Xevoben

Package Leaflet: Information for the Patient

Xevoben, 200 mg + 50 mg, Tablets

Levodopa + Benserazide

Read the Package Leaflet Carefully Before Taking the Medication, as it Contains Important Information for the Patient.

• Keep this leaflet, as you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• This medication has been prescribed specifically for you. Do not pass it on to others. The medication may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including those 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 Xevoben and what is it used for
• 2. Important information before taking Xevoben
• 3. How to take Xevoben
• 4. Possible side effects
• 5. How to store Xevoben
• 6. Contents of the pack and other information

1. What is Xevoben and what is it used for

Xevoben is a medication containing the active substances levodopa and benserazide. The active substance levodopa is a precursor to a substance produced by the human body – dopamine. Insufficient amounts of dopamine in certain parts of the brain are the cause of both Parkinson's disease and restless legs syndrome. This deficiency is supplemented by converting levodopa into dopamine. The second active substance, benserazide, blocks the breakdown of levodopa outside the brain and allows for a smaller dose of levodopa to be taken. Xevoben is used:

• to treat Parkinson's disease (paralytic tremor, a disease characterized by tremors, slowed movements, and muscle stiffness);
• to treat symptoms similar to those of Parkinson's disease, but resulting from poisoning, brain inflammation, and changes in the brain caused by atherosclerosis of the arteries (parkinsonian syndrome). This does not include symptoms similar to Parkinson's disease caused by certain medications (treatment-induced parkinsonism).
• to treat restless legs syndrome of unknown cause;
• to treat restless legs syndrome resulting from renal failure requiring dialysis. Before starting treatment with levodopa and benserazide, the doctor will ensure that the symptoms of restless legs syndrome are not caused by iron deficiency. If this is the case, iron supplementation treatment should be started.

2. Important information before taking Xevoben

When not to take Xevoben

• if the patient is allergic to levodopa, benserazide, or any of the other ingredients of this medication (listed in section 6);
• in patients under 25 years of age (bone growth must be completed);
• in patients with severe disorders of certain hormone-producing organs, such as hyperthyroidism or significantly elevated cortisol levels in the blood (Cushing's syndrome), or with adrenal tumors;
• in patients with severe metabolic disorders, liver, kidney, or bone marrow disorders;
• in patients with severe kidney disease, not treated with dialysis (applies to patients with restless legs syndrome);
• in patients with severe heart disease, such as serious heart rate problems (tachycardia), severe heart rhythm disorders, or heart failure;
• in patients with certain mental disorders (psychosis), which may or may not have a physical origin;
• in patients taking medications for high blood pressure containing the active substance reserpine (see "Xevoben and other medications");
• in patients being treated with non-selective monoamine oxidase inhibitors (MAOIs) (antidepressant medication containing the active substance tranylcypromine) or a combination of selective MAOI-A (antidepressant medication containing the active substance moclobemide) and selective MAOI-B (medication used to treat Parkinson's disease, containing the active substance selegiline or rasagiline) (see "Xevoben and other medications");
• in patients with high intraocular pressure (angle-closure glaucoma);
• in pregnant women;
• in women of childbearing age who do not use effective contraception (see "Pregnancy and breastfeeding").

Warnings and precautions

Before starting treatment with Xevoben, the patient should discuss it with their doctor, pharmacist, or nurse. In susceptible individuals, allergic reactions may occur. Caution should be exercised when taking Xevoben in patients who have experienced excessive daytime sleepiness or sudden, unexpected sleep attacks during treatment with Xevoben. If this applies to the patient, they should consult their doctor (see "Driving and using machines").

Additional warning and precautions for patients with restless legs syndrome

• if the patient has a more severe form of restless legs syndrome and requires a higher dose of Xevoben than that described in section 3, and if symptoms worsen or occur earlier in the day, treatment with Xevoben should be discontinued.

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 disorders and may include addiction to gambling, overeating, or excessive spending, or increased sexual drive or intense sexual thoughts and feelings. It may be necessary to re-evaluate the treatment being taken by the doctor.

Regular medical check-ups are necessary if:

• the patient has had a heart attack in the past;
• the patient currently has irregular heartbeats, reduced blood flow to the coronary arteries, or heart failure;
• the patient has had stomach or intestinal ulcers in the past;
• the patient has reduced bone density;
• the patient has open-angle glaucoma, as levodopa may theoretically increase intraocular pressure;
• the patient has diabetes.

