Ongentys

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ongentys 25 mg hard capsules  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each hard capsule contains 25 mg of opicapone. 
 
Excipient(s) with known effect 
 
Each hard capsule contains 171.9 mg of lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule (capsule) 
 
Light blue capsules, size 1, approximately 19 mm, imprinted “OPC 25” on the cap and “Bial” on the 
body. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ongentys is indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase 
inhibitors (DDCI) in adult patients with Parkinson’s disease and end-of-dose motor fluctuations who 
cannot be stabilised on those combinations.  
 
4.2 Posology and method of administration 
 
Posology 
 
The recommended dose of opicapone is 50 mg.  
Ongentys should be taken once-daily at bedtime at least one hour before or after levodopa 
combinations. 
 
Dose adjustments of antiparkinsonian therapy 
Opicapone enhances the effects of levodopa. Hence, it is often necessary to adjust levodopa dosage 
within the first days to first weeks after initiating the treatment with opicapone (see section 4.4).  
 
Missed dose 
If one dose is missed, the next dose should be taken as scheduled. The patient should not take an extra 
dose to make up for the missed dose.  
 
Special populations 
 
Elderly  



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No dose adjustment is needed for elderly patients (see section 5.2). 
Caution must be exercised in patients ≥ 85 years of age as there is limited experience in this age group. 
 
Renal impairment 
No dose adjustment is necessary in patients with renal impairment, as opicapone is not excreted by the 
kidney (see section 5.2). 
 
Hepatic impairment 
No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh Class A).  
There is limited clinical experience in patients with moderate hepatic impairment (Child-Pugh Class 
B). Caution must be exercised in these patients and dose adjustment may be necessary (see section 
5.2). 
There is no clinical experience in patients with severe hepatic impairment (Child-Pugh Class C), 
therefore, Ongentys is not recommended in these patients (see section 5.2). 
 
Paediatric population 
There is no relevant use of Ongentys in the paediatric population with Parkinson’s disease and motor 
fluctuations. 
 
Method of administration 
 
Oral use. 
 
The capsules should be swallowed whole with water. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Phaeochromocytoma, paraganglioma, or other catecholamine secreting neoplasms. 
 
History of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis. 
 
Concomitant use with monoamine oxidase (MAO-A and MAO-B) inhibitors (e.g. phenelzine, 
tranylcypromine and moclobemide) other than those for the treatment of Parkinson’s disease (see 
section 4.5). 
 
4.4 Special warnings and precautions for use 
 
Dose adjustments of antiparkinsonian therapy 
 
Ongentys is to be administered as an adjunct to levodopa treatment. Hence, the precautions valid for 
levodopa treatment should also be taken into account for Ongentys. Opicapone enhances the effects of 
levodopa. To reduce levodopa-related dopaminergic adverse reactions (e.g. dyskinesia, hallucinations, 
nausea, vomiting and orthostatic hypotension), it is often necessary to adjust the daily dose of 
levodopa by extending the dosing intervals and/or reducing the amount of levodopa per dose within 
the first days to first weeks after initiating treatment with Ongentys, according to the clinical condition 
of the patient (see section 4.2).  
 
If Ongentys is discontinued it is necessary to adjust the dosing of the other antiparkinsonian 
treatments, especially levodopa, to achieve a sufficient level of control of the symptoms. 
 
Psychiatric disorders 
 
Patients and care-givers should be made aware that impulse control disorders including pathological 
gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and 



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compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic 
treatments. Patients should be monitored regularly for the development of impulse control disorders 
and review of treatment is recommended if such symptoms develop. 
 
Others 
 
Increases in liver enzymes were reported in studies with nitrocatechol inhibitors of catechol-O-
methyltransferase (COMT). For patients who experience progressive anorexia, asthenia and weight 
decrease within a relatively short period of time, a general medical evaluation including liver function 
should be considered. 
 
Intolerance to excipients 
 
Ongentys contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp 
lactase deficiency or glucose-galactose malabsorption should not take Ongentys. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Monoamino oxidase (MAO) inhibitors 
 
Combination of opicapone and MAO inhibitors could result in inhibition of the majority of the 
pathways responsible for the metabolism of catecholamines. Because of this, concomitant use of 
opicapone with MAO inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those 
for the treatment of Parkinson’s disease is contraindicated.  
Concomitant use of opicapone and MAO inhibitors for the treatment of Parkinson’s disease, e.g. 
rasagiline (up to 1 mg/day) and selegiline (up to 10 mg/day in oral formulation or 1.25 mg/day in 
buccal absorption formulation), is permissible (see section 4.3).  
 
There is no experience with opicapone when used concomitantly with the MAO-B inhibitor 
safinamide. Therefore, their concomitant use should be considered with appropriate caution. 
 
Medicinal products metabolised by COMT 
 
Opicapone may interfere with the metabolism of medicinal products containing a catechol group that 
are metabolised by COMT, e.g. rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, 
dopexamine or dobutamine, leading to potentiated effects of these medicinal products. Careful 
monitoring of patients being treated with these medicinal products is advised when opicapone is used.  
 
Tricyclic antidepressants and noradrenaline re-uptake inhibitors 
 
There is limited experience with opicapone when used concomitantly with tricyclic antidepressants 
and noradrenaline re-uptake inhibitors (e.g. venlafaxine, maprotiline and desipramine). Thus, their 
concomitant use should be considered with appropriate caution. 
 
CYP2C8 and OATP1B1 substrates 
 
Opicapone is a weak in vitro inhibitor of CYP2C8 and OATP1B1, whereas repaglinide is a sensitive 
CYP2C8 and OATP1B1 substrate. A study conducted in healthy subjects showed that there were no 
changes in repaglinide’s exposure when repaglinide was administered following multiple once-daily 
administration of opicapone 50 mg. 
 
Quinidine 
 
A study conducted in healthy volunteers showed that when a single dose of 50 mg opicapone was co-
administered (within 1 hour) with a single dose of quinidine (600 mg), systemic exposure of 
opicapone decreased by 37% (AUC0-tlast). Thus, particular consideration should be given to cases 



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where quinidine needs to be administered together with opicapone as their co-administration should be 
avoided.  
 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of opicapone in pregnant women. Animal studies 
are insufficient with respect to reproductive toxicity (see section 5.3). Ongentys is not recommended 
during pregnancy and in women of childbearing potential not using contraception. 
 
Breast-feeding 
 
It is unknown whether opicapone or its metabolites are excreted in human milk. A risk to the 
newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with 
Ongentys.  
 
Fertility 
 
The effects of opicapone on fertility in humans have not been studied. Animal studies with opicapone 
do not indicate harmful effects with respect to fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Opicapone in association with levodopa may have major influence on the ability to drive and use 
machines. Opicapone may, together with levodopa, cause dizziness, symptomatic orthostatism and 
somnolence. Therefore, caution should be exercised when driving or using machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common adverse reactions reported were nervous system disorders. Dyskinesia was the most 
frequently reported treatment-emergent adverse reaction (17.7%).  
 
Tabulated list of adverse reactions 
 
In the table below (Table 1) all adverse reactions are presented by System Organ Class and frequency.  
Frequency categories are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), 
uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known 
(cannot be estimated from the available data). 
 
Table 1 – Frequency of adverse reactions (MedDRA) in placebo-controlled Phase 3 studies 
System Organ Class Very common  Common Uncommon 
Metabolism and 
nutrition disorders 

  Decreased appetite, 
Hypertriglyceridaemia 

Psychiatric disorders  Abnormal dreams,  
Hallucination, 
Hallucination visual, 
Insomnia 

Anxiety, Depression, 
Hallucination auditory, 
Nightmare, Sleep 
disorder., 

Nervous system 
disorders 

Dyskinesia 
 

Dizziness, Headache, 
Somnolence 

Dysgeusia, 
Hyperkinesia, Syncope 

Eye disorders   Dry eye 



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Ear and labyrinth 
disorders 

  Ear congestion 

Cardiac disorders   Palpitations 
Vascular disorders  Orthostatic 

Hypotension 
Hypertension, 
Hypotension 

Respiratory, thoracic 
and mediastinal 
disorders 

  Dyspnoea 

Gastrointestinal 
disorders 

 Constipation, Dry 
mouth, Vomiting 

Abdominal distention, 
Abdominal pain, 
Abdominal pain upper, 
Dyspepsia 

Musculoskeletal and 
connective tissue 
disorders 

 Muscle spasms Muscle twitching, 
Musculoskeletal 
stiffness, Myalgia, 
Pain in extremity 

Renal and urinary 
disorders 

  Chromaturia, Nocturia 

Investigations  Blood creatine 
phosphokinase 
increased 

Weight decreased 

 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no known specific antidote. Symptomatic and supportive treatment should be administered as 
appropriate. Removal of opicapone by gastric lavage and/or inactivation by administering activated 
charcoal should be considered. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Anti-parkinson drugs, other dopaminergic agents, ATC code: [not yet 
assigned] 
 
Mechanism of action 
 
Opicapone is a peripheral, selective and reversible catechol-O-methyltransferase (COMT) inhibitor 
endowed with a high binding affinity (sub-picomolar) that translates into a slow complex dissociation 
rate constant and a long duration of action (>24 hours) in vivo.  
 
