Madopar

Package leaflet: Information for the patient

MADOPAR 100 mg + 25 mg hard capsules, 200 mg + 50 mg divisible tablets, 100 mg + 25 mg prolonged-release hard capsules, 100 mg + 25 mg dispersible tablets

Levodopa + Benserazide
Please read all of this leaflet carefully before you start taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What MADOPAR is and what it is used for
2. What you need to know before taking MADOPAR
3. How to take MADOPAR
4. Possible side effects
5. How to store MADOPAR
6. Contents of the pack and other information

1. What MADOPAR is and what it is used for

MADOPAR contains two active substances: levodopa, an anti-Parkinson agent, and benserazide, a
medicinal product that enhances the activity of levodopa.
MADOPAR is indicated in adults for the treatment:

• of Parkinson's disease, a disorder of the central nervous system that impairs control of movement, manifesting for example with tremor, slowness of movement, difficulty in maintaining balance, due to reduced levels in the central nervous system of a substance called dopamine.
• of a condition presenting symptoms similar to Parkinson's disease ( symptomatic parkinsonism ), resulting from other events affecting the central nervous system (e.g. following brain inflammation, disturbances in cerebral blood circulation, intoxication), excluding those caused by the intake of certain medicinal products.

Consult your doctor if you do not feel better or if you feel worse.

2. What you need to know before taking MADOPAR

Do not take MADOPAR

• if you are allergic to levodopa, benserazide, or any of the other ingredients of this medicine (listed in section 6);
• if you are taking medicines called non-selective monoamine oxidase inhibitors (MAO inhibitors) (see section “Other medicines and MADOPAR”);
• if you have a disease of the hormone-producing glands, for example phaeochromocytoma (a tumour of the adrenal glands located above the kidneys, which causes high blood pressure), hyperthyroidism (a condition in which the thyroid gland is overactive), or Cushing's syndrome (another adrenal gland disorder causing a rounded face, upper body obesity, increased hair growth, and irritability);
• if you have a kidney disease (except if you are undergoing dialysis, a blood filtration system, and suffer from restless legs syndrome, a condition causing an irresistible urge to move the legs or arms);
• if you have a liver disease;
• if you have a severe heart disease (for example, irregular heartbeat or heart failure);
• if you are currently experiencing a heart attack (acute phase of myocardial infarction);
• if you have psychosis, even severe (a mental condition characterised by personality disturbances and loss of contact with reality);
• if you have skin cancer (malignant melanoma) or suspicious skin lesions;
• if you have a severe eye disease characterised by increased pressure of the fluid inside the eye (glaucoma with narrow angle);
• if you are under 25 years of age;
• if you are pregnant or if you are a woman of childbearing age who is not using an adequate contraceptive method (see section “Pregnancy, breastfeeding and fertility”).

Warnings and precautions
Talk to your doctor before taking MADOPAR:

• if you have previously had a heart attack (myocardial infarction) and suffer from heart diseases (rhythm disturbances, coronary artery disease, heart failure) or circulatory problems (blood pressure fluctuations). Your doctor will ask you to undergo periodic check-ups, both during the initial phase of treatment and regularly throughout subsequent therapy;
• if you have previously had stomach and/or intestinal damage (gastro-duodenal ulcer) or if you suffer from a bone disease (osteomalacia). Your doctor will ask you to undergo frequent check-ups;
• if you have diabetes. Your doctor will frequently monitor your blood glucose (blood sugar levels) and adjust the dosage of your antidiabetic medicines accordingly;
• if you are prone to allergic reactions, as these may occur during treatment with MADOPAR;
• if you have an eye disease characterised by increased pressure of the fluid inside the eye (glaucoma with open angle). In this case, your doctor will perform regular checks of the intraocular pressure during treatment with MADOPAR;
• if you are at higher risk of experiencing low blood pressure due to changes in posture (orthostatic hypotension), for example if you are elderly, are being treated with blood pressure-lowering medicines (antihypertensives) or other medicines that may cause this effect (see section “Other medicines and MADOPAR”), or if you have previously experienced this condition. Your doctor will closely monitor you and may request blood tests, especially at the beginning of treatment or after dose increases;
• if you experience mental disturbances, depression with or without suicidal thoughts;
• if you are scheduled for surgery requiring general anaesthesia with the medicine halothane (see section “Other medicines and MADOPAR”).

