Entacapone Orion

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Entacapone Orion 200 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 200 mg entacapone.

Excipient with known effect
Each film-coated tablet contains 0.53 mg soya lecithin.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet)

Brownish-orange, oval, biconvex film-coated tablet with "COMT" engraved on one side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Entacapone is indicated as an adjunct to standard preparations of levodopa/benserazide or 
levodopa/carbidopa for use 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

Entacapone should only be used in combination with levodopa/benserazide or levodopa/carbidopa.
The prescribing information for these levodopa preparations is applicable to their concomitant use 
with entacapone.

Posology

One 200 mg tablet is taken with each levodopa/dopa decarboxylase inhibitor dose. The maximum 
recommended dose is 200 mg ten times daily, i.e. 2,000 mg of entacapone.

Entacapone enhances the effects of levodopa. Hence, to reduce levodopa-related dopaminergic 
adverse reactions, e.g. dyskinesias, nausea, vomiting and hallucinations, it is often necessary to 
adjust levodopa dosage within the first days to first weeks after initiating entacapone treatment. The 
daily dose of levodopa should be reduced by about 10-30% by extending the dosing intervals and/or 
by reducing the amount of levodopa per dose, according to the clinical condition of the patient.

If entacapone treatment is discontinued, it is necessary to adjust the dosing of other antiparkinsonian 
treatments, especially levodopa, to achieve a sufficient level of control of the parkinsonian 
symptoms.

Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide 
preparations slightly (5-10%) more than from standard levodopa/carbidopa preparations. Hence, 
patients who are taking standard levodopa/benserazide preparations may need a larger reduction of 
levodopa dose when entacapone is initiated.



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Renal impairment
Renal insufficiency does not affect the pharmacokinetics of entacapone and there is no need for dose 
adjustment. However, for patients who are receiving dialysis therapy, a longer dosing interval may 
be considered (see section 5.2).

Hepatic impairment
See section 4.3.

Elderly
No dosage adjustment of entacapone is required for elderly.

Paediatric population
The safety and efficacy of Entacapone Orion in children below age 18 have not been established. No 
data are available.

Method of administration

Entacapone is administered orally and simultaneously with each levodopa/carbidopa or 
levodopa/benserazide dose.

Entacapone can be taken with or without food (see section 5.2).

4.3 Contraindications

- Hypersensitivity to the active substance or to peanut or soya or to any of the excipients listed 
in section 6.1.

- Hepatic impairment.
- Phaeochromocytoma.
- Concomitant use of entacapone and non-selective monoamine oxidase (MAO-A and MAO-B) 

inhibitors (e.g. phenelzine, tranylcypromine).
- Concomitant use of a selective MAO-A inhibitor plus a selective MAO-B inhibitor and 

entacapone (see section 4.5).
- A previous history of neuroleptic malignant syndrome (NMS) and/or non-traumatic 

rhabdomyolysis.

4.4 Special warnings and precautions for use

Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been 
observed rarely in patients with Parkinson’s disease.

NMS, including rhabdomyolysis and hyperthermia, is characterised by motor symptoms (rigidity, 
myoclonus, tremor), mental status changes (e.g. agitation, confusion, coma), hyperthermia, autonomic 
dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase. In 
individual cases, only some of these symptoms and/or findings may be evident.

Neither NMS nor rhabdomyolysis have been reported in association with entacapone treatment from 
controlled trials in which entacapone was discontinued abruptly. Since the introduction into the 
market, isolated cases of NMS have been reported, especially following abrupt reduction or
discontinuation of entacapone and other concomitant dopaminergic medicinal products. When 
considered necessary, withdrawal of entacapone and other dopaminergic treatment should proceed 
slowly, and if signs and/or symptoms occur despite a slow withdrawal of entacapone, an increase in 
levodopa dosage may be necessary.

Entacapone therapy should be administered cautiously to patients with ischaemic heart disease.

Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal 



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products containing a catechol group and potentiate their action. Thus, entacapone should be 
administered cautiously to patients being treated with medicinal products metabolised by catechol-O-
methyl transferase (COMT), e.g. rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, 
dobutamine, alpha-methyldopa, and apomorphine (see also section 4.5).

Entacapone is always given as an adjunct to levodopa treatment. Hence, the precautions valid for 
levodopa treatment should also be taken into account for entacapone treatment. Entacapone increases 
the bioavailability of levodopa from standard levodopa/benserazide preparations 5-10% more than 
from standard levodopa/carbidopa preparations. Consequently, adverse dopaminergic reactions may 
be more frequent when entacapone is added to levodopa/benserazide treatment (see also section 4.8). 
To reduce levodopa-related dopaminergic adverse reactions, it is often necessary to adjust levodopa 
dosage within the first days to first weeks after initiating entacapone treatment, according to the 
clinical condition of the patient (see sections 4.2 and 4.8).

Entacapone may aggravate levodopa-induced orthostatic hypotension. Entacapone should be given 
cautiously to patients who are taking other medicinal products which may cause orthostatic 
hypotension.

In clinical studies, undesirable dopaminergic effects, e.g. dyskinesia, were more common in patients 
who received entacapone and dopamine agonists (such as bromocriptine), selegiline or amantadine 
compared to those who received placebo with this combination. The doses of other antiparkinsonian 
medicinal products may need to be adjusted when entacapone treatment is initiated.

Entacapone in association with levodopa has been associated with somnolence and episodes of 
sudden sleep onset in patients with Parkinson’s disease and caution should therefore be exercised 
when driving or operating machines (see also section 4.7).

For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid 
potential excessive weight decrease. Prolonged or persistent diarrhoea appearing during use of
entacapone may be a sign of colitis. In the event of prolonged or persistent diarrhoea, the medicinal 
product should be discontinued and appropriate medical therapy and investigations considered.

Patients should be regularly monitored for the development of impulse control disorders. Patients 
and carers should be made aware that behavioural symptoms of impulse control disorders including 
pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge 
eating and compulsive eating can occur in patients treated with dopamine agonists and/or other 
dopaminergic treatments such as Entacapone Orion in association with levodopa. Review of 
treatment is recommended if such symptoms develop.

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.

Entacapone Orion contains soya lecithin. Patients who are hypersensitive to peanut or soya, should 
not use this medicinal product.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction of entacapone with carbidopa has been observed with the recommended treatment 
schedule. Pharmacokinetic interaction with benserazide has not been studied.

In single-dose studies in healthy volunteers, no interactions were observed between entacapone and 
imipramine or between entacapone and moclobemide. Similarly, no interactions between entacapone
and selegiline were observed in repeated-dose studies in parkinsonian patients. However, the 
experience of the clinical use of entacapone with several medicinal products, including MAO-A 
inhibitors, tricyclic antidepressants, noradrenaline reuptake inhibitors such as desipramine, 
maprotiline and venlafaxine, and medicinal products that are metabolised by COMT (e.g. catechol-



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structured compounds: rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, 
alpha-methyldopa, apomorphine, and paroxetine) is still limited. Caution should be exercised when 
these medicinal products are used concomitantly with entacapone (see also sections 4.3 and 4.4).

Entacapone may be used with selegiline (a selective MAO-B inhibitor), but the daily dose of 
selegiline should not exceed 10 mg.

Entacapone may form chelates with iron in the gastrointestinal tract. Entacapone and iron 
preparations should be taken at least 2-3 hours apart (see section 4.8).

Entacapone binds to human albumin binding site II which also binds several other medicinal 
products, including diazepam and ibuprofen. Clinical interaction studies with diazepam and non-
steroidal anti-inflammatory medicinal products have not been carried out. According to in vitro
studies, significant displacement is not anticipated at therapeutic concentrations of the medicinal 
products.

