16/20. Opicapore- (ONGENTYS) @ ( Apr 2020)- Parkinson's Disease
Drug Name:16/20. Opicapore- (ONGENTYS) @ ( Apr 2020)- Parkinson's Disease
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS - summary
1. 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 [see Contraindications (4)]. Selective MAO-B inhibitors can be used concomitantly with ONGENTYS.
2. Effect of ONGENTYS on Other Drugs Drugs Metabolized by Catechol-O-Methyltransferase (COMT)-
Concomitant use of ONGENTYS with drugs metabolized by COMT may affect the pharmacokinetics of those drugs, which may increase the risk of possible arrhythmias, increased heart rate, and excessive changes in blood pressure.
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
Indication:
U.S. FDA APPROVED DRUGS DURING 2020
Sr.No- 16
Adverse Reaction:
Contra-Indications:
Dosages/ Overdosage Etc:
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information). Administration
Instruct patients and/or caregivers that ONGENTYS capsules should be taken at bedtime. Inform patients to not eat food for 1 hour before and for at least 1 hour after intake of ONGENTYS with food
Concomitant Medications- Certain medications can cause an interaction with ONGENTYS. Advise patients and/or caregivers to inform their healthcare provider of all the medicines the patient is taking, including over-the-counter medicines, dietary supplements, and herbal products
Falling Asleep During Activities of Daily Living - Advise patients and/or caregivers that somnolence has been reported with ONGENTYS.
Patients treated with dopaminergic medications have reported falling asleep while engaged in activities of daily living.
These adverse reactions may affect some patients’ ability to drive and operate machinery safely
Hypotension/Syncope- Advise patients that ONGENTYS may cause hypotension or syncope [see Warnings and Precautions (5.3)].
Dyskinesia- Advise patients that ONGENTYS may cause dyskinesia or exacerbate pre-existing dyskinesia
Hallucinations and Psychosis- Advise patients that ONGENTYS may cause hallucinations, delusions, or aggressive behavior and they should report any of these adverse reactions to their healthcare provider
Impulse Control/Compulsive Disorders- Inform patients of the potential for experiencing intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and other intense urges and the inability to control these urges while taking ONGENTYS and one or more medications that increase central dopaminergic tone that are generally used for the treatment of PD.
Advise patients that they should report any of these adverse reactions to their healthcare provider
Withdrawal-Emergent Hyperpyrexia and Confusion - Advise patients to contact their healthcare provider before stopping ONGENTYS.
Tell patients to inform their healthcare provider if they develop symptoms such as fever, confusion, or severe muscle stiffness after stopping ONGENTYS
For further information on ONGENTYS, call 1-833-ONGENTYS (833-664-3689) or visit www.ongentys.com 13 Reference ID: 4597703
Distributed by: Neurocrine Biosciences, Inc., San Diego, CA 92130 Under license from BIAL-Portela & Ca , S.A. ONGENTYS is a registered trademark of BIAL-Portela & Ca , S.A.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action- Opicapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure.
Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine), and their hydroxylated metabolites. When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD).
2. Pharmacodynamics- COMT Activity Once-daily administration of ONGENTYS 50 mg caused inhibition of COMT activity in erythrocytes; the maximal inhibition seen was 84% and was maintained >65% over a 24-hour dosing interval in patients with Parkinson’s disease.
Following termination of treatment, COMT inhibition slowly returns to baseline levels, with >35% inhibition still observed 5 days after the last dose.
Effects on Levodopa- Peak (Cmax) and overall levodopa exposure (AUC) increased by 43-44% and 62-94%, respectively, in PD patients following once-daily administration of ONGENTYS at bedtime with levodopa/carbidopa administered every three or every four hours, as compared to after administration of levodopa/carbidopa alone.
Cardiac Electrophysiology- At a dose 16 times the recommended dosage, ONGENTYS does not prolong the QT interval to any clinically relevant extent.
3. Pharmacokinetics- Opicapone demonstrates dose-proportional pharmacokinetics over a 25 mg (0.5 times the recommended dosage) to 50 mg dose range.
The pharmacokinetics of opicapone are similar in both PD patients and healthy subjects.
Absorption- After single-dose administration of ONGENTYS 50 mg, the median (range) plasma Tmax value was 2.0 (1.0 4.0) hours.
Effect of Food- Following a moderate fat/moderate calorie meal, the mean peak plasma concentration (Cmax) for opicapone decreased 62%, the mean overall plasma exposure (AUC) decreased 31%, and the Tmax was delayed by 4 hours.
Elimination- The mean elimination half-life of opicapone is 1 to 2 hours.
Metabolism- Sulphation is the primary metabolic pathway of opicapone, based on clinical studies and in vitro assessments.
Other metabolic pathways include glucuronidation, methylation (by COMT), reduction, and glutathione conjugation.
