Package Insert: Information for the User

Madopar Retard 100 mg/25 mg Extended-Release Hard Capsules
Levodopa /Benserazide

Read the entire package insert carefully before starting to take the medication, because it contains important information for you.
- Keep this package insert, as you may need to refer to it again.
-If you have any questions, consult your doctor or pharmacist.
- This medication has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.

Madopar Retard is indicated for the treatment of Parkinson's disease

Madopar Retard contains two active ingredients, levodopa and benserazide.

Madopar Retard works as follows:

• In your body, levodopa is converted into dopamine. Dopamine is the active ingredient that your brain needs to treat Parkinson's disease.
• Benserazide allows more levodopa to reach your brain than is administered, before levodopa is converted into dopamine.

Do not take Madopar Retard:

• if you are allergic (hypersensitive) to levodopa or benserazide or to any of the other ingredients of this medicine (listed in section 6).

• if you are taking certain medicines known as non-selective monoamine oxidase inhibitors (MAOIs) or combinations of selective MAO-A and MAO-B inhibitors.

• if you have closed-angle glaucoma (a disease that affects the eyes), high eye pressure.

• if you have severe endocrine disorders: phaeochromocytoma (a tumor of the adrenal gland that causes hypertension), hyperthyroidism (an overactive thyroid gland), Cushing's syndrome (excess cortisol hormone).

• if you have severe kidney, liver or heart disorders.

• if you have severe psychiatric disorders with a psychotic component (alteration of personality and loss of contact with reality).

• if you are under 25 years old.

• if you are pregnant or breastfeeding.

• if you become pregnant during treatment with Madopar Retard, inform your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Madopar Retard:

• if you have mild or moderate liver or kidney disorders
• if you have diabetes (a disease in which blood glucose levels are very high), you may need more frequent blood sugar controls
• if you have open-angle glaucoma (a disease that affects the eyes), your doctor may perform regular intraocular pressure checks
• if you have orthostatic hypotension (low blood pressure associated with changes in posture, which makes you feel dizzy)
• if you have ever had a heart attack or heart problems, your cardiac function will be monitored at the start of treatment and periodically during treatment
• if you notice that you fall asleep suddenly or feel very drowsy (see also section "Driving and operating machinery").
• if you have any other disease before starting treatment with Madopar Retard
• if you are about to undergo surgery, your doctor may interrupt treatment with Madopar Retard.

When starting treatment, you may be asked to have blood tests to monitor liver function and other blood disorders.

It is possible that you will experience a temporary worsening of symptoms at the start of treatment, which improves with the correct adjustment of the dose.

This medicine may affect the results of certain blood tests.

Before starting treatment and during treatment, regular skin examinations should be performed.

After prolonged treatment, involuntary movements, episodes of blockage that can be eliminated or reduced by reducing the dose may occur.

Depression and suicidal thoughts may occur during treatment with Madopar Retard, although they may also be due to your disease. If you feel depressed while on treatment, you should contact your doctor.

In some patients treated with Parkinson's disease medicines, cases of pathological gambling, increased sex drive and excessive sex drive, compulsive buying, eating in excess or compulsively, have been reported, all attributable to taking higher doses of the medication.

You should continue your treatment as long as your doctor tells you to. Stopping suddenly could cause potentially life-threatening side effects (see section 3).

Children and adolescents:

Madopar Retard should not be administered to children or those under 25 years old.

Use of Madopar Retard with other medicines

Inform your doctor or pharmacist if you are taking or have taken recently or may need to take any other medicine.

This is extremely important as taking more than one medicine at the same time can either enhance or weaken the effect of Madopar Retard. Therefore, do not take Madopar Retard with any other medicine unless your doctor has prescribed it.

Madopar Retard should be administered with caution with certain medicines such as:

-monoamine oxidase inhibitors (MAOIs) (used to treat depression), the combination of these medicines with Madopar Retard may cause excessively high blood pressure. This may also occur if you have taken an MAOI in the last 2 weeks (see 'Do not take Madopar Retard', cited above).

-other medicines used to treat Parkinson's disease, as they may increase the adverse effects.

-iron sulphate (used to treat iron deficiency)

-antacids

-metoclopramide and domperidone (used to treat digestive disorders).

-opioid medicines (used to relieve pain).

• medicines for high blood pressure that contain reserpine.

-neuroleptic medicines (used to treat certain psychiatric disorders including anxiety and severe schizophrenia, nausea, dizziness and hypotension).

-antipsychotic medicines

-it is recommended to adjust the dose of levodopa when administered with antidepressant medicines.

-blood pressure medicines: your blood pressure may become too low. Your doctor may need to adjust the dose of your blood pressure medicine.

-medicines that belong to a group called sympathomimetics, such as adrenaline, noradrenaline, isoproterenol, amphetamines, should not be used at the same time as Madopar Retard: the effect of these medicines may be reinforced. Your doctor may need to adjust the dose of your sympathomimetic treatment.

Madopar Retard may interfere with the results of blood tests for certain substances.

Taking Madopar Retard with food and drinks:

The absorption of levodopa may be delayed due to high-protein foods. It is recommended to take the medicine at least 30 minutes before or 1 hour after meals. Gastrointestinal side effects, which may occur mainly at the start of treatment, can be controlled by taking Madopar with a low-protein food (e.g. a biscuit) or with a liquid.

Pregnancy, breastfeeding and fertility:

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medicine.

Madopar Retard should not be taken during pregnancy. There is a possibility of producing skeletal malformations in the fetus.

It is recommended to perform a pregnancy test before treatment to rule out pregnancy.

If you are fertile, you should use reliable contraceptive methods. If you become pregnant while taking this medicine, you should stop treatment immediately.

