Madopar 250 mg

Package Leaflet: Information for the Patient

Warning! The leaflet should be kept. 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.

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

• The leaflet should be kept so that it can be re-read if necessary.
• In case of any doubts, the patient should consult a doctor or pharmacist.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. 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 benserazide hydrochloride).
Madopar 250 mg is indicated for the treatment of Parkinson's disease.
Parkinson's disease is characterized by slow movements, muscle stiffness, and tremors. These symptoms are caused by a lack of dopamine in certain brain centers. The signs 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 in treatment is that dopamine does not pass from the blood into the brain. However, its chemical precursor, levodopa, can pass through without any problems. Unfortunately, most of the 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, more levodopa enters the brain and is converted to dopamine, and there is no conversion of levodopa to dopamine in non-brain 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, attention should be paid to not using 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), mental illnesses with psychotic symptoms, and glaucoma with closed-angle glaucoma;
• in patients under 25 years of age (bone development 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, the patient should discuss with their doctor or pharmacist if:

• the patient has diabetes- blood glucose levels should be checked more frequently and the dosage of antidiabetic drugs should be adjusted accordingly;
• the patient has open-angle glaucoma- intraocular pressure should be measured regularly;
• the patient is scheduled for general anesthesia. In such cases, Madopar 250 mg should be taken for as long as possible before the operation, except for anesthesia using halothane. When using halothane for general anesthesia, Madopar 250 mg should be discontinued 12-48 hours before the procedure, due to the possibility of blood pressure fluctuations and/or cardiac arrhythmias. After the procedure, treatment can be resumed, gradually increasing the doses to the previously used dose;
• the patient has had coronary artery disease, arrhythmias, or heart failure - cardiac function should be carefully monitored, especially during the initiation of treatment, and then regularly during therapy;
• the patient is elderly and taking antihypertensive drugs and other drugs that may cause orthostatic hypotension or has had orthostatic hypotension;
• the patient is taking sympathomimetic drugs, as their action may be enhanced;
• the patient is taking a catechol-O-methyltransferase (COMT) inhibitor;
• the patient is taking anticholinergic drugs, such as amantadine, selegiline, bromocriptine, dopamine agonists; concurrent use of these drugs with Madopar 250 mg may enhance both the therapeutic and adverse effects.

During the dose titration phase, it is recommended to periodically monitor liver, kidney, and cardiovascular function
and monitor blood counts.
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 sleepmay occur. Very rarely, cases of sleep attacks have been reported, which can occur even during daily activities, in some cases without warning or prior sleepiness. Therefore, when taking Madopar 250 mg, caution should be exercised when driving or operating machinery. Patients who have already experienced sleepiness or sleep attacks should not drive or operate machinery. If sleepiness or sleep attacks occur, the doctor should consider reducing the dose or discontinuing treatment.
Hypersensitivity reactionsmay occur in predisposed individuals.
The patient should inform their doctor if they or their relatives notice unusual behaviors resulting from irresistible impulses, compulsions, or repetitive behaviors that are harmful to the patient or others. Such behaviors are called impulse control disordersand may include gambling addiction, compulsive or binge eating, excessive sexual drive, or enhanced sexual thoughts and feelings. It may be necessary to re-evaluate the treatment used by the doctor.
Parkinson's disease patients have an 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. Regular skin examinations for melanoma should be performed 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

The patient should inform their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
If a patient taking a non-selective MAOIis prescribed Madopar 250 mg, at least two weeks should elapse between the end of non-selective MAOI treatment and the start of Madopar 250 mg treatment. 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 is equivalent to non-selective MAO inhibition and therefore should not be used simultaneously with Madopar 250 mg.
In the case of concurrent use of iron sulfate, the maximum plasma concentration of levodopa is reduced.
Metoclopramide increases the absorption rate of levodopa. Domperidone may affect the increased absorption of levodopa in the intestine.
In the case of concurrent use of antihypertensive drugsand Madopar 250 mg, blood pressure should be regularly monitored to allow for dose adjustment of the antihypertensive drugs.
Neuroleptic drugs, opioids, and antihypertensive drugs containing reserpineinhibit the action of Madopar 250 mg.
Concomitant use of Madopar 250 mg with anti-Parkinsonian drugs(amantadine, selegiline, bromocriptine, dopamine agonists, anticholinergic drugs, such as trihexyphenidyl) is allowed, but it should be noted that both the desired and undesired effects of the medicine may be enhanced. Attention should be paid to not abruptly discontinuing anticholinergic drugswhen starting treatment with Madopar 250 mg, as the action of levodopa occurs only after some time.
Concomitant administration of antipsychotic drugs with drugs that block dopamine receptors may counteract the anti-Parkinsonian effect of Madopar 250 mg. Levodopa may counteract the effect of antipsychotic drugs. Caution should be exercised when concomitantly administering these drugs, and the patient should be closely monitored for reduced anti-Parkinsonian drug efficacy and worsening of Parkinson's disease symptoms. Levodopa in Madopar 250 mg may affect the results of laboratory tests for catecholamines, creatinine, uric acid, and glycosuria.
Patients taking Madopar 250 mg may experience false-positive Coombs test resultsand false-positive ketone bodies in the urine.
In the case of general anesthesia using halothane, Madopar 250 mg should be discontinued 12-48 hours before the procedure, 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 weaken 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 operating machinery

When taking Madopar 250 mg, sleepiness may occur, and in rare cases, sudden sleep attacks may occur, so caution should be exercised when driving or operating machinery. Patients who have already experienced sleepiness or sleep attacks during treatment with Madopar 250 mg should refrain from driving or operating machinery, as this 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, which means the medicine is considered "sodium-free".

