Oprymea

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.088 mg tablets
Oprymea 0.18 mg tablets
Oprymea 0.35 mg tablets
Oprymea 0.7 mg tablets
Oprymea 1.1 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Oprymea 0.088 mg tablets
Each tablet contains 0.088 mg pramipexole (as 0.125 mg pramipexole dihydrochloride monohydrate).

Oprymea 0.18 mg tablets
Each tablet contains 0.18 mg pramipexole (as 0.25 mg pramipexole dihydrochloride monohydrate).

Oprymea 0.35 mg tablets
Each tablet contains 0.35 mg pramipexole (as 0.5 mg pramipexole dihydrochloride monohydrate).

Oprymea 0.7 mg tablets
Each tablet contains 0.7 mg pramipexole (as 1 mg pramipexole dihydrochloride monohydrate).

Oprymea 1.1 mg tablets
Each tablet contains 1.1 mg pramipexole (as 1.5 mg pramipexole dihydrochloride monohydrate).

Please note:
Pramipexole doses as published in the literature refer to the salt form.
Therefore, doses will be expressed in terms of both pramipexole base and pramipexole salt (in 
brackets).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet

Oprymea 0.088 mg tablets
White, round, with bevelled edges and imprint "P6" on one side of the tablet.

Oprymea 0.18 mg tablets
White, oval, with bevelled edges, both sides scored, with imprint "P7" on both halves of one side of 
the tablet. The tablet can be divided into equal doses.

Oprymea 0.35 mg tablets
White, oval, with bevelled edges, both sides scored, with imprint "P8" on both halves of one side of 
the tablet. The tablet can be divided into equal doses.

Oprymea 0.7 mg tablets
White, round, with bevelled edges, both sides scored, with imprint "P9" on both halves of one side of 
the tablet. The tablet can be divided into equal doses.

Oprymea 1.1 mg tablets
White, round, with bevelled edges, both sides scored. The tablet can be divided into equal doses.



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4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Oprymea is indicated in adults for treatment of the signs and symptoms of idiopathic Parkinson's 
disease, alone (without levodopa) or in combination with levodopa, i.e. over the course of the disease, 
through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations 
of the therapeutic effect occur (end of dose or “on off” fluctuations).

Oprymea is indicated in adults for symptomatic treatment of moderate to severe idiopathic Restless 
Legs Syndrome in doses up to 0.54 mg of base (0.75 mg of salt) (see section 4.2).

4.2 Posology and method of administration

Posology

Parkinson’s disease

The daily dose is administered in equally divided doses 3 times a day.

Initial treatment
Doses should be increased gradually from a starting-dose of 0.264 mg of base (0.375 mg of salt) per 
day and then increased every 5 - 7 days. Providing patients do not experience intolerable undesirable 
effects, the dose should be titrated to achieve a maximal therapeutic effect.

Ascending – Dose Schedule of Oprymea
Week Dose

(mg of base)
Total Daily Dose
(mg of base)

Dose
(mg of salt)

Total Daily Dose
(mg of salt)

1 3 x 0.088 0.264 3 x 0.125 0.375
2 3 x 0.18 0.54 3 x 0.25 0.75
3 3 x 0.35 1.1 3 x 0.5 1.50

If a further dose increase is necessary the daily dose should be increased by 0.54 mg of base (0.75 mg
of salt) at weekly intervals up to a maximum dose of 3.3 mg of base (4.5 mg of salt) per day.

However, it should be noted that the incidence of somnolence is increased at doses higher than 1.5 mg 
(of salt) per day (see section 4.8).

Maintenance treatment
The individual dose of pramipexole should be in the range of 0.264 mg of base (0.375 mg of salt) to a 
maximum of 3.3 mg of base (4.5 mg of salt) per day. During dose escalation in pivotal studies, 
efficacy was observed starting at a daily dose of 1.1 mg of base (1.5 mg of salt). Further dose 
adjustments should be done based on the clinical response and the occurrence of adverse reactions. In 
clinical trials approximately 5% of patients were treated at doses below 1.1 mg of base (1.5 mg of 
salt). In advanced Parkinson’s disease, pramipexole doses higher than 1.1 mg of base (1.5 mg of salt) 
per day can be useful in patients where a reduction of the levodopa therapy is intended. It is 
recommended that the dose of levodopa is reduced during both the dose escalation and the 
maintenance treatment with Oprymea, depending on reactions in individual patients (see section 4.5).

Treatment discontinuation
Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic 
malignant syndrome or a dopamine agonist withdrawal syndrome. Pramipexole should be tapered off 
at a rate of 0.54 mg of base (0.75 mg of salt) per day until the daily dose has been reduced to 0.54 mg 
of base (0.75 mg of salt). Thereafter the dose should be reduced by 0.264 mg of base (0.375 mg of 
salt) per day (see section 4.4). Dopamine agonist withdrawal syndrome could still appear while 
tapering and a temporary increase of the dose could be necessary before resuming tapering (see 
section 4.4).



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Renal impairment
The elimination of pramipexole is dependent on renal function. The following dose schedule is 
suggested for initiation of therapy:

Patients with a creatinine clearance above 50 ml/min require no reduction in daily dose or dosing 
frequency.

In patients with a creatinine clearance between 20 and 50 ml/min, the initial daily dose of Oprymea 
should be administered in two divided doses, starting at 0.088 mg of base (0.125 mg of salt) twice a 
day (0.176 mg of base/0.25 mg of salt daily). A maximum daily dose of 1.57 mg pramipexole base 
(2.25 mg of salt) should not be exceeded.

In patients with a creatinine clearance less than 20 ml/min, the daily dose of Oprymea should be 
administered in a single dose, starting at 0.088 mg of base (0.125 mg of salt) daily. A maximum daily 
dose of 1.1 mg pramipexole base (1.5 mg of salt) should not be exceeded.

If renal function declines during maintenance therapy the Oprymea daily dose should be reduced by 
the same percentage as the decline in creatinine clearance, i.e. if creatinine clearance declines by 30%, 
then the Oprymea daily dose should be reduced by 30%. The daily dose can be administered in two 
divided doses if creatinine clearance is between 20 and 50 ml/min, and as a single daily dose if 
creatinine clearance is less than 20 ml/min.

Hepatic impairment
Dose adjustment in patients with hepatic failure is probably not necessary, as approx. 90% of absorbed 
active substance is excreted through the kidneys. However, the potential influence of hepatic 
insufficiency on Oprymea pharmacokinetics has not been investigated.

Paediatric population
The safety and efficacy of Oprymea in children below 18 years has not been established. There is no 
relevant use of Oprymea in the paediatric population for the indication of Parkinson’s Disease.

Restless Legs Syndrome

The recommended starting dose of Oprymea is 0.088 mg of base (0.125 mg of salt) taken once daily 
2-3 hours before bedtime. For patients requiring additional symptomatic relief, the dose may be 
increased every 4-7 days to a maximum of 0.54 mg of base (0.75 mg of salt) per day (as shown in the 
table below).

Dose Schedule of Oprymea
Titration Step Once Daily Evening Dose

(mg of base)
Once Daily Evening Dose
(mg of salt)

1 0.088 0.125
2* 0.18 0.25
3* 0.35 0.50
4* 0.54 0.75
* if needed

Patient’s response should be evaluated after 3 months treatment and the need for treatment 
continuation should be reconsidered. If treatment is interrupted for more than a few days it should be 
re-initiated by dose titration carried out as above.

Treatment discontinuation
Since the daily dose for the treatment of Restless Legs Syndrome will not exceed 0.54 mg of base 
(0.75 mg of salt) Oprymea can be discontinued without tapering off. In a 26 week placebo controlled 
trial, rebound of RLS symptoms (worsening of symptom severity as compared to baseline) was 



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observed in 10% of patients (14 out of 135) after abrupt discontinuation of treatment. This effect was 
found to be similar across all doses.

Renal impairment
The elimination of pramipexole is dependent on renal function. Patients with a creatinine clearance 
above 20 ml/min require no reduction in daily dose.
The use of pramipexole has not been studied in haemodialysis patients, or in patients with severe renal 
impairment.

Hepatic impairment
Dose adjustment in patients with hepatic failure is not required, as approx. 90% of absorbed active 
substance is excreted through the kidneys.

Paediatric population
Oprymea is not recommended for use in children and adolescents below 18 years due to a lack of data 
on safety and efficacy.

Tourette Disorder

Paediatric population
Oprymea is not recommended for use in children and adolescents below 18 years since the efficacy 
and safety has not been established in this population. Oprymea should not be used in children or 
adolescents with Tourette Disorder because of a negative benefit-risk balance for this disorder (see 
section 5.1).

Method of administration
The tablets should be taken orally, swallowed with water, and can be taken either with or without 
food.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

When prescribing Oprymea in a patient with Parkinson’s disease with renal impairment a reduced 
dose is suggested in line with section 4.2.

Hallucinations
Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa. Patients 
should be informed that (mostly visual) hallucinations can occur.

Dyskinesia
In advanced Parkinson’s disease, in combination treatment with levodopa, dyskinesia can occur during 
the initial titration of Oprymea. If they occur, the dose of levodopa should be decreased.

Dystonia 
Axial dystonia including antecollis, camptocormia and pleurothotonus (Pisa Syndrome) has 
occasionally been reported in patients with Parkinson’s disease following initiation or incremental 
dose increase of pramipexole. Although dystonia may be a symptom of Parkinson’s disease, the 
symptoms in these patients have improved after reduction or withdrawal of pramipexole. If dystonia 
occurs, the dopaminergic medication regimen should be reviewed and an adjustment in the dose of 
pramipexole considered.

Sudden onset of sleep and somnolence
Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in 
patients with Parkinson’s disease. Sudden onset of sleep during daily activities, in some cases without 



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awareness or warning signs, has been reported uncommonly. Patients must be informed of this and 
advised to exercise caution while driving or operating machines during treatment with Oprymea. 
Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from 
driving or operating machines. Furthermore a reduction of dose or termination of therapy may be 
considered. Because of possible additive effects, caution should be advised when patients are taking 
other sedating medicinal products or alcohol in combination with pramipexole (see sections 4.5, 4.7 
and section 4.8).

Impulse control disorders
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 including pramipexole. 
Dose reduction/tapered discontinuation should be considered if such symptoms develop.

Mania and delirium
Patients should be regularly monitored for the development of mania and delirium. Patients and carers 
should be made aware that mania and delirium can occur in patients treated with pramipexole. Dose 
reduction/tapered discontinuation should be considered if such symptoms develop.

Patients with psychotic disorders
Patients with psychotic disorders should only be treated with dopamine agonists if the potential 
benefits outweigh the risks.

Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see 
section 4.5).

Ophthalmologic monitoring
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.

Severe cardiovascular disease
In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood 
pressure, especially at the beginning of treatment, due to the general risk of postural hypotension 
associated with dopaminergic therapy.

Neuroleptic malignant syndrome
Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal 
of dopaminergic therapy (see section 4.2).

Dopamine agonist withdrawal syndrome (DAWS)
DAWS has been reported with dopamine agonists, including pramipexole (see section 4.8). To 
discontinue treatment in patients with Parkinson’s disease, pramipexole should be tapered off (see 
section 4.2). Limited data suggests that patients with impulse control disorders and those receiving 
high daily dose and/or high cumulative doses of dopamine agonists may be at higher risk for 
developing DAWS. Withdrawal symptoms may include apathy, anxiety, depression, fatigue, sweating 
and pain and do not respond to levodopa. Prior to tapering off and discontinuing pramipexole, patients 
should be informed about potential withdrawal symptoms. Patients should be closely monitored during 
tapering and discontinuation. In case of severe and/or persistent withdrawal symptoms, temporary re-
administration of pramipexole at the lowest effective dose may be considered.

Augmentation
Reports in the literature indicate that treatment of Restless Legs Syndrome with dopaminergic 
medicinal products can result in augmentation. Augmentation refers to the earlier onset of symptoms 
in the evening (or even the afternoon), increase in symptoms, and spread of symptoms to involve other 
extremities. Augmentation was specifically investigated in a controlled clinical trial over 26 weeks. 
Augmentation was observed in 11.8% of patients in the pramipexole group (N = 152) and 9.4% of 
patients in the placebo group (N = 149). Kaplan-Meier analysis of time to augmentation showed no 



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significant difference between pramipexole and placebo groups.

4.5 Interaction with other medicinal products and other forms of interaction

Plasma protein binding
Pramipexole is bound to plasma proteins to a very low (< 20%) extent, and little biotransformation is 
seen in man. Therefore, interactions with other medicinal products affecting plasma protein binding or 
elimination by biotransformation are unlikely. As anticholinergics are mainly eliminated by 
biotransformation, the potential for an interaction is limited, although an interaction with 
anticholinergics has not been investigated. There is no pharmacokinetic interaction with selegiline and 
levodopa.

Inhibitors/competitors of active renal elimination pathway
Cimetidine reduced the renal clearance of pramipexole by approximately 34%, presumably by 
inhibition of the cationic secretory transport system of the renal tubules. Therefore, medicinal products 
that are inhibitors of this active renal elimination pathway or are eliminated by this pathway, such as 
cimetidine,amantadine mexiletine, zidovudine, cisplatin, quinine, and procainamide, may interact with 
pramipexole resulting in reduced clearance of pramipexole. Reduction of the pramipexole dose should 
be considered when these medicinal products are administered concomitantly with Oprymea.

Combination with levodopa
When Oprymea is given in combination with levodopa, it is recommended that the dose of levodopa is 
reduced and the dose of other anti-parkinsonian medicinal products is kept constant while increasing 
the dose of Oprymea.

Because of possible additive effects, caution should be advised when patients are taking other sedating 
medicinal products or alcohol in combination with pramipexole (see sections 4.4, 4.7 and 4.8).

Antipsychotic medicinal products
Co-administration of antipsychotic medicinal products with pramipexole should be avoided (see 
section 4.4), e.g. if antagonistic effects can be expected.

4.6 Fertility, pregnancy and lactation

Pregnancy
The effect on pregnancy and lactation has not been investigated in humans. Pramipexole was not 
teratogenic in rats and rabbits, but was embryotoxic in the rat at maternotoxic doses (see section 5.3). 
Oprymea should not be used during pregnancy unless clearly necessary, i.e. if the potential benefit 
justifies the potential risk to the foetus.

Breast-feeding
As pramipexole treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected. 
The excretion of pramipexole into breast milk has not been studied in women. In rats, the 
concentration of active substance-related radioactivity was higher in breast milk than in plasma. In the 
absence of human data, Oprymea should not be used during breast-feeding. However, if its use is 
unavoidable, breast-feeding should be discontinued.

Fertility
No studies on the effect on human fertility have been conducted. In animal studies, pramipexole 
affected oestrous cycles and reduced female fertility as expected for a dopamine agonist. However, 
these studies did not indicate direct or indirect harmful effects with respect to male fertility.

4.7 Effects on ability to drive and use machines

Oprymea can have a major influence on the ability to drive and use machines.

Hallucinations or somnolence can occur.



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Patients being treated with Oprymea and presenting with somnolence and/or sudden sleep episodes 
must be informed 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 and somnolence have resolved (see also sections 4.4, 4.5, and 4.8).

4.8 Undesirable effects

Based on the analysis of pooled placebo-controlled trials, comprising a total of 1,923 patients on 
pramipexole and 1,354 patients on placebo, adverse drug reactions were frequently reported for both 
groups. 63 % of patients on pramipexole and 52% of patients on placebo reported at least one adverse 
drug reaction.

The majority of adverse drug reactions usually start early in therapy and most tend to disappear even 
as therapy is continued.

Within the system organ classes, adverse reactions are listed under headings of frequency (number of 
patients expected to experience the reaction), using the following categories: 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 .

Parkinson’s disease, most common adverse reactions
The most commonly (≥5%) reported adverse drug reactions in patients with Parkinson’s disease more 
frequent with pramipexole treatment than with placebo were nausea, dyskinesia, hypotension, 
dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue. The incidence of 
somnolence is increased at doses higher than 1.5 mg pramipexole salt per day (see section 4.2). A 
more frequent adverse drug reaction in combination with levodopa was dyskinesia. Hypotension may 
occur at the beginning of treatment, especially if pramipexole is titrated too fast.

Table 1: Parkinson’s disease
Body System 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)

Not known

Infections and 
infestations

pneumonia

Endocrine 
disorders

inappropriate 
antidiuretic
hormone secretion1

Psychiatric 
disorders

Insomnia
hallucinations
abnormal dreams 
confusion 

behavioural 
symptoms of 
impulse control 
disorders and 
compulsions 

compulsive shopping 
pathological 
gambling
restlessness
hypersexuality
delusion
libido disorder
paranoia
delirium
binge eating1

hyperphagia1

mania

Nervous 
system 
disorders

somnolence
dizziness 
dyskinesia 

headache sudden onset of 
sleep
amnesia
hyperkinesia
syncope

Eye disorders visual 
impairment 



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including 
diplopia vision 
blurred 
visual acuity 
reduced

Cardiac 
disorders

cardiac failure1

Vascular 
disorders

hypotension

Respiratory, 
thoracic, and 
mediastinal 
disorders

Dyspnoea
hiccups

Gastrointestinal 
disorders

nausea constipation
vomiting

Skin and 
subcutaneous 
tissue disorders

hypersensitivity 
pruritus
rash

General 
disorders and 
administration 
site conditions

fatigue
peripheral 
oedema

Dopamine 
agonist 
withdrawal 
syndrome 
including 
apathy, 
anxiety, 
depression, 
fatigue, 
sweating 
and pain.

