Tasmar

1 

 
 
 
 
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Tasmar 100 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 100 mg tolcapone. 

Excipients with known effect: Each tablet contains 7.5 mg lactose  

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet. 

Pale to light yellow, hexagonal, biconvex, film-coated tablet. “TASMAR” and “100” are engraved on 

one side.  

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Tasmar is indicated in combination with levodopa/benserazide or levodopa/carbidopa for use in 

patients with levodopa-responsive idiopathic Parkinson’s disease and motor fluctuations, who failed to 

respond to or are intolerant of other catechol-O-methyltransferase COMT inhibitors (see section 5.1). 

Because of the risk of potentially fatal, acute liver injury, Tasmar should not be considered as a first-

line adjunct therapy to levodopa/benserazide or levodopa/carbidopa (see sections 4.4 and 4.8).  

 

Since Tasmar should be used only in combination with levodopa/benserazide and levodopa/carbidopa, 

the prescribing information for these levodopa preparations is also applicable to their concomitant use 

with Tasmar. 

 

4.2 Posology and method of administration 

 

Posology  

 

Paediatric population 

Tasmar is not recommended for use in children below the age of 18 due to insufficient data on safety 

or efficacy. There is no relevant indication for use in children and adolescents. 

 

Elderly patients 

No dose adjustment of Tasmar is recommended for elderly patients. 

 

Patients with hepatic impairment (see section 4.3) 

Tasmar is contraindicated for patients with liver disease or increased liver enzymes. 

 

Patients with renal impairment (see section 5.2) 

No dose adjustment of Tasmar is recommended for patients with mild or moderate renal impairment 

(creatinine clearance of 30 ml/min or greater). Patients with severe renal impairment (creatinine 

clearance <30 ml/min) should be treated with caution. No information on the tolerability of tolcapone 

in these populations is available (see section 5.2) 

 

Method of administration 

The administration of Tasmar is restricted to prescription and supervision by physicians experienced 

in the management of advanced Parkinson's disease. 

 



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Tasmar is administered orally three times daily. 

Tasmar may be taken with or without food (see section 5.2). 

 

Tasmar tablets are film-coated and should be swallowed whole because tolcapone has a bitter taste. 

 

Tasmar can be combined with all pharmaceutical formulations of levodopa/benserazide and 

levodopa/carbidopa (see also section 4.5). 

 

The first dose of the day of Tasmar should be taken together the first dose of the day of a levodopa 

preparation, and the subsequent doses should be given approximately 6 and 12 hours later. Tasmar 

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

The recommended dose of Tasmar is 100 mg three times daily, always as an adjunct to 

levodopa/benserazide or levodopa/carbidopa therapy. Only in exceptional circumstances, when the 

anticipated incremental clinical benefit justifies the increased risk of hepatic reactions, should the dose 

be increased to 200 mg three times daily (see sections 4.4 and 4.8). If substantial clinical benefits are 

not seen within 3 weeks of the initiation of the treatment (regardless of dose) Tasmar should be 

discontinued. 

The maximum therapeutic dose of 200 mg three times daily should not be exceeded, as there is no 

evidence of additional efficacy at higher doses. 

 

Liver function should be checked before starting treatment with Tasmar and then monitored every 2 

weeks for the first year of therapy, every 4 weeks for the next 6 months and every 8 weeks thereafter. 

If the dose is increased to 200 mg tid, liver enzyme monitoring should take place before increasing the 

dose and then be reinitiated following the same sequence of frequencies as above (see sections  4.4 

and 4.8). 

 

Tasmar treatment should also be discontinued if ALT (alanine amino transferase) and/or AST 

(aspartate amino transferase) exceed the upper limit of normal or symptoms or signs suggest the onset 

of hepatic failure (see section 4.4). 

 

Levodopa adjustments during Tasmar treatment:  

As Tasmar decreases the breakdown of levodopa in the body, side effects due to increased levodopa 

concentrations may occur when beginning Tasmar treatment. In clinical trials, more than 70 % of 

patients required a decrease in their daily levodopa dose if their daily dose of levodopa was >600 mg 

or if patients had moderate or severe dyskinesias before beginning treatment. 

The average reduction in daily levodopa dose was about 30 % in those patients requiring a levodopa 

dose reduction. When beginning Tasmar, all patients should be informed of the symptoms of excessive 

levodopa dose and what to do if it occurs. 

Levodopa adjustments when Tasmar is discontinued:  

The following suggestions are based on pharmacological considerations and have not been evaluated 

in clinical trials. Levodopa dose should not be decreased when Tasmar therapy is being discontinued 

due to side effects related to too much levodopa. However, when Tasmar therapy is being 

discontinued for reasons other than too much levodopa, levodopa  dosemay have to be increased to 

levels equal to or greater than before initiation of Tasmar therapy, especially if the patient had large 

decreases in levodopa when starting Tasmar. In all cases, patients should be educated on the 

symptoms of levodopa under-dose and what to do if it occurs. Adjustments in levodopa are most likely 

to be required within 1-2 days of Tasmar discontinuation. 

 

4.3 Contraindications 

 

• Hypersensitivity to tolcapone or any of its other ingredients listed in section 6.1. 

• Evidence of liver disease or increased liver enzymes 

• Severe dyskinesia 

•   A previous history of Neuroleptic Malignant Syndrome (NMS) Symptom Complex  and /or  

            non-traumatic Rhabdomyolysis or Hyperthermia. 



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• Phaeochromocytoma. 

•   Treatment with non-selective mono amino oxidase (MAO) inhibitors 

 

4.4 Special warnings and precautions for use 

 

Tasmar therapy should only be initiated by physicians experienced in the management of advanced 

Parkinson’s disease, to ensure an appropriate risk-benefit assessment. Tasmar should not be prescribed 

until there has been a complete informative discussion of the risks with the patient. 

 

Tasmar should be discontinued if substantial clinical benefits are not seen within 3 weeks of the 

initiation of the treatment regardless of dose. 

 

Liver injury: 

Because of the risk of rare but potentially fatal acute liver injury, Tasmar is only indicated for use in 

patients with levodopa-responsive idiopathic Parkinson’s disease and motor fluctuations, who failed to 

respond to or are intolerant of other COMT inhibitors. Periodic monitoring of liver enzymes cannot 

reliably predict the occurrence of fulminant hepatitis. However, it is generally believed that early 

detection of medicine-induced hepatic injury along with immediate withdrawal of the suspect 

medication enhances the likelihood for recovery. Liver injury has most often occurred between 1 

month and 6 months after starting treatment with Tasmar. Additionally late onset hepatitis after 

approximately 18 months of treatment has been reported rarely.  

It should also be noted that female patients may have a higher risk of liver injury (see  section 4.8). 

 

Before starting treatment: If liver function tests are abnormal or there are signs of impaired liver 

function, Tasmar should not be prescribed. If Tasmar is to be prescribed, the patient should be 

informed about the signs and symptoms which may indicate liver injury, and to contact the physician 

immediately.  

 

During treatment: Liver function should be monitored every 2 weeks for the first year of therapy, 

every 4 weeks for the next 6 months and every 8 weeks thereafter. If the dose is increased to 200 mg 

tid, liver enzyme monitoring should take place before increasing the dose and then be re-initiated 

following the sequence of frequencies as above. Treatment should be immediately discontinued if 

ALT and/or AST exceed the upper limit of normal or if symptoms or signs suggesting the onset of 

hepatic failure (persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, right upper 

quadrant tenderness) develop. 

 

If treatment is discontinued: Patients who show evidence of acute liver injury while on Tasmar and are 

withdrawn from the medicinal product  may be at increased risk for liver injury if Tasmar is re-

introduced. Accordingly, such patients should not be considered for re-treatment. 

 

Neuroleptic Malignant Syndrome (NMS): 

In Parkinson`s patients, NMS tends to occur when discontinuing or stopping dopaminergic-enhancing 

medications. Therefore, if symptoms occur after discontinuing Tasmar, physicians should consider 

increasing the patient’s levodopa dose (see section 4.2). 

 

Isolated cases consistent with NMS have been associated with Tasmar treatment. Symptoms have 

usually onset during Tasmar treatment or shortly after Tasmar has been discontinued. NMS is 

characterised by motor symptoms (rigidity, myoclonus and tremor), mental status changes (agitation, 

confusion, stupor and coma), elevated temperature, autonomic dysfunction (labile blood pressure, 

tachycardia) and elevated serum creatine phosphokinase (CPK) which may be a consequence of 

myolysis. A diagnosis of NMS should be considered even if not all the above findings are present. 

Under such a diagnosis Tasmar should be immediately discontinued and the patient should be 

followed up closely.  

 

Before starting treatment: To reduce the risk of NMS, Tasmar should not be prescribed for patients 

with severe dyskinesia or a previous history of NMS including rhabdomyolysis or hyperthermia (see 

section 4.3). Patients receiving multiple medications with effects on different central nervous system 



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(CNS) pathways (e.g. antidepressants, neuroleptics, anticholinergics) may be at greater risk of 

developing NMS.  

 

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 and/or other dopaminergic treatments such as Tasmar in association with levodopa. Review 

of treatment is recommended if such symptoms develop. 

 

Dyskinesia, nausea and other levodopa-associated adverse reactions: Patients may experience an 

increase in levodopa-associated adverse reactions. Reducing the dose of levodopa (see section 4.2) 

may often mitigate these adverse reactions. 

 

Diarrhoea: In clinical trials, diarrhoea developed in 16 % and 18 % of patients receiving Tasmar 

100 mg tid and 200 mg tid respectively, compared to 8 % of patients receiving placebo. Diarrhoea 

associated with Tasmar usually began 2 to 4 months after initiation of therapy. Diarrhoea led to 

withdrawal of 5% and 6% of patients receiving Tasmar 100 mg tid and 200 mg tid respectively, 

compared to 1 % of patients receiving placebo. 

 

Benserazide interaction: Due to the interaction between high dose benserazide and tolcapone (resulting 

in increased levels of benserazide), the prescriber should, until more experience has been gained, be 

observant of dose-related adverse reactions (see section 4.5). 

 

MAO inhibitors: Tasmar should not be given in conjunction with non-selective monoamine oxidase 

(MAO) inhibitors (e.g. phenelzine and tranylcypromine). The combination of MAO-A and MAO-B 

inhibitors is equivalent to non-selective MAO-inhibition, therefore they should not both be given 

concomitantly with Tasmar and levodopa preparations (see also section 4.5). Selective MAO-B 

inhibitors should not be used at higher than recommended doses (e.g. selegiline 10 mg/day) when co-

administered with Tasmar.  

 

Warfarin: Since clinical information is limited regarding the combination of warfarin and tolcapone, 

coagulation parameters should be monitored when these drugs are co-administered. 

 

Special populations: Patients with severe renal impairment (creatinine clearance <30 ml/min) should 

be treated with caution. No information on the tolerability of tolcapone in these populations is 

available (see section 5.2). 

 

Lactose intolerance: Tasmar contains lactose. Patients with hereditary problems of galactose 

intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this 

medicine. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Tasmar, as a COMT inhibitor, is known to increase the bioavailability of the co-adminstered levodopa. 

The consequent increase in dopaminergic stimulation can lead to the dopaminergic adverse reactions 

observed after treatment with COMT inhibitors. The most common of these are increased dyskinesia, 

nausea, vomiting, abdominal pain, syncope, orthostatic complains, constipation, sleep disorders, 

somnolence, hallucination. 

 

Levodopa has been associated with somnolence and episodes of sudden sleep onset. Sudden onset of 

sleep during daily activities, in some cases without awareness or warning signs, has been reported very 

rarely. Patients must be informed of this and advised to exercise caution while driving or operating 

machines during treatment with levodopa. Patients who have experienced somnolence and/or an 

episode of sudden sleep onset must refrain from driving or operating machines (see section 4.7). 

Furthermore a reduction of levodopa  dose or termination of therapy may be considered.  

 



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Catechols and other drugs metabolised by catechol-O-methyltransferase (COMT): Tolcapone may 

influence the pharmacokinetics of drugs metabolised by COMT. No effects were seen on the 

pharmacokinetics of the COMT substrate carbidopa. An interaction was observed with benserazide, 

which may lead to increased levels of benserazide and its active metabolite. The magnitude of the 

effect was dependent on the dose of benserazide. The plasma concentrations of benserazide observed 

after co-administration of tolcapone and benserazide-25 mg/levodopa were still within the range of 

values observed with levodopa/benserazide alone. On the other hand, after co-administration of 

tolcapone and benserazide-50 mg/levodopa the benserazide plasma concentrations could be increased 

above the levels usually observed with levodopa/benserazide alone. The effect of tolcapone on the 

pharmacokinetics of other drugs metabolised by COMT such as -methyldopa, dobutamine, 
apomorphine, adrenaline and isoprenaline have not been evaluated. The prescriber should be observant 

of adverse reactions caused by putative increased plasma levels of these drugs when combined with 

Tasmar. 