Impulse control disorders
Inform your doctor if you or someone in your family or your caregiver notices that you are developing urges or desires to behave in ways that are unusual or if you cannot resist the impulse or temptation to carry out certain activities that could harm you or others. These behaviours are called impulse control disorders and may include gambling addiction, excessive eating, compulsive spending, or abnormally increased sexual desire or increased sexual thoughts or feelings. In each of these cases, your doctor may consider it necessary to reassess, modify, or discontinue treatment.

Effects on laboratory test results
Treatment with MADOPAR may:

• alter the results of laboratory tests for catecholamines (such as adrenaline, noradrenaline, dopamine), creatinine, uric acid, and glycosuria (sugar levels in urine);
• give a false positive result in urine tests for ketone bodies;
• give a false positive result in the Coombs test, which detects antibodies in the blood directed against red blood cells;
• cause a reddish discoloration of the urine, which tends to darken over time.

During treatment with MADOPAR, especially if prolonged, your doctor:

• will perform frequent blood tests and periodic monitoring of liver, kidney, heart, and circulatory function;
• will advise you to undergo regular skin examinations by qualified medical personnel (e.g. dermatologists), as patients with Parkinson’s disease have a higher risk than the general population of developing skin cancer (melanoma).

Children and adolescents
MADOPAR must not be administered to children and adolescents.

Other medicines and MADOPAR
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including:

• antacids (used to neutralise stomach acidity);
• iron sulphate (used to treat iron deficiency);
• metoclopramide (used to treat digestive disorders);
• domperidone (used to treat vomiting and digestive difficulties);
• neuroleptics (used to treat certain mental disorders);
• opioids (used for pain treatment);
• antihypertensives containing reserpine (used to treat high blood pressure);
• antipsychotics (used to treat certain mental disorders);
• sympathomimetics (such as adrenaline, noradrenaline, isoprenaline, or amphetamines, which stimulate the sympathetic nervous system);
• irreversible and non-selective monoamine oxidase inhibitors (MAO inhibitors) (used to treat depression). Treatment with MADOPAR must not be started until at least 2 weeks after stopping irreversible and non-selective MAO inhibitors, otherwise a dangerous increase in blood pressure is likely (see section “Do not take MADOPAR”);
• vitamin B6 at medium or high doses taken together with MADOPAR, as it counteracts its effects. This counteracting effect does not occur with low-dose vitamin B6, such as that commonly found in vitamin preparations.

Your doctor will carefully evaluate whether to prescribe other medicines for the treatment of Parkinson’s disease (such as anticholinergics, amantadine, selegiline, bromocriptine, or dopamine agonists). Concurrent administration with MADOPAR may intensify both therapeutic and adverse effects. Therefore, your doctor may reduce the dosage of MADOPAR or of the other medicine.

Surgery
If you are scheduled for surgery requiring general anaesthesia, inform your doctor that you are taking MADOPAR. You may need to stop taking MADOPAR before undergoing general anaesthesia.

MADOPAR with food and drink
Madopar 100 mg + 25 mg hard capsules
Madopar 100 mg + 25 mg dispersible tablets
Madopar 200 mg + 50 mg divisible tablets
The effect of MADOPAR is reduced if taken together with a meal high in protein. If possible, take MADOPAR 30 minutes before or 1 hour after meals (see section 3 “How to take MADOPAR”).

Madopar 100 mg + 25 mg prolonged-release hard capsules
Madopar 100 mg + 25 mg prolonged-release hard capsules can be taken with or without food (see section 3 “How to take MADOPAR”). There are no data on the influence of food on efficacy.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not take MADOPAR if you are pregnant or if you are a woman of childbearing age who is not using an adequate contraceptive method (see section “Do not take MADOPAR”).

