Inbrija (levodopa inhalation powder) for Parkinson’s disease
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What is Inbrija for Parkinson’s?
Inbrija (levodopa inhalation powder) is an inhaled therapy approved to ease 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, the add-on medication was developed by Acorda Therapeutics.
Acorda has entered agreements with other companies for marketing the therapy in regions outside the U.S. The company’s partners now include Esteve Pharmaceuticals in Germany and Spain, and Biopas Laboratories in Latin America. In China, rights to the therapy were acquired by Chance Pharmaceuticals, which will be responsible for regulatory submissions in the Asian nation.
Therapy snapshot
| Brand Name: | Inbrija |
| Chemical Name: | Levodopa |
| Usage: | Add-on therapy to reduce off episodes in Parkinson’s patients on carbidopa/levodopa treatment |
| Administration: | Oral inhalation |
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 nerve cells die, dopamine levels in the brain decrease and people with Parkinson’s develop symptoms such as the hallmark 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.
As dopamine’s precursor, levodopa can cross this barrier. Thus, 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, a molecule that blocks the activity of DOPA decarboxylase or DDC, an enzyme that converts levodopa into dopamine outside the brain. This combination increases the levels of levodopa reaching the brain, helping to reduce levodopa doses and the medicine’s associated side effects.
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. A high and precise dose of the medication is delivered 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 other oral forms of the medication.
Who can take Inbrija?
Inbrija was approved by the U.S. Food and Drug Administration in 2018 for treating off episodes in Parkinson’s patients treated with levodopa and carbidopa. The decision made Inbrija the first inhaled levodopa therapy in the U.S. for this indication.
The therapy was approved in the European Union the following year for reducing off periods in people with Parkinson’s treated with a combination of levodopa plus carbidopa or another DDC suppressor.
Who should not take Inbrija?
Inbrija should not be taken by patients taking nonselective monoamine oxidase (MAO) inhibitors — antidepressive medications — or who have received them in the prior two weeks. These therapies, which include phenelzine and tranylcypromine, can result in high blood pressure if used in combination with levodopa.
Also, Inbrija generally is 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 also are not recommended for Inbrija use, as it may tighten the lung airways.
How is Inbrija administered in Parkinson’s?
Inbrija is available in 42-mg white capsules with two black stripes and “A42” printed on one side. The capsules are administered by oral inhalation only and should be used solely with the specialized hand-held Inbrija inhaler.
The medication can be taken as soon as symptoms of an off period start to emerge. The recommended dose is two Inbrija capsules (total 84 mg) that can be taken as needed, up to five times a day. 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
An early Phase 2 trial (NCT01777555), completed in 2014, enrolled 86 people with Parkinson’s, ages 30-80. Results showed that Inbrija significantly reduced the amount of off time, by about 0.9 hours, compared with a placebo. The trial tested a dose of 50 mg per off episode, and a treatment effect was evident as early as 10 minutes after dosing.
Approvals of Inbrija were then supported by positive data from two placebo-controlled Phase 3 clinical trials, SPAN-PD and CVT-301-005.
SPAN-PD
The SPAN-PD trial (NCT02240030), completed in 2016, evaluated the three-month safety and effectiveness of two doses of Inbrija — 60 and 84 mg — against a placebo in 351 adults with mild to moderate Parkinson’s.
Participants, recruited at sites in the U.S. and Europe, were having at least two hours of off time per day despite levodopa and carbidopa treatment, with doses up to 1,600 mg of levodopa per day.
During the study, the assigned treatment could be taken up to five times a day during off episodes.
The results showed that, compared with the placebo, treatment with 84 mg of Inbrija (two 42 mg capsules) 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 taking the higher dose returned to an on state and maintained that state for at least one hour, relative to those on the placebo (58% vs. 36%).
After completing SPAN-PD, patients could choose to enroll in an open-label extension (NCT02242487) meant for participants of previous Inbrija trials. All participants received either dose of the therapy for one year.
Results from that trial’s 325 participants showed the therapy’s safety profile was consistent with previous trials, with no major changes in lung function. Long-term treatment also was seen to lead to a reduction in the duration of off episodes, especially with the 84 mg dose.
CVT-301-005
Another trial, dubbed CVT-301-005 (NCT02352363), evaluated whether Inbrija was associated with lung function changes in 408 adults with Parkinson’s. These participants were having daily off periods of at least two hours. Inbrija was given together with standard of care therapy, at a dose of 84 mg up to five times daily, or patients received 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. Additionally, Inbrija was associated with greater motor symptom control during off periods, whose duration also was 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
- discoloration in mucus 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, 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. Patients should avoid sudden discontinuation or rapid dose reductions of Inbrija to avoid these side effects.
Hallucinations, psychosis, and impulse control
Inbrija may cause psychological symptoms, such as hallucinations (seeing or hearing things that are not real), confusion, psychotic behavior, and impulse control problems, like urges to gamble and eat or increased sexual urges.
Due to a risk of worsening psychosis, patients with a major psychotic disorder generally should not be treated with Inbrija. Treatment reduction or discontinuation also should be considered for patients experiencing impulse control disorders.
Dyskinesia
Inbrija may cause or exacerbate dyskinesia, 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, a tightening of the muscles that line the lung airways. Such bronchospasms can lead to wheezing, coughing, and other symptoms.
As such, the treatment is not recommended for those with asthma, chronic obstructive pulmonary disease, or other chronic underlying lung diseases. If these symptoms occur in other individuals with Parkinson’s, 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 test 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, indicating anemia.
Use in pregnancy and breastfeeding
Inbrija has not been well studied in women who are pregnant or breastfeeding. However, animal studies suggest the therapy may cause harm to a developing fetus and its known mechanism of action indicates it may interfere with lactation.
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.
Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Inbrija
The U.S. Food and Drug Administration (FDA) approved Inbrija in December 2018 as an add-on treatment for off periods in Parkinson’s disease patients on levodopa and carbidopa. That decision made Inbrija the first inhaled levodopa therapy in the U.S. for Parkinson’s off episodes.
Clinical trials of Inbrija have not included pregnant patients, so the therapy’s safety in such conditions remains largely unknown. However, animal data has suggested that it may cause fetal harm. Patients should talk with their doctor about any plans for being pregnant while on Inbrija.
Some people on levodopa-based treatments have reported extreme somnolence or falling asleep during daily activities. Thus, until patients know how the medication affects them, those starting starting Inbrija should avoid driving, operating machinery, or other activities that may result in harm if they suddenly fall asleep.
In the trials that supported Inbrija’s approval, patients experienced reductions in motor symptoms during off periods as early as 10 minutes post-dosing, with significant effects being observed after 30 minutes. Still, as each person can respond differently to a medication, patients are advised to talk with their healthcare team on how Inbrija can help in their particular case.
While hair loss and weight gain have not been reported as side effects of Inbrija in clinical trials, patients may experience weight gain due to the therapy’s potential to cause impulse control disorders, including compulsive eating. Hair and weight loss are reported as potential side effects of the therapy on its European label. Patients should talk with their healthcare team if such events occur while they are taking Inbrija.
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