant [see Use in Specific Populations (8.2) ] .

INSTRUCTIONS FOR USE INBRIJA ® (in-BRIH-jah) (levodopa inhalation powder) For Oral Inhalation Only Read and follow these instructions before you start using INBRIJA and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment. Important Information about using INBRIJA Do not swallow INBRIJA capsules INBRIJA capsules should only be used with the INBRIJA inhaler and inhaled through your mouth (oral inhalation) Overview: A complete dose is 2 capsules. You will load 1 capsule into the inhaler and breathe in (inhale). Then, you will remove the used capsule and load a second capsule into the inhaler and breathe in. Do not swallow INBRIJA capsules. Each carton contains 1 INBRIJA inhaler and capsules in sealed foil packages. When you open a new carton, always use the new inhaler supplied. Do not use capsules after the expiration date printed on the package. Do not load 2 capsules at the same time. Throw out all used capsules immediately after use. Throw out the inhaler after all capsules in the carton have been used. Make sure your hands are clean and dry when using the inhaler and capsules. If you have any questions, ask your healthcare provider or pharmacist. If you have problems using INBRIJA, or if your INBRIJA inhaler becomes lost or damaged and you need a replacement, contact INBRIJA support at 1-800-367-5109. Then, call your healthcare provider for treatment instructions until you receive your replacement inhaler. Parts of your INBRIJA Inhaler (see Figure A ) Capsules (see Figure B ) Each carton includes strips of 4 capsules. (see Figure C ) Prepare and take a total of 2 capsules. Take each capsule 1 at a time for a full dose. (see Figure D ) Full Dose = 2 Capsules Prepare Your Dose Step 1. Gather Supplies Find a clean and dry surface. Make sure your hands are clean and dry. Get inhaler and strip of capsules. Tear off package of 2 capsules (see Figure E ). Step 2. Check Expiration Check the expiration date on the package (see Figure F ). Step 3. Remove Blue Cap Pull the cap straight off (see Figure G ). Place the cap to the side. You will need it later to store the inhaler. Step 4. Twist Off White Mouthpiece Twist and pull off the mouthpiece to separate it from the handle (see Figure H ). Place the mouthpiece and inhaler on a clean and dry surface. Step 5. Remove 1 Capsule From Package Carefully peel back the foil and take out 1 capsule (see Figure I ). Do not try to push the capsule through the back of the foil package. Only remove 1 capsule at a time, and just before use. Do not use any capsule that looks crushed, damaged or wet. Throw it away and get a new capsule. Step 6. Load Capsule Hold the inhaler upright using the handle. Drop 1 capsule into the opening of the capsule chamber (see Figure J ). Do not try to load 2 capsules at the same time. Step 7. Attach White Mouthpiece Line up the white arrows on the handle and mouthpiece (see Figure K ). Firmly push the mouthpiece and handle together until you hear a click. This punctures the capsule (see Figure L ). Release the mouthpiece. The mouthpiece will spring back and stay attached (see Figure M ). Your inhaler is now ready to use. Do not push the handle and mouthpiece together more than 1 time. This may damage the capsule, and you may not get your full dose. If this happens throw the capsule away in your household trash and start over at Step 5. Make sure the mouthpiece is securely attached and will not fall off before moving to step 8. Take Your Dose Step 8. Breathe Out (Exhale) Stand or sit with your head and chest upright. Hold the inhaler level and away from your mouth (see Figure N ). Breathe out completely (see Figure N ). Do not breathe into mouthpiece. Step 9. Breathe In Deeply (Inhale) While keeping the inhaler level, close your lips firmly around the mouthpiece (see Figure O ). Take in a deep, comfortable breath until your lungs feel full. This normally takes several seconds. As you breathe in, you will hear and feel the capsule "whirl" (spin). The whirl means the inhaler is working and you are getting your medicine. If you cough or stop your dose, start again from the beginning of Step 8 using the same capsule. Important: If you did not hear or feel the capsule "whirl" while inhaling you may need to take a deeper, longer breath or may need to clean the mouthpiece. Refer to Step 14 – Clean Mouthpiece. Start again from the beginning of Step 8 using the same capsule. Step 10. Hold Breath, Then Breathe Out Take the inhaler out of your mouth and hold your breath for 5 seconds (see Figure P ). Then breathe out. Step 11. Remove Capsule From Inhaler Twist and pull off the mouthpiece (see Figure Q ) and take out the used capsule (see Figure R ). Step 12. Dose With 2 nd Capsule Repeat Steps 5 to 11 with the second capsule to finish the full dose (see Figure S ). Dispose and Store Step 13. Throw Out Used Capsules Throw out used capsules in the household trash (see Figure T ). Step 14. Clean Mouthpiece It is normal for some powder to remain in or on the inhaler. To avoid powder buildup, clean the powder off of the mouthpiece holes using a circular motion with a new dry cotton swab as needed. First, clean the holes from the top end of the mouthpiece (see Figure U ). Next, clean the holes from the bottom end of the mouthpiece (see Figure V ). You can also use a dry tissue to wipe the outside of the mouthpiece, as needed. Do not clean any other parts of the inhaler. Do not rinse the mouthpiece or get the inhaler wet. Step 15. Store Inhaler Make sure there are no capsules in the inhaler before you store it. Attach the mouthpiece to the handle by pushing until you hear a click (see Figure W ). Attach the cap over the mouthpiece (see Figure X ). Your inhaler is now ready to store (see Figure Y ). INBRIJA Storage, Cleaning and Disposal Storing the Inhaler and Capsules Store the inhaler and capsules in a dry place at room temperature from 68°F to 77°F (20 to 25°C). Keep capsules inside their foil (blister) packages until just before you are ready to use them. Do not store capsules in the inhaler for a future dose. Keep the inhaler and capsules dry. Throw out the inhaler after all capsules in the carton have been used. Use the new inhaler that comes with your prescription refill. Keep INBRIJA and all medicines out of reach of children. Cleaning the Inhaler It is normal for some powder to remain in or on the inhaler. If needed, to avoid powder buildup, you may use a dry cotton swab or a dry tissue to wipe the inside or outside of the mouthpiece. Disposing of the Inhaler and Capsules Throw out all used capsules in your household trash. After all capsules in the carton have been used, throw out the inhaler and use a new carton containing a new inhaler and capsules. This Instructions for Use has been approved by the U.S. Food and Drug Administration Rev: 08/2020 Marketed by: Acorda Therapeutics, Inc. Pearl River, NY 10965 USA Inbrija ® is a trademark of Acorda Therapeutics, Inc. ©2022 Acorda Therapeutics, Inc. All rights reserved. U.S. Patent Nos. 7182961, 8404276, 8545878, 8586093, 8685442, 8945612, 9155699, 9393210 and RE43711 2212342MFPI-0 undefined Figure B Figure C Figure D undefined undefined undefined undefined undefined undefined undefined undefined undefined undefined undefined undefined undefined undefined undefined undefined Figure U Figure V Figure W Figure X Figure Y