3. How to take Madopar 250 mg

This medicine should always be taken according to the doctor's or pharmacist's instructions. In case of doubts, the patient should consult their doctor or pharmacist.
Available on the market are: 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).
Dosing in Parkinson's disease:

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

Treatment with Madopar 250 mg.

Madopar 250 mg should never be taken without a doctor's prescription. In no case should the dosage be changed without the doctor's consent.

Madopar 250 mg should be taken approximately 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, protein-poor meal (e.g., biscuits) or a drink, or by gradually increasing the dose.
For effective treatment, it is essential to take the correct amount of medicine at the right time. The doctor will determine the appropriate amount and frequency of administration individually and, in close cooperation with the patient, will determine the best treatment schedule. Therefore, the patient should strictly follow the doctor's instructions. Generally, at the beginning of treatment, the doctor prescribes Madopar 250 mg in smaller doses and gradually increases the dose. This is done so that the patient's body can adapt to the medicine, thus limiting side effects as much as possible.
Typically, the recommended 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 250 mg equivalent 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 individually by the doctor for each patient, depending on their clinical condition. Madopar HBS and Madopar in the form of 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 drugs may receive Madopar 250 mg. As the patient's condition improves with Madopar 250 mg treatment, the doses of these drugs can be reduced or gradually discontinued.
Madopar in the form of tablets for oral suspensionis particularly recommended 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 during 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 with a standard form or with tablets for oral suspension of Madopar. This method may be particularly useful when administering the first morning dose, which usually should be larger than subsequent doses taken during the day.
The dosing regimen for Madopar HBS is determined individually by the doctor, slowly and with special caution, with intervals of at least 2-3 days between each dose change.
In patients with reduced motor function at night, positive effects are achieved by gradually increasing the last evening dose of Madopar HBS to 250 mg, administered directly before bedtime.
Excessive response (dyskinesia)after administration of Madopar HBS is more beneficial to reduce by prolonging the time interval between individual doses rather than by reducing single doses.
In the case of insufficient clinical response to Madopar HBS, it is recommended to return to previous treatment with standard Madopar or Madopar in the form of tablets for oral suspension.
Taking the medicine
If the doctor has prescribed Madopar 250 mg, the prescribed amount can be divided into smaller parts if necessary to facilitate swallowing.
If the patient feels that the effect of Madopar 250 mg is too strong or too weak, they should consult their doctor.

Taking a higher dose of Madopar 250 mg than recommended

In case of taking a higher dose of the medicine than recommended, the patient should immediately consult their doctor or pharmacist.
The most common symptoms of overdose may be cardiovascular symptoms (arrhythmias), mental 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 anti-arrhythmic drugs and/or respiratory stimulants or neuroleptics.

Missing a dose of Madopar 250 mg

A double dose should not be taken to make up for a missed dose. Subsequent doses of the medicine should be taken according to the schedule established by the doctor.

Stopping treatment with Madopar 250 mg

Madopar 250 mg should not be stopped abruptly. See section 2 Warnings and precautions.
In case of any further doubts about the use of this medicine, the patient should consult their 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 frequently than in 1 in 10 patients
Common: may occur in less than 1 in 10 patients
Uncommon: may occur in less than 1 in 100 patients
Rare: may occur in less than 1 in 1,000 patients
Very rare: may occur in less than 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, periodic monitoring of blood morphology and liver and kidney function is recommended.
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, increased libido, increased sexual drive, compulsive spending or buying, binge eating, or eating disorders.
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 disorders).
Vascular disorders:orthostatic hypotension (blood pressure change related to changing position from lying or sitting to standing). Orthostatic disorders 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 limited 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 worsening symptoms may occur (shift of symptoms in time from the evening/night to 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.
The following side effects may also 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 buying,
• 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). The patient should inform their doctor if they exhibit 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, the patient should inform their doctor or pharmacist.

Reporting side effects

If side effects occur, including any side effects not listed in the leaflet, the patient should inform their doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181 C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Madopar 250 mg

The medicine should be stored out of sight and reach of children.
Do not store above 30°C. The bottle should be kept tightly closed to protect it from moisture. Store in the original packaging.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their 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 levodopa and benserazide (in the form of benserazide hydrochloride) in a ratio of 4:1 (200 mg + 50 mg).
• Other ingredients of the medicine are: mannitol, calcium hydrogen phosphate, microcrystalline cellulose, maize starch, crospovidone, ethyl cellulose, iron oxide red (E 172), anhydrous colloidal silica, sodium lauryl sulfate, magnesium stearate;

What Madopar 250 mg looks like and contents of the pack

The pack contains: 100 tablets.
Light red tablets with the inscription ROCHE and a hexagon on one side, containing 200 mg levodopa and 50 mg benserazide (in the form of benserazide hydrochloride).
For more detailed information, the patient should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in Spain, the 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:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Spanish marketing authorization number: 669770.2

Parallel import authorization number: 134/23

Date of leaflet approval: 07.07.2023

[Information about the trademark]