Investigations weight decrease 
including 
decreased 
appetite

weight increase

1 This side effect has been observed in post-marketing experience. With 95 % certainty, the 
frequency category is not greater than uncommon, but might be lower. A precise frequency 
estimation is not possible as the side effect did not occur in a clinical trial database of 2,762 
patients with Parkinson’s Disease treated with pramipexole.

Restless Legs Syndrome, most common adverse reactions
The most commonly (≥ 5%) reported adverse drug reactions in patients with Restless Legs Syndrome
treated with pramipexole were nausea, headache, dizziness and fatigue. Nausea and fatigue were more 
often reported in female patients (20.8% and 10.5%, respectively) compared to males (6.7% and 7.3%, 
respectively).

Table 2: Restless legs syndrome
Body System Very 

common
(≥1/10)

Common
(≥1/100 to 
<1/10)

Uncommon
(≥1/1,000 to
< 1/100)

Not known

Infections and 
infestations

pneumonia1

Endocrine 
disorders

inappropriate antidiuretic hormone 
secretion1

Psychiatric 
disorders

insomnia
abnormal 
dreams 

restlessness
confusion 
hallucinations



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libido disorder
delusion1

hyperphagia1

paranoia1

mania1

delirium1

behavioural symptoms of impulse 
control disorders and compulsions1

(such as:
compulsive shopping,
pathological gambling,
hypersexuality, binge eating)

Nervous 
system 
disorders

headache
dizziness
somnolance

sudden onset of sleep 
syncope
dyskinesia
amnesia1

hyperkinesia1

Eye disorders visual impairment including 
visual acuity reduced
diplopia 
vision blurred 

Cardiac 
disorders

cardiac failure1

Vascular 
disorders

hypotension

Respiratory, 
thoracic, and 
mediastinal 
disorders

dyspnoea
hiccups

Gastrointestinal 
disorders

nausea constipation
vomiting

Skin and 
subcutaneous 
tissue disorders

hypersensitivity pruritus
rash

General 
disorders and 
administration 
site conditions

fatigue peripheral oedema Dopamine 
agonist 
withdrawal 
syndrome 
including 
apathy, anxiety, 
depression, 
fatigue, 
sweating and 
pain

Investigations weight decrease including 
decreased appetite
weight increase

1 This side effect has been observed in post-marketing experience. With 95 % certainty, the 
frequency category is not greater than uncommon, but might be lower. A precise frequency 
estimation is not possible as the side effect did not occur in a clinical trial database of 1,395 
patients with Restless Legs Syndrome treated with pramipexole.

Description of selected adverse reactions

Somnolence
Pramipexole is commonly associated with somnolence and has been associated uncommonly with 



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excessive daytime somnolence and sudden sleep onset episodes (see also section 4.4).

Libido disorders
Pramipexole may uncommonly be associated with libido disorders (increased or decreased).

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 including Oprymea (see 
section 4.4).

In a cross-sectional, retrospective screening and case-control study including 3,090 Parkinson’s 
disease patients, 13.6% of all patients receiving dopaminergic or non-dopaminergic treatment had 
symptoms of an impulse control disorder during the past six months. Manifestations observed include 
pathological gambling, compulsive shopping, binge eating, and compulsive sexual behaviour 
(hypersexuality). Possible independent risk factors for impulse control disorders included 
dopaminergic treatments and higher doses of dopaminergic treatment, younger age (≤ 65 years), not 
being married and self-reported family history of gambling behaviours.

Dopamine agonist withdrawal syndrome
Non-motor adverse effects may occur when tapering or discontinuing dopamine agonists including 
pramipexole. Symptoms include apathy, anxiety, depression, fatigue, sweating and pain (see section 
4.4).

Cardiac failure
In clinical studies and post-marketing experience cardiac failure has been reported in patients with 
pramipexole. In a pharmacoepidemiological study pramipexole use was associated with an increased 
risk of cardiac failure compared with non-use of pramipexole (observed risk ratio 1.86; 95% CI, 1.21-
2.85).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

There is no clinical experience with massive overdose. The expected adverse drug reactions would be 
those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, 
hyperkinesia, hallucinations, agitation and hypotension. There is no established antidote for overdose 
of a dopamine agonist. If signs of central nervous system stimulation are present, a neuroleptic agent 
may be indicated. Management of the overdose may require general supportive measures, along with 
gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram 
monitoring.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: anti-Parkinson drugs, dopamine agonists, ATC code: N04BC05.

Mechanism of action
Pramipexole is a dopamine agonist that binds with high selectivity and specificity to the D2 subfamily 
of dopamine receptors of which it has a preferential affinity to D3 receptors, and has full intrinsic 
activity.



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Pramipexole alleviates Parkinsonian motor deficits by stimulation of dopamine receptors in the 
striatum. Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and 
turnover.

The mechanism of action of pramipexole as treatment for Restless Legs Syndrome is unknown. 
Neuropharmacological evidence suggests primary dopaminergic system involvement.

Pharmacodynamic effects
In human volunteers, a dose-dependent decrease in prolactin was observed.

Clinical efficacy and safety in Parkinson’s disease

In patients pramipexole alleviates signs and symptoms of idiopathic Parkinson' s disease. Placebo-
controlled clinical trials included approximately 1,800 patients of Hoehn and Yahr stages stages I – V
treated with pramipexole. Out of these, approximately 1,000 were in more advanced stages, received 
concomitant levodopa therapy, and suffered from motor complications.

In early and advanced Parkinson’s disease, efficacy of pramipexole in controlled clinical trials was 
maintained for approximately six months. In open continuation trials lasting for more than three years 
there were no signs of decreasing efficacy.

In a controlled double blind clinical trial of 2 year duration, initial treatment with pramipexole 
significantly delayed the onset of motor complications, and reduced their occurrence compared to 
initial treatment with levodopa. This delay in motor complications with pramipexole should be 
balanced against a greater improvement in motor function with levodopa (as measured by the mean 
change in UPDRS-score). The overall incidence of hallucinations and somnolence was generally 
higher in the escalation phase with the pramipexole group. However there was no significant 
difference during the maintenance phase. These points should be considered when initiating 
pramipexole treatment in patients with Parkinson´s disease.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with 
pramipexole in all subsets of the paediatric population in Parkinson’s Disease (see section 4.2 for 
information on paediatric use).

Clinical efficacy and safety in Restless Legs Syndrome
The efficacy of pramipexole was evaluated in four placebo-controlled clinical trials in approximately 
1,000 patients with moderate to very severe idiopathic Restless Legs Syndrome. 

The mean change from baseline in the Restless Legs Syndrome Rating Scale (IRLS) and the Clinical 
Global Impression-Improvement (CGI-I) were the primary efficacy outcome measures. For both 
primary endpoints statistically significant differences have been observed for the pramipexole dose 
groups 0.25 mg, 0.5 mg and 0.75 mg pramipexole salt in comparison to placebo. After 12 weeks of 
treatment the baseline IRLS score improved from 23.5 to 14.1 points for placebo and from 23.4 to 9.4 
points for pramipexole (doses combined). The adjusted mean difference was -4.3 points (CI 95% -6.4; 
-2.1 points, p-value <0.0001). CGI-I responder rates (improved, very much improved) were 51.2% and 
72.0% for placebo and pramipexole, respectively (difference 20% CI 95%: 8.1%; 31.8%, p<0.0005). 
Efficacy was observed with 0.088 mg of base (0.125 mg of salt) per day after the first week of 
treatment.

In a placebo-controlled polysomnography study over 3 weeks pramipexole significantly reduced the 
number of periodic limb movements during time in bed.

Longer term efficacy was evaluated in a placebo-controlled clinical trial. After 26 weeks of treatment, 
there was an adjusted mean reduction in IRLS total score of 13.7 and 11.1 points in the pramipexole 
and placebo group, respectively, with a statistically significant (p = 0.008) mean treatment difference 
of -2.6. CGI-I responder rates (much improved, very much improved) were 50.3% (80/159) and 68.5% 



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(111/162) for placebo and pramipexole, respectively (p = 0.001), corresponding to a number needed to 
treat (NNT) of 6 patients (95%CI: 3.5, 13.4).

Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with 
pramipexole in one or more subsets of the paediatric population in Restless Legs Syndrome (see 
section 4.2 for information on paediatric use).

Clinical efficacy and safety in Tourette Disorder

The efficacy of pramipexole (0.0625-0.5 mg/day) with paediatric patients aged 6-17 years with 
Tourette Disorder was evaluated in a 6-week, double-blind, randomised, placebo-controlled flexible 
dose study. A total of 63 patients were randomised (43 on pramipexole, 20 on placebo). The primary 
endpoint was change from baseline on the Total Tic Score (TTS) of the Yale Global Tic Severity 
Scale (YGTSS). No difference was observed for pramipexole as compared to placebo for either the
primary endpoint or for any of the secondary efficacy endpoints including YGTSS total score, Patient 
Global Impression of Improvement (PGI-I), Clinical Global Impression of Improvement (CGI-I), or 
Clinical Global Impressions of Severity of Illness (CGI-S). Adverse events occurring in at least 5% of 
patients in the pramipexole group and more common in the pramipexole-treated patients than in 
patients on placebo were: headache (27.9%, placebo 25.0%), somnolence (7.0%, placebo 5.0%), 
nausea (18.6%, placebo 10.0%), vomiting (11.6%, placebo 0.0%), upper abdominal pain (7.0%, 
placebo 5.0%), orthostatic hypotension (9.3%, placebo 5.0%), myalgia (9.3%, placebo 5.0%), sleep 
disorder (7.0%, placebo 0.0%), dyspnoea (7.0%, placebo 0.0%) and upper respiratory tract infection 
(7.0%, placebo 5.0%). Other significant adverse events leading to discontinuation of study medication 
for patients receiving pramipexole were confusional state, speech disorder and aggravated condition 
(see section 4.2).

5.2 Pharmacokinetic properties

Absorption
Pramipexole is rapidly and completely absorbed following oral administration. The absolute 
bioavailability is greater than 90% and the maximum plasma concentrations occur between 1 and 3 
hours. Concomitant administration with food did not reduce the extent of pramipexole absorption, but 
the rate of absorption was reduced. Pramipexole shows linear kinetics and a small inter-patient 
variation of plasma levels.

Distribution
In humans, the protein binding of pramipexole is very low (< 20%) and the volume of distribution is 
large (400 l). High brain tissue concentrations were observed in the rat (approx. 8-fold compared to 
plasma).

Biotransformation
Pramipexole is metabolised in man only to a small extent.

Elimination
Renal excretion of unchanged pramipexole is the major route of elimination. Approximately 90% of 
14C-labelled dose is excreted through the kidneys while less than 2% is found in the faeces. The total 
clearance of pramipexole is approximately 500 ml/min and the renal clearance is approximately 
400 ml/min. The elimination half-life (t½) varies from 8 hours in the young to 12 hours in the elderly.

5.3 Preclinical safety data

Repeated dose toxicity studies showed that pramipexole exerted functional effects, mainly involving 
the CNS and female reproductive system, and probably resulting from an exaggerated 
pharmacodynamic effect of pramipexole.

Decreases in diastolic and systolic pressure and heart rate were noted in the minipig, and a tendency to 



14

a hypotensive effect was discerned in the monkey.

The potential effects of pramipexole on reproductive function have been investigated in rats and 
rabbits. Pramipexole was not teratogenic in rats and rabbits but was embryotoxic in the rat at 
maternally toxic doses. Due to the selection of animal species and the limited parameters investigated, 
the adverse effects of pramipexole on pregnancy and male fertility have not been fully elucidated.

A delay in sexual development (i.e., preputial separation and vaginal opening) was observed in rats. 
The relevance for humans is unknown.

Pramipexole was not genotoxic. In a carcinogenicity study, male rats developed Leydig cell 
hyperplasia and adenomas, explained by the prolactin-inhibiting effect of pramipexole. This finding is 
not clinically relevant to man. The same study also showed that, at doses of 2 mg/kg (of salt) and 
higher, pramipexole was associated with retinal degeneration in albino rats. The latter finding was not 
observed in pigmented rats, nor in a 2-year albino mouse carcinogenicity study or in any other species 
investigated.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Mannitol
Maize starch
Pregelatinised maize starch
Povidone K25
Colloidal anhydrous silica
Magnesium stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store in the original package in order to protect from light.

6.5 Nature and contents of container

Blister pack (Alu/Alu foil): 20, 30, 60, 90 or 100 tablets, in a box.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia



15

8. MARKETING AUTHORISATION NUMBER(S)

Oprymea 0.088 mg tablets
20 tablets: EU/1/08/469/001
30 tablets: EU/1/08/469/002
60 tablets: EU/1/08/469/003
90 tablets: EU/1/08/469/004
100 tablets: EU/1/08/469/005

Oprymea 0.18 mg tablets
20 tablets: EU/1/08/469/006
30 tablets: EU/1/08/469/007
60 tablets: EU/1/08/469/008
90 tablets: EU/1/08/469/009
100 tablets: EU/1/08/469/010

Oprymea 0.35 mg tablets
20 tablets: EU/1/08/469/011
30 tablets: EU/1/08/469/012
60 tablets: EU/1/08/469/013
90 tablets: EU/1/08/469/014
100 tablets: EU/1/08/469/015

Oprymea 0.7 mg tablets
20 tablets: EU/1/08/469/016
30 tablets: EU/1/08/469/017
60 tablets: EU/1/08/469/018
90 tablets: EU/1/08/469/019
100 tablets: EU/1/08/469/020

Oprymea 1.1 mg tablets
20 tablets: EU/1/08/469/021
30 tablets: EU/1/08/469/022
60 tablets: EU/1/08/469/023
90 tablets: EU/1/08/469/024
100 tablets: EU/1/08/469/025

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 12 September 2008
Date of latest renewal: 9 April 2013

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.



16

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.26 mg prolonged-release tablets
Oprymea 0.52 mg prolonged-release tablets
Oprymea 1.05 mg prolonged-release tablets
Oprymea 1.57 mg prolonged-release tablets
Oprymea 2.1 mg prolonged-release tablets
Oprymea 2.62 mg prolonged-release tablets
Oprymea 3.15 mg prolonged-release tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Oprymea 0.26 mg prolonged-release tablets
Each prolonged-release tablet contains 0.26 mg pramipexole (as 0.375 mg pramipexole 
dihydrochloride monohydrate).

Oprymea 0.52 mg prolonged-release tablets
Each prolonged-release tablet contains 0.52 mg pramipexole (as 0.75 mg pramipexole dihydrochloride 
monohydrate).

Oprymea 1.05 mg prolonged-release tablets
Each prolonged-release tablet contains 1.05 mg pramipexole (as 1.5 mg pramipexole dihydrochloride 
monohydrate).

Oprymea 1.57 mg prolonged-release tablets
Each prolonged-release tablet contains 1.57 mg pramipexole (as 2.25 mg pramipexole dihydrochloride 
monohydrate).

Oprymea 2.1 mg prolonged-release tablets
Each prolonged-release tablet contains 2.1 mg pramipexole (as 3 mg pramipexole dihydrochloride 
monohydrate).

Oprymea 2.62 mg prolonged-release tablets
Each prolonged-release tablet contains 2.62 mg pramipexole (as 3.75 mg pramipexole dihydrochloride 
monohydrate).

Oprymea 3.15 mg prolonged-release tablets
Each prolonged-release tablet contains 3.15 mg pramipexole (as 4.5 mg pramipexole dihydrochloride 
monohydrate).

Please note:
Pramipexole doses as published in the literature refer to the salt form.
Therefore, doses will be expressed in terms of both pramipexole base and pramipexole salt (in 
brackets).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Prolonged-release tablet

Oprymea 0.26 mg prolonged-release tablets
White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P1 on one 
side, with bevelled edges and possible spots.



17

Oprymea 0.52 mg prolonged-release tablets
White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P2 on one 
side, with bevelled edges and possible spots.

Oprymea 1.05 mg prolonged-release tablets
White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P3 on one 
side, with bevelled edges and possible spots.

Oprymea 1.57 mg prolonged-release tablets
White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P12 on one 
side, with bevelled edges and possible spots.

Oprymea 2.1 mg prolonged-release tablets
White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P4 on one 
side, with bevelled edges and possible spots.

Oprymea 2.62 mg prolonged-release tablets
White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P13 on one 
side and 262 on the other side, with bevelled edges and possible spots.