Due to its affinity to cytochrome P450 2C9 in vitro (see section 5.2), entacapone may potentially 
interfere with medicinal products with metabolism dependent on this isoenzyme, such as S-warfarin.
However, in an interaction study with healthy volunteers, entacapone did not change the plasma levels 
of S-warfarin, while the AUC for R-warfarin increased on average by 18% [CI90 11–26%]. The INR 
values increased on average by 13% [CI90 6–19%]. Thus, control of INR is recommended when 
entacapone treatment is initiated for patients receiving warfarin.

4.6 Fertility, pregnancy and lactation

Pregnancy
No overt teratogenic or primary foetotoxic effects were observed in animal studies in which the 
exposure levels of entacapone were markedly higher than the therapeutic exposure levels. As there is 
no experience in pregnant women, entacapone should not be used during pregnancy.

Breast-feeding
In animal studies entacapone was excreted in milk. The safety of entacapone in infants is unknown. 
Women should not breast-feed during treatment with entacapone.

4.7 Effects on ability to drive and use machines

Entacapone Orion in association with levodopa may have a major influence on the ability to drive 
and use machines. Entacapone may, together with levodopa, cause dizziness and symptomatic 
orthostatism. Therefore, caution should be exercised when driving or using machines.

Patients being treated with entacapone in association with levodopa and presenting with somnolence 
and/or sudden sleep onset episodes must be instructed to refrain from driving or engaging in 
activities where impaired alertness may put themselves or others at risk of serious injury or death 
(e.g. operating machines) until such recurrent episodes have resolved (see also section 4.4).

4.8 Undesirable effects

Summary of the safety profile
The most frequent adverse reactions caused by entacapone relate to the increased dopaminergic 
activity and occur most commonly at the beginning of treatment. Reduction of levodopa dosage 
decreases the severity and frequency of these reactions. The other major class of adverse reactions 
are gastrointestinal symptoms, including nausea, vomiting, abdominal pain, constipation and 
diarrhoea. Urine may be discoloured reddish-brown by entacapone, but this is a harmless 
phenomenon.

Usually the adverse reactions caused by entacapone are mild to moderate. In clinical studies the most 



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common adverse reactions leading to discontinuation of entacapone treatment have been 
gastrointestinal symptoms (e.g. diarrhoea, 2.5%) and increased dopaminergic adverse reactions of 
levodopa (e.g. dyskinesias, 1.7%).

Dyskinesias (27%), nausea (11%), diarrhoea (8%), abdominal pain (7%) and dry mouth (4.2%) were 
reported significantly more often with entacapone than with placebo in pooled data from clinical 
studies involving 406 patients taking the medicinal product and 296 patients taking placebo.

Some of the adverse reactions, such as dyskinesia, nausea, and abdominal pain, may be more 
common with the higher doses (1,400 to 2,000 mg per day) than with the lower doses of entacapone.

Tabulated list of adverse reactions
The following adverse reactions, listed below in Table 1, have been accumulated both from clinical 
studies with entacapone and since the introduction of entacapone into the market.

Table 1. Adverse drug reactions*

Psychiatric disorders

Common: Insomnia, hallucinations, confusion, paroniria

Very rare: Agitation

Nervous system disorders

Very common: Dyskinesia

Common: Parkinsonism aggravated, dizziness, dystonia, hyperkinesia

Cardiac disorders**

Common: Ischaemic heart disease events other than myocardial
infarction (e.g. angina pectoris)

Uncommon: Myocardial infarction

Gastrointestinal disorders

Very common: Nausea

Common: Diarrhoea, abdominal pain, dry mouth, constipation, vomiting

Very rare: Anorexia

Not known: Colitis

Hepatobiliary disorders

Rare: Hepatic function tests abnormal

Not known: Hepatitis with mainly cholestatic features (see section 4.4.)

Skin and subcutaneous tissue disorders

Rare: Erythematous or maculopapular rash

Very rare: Urticaria 

Not known: Skin, hair, beard and nail discolourations

Renal and urinary disorders

Very common: Urine discoloration

General disorders and administration site conditions

Common: Fatigue, sweating increased, fall

Very rare: Weight decrease

* Adverse reactions are ranked under headings of frequency, the most frequent first, using the 
following convention: 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, since no valid estimate can be derived from clinical trials 
or epidemiological studies).



