These Highlights Do Not Include All The Information Needed To Use Inbrija Safely And Effectively. See Full Prescribing Information For Inbrija.

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.

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.

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.

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: 03/2025

Marketed by:

Merz Pharmaceuticals, LLC

Raleigh, NC 27615

INBRIJA^® is a registered trademark of Merz Pharmaceuticals, LLC.

©2025 Merz Pharmaceuticals, LLC. All rights reserved.

U.S. Patent Nos. 7182961, 8404276, 8545878, 8586093, 8685442, 8945612, 9155699, 9393210 and RE43711

FPI-0053 v2.0

INBRIJA may cause increased intraocular pressure in patients with glaucoma. Monitor patients for increased intraocular pressure during therapy with INBRIJA.

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.

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 C₉H₁₁NO₄. 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.

INBRIJA may cause or exacerbate dyskinesias. If troublesome dyskinesias occur, prescribers may need to consider stopping treatment with INBRIJA and/or adjusting the patient's daily medications for the treatment of Parkinson's disease. In Study 1, 4% of patients treated with INBRIJA 84 mg reported dyskinesia, compared with 1% for patients on placebo [see Adverse Reactions (6.1)] .

Iron salts or multivitamins containing iron salts can form chelates with levodopa and consequently reduce the bioavailability of levodopa.

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 60 INBRIJA capsules (15 blister cards containing 4 capsules each) and 1 INBRIJA inhaler: NDC 0259-6142-60

INBRIJA inhaler consists of a blue cap, blue handle with "INBRIJA" imprinted on it, and white mouthpiece covering the capsule chamber.

Safety and effectiveness in pediatric patients have not been established.

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%.

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).

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)].

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)]

• 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)

There are no relevant data on the pharmacodynamic effects of INBRIJA.

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.

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)].

INBRIJA is indicated for the intermittent treatment of OFF episodes in patients with Parkinson's disease treated with carbidopa/levodopa.

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.

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.

• May cause falling asleep during activities of daily living (5.1)
• Avoid sudden discontinuation or rapid dose reduction to reduce the risk of withdrawal-emergent hyperpyrexia and confusion (5.2)
• Hallucinations/exacerbation of psychosis may occur. Patients with a major psychotic disorder should not be treated with INBRIJA (5.3, 7.2)
• Impulse Control Disorders: consider dose reduction or stopping INBRIJA (5.4)
• May cause or exacerbate dyskinesia: adjustment of levodopa therapy may be considered, including stopping INBRIJA (5.5)
• Not recommended in patients with asthma, COPD, or other chronic underlying lung disease (5.6)

INBRIJA capsules are for oral inhalation only and should be used only with the INBRIJA inhaler.

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.

In placebo-controlled trials [see Clinical Studies (14)], hallucinations were reported in less than 2% of patients treated with INBRIJA. Hallucinations may be responsive to reducing levodopa therapy. Hallucinations may be accompanied by confusion, insomnia, and excessive dreaming. Abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.

Because of the risk of exacerbating psychosis, patients with a major psychotic disorder should ordinarily not be treated with INBRIJA. In addition, medications that antagonize the effects of dopamine used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of INBRIJA [see Drug Interactions (7.2)].

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.

Pregnancy: Based on animal data, may cause fetal harm (8.1)

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.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, AST, ALT, lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen (BUN), hemolytic anemia and positive direct antibody test have also been reported.

Patients taking levodopa or carbidopa-levodopa may have increased levels of catecholamines and their metabolites in plasma and urine giving false positive results suggesting the diagnosis of pheochromocytoma in patients on levodopa and carbidopa-levodopa.

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.

Patients treated with INBRIJA can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued.

Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with INBRIJA. Consider stopping the medication if a patient develops such urges while taking INBRIJA.

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)].

Because of the risk of bronchospasm, use of INBRIJA in patients with asthma, COPD, or other chronic underlying lung disease is not recommended.

In a double-blind, placebo-controlled, crossover clinical study, 25 otherwise healthy subjects with mild or moderate asthma on a stable regimen of asthma medication received placebo or INBRIJA 84 mg every 4 hours for a total of three doses. Cough was the most frequent adverse reaction, reported by 60% of subjects following administration of INBRIJA and 0% following administration of placebo. Following administration of INBRIJA, 10 subjects (40%) had temporary reductions from baseline (between 15% and 59%) for FEV₁; 4 of these subjects also had a reduction in FEV₁ following administration of placebo. Subjects with a reduction in FEV₁ remained asymptomatic and did not require rescue treatment.

A symptom complex that resembles neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy.

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.

NDC 0259-6142-60

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.

MERZ

Patients treated with levodopa, the active ingredient in INBRIJA, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence, some reported no warning signs (sleep attack) and believed that they were alert immediately prior to the event. Some of these events have been reported more than 1 year after the initiation of treatment.

Prescribers should reassess patients for drowsiness or sleepiness. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.

Before initiating treatment with INBRIJA, advise patients about the potential to develop drowsiness and ask about factors that may increase the risk for somnolence with INBRIJA such as the concomitant use of sedating medications and the presence of sleep disorders. Consider discontinuing INBRIJA in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.).

If treatment with INBRIJA continues, patients should be advised not to drive and to avoid other activities that might result in harm if the patients become somnolent. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

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.

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.

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.

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: 03/2025

Marketed by:

Merz Pharmaceuticals, LLC

Raleigh, NC 27615

INBRIJA^® is a registered trademark of Merz Pharmaceuticals, LLC.

©2025 Merz Pharmaceuticals, LLC. All rights reserved.

U.S. Patent Nos. 7182961, 8404276, 8545878, 8586093, 8685442, 8945612, 9155699, 9393210 and RE43711

FPI-0053 v2.0

INBRIJA may cause increased intraocular pressure in patients with glaucoma. Monitor patients for increased intraocular pressure during therapy with INBRIJA.

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.

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 C₉H₁₁NO₄. 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.

INBRIJA may cause or exacerbate dyskinesias. If troublesome dyskinesias occur, prescribers may need to consider stopping treatment with INBRIJA and/or adjusting the patient's daily medications for the treatment of Parkinson's disease. In Study 1, 4% of patients treated with INBRIJA 84 mg reported dyskinesia, compared with 1% for patients on placebo [see Adverse Reactions (6.1)] .

Iron salts or multivitamins containing iron salts can form chelates with levodopa and consequently reduce the bioavailability of levodopa.

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 60 INBRIJA capsules (15 blister cards containing 4 capsules each) and 1 INBRIJA inhaler: NDC 0259-6142-60

INBRIJA inhaler consists of a blue cap, blue handle with "INBRIJA" imprinted on it, and white mouthpiece covering the capsule chamber.

Safety and effectiveness in pediatric patients have not been established.

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%.

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).

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)].

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)]

• 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)

There are no relevant data on the pharmacodynamic effects of INBRIJA.

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.

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)].

INBRIJA is indicated for the intermittent treatment of OFF episodes in patients with Parkinson's disease treated with carbidopa/levodopa.

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.

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.

• May cause falling asleep during activities of daily living (5.1)
• Avoid sudden discontinuation or rapid dose reduction to reduce the risk of withdrawal-emergent hyperpyrexia and confusion (5.2)
• Hallucinations/exacerbation of psychosis may occur. Patients with a major psychotic disorder should not be treated with INBRIJA (5.3, 7.2)
• Impulse Control Disorders: consider dose reduction or stopping INBRIJA (5.4)
• May cause or exacerbate dyskinesia: adjustment of levodopa therapy may be considered, including stopping INBRIJA (5.5)
• Not recommended in patients with asthma, COPD, or other chronic underlying lung disease (5.6)

INBRIJA capsules are for oral inhalation only and should be used only with the INBRIJA inhaler.

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.

In placebo-controlled trials [see Clinical Studies (14)], hallucinations were reported in less than 2% of patients treated with INBRIJA. Hallucinations may be responsive to reducing levodopa therapy. Hallucinations may be accompanied by confusion, insomnia, and excessive dreaming. Abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.

Because of the risk of exacerbating psychosis, patients with a major psychotic disorder should ordinarily not be treated with INBRIJA. In addition, medications that antagonize the effects of dopamine used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of INBRIJA [see Drug Interactions (7.2)].

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.

Pregnancy: Based on animal data, may cause fetal harm (8.1)

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.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, AST, ALT, lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen (BUN), hemolytic anemia and positive direct antibody test have also been reported.

Patients taking levodopa or carbidopa-levodopa may have increased levels of catecholamines and their metabolites in plasma and urine giving false positive results suggesting the diagnosis of pheochromocytoma in patients on levodopa and carbidopa-levodopa.

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.

Patients treated with INBRIJA can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued.

Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with INBRIJA. Consider stopping the medication if a patient develops such urges while taking INBRIJA.

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)].

Because of the risk of bronchospasm, use of INBRIJA in patients with asthma, COPD, or other chronic underlying lung disease is not recommended.

In a double-blind, placebo-controlled, crossover clinical study, 25 otherwise healthy subjects with mild or moderate asthma on a stable regimen of asthma medication received placebo or INBRIJA 84 mg every 4 hours for a total of three doses. Cough was the most frequent adverse reaction, reported by 60% of subjects following administration of INBRIJA and 0% following administration of placebo. Following administration of INBRIJA, 10 subjects (40%) had temporary reductions from baseline (between 15% and 59%) for FEV₁; 4 of these subjects also had a reduction in FEV₁ following administration of placebo. Subjects with a reduction in FEV₁ remained asymptomatic and did not require rescue treatment.

A symptom complex that resembles neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy.

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.

NDC 0259-6142-60

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.

MERZ

Patients treated with levodopa, the active ingredient in INBRIJA, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence, some reported no warning signs (sleep attack) and believed that they were alert immediately prior to the event. Some of these events have been reported more than 1 year after the initiation of treatment.

Prescribers should reassess patients for drowsiness or sleepiness. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.

Before initiating treatment with INBRIJA, advise patients about the potential to develop drowsiness and ask about factors that may increase the risk for somnolence with INBRIJA such as the concomitant use of sedating medications and the presence of sleep disorders. Consider discontinuing INBRIJA in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.).

If treatment with INBRIJA continues, patients should be advised not to drive and to avoid other activities that might result in harm if the patients become somnolent. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.