In addition, it is necessary to periodically check liver, kidney, and cardiovascular function, as well as blood tests. Taking Xevoben may cause circulation problems due to excessively low blood pressure (see section 4). These symptoms usually disappear or improve after reducing the dose of Xevoben. If the patient is elderly or is taking medications for high blood pressure or other medications that may lower blood pressure, or if the patient has circulation problems due to low blood pressure, the doctor will closely monitor the patient, especially at the beginning of treatment or when increasing the dose. Therefore, regular visits scheduled by the doctor are necessary.

Warning

In a small number of patients with Parkinson's disease, cognitive and behavioral disorders may occur, which may be related to taking Xevoben, contrary to the doctor's recommendations, in a much higher dose than required to treat motor disorders. After many years of therapy with a medication containing the same active substances as Xevoben, sudden withdrawal of Xevoben may lead to the occurrence of withdrawal symptoms (called malignant levodopa withdrawal syndrome). Symptoms include very high fever, muscle stiffness, and mental changes. In severe cases, it may lead to the excretion of muscle proteins in the urine (myoglobinuria), muscle fiber breakdown (rhabdomyolysis), acute kidney failure, or complete immobilization. These symptoms are potentially life-threatening. In such a case, the doctor should be notified immediately!

If the patient is scheduled for surgery under general anesthesia, they should take the medication containing levodopa/benserazide for as long as possible before the operation, except when using halothane anesthesia. When using halothane anesthesia, the medication containing levodopa/benserazide should be discontinued 12-48 hours before the procedure, due to the risk of blood pressure fluctuations and/or heart rhythm disorders in patients taking levodopa/benserazide with halothane. After the procedure, treatment can be resumed, gradually increasing the dose to the previously used dose.

Caution

Particularly at the beginning of treatment, gastrointestinal disorders such as dry mouth, nausea, vomiting, or diarrhea may occur (see section 4). These can be significantly reduced or eliminated by taking Xevoben with a small, protein-poor meal (e.g., biscuits, crackers, or similar), drinking fluids, or gradually increasing the dose.

During long-term treatment and/or high doses, involuntary movements may occur (see section 4). These symptoms usually disappear or are less bothersome after reducing the dose.

In patients with Parkinson's disease, there is an increased risk of developing melanoma compared to the general population. It is not clear whether the observed increased risk is due to Parkinson's disease or other factors, such as the use of levodopa in the treatment of Parkinson's disease. During treatment with Xevoben, patients should regularly examine their skin for suspicious changes and undergo periodic skin examinations by a suitable specialist (e.g., dermatologist).

Caution for the patient's environment

Treatment with Xevoben may lead to the occurrence of pathological depression, especially if there are previous predispositions to such symptoms (see section 4). However, depression may be one of the symptoms of Parkinson's disease or restless legs syndrome. Therefore, patients should be closely monitored for psychological changes to detect depression at an early stage. In such a case, the doctor should be consulted.

Xevoben and other medications

The patient should tell their doctor or pharmacist about all medications they are currently taking or have recently taken, as well as any medications they plan to take.

Taking Xevoben with the following active substances or medications may affect their action

• medications used to treat low blood pressure, circulation disorders, irregular heartbeats, medications used to induce labor, or medications used to treat bronchial spasms (called sympathomimetics), such as epinephrine, norepinephrine, isoproterenol, or amphetamine. The action of sympathomimetic medications may be enhanced. Therefore, their concurrent use is not recommended. If concurrent use is necessary, the patient's cardiovascular system should be closely monitored, and the dose of the sympathomimetic medication may need to be reduced.
• medications used to treat high blood pressure (called antihypertensive medications): the action of the antihypertensive medication may be enhanced, and the risk of low blood pressure may increase. Therefore, blood pressure should be regularly monitored (see above). If necessary, the doctor may adjust the dose of Xevoben and/or the dose of the antihypertensive medication.

The following medications may affect the action of Xevoben

Weakening of action by:

• certain pain medications (opioids);
• medications used to treat high blood pressure containing the active substance reserpine. In this case, Xevoben should not be taken (see above);
• certain medications used to treat low mood (neuroleptics).

Enhancement of action and possible enhancement of side effects by:

• medications containing the active substance selegiline (used to treat Parkinson's disease).

Other possible interactions:

• certain medications used to treat depression (called MAOIs): concurrent use of Xevoben and medications containing tranylcypromine as the active substance may dangerously increase blood pressure. This situation may occur up to 2 weeks after stopping tranylcypromine treatment. Xevoben should not be taken in this case (see above). Therefore, a 2-week interval should be maintained between stopping tranylcypromine treatment and starting Xevoben treatment. On the other hand, concurrent use of Xevoben and moclobemide, selegiline, and rasagiline is considered safe.
• concurrent use of Xevoben with domperidone may lead to increased levodopa levels in the blood. Their concurrent administration may increase the risk of heart rhythm disorders.

