Apokyn (apomorphine) for Parkinson’s disease
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What is Apokyn for Parkinson’s disease?
Apokyn (apomorphine hydrochloride injection) is an approved injectable therapy used to reduce off episodes, or periods when symptoms return between doses of standard levodopa treatment, in people with advanced Parkinson’s disease.
The medication was originally developed by Bertek Pharmaceuticals, a subsidiary of Mylan, but was licensed to Britannia Pharmaceuticals in 1999, and ultimately acquired by Supernus Pharmaceuticals in 2020.
Therapy snapshot
| Brand Name: | Apokyn |
| Chemical Name: | Apomorphine hydrochloride |
| Usage: | Add-on therapy to reduce off periods in advanced Parkinson’s disease |
| Administration: | Subcutaneous (under-the-skin) injection |
How does Apokyn work?
Parkinson’s disease is caused by the death and dysfunction of brain cells that produce the signaling chemical dopamine. Apokyn’s active ingredient is a dopamine agonist — meaning it mimics the activity of dopamine by binding to its receptor proteins.
Although the therapy’s exact mechanism of action is incompletely understood, it’s thought that Apokyn broadly works by increasing the potency of dopamine signaling. This is expected to improve motor symptom control in patients who experience off episodes while on levodopa-based therapies, which are a standard treatment for Parkinson’s.
Who can take Apokyn?
The U.S. Food and Drug Administration approved Apokyn in April 2004 to treat off episodes in people with advanced Parkinson’s. These episodes occur when levodopa-based treatments — which provide cells with more raw materials to produce dopamine — stop being effective, causing symptoms to return between doses. The approval made Apokyn the first therapy in the U.S. for these motor fluctuations in advanced Parkinson’s.
Apokyn also is approved in Europe and most of Asia under the brand names APO-go and Apokinon. The therapy is sold on both continents by Britannia Pharmaceuticals. In Canada, it’s marketed as Movapo by Paladin Labs, headquartered in Montreal.
Who should not take Apokyn?
Apokyn is not recommended for anyone with a known allergy to the treatment or its ingredients, which include a sulfite called sodium metabisulfite.
It also should not be used in combination with 5HT3 antagonists. This class of medicines includes treatments for nausea and vomiting — medications such as ondansetron, granisetron, dolasetron, and palonosetron — as well as alosetron, used to treat nausea associated with irritable bowel syndrome.
Elderly and pregnant patients should review the medication’s prescribing information for more information on possible adverse events and side effects.
Also, the therapy is not generally recommended for patients with a major psychotic condition due a potentially higher risk of phychosis exacerbation.
How is Apokyn administered in Parkinson’s?
Apokyn is administered via under-the-skin (subcutaneous) injections using a proprietary pen. It should not be injected directly into the bloodstream (intravenously), as this can cause dangerous blood clotting events.
The therapy is available in single-use cartridges which contain 30 mg of the medication in 3 mL of liquid (10 mg/mL). The recommended starting dosage is 0.1 mL (1 mg) to 0.2 mL (2 mg); in individuals with kidney problems, the lower starting dose should be used. That dose can be adjusted based on efficacy and tolerability up to a maximum of 0.6 mL (6 mg).
The first dose of Apokyn should be given by a healthcare professional. Patients and caregivers can be instructed in how to administer the therapy under appropriate circumstances.
Patients can take Apokyn up to five times daily, but doses should be given no less than two hours apart. If one dose of the therapy is ineffective during an off episode, a second dose should not be administered during that same off episode.
Because nausea and vomiting are common side effects of Apokyn, it’s recommended patients start treatment with the anti-nausea therapy trimethobenzamide three days before the first Apokyn dose. Trimethobenzamide should be given at a dose of 300 mg three times per day.
Apokyn in clinical trials
The FDA’s approval of Apokyn was supported by positive data from three placebo-controlled clinical trials.
Trials supporting approval
The first study enrolled 29 advanced Parkinson’s patients who were experiencing at least two hours of off time per day despite optimal standard treatment. Participants skipped their meds overnight to induce an off state, and then were randomly assigned to receive Apokyn or a placebo.
Treatment was started at a low dose (2 mg), with increasing doses of up to 10 mg given until the participants achieved a clinical response. Specifically, that response was one similar to what they would normally have on levodopa.
The results showed that 18 of the 20 patients given Apokyn achieved a therapeutic response at about 20 minutes after dosing. In comparison, none of the nine patients in the placebo group achieved a response.
Relative to the placebo, Apokyn significantly reduced scores on part three of the Unified Parkinson’s Disease Rating Scale (UPDRS), a measure of motor symptom severity. On UPDRS, higher scores indicate greater disability. In the study, scores were reduced by an average of 23.9 points with Apokyn, compared with 0.1 points with a placebo.
The second and third trials enrolled Parkinson’s patients who had been using Apokyn for at least three months. One study enrolled 17 participants, while the other involved 62 individuals. In both studies, participants were given their normal treatment, and when an off episode occurred, they were randomly assigned to receive either Apokyn or a placebo.
Findings from both studies showed Apokyn significantly outperformed the placebo at improving motor symptoms. The average reduction in UPDRS-part 3 scores was 17 points higher with Apokyn compared with a placebo in the second trial. In the third trial, it was 16.8 points higher.
AM IMPAKT
A Phase 4 open-label study called AM IMPAKT (NCT01770145) was conducted after the therapy’s approval. It tested Apokyn injections in 127 Parkinson’s patients with morning akinesia, or absence of movement, resulting from a delayed effect of their morning levodopa dose.
The results showed that a once-daily injection of Apokyn significantly reduced time-to-on, or the time it took for the levodopa dose to work or show effects. Data also showed the treatment was well tolerated in most patients.
Common side effects of Apokyn
The most common side effects of Apokyn include:
- yawning
- drowsiness and sleepiness
- dyskinesias or sudden uncontrolled movements
- dizziness or postural hypotension, a sudden drop in blood pressure upon moving from lying to sitting or standing
- runny nose
- nausea and vomiting
- hallucinations and confusion
- swelling of extremities.
In clinical studies, dyskinesia or worsening of dyskinesia was reported in more than 20% of patients. Patients also may experience injection site reactions, including bruising, swelling, and itching.
Data from clinical trials also suggest that patients ages 65 and older are more likely to experience certain adverse events with Apokyn, such as confusion, hallucinations, and a higher risk of falls.
Falling asleep during daily activities
Apokyn can cause drowsiness, and there have been reports of patients on the medication who suddenly fall asleep while going about their daily life activities. This risk should be discussed with prescribing healthcare providers, who should assess for any potential factors for increased sleepiness, such as other coprescribed medications.
If sudden sleeping episodes do occur, it’s generally recommended that Apokyn be discontinued. If treatment is not stopped, patients should avoid driving and other activities where falling asleep unexpectedly is dangerous.
Syncope and fall risk
Apokyn may cause changes in blood pressure, particularly orthostatic hypotension. In severe cases, this drop in blood pressure can lead to a loss of consciousness, referred to as syncope.
The risk of orthostatic hypotension, as well as changes in movement that may occur with the therapy, may increase the risk of falls for patients taking this medication.
Mental health, psychosis, and impulse control
There are reports of people experiencing new or worsening mental health problems after starting on Apokyn. These may include confusion and psychotic symptoms such as hallucinations, or seeing or hearing things that are not real. It is generally recommended that Apokyn should not be used to treat patients with a known psychotic disorder, as the treatment can aggravate psychotic symptoms.
Some patients also have experienced sudden problems with impulse control, such as urges to gamble or increased sexual urges, while taking Apokyn and other dopamine agonists. These urges may not feel abnormal to the person experiencing them. If such behavioral complications arise, it’s recommended that the dose of Apokyn be reduced or treatment stopped entirely.
Hemolytic anemia and heart health
There have been reports of patients on Apokyn developing hemolytic anemia, a condition characterized by the excessive destruction of red blood cells. If patients on Apokyn have low red blood cell counts, a workup for hemolytic anemia is recommended; if confirmed, it’s suggested Apokyn be discontinued.
Apokyn has been reported to cause abnormalities in heart rhythms. Heart-related complications, including heart attack and sudden death, also have been observed in patients receiving the medication. The potential risks and benefits of Apokyn should be carefully weighed before the therapy is used to treat individuals with cardiovascular and cerebrovascular problems, and its use should be reevaluated if patients develop any signs of such issues.
Allergic reactions
Apokyn may cause allergic reactions that are usually marked by rash, hives, and itchy skin. They also can result in tissue swelling or asthmatic episodes that can be life-threatening in some cases. One of the ingredients in the medication, called sodium metabisulfite, is known to cause those reactions, although asthmatic people tend to be more sensitive to this component.
Tissue changes and painful erections
Scarring-like tissue changes in the pelvis, lungs, and heart have been reported in some people given medicines similar to Apokyn. The therapy also may cause prolonged, painful erections (priapism) in some patients; in such cases, patients should inform their healthcare provider and seek help in the nearest hospital emergency room.
Use in pregnancy and breastfeeding
Use of Apokyn has not been thoroughly studied in patients who are pregnant or lactating. However, animal data suggest that using the medication during pregnancy could harm a developing fetus.
There also are no data on the presence of Apokyn in human milk, the effects on a breastfed infant, or the effects on milk production in nursing patients. Thus, individuals who are breastfeeding or plan to breastfeed while on the medication are advised to discuss this topic with their healthcare team.
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 Apokyn
The U.S. Food and Drug Administration approved Apokyn in 2004 as an add-on treatment for off periods in people with advanced Parkinson’s disease who are on levodopa-based treatments. The decision marked the first U.S. approval of a medication for off episodes in people with advanced disease.
Clinical trials of Apokyn have not included pregnant or breastfeeding patients, so it is unclear whether the therapy is safe in such conditions. Animal data has suggested, however, that the medication may cause fetal harm. Patients on Apokyn who become or plan to become pregnant should discuss these topics with their doctor.
Given its potential to cause drowsiness, and due to reports of people falling asleep during daily activities while on the therapy, Apokyn’s U.S. label recommends that patients starting the therapy do not drive or engage in other potentially dangerous activities until they know how it affects them. If patients do experience such adverse events, they are recommended to avoid those types of activities until they talk with their doctor.
As each person can respond differently to a medication, there is no standard timeline for when Apokyn starts to work. In the trials that supported the therapy’s approval, a significant reduction in motor symptoms during off periods could be observed in Apokyn-treated patients within 10 minutes, and the best treatment effects were seen after 20 minutes. Still, patients are advised to talk with their healthcare team on how the therapy can help in their particular case.
Hair loss and weight gain have not been reported as side effects of Apokyn in clinical trials, but some studies published after its approval have indicated that some patients can gain weight while on the medication due to compulsive eating, a known side effect of dopamine agonists. Patients should talk with their healthcare team if such events occur.
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