In the presence of a DOPA decarboxylase inhibitor (DDCI), COMT becomes the major metabolising 
enzyme for levodopa, catalysing its conversion to 3-O-methyldopa (3-OMD) in the brain and 
periphery. In patients taking levodopa and a peripheral DDCI, such as carbidopa or benserazide, 
opicapone increases levodopa plasma levels thereby improving the clinical response to levodopa. 
 
Pharmacodynamic effects 
 

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Opicapone showed a marked (>90%) and long-lasting (>24 hours) COMT inhibition in healthy 
subjects after administration of 50 mg opicapone.  
 
At steady state, opicapone 50 mg significantly increased the extent of levodopa systemic exposure 
approximately 2 fold compared to placebo following a single oral administration of either 100/25 mg 
levodopa/carbidopa or 100/25 mg levodopa/benserazide administered 12 h after the opicapone dose.  
 
Clinical efficacy and safety  
 
The efficacy and safety of opicapone has been demonstrated in two Phase 3 double-blind, placebo and 
active (Study 1 only) controlled studies in 1,027 randomized adult patients with Parkinson’s disease 
treated with levodopa/DDCI (alone or in combination with other antiparkinsonian drugs) and end-of-
dose motor fluctuations for up to 15 weeks. At screening, the mean age was similar in all treatment 
groups in both studies, ranging between 61.5 and 65.3 years. Patients had disease severity stages 1 to 3 
(modified Hoehn and Yahr) at ON, were treated with 3 to 8 daily doses of levodopa/DDCI and had a 
daily average OFF-time of at least 1.5 hours. In both studies, 783 patients were treated with 25 mg or 
50 mg of opicapone or placebo. In Study 1, 122 patients were treated with opicapone 5 mg and 122 
patients were treated with entacapone 200 mg (active comparator). The majority of patients treated in 
both pivotal studies were treated with immediate-release levodopa/DDCI. There were 60 patients in 
the combined Phase 3 studies who were predominantly using controlled-release levodopa (i.e. >50% 
of their levodopa/DDCI formulations), 48 of whom were treated solely with controlled-release 
formulations of levodopa. Although there is no evidence that either the efficacy or safety of opicapone 
would be affected by use of controlled-release levodopa preparations, the experience with such 
preparations is limited. 
 
Opicapone demonstrated clinical efficacy superior to placebo during the double-blind treatment, both 
for the primary efficacy variable used in both pivotal studies, i.e. reduction in OFF-time (Table 2), the 
proportion of OFF-time responders (i.e. a subject who had a reduction in OFF-time of at least 1 hour 
from baseline to endpoint) (Table 3) and for most diary-derived secondary endpoints.  
 
The LS mean reduction in absolute OFF-time from baseline to endpoint in the entacapone group 
was -78.7 minutes. The difference in LS mean change in OFF-time of entacapone to placebo in 
Study 1 was -30.5 minutes. The difference in LS mean change in OFF-time of opicapone 50 mg to 
entacapone was -24.8 minutes and non-inferiority of opicapone 50 mg to entacapone was 
demonstrated (95% confidence interval: -61.4, 11.8).  
 
Table 2 – Change in absolute OFF-time and ON-time (minutes) from baseline to endpoint 
Treatment  N LS mean 95% CI p-value 
Study 1     
Change in OFF-time     

Placebo 121 -48.3 -- -- 
OPC 5 mg 122 -77.6 -- -- 
OPC 25 mg 119 -73.2 -- -- 
OPC 50 mg 115 -103.6 -- -- 
OPC 5 mg – Placebo -- -29.3 -65.5, 6.8 0.0558 
OPC 25 mg – Placebo -- -25.0 -61.5, 11.6 0.0902 
OPC 50 mg – Placebo -- -55.3 -92.0, -18.6 0.0016 

Change in total ON-time without troublesome dyskinesiasa  
Placebo 121 40.0 -- -- 
OPC 5 mg 122 75.6 -- -- 
OPC 25 mg 119 78.6 -- -- 
OPC 50 mg 115 100.8 -- -- 
OPC 5 mg – Placebo -- 35.6 -2.5, 73.7 0.0670 
OPC 25 mg – Placebo -- 38.6 0.2, 77.0 0.0489 
OPC 50 mg – Placebo -- 60.8 22.1, 99.6 0.0021 



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Treatment  N LS mean 95% CI p-value 
Study 2     
Change in OFF-time     

Placebo 136 -54.6 -- -- 
OPC 25 mg 125 -93.2 -- -- 
OPC 50 mg 150 -107.0 -- -- 
OPC 25 mg – placebo -- -38.5 -77.0, -0.1 0.0900 
OPC 50 mg – placebo -- -52.4 -89.1, -15.7 0.0101 

Change in total ON-time without troublesome dyskinesiasa  
Placebo 136 37.9 -- -- 
OPC 25 mg 125 79.7 -- -- 
OPC 50 mg 150 77.6 -- -- 
OPC 25 mg – placebo -- 41.8 0.7, 82.9 0.0839 
OPC 50 mg – placebo -- 39.7 0.5, 78.8 0.0852 

 CI = confidence interval; LS mean = least square mean; N = number of non-missing values; OPC = opicapone.  
a. ON-time without troublesome dyskinesias=ON-time with non-troublesome dyskinesias + ON-time without 
dyskinesias 
 
Table 3 – OFF-time responder rates at endpoint 
Response type Placebo 

(N=121) 
Entacapone 

(N=122) 
OPC 5 mg 
(N=122) 

OPC 25 mg 
(N=119) 

OPC 50 mg 
(N=115) 

Study 1      
OFF-time reduction      

Responders, n (%) 55 (45.5) 66 (54.1) 64 (52.5) 66 (55.5) 75 (65.2) 
Difference to 
placebo 

     

p-value -- 0.1845 0.2851 0.1176 0.0036 
(95% CI)  (-0.039; 0.209) (-0.056; 0.193) (-0.025; 0.229) (0.065; 0.316) 

Study 2      
OFF-time reduction      

Responders, n (%) 65 (47.8) NA NA 74 (59.2) 89 (59.3) 
Difference to 
placebo 

     

p-value -- -- -- 0.0506 0.0470 
(95% CI)    (0.001; 0.242) (0.003; 0.232) 

CI = confidence interval; N = total number of patients; n = number of patients with available information; NA 
= not applicable; OPC = opicapone 
Note: A responder was a patient who had a reduction of at least 1 hour in absolute OFF-time (OFF-time 
responder) 
 
The results of the open-label (OL) extension studies of 1 year duration in 862 patients who continued 
treatment from the double-blind studies (Study 1-OL and Study 2-OL) indicated maintenance of the 
effect achieved during DB study periods. In the OL studies, all patients began at a dose of 25 mg 
opicapone for the first week (7 days), regardless of their prior treatment in the double-blind period. If 
end-of-dose motor fluctuations were not sufficiently controlled and tolerability allowed, the opicapone 
dose could be increased to 50 mg. If unacceptable dopaminergic adverse events were seen, the 
levodopa dose was to be adjusted. If not sufficient to manage the adverse events, the opicapone dose 
could then be down titrated. For other adverse events, the levodopa and/or opicapone dose could be 
adjusted. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
opicapone in all subsets of the paediatric population with Parkinson’s disease and motor fluctuations 
(see section 4.2 for information on paediatric use). 



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5.2 Pharmacokinetic properties 
 
Absorption  
 
Opicapone presents a low absorption (~20%). Pharmacokinetic results showed that opicapone is 
rapidly absorbed, with a tmax of 1.0 h to 2.5 h following once-daily multiple-dose administration up to 
50 mg opicapone.  
 
Distribution 
 
In vitro studies over the opicapone concentration range 0.3 to 30 mcg/mL showed that binding of  
14C-opicapone to human plasma proteins is high (99.9%) and concentration-independent. The binding 
of 14C-opicapone to plasma proteins was unaffected by the presence of warfarin, diazepam, digoxin 
and tolbutamide, and the binding of 14C-warfarin, 2-14C-diazepam, 3H-digoxin and 14C-tolbutamide 
was unaffected by the presence of opicapone and opicapone sulphate, the major human metabolite. 
 
After oral administration, the apparent volume of distribution of opicapone at a dose of 50 mg was 
29 L with an inter-subject variability of 36%. 
 
Biotransformation 
 
Sulphation of opicapone appears to be the major metabolic pathway in humans, yielding the inactive 
opicapone sulphate metabolite. Other metabolic pathways include glucuronidation, methylation and 
reduction.  
 
The most abundant peaks in plasma after a single-dose of 100 mg 14C-opicapone are metabolites BIA 
9-1103 (sulphate) and BIA 9-1104 (methylated), 67.1 and 20.5% of radioactive AUC respectively. 
Other metabolites were not found in quantifiable concentrations in the majority of plasma samples 
collected during a clinical mass balance study.  
 
The reduced metabolite of opicapone (found to be active in non-clinical studies) is a minor metabolite 
in human plasma, and represented less than 10% of total systemic exposure to opicapone. 
 
In in vitro studies in human hepatic microsomes, minor inhibition of CYP1A2 and CYP2B6 was 
observed. All reductions in activity essentially occurred at the highest concentration of opicapone 
(10 mcg/mL).  
 
An in vitro study showed opicapone inhibited CYP2C8 activity. A single dose study with opicapone 
25 mg showed an average increase of 30 % in the rate, but not the extent, of exposure to repaglinide (a 
CYP2C8 substrate), when the two drugs were co-administered. A second study conducted showed 
that, at steady state, opicapone 50 mg had no effect on repaglinide systemic exposure.  
Opicapone reduced CYP2C9 activity through competitive / mixed type mode of inhibition. However, 
clinical interaction studies conducted with warfarin showed no effect of opicapone on the 
pharmacodynamics of warfarin, a substrate of CYP2C9. 
 
Elimination 
 
In healthy subjects, the opicapone elimination half-life (t1/2) was 0.7 h to 3.2 h following once-daily 
multiple-dose administration up to 50 mg opicapone. 
Following once-daily multiple oral doses of opicapone in the dose range of 5 to 50 mg, opicapone 
sulphate presented a long terminal phase with elimination half-life values ranging from 94 h to 122 h 
and, as a consequence of this long terminal elimination half-life, opicapone sulphate presented a high 
accumulation ratio in plasma, with values close of up to 6.6. 
 



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After oral administration, the apparent total body clearance of opicapone at a dose of 50 mg was 
22 L/h, with an inter-subject variability of 45%. 
 
Following administration of a single oral dose of 14C-opicapone, the main excretion route of opicapone 
and its metabolites was faeces, accounting for 58.5% to 76.8% of the administered radioactivity (mean 
67.2%). The remainder of the radioactivity was excreted in urine (mean 12.8%) and via expired air 
(mean 15.9%). In urine, the primary metabolite was the glucuronide metabolite of opicapone, while 
parent drug and other metabolites were generally below the limit of quantification. Overall, it can be 
concluded that the kidney is not the primary route of excretion. Therefore, it can be presumed that 
opicapone and its metabolites are mainly excreted in the faeces. 
 
Linearity/non-linearity 
 
Opicapone exposure increased in a dose proportional manner following once-daily multiple dose 
administration up to 50 mg opicapone. 
 
Transporters 
 
Effect of transporters on opicapone 
In vitro studies have shown that opicapone is not transported by OATP1B1, but is transported by 
OATP1B3, and efflux transported by P-gp and BCRP. BIA 9-1103, its major metabolite, was 
transported by OATP1B1 and OATP1B3, and efflux transported by BCRP, but is not a substrate for 
the P-gp/MDR1 efflux transporter. 
 
Effect of opicapone on transporters 
At clinically relevant concentrations, opicapone is not expected to inhibit OAT1, OAT3, OATP1B1, 
OATP1B3, OCT1, OCT2, BCRP, P-gp/MDR1, BSEP, MATE1 and MATE2-K transporters as 
suggested by in vitro and in vivo studies. 
 
Elderly (≥ 65 years old) 
 
The pharmacokinetics of opicapone was evaluated in elderly subjects (aged 65-78 years old) after 7-
day multiple-dose administration of 30 mg. An increase in both the rate and extent of systemic 
exposure was observed for the elderly population when compared to the young population. The S-
COMT activity inhibition was significantly increased in elderly subjects. The magnitude of this effect 
is not considered to be of clinical relevance.  
 
Weight 
 
There is no relationship between exposure of opicapone and body weight over the range of 40-100 kg. 
 
Hepatic impairment 
 
There is limited clinical experience in patients with moderate hepatic impairment (Child-Pugh Class 
B). The pharmacokinetics of opicapone was evaluated in healthy subjects and moderate chronic 
hepatic impaired patients after administration of a single-dose of 50 mg. The bioavailability of 
opicapone was significantly higher in patients with moderate chronic hepatic impairment and no safety 
concerns were observed. However, as opicapone is to be used as adjunctive levodopa-therapy, dose 
adjustments may be considered based on a potentially enhanced levodopa dopaminergic response and 
associated tolerability. There is no clinical experience in patients with severe hepatic impairment 
(Child-Pugh Class C) (see section 4.2). 
 
Renal impairment 
 
The pharmacokinetics of opicapone was not directly evaluated in subjects with chronic renal 
impairment. However, an evaluation with 50 mg opicapone was performed in subjects included in 



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both phase 3 studies with GFR/1.73 m2 <60 mL/min (i.e. moderately decreased renal elimination 
capacity), and using pooled BIA 9-1103 data (major metabolite of opicapone). BIA 9-1103 plasma 
levels were not affected in patients with chronic renal impairment, and as such, no dose adjustment 
needs to be considered. 
 
5.3 Preclinical safety data 
 
Non-clinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.  
 
In rats, opicapone did not affect male and female fertility or prenatal development at exposure levels 
22 times the therapeutic exposure in humans. In pregnant rabbits, opicapone was less well tolerated 
resulting in maximum systemic exposure levels around or below the therapeutic range. Although 
embryo-foetal development was not negatively influenced in rabbits, the study is not considered 
predictive for human risk assessment. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Capsule content  
 
Lactose monohydrate 
Sodium starch glycolate, Type A 
Maize starch, pregelatinized 
Magnesium stearate 
 
Capsule shell 
 
Gelatin 
Indigo carmine aluminium lake (E132) 
Erythrosine (E127) 
Titanium dioxide (E171) 
 
Printing ink  
 
Shellac, propylene glycol, ammonia, indigo carmine aluminium (E132) 
 
6.2 Incompatibilities 
 
Not applicable.  
 
6.3 Shelf life 
 
HDPE bottles: 3 years 
Blisters: 5 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special temperature storage conditions. 
 
Blisters: Store in the original blister in order to protect from moisture. 
 
HDPE bottles: Keep the bottle tightly closed in order to protect from moisture. 
 



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6.5 Nature and contents of container  
 
White high density polyethylene (HDPE) bottles with polypropylene (PP) child resistant closures 
containing 10 or 30 capsules. 
 
OPA/Al/PVC//Al blisters containing 10 or 30 capsules. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Bial - Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal  
Tel:+351 22 986 61 00 
Fax: +351 22 986 61 90 
e-mail: info@bial.com 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1066/001 
EU/1/15/1066/008-010 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 24 June 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ongentys 50 mg hard capsules  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each hard capsule contains 50 mg of opicapone. 
 
Excipient(s) with known effect  
 
Each hard capsule contains 148.2 mg of lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule (capsule)  
 
Dark blue capsules, size 1, approximately 19 mm, imprinted “OPC 50” on the cap and “Bial” on the 
body. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ongentys is indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase 
inhibitors (DDCI) in adult patients with Parkinson’s disease and end-of-dose motor fluctuations who 
cannot be stabilised on those combinations.  
 
4.2 Posology and method of administration 
 
Posology 
 
The recommended dose of opicapone is 50 mg.  
Ongentys should be taken once-daily at bedtime at least one hour before or after levodopa 
combinations. 
 
Dose adjustments of antiparkinsonian therapy 
Opicapone enhances the effects of levodopa. Hence, it is often necessary to adjust levodopa dosage 
within the first days to first weeks after initiating the treatment with opicapone (see section 4.4).  
 
Missed dose 
If one dose is missed, the next dose should be taken as scheduled. The patient should not take an extra 
dose to make up for the missed dose.  
 
Special populations 
 
Elderly  



14 

No dose adjustment is needed for elderly patients (see section 5.2). 
Caution must be exercised in patients ≥ 85 years of age as there is limited experience in this age group. 
 
Renal impairment 
No dose adjustment is necessary in patients with renal impairment, as opicapone is not excreted by the 
kidney (see section 5.2). 
 
Hepatic impairment 
No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh Class A).  
There is limited clinical experience in patients with moderate hepatic impairment (Child-Pugh Class 
B). Caution must be exercised in these patients and dose adjustment may be necessary (see section 
5.2). 
There is no clinical experience in patients with severe hepatic impairment (Child-Pugh Class C), 
therefore, Ongentys is not recommended in these patients (see section 5.2). 
 