Concurrent use of Xevoben with other anti-Parkinsonian medications (e.g., dopamine agonists, amantadine, anticholinergic medications, selegiline, bromocriptine) is allowed. However, it should be noted that not only the desired but also the undesired action of the medication may be enhanced. The doctor may prescribe a reduced dose of Xevoben or another medication. If supportive treatment is started with a medication containing entacapone, it may also be necessary to reduce the dose of Xevoben.

Changes in laboratory diagnostic tests

Changes may occur in the following laboratory tests:

• levodopa may affect the results of laboratory tests for catecholamines, creatinine, uric acid, and glucose (in glucosuria);
• false-positive results for the presence of ketone bodies may occur when using test strips (this reaction does not change when the urine sample is boiled);
• false-negative results for the presence of glucose in the urine may occur when using glucose oxidase;
• false-positive results for the Coombs test may occur.

General anesthesia with halothane

In the case of general anesthesia when halothane is used, the medication containing levodopa/benserazide should be discontinued 12-48 hours before the procedure, due to the risk of blood pressure fluctuations and/or heart rhythm disorders.

Xevoben with food and drink

The patient should avoid consuming protein-rich meals shortly before taking Xevoben, as this may weaken the action of the medication.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medication. Before starting treatment, it is recommended to perform a pregnancy test to rule out pregnancy. Xevoben should not be taken during pregnancy, as there are no available studies in pregnant women, and animal studies have shown a harmful effect on the unborn child of both active substances contained in Xevoben. Women of childbearing age should use effective contraception during treatment with Xevoben. If the patient becomes pregnant or thinks they may be pregnant, they should consult their doctor. The doctor will advise how to discontinue Xevoben treatment. During treatment with Xevoben, breastfeeding should not be performed. If treatment with Xevoben is necessary, breastfeeding should be discontinued.

Driving and using machines

Xevoben may have a major impact on the ability to drive and use machines. In rare cases, taking Xevoben may cause excessive sleepiness or sudden sleep attacks. If this applies to the patient, they should refrain from driving and using machines to avoid the risk of serious injury to themselves or others until the excessive sleepiness or sudden sleep attacks have disappeared.

Xevoben contains sodium

The medication contains less than 1 mmol (23 mg) of sodium per tablet, which means the medication is considered "sodium-free".

3. How to take Xevoben

This medication should always be taken according to the doctor's recommendations. In case of doubts, the patient should consult their doctor or pharmacist. The number of Xevoben tablets taken depends on the severity of the disease and the patient's tolerance to Xevoben. The most optimal dose for the patient is determined by gradually increasing the daily dose. Therefore, the dose prescribed to the patient may differ from the dose prescribed to other patients. The patient should not change the dose determined by their doctor.

Treatment of Parkinson's disease symptoms

Unless the doctor recommends otherwise, the treatment scheme is as follows

Treatment starts with small doses, which are then gradually increased to limit the occurrence of side effects and not reduce the likelihood of a therapeutic effect. In patients who have not been previously treated for Parkinson's disease, treatment starts with 100-200 mg of levodopa and 25-50 mg of benserazide per day. Every 3-7 days, the doctor may increase the daily dose by 50 mg of levodopa + 12.5 mg of benserazide or 100 mg of levodopa + 25 mg of benserazide. The patient should not take more than 800 mg of levodopa and 200 mg of benserazide per day. A summary of dosing in tabular form:

If side effects occur (see section 4 "Possible side effects"), the doctor may reduce the dose of Xevoben. Any subsequent dose increase will be slower. If the treatment scheme is changed from a medication containing only levodopa to Xevoben (a combination of levodopa and benserazide), a similar therapeutic effect can be achieved by taking only 20% of the previous levodopa dose. When making such a change, a 12-hour interval should be maintained between taking the previous and new medication. If the patient is taking another medication for Parkinson's disease, they may also take Xevoben. However, as soon as the patient's condition improves while taking Xevoben, the dose of the other medication should be re-evaluated and reduced, and then, if necessary, gradually discontinued.

Patients with liver or kidney function disorders

In patients with moderate liver function disorders and mild to moderate kidney function disorders (creatinine clearance ≥30 mL/min), dose adjustment of Xevoben is not necessary.