 

Effect of tolcapone on the metabolism of other drugs: Due to its affinity for cytochrome CYP2C9 in 

vitro, tolcapone may interfere with drugs whose clearance is dependent on this metabolic pathway, 

such as tolbutamide and warfarin. In an interaction study, tolcapone did not change the 

pharmacokinetics of tolbutamide. Therefore, clinically relevant interactions involving cytochrome 

CYP2C9 appear unlikely. 

 

Since clinical information is limited regarding the combination of warfarin and tolcapone, coagulation 

parameters should be monitored when these drugs are co-administered. 

 

Drugs that increase catecholamines: Since tolcapone interferes with the metabolism of catecholamines, 

interactions with other drugs affecting catecholamine levels are theoretically possible. 

 

When Tasmar was given together with levodopa/carbidopa and desipramine, there was no significant 

change in blood pressure, pulse rate and plasma concentrations of desipramine. Overall, the frequency 

of adverse reactions increased slightly. These adverse reactions were predictable based on the known 

adverse reactions to each of the three drugs individually. Therefore, caution should be exercised when 

potent noradrenaline uptake inhibitors such as desipramine, maprotiline, or venlafaxine are 

administered to Parkinson’s disease patients being treated with Tasmar and levodopa preparations. 

 

In clinical trials, patients receiving Tasmar/levodopa preparations reported a similar adverse reaction 

profile independent of whether or not they were also concomitantly administered selegiline (a MAO-B 

inhibitor). 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

There are no adequate data from the use of tolcapone in pregnant women. Therefore, Tasmar should 

be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 

 

Breast-feeding 

In animal studies, tolcapone was excreted into maternal milk. 

The safety of tolcapone in infants is unknown; therefore, women should not breast-feed during 

treatment with Tasmar. 

 

Fertility 

In rats and rabbits, embryo-foetal toxicity was observed after tolcapone administration (see section 

5.3). The potential risk for humans is unknown. 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects of Tasmar on the ability to drive and use machines have been performed. 



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There is no evidence from clinical studies that Tasmar adversely influences a patient’s ability to drive 

and use machines. However patients should be advised that their ability to drive and operate machines 

may be compromised due to their Parkinson’s disease symptoms.  

 

Tasmar, as a COMT inhibitor, is known to increase the bioavailability of the co-adminstered levodopa. 

The consequent increase in dopaminergic stimulation can lead to the dopaminergic side effects 

observed after treatment with COMT inhibitors. Patients being treated with Levodopa 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 section 

4.4)  

 

4.8 Undesirable effects 

 

The most commonly observed adverse reactions associated with the use of Tasmar, occurring more 

frequently than in placebo-treated patients are listed in the table below. However, Tasmar, as a COMT 

inhibitor, is known to increase the bioavailability of the co-administered levodopa. The consequent 

increase in dopaminergic stimulation can lead to the dopaminergic side effects observed after 

treatment with COMT inhibitors. The most common of these are increased dyskinesia, nausea, 

vomiting, abdominal pain, syncope, orthostatic complains, constipation, sleep disorders, somnolence, 

hallucination. 

 

The only adverse reactions commonly leading to discontinuation of Tasmar in clinical trials was 

diarrhoea (see section 4.4). 

 

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) 

 

Experience with Tasmar obtained in parallel placebo-controlled randomised studies in patients with 

Parkinson’s disease is shown in the following table, which lists adverse reactions with a potential 

relationship to Tasmar. 

 

Summary of potentially Tasmar-related adverse reactions, with crude incidence rates for the phase III 

placebo-controlled studies: 

 

 

System organ class 

 

Incidence 

 

Adverse Events 

Infections and infestations Common Upper respiratory tract infection 

Psychiatric disorders Very common Sleep disorder 

  Dreaming excessive 

  Somnolence 

  Confusion 

  Hallucination 

 Rare Impulse control disorders* 

(Libido increased, hypersexuality, 

pathological gambling, compulsive 

spending or buying, binge eating, 

compulsive eating (see section 4.4)) 

Nervous system disorders Very common Dyskinesia 

  Dystonia 

  Headache 

  Dizziness 



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System organ class 

 

Incidence 

 

Adverse Events 

  Somnolence 

  Orthostatic complaints 

 Rare Neuroleptic Malignant Syndrome 

Symptom Complex (see section 4.4) 

 Common Hypokinesia 

   

  Syncope 

   

Gastrointestinal disorders Very common Nausea 

   

  Diarrhoea 

 Common Vomiting 

  Constipation 

  Xerostomia 

  Abdominal pain 

  Dyspepsia 

Metabolism and nutrition 

disorders 

Very common Anorexia 

Skin and subcutaneous tissue 

disorders 

Common Sweating increased 

Renal and urinary disorders Common Urine discoloration 

General disorders and 

administration site conditions 

Common Chest pain 

  Influenza like illness 

Hepatobiliary disorders Uncommon Hepatocellular injury, in rare 

cases with fatal outcome* 

(see section 4.4) 

Investigations Common Increase of alanine 

aminotransferase (ALT) 

 

*: Adverse reactions for which no frequency could be derived from clinical studies (i.e. where a 

specific adverse reaction was not observed in clinical trials but was reported post-marketing only) 

are indicated by an asterisk (*), and the frequency category has been calculated according to EU 

Guideline. 
 

 

Increase of alanine aminotransferase 

Increases to more than three times the upper limit of normal (ULN) in alanine aminotransferase 

(ALT)occurred in 1 % of patients receiving Tasmar 100 mg three times daily, and 3 % of patients at 

200 mg three times daily. Increases were approximately two times more likely in females. The 

increases usually appeared within 6 to 12 weeks of starting treatment, and were not associated with 

any clinical signs or symptoms. In about half the cases, transaminase levels returned spontaneously to 

baseline values whilst patients continued Tasmar treatment. For the remainder, when treatment was 

discontinued, transaminase levels returned to pre-treatment levels. 

 

Hepatocellular injury 

Rare cases of severe hepatocellular injury resulting in death have been reported during marketed use 

(see section 4.4).  

 

Neuroleptic Malignant Syndrome Symptom Complex 



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Isolated cases of patients with symptoms suggestive of Neuroleptic Malignant Syndrome Symptom 

Complex (see section 4.4) have been reported following reduction or discontinuation of Tasmar and 

following introduction of Tasmar when this was accompanied by a significant reduction in other 

concomitant dopaminergic medications. In addition, rhabdomyolysis, secondary to NMS or severe 

dyskinesia, has been observed.  

 

Urine discolouration: Tolcapone and its metabolites are yellow and can cause a harmless 

intensification in the colour of the patient’s urine. 

 

Impulse control disorders: Pathological gambling, increased libido, hypersexuality, compulsive 

spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine 

agonists and/or other dopaminergic treatments such as Tasmar in association with Levedopa (see 

section 4.4 `special warnings and precautions for use´). 

 

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 

 

Isolated cases of either accidental or intentional overdose with tolcapone tablets have been reported. 

However clinical circumstances of these cases were so diverse, that no general conclusions can be 

drawn from the cases. 

 

The highest dose of tolcapone administered to humans was 800 mg three times daily, with and without 

levodopa coadministration, in a one week study in healthy elderly volunteers. The peak plasma 

concentrations of tolcapone at this dose were on average 30 µg/ml (compared to 3 and 6 µg/ml with 

100 mg tid and 200 mg tid of tolcapone respectively). Nausea, vomiting and dizziness were observed, 

particularly in combination with levodopa. 

 

Management of overdose: Hospitalisation is advised. General supportive care is indicated. Based on 

the physicochemical properties of the compound, hemodialysis is unlikely to be of benefit. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmaco-therapeutic group: Anti-Parkinson drugs, other dopaminergic agents, ATC code: NO4BX01  

 

Mechanism of action 

Tolcapone is an orally active, selective and reversible catechol-O-methyltransferase (COMT) 

inhibitor. Administered concomitantly with levodopa and an aromatic amino acid decarboxylase 

inhibitor (AADC-I), it leads to more stable plasma levels of levodopa by reducing metabolism of 

levodopa to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD). 

 

High levels of plasma 3-OMD have been associated with poor response to levodopa in Parkinson’s 

disease patients. Tolcapone markedly reduces the formation of 3-OMD. 

 

Pharmacodynamic effects 

Studies in healthy volunteers have shown that tolcapone reversibly inhibits human erythrocyte COMT 

activity after oral administration. The inhibition is closely related to plasma tolcapone concentration. 

With 200 mg tolcapone, maximum inhibition of erythrocyte COMT activity is, on average, greater 



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than 80 %. During dosing with Tasmar 200 mg three times daily, erythrocyte COMT inhibition at 

trough is 30 % to 45 %, with no development of tolerance.  

 

Transient elevation above pretreatment levels of erythrocyte COMT activity was observed after 

withdrawal of tolcapone. However, a study in Parkinson’s patients confirmed that after treatment 

discontinuation there was no significant change in levodopa pharmacokinetics or in patient response to 

levodopa compared to pretreatment levels. 

 

When Tasmar is administered together with levodopa, it increases the relative bioavailability (AUC) 

of levodopa approximately twofold. This is due to a decrease in clearance in L-dopa resulting in a 

prolongation of the terminal elimination half-life (t1/2) of levodopa. In general, the average peak 

levodopa plasma concentration (Cmax) and the time of its occurrence (tmax) were unaffected. The onset 

of effect occurs after the first administration. Studies in healthy volunteers and parkinsonian patients 

have confirmed that the maximum effect occurs with 100 – 200 mg tolcapone. Plasma levels of 3-

OMD were markedly and dose-dependently decreased by tolcapone when given with 

levodopa/AADC-I (aromatic amino acid decarboxylase - inhibitor) (benserazide or carbidopa). 

 

Tolcapone’s effect on levodopa pharmacokinetics is similar with all pharmaceutical formulations of 

levodopa/benserazide and levodopa/carbidopa; it is independent of levodopa dose, levodopa/AADC-I 

(benserazide or carbidopa) ratio and the use of sustained-release formulations. 

 

Clinical Efficacy and Safety 

Double blind placebo controlled clinical studies have shown a significant reduction of approximately 

20 % to 30 % in OFF time and a similar increase in ON time, accompanied by reduced severity of 

symptoms in fluctuating patients receiving Tasmar. Investigator’s global assessments of efficacy also 

showed significant improvement. 

 

A double-blind trial compared Tasmar with entacapone in Parkinson's disease patients who had at least 

three hours of OFF time per day while receiving optimised levodopa therapy. The primary outcome 

was the proportion of patients with a 1 or more hour increase in ON time (see Table 1). 

 

Tab. 1 Primary and Secondary Outcome of double-blind Trial 

 Entacapone 

N=75 

Tolcapon

e N=75 

p value 95 % CI 

Primary Outcome     

Number (proportion) with ≥1 hour ON time response 32 (43 %) 40 (53 %) p=0.191 -5.2;26.6 

Secondary Outcome     

Number (proportion) with moderate or marked 

improvement 

19 (25 %) 29 (39 %) p=0.080 -1.4;28.1 

     

Number (proportion) improved on both primary and 

secondary outcome 

13 (17 %) 24 (32 %) NA NA 

 

5.2 Pharmacokinetic properties 

 

In the therapeutic range, tolcapone pharmacokinetics are linear and independent of levodopa/AADC-I 

(benserazide or carbidopa) coadministration. 

 

Absorption: Tolcapone is rapidly absorbed with a tmax of approximately 2 hours. The absolute 

bioavailability of an oral administration is around 65 %. Tolcapone does not accumulate with three 

times daily dosing of 100 or 200 mg. At these doses, Cmax is approximately 3 and 6 µg/ml, 

respectively. Food delays and decreases the absorption of tolcapone, but the relative bioavailability of 

a dose of tolcapone taken with a meal is still 80 % to 90 %. 

 

Distribution: The volume of distribution (Vss) of tolcapone is small (9 l). Tolcapone does not distribute 

widely into tissues due to its high plasma protein binding (>99.9 %). In vitro experiments have shown 

that tolcapone binds mainly to serum albumin. 



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Biotransformation/Elimination: Tolcapone is almost completely metabolised prior to excretion, with 

only a very small amount (0.5 % of dose) found unchanged in urine. The main metabolic pathway of 

tolcapone is conjugation to its inactive glucuronide. In addition, the compound is methylated by 

COMT to 3-O-methyl-tolcapone and metabolised by cytochromes P450 3A4 and P450 2A6 to a 

primary alcohol (hydroxylation of the methyl group), which is subsequently oxidised to the carboxylic 

acid. The reduction to a putative amine, as well as the subsequent N-acetylation, occurs to a minor 

extent. After oral administration, 60 % of drug-related material is excreted into urine and 40 % into 

faeces. 