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** The incidence rates of myocardial infarction and other ischaemic heart disease events (0.43% 
and 1.54%, respectively) are derived from an analysis of 13 double-blind studies involving 
2,082 patients with end-of-dose motor fluctuations receiving entacapone.

Description of selected adverse reactions
Entacapone in association with levodopa has been associated with isolated cases of excessive 
daytime somnolence and sudden sleep onset episodes.

Impulse control disorders: Pathological gambling, increased libido, hypersexuality, compulsive 
spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine 
agonists and/or other dopaminergic treatments such as Entacapone Orion in association with 
levodopa (see section 4.4).

Isolated cases of NMS have been reported following abrupt reduction or discontinuation of 
entacapone and other dopaminergic treatments.

Isolated cases of rhabdomyolysis have been reported.

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

The post-marketing data include isolated cases of overdose in which the reported highest daily dose of 
entacapone has been 16,000 mg. The acute symptoms and signs in these cases of overdose included 
confusion, decreased activity, somnolence, hypotonia, skin discolouration and urticaria. Management 
of acute overdose is symptomatic.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: other dopaminergic agents, ATC code: N04BX02.

Entacapone belongs to a new therapeutic class, catechol-O-methyl transferase (COMT) inhibitors. It 
is a reversible, specific, and mainly peripherally acting COMT inhibitor designed for concomitant 
administration with levodopa preparations. Entacapone decreases the metabolic loss of levodopa to 
3-O-methyldopa (3-OMD) by inhibiting the COMT enzyme. This leads to a higher levodopa AUC. 
The amount of levodopa available to the brain is increased. Entacapone thus prolongs the clinical 
response to levodopa.

Entacapone inhibits the COMT enzyme mainly in peripheral tissues. COMT inhibition in red blood 
cells closely follows the plasma concentrations of entacapone, thus clearly indicating the reversible 
nature of COMT inhibition.

Clinical studies
In two phase III double-blind studies in a total of 376 patients with Parkinson’s disease and end-of-
dose motor fluctuations, entacapone or placebo was given with each levodopa/dopa decarboxylase 
inhibitor dose. The results are given in Table 2. In study I, daily ON time (hours) was measured from 
home diaries and in study II, the proportion of daily ON time.

Table 2. Daily ON time (Mean ±SD)

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


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Study I: Daily On time (h)
Entacapone (n=85) Placebo (n=86) Difference

Baseline 9.3±2.2 9.2±2.5

Week 8-24 10.7±2.2 9.4±2.6 1 h 20 min
(8.3%)
CI95% 45 min, 1 h 56 min

Study II: Proportion of daily On time (%)
Entacapone (n=103) Placebo (n=102) Difference

Baseline 60.0±15.2 60.8±14.0

Week 8-24 66.8±14.5 62.8±16.80 4.5% (0 h 35 min)
CI95% 0.93%, 7.97%

There were corresponding decreases in OFF time.

The % change from baseline in OFF time was –24% in the entacapone group and 0% in the placebo 
group in study I. The corresponding figures in study II were –18% and –5%.

5.2 Pharmacokinetic properties

General characteristics of the active substance

Absorption
There are large intra- and interindividual variations in the absorption of entacapone.

The peak concentration (Cmax) in plasma is usually reached about one hour after ingestion of a 
200 mg entacapone tablet. The substance is subject to extensive first-pass metabolism. The 
bioavailability of entacapone is about 35% after an oral dose. Food does not affect the absorption of 
entacapone to any significant extent.

Distribution
After absorption from the gastrointestinal tract, entacapone is rapidly distributed to the peripheral 
tissues with a distribution volume of 20 litres at steady state (Vdss). Approximately 92 % of the dose 
is eliminated during ß-phase with a short elimination half-life of 30 minutes. The total clearance of 
entacapone is about 800 ml/min.

