ONAPGO Apomorphine hydrochloride 4.9 mg/mL Injection, Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Dopaminergic Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Apomorphine injection is used to treat ''off'' episodes (times of difficulty moving, walking, and speaking that may happen as medication wears off or at random) in people with Parkinson's disease (PD; a disorder of the nervous system that causes difficulties with movement, muscle control, and balance). Apomorphine injection is in a class of medications called dopamine agonists. It works by acting in place of dopamine (a natural substance produced in the brain) to control movement.
Read the full MedlinePlus article ↗- It's used to treat 'off' episodes in advanced Parkinson's disease — those sudden spells when your regular Parkinson's medication seems to stop working and you feel stiff, slow, or...
- What exactly is apomorphine injection used for?
- Nausea and vomiting are very common with apomorphine — most patients are started on an anti-nausea medication called trimethobenzamide a few days before their first dose to help ma...
- Will I feel sick to my stomach when I use it?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Apomorphine Hydrochloride — tap one for details:
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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0.5 mg / 1 mL
UNII 4VON5FNS3C
Sodium metabisulfite is a preservative derived from sulfur compounds. It prevents microbial growth and oxidation in medicines, helping extend shelf life and maintain product stability.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
3 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $14.03 | $1,402.95 / 100 ml |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Onapgo 4.9 mg/mLthis 27505-0006-05 | MDD | 5 cartridges | — | — | FDA listed | — |
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⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Code | What it grants | Expires |
|---|---|---|
| NP | New Product | Feb 3, 2028 |
Is there a generic version of ONAPGO 98 MG/20 ML CARTRIDGE?
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 27505-0006-05 You're viewing this | 5 CARTRIDGE in 1 CARTON (27505-006-05) / 20 mL in 1 CARTRIDGE (27505-006-01) | 2025-02-04 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE ONAPGO is indicated for the treatment of motor fluctuations in adults with advanced Parkinson's disease. ONAPGO is a dopaminergic agonist indicated for the treatment of motor fluctuations in adults with advanced Parkinson's disease. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For subcutaneous use by infusion only. ( 2.1 ) Maximum recommended total daily dosage of ONAPGO, including the continuous dosage and any extra dose(s), is 98 mg generally administered over the waking day (e.g., 16 hours). ( 2.3 ) The recommended initial continuous dosage is 1 mg/hr with a maximum of 6 mg/hr for up to 16 hours per day.
( 2.3 ) For patients who require an extra dose, initiate the first extra dose at 0.5 mg. Subsequent extra doses may be titrated in increments of 0.1 mg to 1 mg, based on clinical response and tolerability. The maximum extra dose is 2 mg.
Administer with at least 3 hours between extra doses and a maximum of 3 extra doses per day. ( 2.3 ) Treatment with trimethobenzamide is recommended, starting 3 days prior to the first dose of ONAPGO, and should only be continued as long as necessary to control nausea and vomiting, and generally no longer than two months. ( 2.2 , 5.2 , 6.1 , 17 ) ONAPGO is not substitutable for apomorphine products intended for intermittent use.
( 2.3 ) For patients with mild or moderate renal impairment, the recommended initial extra dose is 0.5 mg to 1 mg and should not exceed 1 mg. ( 2.5 )
2.1Important Information ONAPGO is indicated for subcutaneous use by infusion only [see Warnings & Precautions (5.1) ] . Patients selected for treatment with ONAPGO should be capable of understanding and trained on using the delivery system, either themselves or with the assistance of a caregiver [see Healthcare Provider Instructions for Use and Patient Instructions for Use ]. ONAPGO initiation and dose titrations should be done under medical supervision.
The prescribed dose of ONAPGO should be expressed in "mg/hr" for the continuous dosage and "mg" for an extra dose.
