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Opicapone

Opicapone, sold under the brand name Ongentys, is a medication which is administered together with levodopa in people with Parkinson's disease.[3][6][4][5] Opicapone is a catechol-O-methyltransferase (COMT) inhibitor.[3]

Opicapone
Clinical data
Trade namesOngentys, Ontilyv
Other namesBIA 9-1067
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: B2[1]
  • Not recommended
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)[2]
  • US: ℞-only[3]
  • EU: Rx-only[4][5]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability~20%
Protein binding99.9%
MetabolismMainly sulfation, also reduction, glucuronidation, methylation
Elimination half-life0.7 to 3.2 hours
Duration of action>24 hours
ExcretionFeces (67%), urine (13%)
Identifiers
  • 5-[3-(2,5-dichloro-4,6-dimethyl-1-oxidopyridin-1-ium-3-yl)-1,2,4-oxadiazol-5-yl]-3-nitrobenzene-1,2-diol
CAS Number
  • 923287-50-7
PubChem CID
  • 135565903
DrugBank
  • DB11632
ChemSpider
  • 24667564
UNII
  • Y5929UIJ5N
KEGG
  • D10825 Y
ChEBI
  • CHEBI:134699
ChEMBL
  • ChEMBL1089318
Chemical and physical data
FormulaC15H10Cl2N4O6
Molar mass413.17 g·mol−1
3D model (JSmol)
  • Interactive image
  • Cc1c(Cl)c(C)[n+]([O-])c(Cl)c1-c1noc(-c2cc(O)c(O)c([N+](=O)[O-])c2)n1
  • InChI=1S/C15H10Cl2N4O6/c1-5-10(13(17)20(24)6(2)11(5)16)14-18-15(27-19-14)7-3-8(21(25)26)12(23)9(22)4-7/h3-4,22-23H,1-2H3
  • Key:ASOADIZOVZTJSR-UHFFFAOYSA-N

The most common side effects are dyskinesia (difficulty controlling movement), constipation, increased blood creatine kinase, hypotension/syncope, and decreased weight.[3][6]

Opicapone, works to restore the levels of dopamine in the parts of the brain that control movement and coordination.[4] It enhances the effects of levodopa, a copy of the neurotransmitter dopamine that can be taken by mouth.[4] Opicapone blocks an enzyme that is involved in the breakdown of levodopa in the body called catechol-O-methyltransferase (COMT).[3][4] As a result, levodopa remains active for longer.[4] This helps to improve the symptoms of Parkinson's disease, such as stiffness and slowness of movement.[4]

In June 2016, it was authorised for use in the European Union.[4][7][8] It was authorised for use in the United States in April 2020.[9][6][8]

Medical uses edit

In the EU, opicapone is indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors (DDCI) in adults with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations.[4]

In the US, opicapone is indicated as adjunctive treatment to levodopa/carbidopa in people with Parkinson's disease (PD) experiencing "off" episodes.[3][6]

The COMT inhibitor opicapone is used as an additive to a combination of levodopa and a DOPA decarboxylase inhibitor to treat patients with Parkinson's disease experiencing end-of-dose motor fluctuations, if they cannot be stabilised with this drug combination.[10]

Contraindications edit

This drug is contraindicated in people with cancers that secrete catecholamines (for example epinephrine), such as phaeochromocytoma or paraganglioma, because as a COMT inhibitor it blocks catecholamine degradation. Other contraindications are a history of neuroleptic malignant syndrome (NMS) or non-traumatic rhabdomyolysis, and combination with monoamine oxidase inhibitors that are not used as antiparkinsonians, because of possible drug interactions.[10]

NMS and associated rhabdomyolysis have been rarely observed under the older COMT inhibitors tolcapone and entacapone. This typically occurs shortly after the beginning of a COMT inhibitor add-on therapy when the levodopa dose has been reduced, or after discontinuation of a COMT inhibitor.[11]

Opicapone is contraindicated in people with concomitant use of non-selective monoamine oxidase (MAO) inhibitors or people with pheochromocytoma, paraganglioma, or other catecholamine secreting neoplasms.[3][4]

Side effects edit

People taking opicapone very commonly (18%) experience dyskinesia. Other common side effects (in 1 to 10% of patients) include dizziness, strange dreams, hallucinations, constipation, dry mouth, orthostatic hypotension (low blood pressure), and muscle spasms.[10] Apart from spasms, these side effects are also known from tolcapone and entacapone.[11]

