Inbrija

Inbrija (levodopa inhalation powder) is a fast-acting inhaled medicine used to treat OFF episodes in Parkinson's disease; these are the periods when symptoms such as tremor, stiffness, and slowness return between doses of your regular carbidopa/levodopa medicine.

Inbrija started working as early as 10 minutes in some people, and reached a median peak blood level 30 minutes after a dose in Study 1 (NCT02240030). Inbrija works quickly because the powder is absorbed through the lungs rather than the stomach; therefore, it reaches the bloodstream faster.

Inbrija is an as-needed "rescue" treatment, used up to 5 times a day when an OFF episode starts. It does not replace your daily carbidopa/levodopa medicine, and you must keep taking your regular Parkinson's medications while using it. Inbrija must be taken with daily carbidopa and levodopa Parkinson's disease medicine. Inbrija does not replace your daily medicine.

Approved by the FDA in 2018, Inbrija was the first inhaled form of levodopa.

It is not known if Inbrija is safe or effective in children.

In the 12-week clinical trial that supported FDA approval, people using Inbrija had measurably better movement scores 30 minutes after a dose compared with placebo (an average 9.8-point improvement on the UPDRS motor scale, versus 5.9 points with placebo). More than half of people who used Inbrija (58%) returned to an ON state within 60 minutes and stayed ON, compared with 36% of people using placebo.

Levodopa from Inbrija has a half-life of about 2.3 hours, and each dose (2 capsules) is intended to cover a single OFF episode if symptoms return later in the day, a new OFF period can be treated with a new dose (up to 5 doses per day).

Use Inbrija exactly as prescribed. Follow all directions on your prescription label and read the Instructions for Use provided with your medicine.

• Inbrija is for oral inhalation use only. Do not swallow capsules.
• Only use capsules with the Inbrija inhaler. Do not use the inhaler to take any other medicine.
• Take a dose as soon as an OFF episode begins, when you first feel your Parkinson's symptoms returning.
• A full dose is 2 capsules (84 mg total), inhaled one at a time using the Inbrija inhaler. Load one capsule, inhale, remove it, then load and inhale the second.
• Do not take more than 1 dose (2 capsules) for the same OFF period, and do not take more than 5 doses in one day.
• You must be taking a daily Parkinson's disease medicine that contains carbidopa and levodopa with Inbrija. You must not stop taking your daily Parkinson's medicine.
• Keep each capsule sealed in its blister pack until immediately before use, and do not store capsules inside the inhaler.
• Throw the inhaler away when the capsules in the carton run out, and use the new inhaler that comes with each refill.

Inbrija can affect the results of certain lab tests, including liver tests, and can cause false-positive results on tests for pheochromocytoma. Tell any doctor who treats you that you use Inbrija.

Inbrija carries several warnings you should understand before using it. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Falling asleep suddenly. Inbrija can cause you to fall asleep during normal activities such as driving, talking, or eating, sometimes without feeling drowsy first. This has been reported as long as a year after starting treatment. Do not drive until you know how Inbrija affects you, and tell your doctor if you have daytime sleepiness.

Withdrawal reaction if stopped suddenly. Do not stop using Inbrija suddenly after regular use. Rapidly stopping or reducing levodopa can cause a serious reaction with high fever, muscle stiffness, confusion, and changes in breathing and heart rate. Ask your doctor how to stop safely.

Hallucinations and psychosis. Inbrija can cause or worsen hallucinations, confusion, paranoia, disorganized thinking, and aggressive or agitated behavior. Because of this risk, people with a major psychotic disorder should generally not use Inbrija. If these symptoms occur, your doctor may reduce your levodopa dose.

Impulse control and compulsive behaviors. Some people taking levodopa medicines experience intense urges they cannot control, including gambling, increased sexual urges, compulsive spending, or binge eating. You or your family may not recognize these as unusual, so tell your doctor if they develop. Your doctor may consider reducing the dose or stopping Inbrija.

Dyskinesia (uncontrolled movements). Inbrija may cause or worsen involuntary movements of the face, tongue, or body. If troublesome dyskinesia occurs, your doctor may adjust your daily Parkinson's medicines or consider stopping Inbrija.

Bronchospasm in people with lung disease. Inbrija is not recommended if you have asthma, COPD, or another chronic lung disease, because inhaling the powder can cause bronchospasm (wheezing, chest tightness, or trouble breathing). Stop using Inbrija and get medical help right away if this happens.

Increased eye pressure. Inbrija may raise pressure inside the eye in people with glaucoma. Your doctor should monitor your eye pressure during treatment.

Inbrija can also affect certain lab test results, including liver tests, and can cause false-positive results on tests for pheochromocytoma.

You should not use Inbrija if you currently take, or have taken in the past 2 weeks, a nonselective MAO inhibitor such as phenelzine, tranylcypromine, isocarboxazid, or linezolid. Using these together can cause dangerously high blood pressure.

The selective MAO-B inhibitors often prescribed for Parkinson's disease, including rasagiline, selegiline, and safinamide, may be used with Inbrija, but the combination can lower blood pressure when standing. Your doctor will monitor you for dizziness or fainting.

To make sure Inbrija is safe for you, tell your doctor if you have:

• asthma, chronic obstructive pulmonary disease (COPD), or another breathing disorder;
• glaucoma (Inbrija can raise pressure inside the eye, and your eye pressure should be monitored during treatment);
• a history of involuntary muscle movements (dyskinesia);
• a sleep disorder that causes daytime sleepiness;
• dizziness, nausea, or fainting when standing up from sitting or lying down;
• mental illness or psychosis (people with a major psychotic disorder should generally not use Inbrija, because levodopa can worsen psychotic symptoms) or
• intense urges or compulsive behaviors (such as gambling, binge eating, sexual urges, or spending money).

It is not known whether Inbrija will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Levodopa passes into breast milk and may also reduce milk production. It is not known if it can harm your baby. It may not be safe to breastfeed while using this medicine; ask your doctor or healthcare professional about any risk.

Get emergency medical help if you have signs of an allergic reaction to Inbrija: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using Inbrija and call your doctor or seek emergency care if you have wheezing, chest tightness, or trouble breathing after inhaling this medicine.

Call your doctor at once if you have:

• extreme drowsiness, or falling asleep suddenly, even after feeling alert;
• nausea, sweating, and a light-headed feeling, like you might pass out (signs of low blood pressure);
• uncontrolled muscle movements in your face or body (chewing, lip smacking, frowning, tongue movement, blinking) - in the clinical trial, dyskinesia occurred in 4% of people using Inbrija versus 1% on placebo;
• confusion, paranoia, or hallucinations (reported in fewer than 2% of people in trials);
• unusual thoughts or behavior, agitation, or aggression;
• trouble sleeping or increased dreaming;
• eye pain or vision changes; or
• new intense urges including gambling, sexual urges, binge eating, or compulsive spending.

How common are Inbrija side effects? In the 12-week clinical trial, the most common side effects (occurring in at least 5% of people and more often than with placebo) were.

• cough (15%, versus 2% with placebo) - cough was also the most common reason people stopped treatment, though only 2% of Inbrija users discontinued because of it;
• upper respiratory tract infection (6%);
• nausea (5%); and
• discolored sputum (5%). Levodopa can also darken saliva, sweat, or urine - this is harmless.

Cough and other side effects were notably more common in people 65 and older: cough affected 25% of older adults versus 5% of those under 65.

Some people also report a brief sensation of choking immediately after inhaling a dose.

Does Inbrija damage the lungs over time? In a 12-month study of people with Parkinson's disease and no chronic lung disease, lung function (measured by FEV1) declined by the same small amount (0.1 L) in people using Inbrija and in people on oral Parkinson's medications alone, which suggests no additional long-term effect on lung function in people without underlying lung disease.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual Adult Dose for Parkinson's Disease (OFF episodes):

• 84 mg (contents of two 42 mg capsules) by oral inhalation as needed when an OFF period starts
• Maximum dose per OFF period: 84 mg (one dose)
• Maximum: 5 doses (420 mg) per day

• You must be taking a daily Parkinson's disease medicine that contains carbidopa and levodopa before you start taking Inbrija. Do not stop taking your daily Parkinson's medicine. Inbrija does not replace your daily medicine.

Since Inbrija is used as needed for OFF episodes, you are not on a fixed dosing schedule. Never use two doses to treat the same OFF period.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Taking more than one dose for the same OFF period increases the risk of low blood pressure, fast heart rate, and new or worsening psychiatric symptoms such as confusion or hallucinations. Levodopa overdose has also been associated with muscle breakdown (rhabdomyolysis), which can cause muscle pain or weakness, dark urine, and kidney problems.

Avoid driving or hazardous activity until you know how Inbrija will affect you. Dizziness, drowsiness, or falling asleep suddenly can cause falls, accidents, or severe injuries. Alcohol and other sedating medicines can increase these risks.

Tell your doctor and other healthcare professionals about all medicines you take including over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

• Nonselective MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid, linezolid): do not use together - the combination can cause dangerously high blood pressure. Stop these medicines at least 2 weeks before starting Inbrija.
• MAO-B inhibitors (rasagiline, selegiline, safinamide): can be used with Inbrija, but the combination can cause low blood pressure when standing (orthostatic hypotension). Rise slowly and report dizziness or fainting.
• Dopamine-blocking medicines - metoclopramide, risperidone, haloperidol, phenothiazines (such as prochlorperazine), and other antipsychotics - work against levodopa and can make Inbrija less effective, worsening Parkinson's symptoms.
• Isoniazid can also reduce the effectiveness of levodopa.
• Iron supplements and multivitamins containing iron (ferrous sulfate, ferrous fumarate, ferrous gluconate): iron binds to levodopa in the gut and reduces the amount absorbed.

This list is not complete. Other drugs may interact with levodopa, including prescription and over-the-counter medicines, vitamins, and herbal products.

Store at room temperature (68°F to 77°F) away from moisture. Keep each capsule sealed in its blister pack until you are ready to use it, and never store capsules inside the inhaler. Throw away the inhaler when the capsules in the carton are used up. Dispose of unused or expired capsules through a medicine take-back program where available.