Madopar 250 mg

Package leaflet: Information for the patient

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Madopar 250 mg (Madopar 200 mg/50 mg)
200 mg + 50 mg, tablets
Levodopum + Benserazidum
Madopar 250 mg and Madopar 200 mg/50 mg are different trade names for the same medicinal product.
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult 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 identical.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

1. What Madopar 250 mg is and what it is 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 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 result from insufficient levels of dopamine in specific areas of the brain. The severity and combination of symptoms vary among individual patients.
The aim of treating Parkinson's disease is to compensate for the dopamine deficiency in the brain. The difficulty lies in the fact that dopamine itself does not cross from the bloodstream into the brain. However, its chemical precursor—levodopa—readily crosses the blood-brain barrier. Unfortunately, a large portion of levodopa is converted into dopamine before it reaches 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). Due to benserazide, more levodopa reaches the brain, where it is converted into dopamine, while conversion of levodopa into dopamine in peripheral (non-brain) tissues is prevented, thereby reducing the occurrence of adverse effects. Thus, Madopar 250 mg can beneficially influence the 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. Etiological treatment of the disease remains impossible to date.

2. Important information before using Madopar 250 mg

When not to use 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. Concomitant 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 uncorrected disorders: endocrine (pheochromocytoma, hyperthyroidism, Cushing's syndrome), renal or hepatic function, heart disease (e.g. severe cardiac arrhythmias and heart failure), psychiatric disorders with psychotic symptoms, or narrow-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 being treated with Madopar 250 mg, the medicine should be discontinued immediately.

Warnings and precautions
Before starting 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 is scheduled for surgery under general anaesthesia. In such cases, Madopar 250 mg should be continued for as long as possible up to the time of surgery, except when halothane is used. When general anaesthesia with halothane is planned, Madopar 250 mg should be discontinued 12–48 hours before surgery due to the risk of blood pressure fluctuations and/or cardiac arrhythmias (arrhythmia). After surgery, treatment may be resumed gradually, increasing the dose until the previously used dose is reached;
• the patient has a history of coronary artery disease, cardiac arrhythmias, or heart failure – cardiac function should be closely monitored, especially at the beginning of treatment and regularly throughout therapy;
• the patient is elderly and concurrently taking antihypertensive drugs or other medications that may cause orthostatic hypotension, or if the patient has previously experienced hypotension;
• the patient is taking sympathomimetic agents (drugs that stimulate the sympathetic nervous system), as their effects may be enhanced;
• the patient is taking a catechol-O-methyltransferase (COMT) inhibitor;
• the patient is taking anticholinergic drugs such as amantadine, selegiline, bromocriptine, or dopamine agonists; concomitant use with Madopar 250 mg may enhance both therapeutic and adverse effects.

During the dose adjustment phase, liver function, kidney function, and cardiovascular function should be monitored periodically, along with blood tests.
During treatment with Madopar 250 mg, depression may occur, although this may also be related to the underlying disease. Patients receiving Madopar 250 mg should be carefully monitored for psychological changes and depression, with or without suicidal thoughts.
Cognitive and behavioural disturbances may occur in patients receiving Madopar 250 mg.
In rare cases, during levodopa treatment, drowsiness and/or sudden sleep onset may occur. Very rarely, sleep attacks have been reported, which may occur even during daily activities, sometimes without warning or preceding drowsiness. Therefore, caution is required 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 behaviours resulting from an uncontrollable impulse, compulsion, or obsessive performance of certain actions that may be harmful to the patient or others. These behaviours 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 skin examinations for melanoma should be performed during treatment with Madopar 250 mg, regardless of the indication.
Do not stop taking Madopar 250 mg suddenly.
Abrupt discontinuation may lead to a potentially life-threatening condition resembling neuroleptic malignant syndrome (high fever, muscle rigidity, possible psychiatric changes). If such symptoms occur, the patient should be placed under medical supervision, possibly in hospital, and promptly receive appropriate symptomatic treatment.
Potential for drug dependence or misuse
Cognitive and behavioural disturbances have been observed 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 to treat motor impairment).

Madopar 250 mg and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
If a patient receiving a non-selective MAO inhibitor is prescribed Madopar 250 mg, at least two weeks should elapse between stopping the non-selective MAO inhibitor and starting 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 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 concomitantly 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 enhance levodopa absorption in the intestine.
When antihypertensive medicines are used concomitantly 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.
Concomitant use of Madopar 250 mg with anti-parkinsonian drugs (amantadine, selegiline, bromocriptine, dopamine agonists, anticholinergic drugs such as trihexyphenidyl) is permitted, but it should be noted that both desired and adverse effects may be enhanced. Care should be taken not to abruptly discontinue anticholinergic drugs at the beginning of Madopar 250 mg treatment, as the effect of levodopa may take some time to manifest.
Concomitant use of antipsychotic drugs with dopamine receptor-blocking properties may counteract the anti-parkinsonian effect of Madopar 250 mg.
Levodopa may reduce the effectiveness of antipsychotic drugs. Caution is required when administering these drugs 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 urine ketone test results.
In general anaesthesia using halothane, Madopar 250 mg should be discontinued 12–48 hours before the procedure, as concomitant use of Madopar 250 mg and halothane may cause blood pressure fluctuations and/or cardiac arrhythmias.

Taking Madopar 250 mg with food and drink
Concomitant 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.
A pregnancy test should be performed before starting treatment 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 undertaken during treatment with Madopar 250 mg, as the active substances may pass into breast milk and harm the infant.

Driving and operating machinery
Drowsiness may occur during treatment with Madopar 250 mg, and in rare cases sudden sleep attacks may occur. Therefore, caution is always required 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; therefore, the medicine is considered "sodium-free".