As with entacapone, no relevant liver toxicity has been found in studies. This is in contrast to the first COMT inhibitor tolcapone, which could cause – in some cases lethal – liver insufficiency.[11][12]

Overdose edit

No specific antidote is known.[10]

Interactions edit

Monoamine oxidase inhibitors (MAO inhibitors) are another class of drugs blocking catecholamine degradation. Therefore, their combination with opicapone can result in increased catecholamine concentrations in the body and corresponding adverse effects. Combining the antiparkinson MAO inhibitors selegiline or rasagiline with opicapone is considered safe. Potentially, there are also interactions with drugs being metabolised by COMT (for example isoprenaline, epinephrine, dopamine, or dobutamine), tricyclic antidepressants and antidepressants of the norepinephrine reuptake inhibitor type. Possible pharmacokinetic interactions are with substrates of the liver enzyme CYP2C8, such as repaglinide, and the transporter protein SLCO1B1, such as simvastatin.[10]

Pharmacology edit

Mechanism of action edit

Opicapone blocks the enzyme catechol-O-methyltransferase (COMT) effectively (>90% at therapeutic doses), selectively and reversibly, and only outside the central nervous system. It dissociates slowly from COMT, resulting in a duration of action longer than 24 hours despite its short blood plasma half-life.[10][12] As COMT and DOPA decarboxylase are the main enzymes for degrading levodopa, blocking the two effectively increases its concentrations in the bloodstream. More levodopa reaches the brain, where it is activated to dopamine.[13]

Pharmacokinetics edit

 
Opicapone and some of its metabolites: the main inactive metabolite opicapone sulfate (BIA 9–1103), the active reduced derivative (BIA 9–1079), and the inactive glucuronide (BIA 9–1106).[14]

The substance is quickly absorbed from the gut, but only to about 20% of the applied dose. Highest blood plasma concentrations are reached after 1 to 2.5 hours. When in the bloodstream, it is almost completely (99.9%) bound to plasma proteins, but apparently to different binding sites than warfarin, digoxin and other drugs with high plasma protein affinity. It is mainly metabolised to the sulfate, which accounts for 67% of the circulating drug after a single dose, and a methylated derivative, which accounts for 21%. Minor metabolites are a reduced derivative (<10%) and a glucuronide. All of these metabolites are inactive except the reduced derivative. Opicapone is eliminated with a terminal half-life of 0.7 to 3.2 hours. It is mainly excreted via the faeces (67%), and in form of the glucuronide also via the kidney (13%). The sulfate has a much longer half-life of 94 to 122 hours.[10][12][14]

Opicapone sulfate is transported by SLCO1B1; the possibility that it blocks this transporter has not been excluded. Opicapone itself and the sulfate are also transported by a number of other proteins, but given the low concentrations of the free substances in the blood plasma, this is very unlikely to give rise to drug interactions. Opicapone is a weak inhibitor of the liver enzymes CYP1A2, CYP2B6, CYP2C8, and CYP2C9. The only CYP interaction found in studies that is somewhat likely to be relevant is that with repaglinide, which is metabolised by CYP2C8. The metabolism of warfarin, a CYP2C9 substrate, is not measurably affected.[10]

History edit

Opicapone was authorised for medical use in the European Union in June 2016.[4][7][8]

In February 2017, its developer Bial sold exclusive marketing rights for the United States and Canada to Neurocrine Biosciences for an initial payment of US$30 million.[15]

Opicapone was authorised for medical use in the United States in April 2020.[9][6][8]

Opicapone was approved based on evidence from two clinical trials (Trial 1/ NCT01568073, and Trial 2/NCT01227655) of 522 participants with Parkinson's disease (PD) whose symptoms were not well controlled while receiving their regular PD treatment.[6] Trial 1 was conducted at 104 sites in 19 European countries, and Trial 2 was conducted at 69 sites in Argentina, Australia, Belgium, Chile, Czech Republic, Estonia, India, Israel, South Korea, Russia, South Africa and UK.[6]

There were two 12-week trials conducted in Parkinson's disease (PD) participants with inadequate control of their Parkinson's symptom ("off" time) while receiving carbidopa/levodopa PD medications.[6] Participants were randomly selected to receive either opicapone or a placebo capsule once a day.[6] Neither the participants nor the health care providers knew which treatment was being given until the trial was completed.[6]