Oprymea 3.15 mg prolonged-release tablets
White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P5 on one 
side and 315 on the other side, with bevelled edges and possible spots.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Oprymea is indicated in adults for treatment of the signs and symptoms of idiopathic Parkinson’s 
disease, alone (without levodopa) or in combination with levodopa, i.e. over the course of the disease, 
through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations 
of the therapeutic effect occur (end of dose or "on off" fluctuations).

4.2 Posology and method of administration

Posology

Oprymea prolonged-release tablets are a once-a-day oral formulation of pramipexole.

Initial treatment
Doses should be increased gradually from a starting dose of 0.26 mg of base (0.375 mg of salt) per day 
and then increased every 5 - 7 days. Providing patients do not experience intolerable undesirable 
effects, the dose should be titrated to achieve a maximal therapeutic effect.

Ascending dose schedule of Oprymea prolonged-release tablets
Week Daily dose (mg of base) Daily dose (mg of salt)
1 0.26 0.375
2 0.52 0.75
3 1.05 1.5

If a further dose increase is necessary the daily dose should be increased by 0.52 mg of base (0.75 mg 
of salt) at weekly intervals up to a maximum dose of 3.15 mg of base (4.5 mg of salt) per day. 
However, it should be noted that the incidence of somnolence is increased at doses higher than 
1.05 mg of base (1.5 mg of salt) per day (see section 4.8).

Patients already taking Oprymea tablets may be switched to Oprymea prolonged-release tablets 



18

overnight, at the same daily dose. After switching to Oprymea prolonged-release tablets, the dose may 
be adjusted depending on the patient’s therapeutic response (see section 5.1).

Maintenance treatment
The individual dose of pramipexole should be in the range of 0.26 mg of base (0.375 mg of salt) to a 
maximum of 3.15 mg of base (4.5 mg of salt) per day. During dose escalation in pivotal studies, 
efficacy was observed starting at a daily dose of 1.05 mg of base (1.5 mg of salt). Further dose 
adjustments should be done based on the clinical response and the occurrence of adverse reactions. In 
clinical trials approximately 5% of patients were treated at doses below 1.05 mg of base (1.5 mg of 
salt). In advanced Parkinson’s disease, pramipexole doses higher than 1.05 mg of base (1.5 mg of salt) 
per day can be useful in patients where a reduction of the levodopa therapy is intended. It is 
recommended that the dose of levodopa is reduced during both the dose escalation and the
maintenance treatment with Oprymea, depending on reactions in individual patients (see section 4.5).

Missed dose
When the intake of a dose is missed, Oprymea prolonged-release tablets should be taken within 12 
hours after the regularly scheduled time. After 12 hours, the missed dose should be left out and the 
next dose should be taken on the following day at the next regularly scheduled time.

Treatment discontinuation
Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic 
malignant syndrome or a dopamine agonist withdrawal syndrome. Pramipexole should be tapered off 
at a rate of 0.52 mg of base (0.75 mg of salt) per day until the daily dose has been reduced to 0.52 mg 
of base (0.75 mg of salt). Thereafter the dose should be reduced by 0.26 mg of base (0.375 mg of salt) 
per day (see section 4.4). Dopamine agonist withdrawal syndrome could still appear while tapering 
and a temporary increase of the dose could be necessary before resuming tapering (see section 4.4).

Renal impairment
The elimination of pramipexole is dependent on renal function. The following dose schedule is 
suggested:

Patients with a creatinine clearance above 50 ml/min require no reduction in daily dose or dosing 
frequency.

In patients with a creatinine clearance between 30 and 50 ml/min, treatment should be started with 
0.26 mg Oprymea prolonged-release tablets every other day. Caution should be exercised and careful 
assessment of therapeutic response and tolerability should be made before increasing to daily dosing 
after one week. If a further dose increase is necessary, doses should be increased by 0.26 mg 
pramipexole base at weekly intervals up to a maximum dose of 1.57 mg pramipexole base (2.25 mg of 
salt) per day.

The treatment of patients with a creatinine clearance below 30 ml/min with Oprymea prolonged-
release tablets is not recommended as no data are available for this patient population. The use of 
Oprymea tablets should be considered.

If renal function declines during maintenance therapy, the recommendations given above should be 
followed.

Hepatic impairment
Dose adjustment in patients with hepatic failure is probably not necessary, as approx. 90% of absorbed 
active substance is excreted through the kidneys. However, the potential influence of hepatic 
insufficiency on Oprymea pharmacokinetics has not been investigated.

Paediatric population
The safety and efficacy of Oprymea in children below 18 years has not been established. There is no 
relevant use of Oprymea prolonged-release tablets in the paediatric population for the indication of 
Parkinson’s Disease.



19

Method of administration
The tablets should be swallowed whole with water, and must not be chewed, divided or crushed. The 
tablets may be taken either with or without food and should be taken each day at about the same time.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

When prescribing Oprymea in a patient with Parkinson’s disease with renal impairment a reduced 
dose is suggested in line with section 4.2.

Hallucinations
Hallucinations are known as a side effect of treatment with dopamine agonists and levodopa. Patients 
should be informed that (mostly visual) hallucinations can occur.

Dyskinesia
In advanced Parkinson’s disease, in combination treatment with levodopa, dyskinesia can occur during 
the initial titration of Oprymea. If they occur, the dose of levodopa should be decreased.

Dystonia 
Axial dystonia including antecollis, camptocormia and pleurothotonus (Pisa Syndrome) has 
occasionally been reported in patients with Parkinson’s disease following initiation or incremental 
dose increase of pramipexole. Although dystonia may be a symptom of Parkinson’s disease, the 
symptoms in these patients have improved after reduction or withdrawal of pramipexole. If dystonia 
occurs, the dopaminergic medication regimen should be reviewed and an adjustment in the dose of 
pramipexole considered.

Sudden onset of sleep and somnolence
Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in 
patients with Parkinson’s disease. Sudden onset of sleep during daily activities, in some cases without 
awareness or warning signs, has been reported uncommonly. Patients must be informed of this and 
advised to exercise caution while driving or operating machines during treatment with Oprymea. 
Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from 
driving or operating machines. Furthermore a reduction of the dose or termination of therapy may be 
considered. Because of possible additive effects, caution should be advised when patients are taking 
other sedating medicinal products or alcohol in combination with pramipexole (see sections 4.5, 4.7 
and section 4.8).

Impulse control disorders
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 including Oprymea. Dose 
reduction/tapered discontinuation should be considered if such symptoms develop.

Mania and delirium
Patients should be regularly monitored for the development of mania and delirium. Patients and carers 
should be made aware that mania and delirium can occur in patients treated with pramipexole. Dose 
reduction/tapered discontinuation should be considered if such symptoms develop.

Patients with psychotic disorders
Patients with psychotic disorders should only be treated with dopamine agonists if the potential 
benefits outweigh the risks. Co-administration of antipsychotic medicinal products with pramipexole 
should be avoided (see section 4.5).



20

Ophthalmologic monitoring
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.

Severe cardiovascular disease
In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood 
pressure, especially at the beginning of treatment, due to the general risk of postural hypotension 
associated with dopaminergic therapy.

Neuroleptic malignant syndrome
Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal 
of dopaminergic therapy (see section 4.2).

Dopamine agonist withdrawal syndrome (DAWS)
DAWS has been reported with dopamine agonists, including pramipexole (see section 4.8). To 
discontinue treatment in patients with Parkinson’s disease, pramipexole should be tapered off (see 
section 4.2). Limited data suggests that patients with impulse control disorders and those receiving 
high daily dose and/or high cumulative doses of dopamine agonists may be at higher risk for 
developing DAWS. Withdrawal symptoms may include apathy, anxiety, depression, fatigue, sweating 
and pain and do not respond to levodopa. Prior to tapering off and discontinuing pramipexole, patients 
should be informed about potential withdrawal symptoms. Patients should be closely monitored during 
tapering and discontinuation. In case of severe and/or persistent withdrawal symptoms, temporary re-
administration of pramipexole at the lowest effective dose may be considered.

Remnants in stool 
Some patients have reported the occurrence of remnants in faeces which may resemble intact Oprymea 
prolonged-release tablets. If patients report such an observation, the physician should reassess 
patient’s response to therapy.

4.5 Interaction with other medicinal products and other forms of interaction

Plasma protein binding
Pramipexole is bound to plasma proteins to a very low (< 20%) extent, and little biotransformation is 
seen in man. Therefore, interactions with other medicinal products affecting plasma protein binding or 
elimination by biotransformation are unlikely. As anticholinergics are mainly eliminated by 
biotransformation, the potential for an interaction is limited, although an interaction with 
anticholinergics has not been investigated. There is no pharmacokinetic interaction with selegiline and 
levodopa.

Inhibitors/competitors of active renal elimination pathway
Cimetidine reduced the renal clearance of pramipexole by approximately 34%, presumably by 
inhibition of the cationic secretory transport system of the renal tubules. Therefore, medicinal products 
that are inhibitors of this active renal elimination pathway or are eliminated by this pathway, such as 
cimetidine, amantadine, mexiletine, zidovudine, cisplatin, quinine, and procainamide, may interact 
with pramipexole resulting in reduced clearance of pramipexole. Reduction of the pramipexole dose 
should be considered when these medicinal products are administered concomitantly with Oprymea.

Combination with levodopa
When Oprymea is given in combination with levodopa, it is recommended that the dose of levodopa is 
reduced and the dose of other anti-parkinsonian medicinal products is kept constant while increasing 
the dose of Oprymea.

Because of possible additive effects, caution should be advised when patients are taking other sedating 
medicinal products or alcohol in combination with pramipexole (see sections 4.4, 4.7 and 4.8).

Antipsychotic medicinal products
Co-administration of antipsychotic medicinal products with pramipexole should be avoided (see 



21

section 4.4), e.g. if antagonistic effects can be expected.

4.6 Fertility, pregnancy and lactation

Pregnancy
The effect on pregnancy and lactation has not been investigated in humans. Pramipexole was not 
teratogenic in rats and rabbits, but was embryotoxic in the rat at maternotoxic doses (see section 5.3). 
Oprymea should not be used during pregnancy unless clearly necessary, i.e. if the potential benefit 
justifies the potential risk to the foetus.

Breast-feeding
As pramipexole treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected. 
The excretion of pramipexole into breast milk has not been studied in women. In rats, the 
concentration of active substance-related radioactivity was higher in breast milk than in plasma.
In the absence of human data, Oprymea should not be used during breast-feeding. However, if its use 
is unavoidable, breast-feeding should be discontinued.

Fertility
No studies on the effect on human fertility have been conducted. In animal studies, pramipexole 
affected oestrous cycles and reduced female fertility as expected for a dopamine agonist. However, 
these studies did not indicate direct or indirect harmful effects with respect to male fertility.

4.7 Effects on ability to drive and use machines

Oprymea can have a major influence on the ability to drive and use machines.

Hallucinations or somnolence can occur.

Patients being treated with Oprymea and presenting with somnolence and/or sudden sleep episodes 
must be informed 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 and somnolence have resolved (see also sections 4.4, 4.5 and 4.8).

4.8 Undesirable effects

Based on the analysis of pooled placebo-controlled trials, comprising a total of 1,778 Parkinson’s 
disease patients on pramipexole and 1,297 patients on placebo, adverse drug reactions were frequently 
reported for both groups. 67% of patients on pramipexole and 54% of patients on placebo reported at 
least one adverse drug reaction.

The majority of adverse drug reactions usually start early in therapy and most tend to disappear even 
as therapy is continued.

Within the system organ classes, adverse reactions are listed under headings of frequency (number of 
patients expected to experience the reaction), using the following categories: 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).

The most commonly (≥ 5%) reported adverse drug reactions in patients with Parkinson’s disease more 
frequent with pramipexole treatment than with placebo were nausea, dyskinesia, hypotension, 
dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue. The incidence of 
somnolence is increased at doses higher than 1.5 mg pramipexole salt per day (see section 4.2). A 
more frequent adverse drug reaction in combination with levodopa was dyskinesia. Hypotension may 
occur at the beginning of treatment, especially if pramipexole is titrated too fast.



22

Body System 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)

Not known

Infections and 
infestations

pneumonia

Endocrine 
disorders

inappropriate 
antidiuretic
hormone secretion1

Psychiatric 
disorders

Insomnia
hallucinations
abnormal dreams 
confusion 

behavioural 
symptoms of 
impulse control 
disorders and 
compulsions 

compulsive shopping 
pathological 
gambling
restlessness
hypersexuality
delusion
libido disorder
paranoia
delirium
binge eating1

hyperphagia1

mania

Nervous 
system 
disorders

somnolence
dizziness 
dyskinesia 

headache sudden onset of 
sleep
amnesia
hyperkinesia
syncope

Eye disorders visual 
impairment 
including 
diplopia vision 
blurred 
visual acuity 
reduced

Cardiac 
disorders

cardiac failure1

Vascular 
disorders

hypotension

Respiratory, 
thoracic, and 
mediastinal 
disorders

Dyspnoea
hiccups

Gastrointestinal 
disorders

nausea constipation
vomiting

Skin and 
subcutaneous 
tissue disorders

hypersensitivity 
pruritus
rash

General 
disorders and 
administration 
site conditions

fatigue
peripheral 
oedema

Dopamine 
agonist 
withdrawal 
syndrome 
including 
apathy, 
anxiety, 
depression, 
fatigue, 
sweating 
and pain.

Investigations weight decrease weight increase



23

including 
decreased 
appetite

1 This side effect has been observed in post-marketing experience. With 95 % certainty, the 
frequency category is not greater than uncommon, but might be lower. A precise frequency 
estimation is not possible as the side effect did not occur in a clinical trial database of 2,762 
patients with Parkinson’s Disease treated with pramipexole.

Description of selected adverse reactions

Somnolence
Pramipexole is commonly associated with somnolence and has been associated uncommonly with 
excessive daytime somnolence and sudden sleep onset episodes (see also section 4.4).

Libido disorders
Pramipexole may uncommonly be associated with libido disorders (increased or decreased).

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 including Oprymea (see 
section 4.4).

In a cross-sectional, retrospective screening and case-control study including 3,090 Parkinson’s 
disease patients, 13.6% of all patients receiving dopaminergic or non-dopaminergic treatment had 
symptoms of an impulse control disorder during the past six months. Manifestations observed include 
pathological gambling, compulsive shopping, binge eating, and compulsive sexual behaviour 
(hypersexuality). Possible independent risk factors for impulse control disorders included 
dopaminergic treatments and higher doses of dopaminergic treatment, younger age (≤ 65 years), not 
being married and self-reported family history of gambling behaviours.

Dopamine agonist withdrawal syndrome
Non-motor adverse effects may occur when tapering or discontinuing dopamine agonists including 
pramipexole. Symptoms include apathy, anxiety, depression, fatigue, sweating and pain (see section 
4.4).

Cardiac failure
In clinical studies and post-marketing experience cardiac failure has been reported in patients with 
pramipexole. In a pharmacoepidemiological study pramipexole use was associated with an increased 
risk of cardiac failure compared with non-use of pramipexole (observed risk ratio 1.86; 95% CI, 1.21-
2.85).

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

Symptoms
There is no clinical experience with massive overdose. The expected adverse reactions would be those 
related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, 
hyperkinesia, hallucinations, agitation and hypotension. 

Management
There is no established antidote for overdose of a dopamine agonist. If signs of central nervous system 



24

stimulation are present, a neuroleptic agent may be indicated. Management of the overdose may 
require general supportive measures, along with gastric lavage, intravenous fluids, administration of 
activated charcoal and electrocardiogram monitoring.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: anti-Parkinson drugs, dopamine agonists, ATC code: N04BC05.

Mechanism of action
Pramipexole is a dopamine agonist that binds with high selectivity and specificity to the D2 subfamily 
of dopamine receptors of which it has a preferential affinity to D3 receptors, and has full intrinsic 
activity.

Pramipexole alleviates parkinsonian motor deficits by stimulation of dopamine receptors in the 
striatum. Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and 
turnover.

Pharmacodynamic effects
In human volunteers, a dose-dependent decrease in prolactin was observed. In a clinical trial with 
healthy volunteers, where pramipexole prolonged-release tablets were titrated faster (every 3 days) 
than recommended up to 3.15 mg pramipexole base (4.5 mg of salt) per day, an increase in blood 
pressure and heart rate was observed. Such effect was not observed in patient studies.

Clinical efficacy and safety in Parkinson’s disease
In patients pramipexole alleviates signs and symptoms of idiopathic Parkinson’s disease. Placebo-
controlled clinical trials included approximately 1,800 patients of Hoehn and Yahr stages I – V treated 
with pramipexole. Out of these, approximately 1,000 were in more advanced stages, received 
concomitant levodopa therapy, and suffered from motor complications.

In early and advanced Parkinson’s disease, efficacy of pramipexole in controlled clinical trials was 
maintained for approximately six months. In open continuation trials lasting for more than three years 
there were no signs of decreasing efficacy.