 

Tolcapone is a low-extraction-ratio drug (extraction ratio = 0.15), with a moderate systemic clearance 

of about 7 L/h. The t1/2 of tolcapone is approximately 2 hours. 

 

Hepatic impairment: Because of the risk of liver injury observed during post-marketing use, Tasmar is 

contraindicated in patients with liver disease or increased liver enzymes. A study in patients with 

hepatic impairment has shown that moderate non-cirrhotic liver disease had no impact on the 

pharmacokinetics of tolcapone. However, in patients with moderate cirrhotic liver disease, clearance 

of unbound tolcapone was reduced by almost 50 %. This reduction may increase the average 

concentration of unbound drug two-fold. 

 

Renal impairment: The pharmacokinetics of tolcapone have not been investigated in patients with 

renal impairment. However, the relationship of renal function and tolcapone pharmacokinetics has 

been investigated using population pharmacokinetics during clinical trials. The data of more than 400 

patients have confirmed that over a wide range of creatinine clearance values (30-130 mL/min) the 

pharmacokinetics of tolcapone are unaffected by renal function. This could be explained by the fact 

that only a negligible amount of unchanged tolcapone is excreted in the urine, and the main 

metabolite, tolcapone-glucuronide, is excreted both in urine and in bile (faeces). 

 

5.3 Preclinical safety data 

 

Preclinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction. 

 

Carcinogenesis, mutagenesis: 3 % and 5 % of rats in the mid- and high- dose groups, respectively, of 

the 24-month carcinogenicity study were shown to have renal epithelial tumours (adenomas or 

carcinomas). However, no evidence of renal toxicity was observed in the low-dose group. An 

increased incidence of uterine adenocarcinomas was seen in the high-dose group of the rat 

carcinogenicity study. There were no similar renal findings in the mouse or dogs carcinogenicity 

studies.  

Mutagenesis: Tolcapone was shown not to be genotoxic in a complete series of mutagenicity studies. 

 

Toxicity to reproduction: Tolcapone, when administered alone, was shown to be neither teratogenic 

nor to have any relevant effects on fertility. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core: 

Calcium hydrogen phosphate  

Microcrystalline cellulose 

Povidone K30 

Sodium starch glycollate 

Lactose  

Talc 

Magnesium stearate. 



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Film-coat: 

Hydroxypropylmethylcellulose 

Talc 

Yellow iron oxide  

Ethylcellulose 

Titanium dioxide  

Triacetin 

Sodium lauril sulfate 

 

6.2 Incompatibilities 

 

Not applicable 

 

6.3 Shelf life 

 

5 years 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions 

 

6.5 Nature and contents of container 

 

Tasmar is available in PVC/PE/PVDC blisters (pack sizes of 30 and 60 film-coated tablets) and in 

amber glass bottles without desiccant (pack sizes of 30, 60,100 and 200 film-coated tablets).  

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

No special requirements for disposal. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Meda AB 

Pipers väg 2A 

S-170 09 Solna  

Sweden 

 

 

8. MARKETING AUTHORISATION NUMBERS  

 

EU/1/97/044/001-3, 7, 8, 10 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 27 August 1997 

Renewal of the authorisation: 31 August 2004 

Date of latest renewal: 21 July2014 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 



13 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

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

 

 



14 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasmar 200 mg film coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 200 mg tolcapone. 

Excipients with known effect: Each tablet contains 15 mg lactose  

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

 Film-coated tablet. 

Orange yellow to brown yellow, hexagonal, biconvex, film-coated tablet. “TASMAR” and “200” are 

engraved on one side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Tasmar is indicated in combination with levodopa/benserazide or levodopa/carbidopa for use in 

patients with levodopa-responsive idiopathic Parkinson’s disease and motor fluctuations, who failed to 

respond to or are intolerant of other catechol-o-methyltransferase (COMT) inhibitors (see section 5.1). 

Because of the risk of potentially fatal, acute liver injury, Tasmar should not be considered as a first-

line adjunct therapy to levodopa/benserazide or levodopa/carbidopa (see sections 4.4 and 4.8).  

Since Tasmar should be used only in combination with levodopa/benserazide and levodopa/carbidopa, 

the prescribing information for these levodopa preparations is also applicable to their concomitant use 

with Tasmar. 

 

4.2 Posology and method of administration 

 

Posology 

 

Paediatric population 

Tasmar is not recommended for use in children below the age of 18 due to insufficient data on safety 

or efficacy. There is no relevant indication for use in children and adolescents. 

 

Elderly patients 

No dose adjustment of Tasmar is recommended for elderly patients. 

 

Patients with hepatic impairment (see section 4.3) 

Tasmar is contraindicated for patients with liver disease or increased liver enzymes.  

 

Patients with renal impairement (see section 5.2) 

No dose adjustment of Tasmar is recommended for patients with mild or moderate renal impairment 

(creatinine clearance of 30 ml/min or greater). Patients with severe renal impairement (creatinine 

clearance <30 ml/min) should be treated with caution. No information on the tolerability of tolcapone 

in these populations is available (see section 5.2) 

 

Method of administration 

The administration of Tasmar is restricted to prescription and supervision by physicians experienced 

in the management of advanced Parkinson's disease. 

 

Tasmar is administered orally three times daily. 



15 

Tasmar may be taken with or without food (see section 5.2). 

Tasmar tablets are film-coated and should be swallowed whole because tolcapone has a bitter taste. 

 

Tasmar can be combined with all pharmaceutical formulations of levodopa/benserazide and 

levodopa/carbidopa (see also section 4.5). 

 

The first dose of the day of Tasmar should be taken together the first dose of the day of a levodopa 

preparation, and the subsequent doses should be given approximately 6 and 12 hours later. Tasmar 

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

The recommended dose of Tasmar is 100 mg three times daily, always as an adjunct to 

levodopa/benserazide or levodopa/carbidopa therapy. Only in exceptional circumstances, when the 

anticipated incremental clinical benefit justifies the increased risk of hepatic reactions, should the dose 

be increased to 200 mg three times daily. (see sections 4.4 and 4.8). If substantial clinical benefits are 

not seen within 3 weeks of the initiation of the treatment (regardless of dose) Tasmar should be 

discontinued. 

The maximum therapeutic dose of 200 mg three times daily should not be exceeded, as there is no 

evidence of additional efficacy at higher doses. 

 

Liver function should be checked before starting treatment with Tasmar and then monitored every 2 

weeks for the first year of therapy, every 4 weeks for the next 6 months and every 8 weeks thereafter. 

If the dose is increased to 200 mg tid, liver enzyme monitoring should take place before increasing the 

dose and then be reinitiated following the same sequence of frequencies as above (see sections 4.4 and 

4.8). 

 

Tasmar treatment should also be discontinued if ALT (alanine amino transferase) and/or AST 

(aspartate amino transferase) exceed the upper limit of normal or symptoms or signs suggest the onset 

of hepatic failure (see section 4.4). 

 

Levodopa adjustments during Tasmar treatment:  

As Tasmar decreases the breakdown of levodopa in the body, side effects due to increased levodopa 

concentrations may occur when beginning Tasmar treatment. In clinical trials, more than 70 % of 

patients required a decrease in their daily levodopa dose if their daily dose of levodopa was >600 mg 

or if patients had moderate or severe dyskinesias before beginning treatment. 

The average reduction in daily levodopa dose was about 30 % in those patients requiring a levodopa 

dose reduction. When beginning Tasmar, all patients should be informed of the symptoms of excessive 

levodopa dose and what to do if it occurs. 

Levodopa adjustments when Tasmar is discontinued:  

The following suggestions are based on pharmacological considerations and have not been evaluated 

in clinical trials. Levodopa dose should not be decreased when Tasmar therapy is being discontinued 

due to side effects related to too much levodopa. However, when Tasmar therapy is being 

discontinued for reasons other than too much levodopa, levodopa dose may have to be increased to 

levels equal to or greater than before initiation of Tasmar therapy, especially if the patient had large 

decreases in levodopa when starting Tasmar. In all cases, patients should be educated on the 

symptoms of levodopa under-dose and what to do if it occurs. Adjustments in levodopa are most likely 

to be required within 1-2 days of Tasmar discontinuation. 

 

4.3 Contraindications 

 

• Hypersensitivity to tolcapone or any of its other ingredients listed in section 6.1.  

• Evidence of liver disease or increased liver enzymes 

• Severe dyskinesia 

•   A previous history of Neuroleptic Malignant Syndrome (NMS) Symptom Complex  and /or  

            non-traumatic Rhabdomyolysis or Hyperthermia. 

•           Phaeochromocytoma. 

•  Treatment with non-selective mono amino oxidase (MAO) inhibitors 



16 

4.4 Special warnings and precautions for use 

 

Tasmar therapy should only be initiated by physicians experienced in the management of advanced 

Parkinson’s disease, to ensure an appropriate risk-benefit assessment. Tasmar should not be prescribed 

until there has been a complete informative discussion of the risks with the patient. 

 

Tasmar should be discontinued if substantial clinical benefits are not seen within 3 weeks of the 

initiation of the treatment regardless of dose. 

 

Liver injury: 

Because of the risk of rare but potentially fatal acute liver injury, Tasmar is only indicated for use in 

patients with levodopa-responsive idiopathic Parkinson’s disease and motor fluctuations, who failed to 

respond to or are intolerant of other COMT inhibitors. Periodic monitoring of liver enzymes cannot 

reliably predict the occurrence of fulminant hepatitis. However, it is generally believed that early 

detection of medicine-induced hepatic injury along with immediate withdrawal of the suspect 

medication enhances the likelihood for recovery. Liver injury has most often occurred between 1 

month and 6 months after starting treatment with Tasmar. Additionally late onset hepatitis after 

approximately 18 months of treatment has been reported rarely. 

It should also be noted that female patients may have a higher risk of liver injury (see section 4.8). 

 

Before starting treatment: If liver function tests are abnormal or there are signs of impaired liver 

function, Tasmar should not be prescribed. If Tasmar is to be prescribed, the patient should be 

informed about the signs and symptoms which may indicate liver injury, and to contact the physician 

immediately.  

 

During treatment: Liver function should be monitored every 2 weeks for the first year of therapy, 

every 4 weeks for the next 6 months and every 8 weeks thereafter. If the dose is increased to 200 mg 

tid, liver enzyme monitoring should take place before increasing the dose and then be re-initiated 

following the sequence of frequencies as above. Treatment should be immediately discontinued if 

ALT and/or AST exceed the upper limit of normal or if symptoms or signs suggesting the onset of 

hepatic failure (persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, right upper 

quadrant tenderness) develop. 

 

If treatment is discontinued: Patients who show evidence of acute liver injury while on Tasmar and are 

withdrawn from the medicinal product may be at increased risk for liver injury if Tasmar is re-

introduced. Accordingly, such patients should not be considered for re-treatment. 

 

Neuroleptic Malignant Syndrome (NMS): 

In Parkinson`s patients, NMS tends to occur when discontinuing or stopping dopaminergic-enhancing 

medications. Therefore, if symptoms occur after discontinuing Tasmar, physicians should consider 

increasing the patient’s levodopa dose (see section 4.2). 

 

Isolated cases consistent with NMS have been associated with Tasmar treatment. Symptoms have 

usually onset during Tasmar treatment or shortly after Tasmar has been discontinued. NMS is 

characterised by motor symptoms (rigidity, myoclonus and tremor), mental status changes (agitation, 

confusion, stupor and coma), elevated temperature, autonomic dysfunction (labile blood pressure, 

tachycardia) and elevated serum creatine phosphokinase (CPK) which may be a consequence of 

myolysis. A diagnosis of NMS should be considered even if not all the above findings are present. 

Under such a diagnosis Tasmar should be immediately discontinued and the patient should be 

followed up closely.  

 

Before starting treatment: To reduce the risk of NMS, Tasmar should not be prescribed for patients 

with severe dyskinesia or a previous history of NMS including rhabdomyolysis or hyperthermia (see 

section 4.3). Patients receiving multiple medications with effects on different central nervous system 

(CNS) pathways (e.g. antidepressants, neuroleptics, anticholinergics) may be at greater risk of 

developing NMS.  

 



17 

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 and/or other dopaminergic treatments such as Tasmar in association with levodopa. Review 

of treatment is recommended if such symptoms develop. 

 

Dyskinesia, nausea and other levodopa-associated adverse reactions: Patients may experience an 

increase in levodopa-associated adverse reactions. Reducing the dose of levodopa (see section 4.2) 

may often mitigate these adverse reactions. 