Excretion- After administration of a single dose of radiolabeled opicapone 100 mg (2 times the recommended dosage) to healthy subjects, approximately 70% of the dose was recovered in feces (22% as unchanged), 20% in expired air, and 5% in urine (<1% as unchanged).
Specific Populations- No clinically significant differences in the pharmacokinetics of opicapone were observed based on age (i.e., 18 to 40 years of age and = 65 years of age), sex, or race/ethnicity (i.e., Japanese, Caucasian, Asian, and Black).
Renal Impairment- Based on population pharmacokinetic analyses, no clinically significant differences in the pharmacokinetics of opicapone were observed in patients with mild or moderate renal impairment (CLcr 30-89 mL/min using the Cockcroft-Gault equation) relative to those with normal renal function (CLcr >90 mL/min).
Patients with severe renal impairment or ESRD (CLcr <30 mL/min) have not been studied
Hepatic Impairment- The single-dose pharmacokinetics of opicapone was evaluated in subjects with mild (Child-Pugh: A) and moderate (Child-Pugh: B) hepatic impairment.
In subjects with mild hepatic impairment, the mean overall opicapone plasma exposure (AUC) increased by 35%, which is not expected to be clinically significant.
In subjects with moderate hepatic impairment, the mean overall opicapone plasma exposure (AUC) increased by 84%. Dosage adjustment for ONGENTYS is required in subjects with moderate hepatic impairment.
ONGENTYS has not been studied in patients with severe hepatic impairment (Child-Pugh: C)
Drug Interaction Studies- Clinical Studies- No clinically significant differences in the pharmacokinetics of opicapone were observed when administered concomitantly with quinidine (index substrate of P-gp [MDR1]), acetaminophen, or rasagiline.
No clinically significant differences in the pharmacokinetics of the following drugs were observed when administered concomitantly with opicapone: S-warfarin (index substrate of CYP2C9), R-Warfarin (substrate of CYP1A2 and CYP3A4), or repaglinide (index substrate of CYP2C8 and OATP1B1).
No clinically significant differences in the pharmacokinetics of the following drugs for the treatment of Parkinson’s disease were observed when administered concomitantly with opicapone: rasagiline, selegiline, pramipexole, ropinirole, or amantadine.
In Vitro Studies Opicapone does not affect protein binding of warfarin, diazepam, digoxin, or tolbutamide, in vitro. CYP Enzymes: Opicapone is not an inhibitor or inducer of major CYPs.
Transporter Systems: Opicapone is a substrate of P-gp (MDR1) (see Clinical Studies), BCRP, MRP2, OATP1B3, and OATP2B1.
No clinically significant transporter mediated interaction is expected for opicapone. Opicapone is not an inhibitor of P-gp (MDR1), BCRP, OAT1, OAT3, OCT1, OCT2, OATP1B3, BSEP, MATE1, or MATE2-K.
13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No increase in tumors was observed when opicapone was administered orally to mice (0, 100, 375, or 750 mg/kg/day) for up to 2 years (84-93 weeks at the high dose). The highest dose tested is approximately 70 times the recommended dose (RHD) in humans (50 mg/day) on a body surface area (mg/m2 ) basis. No increase in tumors was observed when opicapone was administered orally to rats (0, 100, 500, or 1000 mg/kg/da
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of ONGENTYS in pregnant women.
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.
2. Lactation Risk Summary- There are no data on the presence of opicapone in human milk, the effects on the breastfed infant, or the effects on milk production. In lactating rats, oral administration of opicapone resulted in levels of opicapone or metabolites in milk similar to those in maternal plasma.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ONGENTYS and any potential adverse effects on the breastfed infant from ONGENTYS or from the underlying maternal condition. 6 Reference ID: 4597703
4. Pediatric Use- Safety and effectiveness in pediatric patients have not been established.
5. Geriatric Use- No dose adjustment is required for elderly patients. Of the total number of patients who received ONGENTYS 50 mg 52% of patients were 65 years and older. No overall differences in safety and effectiveness were observed between these patients and younger patients, but greater sensitivity to adverse reactions of some older individuals cannot be ruled out.
6. Renal Impairment- The renal route of elimination plays a minor role in the clearance of opicapone. Avoid use of ONGENTYS in patients with end-stage renal disease (ESRD) (CLcr <15 mL/min).
No dosage adjustment is required for patients with mild, moderate, or severe renal impairment.
However, because of a potential for increased exposure, monitor patients with severe renal impairment for adverse reactions an-d discontinue ONGENTYS if tolerability issues arise.
7. Hepatic Impairment- Opicapone exposure is increased in patients with hepatic impairment. Avoid use of ONGENTYS in patients with severe (Child-Pugh C) hepatic impairment.
Dosage adjustment is recommended for patients with moderate (Child-Pugh B) hepatic impairment
No dosage adjustment is required in patients with mild (Child-Pugh A) hepatic impairment.
OVERDOSAGE- 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
