Madopar 250 mg

Package Leaflet: Information for the Patient

Warning! Keep the 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 trade names for the same medicine.

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet so that you can read it again if you need to.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of Contents of the Leaflet:

• 1. What is Madopar 250 mg and what is it used for
• 2. Important information before taking Madopar 250 mg
• 3. How to take Madopar 250 mg
• 4. Possible side effects
• 5. How to store Madopar 250 mg
• 6. Contents of the pack and other information

1. What is Madopar 250 mg and what is it 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 slowed movements, muscle stiffness, and tremors.
These symptoms are caused by a lack of dopamine in certain brain centers.
The symptoms of the disease occur in individual patients with varying severity.
The goal of treating Parkinson's disease is to supplement the lack of dopamine in the brain. The difficulty
of treatment lies in the fact that dopamine does not pass from the blood into the brain. On the other hand, its chemical precursor - levodopa - passes through without any obstacles.
Unfortunately, most of levodopa is converted to dopamine before it enters the brain. The dopamine produced outside the brain causes unpleasant side effects.
Madopar 250 mg contains two substances: levodopa and benserazide, which inhibits the conversion of levodopa to dopamine outside the brain. After taking the medicine, the following processes occur in the body:
levodopa (the first component of Madopar 250 mg) cannot be converted to dopamine outside the brain - due to benserazide (the second component of Madopar 250 mg). Thanks to benserazide, levodopa penetrates the brain in larger quantities and is converted to dopamine, and there is no conversion of levodopa to dopamine in extracerebral tissues, which results in fewer side effects. Madopar 250 mg can thus have a beneficial effect on the symptoms associated with Parkinson's disease. However, it does not cure the disease, as it does not eliminate the cause of dopamine deficiency in the brain. Causal treatment of the disease is currently impossible.

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 (MAOIs), 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 should be taken not to use both selective MAO-A and MAO-B inhibitors simultaneously with Madopar 250 mg;
• in patients with uncontrolled endocrine, renal, or hepatic disorders, heart diseases (e.g., severe arrhythmias and heart failure), psychiatric diseases with psychotic symptoms, and angle-closure glaucoma;
• in patients under 25 years of age (bone growth must be completed);
• in pregnant or breastfeeding women, or women of childbearing age who do not use effective contraception. If a woman taking Madopar 250 mg becomes pregnant, the medicine should be discontinued immediately.

Warnings and precautions

Before starting to take Madopar 250 mg, you should discuss with your doctor or pharmacist if:

• you have diabetes- you should check your blood glucose levels more often and adjust the dosage of your antidiabetic medicines accordingly;
• you have open-angle glaucoma- you should have your intraocular pressure measured regularly;
• you are scheduled for general anesthesia. In this case, you should take Madopar 250 mg for as long as possible before the operation, except when using halothane anesthesia. When using halothane anesthesia, you should discontinue Madopar 250 mg 12-48 hours before the operation, due to the risk of blood pressure fluctuations and/or cardiac arrhythmias (heart rhythm disturbances). After the operation, treatment can be resumed, gradually increasing the doses to the previously used dose;
• you have had coronary artery disease, arrhythmias, or heart failure - you should be closely monitored for cardiac function, especially during the initial treatment period, and then regularly throughout the treatment period;
• you are elderly and taking antihypertensive medicines and other medicines that may cause orthostatic hypotension or if you have had orthostatic hypotension before;
• you are taking sympathomimetic medicines, as they may enhance their effects;
• you are taking catechol-O-methyltransferase inhibitors (COMT inhibitors);
• you are taking anticholinergic medicines, such as amantadine, selegiline, bromocriptine, dopamine agonists; concomitant use of these medicines with Madopar 250 mg may enhance both the therapeutic and adverse effects.

During the dose titration phase, you should periodically monitor liver, kidney, and cardiovascular function
and check your blood count.
During treatment with Madopar 250 mg, depressionmay occur, which may 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.
Patients taking Madopar 250 mg may experience cognitive and behavioral disorders.
In rare cases, duringlevodopa treatment, sleepiness and/or sudden sleep attacksmay occur. Very rarely, reports of sleep attacks that can occur even during daily activities, in some cases without warning or prior sleepiness, have been made. Therefore, when taking Madopar 250 mg, you should be cautious when driving or operating machinery. Patients who have already experienced sleepiness and/or sleep attacks should not drive or operate machinery. If sleepiness or sleep attacks occur, your doctor should consider reducing the dose or discontinuing treatment.
Hypersensitivity reactionsmay occur in susceptible individuals.
You should inform your doctor if you or your relatives notice unusual behaviors resulting from irresistible impulses, compulsions, or repetitive behaviors that are harmful to you or others. Such behaviors are called impulse control disordersand may include pathological gambling, compulsive or binge eating, excessive sexual drive, or increased sexual thoughts and feelings. It may be necessary to re-evaluate the treatment being used by your doctor.
Parkinson's disease patients are at increased risk of developing malignant melanoma. It is not clear whether the observed increased risk is due to Parkinson's disease or other factors, such as levodopa used to treat Parkinson's disease. You should have regular skin examinations for melanoma during treatment with Madopar 250 mg for any indication.