 

Diarrhoea: In clinical trials, diarrhoea developed in 16 % and 18 % of patients receiving Tasmar 

100 mg tid and 200 mg tid respectively, compared to 8 % of patients receiving placebo. Diarrhoea 

associated with Tasmar usually began 2 to 4 months after initiation of therapy. Diarrhoea led to 

withdrawal of 5% and 6% of patients receiving Tasmar 100 mg tid and 200 mg tid respectively, 

compared to 1 % of patients receiving placebo. 

 

Benserazide interaction: Due to the interaction between high dose benserazide and tolcapone (resulting 

in increased levels of benserazide), the prescriber should, until more experience has been gained, be 

observant of dose-related adverse reactions (see section 4.5). 

 

MAO inhibitors: Tasmar should not be given in conjunction with non-selective monoamine oxidase 

(MAO) inhibitors (e.g. phenelzine and tranylcypromine). The combination of MAO-A and MAO-B 

inhibitors is equivalent to non-selective MAO-inhibition, therefore they should not both be given 

concomitantly with Tasmar and levodopa preparations (see also section 4.5). Selective MAO-B 

inhibitors should not be used at higher than recommended doses (e.g. selegiline 10 mg/day) when co-

administered with Tasmar.  

 

Warfarin: Since clinical information is limited regarding the combination of warfarin and tolcapone, 

coagulation parameters should be monitored when these drugs are co-administered. 

 

Special populations: Patients with severe renal impairment (creatinine clearance <30 ml/min) should 

be treated with caution. No information on the tolerability of tolcapone in these populations is 

available (see section 5.2). 

 

Lactose intolerance: Tasmar contains lactose. Patients with rare hereditary problems of galactose 

intolerance, the Lapp lactase deficiency or glucose malabsorption should not take this medicine. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Tasmar, as a COMT inhibitor, is known to increase the bioavailability of the co-adminstered levodopa. 

The consequent increase in dopaminergic stimulation can lead to the dopaminergic adverse reactions 

observed after treatment with COMT inhibitors. The most common of these are increased dyskinesia, 

nausea, vomiting, abdominal pain, syncope, orthostatic complains, constipation, sleep disorders, 

somnolence, hallucination. 

 

Levodopa has been associated with somnolence and episodes of sudden sleep onset. Sudden onset of 

sleep during daily activities, in some cases without awareness or warning signs, has been reported very 

rarely. Patients must be informed of this and advised to exercise caution while driving or operating 

machines during treatment with levodopa. Patients who have experienced somnolence and/or an 

episode of sudden sleep onset must refrain from driving or operating machines. Furthermore a 

reduction of levodopa dose or termination of therapy may be considered (see section 4.7).  

 

Catechols and other drugs metabolised by catechol-O-methyltransferase (COMT): Tolcapone may 

influence the pharmacokinetics of drugs metabolised by COMT. No effects were seen on the 

pharmacokinetics of the COMT substrate carbidopa. An interaction was observed with benserazide, 

which may lead to increased levels of benserazide and its active metabolite. The magnitude of the 



18 

effect was dependent on the dose of benserazide. The plasma concentrations of benserazide observed 

after co-administration of tolcapone and benserazide-25 mg/levodopa were still within the range of 

values observed with levodopa/benserazide alone. On the other hand, after co-administration of 

tolcapone and benserazide-50 mg/levodopa the benserazide plasma concentrations could be increased 

above the levels usually observed with levodopa/benserazide alone. The effect of tolcapone on the 

pharmacokinetics of other drugs metabolised by COMT such as -methyldopa, dobutamine, 
apomorphine, adrenaline and isoprenaline have not been evaluated. The prescriber should be observant 

of adverse reactions caused by putative increased plasma levels of these drugs when combined with 

Tasmar. 

 

Effect of tolcapone on the metabolism of other drugs: Due to its affinity for cytochrome CYP2C9 in 

vitro, tolcapone may interfere with drugs whose clearance is dependent on this metabolic pathway, 

such as tolbutamide and warfarin. In an interaction study, tolcapone did not change the 

pharmacokinetics of tolbutamide. Therefore, clinically relevant interactions involving cytochrome 

CYP2C9 appear unlikely. 

 

Since clinical information is limited regarding the combination of warfarin and tolcapone, coagulation 

parameters should be monitored when these drugs are co-administered. 

 

Drugs that increase catecholamines: Since tolcapone interferes with the metabolism of catecholamines, 

interactions with other drugs affecting catecholamine levels are theoretically possible. 

 

When Tasmar was given together with levodopa/carbidopa and desipramine, there was no significant 

change in blood pressure, pulse rate and plasma concentrations of desipramine. Overall, the frequency 

of adverse reactions increased slightly. These adverse reactions were predictable based on the known 

adverse reactions to each of the three drugs individually. Therefore, caution should be exercised when 

potent noradrenaline uptake inhibitors such as desipramine, maprotiline, or venlafaxine are 

administered to Parkinson’s disease patients being treated with Tasmar and levodopa preparations. 

 

In clinical trials, patients receiving Tasmar/levodopa preparations reported a similar adverse reaction 

profile independent of whether or not they were also concomitantly administered selegiline (a MAO-B 

inhibitor). 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

There are no adequate data from the use of tolcapone in pregnant women. Therefore, Tasmar should 

be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 

 

Breast-feeding 

In animal studies, tolcapone was excreted into maternal milk. 

 

The safety of tolcapone in infants is unknown; therefore, women should not breast-feed during 

treatment with Tasmar. 

 

Fertility 

In rats and rabbits, embryo-foetal toxicity was observed after tolcapone administration (see section 

5.3). The potential risk for humans is unknown.  

 

 

 

4.7 Effects on ability to drive and use machines 

 

No studies on the effects of Tasmar on the ability to drive and use machines have been performed. 

There is no evidence from clinical studies that Tasmar adversely influences a patient’s ability to drive 

and use machines. However patients should be advised that their ability to drive and operate machines 

may be compromised due to their Parkinson’s disease symptoms.  



19 

 

Tasmar, as a COMT inhibitor, is known to increase the bioavailability of the co-adminstered levodopa. 

The consequent increase in dopaminergic stimulation can lead to the dopaminergic side effects 

observed after treatment with COMT inhibitors. Patients being treated with Levodopa 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 section 

4.4)  

 

4.8 Undesirable effects 

 

The most commonly observed adverse reaction associated with the use of Tasmar, occurring more 

frequently than in placebo-treated patients are listed in the table below. However, Tasmar, as a COMT 

inhibitor, is known to increase the bioavailability of the co-administered levodopa. The consequent 

increase in dopaminergic stimulation can lead to the dopaminergic side effects observed after 

treatment with COMT inhibitors. The most common of these are increased dyskinesia, nausea, 

vomiting, abdominal pain, syncope, orthostatic complains, constipation, sleep disorders, somnolence, 

hallucination. 

 

The only adverse reaction commonly leading to discontinuation of Tasmar in clinical trials was 

diarrhoea (see section 4.4). 

 

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) 

 

Experience with Tasmar obtained in parallel placebo-controlled randomised studies in patients with 

Parkinson’s disease is shown in the following table, which lists adverse reactions with a potential 

relationship to Tasmar. 

Summary of potentially Tasmar-related adverse reactions, with crude incidence rates for the phase III 

placebo-controlled studies: 

 

 

 

System organ class 

 

Incidence 

 

Adverse Events 

Infections and infestations Common Upper respiratory tract infection 

Psychiatric disorders Very common Sleep disorder 

  Dreaming excessive 

  Somnolence 

  Confusion 

  Hallucination 

 Rare Impulse control disorders* 

(Libido increased, hypersexuality, 

pathological gambling, compulsive 

spending or buying, binge eating, 

compulsive eating (see section 4.4)) 

Nervous system disorders Very common Dyskinesia 

  Dystonia 

  Headache 

  Dizziness 

  Somnolence 

  Orthostatic complaints 



20 

 

System organ class 

 

Incidence 

 

Adverse Events 

 Rare Neuroleptic Malignant Syndrome 

Symptom Complex (see section 4.4) 

 Common Hypokinesia 

  Syncope 

Gastrointestinal disorders Very common Nausea 

   

  Diarrhoea 

 Common Vomiting 

  Constipation 

  Xerostomia 

  Abdominal pain 

  Dyspepsia 

Metabolism and nutrition 

disorders 

Very common Anorexia 

Skin and subcutaneous tissue 

disorders 

Common Sweating increased 

Renal and urinary disorders Common Urine discoloration 

General disorders and 

administration site conditions 

Common Chest pain 

  Influenza like illness 

Hepatobiliary disorders Uncommon Hepatocellular injury, in rare cases 

with fatal outcome* (see section 4.4) 

Investigations Common Increase of alanine aminotransferase 

(ALT) 

*: Adverse reactions for which no frequency could be derived from clinical studies (i.e. where a 

specific adverse reaction was not observed in clinical trials but was reported post-marketing only) 

are indicated by an asterisk (*), and the frequency category has been calculated according to EU 

Guideline. 
 

Increase of alanine aminotransferase 

Increases to more than three times the upper limit of normal (ULN) in alanine aminotransferase (ALT) 

occurred in 1 % of patients receiving Tasmar 100 mg three times daily, and 3 % of patients at 200 mg 

three times daily. Increases were approximately two times more likely in females. The increases 

usually appeared within 6 to 12 weeks of starting treatment, and were not associated with any clinical 

signs or symptoms. In about half the cases, transaminase levels returned spontaneously to baseline 

values whilst patients continued Tasmar treatment. For the remainder, when treatment was 

discontinued, transaminase levels returned to pre-treatment levels. 

 

Hepatocellular injury 

Rare cases of severe hepatocellular injury resulting in death have been reported during marketed use 

(see section 4.4).  

 

Neuroleptic Malignant Syndrome Symptom Complex  

Isolated cases of patients with symptoms suggestive of Neuroleptic Malignant Syndrome Symptom 

Complex (see sectiom 4.4) have been reported following reduction or discontinuation of Tasmar and 

following introduction of Tasmar when this was accompanied by a significant reduction in other 

concomitant dopaminergic medications. In addition, rhabdomyolysis, secondary to NMS or severe 

dyskinesia, has been observed.  

 

Urine discolouration: Tolcapone and its metabolites are yellow and can cause a harmless 

intensification in the colour of the patient’s urine. 



21 

 

Impulse control disorders: Pathological gambling, increased libido, hypersexuality, compulsive 

spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine 

agonists and/or other dopaminergic treatments such as Tasmar in association with Levedopa (see 

section 4.4 `special warnings and precautions for use´). 

 

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 

 

Isolated cases of either accidental or intentional overdose with tolcapone tablets have been reported. 

However clinical circumstances of these cases were so diverse, that no general conclusions can be 

drawn from the cases. 

 

The highest dose of tolcapone administered to humans was 800 mg three times daily, with and without 

levodopa coadministration, in a one week study in healthy elderly volunteers. The peak plasma 

concentrations of tolcapone at this dose were on average 30 µg/ml (compared to 3 and 6 µg/ml with 

100 mg tid and 200 mg tid of tolcapone respectively). Nausea, vomiting and dizziness were observed, 

particularly in combination with levodopa. 

 

Management of overdose: Hospitalisation is advised. General supportive care is indicated. Based on 

the physicochemical properties of the compound, hemodialysis is unlikely to be of benefit. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmaco-therapeutic group: Anti-Parkinson drugs, other dopaminergic agents, ATC code: NO4BX01  

 

Mecahnism of action 

Tolcapone is an orally active, selective and reversible catechol-O-methyltransferase (COMT) 

inhibitor. Administered concomitantly with levodopa and an aromatic amino acid decarboxylase 

inhibitor (AADC-I), it leads to more stable plasma levels of levodopa by reducing metabolism of 

levodopa to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD). 

 

High levels of plasma 3-OMD have been associated with poor response to levodopa in Parkinson’s 

disease patients. Tolcapone markedly reduces the formation of 3-OMD. 

 

Pharmacodynamic effects 

Studies in healthy volunteers have shown that tolcapone reversibly inhibits human erythrocyte COMT 

activity after oral administration. The inhibition is closely related to plasma tolcapone concentration. 

With 200 mg tolcapone, maximum inhibition of erythrocyte COMT activity is, on average, greater 

than 80 %. During dosing with Tasmar 200 mg three times daily, erythrocyte COMT inhibition at 

trough is 30 % to 45 %, with no development of tolerance.  

 

Transient elevation above pretreatment levels of erythrocyte COMT activity was observed after 

withdrawal of tolcapone. However, a study in Parkinson’s patients confirmed that after treatment 

discontinuation there was no significant change in levodopa pharmacokinetics or in patient response to 

levodopa compared to pretreatment levels. 

