Last updated Jan. 12, 2023, by Marisa Wexler, MS
Fact-checked by Marta Figueiredo, PhD
What is Apokyn for Parkinson’s disease?
Apokyn (apomorphine hydrochloride injection) is an approved injectable therapy used to treat loss of body movement control in people with advanced Parkinson’s disease in between doses of standard levodopa treatment.
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 exact mechanism of action driving the therapy is incompletely understood, it’s thought that Apokyn works broadly by increasing the potency of dopamine signaling.
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.
Who should not take Apokyn?
Apokyn should not be taken by 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 include treatments for nausea and vomiting (such as ondansetron, granisetron, dolasetron, and palonosetron), as well as alosetron, used to treat nausea associated with irritable bowel syndrome.
Also, the therapy is not generally recommended for patients with psychosis, due to a risk of exacerbation in that disorder.
How is Apokyn administered in Parkinson’s disease?
Apokyn is administered via under-the-skin (subcutaneous) injection using a proprietary pen. It should not be injected directly into the bloodstream, as this can cause dangerous blood clotting events.
The therapy is available in single-use cartridges which contain 3 mL of liquid with 30 mg of the medication (10 mg/mL). The approved 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. The 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 administered by a healthcare professional. Patients and caregivers can be instructed in how to administer the therapy under appropriate circumstances.
Doses of Apokyn 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 that 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 for Parkinson’s disease
Trials supporting approval
The FDA’s approval of Apokyn was supported by positive data from three placebo-controlled clinical trials.
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 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 participants achieved a clinical response. Specifically, that would be a response similar to the one they’d usually have on levodopa.
Results showed that 18 of the 20 patients given Apokyn achieved a therapeutic response at about 20 minutes after dosing. That was in comparison to none of the nine patients in the placebo group. Relative to a placebo, Apokyn significantly reduced scores on part three of the Unified Parkinson’s Disease Rating Scale (UPDRS), which measures the severity of motor symptoms and whose high scores indicate greater disability. 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, the other included 62 individuals. In both studies, participants were given their normal treatment, and then when an “off episode” occurred, they were randomly assigned to receive either Apokyn or a placebo.
Findings from both studies showed that 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 and 16.8 points higher in the third trial.
A Phase 4 open-label study called AM IMPAKT (NCT01770145) was conducted after the therapy’s approval. It tested Apokyn injections in Parkinson’s patients with morning akinesia, or absence of movement, resulting from a delayed effect onset of their morning levodopa dose.
Results showed that a once-daily injection of Apokyn significantly reduced time-to-on, the time it took for the levodopa dose to work or show effects. Data also showed the treatment was well-tolerated in most patients.
Of note, Supernus’ SPN-830, an apomorphine infusion pump that allows continuous treatment administration, is being reviewed by the FDA for the treatment of “off” episodes in adults with Parkinson’s. This mode of administration is expected to be more convenient for patients and to reduce injection site reactions.
Common side effects of Apokyn
The most common side effects of Apokyn include:
- dyskinesias (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. This risk should be discussed with prescribing healthcare providers, who should assess for any risk factors for increased sleepiness, such as other co-prescribed 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 (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.
There have been reports of patients who experience 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 that Apokyn be discontinued.
Apokyn has been reported to cause abnormalities in heart rhythms. Heart-related complications, including heart attack and sudden death, have been reported for patients on 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 re-evaluated if patients develop any signs of cardiovascular and cerebrovascular issues.
Tissue changes and priapism
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 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. However, individuals who are breastfeeding or plan to breastfeed while on the medication are advised to discuss this topic with their healthcare team.
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