Breastfeeding
Do not breastfeed during treatment with MADOPAR. If treatment with MADOPAR becomes necessary during breastfeeding, you must stop breastfeeding and switch to artificial feeding.

Fertility
No data are available.
It is recommended to perform a pregnancy test before starting treatment to exclude possible pregnancy and to use an adequate method of contraception during treatment.

Driving and using machines
MADOPAR may affect your ability to drive or use machines.
During treatment with MADOPAR, exercise particular caution when driving or operating machinery.
If you experience drowsiness and/or sudden sleep attacks, refrain from driving or engaging in any activity where reduced alertness could expose you or others to the risk of serious injury or death (e.g. operating machinery). Avoid driving or using machines until recurrent episodes and drowsiness have resolved.

Madopar 200 mg/50 mg divisible tablets contain sodium
Madopar 200 mg/50 mg divisible tablets contain less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

Madopar 100 mg + 25 mg prolonged-release hard capsules contain hydrogenated soybean oil
Madopar 100 mg + 25 mg prolonged-release hard capsules contain soya. If you are allergic to peanuts or soya, do not use this medicine.

3. How to take MADOPAR

Take this medicine exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Your dose and dosing frequency will be determined by your doctor based on your health status. Your doctor will monitor you closely during the dose adjustment period.
Your doctor will establish the optimal daily dose and how to reach it through a gradual increase in individual doses.
Treatment with MADOPAR 100 mg + 25 mg dispersible tablets is particularly indicated in patients who have difficulty swallowing (dysphagia) or suffer from movement problems (e.g. "morning akinesia" or "afternoon akinesia", "delayed response phenomena", or "end-of-dose deterioration").
Treatment with MADOPAR 100 mg + 25 mg hard capsules with prolonged release is particularly indicated in patients who do not respond adequately to levodopa monotherapy (e.g. "peak-dose dyskinesia" and "end-of-dose deterioration") and for better control of symptoms during the night.
Consider the following instructions only as general guidelines and always follow your prescriber’s specific directions.

HOW MUCH
MADOPAR 100 mg + 25 mg hard capsules
MADOPAR 100 mg + 25 mg hard capsules with prolonged release
MADOPAR 100 mg + 25 mg dispersible tablets
Treatment with MADOPAR usually starts with low doses.
The recommended initial dose is:

• 1 capsule or 1 tablet once daily. The dose may be increased by 1 capsule or 1 tablet every 3 days until the individual effective dose is reached. The effective and maintenance dose ranges between:
• 3–6 capsules or tablets divided into 3 or more daily doses. Your doctor may consider it necessary to increase the number of capsules or tablets taken per day (up to 8–10 capsules or tablets).

MADOPAR 200 mg + 50 mg divisible tablets
The recommended initial dose is:

• 1/2 tablet once daily. The dose may be increased by 1/2 tablet every 3 days until the individual effective dose is reached. The effective and maintenance dose ranges between:
• 1½ – 3 tablets divided into 3 or more daily doses. Your doctor will adjust the dose according to your response to treatment, both in terms of the number of daily doses and their distribution throughout the day. Your doctor may consider it necessary to increase the number of tablets taken per day (up to 4–5 tablets).

HOW TO TAKE
Take MADOPAR ( Madopar 100 mg + 25 mg hard capsules, Madopar 100 mg + 25 mg dispersible tablets, Madopar 200 mg + 50 mg divisible tablets ) preferably 30 minutes before or 1 hour after meals, together with a low-protein snack (e.g. biscuits) or a drink.
Madopar 100 mg + 25 mg hard capsules with prolonged release may be taken with or without food (see section 2 “What you need to know before taking Madopar”).

MADOPAR 100 mg + 25 mg hard capsules
MADOPAR 100 mg + 25 mg hard capsules with prolonged release

• Swallow the capsules whole without chewing. Do not open them or dissolve the contents in any liquid.