 



22 

When Tasmar is administered together with levodopa, it increases the relative bioavailability (AUC) 

of levodopa approximately twofold. This is due to a decrease in clearance in L-dopa resulting in a 

prolongation of the terminal elimination half-life (t1/2) of levodopa. In general, the average peak 

levodopa plasma concentration (Cmax) and the time of its occurrence (tmax) were unaffected. The onset 

of effect occurs after the first administration. Studies in healthy volunteers and parkinsonian patients 

have confirmed that the maximum effect occurs with 100 – 200 mg tolcapone. Plasma levels of 3-

OMD were markedly and dose-dependently decreased by tolcapone when given with 

levodopa/AADC-I (aromatic amino acid decarboxylase - inhibitor) (benserazide or carbidopa). 

 

Tolcapone’s effect on levodopa pharmacokinetics is similar with all pharmaceutical formulations of 

levodopa/benserazide and levodopa/carbidopa; it is independent of levodopa dose, levodopa/AADC-I 

(benserazide or carbidopa) ratio and the use of sustained-release formulations. 

 

Clinical Efficacy and Safety 

Double blind placebo controlled clinical studies have shown a significant reduction of approximately 

20 % to 30 % in OFF time and a similar increase in ON time, accompanied by reduced severity of 

symptoms in fluctuating patients receiving Tasmar. Investigator’s global assessments of efficacy also 

showed significant improvement. 

 

A double-blind trial compared Tasmar with entacapone in Parkinson's disease patients who had at least 

three hours of OFF time per day while receiving optimised levodopa therapy. The primary outcome 

was the proportion of patients with a 1 or more hour increase in ON time (see Table 1). 

 

Tab. 1 Primary and Secondary Outcome of double-blind Trial 

 Entacapone 

N=75 

Tolcapon

e N=75 

p value 95 % CI 

Primary Outcome     

Number (proportion) with ≥1 hour ON time response 32 (43 %) 40 (53 %) p=0.191 -5.2;26.6 

Secondary Outcome     

Number (proportion) with moderate or marked 

improvement 

19 (25 %) 29 (39 %) p=0.080 -1.4;28.1 

     

Number (proportion) improved on both primary and 

secondary outcome 

13 (17 %) 24 (32 %) NA NA 

 

5.2 Pharmacokinetic properties 

 

In the therapeutic range, tolcapone pharmacokinetics are linear and independent of levodopa/AADC-I 

(benserazide or carbidopa) coadministration. 

 

Absorption: Tolcapone is rapidly absorbed with a tmax of approximately 2 hours. The absolute 

bioavailability of an oral administration is around 65 %. Tolcapone does not accumulate with three 

times daily dosing of 100 or 200 mg. At these doses, Cmax is approximately 3 and 6 µg/ml, 

respectively. Food delays and decreases the absorption of tolcapone, but the relative bioavailability of 

a dose of tolcapone taken with a meal is still 80 % to 90 %. 

 

Distribution: The volume of distribution (Vss) of tolcapone is small (9 l). Tolcapone does not distribute 

widely into tissues due to its high plasma protein binding (>99.9 %). In vitro experiments have shown 

that tolcapone binds mainly to serum albumin. 

 

Biotransformation/Elimination: Tolcapone is almost completely metabolised prior to excretion, with 

only a very small amount (0.5 % of dose) found unchanged in urine. The main metabolic pathway of 

tolcapone is conjugation to its inactive glucuronide. In addition, the compound is methylated by 

COMT to 3-O-methyl-tolcapone and metabolised by cytochromes P450 3A4 and P450 2A6 to a 

primary alcohol (hydroxylation of the methyl group), which is subsequently oxidised to the carboxylic 

acid. The reduction to a putative amine, as well as the subsequent N-acetylation, occurs to a minor 



23 

extent. After oral administration, 60 % of drug-related material is excreted into urine and 40 % into 

faeces. 

 

Tolcapone is a low-extraction-ratio drug (extraction ratio = 0.15), with a moderate systemic clearance 

of about 7 L/h. The t1/2 of tolcapone is approximately 2 hours. 

 

Hepatic impairment: Because of the risk of liver injury observed during post-marketing use, Tasmar is 

contraindicated in patients with liver disease or increased liver enzymes. A study in patients with 

hepatic impairment has shown that moderate non-cirrhotic liver disease had no impact on the 

pharmacokinetics of tolcapone. However, in patients with moderate cirrhotic liver disease, clearance 

of unbound tolcapone was reduced by almost 50 %. This reduction may increase the average 

concentration of unbound drug two-fold. 

 

Renal impairment: The pharmacokinetics of tolcapone have not been investigated in patients with 

renal impairment. However, the relationship of renal function and tolcapone pharmacokinetics has 

been investigated using population pharmacokinetics during clinical trials. The data of more than 400 

patients have confirmed that over a wide range of creatinine clearance values (30-130 mL/min) the 

pharmacokinetics of tolcapone are unaffected by renal function. This could be explained by the fact 

that only a negligible amount of unchanged tolcapone is excreted in the urine, and the main 

metabolite, tolcapone-glucuronide, is excreted both in urine and in bile (faeces). 

 

5.3 Preclinical safety data 

 

Preclinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction. 

 

Carcinogenesis, mutagenesis: 3 % and 5 % of rats in the mid- and high- dose groups, respectively, of 

the 24-month carcinogenicity study were shown to have renal epithelial tumours (adenomas or 

carcinomas). However, no evidence of renal toxicity was observed in the low-dose group. An 

increased incidence of uterine adenocarcinomas was seen in the high-dose group of the rat 

carcinogenicity study. There were no similar renal findings in the mouse or dogs carcinogenicity 

studies.  

Mutagenesis: Tolcapone was shown not to be genotoxic in a complete series of mutagenicity studies. 

 

Toxicity to reproduction: Tolcapone, when administered alone, was shown to be neither teratogenic 

nor to have any relevant effects on fertility. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core: 

Calcium hydrogen phosphate  

Microcrystalline cellulose 

Povidone K30 

Sodium starch glycollate 

Lactose  

Talc 

Magnesium stearate. 

 

Film-coat: 

Hydroxypropylmethylcellulose, 

Talc 

Yellow iron oxide  

Ethylcellulose 

Titanium dioxide  



24 

Triacetin 

Sodium lauril sulfate 

 

6.2 Incompatibilities 

 

Not applicable 

 

6.3 Shelf life 

 

5 years 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 

 

Tasmar is available in PVC/PE/PVDC blisters (pack sizes of 30 and 60 film-coated tablets) and in 

amber glass bottles without desiccant (pack sizes of 100 film-coated tablets). 

Not all pack sizes may be marketed 

 

6.6 Special precautions for disposal 

 

No special requirements for disposal. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Meda AB 

Pipers väg 2A 

S-170 09 Solna  

Sweden 

 

 

8. MARKETING AUTHORISATION NUMBERS  

 

EU/1/97/044/004-6 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 27 August 1997 

Renewal of the authorisation: 31 August 2004 

Date of latest renewal: 21 July 2014 

 

 

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. 

 

 

 

 

 

 



25 

 

 

 

 

 

 

 

 

 

 

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 

 



26 

A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

ICN Polfa Rzeszów S.A.  

ul. Przemysłowa 2 

35-959 Rzeszów  

Poland 

 

 

B.       CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  

 

Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 

Characteristics, 4.2) 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  

 

• Periodic Safety Update Reports  
 

The marketing authorisation holder shall submit periodic safety update reports for this product in 

accordance with the requirements set out in the list of Union reference dates (EURD list) ) provided 

for under Article 107c(7) of Directive 2001/83/EC and  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 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. 

 

If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 

time. 

 

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

 

Not applicable 

  



27 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



28 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

Outer Carton  and bottle label, 30, 60, 100, 200 film-coated tablets 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasmar 100 mg film-coated tablets 

Tolcapone 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 100 mg tolcapone 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains lactose. 

See leaflet for further information 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 film-coated tablets 

60 film-coated tablets 

100 film-coated tablets 

200 film-coated tablets 

. 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. For oral use. 

The tablets should be swallowed whole. Do not break or crush tablet. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Meda AB 

Pipers väg 2A 

S-170 09 Solna  

Sweden 

 



30 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/97/044/007  30 tablets 

EU/1/97/044/008  60 tablets 

EU/1/97/044/003 100 tablets 

EU/1/97/044/0010 200 tablets 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasmar 100 mg (only applicable for the outer carton) 

 

17.      UNIQUE IDENTIFIER – 2D BARCODE 

 

     2D barcode carrying the unique identifier included 

 

18.      UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

     PC: 

     SN: 

     NN: 

 

 

 

 

 

 

 

 



31 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

Outer carton for blister packs [ 30 and 60 film-coated tablets] 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasmar 100 mg film-coated tablets 

Tolcapone 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 100 mg tolcapone 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains lactose. 

See leaflet for further information 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 film-coated tablets 

60 film-coated tablets 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. For oral use. 

The tablets should be swallowed whole. Do not break or crush tablet. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Meda AB 

Pipers väg 2A 

S-170 09 Solna  

Sweden 

 



32 

12. MARKETING AUTHORISATION NUMBER 

 

EU/1/97/044/001 30 tablets 

EU/1/97/044/002 60 tablets 

 

13. BATCH NUMBER 

 

 Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasmar 100 mg (only applicable for the outer packaging 

 

 

17.      UNIQUE IDENTIFIER – 2D BARCODE 

 

     2D barcode carrying the unique identifier included 

 

18.      UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

     PC: 

     SN: 

     NN: 

 



33 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasmar 100 mg film-coated tablets 

Tolcapone 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Meda AB.  

 

3. EXPIRY DATE 

 

EXP 

 

4. BATCH NUMBER 

 

Batch 

 

5. OTHER 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



34 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

Outer carton and bottle label, 100 film-coated tablets 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasmar 200 mg film-coated tablets 

Tolcapone 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 200 mg tolcapone 

tolcapone 200 mg 

 

3. LIST OF EXCIPIENTS 

 

Also contains lactose. 

See leaflet for further information  

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 film-coated tablets 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. For oral use. 

The tablets should be swallowed whole. Do not break or crush tablet. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Meda AB 

Pipers väg 2A 

S-170 09 Solna  

Sweden 

 

 

 



35 

12. MARKETING AUTHORISATION NUMBER 

 

 

EU/1/97/044/006 100 tablets 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasmar 200 mg  

 

17.      UNIQUE IDENTIFIER – 2D BARCODE 

 

     2D barcode carrying the unique identifier included 

 

18.      UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

     PC: 

     SN: 

     NN: 

 

  



36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

Outer Carton and blister packs, 30 and 60 film-coated tablets 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasmar 200 mg film-coated tablets 

Tolcapone 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 200 mg tolcapone 

tolcapone 200 mg 

 

3. LIST OF EXCIPIENTS 

 

Also contains lactose 

See leaflet for further information. 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 film-coated tablets 

60 film-coated tablets 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. For oral use 

The tablets should be swallowed whole. Do not break or crush tablet. 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

8. EXPIRY DATE 

 

EXP 

 

9. SPECIAL STORAGE CONDITIONS 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Meda AB 

Pipers väg 2A 

S-170 09 Solna  

Sweden 

 

 

 



37 

12. MARKETING AUTHORISATION NUMBER 

 

EU/1/97/044/004  30 tablets 

EU/1/97/044/005  60 tablets 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Tasmar 200 mg  

 

 

17.      UNIQUE IDENTIFIER – 2D BARCODE 

 

     2D barcode carrying the unique identifier included 

 

18.      UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

     PC: 

     SN: 

     NN: 

 



38 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Tasmar 200 mg film-coated tablets 

Tolcapone 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Meda AB  

 

3. EXPIRY DATE 

 

EXP 

 

4. BATCH NUMBER 

 

Batch 

 

5. OTHER 

  



39 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



40 

Package leaflet: Information for the user 

 

Tasmar 100 mg film-coated tablets 

Tolcapone 

 

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 further questions, please ask your doctor or your pharmacist. 

-   This medicine has been prescribed for you. 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 Tasmar is and what it is used for 

2. What do you need to know before you take Tasmar 

3. How to take Tasmar 

4. Possible side effects 

5. How to store Tasmar 

6. Contents of the pack and other information 

 

 

1. What Tasmar is and what it is used for 

For the treatment of Parkinson´s disease, Tasmar is used together with the medicinal product levodopa 

(as levodopa/benserazide or levodopa/carbidopa). 

Tasmar is used when all other alternative medicines cannot stabilise your Parkinson’s disease.  