In a controlled double blind clinical trial of 2 year duration, initial treatment with pramipexole 
significantly delayed the onset of motor complications, and reduced their occurrence compared to 
initial treatment with levodopa. This delay in motor complications with pramipexole should be 
balanced against a greater improvement in motor function with levodopa (as measured by the mean 
change in UPDRS-score). The overall incidence of hallucinations and somnolence was generally 
higher in the escalation phase with the pramipexole group. However, there was no significant 
difference during the maintenance phase. These points should be considered when initiating 
pramipexole treatment in patients with Parkinson’s disease.

The safety and efficacy of pramipexole prolonged-release tablets in the treatment of Parkinson's 
disease was evaluated in a multinational drug development program consisting of three randomised, 
controlled trials. Two trials were conducted in patients with early Parkinson's disease and one trial was 
conducted in patients with advanced Parkinson's disease.

Superiority of pramipexole prolonged-release tablets over placebo was demonstrated after 18 weeks of 
treatment on both the primary (UPDRS Parts II+III score) and the key secondary (CGI-I and PGI-I 
responder rates) efficacy endpoints in a double-blind placebo-controlled trial including a total of 539 
patients with early Parkinson’s disease. Maintenance of efficacy was shown in patients treated for 
33 weeks. Pramipexole prolonged-release tablets were non-inferior to pramipexole immediate release 
tablets as assessed on the UPDRS Parts II+III score at week 33.



25

In a double-blind placebo-controlled trial including a total of 517 patients with advanced Parkinson’s 
disease who were on concomitant levodopa therapy superiority of pramipexole prolonged-release 
tablets over placebo was demonstrated after 18 weeks of treatment on both the primary (UPDRS Parts 
II+III score) and the key secondary (off-time) efficacy endpoints.

The efficacy and tolerability of an overnight switch from pramipexole tablets to pramipexole 
prolonged-release tablets at the same daily dose were evaluated in a double-blind clinical study in 
patients with early Parkinson’s disease.
Efficacy was maintained in 87 of 103 patients switched to pramipexole prolonged-release tablets. Out 
of these 87 patients, 82.8% did not change their dose, 13.8% increased and 3.4% decreased their dose.
In half of the 16 patients who did not meet the criterion for maintained efficacy on UPDRS Part II+III 
score, the change from baseline was considered not clinically relevant.
Only one patient switched to pramipexole prolonged-release tablets experienced a drug-related 
adverse event leading to withdrawal.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with 
pramipexole in all subsets of the paediatric population in Parkinson’s Disease (see section 4.2 for 
information on paediatric use).

5.2 Pharmacokinetic properties

Absorption
Pramipexole is completely absorbed following oral administration. The absolute bioavailability is 
greater than 90%.

In a Phase I trial, where pramipexole immediate release and prolonged-release tablets were assessed in 
fasted state, the minimum and peak plasma concentration (Cmin, Cmax) and exposure (AUC) of the same 
daily dose of pramipexole prolonged-release tablets given once daily and pramipexole tablets given 
three times a day were equivalent.

The once daily administration of pramipexole prolonged-release tablets causes less frequent 
fluctuations in the pramipexole plasma concentration over 24 hours compared to the three times daily 
administration of pramipexole immediate release tablets.

The maximum plasma concentrations occur at about 6 hours after administration of pramipexole 
prolonged-release tablets once daily. Steady state of exposure is reached at the latest after 5 days of 
continuous dosing.

Concomitant administration with food does generally not affect the bioavailability of pramipexole. 
Intake of a high fat meal induced an increase in peak concentration (Cmax) of about 24% after a single 
dose administration and about 20% after multiple dose administrations and a delay of about 2 hours in 
time to reach peak concentration in healthy volunteers. Total exposure (AUC) was not affected by 
concomitant food intake. The increase in Cmax is not considered clinically relevant. In the Phase III 
studies that established safety and efficacy of pramipexole prolonged-release tablets, patients were 
instructed to take study medication without regard to food intake.

While body weight has no impact on the AUC, it was found to influence the volume of distribution 
and therefore the peak concentrations Cmax. A decreased body weight by 30 kg results in an increase in 
Cmax of 45%. However, in Phase III trials in Parkinson’s disease patients no clinically meaningful 
influence of body weight on the therapeutic effect and tolerability of pramipexole prolonged-release 
tablets was detected.

Pramipexole shows linear kinetics and a small inter-patient variation of plasma levels.

Distribution
In humans, the protein binding of pramipexole is very low (< 20%) and the volume of distribution is 



26

large (400 l). High brain tissue concentrations were observed in the rat (approx. 8-fold compared to 
plasma).

Biotransformation
Pramipexole is metabolised in man only to a small extent.

Elimination
Renal excretion of unchanged pramipexole is the major route of elimination. Approximately 90% of 
14C-labelled dose is excreted through the kidneys while less than 2% is found in the faeces. The total 
clearance of pramipexole is approximately 500 ml/min and the renal clearance is approximately 
400 ml/min. The elimination half-life (t½) varies from 8 hours in the young to 12 hours in the elderly.

5.3 Preclinical safety data

Repeated dose toxicity studies showed that pramipexole exerted functional effects, mainly involving 
the CNS and female reproductive system, and probably resulting from an exaggerated 
pharmacodynamic effect of pramipexole.

Decreases in diastolic and systolic pressure and heart rate were noted in the minipig, and a tendency to 
a hypotensive effect was discerned in the monkey.

The potential effects of pramipexole on reproductive function have been investigated in rats and 
rabbits. Pramipexole was not teratogenic in rats and rabbits but was embryotoxic in the rat at 
maternally toxic doses. Due to the selection of animal species and the limited parameters investigated, 
the adverse effects of pramipexole on pregnancy and male fertility have not been fully elucidated.

A delay in sexual development (i.e., preputial separation and vaginal opening) was observed in rats. 
The relevance for humans is unknown.

Pramipexole was not genotoxic. In a carcinogenicity study, male rats developed Leydig cell 
hyperplasia and adenomas, explained by the prolactin-inhibiting effect of pramipexole. This finding is 
not clinically relevant to man. The same study also showed that, at doses of 2 mg/kg (of salt) and 
higher, pramipexole was associated with retinal degeneration in albino rats. The latter finding was not 
observed in pigmented rats, nor in a 2-year albino mouse carcinogenicity study or in any other species 
investigated.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Hypromellose
Maize starch
Silica, colloidal anhydrous
Magnesium stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store in the original package in order to protect from moisture.



27

This medicinal product does not require any special temperature storage conditions.

6.5 Nature and contents of container

Blister (OPA/Alu/desiccant/PE-Alu foil): 10, 30, 90 or 100 prolonged-release tablets, in a box.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

8. MARKETING AUTHORISATION NUMBER(S)

Oprymea 0.26 mg prolonged-release tablets
10 prolonged-release tablets: EU/1/08/469/026
30 prolonged-release tablets: EU/1/08/469/027
90 prolonged-release tablets: EU/1/08/469/028
100 prolonged-release tablets: EU/1/08/469/029

Oprymea 0.52 mg prolonged-release tablets
10 prolonged-release tablets: EU/1/08/469/030
30 prolonged-release tablets: EU/1/08/469/031
90 prolonged-release tablets: EU/1/08/469/032
100 prolonged-release tablets: EU/1/08/469/033

Oprymea 1.05 mg prolonged-release tablets
10 prolonged-release tablets: EU/1/08/469/034
30 prolonged-release tablets: EU/1/08/469/035
90 prolonged-release tablets: EU/1/08/469/036
100 prolonged-release tablets: EU/1/08/469/037

Oprymea 1.57 mg prolonged-release tablets
10 prolonged-release tablets: EU/1/08/469/038
30 prolonged-release tablets: EU/1/08/469/039
90 prolonged-release tablets: EU/1/08/469/040
100 prolonged-release tablets: EU/1/08/469/041

Oprymea 2.1 mg prolonged-release tablets
10 prolonged-release tablets: EU/1/08/469/042
30 prolonged-release tablets: EU/1/08/469/043
90 prolonged-release tablets: EU/1/08/469/044
100 prolonged-release tablets: EU/1/08/469/045

Oprymea 2.62 mg prolonged-release tablets
10 prolonged-release tablets: EU/1/08/469/046
30 prolonged-release tablets: EU/1/08/469/047
90 prolonged-release tablets: EU/1/08/469/048
100 prolonged-release tablets: EU/1/08/469/049



28

Oprymea 3.15 mg prolonged-release tablets
10 prolonged-release tablets: EU/1/08/469/050
30 prolonged-release tablets: EU/1/08/469/051
90 prolonged-release tablets: EU/1/08/469/052
100 prolonged-release tablets: EU/1/08/469/053

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 12 September 2008
Date of latest renewal: 9 April 2013

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.



29

1. NAME OF THE MEDICINAL PRODUCT

Treatment initiation pack 
Oprymea 0.26 mg prolonged-release tablets
Oprymea 0.52 mg prolonged-release tablets
Oprymea 1.05 mg prolonged-release tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Oprymea 0.26 mg prolonged-release tablets
Each prolonged-release tablet contains 0.26 mg pramipexole (as 0.375 mg pramipexole 
dihydrochloride monohydrate).

Oprymea 0.52 mg prolonged-release tablets 
Each prolonged-release tablet contains 0.52 mg pramipexole (as 0.75 mg pramipexole dihydrochloride 
monohydrate).

Oprymea 1.05 mg prolonged-release tablets 
Each prolonged-release tablet contains 1.05 mg pramipexole (as 1.5 mg pramipexole dihydrochloride 
monohydrate).

Please note:
Pramipexole doses as published in the literature refer to the salt form.
Therefore, doses will be expressed in terms of both pramipexole base and pramipexole salt (in 
brackets).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Prolonged-release tablet

0.26 mg: White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P1 
on one side, with bevelled edges and possible spots.
0.52 mg: White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P2 
on one side, with bevelled edges and possible spots.
1.05 mg: White or almost white, round (diameter 10 mm), slightly biconvex tablets engraved with P3 
on one side, with bevelled edges and possible spots.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Oprymea is indicated in adults for treatment of the signs and symptoms of idiopathic Parkinson’s 
disease, alone (without levodopa) or in combination with levodopa, i.e. over the course of the disease, 
through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations 
of the therapeutic effect occur (end of dose or "on off" fluctuations).

4.2 Posology and method of administration

Posology

Oprymea prolonged-release tablets are a once-a-day oral formulation of pramipexole.



30

Initial treatment
Doses should be increased gradually from a starting dose of 0.26 mg of base (0.375 mg of salt) per day 
and then increased every 5 - 7 days. Providing patients do not experience intolerable undesirable 
effects, the dose should be titrated to achieve a maximal therapeutic effect.

Ascending dose schedule of Oprymea prolonged-release tablets
Week Daily dose (mg of base) Daily dose (mg of salt)
1 0.26 0.375
2 0.52 0.75
3 1.05 1.5

If a further dose increase is necessary the daily dose should be increased by 0.52 mg of base (0.75 mg 
of salt) at weekly intervals up to a maximum dose of 3.15 mg of base (4.5 mg of salt) per day. 
However, it should be noted that the incidence of somnolence is increased at doses higher than 
1.05 mg of base (1.5 mg of salt) per day (see section 4.8).

Patients already taking Oprymea tablets may be switched to Oprymea prolonged-release tablets 
overnight, at the same daily dose. After switching to Oprymea prolonged-release tablets, the dose may 
be adjusted depending on the patient’s therapeutic response (see section 5.1).

Maintenance treatment
The individual dose of pramipexole should be in the range of 0.26 mg of base (0.375 mg of salt) to a 
maximum of 3.15 mg of base (4.5 mg of salt) per day. During dose escalation in pivotal studies, 
efficacy was observed starting at a daily dose of 1.05 mg of base (1.5 mg of salt). Further dose 
adjustments should be done based on the clinical response and the occurrence of adverse reactions. In 
clinical trials approximately 5% of patients were treated at doses below 1.05 mg of base (1.5 mg of 
salt). In advanced Parkinson’s disease, pramipexole doses higher than 1.05 mg of base (1.5 mg of salt) 
per day can be useful in patients where a reduction of the levodopa therapy is intended. It is 
recommended that the dose of levodopa is reduced during both the dose escalation and the
maintenance treatment with Oprymea, depending on reactions in individual patients (see section 4.5).

Missed dose
When the intake of a dose is missed, Oprymea prolonged-release tablets should be taken within 12 
hours after the regularly scheduled time. After 12 hours, the missed dose should be left out and the 
next dose should be taken on the following day at the next regularly scheduled time.

Treatment discontinuation
Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic 
malignant syndrome or a dopamine agonist withdrawal syndrome. Pramipexole should be tapered off 
at a rate of 0.52 mg of base (0.75 mg of salt) per day until the daily dose has been reduced to 0.52 mg 
of base (0.75 mg of salt). Thereafter the dose should be reduced by 0.26 mg of base (0.375 mg of salt) 
per day (see section 4.4). Dopamine agonist withdrawal syndrome could still appear while tapering 
and a temporary increase of the dose could be necessary before resuming tapering (see section 4.4).

Renal impairment
The elimination of pramipexole is dependent on renal function. The following dose schedule is 
suggested:

Patients with a creatinine clearance above 50 ml/min require no reduction in daily dose or dosing 
frequency.

In patients with a creatinine clearance between 30 and 50 ml/min, treatment should be started with 
0.26 mg Oprymea prolonged-release tablets every other day. Caution should be exercised and careful 
assessment of therapeutic response and tolerability should be made before increasing to daily dosing 
after one week. If a further dose increase is necessary, doses should be increased by 0.26 mg 
pramipexole base at weekly intervals up to a maximum dose of 1.57 mg pramipexole base (2.25 mg of 
salt) per day.



31

The treatment of patients with a creatinine clearance below 30 ml/min with Oprymea prolonged-
release tablets is not recommended as no data are available for this patient population. The use of 
Oprymea tablets should be considered.

If renal function declines during maintenance therapy, the recommendations given above should be 
followed.

Hepatic impairment
Dose adjustment in patients with hepatic failure is probably not necessary, as approx. 90% of absorbed 
active substance is excreted through the kidneys. However, the potential influence of hepatic 
insufficiency on Oprymea pharmacokinetics has not been investigated.

Paediatric population
The safety and efficacy of Oprymea in children below 18 years has not been established. There is no 
relevant use of Oprymea prolonged-release tablets in the paediatric population for the indication of 
Parkinson’s Disease.

Method of administration
The tablets should be swallowed whole with water, and must not be chewed, divided or crushed. The 
tablets may be taken either with or without food and should be taken each day at about the same time.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

When prescribing Oprymea in a patient with Parkinson’s disease with renal impairment a reduced 
dose is suggested in line with section 4.2.

Hallucinations
Hallucinations are known as a side effect of treatment with dopamine agonists and levodopa. Patients 
should be informed that (mostly visual) hallucinations can occur.

Dyskinesia
In advanced Parkinson’s disease, in combination treatment with levodopa, dyskinesia can occur during 
the initial titration of Oprymea. If they occur, the dose of levodopa should be decreased.

Dystonia 
Axial dystonia including antecollis, camptocormia and pleurothotonus (Pisa Syndrome) has 
occasionally been reported in patients with Parkinson’s disease following initiation or incremental 
dose increase of pramipexole. Although dystonia may be a symptom of Parkinson’s disease, the 
symptoms in these patients have improved after reduction or withdrawal of pramipexole. If dystonia 
occurs, the dopaminergic medication regimen should be reviewed and an adjustment in the dose of 
pramipexole considered.

Sudden onset of sleep and somnolence
Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in 
patients with Parkinson’s disease. Sudden onset of sleep during daily activities, in some cases without 
awareness or warning signs, has been reported uncommonly. Patients must be informed of this and 
advised to exercise caution while driving or operating machines during treatment with Oprymea. 
Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from 
driving or operating machines. Furthermore a reduction of the dose or termination of therapy may be 
considered. Because of possible additive effects, caution should be advised when patients are taking 
other sedating medicinal products or alcohol in combination with pramipexole (see sections 4.5, 4.7 
and section 4.8).



32

Impulse control disorders
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 including Oprymea. Dose 
reduction/tapered discontinuation should be considered if such symptoms develop.

Mania and delirium
Patients should be regularly monitored for the development of mania and delirium. Patients and carers 
should be made aware that mania and delirium can occur in patients treated with pramipexole. Dose 
reduction/tapered discontinuation should be considered if such symptoms develop.

Patients with psychotic disorders
Patients with psychotic disorders should only be treated with dopamine agonists if the potential 
benefits outweigh the risks. Co-administration of antipsychotic medicinal products with pramipexole 
should be avoided (see section 4.5).

Ophthalmologic monitoring
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.

Severe cardiovascular disease
In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood 
pressure, especially at the beginning of treatment, due to the general risk of postural hypotension 
associated with dopaminergic therapy.

Neuroleptic malignant syndrome
Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal 
of dopaminergic therapy (see section 4.2).