MADOPAR 200 mg + 50 mg divisible tablets

• The tablets have a score line to facilitate breaking if you have difficulty swallowing them whole.

MADOPAR 100 mg + 25 mg dispersible tablets

• You may take the dispersible tablets either by swallowing them whole or after dissolving them in 25–50 ml of water (approximately a quarter of a glass). Do not use orange juice, as this would reduce the effectiveness of the product. The tablets disperse completely within a few minutes, giving the liquid an opalescent appearance. Drink the solution within half an hour of preparation, remembering to mix well before taking.

If you take more MADOPAR than you should
In case of accidental ingestion/overdose of MADOPAR, contact your doctor immediately or go to the nearest hospital.
Symptoms
Accidental ingestion/overdose of MADOPAR may worsen the adverse effects that can occur at prescribed doses of MADOPAR.
Irregular heartbeat, confusion, sleep disturbances, nausea and vomiting, and abnormal involuntary movements may occur.
Treatment
Your doctor will determine appropriate supportive measures based on your clinical condition. In particular, treatment may be required for symptoms affecting the heart and circulation (e.g. administration of antiarrhythmics) or the central nervous system (e.g. administration of respiratory stimulants, neuroleptics).
Additionally, in case of overdose with MADOPAR controlled-release hard capsules, your doctor will need to prevent further drug absorption using an appropriate method.

If you forget to take MADOPAR
Do not take a double dose to make up for the missed dose.

If you stop taking MADOPAR
Do not stop taking MADOPAR abruptly.
When MADOPAR administration has been stopped suddenly, a condition called malignant neuroleptic syndrome has been reported, which may be life-threatening. This condition involves a marked increase in body temperature and muscle rigidity, and in some cases, changes in mental status and elevated creatine phosphokinase, a parameter indicating muscle fatigue. Additional symptoms, in severe cases, may include myoglobinuria (i.e. presence of myoglobin, a muscle protein, in urine), rhabdomyolysis (a process of muscle tissue destruction), and acute renal failure (a rapid decline in kidney function). Therefore, your doctor will closely monitor you when MADOPAR dosage is abruptly reduced or discontinued and will evaluate appropriate treatment should such effects occur.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Impulse control disorders:
If you experience any of the following:

• a strong urge to gamble excessively, despite serious personal or family consequences (pathological gambling),
• increased or altered interest in sex (hypersexuality or increased libido),
• uncontrolled or excessive spending (compulsive buying),
• uncontrolled eating or other eating disorders,

inform your doctor, so that he or she can decide how to manage or reduce the symptoms.
Listed below are the side effects reported after marketing and from literature data following administration of MADOPAR, according to their frequency of occurrence:
Not known (frequency cannot be estimated from the available data)

• decrease in the amount of hemoglobin in the blood due to breakdown of red blood cells (hemolytic anemia),
• temporary decrease in the number of white blood cells (transient leukopenia),
• decrease in the number of platelets (thrombocytopenia),
• decreased appetite,
• excessive intake of medication which may lead to behavioral disturbances (dopamine dysregulation syndrome (DDS)),
• confusion,
• depression,
• agitation*,
• anxiety*,
• insomnia*,
• sensation of seeing things that are not really there (hallucinations)*,
• delirium*,
• loss of orientation in time (temporal disorientation)*,
• loss of taste (ageusia), altered taste (dysgeusia),
• involuntary muscle movements (dyskinesia),
• fluctuations in response to therapy,
• freezing or immobility,
• shorter duration of the therapeutic effect of the drug dose (wearing-off phenomenon),
• alternating periods of good mobility with periods of immobility (on-off phenomenon),
• drowsiness (also during daytime), sudden sleep attacks,
• irregular heartbeat (arrhythmia),
• drop in blood pressure upon changing posture (orthostatic hypotension),
• nausea, vomiting, diarrhea,
• discoloration of saliva, tongue, teeth and mouth,
• increased levels of liver enzymes (transaminases, alkaline phosphatase, gamma-glutamyl transferase),
• itching,
• skin rash,
• onset or worsening of an irresistible urge to move the legs or arms (restless legs syndrome),
• increased blood urea,
• discolored urine (chromaturia).

