INBRIJA (levodopa inhalation powder), 42 mg capsules

As-Needed Therapy for the Return of Parkinson's Symptoms, Selecting Appropriate Patients

(DESCRIPTION)

[Music introduction plays]

(ZEV WINICUR)

Thanks for joining us at the OFF Talk Podcast series where we discuss Parkinson's disease, managing OFF periods and use of on-demand therapies. Each podcast will be a one-on-one discussion with a leading Movement Disorder/Parkinson's specialist. These podcasts also include important safety information.

(VOICE OVER)

INBRIJA® (levodopa inhalation powder) is indicated for intermittent treatment of OFF episodes in patients with Parkinson's disease treated with carbidopa/levodopa. The effect of INBRIJA on non-motor symptoms has not been evaluated. INBRIJA is an inhaled prescription levodopa medication that contains 42 milligrams of levodopa in each capsule. INBRIJA is contraindicated in patients who are taking or who have recently taken, within two weeks, nonselective monoamine oxidase MAO inhibitors, for example, phenelzine and tranylcypromine, due to risk of hypertension. Discontinue use of nonselective MAO inhibitors at least two weeks prior to initiating INBRIJA. Please stay tuned for additional important safety information later in the podcast.

(ZEV WINICUR)

Today's podcast, "As-Needed Therapy for the Return of Parkinson's Symptoms, Selecting Appropriate Patients," is intended for US healthcare professionals and is brought to you by Acorda Therapeutics. My name is Zev Winicur and I'm a Medical Science Liaison with Acorda Therapeutics. I'm joined today by Dr. Rajeev Kumar, the Medical Director of the Rocky Mountain Movement Disorder Center in Englewood, Colorado. Dr. Kumar, thanks for joining us.

(DR. KUMAR)

It's a pleasure to be here today.

(ZEV WINICUR)

Considering the indication for INBRIJA, where does INBRIJA fit into the treatment plan?

(DR. KUMAR)

Well, there are a variety of ways to treat motor fluctuations, which are the return of Parkinson's symptoms. Typically, one may adjust baseline medications, use as-needed or bridge products to reduce symptoms when they recur, or do both. Now, one way of dealing with motor fluctuations is to change the dose or frequency of the oral carbidopa/levodopa, or use an extended release carbidopa/levodopa product, or one can add different classes of maintenance therapies to the baseline carbidopa/levodopa regimen, and these strategies can reduce OFF time. Now, despite use of these strategies, patients can still have OFF symptoms and return of symptoms, and this may occur despite the use of multiple medications and even use of device-aided therapies such as deep brain stimulation. So, when patients continue to have OFF symptoms and return of symptoms, then INBRIJA should be considered as an as-needed or PRN adjunctive treatment. Now, as with other PRN medications, INBRIJA should be considered for use when patients are on baseline medication, but still occasionally symptomatic. So when you start INBRIJA, you don't stop the baseline medications. Now, the return of symptoms or OFF episodes can be unpredictable. And, in fact, at the same time as one adjusts the baseline medication, whether or not that's the levodopa, or changing or adding adjunctive medications, you can prescribe INBRIJA at the same time to give patients more control over their own management.

(ZEV WINICUR)

I see. So INBRIJA is used for patients with OFF periods. Who would INBRIJA not be appropriate for?

(DR. KUMAR)

Well, first, one should not give INBRIJA to patients who are on nonselective MAO inhibitor antidepressants and should not be used typically in a patient who has or is at risk of psychosis, major psychotic disorder, because when you give more levodopa, you could worsen or exacerbate the psychosis. And it's not generally appropriate to use dopamine antagonists or antipsychotic medication to treat most psychosis because most of the typical dopamine antagonists may exacerbate the symptoms of Parkinson's disease and this would, in fact, decrease the efficacy of INBRIJA when it's used in this circumstance. We typically also should recommend against the use of INBRIJA in patients who have asthma, COPD, or other underlying lung disease because it can exacerbate bronchospasm.

(ZEV WINICUR)

Okay, that describes the type of patients that INBRIJA should and should not be used for. How does INBRIJA help with the management of OFF symptoms?