You should not breastfeed during treatment with Madopar Retard. There is a possibility of producing skeletal malformations in the baby.

Driving and operating machinery:

Depending on your response to treatment, Madopar Retard may affect your ability to drive or operate machinery. Therefore, you should use it with caution until you know how you react to this treatment.

Madopar Retard may cause drowsiness (excessive drowsiness) and sudden episodes of sleep. Therefore, if you feel very drowsy or notice that you fall asleep suddenly, wait until you feel fully awake again before driving or doing anything else that requires you to be alert. If you do not do this, you may put yourself and others at risk of serious injury or even death.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist.

Remember to take your medication.

The treatment with Madopar Retard will only be carried out under the control and recommendations of your doctor.

The recommended dose varies from one individual to another, as it depends on the symptoms of each patient and their individual response to treatment. The treatment with Madopar Retard normally replaces a previous treatment with levodopa, which the doctor will change and gradually increase as they check the patient's response. The substitution ratio is as follows:

For every 100 mg of levodopa you were taking, you will now take a Madopar Retard 100mg/25mg capsule.

It is possible that at the beginning of treatment, there may be a temporary worsening of symptoms, which improve with the correct adjustment of the dose.

Madopar Retard capsules should be swallowed whole and not chewed. Madopar Retard can be taken with or without food.

It is recommended to take Madopar Retard half an hour before or one hour after meals. If gastrointestinal discomfort appears, it is recommended to take the capsules with some food or liquid.

Your doctor will indicate the duration of treatment with Madopar Retard.

If you take more Madopar Retard than you should:

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicological Information Service, phone: 91 562.04.20, indicating the medication and the amount taken. It is recommended to bring the packaging and the medication leaflet to the healthcare professional.

In case of overdose, involuntary movements, confusion, and insomnia may appear. Less frequently, nausea, vomiting, or cardiac arrhythmias (heart rhythm disorder) may occur.

If you forgot to take Madopar Retard:

Do not take a double dose to compensate for the missed doses. Take the next dose as usual.

If you interrupt the treatment with Madopar Retard:

The treatment with Madopar Retard should not be stopped abruptly, as it could cause severe adverse effects.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, Madopar Retard can cause side effects, although not everyone will experience them.

Unknown frequency side effects (cannot be estimated from available data) that may occur during treatment with Madopar Retard:

• Fluctuations in response such as "blockade" (suddenly movement becomes difficult), "end of dose" (return of symptoms before the next dose) and "on-off" phenomena (sudden changes from periods of good symptom control to periods where symptoms are less controlled) *

• Distorted or affected voluntary movements (dyskinesia)

• Involuntary movements *

• Hallucinations, especially in the elderly

• Disorientation in time, especially in the elderly

• Skin allergic reactions such as itching and skin rash

• Orthostatic hypotension

• Decrease in the count of red, white or platelet blood cells (hemolytic anemia, leukopenia or thrombocytopenia)

• Alterations in liver enzymes (increase in transaminases and alkaline phosphatase)

• Agitation, especially in the elderly

• Anxiety, especially in the elderly

• Sleep disorders, especially in the elderly

• Delirium, especially in the elderly

• Loss of appetite

• Excessive daytime somnolence (sleep)

• Sudden episodes of sleep

• Abnormal heart rhythm

• Decrease in blood pressure, which improves with dose reduction

• Restless legs syndrome

• Depression **

• Alterations or loss of taste **

• Nausea **

• Vomiting **

• Diarrhea **

• Urine discoloration, usually a reddish tone. Other bodily fluids may also discolor, such as saliva, tongue, teeth or oral mucosa.

• Mild euphoria

• Aggression

• Dopamine dysregulation syndrome: cognitive and behavioral alterations, pathological gambling (ludopathy), increased sexual desire, compulsive buying, excessive eating

• Digestive disorders: discoloration in saliva, tongue, teeth and oral mucosa

• Increased urea levels in the blood

• Redness and sweating

• Eating disorders, anorexia

* In the final stages of treatment, and in many cases after taking the medication for many years, unusual, uncontrollable movements of the arms, legs, face and tongue or fluctuations in response may occur. This may disappear if the daily dose is changed or if the dose extension is improved throughout the day.

** These side effects usually occur at the beginning of treatment and can be controlled by taking Madopar Retard with food or drink and increasing the dose more slowly.

In patients treated with dopaminergic agonists for the treatment of Parkinson's disease, including levodopa, especially at high doses, cases have been reported with signs of pathological gambling (ludopathy), increased sexual desire and excessive sexual desire, compulsive spending to buy, eat compulsively, usually reversible after reducing the dose or suspending treatment.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this prospectus, inform your doctor or pharmacist.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es/. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not store at a temperature above 30°C.

Store in the original packaging.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and medicines you no longer need at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. By doing so, you will help protect the environment.

Composition of Madopar Retard:

The active principles are: levodopa and benserazide (as hydrochloride). Each capsule contains 100 mg of levodopa and 25 mg of benserazide (as hydrochloride).

The other components are:

Capule contents: hypromellose, hydrogenated vegetable oil, anhydrous dibasic calcium phosphate, mannitol (E-421), povidone, talc, and magnesium stearate.

Capsule coating: gelatin, indigo carmine (E-132), yellow iron oxide (E-172), and titanium dioxide (E-171)

Appearance of the product and contents of the packaging:

Madopar Retard is presented in packs of 100 prolonged-release hard capsules

Holder of the marketing authorization and responsible for manufacturing:

Holder of the marketing authorization
ROCHE FARMA, S.A.
C/ Ribera del Loira, 50
28042 Madrid

Responsible for manufacturing

Roche Farma, S.A.

C/ Eratóstenes, 19

Getafe

28906 Madrid

Date of the last review of this leaflet:September 2023

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/