* These side effects may occur particularly in elderly patients and in patients who have previously suffered from such disorders.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MADOPAR

MADOPAR 100 mg + 25 mg dispersible tablets:
Do not store above 30 °C.
Keep the bottle tightly closed to protect the medicine from moisture.
MADOPAR 200 mg + 50 mg divisible tablets:
Do not store above 25 °C.
Keep the bottle tightly closed to protect the medicine from moisture.
MADOPAR 100 mg + 25 mg hard capsules:
Do not store above 30 °C.
Keep the bottle tightly closed to protect the medicine from moisture.
MADOPAR 100 mg + 25 mg prolonged-release hard capsules:
Do not store above 30 °C.
Keep the bottle tightly closed to protect the medicine from moisture.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after “Exp.”
The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What MADOPAR Contains
MADOPAR 100 mg + 25 mg hard capsules
One capsule contains:

• Active substances: Levodopa 100 mg and Benserazide 25 mg (as benserazide hydrochloride 28.5 mg).
• Other components: Capsule contents: povidone K30, talc, magnesium stearate, microcrystalline cellulose. Capsule shell: gelatin, titanium dioxide (E171), red iron oxide (E172), indigotine (E132), printing ink for food use (shellac, potassium hydroxide, black iron oxide (E172)).

MADOPAR 200 mg + 50 mg divisible tablets
One divisible tablet contains:

• Active substances: Levodopa 200 mg and Benserazide 50 mg (as benserazide hydrochloride 57 mg).
• Other components: mannitol (E421), anhydrous dibasic calcium phosphate, microcrystalline cellulose, pregelatinized starch, crospovidone, magnesium stearate, ethylcellulose, red iron oxide (E172), anhydrous colloidal silica, sodium docusate.

MADOPAR 100 mg + 25 mg prolonged-release hard capsules
One capsule contains:

• Active substances: Levodopa 100 mg and Benserazide 25 mg (as benserazide hydrochloride 28.5 mg).
• Other components: Capsule contents: hypromellose, hydrogenated vegetable oil (contains hydrogenated soybean oil), anhydrous dibasic calcium phosphate, mannitol (E421), talc, povidone K30, magnesium stearate.

Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172),
indigotine (E132), printing ink for food use (shellac, potassium hydroxide, red iron oxide (E172)).
MADOPAR 100 mg + 25 mg dispersible tablets
One dispersible tablet contains:

• Active substances: Levodopa 100 mg and Benserazide 25 mg (as benserazide hydrochloride 28.5 mg).
• Other components: anhydrous citric acid, pregelatinized maize starch, microcrystalline cellulose, magnesium stearate.

Description of the Appearance of MADOPAR and Contents of the Package
MADOPAR 100 mg + 25 mg hard capsules
MADOPAR is presented as hard capsules contained in a dark glass bottle with a safety cap made of thermoplastic material, placed in a cardboard carton.
Available in packs of 30 capsules.
MADOPAR 200 mg + 50 mg divisible tablets
MADOPAR is presented as divisible tablets contained in a dark glass bottle with a safety cap made of thermoplastic material, placed in a cardboard carton.
Available in packs of 50 divisible tablets.
MADOPAR 100 mg + 25 mg prolonged-release hard capsules
MADOPAR is presented as prolonged-release hard capsules contained in a dark glass bottle with a safety cap made of thermoplastic material, placed in a cardboard carton.
Available in packs of 30 capsules.
MADOPAR 100 mg + 25 mg dispersible tablets
MADOPAR is presented as dispersible tablets contained in a dark glass bottle with a safety cap made of thermoplastic material, placed in a cardboard carton.
Available in packs of 30 dispersible tablets.
Marketing Authorization Holder
Roche S.p.A. - Viale G.B. Stucchi, 110 - 20900 Monza (MB)
Manufacturer
Roche S.p.A.
Viale G.B. Stucchi, 110
20900 Monza (MB)
Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany