Ongentys Drug Information

ONGENTYS is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease (PD) experiencing “off” episodes.

Dosing and Administration Information

The recommended dosage of ONGENTYS is 50 mg administered orally once daily at bedtime. Patients should not eat food for 1 hour before and for at least 1 hour after intake of ONGENTYS.

Dosage Recommendations for Patients with Hepatic Impairment

In patients with moderate hepatic impairment (Child-Pugh B), the recommended dose of ONGENTYS is 25 mg orally once daily at bedtime. Avoid use of ONGENTYS in patients with severe (Child-Pugh C) hepatic impairment.

D iscontinuation and Missed Dose

When discontinuing ONGENTYS, monitor patients and consider adjustment of other dopaminergic therapies as needed. If a dose of ONGENTYS is missed, the next dose should be taken at the scheduled time the next day.

Clinical 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 practice. All patients were taking a stable dose of levodopa and a DOPA decarboxylase inhibitor, alone or in combination with other PD medications. At baseline, the mean duration of PD was 7.6 years.

The most common adverse reaction leading to discontinuation was dyskinesia, reported in 3% of ONGENTYS 50 mg-treated patients and 0.4% of patients who received placebo. Common Adverse Reactions Adverse reactions that occurred in the pooled studies at an incidence of at least 2% and greater than placebo are presented in Table 1. The most common adverse reactions (incidence at least 4% and greater than placebo) were dyskinesia, constipation, blood creatine kinase increased, hypotension/syncope, and weight decreased.

Table 1: Adverse Reactions with an Incidence of at Least 2 % in Patients Treated with ONGENTYS and Greater than on Placebo, in Pooled Study 1 and Study 2 Includes hallucinations, hallucinations visual, hallucinations auditory, and hallucinations mixed 2 Includes hypotension, orthostatic hypotension, syncope, and presyncope

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of ONGENTYS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. Injury, poisoning and procedural complications: Fall Psychiatric disorder: Confusional state

Non-Selective Monoamine Oxidase (MAO) Inhibitors Both ONGENTYS and non-selective MAO inhibitors (e.g., phenelzine, isocarboxazid, and tranylcypromine) inhibit catecholamine metabolism, leading to increased levels of catecholamines. Concomitant use may increase the risk of possible arrhythmias, increased heart rate, and excessive changes in blood pressure. Concomitant use of ONGENTYS with non-selective MAO inhibitors is contraindicated.

Selective MAO-B inhibitors can be used concomitantly with ONGENTYS.

Drugs known to be metabolized by COMT should be administered with caution. Monitor for changes in heart rate, rhythm, and blood pressure in patients concomitantly treated with ONGENTYS and drugs metabolized by COMT.

Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of ONGENTYS in pregnant women. In animal studies, oral administration of opicapone during pregnancy resulted in adverse effects on embryofetal development (increased incidence of fetal abnormalities) at clinically relevant plasma exposures in one of two species tested. In addition, opicapone is always given concomitantly with levodopa/carbidopa, which is known to cause developmental toxicity in rabbits ( s ee Data ).

The background risk of major birth defects and miscarriage in the U.S. general population is 2-4% and 15-20% of clinically recognized pregnancies, respectively. The background risk for major birth defects and miscarriage in patients with Parkinson’s disease is unknown. Data Animal Data Oral administration of opicapone mg/kg/day to pregnant rats throughout gestation resulted in no adverse effects on embryofetal development.

Plasma exposure (AUC) at the highest dose tested (1000 mg/kg/day) was approximately 40 times that in humans at the recommended human dose (50 mg/day). In pregnant rabbits, oral administration of opicapone mg/kg/day during the period of organogenesis resulted in increased incidence of structural abnormalities at all doses tested; maternal toxicity was observed at all but the lowest dose tested. A no-effect dose for adverse effects on embryofetal development was not identified.

Plasma exposure (AUC) at the low-effect dose (100 mg/kg/day) was less than that in humans at the RHD. Oral administration of opicapone mg/kg/day throughout gestation and lactation resulted in no adverse effects on pre- and postnatal development; however, effects on neurobehavioral development in the offspring were not rigorously assessed. Opicapone is always given concomitantly with levodopa/carbidopa, which is known to cause visceral and skeletal malformations in rabbits.

The developmental toxicity of opicapone in combination with levodopa/carbidopa was not assessed in animals.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

ONGENTYS is contraindicated in patients with: Concomitant use of non-selective monoamine oxidase (MAO) inhibitors. Pheochromocytoma, paraganglioma, or other catecholamine secreting neoplasms. History of pheochromocytoma, paraganglioma, or other catecholamine secreting neoplasms.

No specific antidotes for ONGENTYS are known. As a general measure, removal of ONGENTYS by gastric lavage and/or inactivation by administering activated charcoal should be considered. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement.

If an over-exposure occurs, call your poison control center at 1-800-222-1222 or www.poison.org.