Entacapone is extensively bound to plasma proteins, mainly to albumin. In human plasma the 
unbound fraction is about 2.0% in the therapeutic concentration range. At therapeutic concentrations, 
entacapone does not displace other extensively bound substances (e.g. warfarin, salicylic acid, 
phenylbutazone, or diazepam), nor is it displaced to any significant extent by any of these substances
at therapeutic or higher concentrations.

Biotransformation
A small amount of entacapone, the (E)-isomer, is converted to its (Z)-isomer. The (E)-isomer 
accounts for 95% of the AUC of entacapone. The (Z)-isomer and traces of other metabolites account 
for the remaining 5%.

Data from in vitro studies using human liver microsomal preparations indicate that entacapone 
inhibits cytochrome P450 2C9 (IC50 4 µM). Entacapone showed little or no inhibition of other types 
of P450 isoenzymes (CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A and CYP2C19) (see section 
4.5).

Elimination
The elimination of entacapone occurs mainly by non-renal metabolic routes. It is estimated that 80-
90% of the dose is excreted in faeces, although this has not been confirmed in man. Approximately 



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10-20% is excreted in urine. Only traces of entacapone are found unchanged in urine. The major part 
(95%) of the product excreted in urine is conjugated with glucuronic acid. Of the metabolites found 
in urine only about 1% have been formed through oxidation.

Characteristics in patients

The pharmacokinetic properties of entacapone are similar in both young people and elderly. The 
metabolism of the medicinal product is slowed in patients with mild to moderate liver insufficiency 
(Child-Pugh Class A and B), which leads to an increased plasma concentration of entacapone in both 
the absorption and elimination phases (see section 4.3). Renal impairment does not affect the 
pharmacokinetics of entacapone. However, a longer dosing interval may be considered for patients 
who are receiving dialysis therapy.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential. In repeated dose 
toxicity studies, anaemia most likely due to iron chelating properties of entacapone was observed. 
Regarding reproduction toxicity, decreased foetal weight and a slightly delayed bone development 
were noticed in rabbits at systemic exposure levels in the therapeutic range.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:
Microcrystalline cellulose
Croscarmellose sodium
Povidone
Magnesium stearate

Film-coating:
Polyvinyl alcohol, partly hydrolysed
Talc
Macrogol
Soya lecithin
Yellow iron oxide (E 172)
Red iron oxide (E 172)
Titanium dioxide (E 171)

6.2 Incompatibilities

Not applicable.

6.3 Shelf- life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

White high-density polyethylene (HDPE) bottles with white tamper proof polypropylene (PP) 



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closures containing 30, 60, 100 or 175 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements for disposal.

7. MARKETING AUTHORISATION HOLDER

Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/708/001-004

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 18 August 2011
Date of latest renewal: 8 April 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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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



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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland

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.

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

 Risk Management Plan (RMP)

Not applicable.



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ANNEX III

LABELLING AND PACKAGE LEAFLET



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A. LABELLING



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING

CARTON AND BOTTLE LABEL

1. NAME OF THE MEDICINAL PRODUCT

Entacapone Orion 200 mg film-coated tablets
entacapone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 200 mg of entacapone,

3. LIST OF EXCIPIENTS

soya lecithin.

4. PHARMACEUTICAL FORM AND CONTENTS

Carton

30 film-coated tablets
60 film-coated tablets
100 film-coated tablets
175 film-coated tablets

Bottle label

30 tablets
60 tablets
100 tablets
175 tablets

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



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EXP

9. SPECIAL STORAGE CONDITIONS

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

Carton

Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland

Bottle label

Orion Corporation

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/708/001 30 film-coated tablets
EU/1/11/708/002 60 film-coated tablets
EU/1/11/708/003 100 film-coated tablets
EU/1/11/708/004 175 film-coated tablets

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

entacapone orion 200 mg [carton only]

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included [carton only]



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18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

[carton only]:

