Package leaflet: Information for the patient

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Madopar 250 mg (Madopar 200 mg/50 mg)
200 mg + 50 mg, tablets
Levodopa + Benserazide
Madopar 250 mg and Madopar 200 mg/50 mg are different brand names for the same medicine.
Please read this leaflet carefully before taking the medicine, as it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet:

What Madopar 250 mg is and what it is used for
Important information before taking Madopar 250 mg
How to take Madopar 250 mg
Possible side effects
How to store Madopar 250 mg
Contents of the pack and other information

1. What Madopar 250 mg is and what it is used for
Madopar 250 mg is a combination medicine containing two active substances: levodopa and benserazide
(in the form of hydrochloride).
Madopar 250 mg is indicated for the treatment of Parkinson's disease.
Parkinson's disease is characterized by slowness of movement, muscle stiffness, and tremor.
These symptoms are caused by insufficient dopamine levels in certain areas of the brain.
The severity of symptoms varies among individual patients.
The goal of treating Parkinson's disease is to compensate for the dopamine deficiency in the brain. The difficulty
in treatment lies in the fact that dopamine does not cross from the bloodstream into the brain. However, its chemical
precursor, levodopa, crosses freely. Unfortunately, most of the levodopa is converted into dopamine before
reaching the brain. Dopamine formed outside the brain causes unpleasant side effects.
Madopar 250 mg contains two substances: levodopa and benserazide, which inhibits the conversion of
levodopa into dopamine outside the brain. After administration, the following processes occur in the body:
levodopa (the first component of Madopar 250 mg) cannot be converted into dopamine outside the
brain—thanks to benserazide (the second component of Madopar 250 mg). Thanks to benserazide,
more levodopa reaches the brain, where it is converted into dopamine, and conversion of levodopa into dopamine in extracerebral tissues is prevented, resulting in fewer side effects. Thus, Madopar 250 mg may beneficially affect symptoms associated with Parkinson's disease. However, it does not cure the disease, as it does not eliminate the underlying cause of dopamine deficiency in the brain. Causal treatment of the disease remains impossible to date.

2. Important information before taking Madopar 250 mg

When not to take Madopar 250 mg:

if the patient is allergic to levodopa, benserazide, or any of the other ingredients of this medicine (listed in section 6);
in patients treated with non-selective monoamine oxidase inhibitors (MAO), due to the risk of hypertensive crisis. Concurrent use of Madopar 250 mg with selective MAO-B inhibitors, such as selegiline or rasagiline, or selective MAO-A inhibitors, such as moclobemide, is not contraindicated; however, care must be taken not to use both selective MAO-A and MAO-B inhibitors simultaneously with Madopar 250 mg;
in patients with uncontrolled disorders: endocrine (pheochromocytoma, hyperthyroidism, Cushing's syndrome), renal function (except patients undergoing dialysis for RLS), or liver function, heart disease (e.g., severe cardiac arrhythmias and heart failure), psychiatric disorders with psychotic symptoms, or with closed-angle glaucoma;
in patients under 25 years of age (skeletal development must be complete);
in pregnant women or women of childbearing potential who are not using effective contraceptive methods. If pregnancy occurs in a woman treated with Madopar 250 mg, the medicine should be discontinued immediately.

Warnings and precautions
Before starting treatment with Madopar 250 mg, discuss with your doctor or pharmacist if:

the patient has diabetes – blood glucose levels should be monitored more frequently, and antidiabetic medication doses adjusted accordingly;
the patient has open-angle glaucoma – intraocular pressure should be monitored regularly;
the patient has a planned surgical procedure under general anesthesia. In such cases, Madopar 250 mg should be continued as long as possible before surgery, except when halothane is used for anesthesia. When general anesthesia with halothane is planned, Madopar 250 mg should be discontinued 12–48 hours before the procedure due to the risk of blood pressure fluctuations and/or cardiac arrhythmias. After the procedure, treatment can be resumed, gradually increasing the dose to the previously used level;
the patient has previously had coronary artery disease, cardiac arrhythmias, or heart failure – cardiac function should be closely monitored, especially at the beginning of treatment and then regularly during therapy;
the patient is elderly and concurrently taking antihypertensive medicines or other medicines that may cause orthostatic hypotension, or if the patient previously experienced hypotension;
the patient is taking sympathomimetic medicines (stimulants of the sympathetic nervous system), as their effects may be intensified;
the patient is taking a catechol-O-methyltransferase (COMT) inhibitor;
the patient is taking anticholinergic medicines such as amantadine, selegiline, bromocriptine, or dopamine agonists; concurrent use of these medicines with Madopar 250 mg may intensify both therapeutic and adverse effects.