Dopamine agonist withdrawal syndrome (DAWS)
DAWS has been reported with dopamine agonists, including pramipexole (see section 4.8). To 
discontinue treatment in patients with Parkinson’s disease, pramipexole should be tapered off (see 
section 4.2). Limited data suggests that patients with impulse control disorders and those receiving 
high daily dose and/or high cumulative doses of dopamine agonists may be at higher risk for 
developing DAWS. Withdrawal symptoms may include apathy, anxiety, depression, fatigue, sweating 
and pain and do not respond to levodopa. Prior to tapering off and discontinuing pramipexole, patients 
should be informed about potential withdrawal symptoms. Patients should be closely monitored during 
tapering and discontinuation. In case of severe and/or persistent withdrawal symptoms, temporary re-
administration of pramipexole at the lowest effective dose may be considered.

Remnants in stool 
Some patients have reported the occurrence of remnants in faeces which may resemble intact Oprymea 
prolonged-release tablets. If patients report such an observation, the physician should reassess 
patient’s response to therapy.

4.5 Interaction with other medicinal products and other forms of interaction

Plasma protein binding
Pramipexole is bound to plasma proteins to a very low (< 20%) extent, and little biotransformation is 
seen in man. Therefore, interactions with other medicinal products affecting plasma protein binding or 
elimination by biotransformation are unlikely. As anticholinergics are mainly eliminated by 
biotransformation, the potential for an interaction is limited, although an interaction with 
anticholinergics has not been investigated. There is no pharmacokinetic interaction with selegiline and 
levodopa.

Inhibitors/competitors of active renal elimination pathway



33

Cimetidine reduced the renal clearance of pramipexole by approximately 34%, presumably by 
inhibition of the cationic secretory transport system of the renal tubules. Therefore, medicinal products 
that are inhibitors of this active renal elimination pathway or are eliminated by this pathway, such as 
cimetidine, amantadine, mexiletine, zidovudine, cisplatin, quinine, and procainamide, may interact 
with pramipexole resulting in reduced clearance of pramipexole. Reduction of the pramipexole dose 
should be considered when these medicinal products are administered concomitantly with Oprymea.

Combination with levodopa
When Oprymea is given in combination with levodopa, it is recommended that the dose of levodopa is 
reduced and the dose of other anti-parkinsonian medicinal products is kept constant while increasing 
the dose of Oprymea.

Because of possible additive effects, caution should be advised when patients are taking other sedating 
medicinal products or alcohol in combination with pramipexole (see sections 4.4, 4.7 and 4.8).

Antipsychotic medicinal products
Co-administration of antipsychotic medicinal products with pramipexole should be avoided (see 
section 4.4), e.g. if antagonistic effects can be expected.

4.6 Fertility, pregnancy and lactation

Pregnancy
The effect on pregnancy and lactation has not been investigated in humans. Pramipexole was not 
teratogenic in rats and rabbits, but was embryotoxic in the rat at maternotoxic doses (see section 5.3). 
Oprymea should not be used during pregnancy unless clearly necessary, i.e. if the potential benefit 
justifies the potential risk to the foetus.

Breast-feeding
As pramipexole treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected. 
The excretion of pramipexole into breast milk has not been studied in women. In rats, the 
concentration of active substance-related radioactivity was higher in breast milk than in plasma.
In the absence of human data, Oprymea should not be used during breast-feeding. However, if its use 
is unavoidable, breast-feeding should be discontinued.

Fertility
No studies on the effect on human fertility have been conducted. In animal studies, pramipexole 
affected oestrous cycles and reduced female fertility as expected for a dopamine agonist. However, 
these studies did not indicate direct or indirect harmful effects with respect to male fertility.

4.7 Effects on ability to drive and use machines

Oprymea can have a major influence on the ability to drive and use machines.

Hallucinations or somnolence can occur.

Patients being treated with Oprymea and presenting with somnolence and/or sudden sleep episodes 
must be informed 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 and somnolence have resolved (see also sections 4.4, 4.5 and 4.8).

4.8 Undesirable effects

Based on the analysis of pooled placebo-controlled trials, comprising a total of 1,778 Parkinson’s 
disease patients on pramipexole and 1,297 patients on placebo, adverse drug reactions were frequently 
reported for both groups. 67% of patients on pramipexole and 54% of patients on placebo reported at 
least one adverse drug reaction.



34

The majority of adverse drug reactions usually start early in therapy and most tend to disappear even 
as therapy is continued.

Within the system organ classes, adverse reactions are listed under headings of frequency (number of 
patients expected to experience the reaction), using the following categories: 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).

The most commonly (≥ 5%) reported adverse drug reactions in patients with Parkinson’s disease more 
frequent with pramipexole treatment than with placebo were nausea, dyskinesia, hypotension, 
dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue. The incidence of 
somnolence is increased at doses higher than 1.5 mg pramipexole salt per day (see section 4.2). A 
more frequent adverse drug reaction in combination with levodopa was dyskinesia. Hypotension may 
occur at the beginning of treatment, especially if pramipexole is titrated too fast.
Body System 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)

Not known

Infections and 
infestations

pneumonia

Endocrine 
disorders

inappropriate 
antidiuretic
hormone secretion1

Psychiatric 
disorders

Insomnia
hallucinations
abnormal dreams 
confusion 

behavioural 
symptoms of 
impulse control 
disorders and 
compulsions 

compulsive shopping 
pathological 
gambling
restlessness
hypersexuality
delusion
libido disorder
paranoia
delirium
binge eating1

hyperphagia1

mania

Nervous 
system 
disorders

somnolence
dizziness 
dyskinesia 

headache sudden onset of 
sleep
amnesia
hyperkinesia
syncope

Eye disorders visual 
impairment 
including 
diplopia vision 
blurred 
visual acuity 
reduced

Cardiac 
disorders

cardiac failure1

Vascular 
disorders

hypotension

Respiratory, 
thoracic, and 
mediastinal 
disorders

Dyspnoea
hiccups

Gastrointestinal 
disorders

nausea constipation
vomiting

Skin and hypersensitivity 



35

subcutaneous 
tissue disorders

pruritus
rash

General 
disorders and 
administration 
site conditions

fatigue
peripheral 
oedema

Dopamine 
agonist 
withdrawal 
syndrome 
including 
apathy, 
anxiety, 
depression, 
fatigue, 
sweating 
and pain.

Investigations weight decrease 
including 
decreased 
appetite

weight increase

1 This side effect has been observed in post-marketing experience. With 95 % certainty, the 
frequency category is not greater than uncommon, but might be lower. A precise frequency 
estimation is not possible as the side effect did not occur in a clinical trial database of 2,762 
patients with Parkinson’s Disease treated with pramipexole.

Description of selected adverse reactions

Somnolence
Pramipexole is commonly associated with somnolence and has been associated uncommonly with 
excessive daytime somnolence and sudden sleep onset episodes (see also section 4.4).

Libido disorders
Pramipexole may uncommonly be associated with libido disorders (increased or decreased).

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 including Oprymea (see 
section 4.4).

In a cross-sectional, retrospective screening and case-control study including 3,090 Parkinson’s 
disease patients, 13.6% of all patients receiving dopaminergic or non-dopaminergic treatment had 
symptoms of an impulse control disorder during the past six months. Manifestations observed include 
pathological gambling, compulsive shopping, binge eating, and compulsive sexual behaviour 
(hypersexuality). Possible independent risk factors for impulse control disorders included 
dopaminergic treatments and higher doses of dopaminergic treatment, younger age (≤ 65 years), not 
being married and self-reported family history of gambling behaviours.

Dopamine agonist withdrawal syndrome
Non-motor adverse effects may occur when tapering or discontinuing dopamine agonists including 
pramipexole. Symptoms include apathy, anxiety, depression, fatigue, sweating and pain (see section 
4.4).

Cardiac failure
In clinical studies and post-marketing experience cardiac failure has been reported in patients with 
pramipexole. In a pharmacoepidemiological study pramipexole use was associated with an increased 
risk of cardiac failure compared with non-use of pramipexole (observed risk ratio 1.86; 95% CI, 1.21-
2.85).

Reporting of suspected adverse reactions



36

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

Symptoms
There is no clinical experience with massive overdose. The expected adverse reactions would be those 
related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, 
hyperkinesia, hallucinations, agitation and hypotension. 

Management
There is no established antidote for overdose of a dopamine agonist. If signs of central nervous system 
stimulation are present, a neuroleptic agent may be indicated. Management of the overdose may 
require general supportive measures, along with gastric lavage, intravenous fluids, administration of 
activated charcoal and electrocardiogram monitoring.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: anti-Parkinson drugs, dopamine agonists, ATC code: N04BC05.

Mechanism of action
Pramipexole is a dopamine agonist that binds with high selectivity and specificity to the D2 subfamily 
of dopamine receptors of which it has a preferential affinity to D3 receptors, and has full intrinsic 
activity.

Pramipexole alleviates parkinsonian motor deficits by stimulation of dopamine receptors in the 
striatum. Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and 
turnover.

Pharmacodynamic effects
In human volunteers, a dose-dependent decrease in prolactin was observed. In a clinical trial with 
healthy volunteers, where pramipexole prolonged-release tablets were titrated faster (every 3 days) 
than recommended up to 3.15 mg pramipexole base (4.5 mg of salt) per day, an increase in blood 
pressure and heart rate was observed. Such effect was not observed in patient studies.

Clinical efficacy and safety in Parkinson’s disease
In patients pramipexole alleviates signs and symptoms of idiopathic Parkinson’s disease. Placebo-
controlled clinical trials included approximately 1,800 patients of Hoehn and Yahr stages I – V treated 
with pramipexole. Out of these, approximately 1,000 were in more advanced stages, received 
concomitant levodopa therapy, and suffered from motor complications.

In early and advanced Parkinson’s disease, efficacy of pramipexole in controlled clinical trials was 
maintained for approximately six months. In open continuation trials lasting for more than three years 
there were no signs of decreasing efficacy.

In a controlled double blind clinical trial of 2 year duration, initial treatment with pramipexole 
significantly delayed the onset of motor complications, and reduced their occurrence compared to 
initial treatment with levodopa. This delay in motor complications with pramipexole should be 
balanced against a greater improvement in motor function with levodopa (as measured by the mean 
change in UPDRS-score). The overall incidence of hallucinations and somnolence was generally 
higher in the escalation phase with the pramipexole group. However, there was no significant 
difference during the maintenance phase. These points should be considered when initiating 



37

pramipexole treatment in patients with Parkinson’s disease.

The safety and efficacy of pramipexole prolonged-release tablets in the treatment of Parkinson's 
disease was evaluated in a multinational drug development program consisting of three randomised, 
controlled trials. Two trials were conducted in patients with early Parkinson's disease and one trial was 
conducted in patients with advanced Parkinson's disease.

Superiority of pramipexole prolonged-release tablets over placebo was demonstrated after 18 weeks of 
treatment on both the primary (UPDRS Parts II+III score) and the key secondary (CGI-I and PGI-I 
responder rates) efficacy endpoints in a double-blind placebo-controlled trial including a total of 539 
patients with early Parkinson’s disease. Maintenance of efficacy was shown in patients treated for 
33 weeks. Pramipexole prolonged-release tablets were non-inferior to pramipexole immediate release 
tablets as assessed on the UPDRS Parts II+III score at week 33.

In a double-blind placebo-controlled trial including a total of 517 patients with advanced Parkinson’s 
disease who were on concomitant levodopa therapy superiority of pramipexole prolonged-release 
tablets over placebo was demonstrated after 18 weeks of treatment on both the primary (UPDRS Parts 
II+III score) and the key secondary (off-time) efficacy endpoints.

The efficacy and tolerability of an overnight switch from pramipexole tablets to pramipexole 
prolonged-release tablets at the same daily dose were evaluated in a double-blind clinical study in 
patients with early Parkinson’s disease.
Efficacy was maintained in 87 of 103 patients switched to pramipexole prolonged-release tablets. Out 
of these 87 patients, 82.8% did not change their dose, 13.8% increased and 3.4% decreased their dose.
In half of the 16 patients who did not meet the criterion for maintained efficacy on UPDRS Part II+III 
score, the change from baseline was considered not clinically relevant.
Only one patient switched to pramipexole prolonged-release tablets experienced a drug-related 
adverse event leading to withdrawal.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with 
pramipexole in all subsets of the paediatric population in Parkinson’s Disease (see section 4.2 for 
information on paediatric use).

5.2 Pharmacokinetic properties

Absorption
Pramipexole is completely absorbed following oral administration. The absolute bioavailability is 
greater than 90%.

In a Phase I trial, where pramipexole immediate release and prolonged-release tablets were assessed in 
fasted state, the minimum and peak plasma concentration (Cmin, Cmax) and exposure (AUC) of the same 
daily dose of pramipexole prolonged-release tablets given once daily and pramipexole tablets given 
three times a day were equivalent.

The once daily administration of pramipexole prolonged-release tablets causes less frequent 
fluctuations in the pramipexole plasma concentration over 24 hours compared to the three times daily 
administration of pramipexole immediate release tablets.

The maximum plasma concentrations occur at about 6 hours after administration of pramipexole 
prolonged-release tablets once daily. Steady state of exposure is reached at the latest after 5 days of 
continuous dosing.

Concomitant administration with food does generally not affect the bioavailability of pramipexole. 
Intake of a high fat meal induced an increase in peak concentration (Cmax) of about 24% after a single 
dose administration and about 20% after multiple dose administrations and a delay of about 2 hours in 
time to reach peak concentration in healthy volunteers. Total exposure (AUC) was not affected by 



38

concomitant food intake. The increase in Cmax is not considered clinically relevant. In the Phase III 
studies that established safety and efficacy of pramipexole prolonged-release tablets, patients were 
instructed to take study medication without regard to food intake.

While body weight has no impact on the AUC, it was found to influence the volume of distribution 
and therefore the peak concentrations Cmax. A decreased body weight by 30 kg results in an increase in 
Cmax of 45%. However, in Phase III trials in Parkinson’s disease patients no clinically meaningful 
influence of body weight on the therapeutic effect and tolerability of pramipexole prolonged-release 
tablets was detected.

Pramipexole shows linear kinetics and a small inter-patient variation of plasma levels.

Distribution
In humans, the protein binding of pramipexole is very low (< 20%) and the volume of distribution is 
large (400 l). High brain tissue concentrations were observed in the rat (approx. 8-fold compared to 
plasma).

Biotransformation
Pramipexole is metabolised in man only to a small extent.

Elimination
Renal excretion of unchanged pramipexole is the major route of elimination. Approximately 90% of 
14C-labelled dose is excreted through the kidneys while less than 2% is found in the faeces. The total 
clearance of pramipexole is approximately 500 ml/min and the renal clearance is approximately 
400 ml/min. The elimination half-life (t½) varies from 8 hours in the young to 12 hours in the elderly.

5.3 Preclinical safety data

Repeated dose toxicity studies showed that pramipexole exerted functional effects, mainly involving 
the CNS and female reproductive system, and probably resulting from an exaggerated 
pharmacodynamic effect of pramipexole.

Decreases in diastolic and systolic pressure and heart rate were noted in the minipig, and a tendency to 
a hypotensive effect was discerned in the monkey.

The potential effects of pramipexole on reproductive function have been investigated in rats and 
rabbits. Pramipexole was not teratogenic in rats and rabbits but was embryotoxic in the rat at 
maternally toxic doses. Due to the selection of animal species and the limited parameters investigated, 
the adverse effects of pramipexole on pregnancy and male fertility have not been fully elucidated.

A delay in sexual development (i.e., preputial separation and vaginal opening) was observed in rats. 
The relevance for humans is unknown.

Pramipexole was not genotoxic. In a carcinogenicity study, male rats developed Leydig cell 
hyperplasia and adenomas, explained by the prolactin-inhibiting effect of pramipexole. This finding is 
not clinically relevant to man. The same study also showed that, at doses of 2 mg/kg (of salt) and 
higher, pramipexole was associated with retinal degeneration in albino rats. The latter finding was not 
observed in pigmented rats, nor in a 2-year albino mouse carcinogenicity study or in any other species 
investigated.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Hypromellose
Maize starch



39

Silica, colloidal anhydrous
Magnesium stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Store in the original package in order to protect from moisture.
This medicinal product does not require any special temperature storage conditions.

6.5 Nature and contents of container

3-week treatment initiation pack
Blister (OPA/Alu/desiccant/PE-Alu foil): 21 prolonged-release tablets (3 blisters of 7 tablets):
- 7 prolonged-release tablets of 0.26 mg
- 7 prolonged-release tablets of 0.52 mg
- 7 prolonged-release tablets of 1.05 mg

6.6 Special precautions for disposal

No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

8. MARKETING AUTHORISATION NUMBER(S)

21 prolonged-release tablets: EU/1/08/469/054

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 12 September 2008
Date of latest renewal: 9 April 2013

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.



40

ANNEX II

A. MANUFACTURER(S) 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



41

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

KRKA, d.d., Novo mesto
Šmarješka cesta 6
8501 Novo mesto
Slovenia

TAD Pharma GmbH
Heinz-Lohmann-Straße 5
27472 Cuxhaven
Germany

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 (PSURs)

The requirements for submission of PSURs 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)

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

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.



