Onapgo (apomorphine hydrochloride) for Parkinson’s disease

Last updated Feb. 7, 2025, by Lindsey Shapiro, PhD
Fact-checked by Ana de Barros, PhD

 

What is Onapgo for Parkinson’s disease?

Onapgo (apomorphine hydrochloride), previously known as SPN-830, is a formulation of apomorphine, delivered as a continuous under-the-skin (subcutaneous) infusion, that’s intended to reduce motor symptom fluctuations that emerge between doses of standard levodopa-based treatment in adults with advanced Parkinson’s disease.

The therapy is marketed by Supernus Pharmaceuticals, which acquired the rights to Onapgo from US WorldMeds in 2020.

Onapgo is currently approved only in the U.S., however, in Europe, a similar therapy has been available since the 1990s for severe motor fluctuations. It is generally known as APO-go.

Therapy snapshot

Brand name:	Onapgo
Chemical name:	Apomorphine hydrochloride
Usage:	Used to reduce motor symptom fluctuations in Parkinson’s disease
Administration:	Continuous subcutaneous infusion

 

How does Onapgo work in Parkinson’s disease?

Parkinson’s disease is caused by the progressive loss of nerve cells that produce dopamine, a brain signaling chemical. Patients are treated with levodopa and related therapies, which aim to increase dopamine levels in the brain. However, with long-term use, the effects of these treatments can wear off and symptoms may return between doses. These periods of symptom reemergence are known as motor fluctuations, or off episodes.

Onapgo is a subcutaneous formulation of apomorphine, which is a small molecule that mimics the effect of dopamine in the brain. It’s also known as a dopamine agonist. Delivered continuously through a specialized infusion pump, the therapy is thus expected to reduce off episodes in Parkinson’s patients using levodopa-based therapies.

This delivery method has the potential to be less invasive — requiring fewer injection sites — and more convenient than Supernus’ Apokyn (apomorphine hydrochloride injection), a subcutaneous injection of apomorphine that’s approved for on-demand use to reduce off episodes.

Who can take Onapgo?

The U.S. Food and Drug Administration approved Onapgo in February 2024 for the treatment of motor fluctuations in adults with advanced Parkinson’s disease.

Who should not take Onapgo?

Onapgo should not be used at the same time as 5HT3 antagonists, also known as serotonin receptor antagonists, a class of medications primarily used to control nausea and vomiting. These medications include ondansetron, granisetron, dolasetron, palonosetron, and alosetron.

The therapy is also contraindicated, or not recommended for use, for people with a history of allergic reactions to apomorphine or any of the inactive ingredients in Onapgo, including sulfites such as sodium metabisulfite.

How is Onapgo administered in Parkinson’s?

Onapgo is administered as a continuous subcutaneous infusion during waking hours via a specialized pump, with extra booster doses possible based on individual need. While the therapy can be self-administered with proper training, initiation of Onapgo and any dose adjustments should always be done under medical supervision.

Dosing

Onapgo comes in single-dose cartridges containing 98 milligrams (mg) of apomorphine in 20 milliliters (mL) of a clear solution (4.9 mg/mL). The cartridges are used with an Onapgo pump kit, cartridge holders, and infusion sets that are supplied separately.

The daily dosage of Onapgo, comprising the continuous infusion and any extra needed doses, is determined based on a person’s individual needs but should not exceed 98 mg apomorphine per day.

The continuous infusion is generally given over waking hours, or a period of 16 hours per day. It is recommended to be started at an initial continuous dosage of 1 mg/hr, which can be titrated, or incrementally increased, up to a maximum of 6 mg/hr as needed.

In some cases, extra booster, or bolus, doses of Onapgo may be administered to provide better symptom control beyond the continuous infusion. Circumstances in which extra doses of Onapgo can be administered include:

• upon starting treatment in the morning
• when restarting a continuous dosage after a one-hour or longer break in use
• as a supplement to continuous dosing when off episodes are not controlled.

Extra doses can be titrated up in increments of 0.5 mg or 1 mg depending on a person’s clinical response and tolerability. Subsequent extra doses are between 0.5 and 2 mg, with at least three hours between extra doses and a maximum of 3 extra doses per day. If more than three extra doses are needed in a day, the continuous infusion dosage may need to be adjusted instead.

Sudden discontinuation or rapid dose reductions in Onapgo could cause a patient’s Parkinson’s symptoms to get worse. Where possible, the medication dose should be tapered down before stopping it entirely.

Preparation and administration

Onapgo can be administered by patients or caregivers if they are capable of understanding the delivery system and have been properly trained on its use. A doctor or nurse will program the Onapgo pump so that it is appropriately set up according to a patient’s prescription and will show the patient or caregiver exactly how to use it and keep it clean.

Before starting the infusion, the Onapgo solution should be checked to make sure it is clear and almost colorless, without any visible particulate matter. The infusion site, medication cartridge, and the hands of the person administering the treatment should always be clean before administration.

Once the cartridge is assembled and attached to the infusion pump, a thin tube called a cannula is primed and inserted under the skin to deliver the medication in one of the following areas:

• the abdomen, at least two inches away from the navel
• the top of the thigh
• the lower back
• the upper back, but only if the infusion site is being prepared by a caregiver or healthcare provider.

The infusion site should be rotated every day, and should always be kept clean.  If an infusion site is bruised, has bumps or nodules, or feels irritated, it should not be used.

A new medication cartridge and cartridge holder should be used each day. Any unused portion in the cartridge at the end of the day should be discarded. Onapgo should be stored at room temperature.

The pump must be placed inside the pump pouch provided with the system kit, which is then attached to either an elastic belt or a lanyard. The belt should be secured around the waist, while the lanyard should be placed around the neck.

Onapgo should only be given via subcutaneous infusion and never given directly into a vein, or intravenously, as this could cause serious adverse events such as blood clots. Also, the Onapgo infusion device is designed for continuous apomorphine infusion. It is not a substitute for apomorphine products that are intended for intermittent use.

Other information

Onapgo can cause nausea and vomiting, so it’s recommended that patients be treated with the anti-nausea medication trimethobenzamide (300 mg three times daily) starting three days before the first dose of Onapgo. Such treatment should be continued as long as needed to control nausea and vomiting, but generally not longer than two months, as trimethobenzamide can increase the incidence of side effects such as sleepiness, dizziness, or falls.

Onapgo in Parkinson’s disease clinical trials

Onapgo’s U.S. approval was based largely on data from two Phase 3 clinical trials, TOLEDO and INFUS-ON.

TOLEDO

The Phase 3 TOLEDO study (NCT02006121) was the first placebo-controlled trial evaluating the safety and efficacy of apomorphine continuous subcutaneous infusion in Parkinson’s patients with off periods.

Sponsored by Britannia Pharmaceuticals, which markets APO-go, the Europe-based study enrolled 107 people with Parkinson’s, ages 30 and older. Eligible patients were experiencing at least three hours daily of off time on an optimized levodopa-based treatment regimen.

The participants were randomly assigned to receive a continuous subcutaneous infusion of either an apomorphine solution (at a target rate of 3-8 mg per hour) or a placebo solution during waking hours, typically 14-18 hours per day. The trial spanned 12 weeks, or about three months. In both groups, the solution was delivered through the APO-go pump.

TOLEDO’s main goal was to determine the change in daily off time from the study’s start to the end of the treatment period, as assessed by patient symptom diaries. The results showed that the continuous apomorphine treatment resulted in a significantly greater reduction in daily off time relative to the placebo (by 2.47 vs. 0.58 hours). Also, a greater proportion of apomorphine-treated patients experienced at least a two-hour reduction in daily off time compared with those in the placebo group (62% vs. 29%).

Consistently, daily good on time — when symptoms are adequately controlled without troublesome dyskinesia, or uncontrolled movements — was increased by 2.77 hours in the apomorphine group and by less than an hour in the placebo group. Dyskinesia is a common side effect of levodopa-based therapy.

Other outcome measures also favored the continuous subcutaneous apomorphine infusion, including greater reductions in levodopa doses and improvements in patient-reported outcomes. Moreover, the therapy was generally well tolerated.

After completing the three-month placebo-controlled phase, 84 participants chose to enter the trial’s open-label extension phase, in which all received the apomorphine infusion for one year. Of them, 59 (70.2%) completed the study. Data showed that reductions in daily off time and increases in good on time were sustained through the extension phase.

INFUS-ON

The Phase 3 INFUS-ON trial (NCT02339064), sponsored by US WorldMeds, was designed to support the safety and efficacy findings of the TOLEDO study.

It enrolled 99 patients in the U.S. under similar enrollment criteria as TOLEDO and had a similar study design. The exception was that in INFUS-ON, all participants received the experimental therapy; there was no placebo group.

In this study, three months of SPN-830 treatment led to a significant reduction in daily off time by a mean of three hours, and a three-hour mean increase in daily good on time, the results showed. Also, 62.1% of patients experienced a reduction of two hours or more in daily off time.

Additional analyses showed that the therapy allowed patients to spend more than 80% of their waking hours in a good on state.

Common side effects of Onapgo

The most common side effects of Onapgo include:

• nodules, or lumps, at the infusion site
• nausea
• sleepiness
• infusion site redness, called erythema
• dyskinesia
• headache
• insomnia.

Blood clots

Onapgo should not be administered directly into a vein, as this may cause blood clots.

Nausea and vomiting

Onapgo can cause nausea and vomiting, which may be severe. Certain nausea medicines that block dopamine activity, such as haloperidol, chlorpromazine, promethazine, prochlorperazine, or metoclopramide, could worsen Parkinson’s symptoms, so the benefits and risks of their use with Onapgo should be carefully considered. 5HT3 blockers should not be used.

Excessive sleepiness

Onapgo is commonly associated with excessive sleepiness, known medically as somnolence, and there have been reports of people using apomorphine falling asleep during daily activities.

Before starting treatment, patients should be evaluated for risk factors for drowsiness, such as the use of sedating medications or the presence of other sleep disorders.

All individuals using Onapgo should be monitored for the development of excessive drowsiness.

If a patient does develop significant daytime sleepiness or is falling asleep during daily activities, it’s recommended that Onapgo should be discontinued. If it is continued, patients should be advised not to drive or perform other activities where falling asleep could be dangerous.

Low blood pressure, fainting, and fall risk

Onapgo can cause low blood pressure. This includes situations in which blood pressure drops significantly upon standing from a sitting or lying down position, known as orthostatic hypotension. This can happen at any time, but especially during dose escalation. Patients should be carefully monitored for blood pressure changes when using Onapgo, and should be advised to get up slowly and avoid changing positions too quickly.

Certain medications, especially ones intended to lower blood pressure or increase blood flow, may increase the risk of orthostatic hypotension in people using Onapgo. Alcohol should also be avoided, as this can also exacerbate the medication’s effects on blood pressure.

Blood pressure changes may sometimes lead to syncope, or fainting, as well as an increased risk of falls. Onapgo can also cause new or worsening dyskinesia that could affect movement. Mobility changes, coupled with blood pressure drops, may further increase this fall risk.

Infusion site reactions and infections

Onapgo may cause a variety of infusion site reactions, including nodules, redness, bruising, inflammation, itching, swelling, or discoloration. Infections at the infusion site may also occur. If an infection is suspected, the infusion device should be removed and a new one placed in a different site.

Behavioral changes

There have been reports of alterations in mental status and behavior, including hallucinations or psychotic-like behaviors, in people who use subcutaneous apomorphine. The relative risks and benefits of using Onapgo in a person with an existing psychiatric disorder should be carefully considered due to the possible risk that it will be exacerbated. Certain medications used to treat psychosis could also make Parkinson’s symptoms worse or decrease Onapgo’s effectiveness.

Patients may also experience sudden problems with impulse control, such as intense urges to gamble, spend money, or have sex. Patients may not recognize these impulses as abnormal. If impulse control problems arise, doctors should consider reducing the dose of Onapgo or stopping it entirely.

Dyskinesia

Treatment with Onapgo can lead to dyskinesia — uncontrolled, involuntary movements that can occur in Parkinson’s patients — or worsen existing symptoms.

Hemolytic anemia

Apomorphine can cause hemolytic anemia, characterized by the excessive destruction of red blood cells, which can occur at any time. If patients show signs of hemolytic anemia, they should be thoroughly evaluated for the condition, and if it is confirmed, Onapgo may need to be discontinued.

Patients should tell their healthcare provider if they experience any possible signs of anemia, including: becoming pale, having a fast heartbeat, feeling more tired or weaker than usual, skin or eyes that look yellow, chest pain, shortness of breath, dark urine, fever, dizziness, or confusion.

Heart problems

Onapgo can lead to changes in the heart’s electrical rhythm, and there have been reports of heart complications, including cardiac arrest, in people given apomorphine.  The medication’s use in people with risk factors for these problems should be carefully considered before starting initiation.

Due to its blood pressure-lowering effects, Onapgo could also exacerbate existing heart conditions or the risk of stroke in some individuals. If patients develop signs or symptoms of these conditions, doctors will need to re-evaluate whether Onapgo can be continued.

Allergic reactions

Some patients may experience an allergic reaction to Onapgo, with symptoms such as rash, itching, hives, or swelling. One of the medication’s inactive ingredients, sodium metabisulfite, can cause allergic reactions that affect the airways and that can be life-threatening in rare cases, although such effects are seen more often in people with asthma.

Patients should seek immediate medical attention if they experience symptoms of an allergic reaction.

Tissue changes and painful erections

Medications that mimic the activity of dopamine have been associated with cases of scar tissue buildup, known as fibrosis, and other tissue changes in the lungs, abdomen, and heart, that may or may not resolve after the medication is stopped. It is not known whether Onapgo may also cause these complications.

Apomorphine has been associated with prolonged and painful erections, also known as priapism. Patients should seek medical attention immediately if they have an erection that lasts more than four hours.

Vision problems

In animal studies, degeneration of the retina, a thin layer of tissue located at the back of the eye that is responsible for sensing and transmitting visual information to the brain, was observed. While the clinical significance of this side effect is unknown, it should not be dismissed as it involves a mechanism present in humans.

Pregnancy and breastfeeding

The use of Onapgo in patients who are pregnant has not been studied, but animal studies indicate that using the medication during pregnancy may cause harm to a developing fetus.

No data are available on whether Onapgo passes into human breastmilk or whether it is safe to use the medication while breastfeeding. The benefits of breastfeeding should be weighed with the mother’s need for Onapgo or any potential adverse effects in the breastfed infant.

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