Use in children and adolescents

Xevoben should not be taken by children and adolescents under 25 years of age (see section 2).

Method of administration

Oral administration. Xevoben tablets, 200 mg + 50 mg, can be divided into 2 or 4 equal doses. Whenever possible, Xevoben should be taken 30 minutes before a meal or 1 hour after a meal, drinking the tablet (tablets) with an appropriate amount of fluid (preferably a glass of water) or taking a small, protein-poor meal (e.g., biscuits, crackers, or similar).

Duration of treatment

Xevoben replaces the neurotransmitter dopamine, which is not produced in sufficient amounts by the body. Therefore, treatment with Xevoben is long-term. At least 3 months of treatment may be required for the doctor to assess the effectiveness of the therapy.

Frequency of administration

Initially, the daily dose is divided into 2 to 4 individual doses, and at higher doses, at least 4 individual doses.

Patients who experience significant fluctuations in motor function during the day (the "on-off" phenomenon) should receive smaller doses of Xevoben more frequently throughout the day. If necessary, the doctor may change the treatment to Xevoben, prolonged-release capsules, hard.

Treatment of restless legs syndrome symptoms

The number of Xevoben tablets taken depends on the severity of restless legs syndrome. It may be necessary to determine the most optimal dose for the patient by gradually increasing the daily dose.

RLS with sleep disturbances

Treatment starts with 100 mg of levodopa and 25 mg of benserazide per day (which corresponds to ½ tablet of Xevoben, 200 mg + 50 mg). If the patient still experiences sleep disturbances, the dose of Xevoben can be increased to 200 mg of levodopa and 50 mg of benserazide per day (which corresponds to 1 tablet of Xevoben, 200 mg + 50 mg).

RLS with sleep disturbances and nighttime sleep disorders

In patients with RLS who experience both sleep disturbances and nighttime sleep disorders, a combination of Xevoben tablets and prolonged-release capsules should be used. The patient should take 100 mg of levodopa + 25 mg of benserazide in prolonged-release form, together with ½ tablet of Xevoben, 200 mg + 50 mg, 1 hour before bedtime. If this does not lead to sufficient alleviation of symptoms in the second part of the night, the dose of Xevoben can be increased to 200 mg of levodopa + 50 mg of benserazide in prolonged-release form.

Caution

The maximum daily dose should not exceed 200-300 mg of levodopa and 50-75 mg of benserazide per day (which corresponds to 1-1½ tablets of Xevoben, 200 mg + 50 mg) to avoid worsening of symptoms, involvement of other body parts, or occurrence of RLS symptoms earlier in the day. In such a case, it is important not to increase the dose further. Instead, the doctor should consider additional treatment with a reduced dose of Xevoben or gradual discontinuation of Xevoben and replacement with another medication.

Patients with liver or kidney function disorders

In patients with moderate liver function disorders and mild to moderate kidney function disorders (creatinine clearance ≥30 mL/min), dose adjustment is not necessary.

Use in children and adolescents

Xevoben should not be taken by children and adolescents under 25 years of age (see section 2).

Method of administration

Oral administration. Xevoben tablets, 200 mg + 50 mg, can be divided into 2 or 4 equal doses. Whenever possible, Xevoben should be taken 30 minutes before a meal or 1 hour after a meal, drinking the tablet (tablets) with an appropriate amount of fluid (preferably a glass of water) or taking a small, protein-poor meal (e.g., biscuits, crackers, or similar).

Duration of treatment

The doctor will inform the patient how long they should take Xevoben to treat restless legs syndrome. The tablets are taken for a long time. The doctor will check at regular intervals whether it is necessary to continue taking Xevoben. If the patient feels that the action of the medication is too weak or too strong, they should consult their doctor or pharmacist.

Taking a higher dose of Xevoben than recommended

If the patient accidentally takes a double dose, it does not affect further treatment, and they should continue with the treatment scheme. If the patient takes a significantly higher dose of Xevoben, the side effects listed in section 4 "Possible side effects" may occur. If life-threatening symptoms occur, the patient should immediately contact their doctor! Treatment involves general procedures used in cases of overdose, with particular attention to monitoring cardiovascular parameters.

Missing a dose of Xevoben

In Parkinson's disease/parkinsonian syndrome

The patient should not take a double dose to make up for a missed tablet. If the patient misses a dose of Xevoben only once, they should continue with the treatment scheme. However, the patient should remember that the action of Xevoben is effective only when the medication is taken according to the treatment scheme established by the doctor.