In all of the trials, the participants kept daily diaries of the number of hours of "off" time for the three days before the evaluation visit.[6] The benefit was evaluated by measuring the change from baseline in total daily "off" time in opicapone- and placebo-receiving participants.[6]

Society and culture edit

Legal status edit

On 16 December 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Ontilyv, intended for the treatment of Parkinson's disease.[16] The applicant for this medicinal product is Bial Portela & Companhia S.A.[16] Opicapone was approved for medical use in the European Union in February 2022.[4][17]

References edit

  1. ^ (PDF). Therapeutic Goods Administration. February 2021. Archived from the original (PDF) on 13 June 2021.
  2. ^ "Ongentys 50 mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 18 July 2019. from the original on 4 June 2020. Retrieved 28 April 2020.
  3. ^ a b c d e f g "Ongentys- opicapone capsule". DailyMed. 24 April 2020. from the original on 25 October 2021. Retrieved 30 September 2020.
  4. ^ a b c d e f g h i j k l "Ongentys EPAR". European Medicines Agency. 17 September 2018. from the original on 9 May 2020. Retrieved 28 April 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. ^ a b "Ontilyv EPAR". European Medicines Agency. 14 December 2021. from the original on 7 August 2022. Retrieved 25 August 2022.
  6. ^ a b c d e f g h i j k l "Drug Trials Snapshots: Ongentys". U.S. Food and Drug Administration (FDA). 24 April 2020. from the original on 21 September 2020. Retrieved 13 May 2020.   This article incorporates text from this source, which is in the public domain.
  7. ^ a b "Neurocrine Nabs BIAL's PD Therapy Opicapone for North America". Genetic Engineering & Biotechnology News. 10 February 2017. from the original on 2 July 2018. Retrieved 8 April 2017.
  8. ^ a b c d "Neurocrine Biosciences Announces FDA Approval of Once-Daily Ongentys (opicapone) as an Add-On Treatment for Patients with Parkinson's Disease Experiencing "Off" Episodes". Neurocrine Biosciences (Press release). 27 April 2020. from the original on 28 April 2020. Retrieved 28 April 2020.
  9. ^ a b "Ongentys: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). from the original on 28 April 2020. Retrieved 28 April 2020.
  10. ^ a b c d e f g h "Ongentys: EPAR – Product Information" (PDF). European Medicines Agency (EMA). 28 January 2020. (PDF) from the original on 7 October 2018. Retrieved 26 August 2022.
  11. ^ a b c Haberfeld H, ed. (2017). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Comtan, Tasmar.
  12. ^ a b c Annus Á, Vécsei L (2017). "Spotlight on opicapone as an adjunct to levodopa in Parkinson's disease: design, development and potential place in therapy". Drug Design, Development and Therapy. 11: 143–151. doi:10.2147/DDDT.S104227. PMC 5234693. PMID 28123288.
  13. ^ Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 315. ISBN 3-8047-1763-2.
  14. ^ a b Rocha JF, Almeida L, Falcão A, Palma PN, Loureiro AI, Pinto R, et al. (November 2013). "Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects". British Journal of Clinical Pharmacology. 76 (5): 763–75. doi:10.1111/bcp.12081. PMC 3853535. PMID 23336248.
  15. ^ "Brief: Neurocrine and Bial reports exclusive North American licensing agreement for opicapone". Reuters. 9 February 2017. from the original on 8 August 2019. Retrieved 1 July 2017.
  16. ^ a b "Ontilyv: Pending EC decision". European Medicines Agency. 16 December 2021. from the original on 17 December 2021. Retrieved 18 December 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  17. ^ "Ontilyv Product information". Union Register of medicinal products. from the original on 4 March 2023. Retrieved 3 March 2023.

Further reading edit

  • Rodrigues FB, Ferreira JJ (March 2017). "Opicapone for the treatment of Parkinson's disease" (PDF). Expert Opin Pharmacother. 18 (4): 445–453. doi:10.1080/14656566.2017.1294683. PMID 28234566. S2CID 5251815.
  • Scott LJ (September 2016). "Opicapone: A Review in Parkinson's Disease". Drugs. 76 (13): 1293–1300. doi:10.1007/s40265-016-0623-y. PMID 27498199. S2CID 5787752.

