ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Entacapone Teva 200 mg film-coated tablets
2.
Each film-coated tablet contains 200 mg entacapone.
For a full list of excipients, see section 6.1.
3.
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.
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.
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.
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).
2
Hepatic impairment
: see section 4.3.
Elderly
: 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).
-
Hypersensitivity to the active substance or to any of the excipients.
-
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.
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-
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
3
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 drug should be discontinued
and appropriate medical therapy and investigations considered.
Pathological gambling, increased libido and hypersexuality have been reported in Parkinson’s disease
patients treated with dopamine agonists and other dopaminergic treatments such as entacapone in
association with levodopa.
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.
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).
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.
4
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 % [CI
90
11–26%]. The INR
values increased on average by 13% [CI
90
6–19%]. Thus, control of INR is recommended when
entacapone treatment is initiated for patients receiving warfarin.
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.
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.
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).
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%).
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.
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
5
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.
Entacapone in association with levodopa has been associated with isolated cases of excessive daytime
somnolence and sudden sleep onset episodes.
Parkinson’s disease patients treated with dopamine agonists and other dopaminergic treatments such
as entacapone in association with levodopa, especially at high doses, have been reported as exhibiting
signs of pathological gambling, increased libido and hypersexuality, which were generally reversible
upon reduction of the dose or treatment discontinuation.
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.
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.
6
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
Week 8-24
10.7±2.2
9.4±2.6
1 h 20 min
(8.3%)
CI
95%
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)
CI
95%
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 (C
max
) 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.
7
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 (Vd
ss
). 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.
Metabolism
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 (IC
50
~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.
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.
6.1 List of excipients
Tablet core:
Cellulose, microcrystalline
Povidone
Starch, pregelatinised
Magnesium stearate
8
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.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7.
Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands
8.
9.
Detailed information on this product is available on the website of the European Medicines Agency
9
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDERS
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
10
A. MANUFACTURING AUTHORISATION HOLDERS 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 Santé
Rue Bellocier, 89100 Sens
France
Teva Czech Industries s.r.o.
Ostravska 29, c.p. 305, 74770 Opava-Komarov
Czech Republic
PLIVA Krakow Zakłady Farmaceutyczne S.A.
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 OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
•
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in Module 1.8.1 of
the Marketing Authorisation Application, is in place and functioning before and whilst the
product is on the market.
PSURs
The PSUR submission schedule should follow the PSUR submission schedule for the reference
medicinal product.
11
ANNEX III
LABELLING AND PACKAGE LEAFLET
12
A. LABELLING
13
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON (30, 60, 100 or 175 film-coated tablets)
1.
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.
30 film-coated tablets
60 film-coated tablets
100 film-coated tablets
175 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight 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
14
Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Entacapone Teva 200 mg
15
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
LABEL (30 film-coated tablets)
1.
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
16
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
LABEL (60, 100 or 175 film-coated tablets)
1.
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.
60 film-coated tablets
100 film-coated tablets
175 film-coated tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight 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
17
Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
18
B. PACKAGE LEAFLET
19
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.
-
Keep this leaflet. You may need to read it again.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet:
1.
What Entacapone Teva is and what it is used for
2.
Before you take Entacapone Teva
4.
Possible side effects
5.
How to store Entacapone Teva
6.
Further 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. BEFORE YOU TAKE ENTACAPONE TEVA
Do NOT take Entacapone Teva
•
if you are allergic (hypersensitive) to entacapone or any of the other ingredients of Entacapone
Teva;
•
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.
Take special care with Entacapone Teva
Talk to your doctor if any of the following applies to you:
•
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;
•
if you experience excessive gambling or excessive sexual activity;
20
-
If you have any further questions, ask your doctor or pharmacist.
3.
How to take Entacapone Teva
•
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.
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).
Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken other medicines,
including medicines obtained without a prescription or herbal 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 and breast-feeding
Do not use Entacapone Teva during pregnancy or if you are breast-feeding. Ask your doctor or
pharmacist for advice before taking any 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 Entacapone Teva exactly as your doctor has told you. You should check with your doctor
or pharmacist if you are not sure.
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 usual 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.
21
If you are receiving dialysis for renal insufficiency, your doctor may tell you to increase the time
between doses.
Use in children
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 Take special care.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4. POSSIBLE SIDE EFFECTS
Like all medicines, Entacapone Teva 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.