Paediatric population 
There is no relevant use of Ongentys in the paediatric population with Parkinson’s disease and motor 
fluctuations. 
 
Method of administration 
 
Oral use. 
 
The capsules should be swallowed whole with water. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Phaeochromocytoma, paraganglioma, or other catecholamine secreting neoplasms. 
 
History of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis. 
 
Concomitant use with monoamine oxidase (MAO-A and MAO-B) inhibitors (e.g. phenelzine, 
tranylcypromine and moclobemide) other than those for the treatment of Parkinson’s disease (see 
section 4.5). 
 
4.4 Special warnings and precautions for use 
 
Dose adjustments of antiparkinsonian therapy 
 
Ongentys is to be administered as an adjunct to levodopa treatment. Hence, the precautions valid for 
levodopa treatment should also be taken into account for Ongentys. Opicapone enhances the effects of 
levodopa. To reduce levodopa-related dopaminergic adverse reactions (e.g. dyskinesia, hallucinations, 
nausea, vomiting and orthostatic hypotension), it is often necessary to adjust the daily dose of 
levodopa by extending the dosing intervals and/or reducing the amount of levodopa per dose within 
the first days to first weeks after initiating treatment with Ongentys, according to the clinical condition 
of the patient (see section 4.2).  
 
If Ongentys is discontinued it is necessary to adjust the dosing of the other antiparkinsonian 
treatments, especially levodopa, to achieve a sufficient level of control of the symptoms. 
 
Psychiatric disorders 
 
Patients and care-givers should be made aware that impulse control disorders including pathological 
gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and 



15 

compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic 
treatments. Patients should be monitored regularly for the development of impulse control disorders 
and review of treatment is recommended if such symptoms develop. 
 
Others 
 
Increases in liver enzymes were reported in studies with nitrocatechol inhibitors of catechol-O-
methyltransferase (COMT). For patients who experience progressive anorexia, asthenia and weight 
decrease within a relatively short period of time, a general medical evaluation including liver function 
should be considered. 
 
Intolerance to excipients 
 
Ongentys contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp 
lactase deficiency or glucose-galactose malabsorption should not take Ongentys. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Monoamino oxidase (MAO) inhibitors 
 
Combination of opicapone and MAO inhibitors could result in inhibition of the majority of the 
pathways responsible for the metabolism of catecholamines. Because of this, concomitant use of 
opicapone with MAO inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those 
for the treatment of Parkinson’s disease is contraindicated.  
Concomitant use of opicapone and MAO inhibitors for the treatment of Parkinson’s disease, e.g. 
rasagiline (up to 1 mg/day) and selegiline (up to 10 mg/day in oral formulation or 1.25 mg/day in 
buccal absorption formulation), is permissible (see section 4.3).  
 
There is no experience with opicapone when used concomitantly with the MAO-B inhibitor 
safinamide. Therefore, their concomitant use should be considered with appropriate caution. 
 
Medicinal products metabolised by COMT 
 
Opicapone may interfere with the metabolism of medicinal products containing a catechol group that 
are metabolised by COMT, e.g. rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, 
dopexamine or dobutamine, leading to potentiated effects of these medicinal products. Careful 
monitoring of patients being treated with these medicinal products is advised when opicapone is used.  
 
Tricyclic antidepressants and noradrenaline re-uptake inhibitors 
 
There is limited experience with opicapone when used concomitantly with tricyclic antidepressants 
and noradrenaline re-uptake inhibitors (e.g. venlafaxine, maprotiline and desipramine). Thus, their 
concomitant use should be considered with appropriate caution. 
 
CYP2C8 and OATP1B1 substrates 
 
Opicapone is a weak in vitro inhibitor of CYP2C8 and OATP1B1, whereas repaglinide is a sensitive 
CYP2C8 and OATP1B1 substrate. A study conducted in healthy subjects showed that there were no 
changes in repaglinide’s exposure when repaglinide was administered following multiple once-daily 
administration of opicapone 50 mg. 
 
Quinidine 
 
A study conducted in healthy volunteers showed that when a single dose of 50 mg opicapone was co-
administered (within 1 hour) with a single dose of quinidine (600 mg), systemic exposure of 
opicapone decreased by 37% (AUC0-tlast). Thus, particular consideration should be given to cases 



16 

where quinidine needs to be administered together with opicapone as their co-administration should be 
avoided.  
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of opicapone in pregnant women. Animal studies 
are insufficient with respect to reproductive toxicity (see section 5.3). Ongentys is not recommended 
during pregnancy and in women of childbearing potential not using contraception. 
 
Breast-feeding 
 
It is unknown whether opicapone or its metabolites are excreted in human milk. A risk to the 
newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with 
Ongentys.  
 
Fertility 
 
The effects of opicapone on fertility in humans have not been studied. Animal studies with opicapone 
do not indicate harmful effects with respect to fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Opicapone in association with levodopa may have major influence on the ability to drive and use 
machines. Opicapone may, together with levodopa, cause dizziness, symptomatic orthostatism and 
somnolence. Therefore, caution should be exercised when driving or using machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common adverse reactions reported were nervous system disorders. Dyskinesia was the most 
frequently reported treatment-emergent adverse reaction (17.7%).  
 
Tabulated list of adverse reactions 
 
In the table below (Table 1) all adverse reactions are presented by System Organ Class and frequency.  
Frequency categories are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), 
uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known 
(cannot be estimated from the available data). 
 
Table 1 – Frequency of adverse reactions (MedDRA) in placebo-controlled Phase 3 studies 
System Organ Class Very common  Common Uncommon 
Metabolism and 
nutrition disorders 

  Decreased appetite, 
Hypertriglyceridaemia 

Psychiatric disorders  Abnormal dreams,  
Hallucination, 
Hallucination visual, 
Insomnia 

Anxiety, Depression, 
Hallucination auditory, 
Nightmare, Sleep 
disorder., 

Nervous system 
disorders 

Dyskinesia 
 

Dizziness, Headache, 
Somnolence 

Dysgeusia, 
Hyperkinesia, Syncope 

Eye disorders   Dry eye 
Ear and labyrinth 
disorders 

  Ear congestion 



17 

Cardiac disorders   Palpitations 
Vascular disorders  Orthostatic 

Hypotension 
Hypertension, 
Hypotension 

Respiratory, thoracic 
and mediastinal 
disorders 

  Dyspnoea 

Gastrointestinal 
disorders 

 Constipation, Dry 
mouth, Vomiting 

Abdominal distention, 
Abdominal pain, 
Abdominal pain upper, 
Dyspepsia 

Musculoskeletal and 
connective tissue 
disorders 

 Muscle spasms Muscle twitching, 
Musculoskeletal 
stiffness, Myalgia, 
Pain in extremity 

Renal and urinary 
disorders 

  Chromaturia, Nocturia 

Investigations  Blood creatine 
phosphokinase 
increased 

Weight decreased 

 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no known specific antidote. Symptomatic and supportive treatment should be administered as 
appropriate. Removal of opicapone by gastric lavage and/or inactivation by administering activated 
charcoal should be considered. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Anti-parkinson drugs, other dopaminergic agents, ATC code: [not yet 
assigned] 
 
Mechanism of action 
 
Opicapone is a peripheral, selective and reversible catechol-O-methyltransferase (COMT) inhibitor 
endowed with a high binding affinity (sub-picomolar) that translates into a slow complex dissociation 
rate constant and a long duration of action (>24 hours) in vivo.  
 
In the presence of a DOPA decarboxylase inhibitor (DDCI), COMT becomes the major metabolising 
enzyme for levodopa, catalysing its conversion to 3-O-methyldopa (3-OMD) in the brain and 
periphery. In patients taking levodopa and a peripheral DDCI, such as carbidopa or benserazide, 
opicapone increases levodopa plasma levels thereby improving the clinical response to levodopa. 
 
Pharmacodynamic effects 
 
Opicapone showed a marked (>90%) and long-lasting (>24 hours) COMT inhibition in healthy 
subjects after administration of 50 mg opicapone.  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


18 

 
At steady state, opicapone 50 mg significantly increased the extent of levodopa systemic exposure 
approximately 2 fold compared to placebo following a single oral administration of either 100/25 mg 
levodopa/carbidopa or 100/25 mg levodopa/benserazide administered 12 h after the opicapone dose.  
 