14 CLINICAL STUDIES The efficacy and safety of INBRIJA for the treatment of OFF episodes in patients with Parkinson's disease treated with oral carbidopa/levodopa was evaluated in a 12-week, randomized, placebo-controlled, double-blind study (Study 1; NCT02240030). Study 1: In Study 1, a total of 114 patients were treated with INBRIJA 84 mg (two 42 mg capsules), and 112 patients received placebo. Study medication could be administered up to five times a day. At baseline, patients had at least 2 hours of OFF time per day, and carbidopa/levodopa medication did not exceed 1600 mg levodopa per day. The mean UPDRS Part III scores at screening in the ON state were 14.9 for patients randomized to INBRIJA 84 mg and 16.1 for patients randomized to placebo. The UPDRS part III is designed to assess the severity of the cardinal motor findings (e.g., tremor, rigidity, bradykinesia, postural instability) in patients with Parkinson's disease. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score from pre-dose OFF state to 30 minutes post-dose, measured at Week 12. The average use of INBRIJA 84 mg or placebo was approximately 2 doses per day. At Week 12, the reduction in UPDRS Part III motor score for INBRIJA 84 mg, compared to placebo at 30 minutes post-dose, were -9.8 and -5.9, respectively (See Table 2 and Figure 1 ). The proportion of patients who returned to an ON state and sustained that ON through 60 minutes post-dose was 58% for INBRIJA 84 mg and 36% for placebo (p=0.003). Table 2: Mean Change in UPDRS Part III Motor Score at 30 minutes post-dose (INBRIJA 84 mg) for the Intent-to-Treat Population at Week 12 Treatment group least-squares mean change is a model-based population estimate; the pre-dose and post-dose means are descriptive statistics. Treatment Pre-dose (OFF) UPDRS Part III Motor Score (mean) Post-dose UPDRS Part III Motor Score (mean) Mean Change 30 minutes post-dose Least-squares mean. , Negative numbers indicate improvement as compared with the baseline value. Difference from Placebo (95% confidence interval) p-value Placebo 32.1 25.3 -5.9 — — INBRIJA 84 mg 29.0 19.3 -9.8 -3.92 (-6.84, -1.00) 0.009 Figure 1: Least-squares Mean Change in UPDRS Part III Motor Score After Administration of INBRIJA 84 mg vs. Placebo (at Week 12) Figure 1 Study 2 The effect of INBRIJA on pulmonary function was evaluated in patients with Parkinson's disease treated with oral carbidopa/levodopa in a 12 month, randomized, controlled, open-labeled study (Study 2: NCT02352363). A total of 271 patients were treated with INBRIJA 84 mg (two 42 mg capsules), and 127 patients with Parkinson's disease in a control group were observed on their regular oral medication regimen for the treatment of Parkinson's disease. Patients with chronic obstructive pulmonary disease (COPD), asthma, or other chronic respiratory disease within the last 5 years were excluded [see Warnings and Precautions (5.6) ]. Pulmonary function was assessed by spirometry every 3 months in both groups. After 12 months, the average reduction in the forced expiratory volume in 1 second (FEV 1 ) from baseline was the same in both groups (-0.1 L).

8.5 Geriatric Use Of the Parkinson's disease patients in Study 1 who took INBRIJA 84 mg, 49% (n=56) were 65 years of age and older and 51% (n=58) were under 65 years of age. Of these patients, the following age-related differences in adverse reactions were reported in patients 65 years of age and older vs. in patients under 65 years of age, respectively: cough 25% vs. 5%; upper respiratory tract infection 11% vs. 2%; nausea 7% vs. 3%; vomiting 4% vs. 2%; pain in the extremities 4% vs. 0%; and discolored nasal discharge 4% vs. 0%.

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of INBRIJA in pregnant women. In animal studies, carbidopa/levodopa has been shown to be developmentally toxic (including teratogenic effects) [see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data When administered to pregnant rabbits throughout organogenesis, carbidopa/levodopa caused both visceral and skeletal malformations in rabbits. No teratogenic effects were observed when carbidopa/levodopa was administered to pregnant mice throughout organogenesis. There was a decrease in the number of live pups delivered by rats receiving carbidopa/levodopa during organogenesis.

8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of INBRIJA in pregnant women. In animal studies, carbidopa/levodopa has been shown to be developmentally toxic (including teratogenic effects) [see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data When administered to pregnant rabbits throughout organogenesis, carbidopa/levodopa caused both visceral and skeletal malformations in rabbits. No teratogenic effects were observed when carbidopa/levodopa was administered to pregnant mice throughout organogenesis. There was a decrease in the number of live pups delivered by rats receiving carbidopa/levodopa during organogenesis. 8.2 Lactation Risk Summary The prolactin-lowering action of dopamine suggests that levodopa may interfere with lactation, although there are limited data on the effects of levodopa on milk production in lactating women. Levodopa has been detected in human milk. There are no adequate data on the effects of levodopa on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for INBRIJA and any potential adverse effects on the breastfed infant from INBRIJA or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Of the Parkinson's disease patients in Study 1 who took INBRIJA 84 mg, 49% (n=56) were 65 years of age and older and 51% (n=58) were under 65 years of age. Of these patients, the following age-related differences in adverse reactions were reported in patients 65 years of age and older vs. in patients under 65 years of age, respectively: cough 25% vs. 5%; upper respiratory tract infection 11% vs. 2%; nausea 7% vs. 3%; vomiting 4% vs. 2%; pain in the extremities 4% vs. 0%; and discolored nasal discharge 4% vs. 0%.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied INBRIJA 42 mg contains foil blister strips of INBRIJA (levodopa inhalation powder) white capsules with two black bands on the body and "A42" in black on the cap, and one INBRIJA inhaler. Carton containing 4 INBRIJA capsules (1 blister card containing 4 capsules) and 1 INBRIJA inhaler: NDC 10144-342-04 Carton containing 12 INBRIJA capsules (3 blister cards containing 4 capsules each) and 1 INBRIJA inhaler: NDC 10144-342-12 Carton containing 60 INBRIJA capsules (15 blister cards containing 4 capsules each) and 1 INBRIJA inhaler: NDC 10144-342-60 Carton containing 92 INBRIJA capsules (23 blister cards containing 4 capsules each) and 1 INBRIJA inhaler: NDC 10144-342-92 INBRIJA inhaler consists of a blue cap, blue handle with "INBRIJA" imprinted on it, and white mouthpiece covering the capsule chamber. 16.2 Storage and Handling Store in a dry place between 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). INBRIJA capsules should always be stored in the blister packaging and only removed immediately before use. INBRIJA capsules should not be stored inside the INBRIJA inhaler. INBRIJA capsules should be used only with the INBRIJA inhaler. The INBRIJA inhaler should not be used to administer any other medicines.

16.2 Storage and Handling Store in a dry place between 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). INBRIJA capsules should always be stored in the blister packaging and only removed immediately before use. INBRIJA capsules should not be stored inside the INBRIJA inhaler. INBRIJA capsules should be used only with the INBRIJA inhaler. The INBRIJA inhaler should not be used to administer any other medicines.