 

For the treatment of your Parkinson´s disease you already take levodopa. 

A natural protein (enzyme) in your body, the (COMT) Catechol-O-methyltransferase breaks down the 

levodopa. . Tasmar blocks this enzyme and thus slows the breakdown of levodopa. This means when it 

is taken together with levodopa (as levodopa/benserazide or levodopa/carbidopa) you should have an 

improvement in the symptoms of your Parkinson’s disease.  

 

 

2. What you need to know before you take Tasmar 

Do not take Tasmar: 

- if you have liver disease or increased liver enzymes 

- if you have severe involuntary movement (dyskinesia) 

-   if you have a previous history of severe symptoms of muscle stiffening, fever or mental   

            confusion (Neuroleptic Malignant Syndrome (NMS) Symptom Complex ) and /or if you have 

 damage of skeletal muscle tissue (non-traumatic Rhabdomyolysis) or fever (Hyperthermia). 

-  if you are hypersensitive (allergic) to the active substance tolcapone or to any of the other 

 ingredients of Tasmar. 

-  if you have a special type of tumor in the adrenal medulla (Phaeochromocytoma) 

-  if you take a certain medication to treat depression and anxiety, called  non-selective mono 

amino oxidase (MAO) inhibitors  

 

Warnings and precautions 

Talk to your doctor or pharmacist before taking Tasmar.  

You should not start taking Tasmar until your doctor 

- has described the risks of treatment with Tasmar, 

- has explained the measures necessary to minimise those risks, 

- has answered any questions you may have. 



41 

- if you are pregnant or intend to become pregnant. Your doctor will discuss the risks and benefits 

of taking Tasmar during pregnancy. The effects of Tasmar have not been studied in infants. You 

should not breast-feed your infant during treatment with Tasmar. 

 

Tell your doctor if you or your family/ carer notices you are developing urges or cravings to behave in 

ways that are unusual for you or you cannot resist the impulse, drive or temptation to carry out certain 

activities that could harm yourself or others. These behaviours are called impulse control disorders and 

can include addictive gambling, excessive eating or spending, an abnormally high sex drive or a 

preoccupation with an increase in sexual thoughts or feelings. Your doctor may need to review your 

treatments. 

 

You should only receive Tasmar if your Parkinson’s disease is not adequately controlled by the use of  

other therapies. 

 

In addition, your doctor will stop Tasmar treatment if after 3 weeks you do not improve enough to 

justify the risks of continuing treatment. 

 

Liver Injury: 

Tasmar may cause rare but potentially fatal liver injury. Liver injury has occurred most often after 1 

month and before 6 months. It should also be noted that female patients may have a higher risk of liver 

injury. Therefore, the following preventive measures have to be considered. 

 

Before beginning treatment:  

To reduce the risk of liver injury you should not use Tasmar if  

- you have a liver disease  
- in case of elevated liver function tests in the blood test done before starting treatment (tests of  

  alanine amino transferase (ALT) and aspartate amino transferase (AST)).  

 

While receiving treatment: 

During treatment, blood tests will be done in the following time intervals: 

- every 2 weeks during the first 12 months of therapy, 
- every 4 weeks during the following 6 months of therapy, 
- every 8 weeks during further treatment. 
The treatment will be stopped, if these blood tests become abnormal.  

 

The treatment with Tasmar may sometimes lead to disturbances in the way the liver works. Therefore, 

you should contact your doctor immediately if you experience symptoms such as nausea, vomiting, 

pain in your stomach (particulary over the liver in the right upper area), loss of appetite, weakness, 

fever, darkening of urine, jaundice (yellow skin or eyes) or if you tire more easily. 

If you have been already treated with Tasmar and developed acute liver injury during treatment, 

Tasmar should not be re-introduced again. 

 

NMS (Neuroleptic Malignant Syndrome):  

Symptoms of Neuroleptic Malignant Syndrome (NMS) may occur during Tasmar treatment. 

The NMS consists of some or all of the following: 

- severe muscle stiffness, jerking movements of muscles, arms or legs, and soreness of muscles. 
Muscle injury can sometimes cause dark urine. 

- other important symptoms are high fever and mental confusion. 
 

Rarely, after abruptly reducing or stopping Tasmar or other antiparkinsonian drugs, you may 

experience severe symptoms of muscle stiffening, fever or mental confusion. If this happens notify 

your doctor. 

 

The following preventive measures have to be considered. 

Before beginning treatment: 



42 

To reduce the risk of NMS you should not use Tasmar if your doctor says you have severe involuntary 

movement (dyskinesia) or a previous illness that may have been NMS. 

Inform your doctor about all prescription and non-prescription medications as the risk of NMS may be 

increased if you are taking some specific medications. 

 

While receiving treatment: 

If you develop any symptoms as described above, that you think may be NMS, you should report them 

to your doctor immediately.  

Do not stop Tasmar or any other Parkinson’s medications without telling your doctor as this may 

increase the risk of NMS. 

 

Inform your doctor also: 

- if you have any illnesses other than Parkinson’s disease, 

- if you are allergic to other medicines, food and dyes, 

- if soon after beginning and during treatment with Tasmar you have symptoms which may be 

caused by levodopa such as involuntary movement (dyskinesia) and nausea. 

 

If you feel unwell, you should contact your doctor because you may need to take less levodopa. 

 

Children and adolescents 

Tasmar is not recommended for use in children below the age of 18 due to insufficient data on safety 

or efficacy. There is no relevant indication for use in children and adolescents. 

 

Other Medicines and Tasmar 

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 

even those not prescribed (non-prescription medicines and herbals). 

 

Please inform your doctor about all other medicines you are taking especially:  

- antidepressants, 

- alpha-methyldopa (used to treat increased blood pressure), 

- apomorphine (used for Parkinson’s disease), 

- dobutamine (used for the chronic heart disease), 

- adrenaline  and isoprenaline (both used for heart attacks), 

-   anticoagulants of the warfarin type (that prevent blood clotting). In this case your doctor may  

             perform regular blood tests to monitor how easily your blood clots. 

 

If you go to hospital or if you are prescribed a new medicine, you must tell your doctor that you are 

taking Tasmar. 

 

Tasmar with food and drink and alcohol 

Tasmar can be taken with or without food. 

Tasmar should be taken with 1 glass of water. 

 

Pregnancy and breast-feeding and fertility 

You must tell your doctor if you are pregnant or intend to become pregnant. Your doctor will discuss 

the risks and benefits of taking Tasmar during pregnancy. 

 

The effects of Tasmar have not been studied in infants. You should not breast-feed your infant during 

treatment with Tasmar. 

 

Driving and using machines 

Since your ability to drive a car or operate machinery may be affected by Parkinson’s disease, you 

should discuss this with your doctor. 

 

Tasmar has an effect on the symptoms of your Parkinson’s disease. 



43 

Tasmar used with your other Parkinson medicines can cause excessive drowsiness (somnolence ) and 

sudden sleep onset episodes (you may suddenly fall asleep). Therefore you must refrain from driving 

or operating machines until such recurrent episodes and excessive drowsiness have resolved.  

 

Tasmar contains lactose 

 

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 

before taking this medicine. 

 

 

3. How to take Tasmar 

 

Always take Tasmar exactly as your doctor has told you. You should check with your doctor or 

pharmacist if you are unsure.  

 

Dose and frequency of administration 

Your doctor should always begin your treatment with the standard dose of 3 times daily 1 tablet 

(100 mg (1 tablet)).  

If benefits are not seen within 3 weeks of the initiation of the treatment, Tasmar should be 

discontinued. 

To improve efficacy your doctor should only increase the dose to 3 times daily 2 tablets (200 mg three 

times a day) if the increase in how your Parkinson´s disease symptoms are controlled outweighs the 

expected increase in side effects.The side effects at the higher dose can often be severe and affect your 

liver. If you do not get better at the higher dose after a total of 3 weeks, your doctor should stop your 

treatment with Tasmar.  

 

When beginning and during treatment with Tasmar, your dose of levodopa may need to be changed. 

Your doctor will advise you what to do. 

 

How to take the medication: 

Swallow Tasmar with 1 glass of water. 

Do not break or crush the tablets. 

The first tablet Tasmar is to be taken in the morning together with your other parkinsonian medicine 

‘levodopa’. 

The following doses of Tasmar should be taken 6 and 12 hours later. 

 

Time of day Dose Note 

Morning 1 film-coated tablet Tasmar Together with the first daily dose 

´levodopa’ 

During the day 1 film-coated tablet Tasmar  

Evening 1 film-coated tablet Tasmar  

 

If you take more Tasmar than you should 

Contact your doctor, pharmacist or hospital immediately as you may need urgent medical attention. 

If another person accidentally takes your medicine, contact a doctor or hospital immediately as he or 

she may need urgent medical attention. 

 

Symptoms of overdose may include nausea, vomiting, dizziness and breathing difficulties.  

 

If you forget to take Tasmar 

Take it as soon as you remember, then continue to take it at the usual times. However, if taking the 

next dose should be directly ahead, do not make up for the forgotten dose.. Do not take a double dose 

to make up for forgotten individual doses. If you have missed several doses, please inform your doctor 

and follow the advice given to you 

 

If you stop taking Tasmar 



44 

Do not reduce or stop taking your medicine unless your doctor tells you. Always follow the 

instructions of your doctor about the duration of the treatment with Tasmar. 

 

 

4. Possible side effects  

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

 

The frequency of possible side effects listed below is defined using the following convention: 

 

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 

 

Tell your doctor or a pharmacist as soon as possible: 

- if you do not feel well while you are taking Tasmar  

- if you experience symptoms such as nausea, vomiting, abdominal pain, loss of appetite, 
  weakness, fever, darkening of urine or jaundice since uncommonly  

  disturbances in the way the liver works, sometimes severe hepatitis was observed, 

- if you notice a darkening of your urine since this could be a sign of  a muscular or liver 
injury. 

  Any other yellow urine discolouring is usually harmless. 

- if you develop persistent or severe diarrhoea  
 

Soon after beginning and during your treatment with Tasmar, you may have symptoms caused by 

levodopa such as involuntary movement and nausea. Therefore, if you feel unwell, you should contact 

your doctor since you may need to have your levodopa dose changed. 

 

Other possible side effects: 

 
Very common: 

- involuntary movement (dyskinesia), 
- nausea, decreased appetite, diarrhoea, 
- headache, dizziness 
- sleep problems, somnolence, 
- feeling lightheaded while you stand, (orthostatic complaints),mental confusion and 
hallucinations, 

- movement disorder with involuntary muscle spasms or malpositions (dystonia), 
- dreaming excessive. 
 

Common: 

- chest pain, 
- constipation, dyspepsia, stomach ache, vomiting, dry mouth, 

- fainting, 
- increased sweating, 
- influenza-like symptoms, 
- reduced voluntary and involuntary movement (hypokinesia), 
- upper respiratory tract infection, 
- increase of specific liver enzymes, 
- urine discoloration. 
 

Uncommon: 

- liver injury, in rare cases with fatal outcome 

 



45 

Rare: 

- severe symptoms of muscle stiffening, fever or mental confusion (Neuroleptic Malignant 
Syndrome) when antiparkinsonian treatments are abruptly reduced or withdrawn. 

- Impulse control disorders (inability to resist the impulse of an action that could be harmful). 

This may include: 

o            Strong impulse to gamble excessively despite serious personal or family 

consequences. 

o  Altered or increased sexual interest and behaviour of significant concern to you or 

to others, for example, an increased sexual drive. 

o  Uncontrolled excessive shopping or spending. 

o  Binge eating (eating large amounts of food in a short time period) or compulsive 

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

 

Tell your doctor if you experience any of these behaviours; these will discuss ways of managing 

or reducing the symptoms. 

 

Reporting of side effects 

If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via  

 

the national reporting system listed in Appendix V*.  

 

By reporting side effects you can help provide more information on the safety of this medicine. 

 

 

5.  How to store Tasmar 

Keep this medicine out of the sight and reach of children. 

 

Do not use after the expiry date stated on the pack. 

 

This medicinal product does not require any special storage conditions 

 

Do not use Tasmar if you notice that the tablets are damaged. 

 

 

6. Contents of the pack and other information 

 

What Tasmar contains 

- The active substance is tolcapone (100 mg in each film- coated tablet) 

- The other ingredients are: 

 Tablet core: Calcium hydrogen phosphate, Microcrystalline cellulose, 

 Povidone K30, Sodium starch glycollate, Lactose, Talc, Magnesium stearate. 

  Film-coat: Hydroxypropylmethylcellulose, Talc, Yellow iron oxide, Ethylcellulose, 

 Titanium dioxide, Triacetin, Sodium lauril sulfate. 