Clinical efficacy and safety  
 
The efficacy and safety of opicapone has been demonstrated in two Phase 3 double-blind, placebo and 
active (Study 1 only) controlled studies in 1,027 randomized adult patients with Parkinson’s disease 
treated with levodopa/DDCI (alone or in combination with other antiparkinsonian drugs) and end-of- 
dose motor fluctuations for up to 15 weeks. At screening, the mean age was similar in all treatment 
groups in both studies, ranging between 61.5 and 65.3 years. Patients had disease severity stages 1 to 3 
(modified Hoehn and Yahr) at ON, were treated with 3 to 8 daily doses of levodopa/DDCI and had a 
daily average OFF-time of at least 1.5 hours. In both studies, 783 patients were treated with 25 mg or 
50 mg of opicapone or placebo. In Study 1, 122 patients were treated with opicapone 5 mg and 122 
patients were treated with entacapone 200 mg (active comparator). The majority of patients treated in 
both pivotal studies were treated with immediate-release levodopa/DDCI. There were 60 patients in 
the combined Phase 3 studies who were predominantly using controlled-release levodopa (i.e. >50% 
of their levodopa/DDCI formulations), 48 of whom were treated solely with controlled-release 
formulations of levodopa. Although there is no evidence that either the efficacy or safety of opicapone 
would be affected by use of controlled-release levodopa preparations, the experience with such 
preparations is limited. 
 
Opicapone demonstrated clinical efficacy superior to placebo during the double-blind treatment, both 
for the primary efficacy variable used in both pivotal studies, i.e. reduction in OFF-time (Table 2), the 
proportion of OFF-time responders (i.e. a subject who had a reduction in OFF-time of at least 1 hour 
from baseline to endpoint) (Table 3) and for most diary derived secondary endpoints. 
 
The LS mean reduction in absolute OFF-time from baseline to endpoint in the entacapone group 
was -78.7 minutes. The difference in LS mean change in OFF-time of entacapone to placebo in 
Study 1 was -30.5 minutes. The difference in LS mean change in OFF-time of opicapone 50 mg to 
entacapone was -24.8 minutes and non-inferiority of opicapone 50 mg to entacapone was 
demonstrated (95% confidence interval: -61.4, 11.8).  
 
Table 2 – Change in absolute OFF-time and ON-time (minutes) from baseline to endpoint 
Treatment  N LS mean 95% CI p-value 
Study 1     
Change in OFF-time     

Placebo 121 -48.3 -- -- 
OPC 5 mg 122 -77.6 -- -- 
OPC 25 mg 119 -73.2 -- -- 
OPC 50 mg 115 -103.6 -- -- 
OPC 5 mg – Placebo -- -29.3 -65.5, 6.8 0.0558 
OPC 25 mg – Placebo -- -25.0 -61.5, 11.6 0.0902 
OPC 50 mg – Placebo -- -55.3 -92.0, -18.6 0.0016 

Change in total ON-time without troublesome dyskinesiasa  
Placebo 121 40.0 -- -- 
OPC 5 mg 122 75.6 -- -- 
OPC 25 mg 119 78.6 -- -- 
OPC 50 mg 115 100.8 -- -- 
OPC 5 mg – Placebo -- 35.6 -2.5, 73.7 0.0670 
OPC 25 mg – Placebo -- 38.6 0.2, 77.0 0.0489 
OPC 50 mg – Placebo -- 60.8 22.1, 99.6 0.0021 

Study 2     
Change in OFF-time     



19 

Treatment  N LS mean 95% CI p-value 
Placebo 136 -54.6 -- -- 
OPC 25 mg 125 -93.2 -- -- 
OPC 50 mg 150 -107.0 -- -- 
OPC 25 mg – placebo -- -38.5 -77.0, -0.1 0.0900 
OPC 50 mg – placebo -- -52.4 -89.1, -15.7 0.0101 

Change in total ON-time without troublesome dyskinesiasa  
Placebo 136 37.9 -- -- 
OPC 25 mg 125 79.7 -- -- 
OPC 50 mg 150 77.6 -- -- 
OPC 25 mg – placebo -- 41.8 0.7, 82.9 0.0839 
OPC 50 mg – placebo -- 39.7 0.5, 78.8 0.0852 

 CI = confidence interval; LS mean = least square mean; N = number of non-missing values; OPC = opicapone.  
a. ON-time without troublesome dyskinesias=ON-time with non-troublesome dyskinesias + ON-time without 
dyskinesias 
 
Table 3 – OFF-time responder rates at endpoint 
Response type Placebo 

(N=121) 
Entacapone 

(N=122) 
OPC 5 mg 
(N=122) 

OPC 25 mg 
(N=119) 

OPC 50 mg 
(N=115) 

Study 1      
OFF-time reduction      

Responders, n (%) 55 (45.5) 66 (54.1) 64 (52.5) 66 (55.5) 75 (65.2) 
Difference to 
placebo 

     

p-value -- 0.1845 0.2851 0.1176 0.0036 
(95% CI)  (-0.039; 0.209) (-0.056; 0.193) (-0.025; 0.229) (0.065; 0.316) 

Study 2      
OFF-time reduction      

Responders, n (%) 65 (47.8) NA NA 74 (59.2) 89 (59.3) 
Difference to 
placebo 

     

p-value -- -- -- 0.0506 0.0470 
(95% CI)    (0.001; 0.242) (0.003; 0.232) 

CI = confidence interval; N = total number of patients; n = number of patients with available information; NA 
= not applicable; OPC = opicapone 
Note: A responder was a patient who had a reduction of at least 1 hour in absolute OFF-time (OFF-time 
responder) 
 
The results of the open-label (OL) extension studies of 1 year duration in 862 patients who continued 
treatment from the double-blind studies (Study 1-OL and Study 2-OL) indicated maintenance of the 
effect achieved during DB study periods. In the OL studies, all patients began at a dose of 25 mg 
opicapone for the first week (7 days), regardless of their prior treatment in the double-blind period. If 
end-of-dose motor fluctuations were not sufficiently controlled and tolerability allowed, the opicapone 
dose could be increased to 50 mg. If unacceptable dopaminergic adverse events were seen, the 
levodopa dose was to be adjusted. If not sufficient to manage the adverse events, the opicapone dose 
could then be down titrated. For other adverse events, the levodopa and/or opicapone dose could be 
adjusted. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
opicapone in all subsets of the paediatric population with Parkinson’s disease and motor fluctuations 
(see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 



20 

 
Absorption  
 
Opicapone presents a low absorption (~20%). Pharmacokinetic results showed that opicapone is 
rapidly absorbed, with a tmax of 1.0 h to 2.5 h following once-daily multiple-dose administration up to 
50 mg opicapone.  
 
Distribution 
 
In vitro studies over the opicapone concentration range 0.3 to 30 mcg/mL showed that binding of  
14C-opicapone to human plasma proteins is high (99.9%) and concentration-independent. The binding 
of 14C-opicapone to plasma proteins was unaffected by the presence of warfarin, diazepam, digoxin 
and tolbutamide, and the binding of 14C-warfarin, 2-14C-diazepam, 3H-digoxin and 14C-tolbutamide 
was unaffected by the presence of opicapone and opicapone sulphate, the major human metabolite. 
 
After oral administration, the apparent volume of distribution of opicapone at a dose of 50 mg was 
29 L with an inter-subject variability of 36%. 
 
Biotransformation 
 
Sulphation of opicapone appears to be the major metabolic pathway in humans, yielding the inactive 
opicapone sulphate metabolite. Other metabolic pathways include glucuronidation, methylation and 
reduction.  
 
The most abundant peaks in plasma after a single-dose of 100 mg 14C-opicapone are metabolites 
BIA 9-1103 (sulphate) and BIA 9-1104 (methylated), 67.1 and 20.5% of radioactive AUC 
respectively. Other metabolites were not found in quantifiable concentrations in the majority of plasma 
samples collected during a clinical mass balance study.. 
 
The reduced metabolite of opicapone (found to be active in non-clinical studies) is a minor metabolite 
in human plasma, and represented less than 10% of total systemic exposure to opicapone. 
 
In in vitro studies in human hepatic microsomes, minor inhibition of CYP1A2 and CYP2B6 was 
observed. All reductions in activity essentially occurred at the highest concentration of opicapone  
(10 mcg/mL).  
An in vitro study showed opicapone inhibited CYP2C8 activity. A single dose study with opicapone 
25 mg showed an average increase of 30 % in the rate, but not the extent, of exposure to repaglinide (a 
CYP2C8 substrate), when the two drugs were co-administered. A second study conducted showed 
that, at steady state, opicapone 50 mg had no effect on repaglinide systemic exposure. 
Opicapone reduced CYP2C9 activity through competitive / mixed type mode of inhibition. However, 
clinical interaction studies conducted with warfarin showed no effect of opicapone on the 
pharmacodynamics of warfarin, a substrate of CYP2C9. 
 
Elimination 
 
In healthy subjects, the opicapone elimination half-life (t1/2) was 0.7 h to 3.2 h following once-daily 
multiple-dose administration up to 50 mg opicapone. 
Following once-daily multiple oral doses of opicapone in the dose range of 5 to 50 mg, opicapone 
sulphate presented a long terminal phase with elimination half-life values ranging from 94 h to 122 h 
and, as a consequence of this long terminal elimination half-life, opicapone sulphate presented a high 
accumulation ratio in plasma, with values close of up to 6.6. 
 
After oral administration, the apparent total body clearance of opicapone at a dose of 50 mg was 
22 L/h, with an inter-subject variability of 45%. 
 



21 

Following administration of a single oral dose of 14C-opicapone, the main excretion route of opicapone 
and its metabolites was faeces, accounting for 58.5% to 76.8% of the administered radioactivity (mean 
67.2%). The remainder of the radioactivity was excreted in urine (mean 12.8%) and via expired air 
(mean 15.9%). In urine, the primary metabolite was the glucuronide metabolite of opicapone, while 
parent drug and other metabolites were generally below the limit of quantification. Overall, it can be 
concluded that the kidney is not the primary route of excretion. Therefore, it can be presumed that 
opicapone and its metabolites are mainly excreted in the faeces. 
 
Linearity/non-linearity 
 
Opicapone exposure increased in a dose proportional manner following once-daily multiple dose 
administration up to 50 mg opicapone. 
 
Transporters 
 
Effect of transporters on opicapone 
In vitro studies have shown that opicapone is not transported by OATP1B1, but is transported by 
OATP1B3, and efflux transported by P-gp and BCRP. BIA 9-1103, its major metabolite, was 
transported by OATP1B1 and OATP1B3, and efflux transported by BCRP, but is not a substrate for 
the P-gp/MDR1 efflux transporter. 
 
Effect of opicapone on transporters 
At clinically relevant concentrations, opicapone is not expected to inhibit OAT1, OAT3, OATP1B1, 
OATP1B3, OCT1, OCT2, BCRP, P-gp/MDR1, BSEP, MATE1 and MATE2-K transporters as 
suggested by in vitro and in vivo studies. 
 
Elderly (≥ 65 years old) 
 
The pharmacokinetics of opicapone was evaluated in elderly subjects (aged 65-78 years old) after 7-
day multiple-dose administration of 30 mg. An increase in both the rate and extent of systemic 
exposure was observed for the elderly population when compared to the young population. The S-
COMT activity inhibition was significantly increased in elderly subjects. The magnitude of this effect 
is not considered to be of clinical relevance.  
 
Weight 
 
There is no relationship between exposure of opicapone and body weight over the range of 40-100 kg. 
 
Hepatic impairment 
 
There is limited clinical experience in patients with moderate hepatic impairment (Child-Pugh Class 
B). The pharmacokinetics of opicapone was evaluated in healthy subjects and moderate chronic 
hepatic impaired patients after administration of a single-dose of 50 mg. The bioavailability of 
opicapone was significantly higher in patients with moderate chronic hepatic impairment and no safety 
concerns were observed. However, as opicapone is to be used as adjunctive levodopa-therapy, dose 
adjustments may be considered based on a potentially enhanced levodopa dopaminergic response and 
associated tolerability. There is no clinical experience in patients with severe hepatic impairment 
(Child-Pugh Class C) (see section 4.2). 
 
Renal impairment 
 
The pharmacokinetics of opicapone was not directly evaluated in subjects with chronic renal 
impairment. However, an evaluation with 50 mg opicapone was performed in subjects included in 
both phase 3 studies with GFR/1.73 m2 <60 mL/min (i.e. moderately decreased renal elimination 
capacity), and using pooled BIA 9-1103 data (major metabolite of opicapone). BIA 9-1103 plasma 



22 

levels were not affected in patients with chronic renal impairment, and as such, no dose adjustment 
needs to be considered. 
 
5.3 Preclinical safety data 
 
Non-clinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.  
 
In rats, opicapone did not affect male and female fertility or prenatal development at exposure levels 
22 times the therapeutic exposure in humans. In pregnant rabbits, opicapone was less well tolerated 
resulting in maximum systemic exposure levels around or below the therapeutic range. Although 
embryo-foetal development was not negatively influenced in rabbits, the study is not considered 
predictive for human risk assessment. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Capsule content  
 
Lactose monohydrate 
Sodium starch glycolate, Type A 
Maize starch, pregelatinized 
Magnesium stearate 
 
Capsule shell 
 
Gelatin 
Indigo carmine aluminium lake (E132) 
Erythrosine (E127) 
Titanium dioxide (E171) 
 
Printing ink 
 
Shellac, titanium dioxide (E171), propylene glycol, ammonia, simethicone  
 
6.2 Incompatibilities 
 
Not applicable.  
 
6.3 Shelf life 
 
HDPE bottles: 3 years 
Blisters: 5 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special temperature storage conditions. 
 
Blisters: Store in the original blister in order to protect from moisture. 
 
HDPE bottles: Keep the bottle tightly closed in order to protect from moisture. 
 
6.5 Nature and contents of container  
 



23 

White high density polyethylene (HDPE) bottles with polypropylene (PP) child resistant closures 
containing 10, 30 or 90 capsules. 
 
OPA/Al/PVC//Al blisters containing 10, 30 or 90 capsules 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Bial - Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal  
Tel:+351 22 986 61 00 
Fax: +351 22 986 61 90 
e-mail: info@bial.com 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1066/002-007 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 24 June 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE 
AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 



25 

  A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer responsible for batch release 

Bial - Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

Medicinal product subject to medical prescription. 
 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING        
AUTHORISATION  

 

• Periodic safety update reports  
 

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 

The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation. 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



28 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
HDPE BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ongentys 25 mg hard capsules 
opicapone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 25 mg of opicapone. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 hard capsules 
30 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



29 

Keep the bottle tightly closed in order to protect from moisture 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bial - Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal  
(only for outer packaging) 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1066/009 10 hard capsules 
EU/1/15/1066/010 30 hard capsules 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
ongentys 25 mg (only on the outer packaging) 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
(only for outer packaging) 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
(only for outer packaging) 
 
 



30 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
BOX (BLISTER OPA/Al/PVC//Al) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ongentys 25 mg hard capsules 
opicapone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 25 mg of opicapone. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 hard capsules 
30 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original blister in order to protect from moisture.  



31 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bial - Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1066/001 10 hard capsules 
EU/1/15/1066/008 30 hard capsules 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
ongentys 25 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



32 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER OPA/Al/PVC//Al 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ongentys 25 mg capsules 
opicapone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BIAL 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
HDPE BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ongentys 50 mg hard capsules 
opicapone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 50 mg of opicapone. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 hard capsules 
30 hard capsules 
90 hard capsules  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



34 

Keep the bottle tightly closed in order to protect from moisture 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bial - Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal  
(only for outer packaging) 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1066/005 10 hard capsules 
EU/1/15/1066/006 30 hard capsules 
EU/1/15/1066/007 90 hard capsules 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
ongentys 50 mg (only on the outer packaging) 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
(only for outer packaging) 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
(only for outer packaging) 
 
 



35 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
BOX (BLISTER OPA/Al/PVC//Al) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ongentys 50 mg hard capsules 
opicapone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 50 mg of opicapone. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. 
 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 hard capsules 
30 hard capsules 
90 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



36 

Store in the original blister in order to protect from moisture.  
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bial - Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1066/002 10 hard capsules 
EU/1/15/1066/003 30 hard capsules 
EU/1/15/1066/004 90 hard capsules 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
ongentys 50 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



37 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER OPA/Al/PVC//Al 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ongentys 50 mg capsules 
opicapone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BIAL 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



39 

 
Package leaflet: Information for the patient 

 
Ongentys 25 mg hard capsules 

opicapone 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
1. What Ongentys is and what it is used for 
2. What you need to know before you take Ongentys 
3. How to take Ongentys 
4. Possible side effects 
5. How to store Ongentys 
6. Contents of the pack and other information 
 
 
1. What Ongentys is and what it is used for 
 
Ongentys is a medicine that contains the active substance opicapone. It is used to treat Parkinson’s 
disease and associated movement problems. Parkinson's disease is a progressive disease of the nervous 
system that causes shaking and affects your movement. 
 
Ongentys is for use in adults who are already taking medicines containing levodopa and DOPA 
decarboxylase inhibitors. It increases the effects of levodopa and helps to relieve the symptoms of 
Parkinson’s disease and movement problems.  
 
 
2. What you need to know before you take Ongentys 
 
Do not take Ongentys: 
- if you are allergic to opicapone or any of the other ingredients of this medicine (listed in section 

6); 
- if you have a tumour of the adrenal gland (known as phaeochromocytoma), or of the nervous 

system (known as paraganglioma), or any other tumour which increase the risk of severe high 
blood pressure; 

- if you have ever suffered from neuroleptic malignant syndrome which is a rare reaction to 
antipsychotic medicines; 

- if you have ever suffered from a rare muscle disorder called rhabdomyolysis which was not 
caused by injury; 

- if you are taking certain antidepressants called monoamine-oxidase (MAO) inhibitors (e.g. 
phenelzine, tranylcypromine or moclobemide). Ask your doctor or pharmacist if you can take 
your antidepressant together with Ongentys. 