During the dose adjustment phase, periodic monitoring of liver and kidney function, cardiovascular function,
and blood count should be performed.
During treatment with Madopar 250 mg, depression may occur, although it may also be related to the underlying disease. Patients taking Madopar 250 mg should be closely monitored for psychological changes and depression, with or without suicidal thoughts.
Cognitive and behavioral disturbances may occur in patients taking Madopar 250 mg.
Rarely, during levodopa treatment, drowsiness and/or sudden sleep attacks may occur. Very rarely, cases of sleep attacks have been reported, which may occur even during daily activities, sometimes without warning or preceding drowsiness. Therefore, caution is advised when driving or operating machinery during treatment with Madopar 250 mg. Patients who have previously experienced drowsiness and/or sleep attacks must not drive or operate machinery. If drowsiness or sleep attacks occur, the doctor should consider reducing the dose or discontinuing treatment.
Hypersensitivity reactions may occur in predisposed individuals.
Inform your doctor if you or your family members notice unusual behaviors resulting from irresistible impulses, compulsions, or obsessive performance of certain actions harmful to the patient or others. These behaviors are known as impulse control disorders and may include gambling addiction, compulsive or binge eating, increased sexual drive, or intense sexual thoughts and feelings. It may be necessary for the doctor to re-evaluate the ongoing treatment.
Patients with Parkinson's disease have an increased risk of developing melanoma. It is unclear whether this increased risk is due to Parkinson's disease itself or other factors, such as levodopa used in its treatment. Regular periodic skin examinations for melanoma should be performed during treatment with Madopar 250 mg, regardless of indication.
Do not stop taking Madopar 250 mg abruptly
Sudden discontinuation of the medicine may lead to a potentially life-threatening condition resembling neuroleptic malignant syndrome (high fever, muscle rigidity, possible mental changes). If such symptoms occur, the patient should be placed under medical supervision, possibly in a hospital, and promptly receive appropriate symptomatic treatment.
Potential for dependence or misuse of the medicine
Cognitive and behavioral disturbances may occur in a small number of patients, which may be directly related to taking higher-than-recommended doses of the medicine (doses significantly exceeding those required for treating motor impairment).
Madopar 250 mg and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
If a doctor prescribes Madopar 250 mg for patients who have been taking a non-selective MAO inhibitor, at least two weeks should elapse between stopping the non-selective MAO inhibitor and starting Madopar 250 mg. Concurrent use of Madopar 250 mg with selective MAO-B inhibitors such as selegiline and rasagiline, or selective MAO-A inhibitors such as moclobemide, is permitted. However, simultaneous administration of a selective MAO-A inhibitor and a selective MAO-B inhibitor is equivalent to non-selective MAO inhibition and therefore should not be used concurrently with Madopar 250 mg.
Concurrent use of iron sulfate reduces the maximum plasma concentration of levodopa.
Metoclopramide increases the rate of levodopa absorption. Domperidone may enhance levodopa absorption in the intestine.
When antihypertensive medicines are used concurrently with Madopar 250 mg, blood pressure should be monitored regularly to allow dose adjustments.
Neuroleptics, opioids, and antihypertensive preparations containing reserpine inhibit the effect of Madopar 250 mg.
Concurrent use of Madopar 250 mg with anti-parkinsonian medicines (amantadine, selegiline, bromocriptine, dopamine agonists, anticholinergic medicines such as trihexyphenidyl) is permitted, but it should be noted that both desired and undesired effects may be enhanced. Care should be taken not to discontinue anticholinergic medicines abruptly at the beginning of Madopar 250 mg treatment, as the effect of levodopa takes some time to develop.
Concurrent administration of antipsychotic medicines with dopamine receptor-blocking properties may counteract the anti-parkinsonian effect of Madopar 250 mg.
Levodopa may counteract the effects of antipsychotic medicines. Caution is advised when administering these medicines together, and patients should be closely observed for reduced anti-parkinsonian effects and worsening Parkinson's symptoms.
Levodopa contained in Madopar 250 mg may affect laboratory test results for catecholamines, creatinine, uric acid, and glucosuria.
Patients taking Madopar 250 mg may have falsely positive Coombs test results and falsely positive tests for urinary ketones.
During general anesthesia with halothane, Madopar 250 mg should be discontinued 12–48 hours before the procedure, as concurrent administration of Madopar 250 mg and halothane may cause blood pressure fluctuations and/or cardiac arrhythmias.
Taking Madopar 250 mg with food and drink
Concurrent intake of high-protein meals may reduce the effectiveness of the medicine.
Pregnancy and breastfeeding
Madopar 250 mg must not be used during pregnancy or in women of childbearing potential who are not using effective contraceptive methods.
Before starting treatment, a pregnancy test should be performed to exclude pregnancy.
If a woman taking Madopar 250 mg becomes pregnant, the medicine should be discontinued (after consultation with the attending physician).
Breastfeeding must not be performed during treatment with Madopar 250 mg, as the active substances may pass into breast milk and harm the infant.
Driving and operating machinery
During treatment with Madopar 250 mg, drowsiness may occur, and in rare cases, sudden sleep attacks. Therefore, caution must always be exercised when driving or operating machinery while taking Madopar 250 mg. Patients who experience drowsiness or sleep attacks during treatment with Madopar 250 mg must refrain from driving motor vehicles or performing certain other activities (such as operating machinery), as impaired concentration may pose a risk of serious injury or death to themselves or others.
Madopar 250 mg contains sodium
Madopar 250 mg contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free."