 

What Tasmar looks like and contents of the pack 

Tasmar is a pale to light yellow, oval shaped, film-coated tablet. “TASMAR” and “100” are engraved 

on one side. Tasmar is supplied as film-coated tablets containing 100 mg tolcapone. It is available in 

blisters in pack sizes of 30 and 60 tablets and in glass bottles in pack sizes of 30, 60 ,100 and 200 film-

coated tablets. 

 

Not all pack-sizes may be marketed. 

 

 

 

 



46 

Marketing Authorisation Holder and Manufacturer 

 

 

Marketing Authorisation Holder: 

Meda AB 

Pipers väg 2A 

S-170 09 Solna  

Sweden 

 

Manufacturer: 

ICN Polfa Rzeszów S.A.  

ul. Przemysłowa 2 

35-959 Rzeszów  

Poland 

 

For any information about this medicinal product, please contact the local representative of the 

Marketing Authorisation Holder. 

 

België/Belgique/Belgien 

MEDA Pharma S.A./N.V. 

Chaussée de la Hulpe 166/ 

Terhulpsesteenweg 166 

B-1170 Brussels 

Tél/Tel: +32 2 5 04 08 11 

 

Luxembourg/Luxemburg 

MEDA Pharma S.A./N.V. 

Chaussée de la Hulpe 166/ 

Terhulpsesteenweg 166 

B-1170 Brussels 

Belgique/Belgien 

Tél/Tel: +32 2 5 04 08 11 

 

България 

 

Майлан ЕООД 

бул. Ситняково 48, ет. 7 

Офис сграда „Сердика Офиси“ 

1505 София 
Тел: +359 2 44 55400 

 

 

Magyarország 

Mylan EPD Kft. 

H-1138 Budapest, 

Váci út 150. 

Tel.: +36 1 465 2100 

 

Česká republika 

MEDA Pharma s.r.o. 

Evropská 2590/33C 

Prague 6 160 00 

Czech Republic 

Tel:  +420 234 064 203 

 

Malta 

Alfred Gera & Sons Ltd. 

10, Triq il-Masġar 

Qormi QRM 3217 

Tel:+356 21 446 205 

 

Danmark 

Meda A/S 

Solvang 8 

DK-3450 Allerød 

Tlf: +45 44 52 88 88 

 

Nederland 

Mylan Healthcare B.V. 

Krijgsman 20 

NL-1186 DM Amstelveen 

Tel: +31 20 751 65 00 

 

Deutschland 

MEDA Pharma GmbH & Co. KG 

Benzstraße 1 

D-61352 Bad Homburg v.d.H. 

Tel: + 49 6172 888 01 

 

Norge 

Meda A/S 

Askerveien 61 

N-1384 Asker 

Tlf: +47 66 75 33 00 



47 

Eesti 

Meda Pharma SIA  

Liivalaia 13/14 

11018 Tallinn  

Tel: +372 62 61 025  

 

Österreich 

MEDA Pharma GmbH 

Guglgasse 15 

A-1110 Wien 

Tel: + 43 1 86 390 0 

Ελλάδα 

MEDA Pharmaceuticals A.E. 

Αγίου Δημητρίου 63 

17456 Άλιμος  

Τηλ: +30 210 6 77 5690 

 

Polska 

Mylan Healthcare Sp.z o.o.  

ul. Postepu 21 B 

02-676 Warszawa  

Tel: +48 22 5466400 

España 

Mylan Pharmaceuticals S.L. 

C/Plom, 2-4, 5ª planta 

08038 - Barcelona 

Tel: +34 900 102 712 

 

Portugal 

BGP Products, Unipessoal, Lda. 

Av. D. João II,  

Edifício Atlantis, nº 44C – 7.3 e 7 

1990-095 Lisboa 

Tel:+351 214 127 200 

France 

 Mylan Medical SAS  

40-44 rue Washington 

75008 Paris  

Tél: +33 1 56 64 10 70 

 

Hrvatska 

Mylan Hrvatska d.o.o. 

Koranska 2 

10 000  Zagreb 

Tel: +385 1 235 059 90 

 

România 

 

BGP PRODUCTS SRL 

Reprezentanța Romania 

Calea Floreasca nr. 169A 

Floreasca Business Park 

014459 București 

Tel.: +40372 579 000 

 

Ireland 

Meda Health Sales Ireland Ltd.  

Unit 34/35, Block A  

Dunboyne Business Park 

Dunboyne  

IRL - Co Meath 

Tel: +353 1 802 66 24 

 

Slovenija  

GSP Proizvodi d.o.o. 

Dolenjska cesta 242c 

1000 Ljubljana 

Tel: +386 1 23 63 180 

 

 

Ísland 

Meda AB 

Box 906 

S-170 09 Solna 

Svíþjóð. 

Sími: +46 8 630 1900 

 

Slovenská republika 

MEDA Pharma spol. s. r.o. 

Trnavská cesta 50 

821 02 Bratislava 

Tel: +421 2 32 199 100 

 

Italia 

Meda Pharma S.p.A.  

Via Felice Casati, 20  

20124 Milano  

Tel: +39 039 73901  

 

Suomi/Finland 

Meda Oy 

Vaisalantie 4/ Vaisalavägen 4 

FI-02130 Espoo/ Esbo 

Puh/Tel: +358 20 720 9550 

Κύπρος 

Χρ.Γ. Παπαλοΐζου Λτδ 

Λεωφ. Κιλκίς 35 

2234 Λατσιά 

Τηλ. +357 22 49 03 05 

Sverige 

Meda AB 

Box 906 

S-170 09 Solna 

Tel: +46 8 630 1900 



48 

 

Latvija 

Meda Pharma SIA 

101 Mūkusalas str. 

Rīga LV‐1004 

Tālr: +371 67616137 

 

United Kingdom 

Mylan Products Ltd.,  

Station Close,  

Potters Bar,  

Hertfordshire,  

EN6 1TL, UK 

+44 (0) 1707 853000 

 

Lietuva 

Meda Pharma SIA 

Žalgirio str. 92, #2 

Vilnius LT-09303  

Tel. + 370 52059367 

 

 

 

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. 

 



49 

Package leaflet: Information for the user 

 

Tasmar 200 mg film-coated tablets 

Tolcapone 

 

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 further questions, please ask your doctor or your pharmacist. 

-   This medicine has been prescribed for you. 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 you doctor or pharmacist. This includes any possible side 

           effects not listed in this leaflet. See section 4. 

 

 

What is in this leaflet:  

1. What Tasmar is and what it is used for 

2. What do you need to know before you take Tasmar 

3. How to take Tasmar 

4. Possible side effects 

5. How to store Tasmar 

6. Contents of the pack and other information 

 

 

1. What Tasmar is and what it is used for 

For the treatment of Parkinson´s disease, Tasmar is used together with the medicinal product levodopa 

(as levodopa/benserazide or levodopa/carbidopa). 

Tasmar is used when all other alternative medicines cannot stabilise your Parkinson’s disease.  

 

For the treatment of your Parkinson´s disease you already take levodopa. 

A natural protein (enzyme) in your body, the (COMT) Catechol-O-methyltransferase in your body 

breaks down levodopa. Tasmar blocks this enzyme and thus slows the breakdown of levodopa. This 

means when it is taken together with levodopa (as levodopa/benserazide or levodopa/carbidopa) you 

should have an improvement in the symptoms of your Parkinson’s disease.  

 

 

2. What do you need to know before you take Tasmar 

Do not take Tasmar: 

- if you have liver disease or increased liver enzymes 

- if you have severe involuntary movement (dyskinesia) 

-   if you have a previous history of severe symptoms of muscle stiffening, fever or mental  

            confusion (Neuroleptic Malignant Syndrome (NMS) Symptom Complex) and /or if you have  

            damage of skeletal muscle tissue (non-traumatic Rhabdomyolysis)  

-  if you are hypersensitive (allergic) to the active substance tolcapone or to any of the other  

           ingredients of Tasmar. 

- if you have a special type of tumor in the adrenal medulla  

(Phaeochromocytoma) 

- if you take a certain medication to treat depression and anxiety, called non-selective mono 

amino oxidase (MAO) inhibitors  

 

Warnings and precautions 

Talk to your doctor or pharmacist before taking Tasmar. 

You should not start taking Tasmar until your doctor 

- has described the risks of treatment with Tasmar, 

- has explained the measures necessary to minimise those risks, 

- has answered any questions you may have. 



50 

- if you are pregnant or intend to become pregnant. Your doctor will discuss the risks and benefits 

of taking Tasmar during pregnancy. The effects of Tasmar have not been studied in infants. You 

should not breast-feed your infant during treatment with Tasmar. 

 

Tell your doctor if you or your family/ carer notices you are developing urges or cravings to behave in 

ways that are unusual for you or you cannot resist the impulse, drive or temptation to carry out certain 

activities that could harm yourself or others. These behaviours are called impulse control disorders and 

can include addictive gambling, excessive eating or spending, an abnormally high sex drive or a 

preoccupation with an increase in sexual thoughts or feelings. Your doctor may need to review your 

treatments. 

 

You should only receive Tasmar if your Parkinson’s disease is not adequately controlled by the use of  

other therapies. 

 

In addition, your doctor will stop Tasmar treatment if after 3 weeks you do not improve enough to 

justify the risks of continuing treatment. 

 

Liver Injury: 

Tasmar may cause rare but potentially fatal liver injury. Liver injury has occurred most often after 1 

month and before 6 months. It should also be noted that female patients may have a higher risk of liver 

injury. Therefore, the following preventive measures have to be considered. 

 

Before beginning treatment:  

To reduce the risk of liver injury you should not use Tasmar if  

- you have a liver disease  
- in case of elevated liver function tests in the blood test done before starting treatment (tests of  

  alanine amino transferase (ALT) and aspartate amino transferase (AST)).  

 

While receiving treatment: 

During treatment, blood tests will be done in the following time intervals: 

- every 2 weeks during the first 12 months of therapy, 
- every 4 weeks during the following 6 months of therapy, 
- every 8 weeks during further treatment. 
The treatment will be stopped, if these blood tests become abnormal.  

 

The treatment with Tasmar may sometimes lead to disturbances in the way the liver works. Therefore, 

you should contact your doctor immediately if you experience symptoms such as nausea, vomiting, 

pain in your stomach (particulary over the liver in the right upper area), loss of appetite, weakness, 

fever, darkening of urine, jaundice (yellow skin or eyes) or if you tire more easily. 

If you have been already treated with Tasmar and developed acute liver injury during treatment, 

Tasmar should not be re-introduced again. 

 

NMS (Neuroleptic Malignant Syndrome):  

Symptoms of Neuroleptic Malignant Syndrome (NMS) may occur during Tasmar treatment. 

The NMS consists of some or all of the following: 

- severe muscle stiffness, jerking movements of muscles, arms or legs, and soreness of muscles. 
  Muscle injury can sometimes cause dark urine. 

- other important symptoms are high fever and mental confusion. 
 

Rarely, after abruptly reducing or stopping Tasmar or other antiparkinsonian drugs, you may 

experience severe symptoms of muscle stiffening, fever or mental confusion. If this happens notify 

your doctor. 

 

The following preventive measures have to be considered. 

 

Before beginning treatment: 



51 

To reduce the risk of NMS you should not use Tasmar if your doctor says you have severe involuntary 

movement (dyskinesia) or a previous illness that may have been NMS. 

Inform your doctor about all prescription and non-prescription medications as the risk of NMS may be 

increased if you are taking some specific medications. 

 

While receiving treatment: 

If you develop any symptoms as described above, that you think may be NMS, you should report them 

to your doctor immediately.  

Do not stop Tasmar or any other Parkinson’s medications without telling your doctor as this may 

increase the risk of NMS. 

 

Inform your doctor also: 

- if you have any illnesses other than Parkinson’s disease, 

- if you are allergic to other medicines, food and dyes, 

- if soon after beginning and during treatment with Tasmar you have symptoms which may be 

caused by levodopa such as involuntary movement (dyskinesia) and nausea. 

 

If you feel unwell, you should contact your doctor because you may need to take less levodopa. 

 

Children and adolescents 

Tasmar is not recommended for use in children below the age of 18 due to insufficient data on safety 

or efficacy. There is no relevant indication for use in children and adolescents. 

 

Other Medicines and Tasmar 

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 

even those not prescribed (non-prescription medicines and herbals). 

 

Please inform your doctor about all other medicines you are taking especially: 

- antidepressants, 

- alpha-methyldopa (used to treat increased blood pressure), 

- apomorphine (used for Parkinson’s disease), 

- dobutamine (used for the chronic heart disease), 

- adrenaline  and isoprenaline (both used for heart attacks) 

- anticoagulants of the warfarin type (that prevent blood clotting). In this case your doctor may 

  perform regular blood tests to monitor how easily your blood clots. 