 
Warnings and precautions 



40 

Talk to your doctor or pharmacist before taking Ongentys: 
- if you have severe liver problems and suffered from loss of appetite, weight loss, weakness, or 

exhaustion within a short period of time. Your doctor may need to reconsider your treatment. 
 
Talk to your doctor or pharmacist if you or your family/carer notices you are developing urges or 
cravings to behave in ways that are unusual for you or you cannot resist the impulse, drive or 
temptation to carry out certain activities that could harm you or others. These behaviours are called 
‘impulse control disorders’ and can include: addictive gambling, an abnormally high sex drive or an 
increased preoccupation with sexual thoughts or feelings. Behaviours such as these have been reported 
in patients using other medicines for Parkinsons´s disease.  
Your doctor may need to review your treatments. 
 
Other levodopa medicines 
As Ongentys will be used with other levodopa medicines, please also read the package leaflets of these 
medicines carefully. 
 
Children and adolescents 
Children and adolescents under the age of 18 years must not take this medicine as it has not been 
studied in these age groups. 
 
Other medicines and Ongentys 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Tell your doctor if you are taking:  
- medicines for depression or anxiety such as venlafaxine, maprotiline and desipramine. Taking 

Ongentys with these medicines may increase the risk of side effects. Your doctor may need to 
adjust your treatment; 

- safinamide used for Parkinson’s disease. There is no experience taking Ongentys and 
safinamide together. Your doctor may need to adjust your treatment; 

- medicines to treat asthma such as rimiterole or isoprenaline. Ongentys may increase their effect; 
- medicines used to treat allergic reactions such as adrenaline. Ongentys may increase their effect; 
- medicines used to treat heart failure such as dobutamine, dopamine or dopexamine. Ongentys 

may increase their effects; 
- medicines for high cholesterol such as rosuvastatin, simvastatin, atorvastatin or pravastatin 

Ongentys may increase their effects;  
- medicines that affect the immune system such as methotrexate. Ongentys may increase its 

effect; 
- medicines containing quinidine, a medicine used to treat abnormal heart rhythms or malaria. 

Taking Ongentys and quinidine together, i.e. at the same time, may decrease the effect of 
Ongentys. 

 
Pregnancy and breast-feeding 
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine. 
 
It is not known if Ongentys passes into breast milk in humans. Since the risk to the baby/infant cannot 
be excluded, you should stop breast-feeding during treatment with Ongentys.  
 
Driving and using machines 
Ongentys taken with levodopa may make you feel light-headed, dizzy, or sleepy. 
Do not drive or operate machinery if you experience any of these side effects. 
 
Ongentys contains lactose 
If you have been told by your doctor that you have intolerance to some sugars, contact your doctor 
before taking this medicine. 
 



41 

 
3. How to take Ongentys 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
The recommended dose is 50 mg once daily. 
Ongentys should be taken preferably at bedtime. 
 
Take Ongentys at least one hour before or after taking your levodopa medicine. 
 
Ongentys is for oral use. 
Swallow the capsule whole with a glass of water.  
 
Doses of other medicines to treat Parkinson’s disease 
The dose of other medicines to treat Parkinson’s disease may need to be adjusted when you start 
taking Ongentys. Follow the instructions that your doctor has given you. 
 
If you take more Ongentys than you should 
If you take more Ongentys than you should, tell your doctor or pharmacist, or go to a hospital 
immediately. Take the medicine package and this leaflet with you. This will help the doctor identify 
what you have taken. 
 
If you forget to take Ongentys 
If you forget to take one dose, you should continue the treatment and take the next dose as scheduled.  
Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking Ongentys 
Do not stop taking Ongentys unless your doctor tells you to as your symptoms may get worse. 
If you stop taking Ongentys your doctor may need to adjust the dose of other medicines that you are 
taking to treat Parkinson’s disease. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Side effects caused by Ongentys are usually mild to moderate and occur mostly within the first weeks 
of treatment. Some side effects may be caused by the increased effects of using Ongentys together 
with levodopa. 
 
Contact your doctor straight away if you experience any side effects at the start of treatment. Many of 
the side effects can be managed by your doctor adjusting your levodopa medicine. 
 
Tell your doctor as soon as possible if you notice any of the following side effects: 
 
Very common: may affect more than 1 in 10 people 
- involuntary and uncontrollable, or difficult or painful body movements 
 
Common: may affect up to 1 in 10 people 
- constipation 
- dry mouth 
- vomiting (being sick) 
- increased levels of the enzyme (creatine kinase) in your blood 
- muscle spasm 



42 

- dizziness 
- headache 
- sleepiness 
- difficulty falling or staying asleep  
- strange dreams  
- experiencing or seeing things which do not exist (hallucinations) 
- a fall in blood pressure on standing up which causes dizziness, light-headedness or fainting 
Uncommon: may affect up to 1 in 100 people 
- palpitations or irregular heartbeat 
- blocked ear 
- dry eye 
- pain or swelling of the abdomen 
- indigestion 
- weight loss 
- loss of appetite 
- increased levels of triglycerides (fats) in your blood 
- muscle twitching, stiffness or pain 
- pain in arms or legs 
- altered sense of taste 
- excessive body movements  
- fainting 
- anxiety 
- depression 
- hearing things which do not exist 
- nightmares 
- sleep disorder 
- abnormal colour of urine 
- need to wake and pass urine at night 
- shortness of breath 
- high or low blood pressure 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Ongentys 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the bottle/blister/carton after EXP. 
The expiry date refers to the last day of that month. 
 
This medicine does not require any special temperature storage conditions. 
Blisters: Store in the original blister in order to protect from moisture. 
Bottles: Keep the bottle tightly closed in order to protect from moisture. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Ongentys contains  
- The active substance is opicapone. Each hard capsule contains 25 mg of opicapone. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


43 

- The other ingredients are:  
o capsule content: lactose monohydrate, sodium starch glycolate (Type A), pregelatinized 

maize starch and magnesium stearate 
o capsule shell: gelatine, indigo carmine aluminium lake (E132), erythrosine (E127) and 

titanium dioxide (E171) 
o printing ink: shellac, propylene glycol, ammonia, indigo carmine aluminium (E132)  

 
What Ongentys looks like and contents of the pack 
Ongentys 25 mg hard capsules are light blue, approximately 19 mm length, with “OPC 25” and “Bial” 
printed on the capsules.  
 
The capsules are packaged in bottles or blisters. 
 
Bottles: 10 or 30 capsules. 
Blisters: 10 or 30 capsules. 
 
Not all packs may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Bial - Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal  
tel: +351 22 986 61 00 
fax: +351 22 986 61 90 
e-mail: info@bial.com 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien/България/Česká republika/ 
Deutschland/Eesti/Ελλάδα/France/ 
Hrvatska/Ireland/ Italia/Κύπρος/Latvija/ 
Lietuva/Luxembourg/Luxemburg/Magyarország/ 
Malta/Nederland/ Österreich/Polska/Portugal/ 
România/Slovenija/Slovenská republika/ United 
Kingdom 
BIAL - Portela & Cª, S.A. 
Tél/Tel/Teл./Tlf/Τηλ: + 351 22 986 61 00 
 

España 
Laboratorios BIAL, S.A. 
Tel: + 34 91 562 41 96 
 
Danmark 
Nordicinfu Care AB 
Tlf: +45 (0) 70 28 10 24 
 
Suomi/Finland 
Nordicinfu Care AB 
Puh/Tel: +358 (0) 207 348 760 
 
Ísland / Sverige  
Nordicinfu Care AB 
Tel / Sími: +46 (0) 8 601 24 40 
 
Norge 
Nordicinfu Care AB 
Tlf: +47 (0) 22 20 60 00 
 
 

 
This leaflet was last revised in {MM/YYYY}. 
 
 



44 

Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.   
 
 
 
 
 
 
 
 

http://www.ema.europa.eu/


45 

 
Package leaflet: Information for the patient 

 
Ongentys 50 mg hard capsules 

opicapone 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
1. What Ongentys is and what it is used for 
2. What you need to know before you take Ongentys 
3. How to take Ongentys 
4. Possible side effects 
5. How to store Ongentys 
6. Contents of the pack and other information 
 
 
1. What Ongentys is and what it is used for 
 
Ongentys is a medicine that contains the active substance opicapone. It is used to treat Parkinson’s 
disease and associated movement problems. Parkinson's disease is a progressive disease of the nervous 
system that causes shaking and affects your movement. 
 