In restless legs syndrome

The patient should not take a double dose to make up for a missed dose. If the patient misses a dose of Xevoben, they should take the missed tablet in the evening or at night, as soon as they remember. If the patient does not take the missed tablet until the next morning, they should continue taking Xevoben as before, i.e., they should not take a double dose. However, the patient should remember that the action of Xevoben is effective only when the medication is taken according to the treatment scheme established by the doctor.

Discontinuing Xevoben

The patient should consult their doctor if they experience any side effects. The doctor will discuss other available treatment options and whether other treatment methods are available. The patient should not discontinue Xevoben on their own, as the symptoms may worsen. In case of any further doubts about taking this medication, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medications, Xevoben can cause side effects, although not everybody gets them. The frequency of side effects during treatment with Xevoben is unknown. Possible side effects:

• Cold, bronchitis, infections with fever.
• Decreased number of platelets, white and red blood cells.
• Decreased appetite.
• Cognitive and behavioral disorders after taking higher doses of Xevoben than recommended (see section 2).
• Confusion, pathological depression, which may be one of the clinical symptoms of Parkinson's disease or restless legs syndrome (see section 2 "Caution for the patient's environment"), inner restlessness, anxiety, sensory illusions, delusions, disturbed sense of time.
• The patient may experience an inability to resist impulses, temptations, or compulsions to perform actions that may be harmful to the patient or others, which may include:
• addiction to gambling, despite serious personal or family consequences,
• changed 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 compulsive shopping,
• episodic overeating (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, so that ways to control or limit these symptoms can be discussed.
• Lack of taste, taste disorders, involuntary movements resulting from long-term treatment and/or high doses of Xevoben (see section 2), fatigue, excessive daytime sleepiness, sudden sleep attacks (see section 2 "Warnings and precautions"), dizziness, headache, dry mouth.
• Irregular heart rhythm.
• Low blood pressure, which causes dizziness and fainting (see section 2).
• Nausea, vomiting, diarrhea, especially at the beginning of treatment (see section 2), change in saliva, tongue, teeth, and mucous membrane of the mouth.
• Increased activity of transaminases, increased activity of alkaline phosphatase, increased activity of gamma-glutamyltransferase.
• Skin hypersensitivity reactions such as itching and rash.
• Increased urea levels in the blood, change in urine color (urine usually turns red and darkens after settling).

Psychiatric disorders such as inner restlessness, anxiety, sleep disorders, sensory illusions, delusions, disturbed sense of time occur especially in elderly patients or patients who have had previous predispositions to such disorders.

Additional side effects in patients with Parkinson's disease/parkinsonian syndrome

• significant coordination disorders after prolonged treatment;
• sleep disorders.

Additional side effects in patients with restless legs syndrome

• worsening or earlier occurrence of symptoms in the afternoon or early evening during prolonged treatment and/or high doses of Xevoben (see section 3, "Caution");
• sleep disorders unrelated to restless legs syndrome.

Reporting side effects

If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Medicinal Product Monitoring, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych, 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, more information can be collected on the safety of the medication.

5. How to store Xevoben

The medication should be stored out of sight and reach of children. Do not take this medication after the expiry date stated on the label or carton after: EXP. The expiry date refers to the last day of the month stated. There are no special storage instructions for the medication. The bottle should be kept tightly closed to protect it from moisture. Medications should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Xevoben contains

• The active substances of Xevoben are levodopa and benserazide. One tablet contains 200 mg of levodopa + 50 mg of benserazide (in the form of hydrochloride).
• Other ingredients are: sodium stearyl fumarate, red iron oxide (E172), ethylcellulose 20 cps, anhydrous colloidal silica, microcrystalline cellulose, pregelatinized corn starch, mannitol, calcium hydrogen phosphate, crospovidone type A, magnesium stearate.

What Xevoben looks like and contents of the pack

Round, pale red tablets with a diameter of approximately 13 mm, with the inscription "250T" on one side of the tablet, with two intersecting dividing lines on both sides. Xevoben is available in an HDPE bottle containing a desiccant, closed with a white, child-resistant PE cap, containing 20, 50, or 100 tablets in a cardboard box. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Farmak International Sp. z o.o., ul. Koszykowa 65, 00-667 Warsaw, tel.: +48 22 822 93 06, e-mail: [email protected]

Manufacturer/Importer

Farmak International Sp. z o.o., ul. Chełmżyńska 249, 04-458 Warsaw

This medicinal product is authorized in the Member States of the European Economic Area:

Poland: Xevoben

Date of last revision of the leaflet:May 2025