42

ANNEX III

LABELLING AND PACKAGE LEAFLET



43

A. LABELLING



44

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.088 mg tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 0.088 mg pramipexole (as 0.125 mg pramipexole dihydrochloride monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet

20 tablets
30 tablets
60 tablets
90 tablets
100 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

Store in the original package in order to protect from light.



45

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/001[20 tablets]
EU/1/08/469/002 [30 tablets]
EU/1/08/469/003 [60 tablets]
EU/1/08/469/004 [90 tablets]
EU/1/08/469/005 [100 tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.088 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN-



46

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER/(Alu/Alu)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.088 mg tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



47

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.18 mg tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 0.18 mg pramipexole (as 0.25 mg pramipexole dihydrochloride monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet

20 tablets
30 tablets
60 tablets
90 tablets
100 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

Store in the original package in order to protect from light.



48

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/006 [20 tablets]
EU/1/08/469/007 [30 tablets]
EU/1/08/469/008 [60 tablets]
EU/1/08/469/009 [90 tablets]
EU/1/08/469/010 [100 tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.18 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



49

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER/(Alu/Alu)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.18 mg tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



50

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.35 mg tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 0.35 mg pramipexole (as 0.5 mg pramipexole dihydrochloride monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet

20 tablets
30 tablets
60 tablets
90 tablets
100 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

Store in the original package in order to protect from light.



51

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/011 [20 tablets]
EU/1/08/469/012 [30 tablets]
EU/1/08/469/013 [60 tablets]
EU/1/08/469/014 [90 tablets]
EU/1/08/469/015 [100 tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.35 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



52

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER/(Alu/Alu)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.35 mg tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



53

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.7 mg tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 0.7 mg pramipexole (as 1 mg pramipexole dihydrochloride monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet

20 tablets
30 tablets
60 tablets
90 tablets
100 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

Store in the original package in order to protect from light.



54

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/016 [20 tablets]
EU/1/08/469/017 [30 tablets]
EU/1/08/469/018 [60 tablets]
EU/1/08/469/019 [90 tablets]
EU/1/08/469/020 [100 tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.7 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



55

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER/(Alu/Alu)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.7 mg tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



56

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 1.1 mg tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 1.1 mg pramipexole (as 1.5 mg pramipexole dihydrochloride monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Tablet

20 tablets
30 tablets
60 tablets
90 tablets
100 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

Store in the original package in order to protect from light.



57

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/021 [20 tablets]
EU/1/08/469/022 [30 tablets]
EU/1/08/469/023 [60 tablets]
EU/1/08/469/024 [90 tablets]
EU/1/08/469/025 [100 tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 1.1 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN-



58

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTER/(Alu/Alu)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 1.1 mg tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



59

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.26 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 0.26 mg pramipexole (as 0.375 mg pramipexole 
dihydrochloride monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

10 prolonged-release tablets
30 prolonged-release tablets
90 prolonged-release tablets
100 prolonged-release tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before 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



60

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/026 [10 prolonged-release tablets]
EU/1/08/469/027 [30 prolonged-release tablets]
EU/1/08/469/028 [90 prolonged-release tablets]
EU/1/08/469/029 [100 prolonged-release tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.26 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



61

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.26 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



62

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.52 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 0.52 mg pramipexole (as 0.75 mg pramipexole dihydrochloride 
monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

10 prolonged-release tablets
30 prolonged-release tablets
90 prolonged-release tablets
100 prolonged-release tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before 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



63

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/030 [10 prolonged-release tablets]
EU/1/08/469/031[30 prolonged-release tablets]
EU/1/08/469/032[90 prolonged-release tablets]
EU/1/08/469/033[100 prolonged-release tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.52 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



64

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.52 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



65

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 1.05 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 1.05 mg pramipexole (as 1.5 mg pramipexole dihydrochloride 
monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

10 prolonged-release tablets
30 prolonged-release tablets
90 prolonged-release tablets
100 prolonged-release tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before 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



66

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/034 [10 prolonged-release tablets]
EU/1/08/469/035 [30 prolonged-release tablets]
EU/1/08/469/036 [90 prolonged-release tablets]
EU/1/08/469/037 [100 prolonged-release tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 1.05 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



67

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 1.05 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



68

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 1.57 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 1.57 mg pramipexole (as 2.25 mg pramipexole dihydrochloride 
monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

10 prolonged-release tablets
30 prolonged-release tablets
90 prolonged-release tablets
100 prolonged-release tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before 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



69

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/038 [10 prolonged-release tablets]
EU/1/08/469/039 [30 prolonged-release tablets]
EU/1/08/469/040 [90 prolonged-release tablets]
EU/1/08/469/041 [100 prolonged-release tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 1.57 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



70

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 1.57 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



71

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 2.1 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 2.1 mg pramipexole (as 3 mg pramipexole dihydrochloride 
monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

10 prolonged-release tablets
30 prolonged-release tablets
90 prolonged-release tablets
100 prolonged-release tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before 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



72

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/042 [10 prolonged-release tablets]
EU/1/08/469/043 [30 prolonged-release tablets]
EU/1/08/469/044 [90 prolonged-release tablets]
EU/1/08/469/045 [100 prolonged-release tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 2.1 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



73

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 2.1 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



74

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 2.62 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 2.62 mg pramipexole (as 3.75 mg pramipexole dihydrochloride 
monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

10 prolonged-release tablets
30 prolonged-release tablets
90 prolonged-release tablets
100 prolonged-release tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.



75

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/046 [10 prolonged-release tablets]
EU/1/08/469/047 [30 prolonged-release tablets]
EU/1/08/469/048 [90 prolonged-release tablets]
EU/1/08/469/049 [100 prolonged-release tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 2.62 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

I



76

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 2.62 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



77

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

BOX for blisters

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 3.15 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 3.15 mg pramipexole (as 4.5 mg pramipexole dihydrochloride 
monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

10 prolonged-release tablets
30 prolonged-release tablets
90 prolonged-release tablets
100 prolonged-release tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before 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



78

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/050 [10 prolonged-release tablets]
EU/1/08/469/051 [30 prolonged-release tablets]
EU/1/08/469/052 [90 prolonged-release tablets]
EU/1/08/469/053 [100 prolonged-release tablets]

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 3.15 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



79

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 3.15 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



80

TREATMENT INITIATION PACK ONLY
PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER BOX (treatment initiation pack containing 3 boxes of 7 prolonged-release tablets)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.26 mg
Oprymea 0.52 mg
Oprymea 1.05 mg
prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Oprymea 0.26 mg: Each prolonged-release tablet contains 0.26 mg pramipexole (as 0.375 mg 
pramipexole dihydrochloride monohydrate).
Oprymea 0.52 mg: Each prolonged-release tablet contains 0.52 mg pramipexole (as 0.75 mg 
pramipexole dihydrochloride monohydrate).
Oprymea 1.05 mg: Each prolonged-release tablet contains 1.05 mg pramipexole (as 1.5 mg 
pramipexole dihydrochloride monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

Treatment initiation pack
Each pack of 21 prolonged-release tablets for a 3-week treatment schedule contains:
7 tablets of Oprymea 0.26 mg
7 tablets of Oprymea 0.52 mg
7 tablets of Oprymea 1.05 mg

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before 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



81

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/054

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.26 mg
Oprymea 0.52 mg
Oprymea 1.05 mg
prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN



82

NN.



83

TREATMENT INITIATION PACK ONLY
PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INNER BOX (week 1)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.26 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 0.26 mg pramipexole (as 0.375 mg pramipexole 
dihydrochloride monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

7 prolonged-release tablets
Week 1

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.



84

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/054

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.26 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

Not applicable.



85

TREATMENT INITIATION PACK ONLY
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister (week 1)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.26 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Week 1



86

TREATMENT INITIATION PACK ONLY
PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INNER BOX (week 2)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.52 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 0.52 mg pramipexole (as 0.75 mg pramipexole dihydrochloride 
monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

7 prolonged-release tablets 
Week 2

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.



87

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/054

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 0.52 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

Not applicable.



88

TREATMENT INITIATION PACK ONLY
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister (week 2)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 0.52 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Week 2



89

TREATMENT INITIATION PACK ONLY
PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INNER BOX (week 3)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 1.05 mg prolonged-release tablets
pramipexole

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each prolonged-release tablet contains 1.05 mg pramipexole (as 1.5 mg pramipexole dihydrochloride 
monohydrate).

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged-release tablet

7 prolonged-release tablets
Week 3

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Once daily.
Swallow whole, do not chew, divide or crush.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from moisture.



90

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/08/469/054

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Oprymea 1.05 mg prolonged-release tablets

17. UNIQUE IDENTIFIER – 2D BARCODE

Not applicable.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

Not applicable.



91

TREATMENT INITIATION PACK ONLY
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister (week 3)

1. NAME OF THE MEDICINAL PRODUCT

Oprymea 1.05 mg prolonged-release tablets
pramipexole

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Week 3



92

B. PACKAGE LEAFLET



93

Package leaflet: Information for the patient

Oprymea 0.088 mg tablets
Oprymea 0.18 mg tablets
Oprymea 0.35 mg tablets
Oprymea 0.7 mg tablets
Oprymea 1.1 mg tablets

pramipexole

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

1. What Oprymea is and what it is used for

Oprymea contains the active substance pramipexole and belongs to a group of medicines known as 
dopamine agonists which stimulate dopamine receptors in the brain. Stimulation of the dopamine 
receptors triggers nerve impulses in the brain that help to control body movements.

Oprymea is used to:
- treat the symptoms of primary Parkinson's disease in adults. It can be used alone or in 

combination with levodopa (another medicine for Parkinson’s disease).
- treat the symptoms of moderate to severe primary Restless Legs Syndrome in adults.

2. What you need to know before you take Oprymea

Do not take Oprymea
- if you are allergic to pramipexole or any of the other ingredients of this medicine (listed in 

section 6).

Warnings and precautions
Talk to your doctor before taking Oprymea. Tell your doctor if you have or have had or develop any 
medical conditions or symptoms, especially any of the following:
- Kidney disease
- Hallucinations (seeing, hearing or feeling things that are not there). Most hallucinations are 

visual
- Dyskinesia (e.g. abnormal, uncontrolled movements of the limbs). If you have advanced 

Parkinson’s disease and are also taking levodopa, you might develop dyskinesia during the 
up-titration of Oprymea

- Dystonia (inability of keeping your body and neck straight and upright (axial dystonia)). In 
particular, you may experience forward flexion of the head and neck (also called antecollis), 
forward bending of the lower back (also called camptocormia) or sidewards bending of the back 



94

(also called pleurothotonus or Pisa Syndrome). If this happens, your doctor may want to change 
your medication. 

- Sleepiness and episodes of suddenly falling asleep
- Psychosis (e.g. comparable with symptoms of schizophrenia)
- Vision impairment. You should have regular eye examinations during treatment with Oprymea
- Severe heart or blood vessels disease. You will need to have your blood pressure checked 

regularly, especially at the beginning of treatment. This is to avoid postural hypotension (a fall 
in blood pressure on standing up).

- Augmentation. You may experience that symptoms start earlier than usual, be more intense and 
involve other limbs.

Tell your doctor if you or your family/carer notices that you are developing urges or cravings to 
behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry 
out certain activities that could harm yourself or others. These are called impulse control disorders and 
can include behaviours such as addictive gambling, excessive eating or spending, an abnormally high 
sex drive or preoccupation with an increase in sexual thoughts or feelings. Your doctor may need to 
adjust or stop your dose.

Tell your doctor if you or your family/carer notices that you are developing mania (agitation, feeling 
elated or over-excited) or delirium (decreased awareness, confusion or loss of reality). Your doctor 
may need to adjust or stop your dose.

Tell your doctor if you experience symptoms such as depression, apathy, anxiety, fatigue, sweating or 
pain after stopping or reducing your Oprymea treatment. If the problems persist more than a few 
weeks, your doctor may need to adjust your treatment.

Children and adolescents
Oprymea is not recommended for use in children or adolescents under 18 years.

Other medicines and Oprymea
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This includes medicines, herbal remedies, health foods or supplements that you have 
obtained without a prescription.

You should avoid taking Oprymea together with antipsychotic medicines.

Take care if you are taking the following medicines:
- cimetidine (to treat excess stomach acid and stomach ulcers)
- amantadine (which can be used to treat Parkinson’s disease)
- mexiletine (to treat irregular heartbeats, a condition known as ventricular arrhythmia)
- zidovudine (which can be used to treat the acquired immune deficiency syndrome (AIDS), a 

disease of the human immune system)
- cisplatin (to treat various types of cancers)
- quinine (which can be used for the prevention of painful night-time leg cramps and for the 

treatment of a type of malaria known as falciparum malaria (malignant malaria))
- procainamide (to treat irregular heart beat)

If you are taking levodopa, the dose of levodopa is recommended to be reduced when you start 
treatment with Oprymea.

Take care if you are using any medicines that calm you down (have a sedative effect) or if you are
drinking alcohol. In these cases Oprymea may affect your ability to drive and operate machinery.

Oprymea with food, drink and alcohol
You should be cautious while drinking alcohol during treatment with Oprymea.
Oprymea can be taken with or without food.



95

Pregnancy and 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. Your doctor will then discuss with 
you if you should continue to take Oprymea.

The effect of Oprymea on the unborn child is not known. Therefore, do not take Oprymea if you are 
pregnant unless your doctor tells you to do so.

Oprymea should not be used during breast-feeding. Oprymea can reduce the production of breast milk. 
Also, it can pass into the breast milk and can reach your baby. If use of Oprymea is unavoidable, 
breast-feeding should be stopped.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Oprymea can cause hallucinations (seeing, hearing or feeling things that are not there). If affected, do 
not drive or use machines.
Oprymea has been associated with sleepiness and episodes of suddenly falling asleep, particularly in 
patients with Parkinson’s disease. If you experience these side effects, you must not drive or operate 
machinery. Please tell your doctor if this occurs.

3. How to take Oprymea

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. The doctor will advise you on the right dosing.

You can take Oprymea with or without food. Swallow the tablets with water.

Parkinson’s disease
The daily dose is to be taken divided into 3 equal doses.

During the first week, the usual dose is 1 tablet Oprymea 0.088 mg three times a day (equivalent to 
0.264 mg daily):

1st week
Number of tablets 1 tablet Oprymea 0.088 mg three times a day
Total daily dose (mg) 0.264

This will be increased every 5 – 7 days as directed by your doctor until your symptoms are controlled 
(maintenance dose).

2nd week 3rd week
Number of tablets 1 tablet Oprymea 0.18 mg 

three times a day
OR
2 tablets Oprymea 0.088 mg 
three times a day

1 tablet Oprymea 0.35 mg 
three times a day
OR
2 tablets Oprymea 0.18 mg 
three times a day

Total daily dose (mg) 0.54 1.1

The usual maintenance dose is 1.1 mg per day. However, your dose may have to be increased even 
further. If necessary, your doctor may increase your tablet dose up to a maximum of 3.3 mg of 
pramipexole a day. A lower maintenance dose of three Oprymea 0.088 mg tablets a day is also 
possible.

Lowest maintenance dose Highest maintenance dose
Number of tablets 1 tablet Oprymea 0.088 mg 1 tablet Oprymea 1.1 mg three 



96

three times a day times a day
Total daily dose (mg) 0.264 3.3

Patients with kidney disease
If you have moderate or severe kidney disease, your doctor will prescribe a lower dose. In this case, 
you will have to take the tablets only once or twice a day. If you have moderate kidney disease, the 
usual starting dose is 1 tablet Oprymea 0.088 mg twice a day. In severe kidney disease, the usual 
starting dose is just 1 tablet Oprymea 0.088 mg a day.

Restless Legs Syndrome
The dose is usually taken once a day, in the evening, 2-3 hours before bedtime.

During the first week, the usual dose is 1 tablet Oprymea 0.088 mg once a day (equivalent to 0.088 mg 
daily):

1st week
Number of tablets 1 tablet Oprymea 0.088 mg
Total daily dose (mg) 0.088

This will be increased every 4-7 days as directed by your doctor until your symptoms are controlled 
(maintenance dose).

2nd week 3rd week 4th week
Number of 
tablets

1 tablet Oprymea 0.18 mg
OR
2 tablets Oprymea 
0.088 mg

1 tablet Oprymea 0.35 mg
OR
2 tablets Oprymea
0.18 mg 
OR
4 tablets Oprymea
0.088 mg

1 tablet Oprymea 0.35 mg 
and 1 tablet Oprymea
0.18 mg
OR
3 tablets Oprymea 0.18 mg
OR
6 tablets Oprymea 0.088 mg

Total daily 
dose (mg)

0.18 0.35 0.54

The daily dose should not exceed 6 tablets Oprymea 0.088 mg or a dose of 0.54 mg (0.75 mg 
pramipexole salt).

If you stop taking your tablets for more than a few days and want to restart the treatment, you must 
start again at the lowest dose. You can then build up the dose again, as you did the first time. Ask your 
doctor for advice.

Your doctor will review your treatment after 3 months to decide whether or not to continue the 
treatment.

Patients with kidney disease
If you have severe kidney disease, Oprymea may not be a suitable treatment for you.

If you take more Oprymea than you should
If you accidentally take too many tablets:
- Contact your doctor or nearest hospital casualty department immediately for advice.
- You may experience vomiting, restlessness, or any of the side effects as described in section 4. 

"Possible side effects".

If you forget to take Oprymea
Do not worry. Simply leave out that dose completely and then take your next dose at the right time.
Do not try to make up for the missed dose.

If you stop taking Oprymea



97

Do not stop taking Oprymea without first talking to your doctor. If you have to stop taking this 
medicine, your doctor will reduce the dose gradually. This reduces the risk of worsening symptoms.

If you suffer from Parkinson’s disease you should not stop treatment with Oprymea abruptly. A 
sudden stop could cause you to develop a medical condition called neuroleptic malignant syndrome 
which may represent a major health risk. The symptoms include:
- akinesia (loss of muscle movement)
- rigid muscles
- fever
- unstable blood pressure
- tachycardia (increased heart rate)
- confusion
- depressed level of consciousness (e.g. coma).

If you stop or reduce Oprymea you may also develop a medical condition called dopamine agonist 
withdrawal syndrome. The symptoms include depression, apathy, anxiety, fatigue, sweating or pain. If 
you experience these symptoms you should contact your physician.

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. Evaluation 
of these side effects is based on the following frequencies:

Very common may affect more than 1 in 10 people
Common may affect up to 1 in 10 people
Uncommon may affect up to 1 in 100 people
Rare may affect up to 1 in 1,000 people
Very rare may affect up to 1 in 10,000 people
Not known Frequency cannot be estimated from the available data

If you suffer from Parkinson’s disease, you may experience the following side effects:

Very common:
- Dyskinesia (e.g. abnormal, uncontrolled movements of the limbs)
- Sleepiness
- Dizziness
- Nausea (sickness)

Common:
- Urge to behave in an unusual way
- Hallucinations (seeing, hearing or feeling things that are not there)
- Confusion
- Tiredness (fatigue)
- Sleeplessness (insomnia)
- Excess of fluid, usually in the legs (peripheral oedema)
- Headache
- Hypotension (low blood pressure)
- Abnormal dreams
- Constipation
- Visual impairment
- Vomiting (being sick)
- Weight loss including decreased appetite

Uncommon:



98

- Paranoia (e.g. excessive fear for one’s own well-being)
- Delusion
- Excessive daytime sleepiness and suddenly falling asleep
- Amnesia (memory disturbance)
- Hyperkinesia (increased movements and inability to keep still)
- Weight increase
- Allergic reactions (e.g. rash, itching, hypersensitivity)
- Fainting
- Cardiac failure (heart problems which can cause shortness of breath or ankle swelling)*
- Inappropriate antidiuretic hormone secretion*
- Restlessness
- Dyspnoea (difficulties to breathe)
- Hiccups
- Pneumonia (infection of the lungs)
- Inability to resist the impulse, drive or temptation to perform an action that could be harmful to 

you or others, 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)*
- Delirium (decreased awareness, confusion, loss of reality)

Rare:
- Mania (agitation, feeling elated or over-excited)

Not known:
- After stopping or reducing your Oprymea treatment: Depression, apathy, anxiety, fatigue, 

sweating or pain may occur (called dopamine agonist withdrawal syndrome or DAWS). 

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

For the side effects marked with * a precise frequency estimation is not possible, since these side 
effects were not observed in clinical studies among 2,762 patients treated with pramipexole. The 
frequency category is probably not greater than "uncommon".

If you suffer from Restless Legs Syndrome, you may experience the following side effects:

Very common:
- Nausea (sickness).

Common:
- Changes in sleep pattern, such as sleeplessness (insomnia) and sleepiness
- Tiredness (fatigue)
- Headache
- Abnormal dreams
- Constipation
- Dizziness
- Vomiting (being sick)

Uncommon:
- Urge to behave in an unusual way*
- Cardiac failure (heart problems which can cause shortness of breath or ankle swelling)*
- Inappropriate antidiuretic hormone secretion*
- Dyskinesia (e.g. abnormal, uncontrolled movements of the limbs)



99

- Hyperkinesia (increased movements and inability to keep still)*
- Paranoia (e.g. excessive fear for one’s own well-being)*
- Delusion*
- Amnesia (memory disturbance)*
- Hallucinations (seeing, hearing or feeling things that are not there)
- Confusion
- Excessive daytime sleepiness and suddenly falling asleep
- Weight increase
- Hypotension (low blood pressure)
- Excess of fluid, usually in the legs (peripheral oedema)
- Allergic reactions (e.g. rash, itching, hypersensitivity)
- Fainting
- Restlessness
- Visual impairment
- Weight loss including decreased appetite
- Dyspnoea (difficulties to breathe)
- Hiccups
- Pneumonia (infection of the lungs)*
- Inability to resist the impulse, drive or temptation to perform an action that could be harmful to 

you or others, 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)*
- Mania (agitation, feeling elated or over-excited)*
- Delirium (decreased awareness, confusion, loss of reality)*

Not known:
- After stopping or reducing your Oprymea treatment: Depression, apathy, anxiety, fatigue, 

sweating or pain may occur (called dopamine agonist withdrawal syndrome or DAWS). 

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

For the side effects marked with * a precise frequency estimation is not possible, since these side 
effects were not observed in clinical studies among 1,395 patients treated with pramipexole. The 
frequency category is probably not greater than "uncommon".

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 Oprymea

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 packaging after EXP. The expiry 
date refers to the last day of that month.

Store in the original package in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 



100

throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Oprymea contains
- The active substance is pramipexole. Each tablet contains 0.088 mg, 0.18 mg, 0.35 mg, 0.7 mg 

or 1.1 mg pramipexole as 0.125 mg, 0.25 mg, 0.5 mg, 1 mg or 1.5 mg pramipexole 
dihydrochloride monohydrate, respectively.

- The other ingredients are mannitol, maize starch, pregelatinised maize starch, povidone K25, 
colloidal anhydrous silica and magnesium stearate.

What Oprymea looks like and contents of the pack
Oprymea 0.088 mg tablets are white, round, with bevelled edges and imprint "P6" on one side of the 
tablet.
Oprymea 0.18 mg tablets are white, oval, with bevelled edges, both sides scored, with imprint "P7" on 
both halves of one side of the tablet. The tablet can be divided into equal doses.
Oprymea 0.35 mg tablets are white, oval, with bevelled edges, both sides scored, with imprint "P8" on 
both halves of one side of the tablet. The tablet can be divided into equal doses.
Oprymea 0.70 mg tablets are white, round, with bevelled edges, both sides scored, with imprint "P9" 
on both halves of one side of the tablet. The tablet can be divided into equal doses.
Oprymea 1.1 mg tablets are white, round, with bevelled edges, both sides scored. The tablet can be 
divided into equal doses.

Boxes of 20, 30, 60, 90 and 100 tablets in blisters of 10 tablets are available.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

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

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 36 (1) 355 8490

Danmark
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Malta
E. J. Busuttil Ltd.
Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
Focus Care Pharmaceuticals B.V.
Tel: +31 (0)75 612 05 11



101

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
QUALIA PHARMA S.A.
Τηλ: + 30 210 6256177

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 81

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 293 91 80

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland
LYFIS ehf.
Sími: + 354 534 3500

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

Κύπρος
KI.PA. (PHARMACAL) LIMITED
Τηλ: + 357 24 651 882

Sverige
KRKA Sverige AB
Tel: + 46 (0)8 643 67 66 (SE)

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom
Consilient Health (UK) Ltd.
Tel: + 44 (0)203 751 1888

This leaflet was last revised in.

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



102

Package leaflet: Information for the patient

Oprymea 0.26 mg prolonged-release tablets
Oprymea 0.52 mg prolonged-release tablets
Oprymea 1.05 mg prolonged-release tablets
Oprymea 1.57 mg prolonged-release tablets
Oprymea 2.1 mg prolonged-release tablets 

Oprymea 2.62 mg prolonged-release tablets
Oprymea 3.15 mg prolonged-release tablets

pramipexole

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

1. What Oprymea is and what it is used for

Oprymea contains the active substance pramipexole and belongs to a group of medicines known as 
dopamine agonists, which stimulate dopamine receptors in the brain. Stimulation of the dopamine
receptors triggers nerve impulses in the brain that help to control body movements.

Oprymea is used to treat the symptoms of primary Parkinson’s disease in adults. It can be used alone 
or in combination with levodopa (another medicine for Parkinson’s disease).

2. What you need to know before you take Oprymea

Do not take Oprymea
- if you are allergic to pramipexole or any of the other ingredients of this medicine (listed in 

section 6).

Warnings and precautions
Talk to your doctor before taking Oprymea. Tell your doctor if you have (had) or develop any medical 
conditions or symptoms, especially any of the following:
- Kidney disease
- Hallucinations (seeing, hearing or feeling things that are not there). Most hallucinations are 

visual
- Dyskinesia (e.g. abnormal, uncontrolled movements of the limbs). If you have advanced 

Parkinson’s disease and are also taking levodopa, you might develop dyskinesia during the up-
titration of Oprymea

- Dystonia (inability of keeping your body and neck straight and upright (axial dystonia)). In 
particular, you may experience forward flexion of the head and neck (also called antecollis), 
forward bending of the lower back (also called camptocormia) or sidewards bending of the back 



103

(also called pleurothotonus or Pisa Syndrome). If this happens, your doctor may want to change 
your medication. 

- Sleepiness and episodes of suddenly falling asleep
- Psychosis (e.g. comparable with symptoms of schizophrenia)
- Vision impairment. You should have regular eye examinations during treatment with Oprymea
- Severe heart or blood vessels disease. You will need to have your blood pressure checked 

regularly, especially at the beginning of treatment. This is to avoid postural hypotension (a fall 
in blood pressure on standing up).

Tell your doctor if you or your family/carer notices that you are developing urges or cravings to 
behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry 
out certain activities that could harm yourself or others. These are called impulse control disorders and 
can include behaviours such as addictive gambling, excessive eating or spending, an abnormally high 
sex drive or preoccupation with an increase in sexual thoughts or feelings. Your doctor may need to 
adjust or stop your dose.

Tell your doctor if you or your family/carer notices that you are developing mania (agitation, feeling 
elated or over-excited) or delirium (decreased awareness, confusion or loss of reality). Your doctor 
may need to adjust or stop your dose.

Tell your doctor if you experience symptoms such as depression, apathy, anxiety, fatigue, sweating or 
pain after stopping or reducing your Oprymea treatment. If the problems persist more than a few 
weeks, your doctor may need to adjust your treatment.

Oprymea prolonged-release tablet is a specially designed tablet from which the active ingredient is 
gradually released, once the tablet has been ingested. Parts of tablets may occasionally be passed and 
seen in the stool (faeces) and may look like whole tablets. Inform your doctor if you find tablet pieces 
in your faeces.

Children and adolescents
Oprymea is not recommended for use in children or adolescents under 18 years.

Other medicines and Oprymea
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This includes medicines, herbal remedies, health foods or supplements that you have 
obtained without a prescription.

You should avoid taking Oprymea together with antipsychotic medicines.

Take care if you are taking the following medicines:
- cimetidine (to treat excess stomach acid and stomach ulcers)
- amantadine (which can be used to treat Parkinson’s disease)
- mexiletine (to treat irregular heartbeats, a condition known as ventricular arrhythmia)
- zidovudine (which can be used to treat the acquired immune deficiency syndrome (AIDS), a 

disease of the human immune system)
- cisplatin (to treat various types of cancers)
- quinine (which can be used for the prevention of painful night-time leg cramps and for the 

treatment of a type of malaria known as falciparum malaria (malignant malaria))
- procainamide (to treat irregular heart beat).

If you are taking levodopa, the dose of levodopa is recommended to be reduced when you start 
treatment with Oprymea.

Take care if you are using any medicines that calm you down (have a sedative effect) or if you are 
drinking alcohol. In these cases Oprymea may affect your ability to drive and operate machinery.

Oprymea with food, drink and alcohol



104

You should be cautious while drinking alcohol during treatment with Oprymea.
Oprymea can be taken with or without food.

Pregnancy and 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. Your doctor will then discuss with 
you if you should continue to take Oprymea.

The effect of Oprymea on the unborn child is not known. Therefore, do not take Oprymea if you are 
pregnant unless your doctor tells you to do so.

Oprymea should not be used during breast-feeding. Oprymea can reduce the production of breast milk. 
Also, it can pass into the breast milk and can reach your baby. If use of Oprymea is unavoidable, 
breast-feeding should be stopped.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Oprymea can cause hallucinations (seeing, hearing or feeling things that are not there). If affected, do 
not drive or use machines.

Oprymea has been associated with sleepiness and episodes of suddenly falling asleep, particularly in 
patients with Parkinson’s disease. If you experience these side effects, you must not drive or operate 
machinery. You should tell your doctor if this occurs.

3. How to take Oprymea

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. The doctor will advise you on the right dosing.

Take Oprymea prolonged-release tablets only once a day and each day at about the same time.

You can take Oprymea with or without food. Swallow the tablets whole with water.

Do not chew, divide or crush the prolonged-release tablets. If you do, there is a 
danger you could overdose, because the medicine may be released into your 
body too quickly.

During the first week, the usual daily dose is 0.26 mg pramipexole. The dose will be increased every 
5-7 days as directed by your doctor until your symptoms are controlled (maintenance dose).

Ascending dose schedule of Oprymea prolonged-release tablets
Week Daily dose (mg) Number of tablets
1 0.26 One Oprymea 0.26 mg prolonged-release tablet.
2 0.52 One Oprymea 0.52 mg prolonged-release tablet,

OR
two Oprymea 0.26 mg prolonged-release tablets.

3 1.05 One Oprymea 1.05 mg prolonged-release tablet,
OR
two Oprymea 0.52 mg prolonged-release tablets,
OR
four Oprymea 0.26 mg prolonged-release tablets.



105

The usual maintenance dose is 1.05 mg per day. However, your dose may have to be increased even 
further. If necessary, your doctor may increase your dose up to a maximum of 3.15 mg of pramipexole 
a day. A lower maintenance dose of one Oprymea 0.26 mg prolonged-release tablet a day is also 
possible.

Patients with kidney disease
If you have kidney disease, your doctor may advise you to take the usual starting dose of 0.26 mg
prolonged-release tablets only every other day for the first week. After that, your doctor may increase 
the dosing frequency to one 0.26 mg prolonged-release tablet every day. If a further dose increase is 
necessary, your doctor may adjust it in steps of 0.26 mg pramipexole.

If you have serious kidney problems, your doctor may need to switch you to a different pramipexole 
medicine. If during treatment your kidney problems get worse, you should contact your doctor as soon 
as possible.

If you are switching from Oprymea (immediate release) tablets
Your doctor will base your dose of Oprymea prolonged-release tablets on the dose of Oprymea
(immediate release) tablets you were taking.

Take your Oprymea (immediate release) tablets as normal the day before you switch. Then take your 
Oprymea prolonged-release tablets next morning and do not take any more Oprymea (immediate 
release) tablets.

If you take more Oprymea than you should
If you accidentally take too many tablets,
- Contact your doctor or nearest hospital casualty department immediately for advice.
- You may experience vomiting, restlessness, or any of the side effects as described in chapter 4 

"Possible side effects".

If you forget to take Oprymea
If you forget to take a dose of Oprymea, but remember within 12 hours of your usual time, take your 
tablet straightaway and then take your next tablet at the usual time.
If you forget for more than 12 hours, simply take the next single dose at the usual time. Do not take a 
double dose to make up for a forgotten tablet dose.

If you stop taking Oprymea
Do not stop taking Oprymea without first talking to your doctor. If you have to stop taking this 
medicine, your doctor will reduce the dose gradually. This reduces the risk of worsening symptoms.

If you suffer from Parkinson’s disease you should not stop treatment with Oprymea abruptly. A 
sudden stop could cause you to develop a medical condition called neuroleptic malignant syndrome 
which may represent a major health risk. The symptoms include:
- akinesia (loss of muscle movement)
- rigid muscles
- fever
- unstable blood pressure
- tachycardia (increased heart rate)
- confusion
- depressed level of consciousness (e.g. coma).

If you stop or reduce Oprymea you may also develop a medical condition called dopamine agonist 
withdrawal syndrome. The symptoms include depression, apathy, anxiety, fatigue, sweating or pain. If 
you experience these symptoms you should contact your physician.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.