 

If you go to hospital or if you are prescribed a new medicine, you must tell your doctor that you are 

taking Tasmar. 

 

Tasmar with food and drink and alcohol 

Tasmar can be taken with or without food. 

Tasmar should be taken with 1 glass of water. 

 

Pregnancy and breast-feeding and fertility 

You must tell your doctor if you are pregnant or intend to become pregnant. Your doctor will discuss 

the risks and benefits of taking Tasmar during pregnancy. 

 

The effects of Tasmar have not been studied in infants. You should not breast-feed your infant during 

treatment with Tasmar. 

 

Driving and using machines 

Since your ability to drive a car or operate machinery may be affected by Parkinson’s disease, you 

should discuss this with your doctor. 

 

Tasmar has an effect on the symptoms of your Parkinson’s disease. 



52 

Tasmar used with your other Parkinson medicines can cause excessive drowsiness (somnolence) and 

sudden sleep onset episodes (you may suddenly fall asleep). Therefore you must refrain from driving 

or operating machines until such recurrent episodes and excessive drowsiness have resolved.  

 

Tasmar contains lactose 

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 

before taking this medicine. 

 

 

3. How to take Tasmar 

 

Always take Tasmar exactly as your doctor has told you. You should check with your doctor or 

pharmacist if you are unsure.  

 

Dose and frequency of administration 

Your doctor should always begin your treatment with the standard dose of 3 times daily 1 tablet 

(100 mg (1 tablet)). 

If benefits are not seen within 3 weeks of the initiation of the treatment, Tasmar should be 

discontinued. 

To improve efficacy, your doctor should only increase the dose to the higher dose (200 mg three times 

a day) if the increase in how your Parkinson’s disease symptoms are controlled outweighs the 

expected increase in side effects. The side effects at the higher dose can often be severe and affect 

your liver, If you do not get better at the higher dose after a total of 3 weeks, your doctor should stop 

your treatment with Tasmar.  

 

When beginning and during treatment with Tasmar, your dose of Levodopa may need to be changed. 

Your doctor will advise you what to do. 

 

How to take the medication: 

Swallow Tasmar with 1 glass of water. 

Do not break or crush the tablets. 

The first tablet Tasmar is to be taken in the morning together with your other parkinsonian medicine 

‘levodopa’. 

The following doses of Tasmar should be taken 6 and 12 hours later. 

 

Time of day Dose Note 

Morning 1 film-coated tablet Tasmar Together with the first daily dose 

‚levodopa’ 

During the day 1 film-coated tablet Tasmar  

Evening 1 film-coated tablet Tasmar  

 

If you take more Tasmar than you should 

Contact your doctor, pharmacist or hospital immediately as you may need urgent medical attention. 

If another person accidentally takes your medicine, contact a doctor or hospital immediately as he or 

she may need urgent medical attention. 

 

Symptoms of overdose may include nausea, vomiting, dizziness and breathing difficulties.  

 

If you forget to take Tasmar 

Take it as soon as you remember, then continue to take it at the usual times. However, if taking the 

next dose should be directly ahead, do not make up for the forgotten dose. Do not take a double dose 

to make up for forgotten individual doses. If you have forgotten several doses, please inform your 

doctor and follow the advice given to you. 

 

If you stop taking Tasmar 



53 

Do not reduce or stop taking your medicine unless your doctor tells you to. Always follow the 

instructions of your doctor about the duration of the treatment with Tasmar. 

 

 

4. Possible side effects  

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

 

The frequency of possible side effects listed below is defined using the following convention: 

 

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 

 

Tell your doctor or pharmacist as soon as possible 

- if you do not feel well while you are taking Tasmar 
- if you experience symptoms such as nausea, vomiting, abdominal pain, loss of appetite, 

  weakness, fever, darkening of urine or jaundice since uncommonly 

  disturbances in the way the liver works, sometimes severe hepatitis was observed, 

- if you notice a darkening of your urine since this could be a sign of  a muscular or liver 
injury. 

  Any other yellow urine discolouring is usually harmless. 

- if you develop persistent or severe diarrhoea  
 

Soon after beginning and during your treatment with Tasmar, you may have symptoms caused by 

levodopa such as involuntary movement and nausea. Therefore, if you feel unwell, you should contact 

your doctor since you may need to have your levodopa dose changed. 

 

Other possible side effects: 

 
Very common: 

- involuntary movement (dyskinesia), 
- nausea, decreased appetite, diarrhoea, 
- headache, dizziness 
- sleep problems, somnolence, 
- feeling lightheaded while you stand, (orthostatic complaints), 
- mental confusion and hallucinations, 
- movement disorder with involuntary muscle spasms or malpositions (dystonia). 
- dreaming excessive. 
 

Common: 

- chest pain, 
- constipation, dyspepsia, stomach ache, vomiting, dry mouth, 
- fainting 
- increased sweating, 
- influenza-like symptoms 
- reduced voluntary and involuntary movement (hypokinesia) 
- upper respiratory tract infection 
- increase of specific liver enzymes, 
- urine discoloration 
 

Uncommon: 

- liver injury, in rare cases with fatal outcome 

 



54 

Rare: 

- severe symptoms of muscle stiffening, fever or mental confusion (Neuroleptic Malignant 
Syndrome) when antiparkinsonian treatments are abruptly reduced or withdrawn 

- Impulse control disorders (inability to resist the impulse of an action that could be harmful). 

This may include: 

o           Strong impulse to gamble excessively despite serious personal or family consequences. 

o           Altered or increased sexual interest and behaviour of significant concern to you or 

          to others, for example, an increased sexual drive. 

o           Uncontrolled excessive shopping or spending. 

o           Binge eating (eating large amounts of food in a short time period) or compulsive eating   

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

 

Tell your doctor if you experience any of these behaviours; these will discuss ways of managing 

or reducing the symptoms. 

 

Reporting of side effects 

If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via  

 

the national reporting system listed in Appendix V*.  

 

By reporting side effects you can help provide more information on the safety of this medicine. 

 

5. How to store Tasmar 

Keep out of the sight and reach of children. 

 

Do not use after the expiry date on the pack. 

 

This medicinal product does not require any special storage conditions 

 

Do not use Tasmar if you notice that the tablets are damaged. 

 

 

6. Contents of the pack and other information 

 

What Tasmar contains 

- The active substance is tolcapone (200 mg in each film- coated tablet) 

- The other ingredients are: 

 Tablet core: Calcium hydrogen phosphate, Microcrystalline cellulose, 

   Povidone K30, Sodium starch glycollate, Lactose monohydrate, Talc, Magnesium stearate. 

   Film-coat: Hydroxypropylmethylcellulose, Talc, Yellow iron oxide, Ethylcellulose, 

 Titanium dioxide, Triacetin, Sodium lauril sulfate. 

 

What Tasmar looks like and contents of the pack 

Tasmar is an orange yellow to brown yellow, oval shaped, film-coated tablet. “TASMAR” and “200” 

are engraved on one side. Tasmar is supplied as film-coated tablets containing 200 mg tolcapone. It 

is available in blisters in pack sizes of 30 and 60 tablets and in glass bottles in pack sizes of 100 

tablets. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder: 

Meda AB 

Pipers väg 2A 

S-170 09 Solna  

Sweden 



55 

 

Manufacturer: 

ICN Polfa Rzeszów S.A.  

ul. Przemysłowa 2 

35-959 Rzeszów  

Poland 

 

For any information about this medicinal product, please contact the local representative of the 

Marketing Authorisation Holder. 

 

België/Belgique/Belgien 

MEDA Pharma S.A./N.V. 

Chaussée de la Hulpe 166/ 

Terhulpsesteenweg 166 

B-1170 Brussels 

Tél/Tel: +32 2 5 04 08 11 

 

Luxembourg/Luxemburg 

MEDA Pharma S.A./N.V. 

Chaussée de la Hulpe 166/ 

Terhulpsesteenweg 166 

B-1170 Brussels 

Belgique/Belgien 

Tél/Tel: +32 2 5 04 08 11 

 

България 

Майлан ЕООД 

бул. Ситняково 48, ет. 7 

Офис сграда „Сердика Офиси“ 

1505 София 
Тел: +359 2 44 55400 

 

Magyarország 

Mylan EPD Kft. 

H-1138 Budapest, 

Váci út 150. 

Tel.: +36 1 465 2100 

 

Česká republika 

MEDA Pharma s.r.o. 

Evropská 2590/33C 

Prague 6 160 00 

Czech Republic 

Tel:  +420 234 064 203 

 

Malta 

Alfred Gera & Sons Ltd. 

10, Triq il-Masġar 

Qormi QRM 3217 

Tel:+356 21 446 205 

 

Danmark 

Meda A/S 

Solvang 8 

DK-3450 Allerød 

Tlf: +45 44 52 88 88 

 

Nederland 

Mylan Healthcare B.V 

Krijgsman 20 

NL-1186 DM Amstelveen 

Tel: +31 20 751 65 00 

 

Deutschland 

MEDA Pharma GmbH & Co. KG 

Benzstraße 1 

D-61352 Bad Homburg v.d.H. 

Tel: + 49 6172 888 01 

 

Norge 

Meda A/S 

Askerveien 61 

N-1384 Asker 

Tlf: +47 66 75 33 00 

Eesti 

Meda Pharma SIA  

Liivalaia 13/14 

11018 Tallinn  

Tel: +372 62 61 025  

 

Österreich 

MEDA Pharma GmbH 

Guglgasse 15 

A-1110 Wien 

Tel: + 43 1 86 390 0 

Ελλάδα 

MEDA Pharmaceuticals A.E. 

Αγίου Δημητρίου 63 

17456 Άλιμος  

Τηλ: +30 210 6 77 5690 

 

Polska 

 Mylan Healthcare Sp.z o.o.  

ul. Postepu 21 B 

02-676 Warszawa  

Tel: +48 5466400 



56 

 

España 

Mylan Pharmaceuticals S.L. 

C/Plom, 2-4, 5ª planta 

08038 - Barcelona 

Tel: +34 900 102 712 

 

Portugal 

BGP Products, Unipessoal, Lda. 

Av. D. João II,  

Edifício Atlantis, nº 44C – 7.3 e 7 

1990-095 Lisboa 

Tel:+351 214 127 200 

 

France 

Mylan Medical SAS 

40-44 rue Washington 

75008 Paris  

Tél: +33 (0)1 56 64 10 70 

România 

BGP PRODUCTS SRL 

Reprezentanța Romania 

Calea Floreasca nr. 169A 

Floreasca Business Park 

014459 București 

Tel.: +40372 579 000 

 

 

Hrvatska 

Mylan Hrvatska d.o.o. 

Koranska 2 

10 000  Zagreb 

Tel: +385 1 235 059 90 

 

 

Ireland 

Meda Health Sales Ireland Ltd.  

Unit 34/35, Block A  

Dunboyne Business Park 

Dunboyne  

IRL - Co Meath 

Tel: +353 1 802 66 24 

 

Slovenija  

GSP Proizvodi d.o.o. 

Dolenjska cesta 242c 

1000 Ljubljana 

Tel: +386 1 23 63 180 

 

Ísland 

Meda AB 

Box 906 

S-170 09 Solna 

Svíþjóð. 

Sími: +46 8 630 1900 

 

Slovenská republika 

MEDA Pharma spol. s. r.o. 

Trnavská cesta 50 

821 02 Bratislava 

Tel: +421 2 32 199 100 

 

Italia 

Meda Pharma S.p.A.  

Via Felice Casati, 20  

20124 Milano  

Tel: +39 039 73901  

 

Suomi/Finland 

Meda Oy 

Vaisalantie 4/ Vaisalavägen 4 

FI-02130 Espoo/ Esbo 

Puh/Tel: +358 20 720 9550 

Κύπρος 

Χρ.Γ. Παπαλοΐζου Λτδ 

Λεωφ. Κιλκίς 35 

2234 Λατσιά 

Τηλ. +357 22 49 03 05 

 

 

Sverige 

Meda AB 

Box 906 

S-170 09 Solna 

Tel: +46 8 630 1900 



57 

Latvija 

Meda Pharma SIA 

101 Mūkusalas str. 

Rīga LV‐1004 

Tālr: +371 67616137 

 

 

United Kingdom 

Mylan Products Ltd.,  

Station Close,  

Potters Bar,  

Hertfordshire,  

EN6 1TL, UK 

+44 (0) 1707 853000 

 

Lietuva 

Meda Pharma SIA 

Žalgirio str. 92, #2 

Vilnius LT-09303  

Tel. + 370 52059367 

 

 

 

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) RESPONSIBLEFOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLYAND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THEMARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFEAND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET