Last updated Jan. 30, 2023, by Teresa Carvalho, MS
Fact-checked by Marta Figueiredo, PhD
What is Inbrija for Parkinson’s disease?
Inbrija (levodopa inhalation powder) is an inhaled therapy used to treat symptoms of Parkinson’s disease during “off” episodes, or periods when standard levodopa-based treatments stop working and motor symptoms return.
Formerly known as CVT-301, it was developed by Acorda Therapeutics.
Acorda has entered commercialization agreements with other companies for marketing the therapy in regions outside the U.S. These include Esteve Pharmaceuticals in Germany and soon in Spain, and Biopas Laboratories in Latin America.
How does Inbrija work?
Parkinson’s is a neurodegenerative disorder caused by the progressive death of nerve cells in the brain, specifically those that produce a neurotransmitter called dopamine. Neurotransmitters are chemical messengers that pass signals between nerve cells. Dopamine is involved in signaling pathways for coordinating voluntary movement.
As these nerve cells die, dopamine levels in the brain decrease and Parkinson’s patients have symptoms such as the lack of motor control.
Dopamine can’t be directly administered to patients because it cannot cross the blood-brain barrier, a highly selective membrane that prevents microbes and large molecules in circulation from entering the brain and spinal cord.
Dopamine’s precursor, levodopa, can cross this barrier, and levodopa-based therapies are prescribed to increase dopamine levels in the brain of Parkinson’s patients. However, traditional tablet forms of levodopa may result in a variable dosage reaching the brain, due to varying amounts of levodopa being absorbed in the digestive system.
Levodopa is usually given in combination with carbidopa, which prevents levodopa from being converted into dopamine before it reaches the brain. Still, long-term use of levodopa-based treatments can lead to a reduction in the treatment’s effectiveness and, consequently, an increase in off periods.
Inbrija is a dry powder formulation of levodopa delivered via a specialized hand-held inhaler at a high and precise dose into the lungs, where it can be absorbed easily into the bloodstream. By avoiding the digestive system, it’s expected to deliver a higher and more consistent dose of levodopa to the brain and start working faster than the oral form of the medication.
Who can take Inbrija?
Inbrija was approved by the U.S. Food and Drug Administration (FDA) in 2018 for treating off episodes in Parkinson’s patients treated with carbidopa/levodopa.
It was approved for the same indication in the European Union the following year.
Who should not take Inbrija?
Inbrija should not be taken by patients taking nonselective monoamine oxidase (MAO) inhibitors or who have recently (within two weeks) received this medication. This type of therapy is used to treat depression and includes phenelzine and tranylcypromine.
Also, it’s generally not recommended for patients with a major psychotic disorder, due to a risk of psychosis exacerbation. Patients with asthma, chronic obstructive pulmonary disease (COPD), or other chronic underlying lung diseases are also not recommended to take Inbrija, as it may tighten the lung airways.
How is Inbrija administered in Parkinson’s disease?
Inbrija is available in 42-mg white-colored capsules with two black stripes and “A42” printed on one side. The capsules are administered by oral inhalation only and by using the specialized hand-held Inbrija inhaler.
Two Inbrija capsules (total, 84 mg) can be taken up to five times a day to treat off episodes. The maximum dose per off episode is 84 mg and the maximum recommended daily dose is 420 mg.
Capsules should be stored inside the blister set and only removed immediately before use. Inbrija capsules should not be swallowed.
Inbrija in clinical trials for Parkinson’s disease
Approvals of Inbrija were mainly supported by positive data from two placebo-controlled clinical trials.
SPAN-PD
The Phase 3 SPAN-PD trial (NCT02240030) evaluated the 3-month safety and effectiveness of two doses of Inbrija (60 and 84 mg) against a placebo in 351 adults with Parkinson’s.
Participants, recruited at sites in the U.S. and Europe, were having at least two hours of “off” time per day despite carbidopa/levodopa treatment (up to 1,600 mg of levodopa per day). Patients could take Inbrija or a placebo up to five times a day during off episodes.