106

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Evaluation of these side effects is based on the following frequencies:

Very common may affect more than 1 in 10 people
Common may affect up to 1 in 10 people
Uncommon may affect up to 1 in 100 people
Rare may affect up to 1 in 1,000 people
Very rare may affect up to 1 in 10,000 people
Not known Frequency cannot be estimated from the available data

You may experience the following side effects:

Very common:
- Dyskinesia (e.g. abnormal, uncontrolled movements of the limbs)
- Sleepiness
- Dizziness
- Nausea (sickness)

Common:
- Urge to behave in an unusual way
- Hallucinations (seeing, hearing or feeling things that are not there)
- Confusion
- Tiredness (fatigue)
- Sleeplessness (insomnia)
- Excess of fluid, usually in the legs (peripheral oedema)
- Headache
- Hypotension (low blood pressure)
- Abnormal dreams
- Constipation
- Visual impairment
- Vomiting (being sick)
- Weight loss including decreased appetite

Uncommon:
- Paranoia (e.g. excessive fear for one’s own well-being)
- Delusion
- Excessive daytime sleepiness and suddenly falling asleep
- Amnesia (memory disturbance)
- Hyperkinesia (increased movements and inability to keep still)
- Weight increase
- Allergic reactions (e.g. rash, itching, hypersensitivity)
- Fainting
- Cardiac failure (heart problems which can cause shortness of breath or ankle swelling)*
- Inappropriate antidiuretic hormone secretion*
- Restlessness
- Dyspnoea (difficulties to breathe)
- Hiccups
- Pneumonia (infection of the lungs)
- Inability to resist the impulse, drive or temptation to perform an action that could be harmful to 

you or others, 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.



107

- 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)*
- Delirium (decreased awareness, confusion, loss of reality)

Rare:
- Mania (agitation, feeling elated or over-excited)

Not known:
- After stopping or reducing your Oprymea treatment: Depression, apathy, anxiety, fatigue, 

sweating or pain may occur (called dopamine agonist withdrawal syndrome or DAWS).

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

For the side effects marked with * a precise frequency estimation is not possible, since these side 
effects were not observed in clinical studies among 2,762 patients treated with pramipexole. The 
frequency category is probably not greater than "uncommon".

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 Oprymea

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 packaging after EXP. The expiry 
date refers to the last day of that month.

Store in the original package in order to protect from moisture.
This medicine does not require any special temperature storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Oprymea contains
- The active substance is pramipexole. Each prolonged-release tablet contains 0.26 mg, 0.52 mg, 

1.05 mg, 1.57 mg, 2.1 mg, 2.62 mg or 3.15 mg pramipexole as 0.375 mg, 0.75 mg, 1.5 mg, 
2.25 mg, 3 mg, 3.75 mg or 4.5 mg pramipexole dihydrochloride monohydrate, respectively.

- The other ingredients are hypromellose, maize starch, colloidal anhydrous silica and magnesium 
stearate.

What Oprymea looks like and contents of the pack
Oprymea 0.26 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P1 on one side, with bevelled edges and possible spots.
Oprymea 0.52 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P2 on one side, with bevelled edges and possible spots.
Oprymea 1.05 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P3 on one side, with bevelled edges and possible spots.
Oprymea 1.57 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 



108

slightly biconvex tablets engraved with P12 on one side, with bevelled edges and possible spots.
Oprymea 2.1 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P4 on one side, with bevelled edges and possible spots.
Oprymea 2.62 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P13 on one side and 262 on the other side, with bevelled edges 
and possible spots.
Oprymea 3.15 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P5 on one side and 315 on the other side, with bevelled edges 
and possible spots.

Boxes of 10, 30, 90 and 100 tablets in blisters of 10 tablets are available.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

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

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 36 (1) 355 8490

Danmark
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Malta
E. J. Busuttil Ltd.
Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
Focus Care Pharmaceuticals B.V.
Tel: +31 (0)75 612 05 11

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
QUALIA PHARMA S.A.
Τηλ: + 30 210 6256177

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 81

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.



109

Tél: + 33 (0)1 57 40 82 25 Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 293 91 80

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland
LYFIS ehf.
Sími: + 354 534 3500

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

Κύπρος
KI.PA. (PHARMACAL) LIMITED
Τηλ: + 357 24 651 882

Sverige
KRKA Sverige AB
Tel: + 46 (0)8 643 67 66 (SE)

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom
Consilient Health (UK) Ltd.
Tel: + 44 (0)203 751 1888

This leaflet was last revised in

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



110

Package leaflet: Information for the patient

Oprymea 0.26 mg prolonged-release tablets
Oprymea 0.52 mg prolonged-release tablets 
Oprymea 1.05 mg prolonged-release tablets 

pramipexole

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

1. What Oprymea is and what it is used for

Oprymea contains the active substance pramipexole and belongs to a group of medicines known as 
dopamine agonists, which stimulate dopamine receptors in the brain. Stimulation of the dopamine 
receptors triggers nerve impulses in the brain that help to control body movements.

Oprymea is used to treat the symptoms of primary Parkinson’s disease in adults. It can be used alone 
or in combination with levodopa (another medicine for Parkinson’s disease).

2. What you need to know before you take Oprymea

Do not take Oprymea
- if you are allergic to pramipexole or any of the other ingredients of this medicine (listed in 

section 6).

Warnings and precautions
Talk to your doctor before taking Oprymea. Tell your doctor if you have (had) or develop any medical 
conditions or symptoms, especially any of the following:
- Kidney disease
- Hallucinations (seeing, hearing or feeling things that are not there). Most hallucinations are 

visual
- Dyskinesia (e.g. abnormal, uncontrolled movements of the limbs). If you have advanced 

Parkinson’s disease and are also taking levodopa, you might develop dyskinesia during the up-
titration of Oprymea

- Dystonia (inability of keeping your body and neck straight and upright (axial dystonia)). In 
particular, you may experience forward flexion of the head and neck (also called antecollis), 
forward bending of the lower back (also called camptocormia) or sidewards bending of the back 
(also called pleurothotonus or Pisa Syndrome). If this happens, your doctor may want to change 
your medication. 

- Sleepiness and episodes of suddenly falling asleep
- Psychosis (e.g. comparable with symptoms of schizophrenia)



111

- Vision impairment. You should have regular eye examinations during treatment with Oprymea
- Severe heart or blood vessels disease. You will need to have your blood pressure checked 

regularly, especially at the beginning of treatment. This is to avoid postural hypotension (a fall 
in blood pressure on standing up).

Tell your doctor if you or your family/carer notices that you are developing urges or cravings to 
behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry 
out certain activities that could harm yourself or others. These are called impulse control disorders and 
can include behaviours such as addictive gambling, excessive eating or spending, an abnormally high 
sex drive or preoccupation with an increase in sexual thoughts or feelings. Your doctor may need to 
adjust or stop your dose.

Tell your doctor if you or your family/carer notices that you are developing mania (agitation, feeling 
elated or over-excited) or delirium (decreased awareness, confusion or loss of reality). Your doctor 
may need to adjust or stop your dose.

Tell your doctor if you experience symptoms such as depression, apathy, anxiety, fatigue, sweating or 
pain after stopping or reducing your Oprymea treatment. If the problems persist more than a few 
weeks, your doctor may need to adjust your treatment.

Oprymea prolonged-release tablet is a specially designed tablet from which the active ingredient is 
gradually released, once the tablet has been ingested. Parts of tablets may occasionally be passed and 
seen in the stool (faeces) and may look like whole tablets. Inform your doctor if you find tablet pieces 
in your faeces.

Children and adolescents
Oprymea is not recommended for use in children or adolescents under 18 years.

Other medicines and Oprymea
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This includes medicines, herbal remedies, health foods or supplements that you have 
obtained without a prescription.

You should avoid taking Oprymea together with antipsychotic medicines.

Take care if you are taking the following medicines:
- cimetidine (to treat excess stomach acid and stomach ulcers);
- amantadine (which can be used to treat Parkinson’s disease);
- mexiletine (to treat irregular heartbeats, a condition known as ventricular arrhythmia);
- zidovudine (which can be used to treat the acquired immune deficiency syndrome (AIDS), a 

disease of the human immune system);
- cisplatin (to treat various types of cancers);
- quinine (which can be used for the prevention of painful night-time leg cramps and for the 

treatment of a type of malaria known as falciparum malaria (malignant malaria));
- procainamide (to treat irregular heart beat).

If you are taking levodopa, the dose of levodopa is recommended to be reduced when you start 
treatment with Oprymea.

Take care if you are using any medicines that calm you down (have a sedative effect) or if you are 
drinking alcohol. In these cases Oprymea may affect your ability to drive and operate machinery.

Oprymea with food, drink and alcohol
You should be cautious while drinking alcohol during treatment with Oprymea.
Oprymea can be taken with or without food.

Pregnancy and breast-feeding



112

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. Your doctor will then discuss with 
you if you should continue to take Oprymea.

The effect of Oprymea on the unborn child is not known. Therefore, do not take Oprymea if you are 
pregnant unless your doctor tells you to do so.

Oprymea should not be used during breast-feeding. Oprymea can reduce the production of breast milk. 
Also, it can pass into the breast milk and can reach your baby. If use of Oprymea is unavoidable, 
breast-feeding should be stopped.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Oprymea can cause hallucinations (seeing, hearing or feeling things that are not there). If affected, do 
not drive or use machines.

Oprymea has been associated with sleepiness and episodes of suddenly falling asleep, particularly in 
patients with Parkinson’s disease. If you experience these side effects, you must not drive or operate 
machinery. You should tell your doctor if this occurs.

3. How to take Oprymea

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. The doctor will advise you on the right dosing.

Take Oprymea prolonged-release tablets only once a day and each day at about the same time.

You can take Oprymea with or without food. Swallow the tablets whole with water.

Do not chew, divide or crush the prolonged-release tablets. If you do, there is a 
danger you could overdose, because the medicine may be released into your 
body too quickly.

During the first week, the usual daily dose is 0.26 mg pramipexole. The dose will be increased every 
5-7 days as directed by your doctor until your symptoms are controlled (maintenance dose).

The Oprymea treatment initiation pack is only to be used for the beginning of the treatment with 
Oprymea.
The Oprymea treatment initiation pack contains three blister strips of tablets - one strip for each of the 
first three weeks of your treatment. The three strips are marked with "Week 1", "Week 2" and 
"Week 3".
The daily dose you take of Oprymea increases each week.

Ascending dose schedule of Oprymea prolonged-release tablets
Week Daily dose (mg) Number of tablets
1 0.26 One Oprymea 0.26 mg prolonged-release tablet on blister "Week 1".
2 0.52 One Oprymea 0.52 mg prolonged-release tablet on blister "Week 2".
3 1.05 One Oprymea 1.05 mg prolonged-release tablet on blister "Week 3".

The usual maintenance dose is 1.05 mg per day. However, your dose may have to be increased even 
further. If necessary, your doctor may increase your dose up to a maximum of 3.15 mg of pramipexole 



113

a day. A lower maintenance dose of one Oprymea 0.26 mg prolonged-release tablet a day is also 
possible.

Patients with kidney disease
If you have kidney disease, your doctor may advise you to take the usual starting dose of 0.26 mg 
prolonged-release tablets only every other day for the first week. After that, your doctor may increase 
the dosing frequency to one 0.26 mg prolonged-release tablet every day. If a further dose increase is 
necessary, your doctor may adjust it in steps of 0.26 mg pramipexole.

If you have serious kidney problems, your doctor may need to switch you to a different pramipexole 
medicine. If during treatment your kidney problems get worse, you should contact your doctor as soon 
as possible.

If you are switching from Oprymea (immediate release) tablets
Your doctor will base your dose of Oprymea prolonged-release tablets on the dose of Oprymea 
(immediate release) tablets you were taking.

Take your Oprymea (immediate release) tablets as normal the day before you switch. Then take your 
Oprymea prolonged-release tablets next morning and do not take any more Oprymea (immediate 
release) tablets.

If you take more Oprymea than you should
If you accidentally take too many tablets,
- Contact your doctor or nearest hospital casualty department immediately for advice.
- You may experience vomiting, restlessness, or any of the side effects as described in chapter 4 

"Possible side effects".

If you forget to take Oprymea
If you forget to take a dose of Oprymea, but remember within 12 hours of your usual time, take your 
tablet straightaway and then take your next tablet at the usual time.
If you forget for more than 12 hours, simply take the next single dose at the usual time. Do not take a 
double dose to make up for a forgotten tablet dose.

If you stop taking Oprymea
Do not stop taking Oprymea without first talking to your doctor. If you have to stop taking this 
medicine, your doctor will reduce the dose gradually. This reduces the risk of worsening symptoms.

If you suffer from Parkinson’s disease you should not stop treatment with Oprymea abruptly. A 
sudden stop could cause you to develop a medical condition called neuroleptic malignant syndrome 
which may represent a major health risk. The symptoms include:
- akinesia (loss of muscle movement)
- rigid muscles
- fever
- unstable blood pressure
- tachycardia (increased heart rate)
- confusion
- depressed level of consciousness (e.g. coma).

If you stop or reduce Oprymea you may also develop a medical condition called dopamine agonist 
withdrawal syndrome. The symptoms include depression, apathy, anxiety, fatigue, sweating or pain. If 
you experience these symptoms you should contact your physician.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects



114

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Evaluation of these side effects is based on the following frequencies:

Very common may affect more than 1 in 10 people
Common may affect up to 1 in 10 people
Uncommon may affect up to 1 in 100 people
Rare may affect up to 1 in 1,000 people
Very rare may affect up to 1 in 10,000 people
Not known Frequency cannot be estimated from the available data

You may experience the following side effects:

Very common:
- Dyskinesia (e.g. abnormal, uncontrolled movements of the limbs)
- Sleepiness
- Dizziness
- Nausea (sickness)

Common:
- Urge to behave in an unusual way
- Hallucinations (seeing, hearing or feeling things that are not there)
- Confusion
- Tiredness (fatigue)
- Sleeplessness (insomnia)
- Excess of fluid, usually in the legs (peripheral oedema)
- Headache
- Hypotension (low blood pressure)
- Abnormal dreams
- Constipation
- Visual impairment
- Vomiting (being sick)
- Weight loss including decreased appetite

Uncommon:
- Paranoia (e.g. excessive fear for one’s own well-being)
- Delusion
- Excessive daytime sleepiness and suddenly falling asleep
- Amnesia (memory disturbance)
- Hyperkinesia (increased movements and inability to keep still)
- Weight increase
- Allergic reactions (e.g. rash, itching, hypersensitivity)
- Fainting
- Cardiac failure (heart problems which can cause shortness of breath or ankle swelling)*
- Inappropriate antidiuretic hormone secretion*
- Restlessness
- Dyspnoea (difficulties to breathe)
- Hiccups
- Pneumonia (infection of the lungs)
- Inability to resist the impulse, drive or temptation to perform an action that could be harmful to 

you or others, 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)*



115

- Delirium (decreased awareness, confusion, loss of reality)

Rare:
- Mania (agitation, feeling elated or over-excited)

Not known:
- After stopping or reducing your Opymea treatment: Depression, apathy, anxiety, fatigue, 

sweating or pain may occur (called dopamine agonist withdrawal syndrome or DAWS). 

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

For the side effects marked with * a precise frequency estimation is not possible, since these side 
effects were not observed in clinical studies among 2,762 patients treated with pramipexole. The 
frequency category is probably not greater than "uncommon".

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 Oprymea

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 packaging after EXP. The expiry 
date refers to the last day of that month.

Store in the original package in order to protect from moisture.
This medicine does not require any special temperature storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Oprymea contains
- The active substance is pramipexole. Each prolonged-release tablet contains 0.26 mg, 0.52 mg

or 1.05 mg pramipexole as 0.375 mg, 0.75 mg or 1.5 mg pramipexole dihydrochloride 
monohydrate, respectively.

- The other ingredients are hypromellose, maize starch, colloidal anhydrous silica and magnesium 
stearate.

What Oprymea looks like and contents of the pack
Oprymea 0.26 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P1 on one side, with bevelled edges and possible spots.
Oprymea 0.52 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P2 on one side, with bevelled edges and possible spots.
Oprymea 1.05 mg prolonged-release tablets are white or almost white, round (diameter 10 mm), 
slightly biconvex tablets engraved with P3 on one side, with bevelled edges and possible spots.

3-week treatment initiation pack contains 21 prolonged-release tablets in 3 packages: 
- the package marked "Week 1" contains 1 blister of 7 tablets of 0.26 mg,
- the package marked "Week 2" contains 1 blister of 7 tablets of 0.52 mg,



116

- the package marked "Week 3" contains 1 blister of 7 tablets of 1.05 mg.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

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

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 36 (1) 355 8490

Danmark
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Malta
E. J. Busuttil Ltd.
Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
Focus Care Pharmaceuticals B.V.
Tel: +31 (0)75 612 05 11

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
QUALIA PHARMA S.A.
Τηλ: + 30 210 6256177

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 81

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 293 91 80

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland Slovenská republika



117

LYFIS ehf.
Sími: + 354 534 3500

KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

Κύπρος
KI.PA. (PHARMACAL) LIMITED
Τηλ: + 357 24 651 882

Sverige
KRKA Sverige AB
Tel: + 46 (0)8 643 67 66 (SE)

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom
Consilient Health (UK) Ltd.
Tel: + 44 (0)203 751 1888

This leaflet was last revised in

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


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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