PC: {number}
SN: {number}
< NN: {number} >



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B. PACKAGE LEAFLET



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Package leaflet: Information for the user

Entacapone Orion 200 mg film-coated tablets
Entacapone

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 Entacapone Orion is and what it is used for
2. What you need to know before you take Entacapone Orion
3. How to take Entacapone Orion
4. Possible side effects
5. How to store Entacapone Orion
6. Contents of the pack and other information

1. What Entacapone Orion is and what it is used for

Entacapone Orion tablets contain entacapone and are used together with levodopa to treat 
Parkinson’s disease. Entacapone Orion aids levodopa in relieving the symptoms of Parkinson's 
disease. Entacapone Orion has no effect on relieving the symptoms of Parkinson’s disease unless 
taken with levodopa.

2. What you need to know before you take Entacapone Orion

Do not take Entacapone Orion
 if you are allergic to entacapone or to peanut or soya or any of the other ingredients of this 

medicine (listed in section 6);
 if you have a tumour of the adrenal gland (known as pheochromocytoma; this may increase the 

risk of severe high blood pressure);
 if you are taking certain antidepressants (ask your doctor or pharmacist whether your 

antidepressive medicine can be taken together with Entacapone Orion);
 if you have liver disease;
 if you have ever suffered from a rare reaction to antipsychotic medicines called neuroleptic 

malignant syndrome (NMS). See section 4 Possible side effects for the characteristics of 
NMS;

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Entacapone Orion:
 if you have ever had a heart attack or any other diseases of the heart;
 if you are taking a medicine which may cause dizziness or light-headedness (low blood 

pressure) when rising from a chair or bed;
 if you experience prolonged diarrhoea consult your doctor as it may be a sign of inflammation 

of the colon;



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 if you experience diarrhoea, monitoring of your weight is recommended in order to avoid 
potentially excessive weight loss;

 if you experience increasing loss of appetite, weakness, exhaustion and weight loss within a 
relatively short period of time, a general medical evaluation including liver function should be 
considered.

Tell your doctor 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 yourself or others. These behaviours are called impulse control disorders 
and can include addictive gambling, excessive eating or spending, an abnormally high sex drive or a 
preoccupation with an increase in sexual thoughts or feelings. Your doctor may need to review your 
treatments.

As Entacapone Orion tablets will be taken together with other levodopa medicines, please also read 
the package leaflets of these medicines carefully.

The dose of other medicines to treat Parkinson’s disease may need to be adjusted when you start 
taking Entacapone Orion. Follow the instructions that your doctor has given you.

Neuroleptic Malignant Syndrome (NMS) is a serious but rare reaction to certain medicines, and may 
occur especially when Entacapone Orion and other medicines to treat Parkinson’s disease are 
suddenly stopped or the dose is suddenly reduced. For the characteristics of NMS see Section 4 
Possible side effects. Your doctor may advise you to slowly discontinue the treatment with 
Entacapone Orion and other medicines to treat Parkinson’s disease.

Entacapone Orion taken with levodopa may cause drowsiness and may cause you to sometimes 
suddenly fall asleep. If this happens, you should not drive or use any tools or machines (see Driving 
and using machines).

Other medicines and Entacapone Orion
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. In particular please tell your doctor if you are taking any of the following:
 rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, alpha-methyldopa, 

apomorphine;
 antidepressants including desipramine, maprotiline, venlafaxine, paroxetine;
 warfarin used to thin the blood;
 iron supplements. Entacapone Orion may make it harder for you to digest iron. Therefore, do 

not take Entacapone Orion and iron supplements at the same time. After taking one of them, 
wait at least 2 to 3 hours before taking the other.

Pregnancy, breast-feeding and fertility
Do not use Entacapone Orion during pregnancy or if you are breast-feeding.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
Entacapone Orion taken together with levodopa may lower your blood pressure, which may make 
you feel light-headed or dizzy. Be particularly careful when you drive or when you use tools or 
machinery.

In addition, Entacapone Orion taken with levodopa may make you feel very drowsy, or cause you to 
sometimes suddenly fall asleep.
Do not drive or operate machinery if you experience these side effects.

Entacapone Orion contains soya lecithin



21

Entacapone Orion contains soya lecithin. If you are allergic to peanut or soya, do not use this 
medicine.

3. How to take Entacapone Orion

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

Entacapone Orion is taken together with medicines containing levodopa (either levodopa/carbidopa 
preparations or levodopa/benserazide preparations). You may also use other medicines to treat 
Parkinson’s disease at the same time.

The recommended dose of Entacapone Orion is one 200 mg tablet with each levodopa dose. The 
maximum recommended dose is 10 tablets per day, i.e. 2,000 mg of Entacapone Orion.

If you are receiving dialysis for renal insufficiency, your doctor may tell you to increase the time
between doses.

To open the bottle for the first time: open the closure, 
and then press with your thumb on the seal until it 
breaks. See picture 1.

Picture 1

Use in children and adolescents
Experience with Entacapone Orion in patients under 18 years is limited. Therefore, the use of 
Entacapone Orion in children or adolescents cannot be recommended.

If you take more Entacapone Orion than you should
In the event of an overdose, consult your doctor, pharmacist or the nearest hospital immediately.

If you forget to take Entacapone Orion
If you forget to take the Entacapone Orion tablet with your levodopa dose, you should continue the 
treatment by taking the next Entacapone Orion tablet with your next levodopa dose.

Do not take a double dose to make up for a forgotten tablet.

If you stop taking Entacapone Orion
Do not stop taking Entacapone Orion unless your doctor tells you to.

When stopping your doctor may need to re-adjust the dosage of your other medicines to treat 
Parkinson´s disease. Suddenly stopping Entacapone Orion and other medicines to treat Parkinson´s
disease may result in unwanted side effects. See Section 2 Warnings and precautions.

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. Usually 
side effects caused by Entacapone Orion are mild to moderate.

Some of the side effects are often caused by the increased effects of levodopa therapy and are most 
common at the start of treatment. If you experience such effects at the start of treatment with 
Entacapone Orion you should contact your doctor who may decide to adjust your dosage of 



22

levodopa.

Very common (may affect more than 1 in 10 people):
 Uncontrollable movements with difficulty in performing voluntary movements (dyskinesias);
 feeling sick (nausea);
 harmless reddish-brown discolouration of urine.

Common (may affect up to 1 in 10 people):
 Excessive movements (hyperkinesias), worsening of symptoms of Parkinson´s disease, 

prolonged muscle cramps (dystonia);
 being sick (vomiting), diarrhoea, abdominal pain, constipation, dry mouth;
 dizziness, tiredness, increased sweating, fall;
 hallucinations (seeing/hearing/feeling/smelling things that are not really there), sleeplessness,

vivid dreams, and confusion;
 heart or artery disease events (e.g. chest pain).

Uncommon (may affect up to 1 in 100 people):
 Heart attack.

Rare (may affect up to 1 in 1,000 people):
 Rashes;
 abnormal results in liver function test.

Very rare (may affect up to 1 in 10,000 people):
 Agitation;
 decreased appetite, weight loss;
 hives.

Not known (frequency cannot be estimated from the available data):
 Inflammation of the colon (colitis), inflammation of the liver (hepatitis) with yellowing of the 

skin and whites of the eyes;
 discolouration of skin, hair, beard and nails.

When Entacapone Orion is given at higher doses:
In doses of 1,400 to 2,000 mg per day, the following side effects are more common:
 Uncontrollable movements;
 nausea;
 abdominal pain.

Other important side effects which may occur:
 Entacapone Orion taken with levodopa may rarely make you feel very drowsy during the day, 

and cause you to suddenly fall asleep;

 Neuroleptic Malignant Syndrome (NMS) is a rare severe reaction to medicines used to treat 
disorders of the nervous system. It is characterised by stiffness, muscle twitching, shaking, 
agitation and confusion, coma, high body temperature, increased heart rate, and unstable blood 
pressure;

 a rare severe muscle disorder (rhabdomyolysis) which causes pain, tenderness and weakness 
of the muscles and may lead to kidney problems.

You may experience the following side effects: 
 Inability to resist the impulse to perform an action that could be harmful, which may include:

 strong impulse to gamble excessively despite serious personal or family consequences;



23

 altered or increased sexual interest and behaviour of significant concern to you or to others, 
for example, an increased sexual drive;

 uncontrollable excessive shopping or spending;
 binge eating (eating large amounts of food in a short time period) or compulsive eating 

(eating more food than normal and more than is needed to satisfy your hunger).

Tell your doctor if you experience any of these behaviours; they will discuss ways of managing 
or reducing the symptoms.

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 Entacapone Orion

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 carton and on the bottle label. The 
expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater. 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 Entacapone Orion contains
- The active substance is entacapone. Each tablet contains 200 mg of entacapone.
- The other ingredients in the tablet core are microcrystalline cellulose, croscarmellose sodium, 

povidone and magnesium stearate.
- The film-coating contains partly hydrolysed polyvinyl alcohol, talc, macrogol, soya lecithin, 

yellow iron oxide (E 172), red iron oxide (E 172) and titanium dioxide (E 171).

What Entacapone Orion looks like and contents of the pack
Entacapone Orion 200 mg film-coated tablets are brownish-orange, oval tablets with "COMT"
engraved on one side. They are packed in bottles. 

There are four different pack sizes (bottles containing 30, 60, 100 or 175 tablets). Not all pack sizes 
may be marketed.

Marketing Authorisation Holder and Manufacturer:
Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland

For further information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

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


24

Belgique/België/Belgien
Orion Corporation
Tél./Tel: +358 10 4261

Lietuva
UAB Orion Pharma
Tel: +370 5 276 9499

България
Orion Corporation
Тел.: +358 10 4261

Luxembourg/Luxemburg
Orion Corporation
Tél./Tel: +358 10 4261

Česká republika
Orion Corporation
Tel: +358 10 4261

Magyarország
Orion Corporation
Tel.: +358 10 4261

Danmark
Orion Pharma A/S
Tlf: +45 8614 0000

Malta
Orion Corporation
Tel: +358 10 4261

Deutschland
Orion Pharma GmbH
Tel: +49 40 899 689-0

Nederland
Orion Corporation
Tel: +358 10 4261

Eesti
Orion Pharma Eesti OÜ
Tel: +372 66 44 550

Norge
Orion Pharma AS
Tlf.: +47 40 00 42 10

Ελλάδα
ORION PHARMA HELLAS Μ.Ε.Π.Ε
Tηλ: + 30 210 9803355

Österreich
Orion Corporation
Tel: +358 10 4261

España
Orion Corporation
Tel.: +358 10 4261

Polska
Orion Pharma Poland Sp. z o.o.
Tel.: +48 22 8333177

France
Orion Corporation
Tél.: +358 10 4261

Portugal
Orion Corporation
Tel: +358 10 4261

Hrvatska
Orion Corporation
Tel.: +358 10 4261

România
Orion Corporation
Tel: +358 10 4261

Ireland
Orion Pharma (Ireland) Ltd.
c/o Allphar Services Ltd.
Tel: +353 1 428 7777

Slovenija
Orion Corporation
Tel: +358 10 4261

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Orion Corporation
Tel: +358 10 4261

Italia
Orion Corporation
Tel: +358 10 4261

Suomi/Finland
Orion Corporation
Puh./Tel: +358 10 4261



25

Κύπρος
Orion Corporation
Tηλ: +358 10 4261

Sverige
Orion Pharma AB
Tel: +46 8 623 6440

Latvija
JSC Olainfarm
Tel: +371 67013701

United Kingdom
Orion Pharma (UK) Ltd.
Tel: +44 1635 520 300

This leaflet was last revised in

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency website: 
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