Inbrija Drug Information

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

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 .

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.

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. 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.

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.

Monoamine Oxidase (MAO) Inhibitors

The use of nonselective MAO inhibitors with INBRIJA is contraindicated . 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.

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.

Iron Salts Iron salts or multivitamins containing iron salts can form chelates

with levodopa and consequently reduce the bioavailability of levodopa.

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). 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.

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

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. 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

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.