Do not stop taking Madopar 250 mg abruptly

Abrupt discontinuation of the medicine may lead to the occurrence of a potentially life-threatening condition resembling malignant neuroleptic syndrome (high fever, muscle stiffness, possible mental changes). If such symptoms occur, the patient should be under medical supervision, if necessary in a hospital, and receive prompt symptomatic treatment.

Possibility of dependence on the medicine or its abuse

A small number of patients may experience cognitive and behavioral disorders, which may be directly related to taking a higher dose of the medicine than recommended (a dose significantly exceeding the dose of the medicine required to treat motor impairment).

Madopar 250 mg and other medicines

You should tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
If a non-selective MAOI is being taken and your doctor has prescribed Madopar 250 mg, at least two weeks should elapse between the end of treatment with the non-selective MAOI and the start of treatment with Madopar 250 mg. Concomitant use of Madopar 250 mg with selective MAO-B inhibitors, such as selegiline and rasagiline, or selective MAO-A inhibitors, such as moclobemide, is allowed.However, concurrent administration of a selective MAO-A inhibitor and a selective MAO-B inhibitor corresponds to non-selective MAO inhibition and therefore should not be used simultaneously with Madopar 250 mg.
Concomitant use of iron sulfate reduces the maximum plasma concentration of levodopa.
Metoclopramide increases the absorption rate of levodopa. Domperidone may affect increased absorption of levodopa in the intestine.
When taking antihypertensive medicinesand Madopar 250 mg, you should regularly check your blood pressure to allow for dose adjustments of the antihypertensive medicines.
Neuroleptic medicines, opioids, and antihypertensive medicines containing reserpineinhibit the action of Madopar 250 mg.
Concomitant use of Madopar 250 mg with anti-Parkinsonian medicines(amantadine, selegiline, bromocriptine, dopamine agonists, anticholinergic medicines, such as trihexyphenidyl) is allowed, but you should be aware that both the desired and undesired effects of the medicine may be enhanced. You should not abruptly discontinue anticholinergic medicineswhen starting treatment with Madopar 250 mg, as the effect of levodopa occurs only after some time.
Concomitant administration of antipsychotic medicines with medicines that block dopamine receptors may counteract the anti-Parkinsonian effect of Madopar 250 mg. Levodopa may counteract the effects of antipsychotic medicines. You should be cautious when concomitantly administering these medicines and closely monitor the patient for reduced efficacy of anti-Parkinsonian medicines and worsening of Parkinson's disease symptoms. Levodopa contained in Madopar 250 mg may affect the results of laboratory tests for catecholamines, creatinine, uric acid, and glucosuria.
Patients taking Madopar 250 mg may experience false-positive Coombs test resultsand false-positive results for ketone bodies in the urine.
In case of general anesthesia using halothane, you should discontinue Madopar 250 mg 12-48 hours before the operation, as concomitant administration of Madopar 250 mg and halothane may cause blood pressure fluctuations and/or cardiac arrhythmias.

Taking Madopar 250 mg with food and drink

Concomitant consumption of protein-rich meals may reduce the effect of the medicine.

Pregnancy and breastfeeding

Madopar 250 mg should not be used during pregnancy or in women of childbearing age who do not use effective contraception.
Before starting treatment, a pregnancy test is recommended to rule out pregnancy.
If a woman taking Madopar 250 mg becomes pregnant, the medicine should be discontinued (after consultation with the treating doctor).
Madopar 250 mg should not be used during breastfeeding, as the active substances of the medicine may pass into breast milk and harm the baby.

Driving and using machines

When taking Madopar 250 mg, sleepiness may occur, and in rare cases, sudden sleep attacks, so you should always be cautious when driving or operating machinery. Patients who have already experienced sleepiness or sleep attacks during treatment with Madopar 250 mg should avoid driving or operating machinery, as their concentration may be impaired, posing 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, which means the medicine is considered "sodium-free".

3. How to take Madopar 250 mg

This medicine should always be taken as directed by your doctor or pharmacist. If you have any doubts, you should consult your doctor or pharmacist.
Dosing in Parkinson's disease

The patient with Parkinson's disease must be under close medical supervision and must not start any other treatment for this disease without consulting their doctor. If it is necessary to change doctors or visit another doctor, they should be informed immediately about the treatment with Madopar 250 mg.