opicapone, sold, under, brand, name, ongentys, medication, which, administered, together, with, levodopa, people, with, parkinson, disease, catechol, methyltransferase, comt, inhibitor, clinical, datatrade, namesongentys, ontilyvother, namesbia, 1067ahfs, drug. Opicapone sold under the brand name Ongentys is a medication which is administered together with levodopa in people with Parkinson s disease 3 6 4 5 Opicapone is a catechol O methyltransferase COMT inhibitor 3 OpicaponeClinical dataTrade namesOngentys OntilyvOther namesBIA 9 1067AHFS Drugs comMonographLicense dataEU EMA by INN US DailyMed OpicaponePregnancycategoryAU B2 1 Not recommendedRoutes ofadministrationBy mouthATC codeN04BX04 WHO Legal statusLegal statusAU S4 Prescription only UK POM Prescription only 2 US only 3 EU Rx only 4 5 In general Prescription only Pharmacokinetic dataBioavailability 20 Protein binding99 9 MetabolismMainly sulfation also reduction glucuronidation methylationElimination half life0 7 to 3 2 hoursDuration of action gt 24 hoursExcretionFeces 67 urine 13 IdentifiersIUPAC name 5 3 2 5 dichloro 4 6 dimethyl 1 oxidopyridin 1 ium 3 yl 1 2 4 oxadiazol 5 yl 3 nitrobenzene 1 2 diolCAS Number923287 50 7PubChem CID135565903DrugBankDB11632ChemSpider24667564UNIIY5929UIJ5NKEGGD10825 YChEBICHEBI 134699ChEMBLChEMBL1089318Chemical and physical dataFormulaC 15H 10Cl 2N 4O 6Molar mass413 17 g mol 13D model JSmol Interactive imageSMILES Cc1c Cl c C n O c Cl c1 c1noc c2cc O c O c N O O c2 n1InChI InChI 1S C15H10Cl2N4O6 c1 5 10 13 17 20 24 6 2 11 5 16 14 18 15 27 19 14 7 3 8 21 25 26 12 23 9 22 4 7 h3 4 22 23H 1 2H3Key ASOADIZOVZTJSR UHFFFAOYSA NThe most common side effects are dyskinesia difficulty controlling movement constipation increased blood creatine kinase hypotension syncope and decreased weight 3 6 Opicapone works to restore the levels of dopamine in the parts of the brain that control movement and coordination 4 It enhances the effects of levodopa a copy of the neurotransmitter dopamine that can be taken by mouth 4 Opicapone blocks an enzyme that is involved in the breakdown of levodopa in the body called catechol O methyltransferase COMT 3 4 As a result levodopa remains active for longer 4 This helps to improve the symptoms of Parkinson s disease such as stiffness and slowness of movement 4 In June 2016 it was authorised for use in the European Union 4 7 8 It was authorised for use in the United States in April 2020 9 6 8 Contents 1 Medical uses 2 Contraindications 3 Side effects 4 Overdose 5 Interactions 6 Pharmacology 6 1 Mechanism of action 6 2 Pharmacokinetics 7 History 8 Society and culture 8 1 Legal status 9 References 10 Further readingMedical uses editIn the EU opicapone is indicated as adjunctive therapy to preparations of levodopa DOPA decarboxylase inhibitors DDCI in adults with Parkinson s disease and end of dose motor fluctuations who cannot be stabilised on those combinations 4 In the US opicapone is indicated as adjunctive treatment to levodopa carbidopa in people with Parkinson s disease PD experiencing off episodes 3 6 The COMT inhibitor opicapone is used as an additive to a combination of levodopa and a DOPA decarboxylase inhibitor to treat patients with Parkinson s disease experiencing end of dose motor fluctuations if they cannot be stabilised with this drug combination 10 Contraindications editThis drug is contraindicated in people with cancers that secrete catecholamines for example epinephrine such as phaeochromocytoma or paraganglioma because as a COMT inhibitor it blocks catecholamine degradation Other contraindications are a history of neuroleptic malignant syndrome NMS or non traumatic rhabdomyolysis and combination with monoamine oxidase inhibitors that are not used as antiparkinsonians because of possible drug interactions 10 NMS and associated rhabdomyolysis have been rarely observed under the older COMT inhibitors tolcapone and entacapone This typically occurs shortly after the beginning of a COMT inhibitor add on therapy when the levodopa dose has been reduced or after discontinuation of a COMT inhibitor 11 Opicapone is contraindicated in people with concomitant use of non selective monoamine oxidase MAO inhibitors or people with pheochromocytoma paraganglioma or other catecholamine secreting neoplasms 3 4 Side effects editPeople taking opicapone very commonly 18 experience dyskinesia Other common side effects in 1 to 10 of patients include dizziness strange dreams hallucinations constipation dry mouth orthostatic hypotension low blood pressure and muscle spasms 10 Apart from spasms these side effects