(DR. KUMAR)

Some patients may need symptom management strategies in addition to what might be achieved with the adjustment of the baseline measurement or during the titration phase of the baseline regimen. Adjusting the baseline carbidopa/levodopa regimen or adding other baseline adjuvant therapies, patients may still have returning Parkinson's symptoms. With INBRIJA, patients have access to an additional option that is used as-needed to address their OFF symptoms when they first begin to reappear. Patients should take no more than one dose each OFF episode with a maximum of five doses in a day. Now, again, you should remember that one dose consists of inhaling two capsules. Other patients have only limited OFF periods on their current baseline therapy regimen. For example, they may have unpredictable OFFs only once or twice a week. Such patients might not require an adjustment of their baseline regimen because they're doing fairly well. But provision of INBRIJA may allow patients to treat these residual and sometimes troubling OFF periods without the need for additional daily baseline medication. INBRIJA offers a treatment option for these patients to address symptoms as they occur.

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Please listen to this selected important safety information. Patients treated with levodopa, the active ingredient in INBRIJA, have reported falling asleep during activities of daily living, including operation of motor vehicles, which sometimes resulted in accidents. Many patients reported somnolence but some reported no warning signs or sleep attack. This may occur more than a year after initiating treatment. Reassess patients for drowsiness or sleepiness, including occurrence during specific activities. Advise patients of potential for drowsiness and ask about factors that may increase this risk, for example, sedating medications or sleep disorders. Consider discontinuing INBRIJA in patients who report significant daytime sleepiness or falling asleep during activities that require active participation. If continuing INBRIJA, advise patients not to drive and to avoid activities that may result in harm. There is insufficient information that dose reduction will eliminate episodes of falling asleep during activities of daily living. Please stay tuned for additional important safety information later in the podcast.

(ZEV WINICUR)

Dr. Kumar, thank you for that information on symptom management. Tell me, how do you instruct your patients to use INBRIJA?

(DR. KUMAR)

Well, understanding how to use INBRIJA is very important, and it's important to instruct them appropriately. We have some resources. There is both the Instructions for Use, as well as a video card that comes with the INBRIJA packet. So a dose, as I mentioned before, consists of two inhaled capsules per OFF period, and patients should not take more than one dose per OFF and no more than five doses in a day. If someone is using INBRIJA frequently, that can be an indicator that the baseline therapy regimen should be adjusted to reduce the frequency of these OFF periods. Patients should be sure to read the Instructions for Use, as I mentioned, before using INBRIJA. And it should be noted that the inhaler for INBRIJA should only be used with INBRIJA capsules, not with other medicines, for example. The capsules are for inhalation and should not be swallowed. The capsules should be kept in the original blister packaging until just before use.

(ZEV WINICUR)

Thank you. You mentioned that patients should only take two capsules per OFF period. Given that, when should patients take INBRIJA and how does it exert its pharmacologic effect?

(DR. KUMAR)

They should take INBRIJA at the beginning of an OFF period, when they first begin to notice that their Parkinson's symptoms are returning. They should be instructed not to wait until they're fully OFF. So, again, take it when they just begin to wear OFF. In that way, INBRIJA can allow the patient to turn back ON again. The amount of absorbable levodopa in one dose is 50 milligrams and that's the amount that's thought to reach the lungs, of levodopa. The addition of INBRIJA then boost the plasma levodopa level, which would then need to be converted to dopamine in the brain, and then the increased brain dopamine levels are sufficient for improvement in motor function. INBRIJA does not contain carbidopa, so it relies on carbidopa present in the baseline oral carbidopa/levodopa regimen, and it's only been shown to work in patients taking oral carbidopa/levodopa. So patients, of course, then must continue or maintain their oral carbidopa/levodopa regimen.

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And here is some more important safety information for INBRIJA. Neuroleptic malignant syndrome-like symptoms, for example, elevated temperature, muscular rigidity, altered consciousness and autonomic instability have been reported with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy. Hallucinations, with or without confusion, insomnia and excessive dreaming may occur and may respond to reducing levodopa therapy. Abnormal thinking and behavior may present with paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation and delirium. Patients on medications that increase central dopaminergic tone such as INBRIJA can experience intense urges to gamble or spend money, increased sexual urges, binge eating and/or other intense urges and inability to control them. In some cases, these urges stopped with dose reduction or medication discontinuation. Since some patients may not recognize these behaviors as abnormal, ask patients or their caregivers about development of new or increased urges and consider stopping INBRIJA if this occurs. INBRIJA may cause or exacerbate dyskinesias. If troublesome dyskinesias occur, consider stopping INBRIJA or adjusting other Parkinson's medications. Please stay tuned for additional important safety information later in the podcast.

(ZEV WINICUR)

Dr. Kumar, you said that patients should be advised to use INBRIJA at the beginning of an OFF period, when symptoms start to return. Would you provide us some other practical advice for the neurologist who wants to prescribe INBRIJA?