Madopar 250 mg should never be taken without a doctor's prescription.

Never change the dose of Madopar 250 mg without consulting your doctor.

Madopar 250 mg should be taken about 30 minutes before a meal or 1 hour after a meal. Unpleasant gastrointestinal symptoms that occur mainly in the initial phase of treatment can usually be avoided by taking Madopar 250 mg with a small meal (e.g., biscuits) or a drink, or by gradually increasing the dose.
For the treatment to be effective, it is essential to take the correct amount of medicine at the right time.
Your doctor will determine the appropriate amount and frequency of taking the medicine individually and, in close cooperation with you, will determine the best treatment schedule for you. Therefore, you should strictly follow their instructions. Generally, at the beginning of treatment, your doctor will prescribe Madopar 250 mg in smaller doses and gradually increase the dose. This is done so that your body can get used to the medicine. This helps to minimize side effects as much as possible.
Madopar is available in different strengths and forms:

• 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, tablets for oral suspension
• Madopar 125 mg, 100 mg + 25 mg, tablets for oral suspension.

The usual dose of the medicine is:
In the early stages of Parkinson's disease, treatment usually starts with one capsule of Madopar 62.5 mg (50 mg levodopa + 12.5 mg benserazide) three to four times a day.
Optimal therapeutic effectis usually achieved with a daily dose of Madopar corresponding to 300-800 mg levodopa + 75-200 mg benserazide, taken in at least 3 divided doses over a period of 4 to 6 weeks.
The average maintenance dosecorresponds to 1 capsule of Madopar 125 mg, taken 3 to 6 times a day. The number of divided doses and their distribution throughout the day should be determined by your doctor individually for each patient, depending on their clinical condition. Madopar HBS and Madopar tablets for oral suspension can be used interchangeably with standard Madopar forms (capsules and tablets) to achieve optimal therapeutic effect.

Special dosing instructions

Parkinson's disease:
All patients should have their dose carefully determined. Patients treated with other anti-Parkinsonian medicines may receive Madopar 250 mg. As the patient's condition improves while taking Madopar 250 mg, the doses of these medicines can be reduced or gradually discontinued.
Madopar tablets for oral suspension are particularly suitable for patients with dysphagia (swallowing disorders) or when rapid onset of action is desired.
Patients who experience large fluctuations in the effect of the medicine throughout the dayshould receive smaller doses more frequently throughout the day or Madopar HBS should be recommended.
Switching from a standard form to Madopar HBSshould be done from day to day, starting with the first morning dose. The same daily dose and distribution of doses should be maintained as with the standard form.
After 2-3 days, the dose should be gradually increased by about 50%. There is a possibility of transient worsening of the condition.
The properties of Madopar HBScause its onset of action to occur later than with standard preparations. The desired effect can be achieved faster by administering Madopar HBS together with a standard form or with Madopar tablets for oral suspension. This method may be particularly useful when administering the first morning dose, which usually should be larger than subsequent doses taken throughout the day.
The dosing regimen for Madopar HBS is determined by your doctor individually, slowly and with special caution, at intervals of at least 2-3 days between each dose change.
In patients with reduced motor function at night, positive effectsare achieved by gradually increasing the last evening dose of Madopar HBS to 250 mg, administered before bedtime.
Excessive response (dyskinesia)after taking Madopar HBS is more beneficial to reduce by prolonging the time interval between individual doses rather than reducing single doses.
In case of insufficient clinical response to Madopar HBS, it is recommended to return to previous treatment with standard Madopar.
Taking Madopar 250 mg
If your doctor has prescribed Madopar 250 mg, you can divide the prescribed amount into smaller parts if necessary 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 dose of Madopar 250 mg than recommended

If you have taken a higher dose of the medicine than recommended, you should immediately consult your doctor or pharmacist.
The most common symptoms of overdose may include cardiovascular symptoms (arrhythmias), psychiatric disorders (e.g., disorientation and insomnia), gastrointestinal symptoms (e.g., nausea and vomiting), and involuntary movements.
Overdose of Madopar 250 mg requires immediate medical attention, if necessary in a hospital or intensive care unit. It is recommended to monitor the patient's vital functions and other parameters according to their clinical condition.
Patients may require treatment for cardiovascular symptoms (e.g., arrhythmias) or central nervous system disorders. It may be necessary to administer antiarrhythmic or respiratory stimulant medicines, or neuroleptics.

Missing a dose of Madopar 250 mg

You should not take a double dose to make up for a missed dose. You should take the next doses according to the schedule determined by your doctor.