3. How to take Madopar 250 mg

This medicine should always be taken exactly as prescribed by your doctor or pharmacist. If in doubt,
you should consult your doctor or pharmacist.
Dosing in Parkinson's disease
A patient with Parkinson's disease must remain under strict medical supervision and must not
initiate any other treatment for this condition without prior agreement with the doctor. If changing
doctors or visiting another physician, the treating physician must be promptly informed about
therapy with Madopar 250 mg.
Never take Madopar 250 mg without a doctor's prescription. Under no circumstances should the
dose be changed without the doctor's approval.
Madopar 250 mg should preferably be taken 30 minutes before a meal or one hour after a meal.
Gastrointestinal side effects, which mainly occur during the initial phase of treatment, can usually be
avoided by taking Madopar 250 mg with a light snack (e.g. biscuits) or with a drink, or by gradually
increasing the dose.
For effective treatment, it is essential to take the correct amount of medicine at the correct time.
The doctor will individually determine the appropriate dosage and frequency of administration and,
in close cooperation with the patient, establish the optimal treatment regimen. Therefore, it is
important to strictly follow the doctor's instructions. Generally, at the beginning of treatment, the
doctor prescribes a lower dose of Madopar 250 mg and gradually increases it. This approach allows
the patient's body to adapt to the medicine, thereby minimizing adverse effects as much as possible.
Madopar is available in various strengths and formulations:

Madopar 62.5 mg, 50 mg + 12.5 mg, capsules
Madopar 125 mg, 100 mg + 25 mg, capsules
Madopar, 200 mg + 50 mg, capsules
Madopar HBS, 100 mg + 25 mg, capsules
Madopar 250 mg, 200 mg + 50 mg, tablets
Madopar 62.5 mg, 50 mg + 12.5 mg, oral suspension tablets
Madopar 125 mg, 100 mg + 25 mg, oral suspension tablets