The frequencies are defined as:
Very common:
affects more than 1 user in 10
Common:
affects 1 to 10 users in 100
Uncommon:
affects 1 to 10 users in 1,000
Rare:
affects 1 to 10 users in 10,000
Very Rare:
affects less than 1 user in 10,000
Not known:
frequency cannot be estimated from the available data
Very common:
-
Uncontrollable movements with difficulty in performing voluntary movements (dyskinesias);
-
feeling sick (nausea);
-
harmless reddish-brown discoloration of urine.
Common:
-
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;
22
-
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:
-
Heart attack.
Rare:
-
Rashes;
-
abnormal results in liver function test.
Very rare:
-
Agitation;
-
decreased appetite, weight loss;
-
hives.
Not known:
-
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;
-
behavioural changes may occur such as an urge to gamble (pathological gambling) or increased
sexual desire and urges (increased libido and hypersexuality).
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet please
tell your doctor.
5. HOW TO STORE ENTACAPONE TEVA
Keep out of the reach and sight of children.
Do not use Entacapone Teva after the expiry date which is stated on the carton and tablet container
label. The expiry date refers to the last day of that month.
This medicinal product does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
23
6. FURTHER 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 and Manufacturer
Marketing Authorisation Holder:
Teva Pharma B.V.
Computerweg 10,
3542 DR Utrecht,
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 Santé Sa
Rue Bellocier,
89100 Sens,
France
Teva Czech Industries s.r.o.
Ostravska 29, c.p. 305,
74770 Opava-Komarov,
Czech Republic
PLIVA Krakow Zakłady Farmaceutyczne S.A.
ul. Mogilska 80,
24
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.
Tel/Tél: +32 3 820 73 73
Luxembourg/Luxemburg
Teva Pharma Belgium S.A.
Tél/Tel: +32 3 820 73 73
България
Тева Фармасютикълс България ЕООД
Teл: +359 2 489 95 82
Magyarország
Teva Magyarország Zrt
Tel.: +36 1 288 64 00
Česká republika
Teva Pharmaceuticals CR, s.r.o.
Tel: +420 251 007 111
Malta
Teva Ελλάς Α.Ε.
Τel: +30 210 72 79 099
Danmark
Teva Denmark ApS
Tlf: +45 44 98 55 11
Nederland
Teva Nederland B.V.
Tel: +31 (0) 800 0228400
Deutschland
Teva GmbH
Tel: (49) 351 834 0
Norge
Teva Sweden AB
Tlf: (46) 42 12 11 00
Eesti
Teva Eesti esindus UAB Sicor Biotech
Eesti filiaal
Tel: +372 611 2409
Österreich
Teva GmbH
Tel: (49) 351 834 0
Ελλάδα
Teva Ελλάς Α.Ε.
Τηλ: +30 210 72 79 099
Polska
Teva Pharmaceuticals Polska Sp. z o.o.
Tel.: +(48) 22 345 93 00
España
Teva Pharma, S.L.U.
Tél: +(34) 91 387 32 80
Portugal
Teva Pharma - Produtos Farmacêuticos Lda
Tel: (351) 214 235 910
France
Teva Santé
Tél: +(33) 1 55 91 7800
România
Teva Pharmaceuticals S.R.L
Tel: +4021 230 65 24
Ireland
Teva Pharmaceuticals Ireland
Tel: +353 (0)42 9395 892
Slovenija
Pliva Ljubljana d.o.o.
Tel: +386 1 58 90 390
Ísland
Teva UK Limited
Sími: +(44) 1323 501 111
Slovenská republika
Teva Pharmaceuticals Slovakia s.r.o.
Tel: +(421) 2 5726 7911
Italia
Teva Italia S.r.l.
Tel: +(39) 0289179805
Suomi/Finland
Teva Sweden AB
Puh/Tel: +(46) 42 12 11 00
25
Κύπρος
Teva Ελλάς Α.Ε.
Τηλ: +30 210 72 79 099
Sverige
Teva Sweden AB
Tel: +(46) 42 12 11 00
Latvija
UAB Sicor Biotech filiāle Latvijā
Tel: +371 67 784 980
United Kingdom
Teva UK Limited
Tel: +(44) 1323 501 111
Lietuva
UAB “Sicor Biotech”
Tel: +370 5 266 02 03
This leaflet was last approved in
MM/YYYY.
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu
26
Source: European Medicines Agency
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