Stopping treatment with Madopar 250 mg

You should not stop taking Madopar 250 mg abruptly. See section 2: Warnings and precautions.
If you have any further doubts about the use of this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Madopar 250 mg can cause side effects, although not everybody gets them.
Frequency categories
Very common: may occur more often than in 1 in 10 patients
Common: may occur up to 1 in 10 patients
Uncommon: may occur up to 1 in 100 patients
Rare: may occur up to 1 in 1,000 patients
Very rare: may occur up to 1 in 10,000 patients
Unknown (frequency cannot be estimated from available data)
In clinical trials with levodopa/benserazide in restless legs syndrome, common side effects included headache, worsening of restless legs syndrome symptoms, dizziness, infection with fever, cold, bronchitis, dry mouth, diarrhea, nausea, and changes in ECG (arrhythmia).
During treatment with Madopar 250 mg, the following side effects have occurred, all with unknown frequency.
Blood and lymphatic system disorders: blood disorders such as hemolytic anemia, leukopenia, thrombocytopenia. For this reason - as with long-term treatment with levodopa - it is recommended to periodically monitor blood morphology and liver and kidney function.
Metabolism and nutrition disorders: decreased appetite.
Psychiatric disorders: dopamine dysregulation syndrome (cognitive and behavioral disorders that may be directly related to taking a higher dose of the medicine than recommended), confusion, depression, agitation, anxiety, insomnia, hallucinations, delusions, disorientation, pathological gambling, compulsive or binge eating, excessive sexual drive, or increased sexual thoughts and feelings.
Nervous system disorders: loss of taste, taste disorders, involuntary movements (e.g., movements that disrupt normal coordination. They can usually be eliminated or reduced by reducing the dose of the medicine), changes in treatment response during the day (can be eliminated or reduced by adjusting the dose of the medicine or by administering smaller single doses at shorter intervals), sleepiness, sudden sleep attacks, freezing (sudden immobility).
Cardiac disorders: arrhythmia (heart rhythm disturbances).
Vascular disorders: orthostatic hypotension (blood pressure change related to changing position from lying or sitting to standing). Orthostatic disturbances can usually be reduced by reducing the dose of Madopar 250 mg.
Gastrointestinal disorders: nausea, vomiting, diarrhea, change in saliva color, change in tongue color, change in tooth color, change in oral mucosa color. Gastrointestinal side effects occur mainly in the early treatment phase and can be largely reduced by taking Madopar 250 mg with a small protein-poor meal, drinking a liquid, 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, the phenomenon of symptom worsening may occur (shift of symptoms from the evening/night period to the early afternoon and evening before taking the next nocturnal dose).
Investigations:increased blood urea levels, chromaturia (change in urine color. The urine usually turns red, and after settling, it darkens). The color change or discoloration may also affect other body fluids and tissues, including saliva, tongue, teeth, and oral mucosa.
You should also be aware that the following side effects may occur:

• dopamine dysregulation syndrome (cognitive and behavioral disorders that may be directly related to taking a higher dose of the medicine than recommended);
• impulse control disorders, including:
• strong impulse to gamble excessively, despite significant personal or family consequences,
• altered or increased sexual interests and behaviors of great importance to the patient or others, e.g., activities related to increased sexual drive,
• compulsive, uncontrolled spending or shopping,
• binge eating (consuming large amounts of food in a short time) or compulsive eating (consuming more food than normal and more than needed to satisfy hunger). You should inform your doctor if you experience any of these behaviors to discuss ways to control or limit these symptoms. If any side effect worsens or any side effects not listed in the leaflet occur, you should inform your doctor or pharmacist.

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, 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.
By reporting side effects, you can help gather more information on the safety of the medicine.

5. How to store Madopar 250 mg

Keep the medicine out of the sight and reach of children.
Store in a temperature below 25°C. Keep the bottle tightly closed to protect it from light and moisture.
Do not use the medicine after the expiration date stated on the packaging. The expiration date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Madopar 250 mg contains

• The active substances of the medicine are levodopa and benserazide. Each tablet of Madopar 250 mg contains 200 mg levodopa and 50 mg benserazide (in the form of hydrochloride).
• Other ingredients of the medicine are: mannitol, calcium hydrogen phosphate, microcrystalline cellulose, maize starch, crospovidone, ethyl cellulose, red iron oxide, anhydrous colloidal silica, sodium docusate, 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 round, biconvex, light red, slightly speckled tablets with a cross-shaped notch and the code ROCHE and logo embossed on one side.
For more detailed information, you should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in the Czech Republic, the country of export:

Roche s.r.o.
Sokolovská 685/136f
186 00 Prague 8
Czech Republic

Manufacturer:

Roche s.r.o.
Sokolovská 685/136f
186 00 Prague 8
Czech Republic

Parallel importer:

InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw

Repackaged by:

InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing authorization number in the Czech Republic, the country of export:27/391/01-C

Parallel import authorization number: 289/22 Date of leaflet approval: 20.07.2022

[Information about the trademark]