FDA

Onapgo

Approved 3 Feb 2025SubcutaneousSolution

Indications

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 )

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 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.

At a glance

Brand name: Onapgo
Active substance: apomorphine hydrochloride
Route: Subcutaneous
Dosage form: Solution
Applicant: MDD US
Status: Prescription
FDA approval: 3 Feb 2025
Application: NDA214056-001

Contraindications

Warnings and precautions

( 5.12 )

5.1Serious Adverse Reactions After Intravenous Administration Do

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 .

7.3 Alcohol 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) ] .

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. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hematologic and Lymphatic Systems: hemolytic anemia [see Warnings and Precautions (5.9) ]

Onapgo

Indications

Contraindications

Warnings and precautions

5.1Serious Adverse Reactions After Intravenous Administration Do

At a glance

Two medicines in one question?

Onapgo

Indications

Contraindications

Warnings and precautions

5.1Serious Adverse Reactions After Intravenous Administration Do

At a glance

Two medicines in one question?

5.2Nausea and Vomiting

5.3Falling Asleep During Activities of Daily Living and Somnolence

5.4Syncope/Hypotension/Orthostatic Hypotension

5.6Infusion Site Reactions and Infections

Interactions

7.2Antihypertensive Medications and Vasodilators

7.4Dopamine Antagonists Because

7.5Drugs Prolonging the QT/QTc Interval

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information