are also known from tolcapone and entacapone 11 As with entacapone no relevant liver toxicity has been found in studies This is in contrast to the first COMT inhibitor tolcapone which could cause in some cases lethal liver insufficiency 11 12 Overdose editNo specific antidote is known 10 Interactions editMonoamine oxidase inhibitors MAO inhibitors are another class of drugs blocking catecholamine degradation Therefore their combination with opicapone can result in increased catecholamine concentrations in the body and corresponding adverse effects Combining the antiparkinson MAO inhibitors selegiline or rasagiline with opicapone is considered safe Potentially there are also interactions with drugs being metabolised by COMT for example isoprenaline epinephrine dopamine or dobutamine tricyclic antidepressants and antidepressants of the norepinephrine reuptake inhibitor type Possible pharmacokinetic interactions are with substrates of the liver enzyme CYP2C8 such as repaglinide and the transporter protein SLCO1B1 such as simvastatin 10 Pharmacology editMechanism of action edit Opicapone blocks the enzyme catechol O methyltransferase COMT effectively gt 90 at therapeutic doses selectively and reversibly and only outside the central nervous system It dissociates slowly from COMT resulting in a duration of action longer than 24 hours despite its short blood plasma half life 10 12 As COMT and DOPA decarboxylase are the main enzymes for degrading levodopa blocking the two effectively increases its concentrations in the bloodstream More levodopa reaches the brain where it is activated to dopamine 13 Pharmacokinetics edit nbsp Opicapone and some of its metabolites the main inactive metabolite opicapone sulfate BIA 9 1103 the active reduced derivative BIA 9 1079 and the inactive glucuronide BIA 9 1106 14 The substance is quickly absorbed from the gut but only to about 20 of the applied dose Highest blood plasma concentrations are reached after 1 to 2 5 hours When in the bloodstream it is almost completely 99 9 bound to plasma proteins but apparently to different binding sites than warfarin digoxin and other drugs with high plasma protein affinity It is mainly metabolised to the sulfate which accounts for 67 of the circulating drug after a single dose and a methylated derivative which accounts for 21 Minor metabolites are a reduced derivative lt 10 and a glucuronide All of these metabolites are inactive except the reduced derivative Opicapone is eliminated with a terminal half life of 0 7 to 3 2 hours It is mainly excreted via the faeces 67 and in form of the glucuronide also via the kidney 13 The sulfate has a much longer half life of 94 to 122 hours 10 12 14 Opicapone sulfate is transported by SLCO1B1 the possibility that it blocks this transporter has not been excluded Opicapone itself and the sulfate are also transported by a number of other proteins but given the low concentrations of the free substances in the blood plasma this is very unlikely to give rise to drug interactions Opicapone is a weak inhibitor of the liver enzymes CYP1A2 CYP2B6 CYP2C8 and CYP2C9 The only CYP interaction found in studies that is somewhat likely to be relevant is that with repaglinide which is metabolised by CYP2C8 The metabolism of warfarin a CYP2C9 substrate is not measurably affected 10 History editOpicapone was authorised for medical use in the European Union in June 2016 4 7 8 In February 2017 its developer Bial sold exclusive marketing rights for the United States and Canada to Neurocrine Biosciences for an initial payment of US 30 million 15 Opicapone was authorised for medical use in the United States in April 2020 9 6 8 Opicapone was approved based on evidence from two clinical trials Trial 1 NCT01568073 and Trial 2 NCT01227655 of 522 participants with Parkinson s disease PD whose symptoms were not well controlled while receiving their regular PD treatment 6 Trial 1 was conducted at 104 sites in 19 European countries and Trial 2 was conducted at 69 sites in Argentina Australia Belgium Chile Czech Republic Estonia India Israel South Korea Russia South Africa and UK 6 There were two 12 week trials conducted in Parkinson s disease PD participants with inadequate control of their Parkinson s symptom off time while receiving carbidopa levodopa PD medications 6 Participants were randomly selected to receive either opicapone or a placebo capsule once a day 6 Neither the participants nor the health care providers knew which treatment was being given until the trial was completed 6 In all of the trials the participants kept daily diaries