Typical dosage:
In the early stage of Parkinson's disease, treatment usually begins with one capsule of Madopar
62.5 mg (50 mg levodopa + 12.5 mg benserazide) taken three to four times daily.
The optimal therapeutic effect is usually achieved with a daily dose of Madopar equivalent to
300–800 mg levodopa + 75–200 mg benserazide, administered in at least three divided doses over
a period of 4 to 6 weeks.
The average maintenance dose corresponds to one capsule of Madopar 125 mg taken three to six
times daily. The number of divided doses and their distribution throughout the day should be
individually determined by the doctor for each patient, depending on the clinical condition.
Madopar HBS and Madopar oral suspension tablets may be used interchangeably with standard
formulations of Madopar (capsules and tablets) to achieve the optimal therapeutic effect.
Special dosing instructions
Parkinson's disease:
The dose should be carefully determined for each patient. Patients previously treated with other
anti-parkinsonian drugs may be prescribed Madopar 250 mg. As the patient's condition improves
with Madopar 250 mg, the doses of these other drugs may be reduced or gradually discontinued.
Madopar oral suspension tablets are particularly indicated for patients with dysphagia (swallowing
difficulties) or when a faster onset of action is desired.
Patients who experience significant fluctuations in drug effect during the day should receive
smaller doses more frequently throughout the day, or it is recommended to switch from standard
formulations to Madopar HBS.
Switching from standard formulations to Madopar HBS should be done from one day to the next,
starting with the first morning dose. The same total daily dose and dose distribution as with the
standard formulation should be maintained.
After 2–3 days, the dose should be gradually increased by approximately 50%. A temporary
worsening of health status may occur.
The properties of Madopar HBS result in a later onset of action compared to standard formulations.
The desired effect may be achieved more quickly by administering Madopar HBS together with the
standard formulation or with Madopar oral suspension tablets. This approach may be particularly
useful for the first morning dose, which is usually larger than subsequent daytime doses.
The dosing regimen for Madopar HBS should be individually determined by the doctor, slowly and
with special caution, with intervals of at least 2–3 days between each dose adjustment.
In patients with reduced motor function at night, positive effects can be achieved by gradually
increasing the last evening dose of Madopar HBS to 250 mg, taken immediately before bedtime.
For excessive response (dyskinesias) after administration of Madopar HBS, it is preferable to
reduce symptoms by extending the interval between doses rather than by reducing individual doses.
If there is no satisfactory clinical response after using Madopar HBS, it is recommended to return to
the previous treatment with standard Madopar.
Taking Madopar 250 mg
If your doctor has prescribed Madopar 250 mg, the prescribed amount may be crushed as needed to
facilitate swallowing.
If you feel that the effect of Madopar 250 mg is too strong or too weak, you should consult your
doctor.
Taking a higher than recommended dose of Madopar 250 mg
If a higher than recommended dose is taken, you should immediately consult your doctor or
pharmacist.
The most common symptoms of overdose may include cardiovascular effects (e.g. cardiac arrhythmia),
psychiatric disturbances (e.g. disorientation and insomnia), gastrointestinal symptoms (e.g. nausea and
vomiting), and involuntary movements.
Overdose with Madopar 250 mg requires immediate medical attention, possibly in a hospital setting
or in an intensive care unit. Monitoring of vital functions and other parameters according to the
clinical condition is indicated. Patients may require treatment for cardiovascular symptoms (e.g.
cardiac arrhythmias) or central nervous system dysfunction. Administration of antiarrhythmic and/or
respiratory stimulants or neuroleptics may be necessary.
Missing a dose of Madopar 250 mg
Do not take a double dose to make up for a missed dose. Continue taking the medicine according to
the schedule prescribed by your doctor.
Stopping Madopar 250 mg
Do not abruptly discontinue Madopar 250 mg. See section 2: Warnings and precautions.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects
Like all medicines, this product can cause side effects, although not everyone will experience them.
Frequency categories
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 available data)

In clinical trials using levodopa/benserazide in restless legs syndrome, frequent reports included
headache, worsening of restless legs syndrome symptoms, dizziness, fever with infection, cold,
bronchitis, dry mouth, diarrhoea, nausea, ECG changes (arrhythmia), and increased blood pressure.

The following side effects have been reported during treatment with Madopar 250 mg, all with
unknown frequency.