3. How to take Madopar 250 mg

This medicine should always be taken exactly as directed by your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist.
The following products are available on the market: 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).
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 consultation with the doctor. If a
change of physician or a visit to another doctor becomes necessary, the new physician must be
promptly informed about the treatment 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 small, low-protein meal (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 determines individually the appropriate amount and frequency of administration and, in
close cooperation with the patient, establishes the optimal treatment regimen. Therefore, it is important
to strictly follow the doctor's instructions. Generally, at the beginning of treatment, the doctor prescribes
Madopar 250 mg in lower doses and gradually increases the dose. This approach allows the patient's
body to adapt to the medicine, thereby minimizing adverse effects as much as possible.
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.
Optimal therapeutic effect is usually achieved with a daily dose of Madopar 250 mg 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.
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 in the form of oral suspension tablets may be used interchangeably with standard formulations
of Madopar (capsules and tablets) to achieve optimal therapeutic effect.
Special dosing instructions
Parkinson's disease:
Dosage must be carefully established for all patients. Patients previously treated with other
anti-parkinsonian drugs may be switched to Madopar 250 mg. As the patient's condition improves with
Madopar 250 mg, doses of other medications may be reduced or gradually discontinued.
Madopar in the form of oral suspension tablets is particularly indicated in patients with dysphagia
(difficulty swallowing) 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 day by day, starting with
the first morning dose. The same total daily dose and the same distribution of doses as with standard
formulations should be maintained.
After 2–3 days, the dose should be gradually increased by approximately 50%. A transient
worsening of health 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 when administering the first morning dose, which is usually larger than subsequent daytime
doses.
The dosing regimen for Madopar HBS must 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.
Excessive response (dyskinesias) following administration of Madopar HBS is best managed by
extending the interval between doses rather than by reducing individual doses.
If an adequate clinical response is not achieved with Madopar HBS, it is recommended to return to
previous treatment with standard Madopar or Madopar oral suspension tablets.
Taking the medicine
If your doctor has prescribed Madopar 250 mg tablets, the prescribed amount may be crushed if
necessary to facilitate swallowing.
If you feel that the effect of Madopar 250 mg is too strong or too weak, consult your doctor.
Taking a higher than recommended dose of Madopar 250 mg
If more medicine than prescribed has been taken, seek immediate advice from a 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 drugs
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 stop taking Madopar 250 mg abruptly. See section 2 Warnings and precautions.
If you have any further questions about 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 patients
Common: may affect up to 1 in 10 patients
Uncommon: may affect up to 1 in 100 patients
Rare: may affect up to 1 in 1,000 patients
Very rare: may affect up to 1 in 10,000 patients
Not known (frequency cannot be estimated from available data)
In clinical trials using levodopa/benserazide in restless legs syndrome, frequent occurrences of
headache, worsening of restless legs syndrome symptoms, dizziness, infection with fever, cold,
bronchitis, dry mouth, diarrhoea, nausea, ECG changes (arrhythmia), and increased blood pressure
were reported.
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 count as well as 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
behaviour, increased libido, increased sexual drive, 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), fluctuations in response during the day (can be eliminated or reduced by appropriate dose
adjustment or by administering smaller doses at shorter intervals), somnolence, sudden sleep attacks,
freezing (sudden immobility).
Cardiac disorders: arrhythmia (irregular heartbeat).
Vascular disorders: orthostatic hypotension (blood pressure changes related to changing from lying
or sitting to standing position). Orthostatic disturbances can usually be reduced by decreasing the dose
of Madopar 250 mg.
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, with a drink, or by gradually increasing the dose.
Hepatobiliary disorders: increased transaminase activity, increased alkaline phosphatase activity,
increased gamma-glutamyl transferase activity.
Skin and subcutaneous tissue disorders: itching, rash.
Musculoskeletal and connective tissue disorders: in restless legs syndrome, symptom augmentation
(movement of symptoms from evening/night to early afternoon and evening before taking the next
night dose) may occur.
Investigations: increased blood urea concentration, chromaturia (discoloration of urine; urine usually
becomes reddish and darkens upon standing). Discoloration may also affect other body fluids and
tissues, including saliva, tongue, teeth, and oral mucosa.
Please note 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 impulse to engage in uncontrollable gambling 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 increased 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).
  Inform your doctor if any of these behaviours occur, so that ways to control or reduce these symptoms can be discussed.

If any of the side effects worsen or if any side effects not listed in this leaflet occur, 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,
pharmacist, or nurse.
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 181 C
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 this medicine.

5. How to store Madopar 250 mg

Keep the 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 stated month.
Medicines must not be disposed of via sewage or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Madopar 250 mg contains

• The active substances in this medicine are levodopa and benserazide. Each tablet of Madopar 250 mg contains levodopa and benserazide (as benserazide hydrochloride) in a 4:1 ratio (200 mg + 50 mg).
• Other components of the medicine are: mannitol, calcium hydrogen phosphate, microcrystalline cellulose, pregelatinized corn starch, crospovidone, ethylcellulose, iron oxide red (E 172), colloidal anhydrous silica, sodium docusate, magnesium stearate.

What Madopar 250 mg looks like and contents of the pack
Pack contains: 100 tablets.
Light red tablets with the imprint ROCHE and a hexagon on one side, containing 200 mg of levodopa and 50 mg of benserazide (as benserazide hydrochloride).
For further detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing Authorisation 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 in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Marketing Authorisation Number in Spain, the country of export: 669770.2
Parallel Import Licence Number: 134/23