Results showed compared with a placebo, treatment with 84 mg of Inbrija resulted in a significantly greater reduction of motor symptoms 30 minutes after dosing, as assessed with the Unified Parkinson’s Disease Rating Scale-part 3 score.
Also, a significantly greater proportion of patients on the higher dose returned to an “on” state and were maintained in that state for at least one hour relative to those on a placebo (58% vs. 36%).
After completing SPAN-PD, patients could choose to enroll in an open-label extension Phase 3 study (NCT02242487) meant for participants of previous Inbrija trials, in which all received either dose of the therapy for one year.
Results from the trial’s 325 participants showed the therapy’s safety profile was consistent with previous trials, with no major changes in lung function, and that long-term treatment led to a reduction in the duration of off episodes, especially with the 84-mg dose.
CVT-301-005
A Phase 3 trial, dubbed CVT-301-005 (NCT02352363), evaluated whether Inbrija was associated with lung function changes in 408 adults with Parkinson’s who were having daily off periods of at least two hours. Participants were given either 84 mg of Inbrija up to five times daily together with standard of care, or standard of care alone.
The results showed no significant differences in lung function measures between the Inbrija and standard care groups, suggesting Inbrija does not affect lung function. Also, Inbrija was associated with greater motor symptom control during off periods, whose duration was also reduced, when compared with standard of care alone.
Common side effects of Inbrija
The most common side effects related to treatment with Inbrija are:
- cough
- nausea
- upper respiratory tract infection
- discolored mucus that is coughed up from the lungs (a potential sign of infection)
Falling asleep during daily activities
There are reports of people falling asleep during daily activities while on levodopa-based treatments. Before initiating Inbrija treatment, any risk factors for increased sleepiness, such as sleep disorders and other co-prescribed medications, should be assessed by and discussed with prescribing healthcare providers.
Discontinuing treatment should be considered in severe cases of daytime sleepiness or episodes of falling asleep during daily activities. Patients in whom the therapy is not stopped should avoid driving and other activities where falling asleep unexpectedly can be dangerous.
Withdrawal-related high fever and confusion
High fever, stiff muscles, changes in breathing and heartbeat, and confusion following rapid dose reduction or discontinuation of Parkinson’s therapies have been reported.
Hallucinations, psychosis, and impulse control
Inbrija may cause psychological symptoms, such hallucinations (seeing or hearing things that are not real), confusion, psychotic behavior, and impulse control problems, such as urges to gamble and eat or increased sexual urges.
Due to a risk of worsening psychosis, patients with a major psychotic disorder should not be treated with Inbrija.
Treatment reduction or discontinuation should be considered for patients experiencing impulse control disorders.
Dyskinesia
Inbrija may cause or exacerbate dyskinesias, or uncontrolled, involuntary movements. If troublesome dyskinesias occur, it’s recommended that Inbrija treatment be stopped entirely or that the patient’s daily dose of Parkinson’s medications be adjusted.
Lung problems
Patients taking Inbrija are at increased risk of developing bronchospasm, the tightening of the muscles that line the lung airways that lead to wheezing, coughing, and other symptoms.
As such, the treatment is not recommended for those with asthma, COPD, or other chronic underlying lung diseases. If these symptoms occur in these patients, treatment should be stopped and patients should seek immediate medical attention.
Eye issues in patients with glaucoma
Inbrija may cause the fluid pressure of the eye to increase in patients with glaucoma, an eye condition. This complication should therefore be monitored while on Inbrija.
Abnormal blood tests results
There are reports of abnormal lab test results in patients treated with Inbrija. These may include increased levels of liver enzymes (a sign of liver injury), abnormal levels of urea nitrogen (a marker of kidney damage), and low levels of red blood cells.
Use in pregnancy and breastfeeding
Inbrija has not been well studied in women who are pregnant or breastfeeding. Based on animal studies, the therapy may cause harm to a developing fetus. Traces of levodopa were found in human breast milk, but the effects on a breastfed infant, or the effects on milk production in nursing patients remain largely unclear. As such, patients planning to be pregnant or breastfeed should discuss this issue with their healthcare providers.
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