(DR. KUMAR)

Sure. Well, in addition to Instructions for Use that come with INBRIJA and the demonstration video on the website and in the patient starter kit, it's helpful to share some tips on using INBRIJA with patients. First of all, posture's important. Patients should be advised to stand or sit up straight and look ahead and hold the inhaler level while breathing in. They should breathe in slowly and gently, not too fast, just enough to hear or feel the capsule whirl, and then hold their breath after they breathe in the medicine. Hold the breath for a few seconds. Patients should breathe in just enough, which means the inhaler is working when they hear the capsule whirl and they're getting the medicine. If they don't hear or feel the whirl, then they should take gradually stronger breaths until they do. If it's easier for the patient, they can take more than one breath per capsule so they can get all of the medicine in. In addition, anecdotally, something that might help with coughing is to have patients take a small sip of water before and after INBRIJA inhalation. INBRIJA is orally inhaled and cough, as I just mentioned, may be, in fact is, the most common adverse reaction. In the Phase three clinical trial, 15% of the 114 patients on INBRIJA reported cough, compared to 2% of the 112 patients on placebo. Now, of the 17 patients that reported cough in INBRIJA treatment arm, 11 reported that the cough was mild. Six reported the cough was moderate and no severe cough was reported. And in the 17 patients, 14 of them reported cough within the first 30 days of treatment, so it tends to occur pretty early. And two of the patients discontinued from the trial because of cough. Patients should be aware that levodopa can become oxidized, which means that it can result in dark discoloration of body fluids, especially the saliva or sputum, but occasionally nasal discharge or even sweat or urine. If there is residual levodopa powder left in the inhaler, oxidation may occur and this will result in discoloration of the powder. Now, it's normal for some powder to remain on the inhaler and patients can be advised that they may clean it with a dry cotton swab or dry tissue to wipe the inside or the outside of the mouthpiece. Always keep the inhaler and capsules dry. Do not rinse the mouthpiece or get the inhaler wet. Patients are provided with a new inhaler with each package of INBRIJA, so they should be reminded to throw out the old one.

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And here's the remaining important safety information for INBRIJA. Monitor patients with glaucoma for increased intraocular pressure. Abnormalities in laboratory tests may include elevations of liver function tests, for example, alkaline phosphatase, AST, ALT, lactic dehydrogenase and bilirubin, as well as blood urea nitrogen, hemolytic anemia and positive direct antibody test. Increased levels of catecholamines and their metabolites in plasma and urine may result in false positive results, suggesting pheochromocytoma. The most common adverse reactions that occurred at an incidence of at least five percent and greater than placebo were: cough (15% vs 2%), upper respiratory tract infection (6% vs 3%), nausea (5% vs 3%), and sputum discolored (5% vs 0%). Use of selective MAO-B inhibitors with INBRIJA may be associated with orthostatic hypotension. Monitor patients taking these drugs concurrently. Isoniazid and dopamine D2 receptor antagonists, for example, phenothiazines, butyrophenones, risperidone, metoclopramide, may reduce levodopa efficacy. Monitor for worsening symptoms. Iron salts or multivitamins with iron salts may reduce levodopa bioavailability. INBRIJA should be used during pregnancy or nursing only if potential benefit justifies potential risk. There are no adequate data on INBRIJA in pregnant women or breastfed infants. Animal data shows carbidopa/levodopa is developmentally toxic, including teratogenicity. Levodopa may affect milk production interfering with lactation. Levodopa has been detected in human milk. Safety and effectiveness in pediatric patients have not been established. 56 geriatric patients experienced more of the following adverse reactions than 58 patients younger than 65: cough (25% vs 5%), upper respiratory tract infection (11% vs 2%), nausea (7% vs 3%), vomiting (4% vs 2%), pain in extremities (4% vs 0%), and discolored nasal discharge (4% vs 0%).

(ZEV WINICUR)

Thank you, Dr. Kumar, for your time today and for giving us your perspective on selecting appropriate patients for INBRIJA.

(DR. KUMAR)

It's been a pleasure speaking with you.

(ZEV WINICUR)

Please refer to the Full Prescribing Information, including the Instructions for Use, available at InbrijaFullPI.com. There are additional resources at Inbrija-HCP.com. Acorda Therapeutics, the stylized Acorda Therapeutics logo, and INBRIJA are all trademarks of Acorda Therapeutics Incorporated. Copyright 2020, Acorda Therapeutics, Incorporated. All rights reserved.

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