Ongentys is for use in adults who are already taking medicines containing levodopa and DOPA 
decarboxylase inhibitors. It increases the effects of levodopa and helps to relieve the symptoms of 
Parkinson’s disease and movement problems.  
 
 
2. What you need to know before you take Ongentys 
 
Do not take Ongentys: 
- if you are allergic to opicapone or any of the other ingredients of this medicine (listed in section 

6); 
- if you have a tumour of the adrenal gland (known as phaeochromocytoma), or of the nervous 

system (known as paraganglioma), or any other tumour which increase the risk of severe high 
blood pressure; 

- if you have ever suffered from neuroleptic malignant syndrome which is a rare reaction to 
antipsychotic medicines; 

- if you have ever suffered from a rare muscle disorder called rhabdomyolysis which was not 
caused by injury; 

- if you are taking certain antidepressants called monoamine-oxidase (MAO) inhibitors (e.g. 
phenelzine, tranylcypromine or moclobemide). Ask your doctor or pharmacist if you can take 
your antidepressant together with Ongentys. 

 
Warnings and precautions 



46 

Talk to your doctor or pharmacist before taking Ongentys: 
- if you have severe liver problems and suffered from loss of appetite, weight loss, weakness, or 

exhaustion within a short period of time. Your doctor may need to reconsider your treatment. 
 
Talk to your doctor or pharmacist if you or your family/carer notices you are developing urges or 
cravings to behave in ways that are unusual for you or you cannot resist the impulse, drive or 
temptation to carry out certain activities that could harm you or others. These behaviours are called 
‘impulse control disorders’ and can include: addictive gambling, an abnormally high sex drive or an 
increased preoccupation with sexual thoughts or feelings. Behaviours such as these have been reported 
in patients using other medicines for Parkinsons´s disease.  
Your doctor may need to review your treatments. 
 
Other levodopa medicines 
As Ongentys will be used with other levodopa medicines, please also read the package leaflets of these 
medicines carefully. 
 
Children and adolescents 
Children and adolescents under the age of 18 years must not take this medicine as it has not been 
studied in these age groups. 
 
Other medicines and Ongentys 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
 
Tell your doctor if you are taking:  
- medicines for depression or anxiety such as venlafaxine, maprotiline and desipramine. Taking 

Ongentys with these medicines may increase the risk of side effects. Your doctor may need to 
adjust your treatment; 

- safinamide used for Parkinson’s disease. There is no experience taking Ongentys and 
safinamide together. Your doctor may need to adjust your treatment;  

- medicines to treat asthma such as rimiterole or isoprenaline. Ongentys may increase their effect; 
- medicines used to treat allergic reactions such as adrenaline. Ongentys may increase their effect; 
- medicines used to treat heart failure such as dobutamine, dopamine or dopexamine. Ongentys 

may increase their effects; 
- medicines for high cholesterol such as rosuvastatin, simvastatin, atorvastatin or pravastatin 

Ongentys may increase their effects;  
- medicines that affect the immune system such as methotrexate. Ongentys may increase its effect 
- medicines containing quinidine, a medicine used to treat abnormal heart rhythms or malaria. 

Taking Ongentys and quinidine together, i.e. at the same time, may decrease the effect of 
Ongentys. 

 
Pregnancy and breast-feeding 
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine. 
 
It is not known if Ongentys passes into breast milk in humans. Since the risk to the baby/infant cannot 
be excluded, you should stop breast-feeding during treatment with Ongentys.  
 
Driving and using machines 
Ongentys taken with levodopa may make you feel light-headed, dizzy, or sleepy. 
Do not drive or operate machinery if you experience any of these side effects. 
 
Ongentys contains lactose 
If you have been told by your doctor that you have intolerance to some sugars, contact your doctor 
before taking this medicine. 
 



47 

 
3. How to take Ongentys 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
The recommended dose is 50 mg once daily. 
 
Ongentys should be taken preferably at bedtime. 
 
Take Ongentys at least one hour before or after taking your levodopa medicine. 
 
Ongentys is for oral use. 
Swallow the capsule whole with a glass of water.  
 
Doses of other medicines to treat Parkinson’s disease 
The dose of other medicines to treat Parkinson’s disease may need to be adjusted when you start 
taking Ongentys. Follow the instructions that your doctor has given you. 
 
If you take more Ongentys than you should 
If you take more Ongentys than you should, tell your doctor or pharmacist, or go to a hospital 
immediately. Take the medicine package and this leaflet with you. This will help the doctor identify 
what you have taken. 
 
If you forget to take Ongentys 
If you forget to take one dose, you should continue the treatment and take the next dose as scheduled.  
Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking Ongentys 
Do not stop taking Ongentys unless your doctor tells you to as your symptoms may get worse. 
If you stop taking Ongentys your doctor may need to adjust the dose of other medicines that you are 
taking to treat Parkinson’s disease. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Side effects caused by Ongentys are usually mild to moderate and occur mostly within the first weeks 
of treatment. Some side effects may be caused by the increased effects of using Ongentys together 
with levodopa. 
 
Contact your doctor straight away if you experience any side effects at the start of treatment. Many of 
the side effects can be managed by your doctor adjusting your levodopa medicine. 
 
Tell your doctor as soon as possible if you notice any of the following side effects: 
 
Very common: may affect more than 1 in 10 people 
- involuntary and uncontrollable, or difficult or painful body movements 
 
Common: may affect up to 1 in 10 people 
- constipation 
- dry mouth 
- vomiting (being sick) 
- increased levels of the enzyme (creatine kinase) in your blood 



48 

- muscle spasm 
- dizziness 
- headache 
- sleepiness 
- difficulty falling or staying asleep  
- strange dreams  
- experiencing or seeing things which do not exist (hallucinations) 
- a fall in blood pressure on standing up which causes dizziness, light-headedness or fainting 
 
Uncommon: may affect up to 1 in 100 people 
- palpitations or irregular heartbeat 
- blocked ear 
- dry eye 
- pain or swelling of the abdomen 
- indigestion 
- weight loss 
- loss of appetite 
- increased levels of triglycerides (fats) in your blood 
- muscle twitching, stiffness or pain 
- pain in arms or legs 
- altered sense of taste 
- excessive body movements  
- fainting 
- anxiety 
- depression 
- hearing things which do not exist 
- nightmares 
- sleep disorder 
- abnormal colour of urine 
- need to wake and pass urine at night 
- shortness of breath 
- high or low blood pressure 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Ongentys 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the bottle/blister/carton after EXP. 
The expiry date refers to the last day of that month. 
 
This medicine does not require any special temperature storage conditions. 
Blisters: Store in the original blister in order to protect from moisture. 
Bottles: Keep the bottle tightly closed in order to protect from moisture. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


49 

What Ongentys contains  
- The active substance is opicapone. Each hard capsule contains 50 mg of opicapone. 
- The other ingredients are:  

o capsule content: lactose monohydrate, sodium starch glycolate (Type A), pregelatinized 
maize starch and magnesium stearate 

o capsule shell: gelatine, indigo carmine aluminium lake (E132), erythrosine (E127) and 
titanium dioxide (E171) 

o printing ink: shellac, titanium dioxide (E171), propylene glycol, ammonia, simethicone 
 
What Ongentys looks like and contents of the pack 
Ongentys 50 mg hard capsules are dark blue, approximately 19 mm length, with “OPC 50” and “Bial” 
printed on the capsules.  
 
The capsules are packaged in bottles or blisters. 
 
Bottles: 10, 30 or 90 capsules. 
Blisters: 10, 30 or 90 capsules. 
 
Not all packs may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Bial - Portela & Cª., S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal  
tel: +351 22 986 61 00 
fax: +351 22 986 61 90 
e-mail: info@bial.com 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien/България/Česká republika/ 
Deutschland/Eesti/Ελλάδα/France/ 
Hrvatska/Ireland/ Italia/Κύπρος/Latvija/ 
Lietuva/Luxembourg/Luxemburg/Magyarország/ 
Malta/Nederland/ Österreich/Polska/Portugal/ 
România/Slovenija/Slovenská republika/ United 
Kingdom 
BIAL - Portela & Cª, S.A. 
Tél/Tel/Teл./Tlf/Τηλ: + 351 22 986 61 00 
 

España 
Laboratorios BIAL, S.A. 
Tel: + 34 91 562 41 96 
 
Danmark 
Nordicinfu Care AB 
Tlf: +45 (0) 70 28 10 24 
 
Suomi/Finland 
Nordicinfu Care AB 
Puh/Tel: +358 (0) 207 348 760 
 
Ísland / Sverige  
Nordicinfu Care AB 
Tel / Sími: +46 (0) 8 601 24 40 
 
Norge 
Nordicinfu Care AB 
Tlf: +47 (0) 22 20 60 00 
 

 
This leaflet was last revised in {MM/YYYY}. 
 
 



50 

Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.   
 
 
 
 
 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING        AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET