Entacapone Teva

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Entacapone Teva 200 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 200 mg entacapone. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Light brown, biconvex, ellipse-shaped film-coated tablets with approximately 18 mm length and 
10 mm width, embossed ‘E200’ on one side, plain on the other 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. 
 
Patients with renal impairment  

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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). 
 
Patients with hepatic impairment  
See section 4.3. 
 
Elderly patients  
No dosage adjustment of entacapone is required for elderly patients. 
 
Paediatric population  
The safety and efficacy of Entacapone Teva 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 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 ischemic heart disease. 
 
Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal 
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-

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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, adverse dopaminergic reactions, 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 Teva 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. 
 
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-
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). 
 

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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 Teva in association with levodopa may have 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 the 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 
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%). 
 

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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:  Ischemic 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 discolorations 
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). 

** The incidence rates of myocardial infarction and other ischemic heart disease events (0.43% 
and 1.54%, respectively) are derived from an analysis of 13 double-blind studies involving 
2082 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. 
 

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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 Teva 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) 
 
Study I: Daily On time (h) 
 Entacapone (n=85) Placebo (n=86) Difference 
    
Baseline 9.3±2.2 9.2±2.5  

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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 
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. 

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Characteristics in patients 
 
The pharmacokinetic properties of entacapone are similar in both young and elderly adults. 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 
 
Cellulose, microcrystalline 
Povidone 
Starch, pregelatinised 
Magnesium stearate 
 
Film-coating 
 
Poly(vinyl alcohol) 
Talc 
Titanium dioxide (E171) 
Macrogol 
Iron oxide yellow (E172) 
Lecithin (soya) 
Iron oxide red (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
28 months. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
HDPE tablet containers with polypropylene screw caps with desiccant insert containing 30, 60, 100 or 
175 film-coated tablets. 

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Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements for disposal. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/665/001 - 30 tablets 
EU/1/10/665/002 - 60 tablets 
EU/1/10/665/003 - 100 tablets 
EU/1/10/665/004 - 175 tablets 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 18/02/2011 
 
Date of latest renewal: 19/11/2015 
 
 
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 
 

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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 

 11 



A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
TEVA Pharmaceutical Works Private Limited Company 
Pallagi út 13, 4042 Debrecen 
Hungary 
 
TEVA UK Ltd 
Brampton Road, Hampden Park, Eastbourne, East Sussex, 
BN22 9AG 
United Kingdom 
 
Pharmachemie B.V. 
Swensweg 5, 2031 GA Haarlem 
The Netherlands 
 
Teva Czech Industries s.r.o. 
Ostravska 29, c.p. 305, 74770 Opava-Komarov 
Czech Republic 
 
Teva Operations Poland Sp.z.o.o. 
ul. Mogilska 80, 31-546, Krakow 
Poland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
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.

 12 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

 13 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 

 14 



 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (30, 60, 100 or 175 film-coated tablets) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Entacapone Teva 200 mg film-coated tablets 
entacapone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 200 mg of entacapone 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
60 film-coated tablets 
100 film-coated tablets 
175 film-coated 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 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 

 15 



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 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/665/001 - 30 tablets 
EU/1/10/665/002 - 60 tablets 
EU/1/10/665/003 - 100 tablets 
EU/1/10/665/004 - 175 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Entacapone Teva 200 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 

 16 



MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL (30 film-coated tablets) 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE (S) OF ADMINISTRATION 
 
Entacapone Teva 200 mg film-coated tablets 
entacapone 
oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 film-coated tablets 
 
 
6. OTHER 
 

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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
LABEL (60, 100 or 175 film-coated tablets) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Entacapone Teva 200 mg film-coated tablets 
entacapone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 200 mg of entacapone 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets 
100 film-coated tablets 
175 film-coated 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 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 18 



 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/665/002 - 60 tablets 
EU/1/10/665/003 - 100 tablets 
EU/1/10/665/004 - 175 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 

 19 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

 20 



Package leaflet: information for the user 
 

Entacapone Teva 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 Teva is and what it is used for 
2. What you need to know before you take Entacapone Teva  
3. How to take Entacapone Teva 
4. Possible side effects 
5. How to store Entacapone Teva  
6. Contents of the pack and other information 
 
 
1. What Entacapone Teva is and what it is used for  
 
Entacapone Teva tablets contain entacapone and are used together with levodopa to treat Parkinson’s 
disease. Entacapone Teva aids levodopa in relieving the symptoms of Parkinson's disease. Entacapone 
Teva 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 Teva 
 
Do NOT take Entacapone Teva 
• if you are allergic to entacapone 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 Teva);  
• 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 Teva: 
• 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; 
• if you experience diarrhoea, monitoring of your weight is recommended in order to avoid 

potentially excessive weight loss;  

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• 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 Teva 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 Teva. 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 Teva 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 Teva and 
other medicines to treat Parkinson’s disease. 
 
Entacapone Teva 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 Teva 
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 Teva may make it harder for you to digest iron. Therefore, do 

not take Entacapone Teva 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 Teva 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 Teva 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 Teva taken with levodopa may make you feel very drowsy, or cause you to 
sometimes find yourself suddenly fall asleep. 
Do not drive or operate machinery if you experience these side effects. 
 
3. How to take Entacapone Teva 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  

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Entacapone Teva 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 Teva 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 Teva. 
 
If you are receiving dialysis for renal insufficiency, your doctor may tell you to increase the time 
between doses.  
 
Use in children and adolescents 
Experience with Entacapone Teva in patients under 18 years is limited. Therefore, the use of 
Entacapone Teva in children cannot be recommended. 
 
If you take more Entacapone Teva than you should  
In the event of an overdose, consult your doctor, pharmacist or the nearest hospital immediately.  
 
If you forget to take Entacapone Teva  
If you forget to take the Entacapone Teva tablet with your levodopa dose, you should continue the 
treatment by taking the next Entacapone Teva tablet with your next levodopa dose.  
 
Do not take a double dose to make up for a forgotten tablet. 
 
If you stop taking Entacapone Teva 
Do not stop taking Entacapone Teva 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 Teva 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 Teva 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 Teva you should contact your doctor who may decide to adjust your dosage of 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 discoloration 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). 

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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 Teva 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 Teva 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; 
- 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 Teva 
 
Keep this medicine out of the sight and reach of children. 

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Do not use this medicine after the expiry date which is stated on the carton and tablet container label 
after EXP. 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 Teva contains 
• The active substance is entacapone. Each film-coated tablet contains 200 mg of entacapone. 
• The other ingredients in the tablet core are cellulose microcrystalline, povidone, starch 

pregelatinised, magnesium stearate and in the film-coating are poly(vinyl alcohol), talc, titanium 
dioxide (E171), macrogol, iron oxide yellow (E172), lecithin (soya), iron oxide red (E172). 

 
What Entacapone Teva looks like and contents of the pack  
Entacapone Teva film-coated tablets are light brown, biconvex ellipse-shaped with approximately 
18 mm length and 10 mm width, embossed with “E200” on one side and plain on the other side.  
 
Entacapone Teva is available in HDPE tablet containers with polypropylene screw caps with 
desiccant insert containing 30, 60, 100 or 175 film-coated tablets. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
  
Manufacturer 
TEVA Pharmaceutical Works Private Limited Company 
Pallagi út 13, 
4042 Debrecen, 
Hungary 
 
TEVA UK Ltd 
Brampton Road, 
Hampden Park, 
Eastbourne, 
East Sussex, 
BN22 9AG, 
United Kingdom 
 
Pharmachemie B.V.  
Swensweg 5, 
2031 GA Haarlem,  
The Netherlands  
 
Teva Czech Industries s.r.o.  
Ostravska 29, c.p. 305, 
74770 Opava-Komarov, 
Czech Republic 
 

 25 



Teva Operations Poland Sp.z.o.o 
ul. Mogilska 80, 
31-546, Krakow, 
Poland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73  

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 
 

България  
Тева Фармасютикълс България ЕООД 
Teл: +359 2 489 95 82  

Luxembourg/Luxemburg  
ratiopharm GmbH  
Allemagne/Deutschland 
Tél/Tel: +49 731 402 02  
 

Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  

Magyarország  
Teva Gyógyszergyár Zrt  
Tel.: +36 1 288 64 00 
 

Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  

Malta  
Teva Pharmaceuticals Ireland 
L-Irlanda 
Tel: +353 51 321740  
 

Deutschland 
Teva GmbH 
Tel: +49 731 402 08 

Nederland  
Teva Nederland B.V. 
Tel: +31 (0) 800 0228400 
 

Eesti 
Teva Eesti esindus UAB Sicor Biotech 
Eesti filiaal 
Tel: +372 661 0801 

Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 
 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

Österreich 
ratiopharm Arzneimittel Vertriebs-
GmbHTel: +43/1/97007-0 
 

España 
Teva Pharma, S.L.U. 
Tél: +(34) 91 387 32 80   

Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +(48) 22 345 93 00 
 

France 
Teva Santé 
Tél: +(33) 1 55 91 7800 

Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: (351) 21 476 75 50 
 

Hrvatska 
Pliva Hrvatska d.o.o. 
Tel: +385 1 37 20 000 
 

România 
Teva Pharmaceuticals S.R.L 
Tel: +4021 230 65 24 
 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 (0)51 321 740 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 
 

 26 



Ísland 
ratiopharm Oy 
Finnland 
Puh/Tel:+358 20 180 5900 

Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +(421) 2 5726 7911 
 
 

Italia 
Teva Italia S.r.l. 
Tel: +(39) 028917981 
 

Suomi/Finland 
ratiopharm OyPuh/Tel: +358 20 180 5900 
 

Κύπρος 
Teva Ελλάς Α.Ε. 
Ελλάδα 
Τηλ: +30 210 72 79 099 

Sverige 
Teva Sweden AB 
Tel: +(46) 42 12 11 00 
 
 

Latvija 
Sicor Biotech filiāle Latvijā 
Tel: + 37167323666 
 

United Kingdom 
Teva UK Limited 
Tel: +(44) 1977 628 500 

 
 
This leaflet was last revised in MM/YYYY. 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu  
 
 
 
 

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	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