2.2Premedication and Concomitant Medication Because of the incidence of nausea and vomiting with ONAPGO, it is recommended that treatment with trimethobenzamide 300 mg three times a day start 3 days prior to the initial dose of ONAPGO [see Adverse Reactions (6.1) and Warnings and Precautions (5.2) ] . Alternatively, consider starting ONAPGO therapy, without antiemetics, at 1 mg/hour and titrate based upon effectiveness and tolerance. If trimethobenzamide is used, it should be continued only as long as necessary to control nausea and vomiting, and generally no longer than two months after initiation of treatment with ONAPGO, as trimethobenzamide increases the incidence of somnolence, dizziness, and falls in patients treated with ONAPGO [see Warnings and Precautions (5.2) ] .
Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with drugs of the 5HT 3 antagonist class including antiemetics (e.g., ondansetron, granisetron, dolasetron, palonosetron) and alosetron are contraindicated [see Contraindications (4) ] . After starting ONAPGO, adjustment of concomitant anti-Parkinson's disease medications may be necessary.
2.3Recommended Dosage ONAPGO (apomorphine hydrochloride) is administered as a subcutaneous infusion with the ONAPGO pump [see Dosage and Administration (2.3) , Healthcare Provider Instructions for Use, and Patient Instructions for Use ]. The daily dosage is determined by individualized patient titration and is composed of a continuous dosage and as needed extra dose(s). The maximum recommended total daily dosage of ONAPGO, including the continuous dosage and any extra dose(s), is 98 mg per day, generally administered over the waking day (e.g., 16 hours).
Continuous Dosage The recommended initial continuous dosage (continuous infusion) of ONAPGO is 1 mg/hr. Titrate the continuous dosage, as needed, in 0.1 mg/hr to 1 mg/hr increments. Dose adjustments may be made daily, or at longer intervals, through the titration process.
Patients in clinical studies used a mean of 4 mg/hr of ONAPGO. The maximum continuous dosage is 6 mg/hour administered over the waking day (e.g., 16 hours). Extra Dose Extr…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 98 mg/20 mL (4.9 mg/mL) apomorphine hydrochloride is a clear, almost colorless solution available in a single-dose prefilled cartridge. Injection: 98 mg/20 mL (4.9 mg/mL) of apomorphine hydrochloride in single-dose cartridges. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS ONAPGO is contraindicated in patients: Using concomitant 5HT 3 antagonists, including antiemetics (e.g., ondansetron, granisetron, dolasetron, palonosetron) and alosetron [see Drug Interactions (7.1) ] . There have been reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron. With hypersensitivity/allergic reaction to apomorphine or any of the excipients of ONAPGO, including sulfite (i.e., sodium metabisulfite).
Angioedema or anaphylaxis may occur [see Warnings and Precautions (5.13) ]. Concomitant use of ONAPGO with 5HT 3 antagonists, including antiemetics (e.g., ondansetron, granisetron, dolasetron, palonosetron) and alosetron. ( 4 , 7.1 ) Hypersensitivity to apomorphine or the excipients of ONAPGO, including sulfite (i.e., sodium metabisulfite).
( 4 , 5.13 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Subcutaneous use only; thrombus formation and pulmonary embolism have followed intravenous administration of ONAPGO. ( 5.1 ) May cause nausea and vomiting. ( 2.2 , 5.2 ) Falling asleep during activities of daily living and daytime somnolence may occur.
( 5.3 ) May cause hypotension/orthostatic hypotension and syncope may occur. ( 5.4 ) May cause or increase the risk of falls. ( 5.5 ) May cause infusion site reactions and infections.
Monitor and change infusion site every day. ( 2.4 , 5.6 ) May cause hallucinations and psychotic-like behavior. ( 5.7 ) May cause dyskinesia or exacerbate pre-existing dyskinesia.
( 5.8 ) May cause hemolytic anemia. ( 5.9 ) May cause impulse control/compulsive and impulsive behaviors. Consider dose reductions or stopping ONAPGO.
( 5.10 ) May cause cardiac events. ( 5.11 ) May prolong QTc and cause torsades de pointes or sudden death. ( 5.12 )
5.1Serious Adverse Reactions After Intravenous Administration Do not administer ONAPGO intravenously. Following intravenous administration of apomorphine, serious adverse reactions including thrombus formation and pulmonary embolism caused by intravenous crystallization of apomorphine have occurred.