of the number of hours of off time for the three days before the evaluation visit 6 The benefit was evaluated by measuring the change from baseline in total daily off time in opicapone and placebo receiving participants 6 Society and culture editLegal status edit On 16 December 2021 the Committee for Medicinal Products for Human Use CHMP of the European Medicines Agency EMA adopted a positive opinion recommending the granting of a marketing authorisation for the medicinal product Ontilyv intended for the treatment of Parkinson s disease 16 The applicant for this medicinal product is Bial Portela amp Companhia S A 16 Opicapone was approved for medical use in the European Union in February 2022 4 17 References edit Australian Public Assessment Report for Opicapone PDF Therapeutic Goods Administration February 2021 Archived from the original PDF on 13 June 2021 Ongentys 50 mg hard capsules Summary of Product Characteristics SmPC emc 18 July 2019 Archived from the original on 4 June 2020 Retrieved 28 April 2020 a b c d e f g Ongentys opicapone capsule DailyMed 24 April 2020 Archived from the original on 25 October 2021 Retrieved 30 September 2020 a b c d e f g h i j k l Ongentys EPAR European Medicines Agency 17 September 2018 Archived from the original on 9 May 2020 Retrieved 28 April 2020 Text was copied from this source which is c European Medicines Agency Reproduction is authorized provided the source is acknowledged a b Ontilyv EPAR European Medicines Agency 14 December 2021 Archived from the original on 7 August 2022 Retrieved 25 August 2022 a b c d e f g h i j k l Drug Trials Snapshots Ongentys U S Food and Drug Administration FDA 24 April 2020 Archived from the original on 21 September 2020 Retrieved 13 May 2020 nbsp This article incorporates text from this source which is in the public domain a b Neurocrine Nabs BIAL s PD Therapy Opicapone for North America Genetic Engineering amp Biotechnology News 10 February 2017 Archived from the original on 2 July 2018 Retrieved 8 April 2017 a b c d Neurocrine Biosciences Announces FDA Approval of Once Daily Ongentys opicapone as an Add On Treatment for Patients with Parkinson s Disease Experiencing Off Episodes Neurocrine Biosciences Press release 27 April 2020 Archived from the original on 28 April 2020 Retrieved 28 April 2020 a b Ongentys FDA Approved Drugs U S Food and Drug Administration FDA Archived from the original on 28 April 2020 Retrieved 28 April 2020 a b c d e f g h Ongentys EPAR Product Information PDF European Medicines Agency EMA 28 January 2020 Archived PDF from the original on 7 October 2018 Retrieved 26 August 2022 a b c Haberfeld H ed 2017 Austria Codex in German Vienna Osterreichischer Apothekerverlag Comtan Tasmar a b c Annus A Vecsei L 2017 Spotlight on opicapone as an adjunct to levodopa in Parkinson s disease design development and potential place in therapy Drug Design Development and Therapy 11 143 151 doi 10 2147 DDDT S104227 PMC 5234693 PMID 28123288 Mutschler E Schafer Korting M 2001 Arzneimittelwirkungen in German 8th ed Stuttgart Wissenschaftliche Verlagsgesellschaft p 315 ISBN 3 8047 1763 2 a b Rocha JF Almeida L Falcao A Palma PN Loureiro AI Pinto R et al November 2013 Opicapone a short lived and very long acting novel catechol O methyltransferase inhibitor following multiple dose administration in healthy subjects British Journal of Clinical Pharmacology 76 5 763 75 doi 10 1111 bcp 12081 PMC 3853535 PMID 23336248 Brief Neurocrine and Bial reports exclusive North American licensing agreement for opicapone Reuters 9 February 2017 Archived from the original on 8 August 2019 Retrieved 1 July 2017 a b Ontilyv Pending EC decision European Medicines Agency 16 December 2021 Archived from the original on 17 December 2021 Retrieved 18 December 2021 Text was copied from this source which is copyright European Medicines Agency Reproduction is authorized provided the source is acknowledged Ontilyv Product information Union Register of medicinal products Archived from the original on 4 March 2023 Retrieved 3 March 2023 Further reading editRodrigues FB Ferreira JJ March 2017 Opicapone for the treatment of Parkinson s disease PDF Expert Opin Pharmacother 18 4 445 453 doi 10 1080 14656566 2017 1294683 PMID 28234566 S2CID 5251815 Scott LJ September 2016 Opicapone A Review in Parkinson s Disease Drugs 76 13 1293 1300 doi 10 1007 s40265 016 0623 y PMID 27498199 S2CID 5787752 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Opicapone amp oldid 1175657173, wikipedia, wiki, book, books, library,

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