Blood and lymphatic system disorders: blood disorders such as haemolytic anaemia, leukopenia,
thrombocytopenia. For this reason – as always during long-term treatment with levodopa – periodic
monitoring of blood counts and liver and kidney function is recommended.
Metabolism and nutrition disorders: decreased appetite.
Psychiatric disorders: dopamine dysregulation syndrome (cognitive and behavioural disturbances
that may be directly related to taking higher than recommended doses of the medicine), confusion,
depression, agitation, anxiety, insomnia, hallucinations, delusions, disorientation, pathological
gambling, increased libido, increased sexual arousal, compulsive spending or shopping, binge eating,
eating disorders.
Nervous system disorders: loss of taste, taste disturbances, involuntary movements (e.g. movements
disrupting normal motor coordination). These can usually be eliminated or reduced by decreasing the
dose. Changes in response to treatment during the day (can be eliminated or reduced by adjusting the
dose appropriately or by administering smaller individual doses at shorter intervals), drowsiness,
sudden sleep attacks, freezing (sudden immobility).
Cardiac disorders: arrhythmia (irregular heartbeat).
Vascular disorders: orthostatic hypotension (blood pressure changes associated with changing from
lying or sitting to standing position). Orthostatic disturbances can usually be reduced by decreasing
the dose of Madopar.
Gastrointestinal disorders: nausea, vomiting, diarrhoea, discoloration of saliva, discoloration of the
tongue, discoloration of teeth, discoloration of the oral mucosa. Gastrointestinal side effects occur
mainly during the early phase of treatment and can be significantly reduced by taking Madopar 250 mg
with a small, low-protein meal, taking the medicine with a drink, or gradually increasing the dose.
Hepatobiliary disorders: increased transaminase activity, increased alkaline phosphatase activity,
increased gamma-glutamyltransferase activity.
Skin and subcutaneous tissue disorders: itching, rash.
Musculoskeletal and connective tissue disorders: in restless legs syndrome, symptom exacerbation
may occur (shifting of symptoms from evening/night to early afternoon and evening before taking
the next nighttime dose).
Investigations: increased blood urea concentration, chromaturia (discoloration of urine. Urine
typically becomes reddish and darkens upon standing). Discoloration may also affect other body
fluids and tissues, including saliva, tongue, teeth, and oral mucosa.

It should be noted that the following side effects may also occur:

Dopamine dysregulation syndrome (cognitive and behavioural disturbances that may be directly related to taking higher than recommended doses of the medicine);
Inability to resist impulses, urges, or compulsions to perform actions that may be harmful to the patient or others; this includes:
- a strong urge to gamble uncontrollably, despite serious personal or family consequences,
- altered or increased sexual interests and behaviours of significant concern to the patient or others, e.g. activities related to heightened sexual drive,
- compulsive, uncontrolled spending or shopping,
- binge eating (consuming large amounts of food in a short time) or compulsive eating (eating more food than normal and more than needed to satisfy hunger).
  Patients should inform their doctor if they experience any of these behaviours, so that ways to manage or reduce these symptoms can be discussed.

If any of the side effects worsen or if any unlisted side effects occur, you should inform your doctor or pharmacist.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting side effects helps to provide more information on the safety of the medicine.

5. How to store Madopar 250 mg

Keep this medicine out of the sight and reach of children.
Do not store above 30°C. Keep the bottle tightly closed to protect from moisture.
Store in the original packaging.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the packaging and other information

What Madopar 250 mg contains

The active substances are levodopa and benserazide. Each Madopar 250 mg tablet contains 200 mg of levodopa and 50 mg of benserazide (as hydrochloride).
Other components are: mannitol, calcium hydrogen phosphate, microcrystalline cellulose, pregelatinized corn starch, crospovidone, ethylcellulose, iron oxide red (E 172), colloidal anhydrous silica, sodium docucyl sulfate, magnesium stearate.

What Madopar 250 mg looks like and contents of the pack
The pack contains 100 tablets.
Madopar 250 mg, 200 mg + 50 mg, tablets are pale red, slightly mottled, cylindrical,
biconvex tablets, embossed with the word “ROCHE” and a hexagon on one side
and a division line on both sides (with a cross-score).
For more detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Spain, country of export:
ROCHE FARMA, S.A.
C/ Ribera del Loira, 50
28042 Madrid, Spain
Manufacturer:
Roche Farma, S.A.
C/ Eratóstenes, 19
Getafe
28906 Madrid, Spain
Parallel importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing authorisation number in Spain, country of export: 669770.2
Parallel import authorisation number: 228/22