5.2Nausea and Vomiting ONAPGO is known to cause nausea and vomiting, which may be severe. In Study 1 [see Clinical Studies (14) ] 87% of patients were pretreated with an antiemetic. Twenty-two percent of patients treated with ONAPGO reported nausea and 7% reported vomiting, compared to 9% and 4%, respectively, of patients who received placebo.
The ability of concomitantly administered antiemetic drugs (other than trimethobenzamide) to reduce apomorphine-associated nausea/vomiting has not been studied. Antiemetics with anti-dopaminergic actions (e.g., haloperidol, chlorpromazine, promethazine, prochlorperazine, metoclopramide) have the potential to worsen the symptoms in patients with Parkinson's disease (PD) and therefore the benefits and risks of treatment with these antiemetics should be carefully considered. The use of ONAPGO with 5HT 3 antiemetics is contraindicated.
5.3Falling Asleep During Activities of Daily Living and Somnolence Somnolence is commonly associated with ONAPGO . Patients treated with dopaminergic medications, including apomorphine, have also reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event.
In the double-blind placebo-controlled trial (Study 1), somnolence was reported in 22% of patients treated with ONAPGO and 4% of patients in the placebo group. Falling asleep while engaged in activities of daily living usually occurs in patients experiencing preexisting somnolence, although patients may not give such a history. Therefore, prescribers should reassess patients for drowsiness or sleepiness while using ONAPGO, especially because some of the events occur well after the start of treatment.
Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Before initiating treatment with ONAPGO, advise patients of the risk of drowsiness and ask them about factors that could increase the risk with ONAPGO, such as concomitant sedating medications and the presence of sleep disorders. If a patient develops significant daytime sleepiness or falls asleep during activities that require active participation (e.g., conversations, eating, etc.), ONAPGO should ordinarily be discontinued.
If a decision is made to continue ONAPGO, patients should be advised not to drive and to avoid other potentially dangerous activities. There is insufficient information to determine whether dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
5.4 Syncope/H…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Adverse Reactions After Intravenous Administration [see Warnings and Precautions (5.1) ] Nausea and Vomiting [see Warnings and Precautions (5.2) ] Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.3) ] Syncope/Hypotension/Orthostatic Hypotension [see Warnings and Precautions (5.4) ] Falls [see Warnings and Precautions (5.5) ] Infusion Site Reactions and Infections [see Warnings and Precautions (5.6) ] Hallucinations/Psychotic-Like Behavior [see Warnings and Precautions (5.7) ] Dyskinesia [see Warnings and Precautions (5.8) ] Hemolytic Anemia [see Warnings and Precautions (5.9) ] Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.10) ] Cardiac Events [see Warnings and Precautions (5.11) ] QTc Prolongation and Potential for Proarrhythmic Effects [see Warnings and Precautions (5.12) ] Hypersensitivity [see Warnings and Precautions (5.13) ] Fibrotic Complications [see Warnings and Precautions (5.14) ] Priapism [see Warnings and Precautions (5.15) ] Most common adverse reactions (incidence ≥10% on ONAPGO and at least twice the rate of placebo) were infusion site nodule, nausea, somnolence, infusion site erythema, dyskinesia, headache, and insomnia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact MDD US Operations, LLC, a subsidiary of Supernus Pharmaceuticals, Inc. at toll-free number 1-833-366-2746 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 197 Parkinson's disease patients were exposed to ONAPGO in Study 1 and subsequent open-label studies. In Study 1 [see Clinical Studies (14) ], the most common adverse reactions (incidence 10% or greater in patients treated with ONAPGO and at a rate at least twice the placebo rate) were infusion site nodule, nausea, somnolence, infusion site erythema, dyskinesia, headache, and insomnia.
Table 1 presents adverse reactions that occurred in ≥5% of patients treated with ONAPGO and that occurred more frequently than placebo in patients who were enrolled in Study 1. Table 1: Adverse Reactions Reported by ≥5% of Patients Treated with ONAPGO and More Frequently than Placebo in Study 1 ONAPGO Variable doses [see Dosage and Administration (2.3)] N=54 % Placebo N=53 % Infusion site nodule 44 0 Nausea 22 9 Somnolence 22 4 Infusion site erythema 17 4 Dyskinesia 15 0 Headache 13 4 Insomnia 11 2 Dizziness 9 4 Hypotension 7 0 Asthenia 7 0 Fatigue 7 2 Constipation 7 6 Vomiting 7 4 Infusion Site Reactions In Study 1, infusion site reactions were most commonly reported as nodule formation (44% of patients treated with ONAPGO compared to no patients who received placebo) or erythema (17% of patients treated with ONAPGO compared to 4% of patients who received placebo).
Less Common Adverse Reactions Other adverse reactions, including hallucinations, psychotic disorder, impulse control disorder, prolonged QT interval, and infusion site infections [see Warnings and Precautions (5.6) ] , have been reported in patients treated with ONAPGO [see Warnings and Precautions (5.7 , 5.10 . 5.12) ]. Adverse Reactions Leading to Discontinuation of ONAPGO Treatment Six (11%) patients treated with ONAPGO reported one of the following adverse reactions as the reason for discontinuing from Study 1: nausea, orthostatic intolerance, visual hallucination, gait disturbance, infusion site nodule, and hypotension.
None of the patients who received placebo discontinued from Study 1 because of an adverse reaction.
6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of apomorphine…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Concomitant use of antihypertensive medications and vasodilators: increased risk for hypotension, falls, and injuries. ( 7.2 ) Dopamine antagonists, such as neuroleptics or metoclopramide, may diminish the effectiveness of ONAPGO. ( 7.4 ) 7.1 5HT 3 Antagonists Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of ONAPGO with 5HT 3 antagonists, including antiemetics (e.g., ondansetron, granisetron, palonosetron) and alosetron, is contraindicated [see Warnings and Precautions (5.4) ].
7.2Antihypertensive Medications and Vasodilators In clinical studies with intermittent subcutaneous administration of apomorphine, the following adverse reactions were experienced more commonly in patients receiving concomitant antihypertensive medications or vasodilators (n=94) than in patients not receiving these medications (n=456): hypotension (10% vs 4%), myocardial infarction (3% vs 1%), [see Warnings and Precautions (5.4 , 5.11) ]. In a study of healthy subjects, concomitant administration of 0.4 mg sublingual nitroglycerin with subcutaneous apomorphine caused greater decreases in blood pressure than with subcutaneous apomorphine alone [see Clinical Pharmacology (12.3) ].
Patients treated with ONAPGO should lie down before and after taking sublingual nitroglycerin to decrease the potential risks associated with hypotension .
7.3Alcohol In a study of healthy subjects, concomitant administration of high dose (0.6 g/kg) or low dose (0.3 g/kg) ethanol with apomorphine caused greater decreases in blood pressure than with apomorphine alone [see Clinical Pharmacology (12.3) ] . Patients should be advised not to consume alcohol while treated with ONAPGO because it may cause greater decreases in blood pressure [see Warnings and Precautions (5.4) ] .
7.4Dopamine Antagonists Because ONAPGO is a dopamine agonist, it is possible that concomitant use of dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of ONAPGO. Antiemetics with anti-dopaminergic actions should be avoided [see Warnings and Precautions (5.2) ]. Patients with major psychotic disorders, treated with neuroleptics, should be treated with dopamine agonists only if the potential benefits outweigh the risks [see Warnings and Precautions (5.7) ].
7.5Drugs Prolonging the QT/QTc Interval Caution should be exercised when prescribing ONAPGO concomitantly with drugs that prolong the QT/QTc interval [see Warnings and Precautions (5.12) and Clinical Pharmacology (12.2) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 )
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of ONAPGO in pregnant women. In animal reproduction studies, apomorphine had adverse developmental effects in rats (increased neonatal deaths) and rabbits (increased incidence of malformation) when administered during pregnancy at clinically relevant doses. These doses were also associated with maternal toxicity.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data No adverse developmental effects were observed when apomorphine (0.3, 1, or 3 mg/kg/day) was administered by subcutaneous injection to pregnant rats throughout organogenesis; the highest dose tested is less than the maximum recommended human dose (MRHD) of 98 mg on a mg/m 2 basis.
Administration of apomorphine (0.3, 1, or 3 mg/kg/day) by subcutaneous injection to pregnant rabbits throughout organogenesis resulted in an increased incidence of malformations of the heart and/or great vessels at the mid and high doses; maternal toxicity was observed at the highest dose tested. The no-effect dose (0.3 mg/kg/day) for adverse effects is less than the MRHD on a mg/m 2 basis. Apomorphine (0.3, 1, or 3 mg/kg/day), administered by subcutaneous injection to female rats throughout gestation and lactation, resulted in increased offspring mortality at the highest dose tested, which was associated with maternal toxicity.
There were no effects on developmental parameters or reproductive performance in surviving offspring. The no-effect dose (1 mg/kg/day) for developmental toxicity is less than the MRHD on a mg/m 2 basis.
8.2Lactation Risk Summary There are no data on the presence of apomorphine in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ONAPGO and any potential adverse effects on the breastfed infant from ONAPGO or from the underlying maternal condition.
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
8.5Geriatric Use In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of comorbid disease or other drug therapy. Clinical studies of ONAPGO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Clinical experience with intermittent subcutaneous use of apomorphine has shown that the following adverse reactions were reported more frequently in patients 65 years of age or older (n=311) compared to patients less than 65 years of age (n=239): confusion; hallucinations; serious adverse reactions (life-threatening events or events resulting in hospitalization and/or increased disability); falls (experiencing bone and joint injuries); cardiovascular events; respiratory disorders; gastrointestinal events; and discontinuation of treatment as a result of one or more adverse reactions.
8.6Renal Impairment The initial extra dose of ONAPGO should not exceed 1 mg in patients with mild or moderate renal impairment because of increased apomorphine concentration and exposure (C max and AUC) in these patients. Studies in patients with severe renal impairment have not been conducted [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ].
8.7Hepatic Impairment Exercise caution and closely monitor if ONAPGO is administered to patients with mild or moderate hepatic impairment because of increased apomorphine concentration and…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of ONAPGO in pregnant women. In animal reproduction studies, apomorphine had adverse developmental effects in rats (increased neonatal deaths) and rabbits (increased incidence of malformation) when administered during pregnancy at clinically relevant doses. These doses were also associated with maternal toxicity.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data No adverse developmental effects were observed when apomorphine (0.3, 1, or 3 mg/kg/day) was administered by subcutaneous injection to pregnant rats throughout organogenesis; the highest dose tested is less than the maximum recommended human dose (MRHD) of 98 mg on a mg/m 2 basis.
Administration of apomorphine (0.3, 1, or 3 mg/kg/day) by subcutaneous injection to pregnant rabbits throughout organogenesis resulted in an increased incidence of malformations of the heart and/or great vessels at the mid and high doses; maternal toxicity was observed at the highest dose tested. The no-effect dose (0.3 mg/kg/day) for adverse effects is less than the MRHD on a mg/m 2 basis. Apomorphine (0.3, 1, or 3 mg/kg/day), administered by subcutaneous injection to female rats throughout gestation and lactation, resulted in increased offspring mortality at the highest dose tested, which was associated with maternal toxicity.
There were no effects on developmental parameters or reproductive performance in surviving offspring. The no-effect dose (1 mg/kg/day) for developmental toxicity is less than the MRHD on a mg/m 2 basis.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of comorbid disease or other drug therapy. Clinical studies of ONAPGO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Clinical experience with intermittent subcutaneous use of apomorphine has shown that the following adverse reactions were reported more frequently in patients 65 years of age or older (n=311) compared to patients less than 65 years of age (n=239): confusion; hallucinations; serious adverse reactions (life-threatening events or events resulting in hospitalization and/or increased disability); falls (experiencing bone and joint injuries); cardiovascular events; respiratory disorders; gastrointestinal events; and discontinuation of treatment as a result of one or more adverse reactions.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action ONAPGO is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors. The precise mechanism of action of ONAPGO as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.
12.2Pharmacodynamics Prolongation of the QTc Interval and Cardiac Electrophysiology In a thorough QT study, the mean increase in QTcF was 12.5 ms (90% two-sided upper confidence interval = 18.0 ms) after administration of a continuous dose of ONAPGO 6 mg/hr (maximum recommended infusion rate) in healthy subjects. A mean increase in QTcF of 14.6 ms (90% two-sided confidence interval = 20.1 ms) was observed at a dose and exposure similar to that expected with the maximum recommended total daily dosage of 98 mg. The maximum placebo-corrected increase in heart rate was 14.1 bpm (90% two-sided upper confidence interval = 17.4 bpm) at the dose and exposure similar to that expected with the maximum recommended total daily dose of 98 mg.
12.3Pharmacokinetics Absorption After subcutaneous administration, apomorphine appears to have bioavailability equal to that of intravenous administration. Steady-state concentrations are reached in approximately two hours after initiation of a continuous dose. If an extra dose is administered at the initiation of the continuous dose [see Dosage and Administration (2.3) ] , time to reach half (50%) of infusion steady-state concentrations can be shortened by 50-75%.
If an extra dose is administered two hours or later following initiation of a continuous dose, the supplemental exposure from the extra dose reaches peak concentration in 20-40 minutes. Distribution and Binding The plasma-to-whole blood apomorphine concentration ratio is equal to one. Mean (range) apparent volume of distribution was 218 L (123 to 404 L).
Protein binding in humans is 89% and concentration independent. Elimination The mean apparent clearance of apomorphine from plasma is 261 to 280 L/hr for ONAPGO with infusion rates ranging from 2 to 6 mg/hr. After administration of an extra dose, the mean elimination half-life is approximately 40 minutes.
Metabolism Apomorphine metabolism is primarily via conjugation. Within 0.5 hours of administering a subcutaneous dose of 14 C-apomorphine, only 8.3% of plasma radioactivity was apomorphine, while 83% was associated with apomorphine sulfate, 3.5% with apomorphine glucuronide, and 1% with nor-apomorphine glucuronide. Excretion Eighty-six percent of the subcutaneously administered dose of 14 C-apomorphine was recovered in the urine within 48 hours as apomorphine sulfate, apomorphine glucuronide, and nor-apomorphine glucuronide.
Another 4.6% of the administered dose was recovered in the feces over 144 hours as apomorphine sulfate, apomorphine glucuronide, and apomorphine. Specific Populations No clinically significant differences in the pharmacokinetics of apomorphine were observed based on age, gender, weight, duration of Parkinson's disease, levodopa dose, or duration of therapy. Renal Impairment In a study comparing patients with renal impairment (moderately impaired as determined by estimated creatinine clearance) to healthy matched volunteers, the AUC 0-inf and C max were increased by approximately 16% and 50%, respectively, following a single subcutaneous administration of apomorphine into the abdominal wall.
The mean time to peak concentrations and the mean terminal half-life of apomorphine were unaffected by the renal status of the individual. Studies in patients with severe renal impairment have not been conducted [see Dosage and Administration (2.5) and Use in Specific Populations (8.6) ] . Hepatic Impairment In a study comparing patients with hepatic impairment (moderately impaired as determined by the Child-P…
🧬 Mechanism of Action ▾
12.1Mechanism of Action ONAPGO is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors. The precise mechanism of action of ONAPGO as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied ONAPGO injection is supplied as one carton (NDC 27505-006-05) that contains five single-dose prefilled glass cartridges (NDC 27505-006-01), each containing 98 mg/20 mL (4.9 mg/mL) apomorphine hydrochloride as a clear, almost colorless solution. The ONAPGO Pump Kit, ONAPGO Cartridge Holders, and appropriate infusion sets are supplied separately.
16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .
📦 Storage and Handling ▾
16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .
📋 Description ▾
11 DESCRIPTION ONAPGO (apomorphine hydrochloride) contains apomorphine hydrochloride hemihydrate, a non-ergoline dopamine agonist. It is chemically designated as 6aβ-aporphine-10,11-diol hydrochloride hemihydrate with a molecular formula of C 17 H 17 NO 2 ∙HCl∙½H 2 O. Its structural formula and molecular weight are: Apomorphine hydrochloride hemihydrate appears as minute, white or grayish-white glistening crystals or as white powder that is soluble in water at 80°C.
ONAPGO injection is a clear, almost colorless, sterile solution for subcutaneous infusion and is available in 98 mg/20 mL (4.9 mg/mL) single-dose prefilled cartridges. The solution has a pH of 3.0-4.0. Each mL contains 4.9 mg of apomorphine hydrochloride (equivalent to 4.27 mg apomorphine) and 0.5 mg of sodium metabisulfite in water for injection.
In addition, each mL may contain hydrochloric acid used to adjust the pH. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Administration Information Refer patients to the Instructions for Use for complete administration instructions. Inform patients of aseptic technique and of subcutaneous administration site selection and rotation [see Dosage and Administration (2.4) ].
Advise patients that a new single-dose cartridge and cartridge holder and a new infusion line should be used each day. Advise patients that ONAPGO is intended only for subcutaneous use and must not be given intravenously because of the risk of serious complications, such as thrombus formation and pulmonary embolism due to crystallization [see Warnings and Precautions (5.1) ] . Hypersensitivity/Allergic Reactions Advise patients that hypersensitivity/allergic reactions characterized by urticaria, rash, pruritus, and/or various manifestations of angioedema may occur because of ONAPGO or any of its excipients, including a sulfite (i.e., sodium metabisulfite).
Inform patients with a sulfite sensitivity that they may experience various allergic-type reactions, including anaphylactic symptoms and life-threatening asthmatic attacks [see Warnings and Precautions (5.13) ] . Advise patients who experience any hypersensitivity/allergic reaction to ONAPGO that they should not take ONAPGO again [see Contraindications (4) ]. Nausea and Vomiting Advise patients that they may experience nausea and vomiting, which may be severe.
Advise patients that their ONAPGO dosage may be adjusted to start at 1 mg/hr, and titration can be based upon effectiveness and tolerability. Treatment with an antiemetic that is a non-5HT 3 antagonist may be used if needed. Oral trimethobenzamide 300 mg 3 times per day for 3 days prior to starting ONAPGO infusion has been used in clinical studies to help lessen these symptoms.
Advise patients that ONAPGO taken with trimethobenzamide may increase the risk for somnolence, dizziness, and falls, and to consult their healthcare provider before discontinuing trimethobenzamide [see Warnings and Precautions (5.2) ]. Falling Asleep Suddenly and Sedation/Sleepiness Alert patients to the potential sedating effects of ONAPGO, including somnolence and falling asleep while engaged in activities of daily living. Instruct patients not to drive a car or engage in other potentially dangerous activities until they have gained sufficient experience with ONAPGO to gauge whether or not it affects their mental and/or motor performance adversely.
Advise patients that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., watching television, passenger in a car, etc.) occur, they should not drive or participate in potentially dangerous activities until they have contacted their physician [see Warnings and Precautions (5.3) ]. Hypotension/Orthostatic Hypotension Advise patients that they may develop postural (orthostatic) hypotension with or without symptoms such as dizziness, nausea, syncope, and sometimes sweating. Hypotension and/or orthostatic symptoms may occur more frequently during initial therapy or with an increase in dose at any time (cases have been seen after months of treatment).
Instruct patients to rise slowly after sitting or lying down while using ONAPGO. Inform patients that alcohol and nitroglycerin (and possibly other vasodilators and antihypertensive medications) may worsen the potential effects of hypotension caused by ONAPGO [see Warnings and Precautions (5.4) ]. Instruct patients ideally to lie down before taking sublingual nitroglycerin and to remain supine and avoid standing for at least 45 minutes after nitroglycerin.
Instruct patients to avoid alcohol while using ONAPGO. Falls Alert patients that they may have increased risk for falling when using ONAPGO [see Warnings and Precautions (5.5) ]. Infusion Site Reactions and Infections Inform patients that infusion of ONAPGO may result in infus…