Contraindications Concomitant use of ONAPGO with 5HT₃ antagonists is contraindicated based on reports of profound hypotension and loss of consciousness when ONAPGO was administered with ondansetron.
ONAPGO is contraindicated in patients who have demonstrated hypersensitivity/allergic reaction to the drug or any of its excipients (notably sodium metabisulfite). Angioedema or anaphylaxis may occur.

Warnings and Precautions

Serious Adverse Reactions After Intravenous Administration: Following intravenous administration of apomorphine, serious adverse reactions including thrombus formation and pulmonary embolism have occurred. ONAPGO should not be administered intravenously.

Nausea and Vomiting: ONAPGO is known to cause nausea and vomiting when administered at recommended doses. In a clinical study, 3 days of pre-medication followed by concomitant treatment with trimethobenzamide was recommended. With the concomitant use of trimethobenzamide, 30% and 5% of the ONAPGO-treated patients had nausea and vomiting, respectively, and 3% and 0% of patients discontinued ONAPGO due to nausea and vomiting, respectively. The incidence of nausea and/or vomiting on Day 1 of apomorphine initiation was not statistically different between the trimethobenzamide and placebo groups. Similarly, there was no difference between the trimethobenzamide and placebo groups after 2 months of treatment.

Falling Asleep During Activities of Daily Living (ADL) and Somnolence: In ONAPGO clinical studies, 2 patients (~2%) reported “sleep attacks” without prior warning of sleepiness while engaged in ADL. Somnolence is commonly associated with ONAPGO, and it is reported that falling asleep while engaged in ADL always occurs in a setting of pre-existing somnolence. Before initiating treatment with ONAPGO, advise patients of the risk of drowsiness and ask about factors that could increase the risk, such as concomitant sedating medications and the presence of sleep disorders. If a patient develops significant daytime sleepiness or falls asleep during ADL, 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 ADL.

Syncope/Hypotension/Orthostatic Hypotension: Dopamine agonists, including ONAPGO, may cause orthostatic hypotension at any time, but especially during dose escalation. Alcohol, antihypertensive medications, and vasodilating medications may potentiate the hypotensive effect of apomorphine. Patients should avoid alcohol when using ONAPGO. Patients taking ONAPGO should lie down before and after taking sublingual nitroglycerin. Monitor patients taking concomitant antihypertensive medications or vasodilators for hypotension and orthostatic hypotension.

Falls: Patients with PD are at risk of falling due to underlying postural instability, possible concomitant autonomic instability, and from syncope caused by the blood pressure lowering effects of the drugs used to treat PD. ONAPGO might increase the risk of falling by simultaneously lowering blood pressure and altering mobility.

Hallucinations/Psychotic-like Behavior: Patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior after starting or increasing the dose of ONAPGO. Patients with a major psychotic disorder should ordinarily not be treated with ONAPGO because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of PD and may decrease the effectiveness of ONAPGO.

Dyskinesias: ONAPGO may cause dyskinesia or exacerbate pre-existing dyskinesia.

Hemolytic Anemia: Hemolytic anemia requiring hospitalization has been reported and can appear at any time after treatment. Many reported cases included positive Coombs test, suggesting a potential immune-mediated hemolysis. Severe anemia, angina, and dyspnea occurred. Some patients were treated with high-dose glucocorticoids or blood transfusions. If a patient develops anemia while taking ONAPGO, consider a workup for hemolytic anemia; if it occurs, consider discontinuing ONAPGO treatment.

Impulse Control/Compulsive Behaviors: Patients may experience intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, and other intense urges and inability to control these urges while taking PD medications that increase central dopaminergic tone, including ONAPGO. In some cases, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated with ONAPGO. Consider dose reduction or stopping the medication if a patient develops such urges while taking ONAPGO.

Coronary Events: ONAPGO has been shown to reduce resting systolic and diastolic blood pressure and may have the potential to exacerbate coronary (and cerebral) ischemia in patients with known cardiovascular and cerebrovascular disease. If patients develop signs and symptoms of coronary or cerebral ischemia, prescribers should re-evaluate the continued use of ONAPGO.

QTc Prolongation and Potential for Proarrhythmic Effects: There is a dose-related prolongation of QTc interval after apomorphine exposure similar to that achieved with therapeutic doses of ONAPGO. Drugs that prolong the QTc interval have been associated with torsades de pointes and sudden death. The risks and benefits of ONAPGO treatment should be considered prior to initiating treatment in patients with risk factors for prolonged QTc.

Withdrawal-Emergent Hyperpyrexia and Confusion: A symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in anti-PD therapy.

Hypersensitivity: Hypersensitivity/allergic reactions characterized by urticaria, rash, pruritus, and/or various manifestations of angioedema may occur because of ONAPGO or its sulfite excipient sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.

Fibrotic Complications: Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, and cardiac valvulopathy have been reported with ergot-derived dopaminergic agents. Complete resolution does not always occur when drug is discontinued. Although these reactions are believed to be related to ergoline structure, whether other, non-ergot derived dopamine agonists, such as ONAPGO, can cause these reactions is unknown.

Priapism: ONAPGO may cause prolonged painful erections in some patients. Although no patients in the clinical studies required surgical intervention, severe priapism may require surgical intervention.

Adverse Reactions

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.

Indication

ONAPGO is a dopaminergic agonist indicated for the continuous treatment of motor fluctuations (OFF episodes) in Parkinson’s disease (PD) patients that are not adequately controlled with oral levodopa and one or more adjunct PD medications.

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