Xevoben Xr

Leaflet accompanying the packaging: patient information

Xevoben XR, 100 mg + 25 mg, prolonged-release hard capsules

Levodopa + Benserazide

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Xevoben XR and what is it used for
• 2. Important information before taking Xevoben XR
• 3. How to take Xevoben XR
• 4. Possible side effects
• 5. How to store Xevoben XR
• 6. Contents of the pack and other information

1. What is Xevoben XR and what is it used for

Xevoben XR is a medicine that contains 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. The active substances levodopa and benserazide are released with a delay over a longer period from a special pharmaceutical form (prolonged-release hard capsules). Xevoben XR is used:

• to treat Parkinson's disease (paralytic tremor, a disease characterized by tremors, slowed movements, and muscle stiffness), if the patient is already taking levodopa in combination with benserazide or carbidopa in an immediate-release form;
• to treat restless legs syndrome of unknown cause, if the patient is already taking levodopa in combination with benserazide or carbidopa in an immediate-release form;
• to treat restless legs syndrome resulting from renal failure requiring dialysis, if the patient is already taking levodopa in combination with benserazide or carbidopa in an immediate-release form.

Additional information for patients with Parkinson's disease
There is a lack of sufficient clinical experience with the use of Xevoben XR in patients who have not been previously treated with levodopa or in combination with other anti-parkinsonian medications, or in long-term treatment. Xevoben XR should not be used to treat symptoms similar to those of Parkinson's disease caused by certain medications (drug-induced parkinsonism), as well as Huntington's disease.
Additional information for patients with restless legs syndrome
There is a lack of sufficient clinical experience with the use of Xevoben XR in patients who have not been previously treated with levodopa in combination with benserazide in an immediate-release form. Before starting treatment with levodopa and benserazide, the doctor will ensure that the symptoms of restless legs syndrome are not caused by iron deficiency. In such a case, the deficiency should be treated through iron supplementation.

2. Important information before taking Xevoben XR

When not to take Xevoben XR

• 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 an adrenal tumor;
• 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 arrhythmias, 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 that contain the active substance reserpine (see "Xevoben XR and other medicines");
• 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, which contains the active substance selegiline or rasagiline) (see "Xevoben XR and other medicines");
• 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 XR, discuss it with your doctor, pharmacist, or nurse. In susceptible individuals, allergic reactions may occur. Caution should be exercised when taking Xevoben XR in patients who have experienced excessive daytime sleepiness or sudden, unexpected sleep attacks during treatment with Xevoben XR. 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

Tell your doctor if you or your loved ones notice unusual behaviors resulting from irresistible impulses, compulsions, or urges to perform certain actions that may be harmful to you or others. Such behaviors are called impulse control disorders and may include addiction to gambling, overeating, or excessive spending, increased sexual drive, or intense sexual thoughts and feelings. It may be necessary to re-evaluate the treatment being used by your 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 XR 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 XR. If the patient is elderly or is also taking medications for high blood pressure or other medications that may lower blood pressure, or 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 XR, contrary to the doctor's recommendations, in significantly higher doses than required to treat motor disorders.
After many years of therapy with a medicine containing the same active substances as Xevoben XR, sudden discontinuation of Xevoben XR 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 levodopa/benserazide medicine for as long as possible before the operation, except when using halothane anesthesia. When using halothane anesthesia, the levodopa/benserazide medicine should be discontinued 12-48 hours before the procedure, due to the possibility of blood pressure fluctuations and/or arrhythmias 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). They can be significantly reduced or eliminated by taking Xevoben XR with a small, protein-poor meal (e.g., biscuits, crackers, or similar), drinking a liquid, 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 troublesome 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 XR, patients should regularly examine their skin for suspicious changes and undergo periodic skin examinations by a suitable specialist (e.g., dermatologist).
Caution for people around the patient
Treatment with Xevoben XR 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 contacted.

Xevoben XR and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take.
Taking Xevoben XR with the following active substances or medicines may affect their action

• medicines used to treat low blood pressure, circulation disorders, irregular heartbeat, medicines that induce labor, or medicines used to treat bronchial spasms (called sympathomimetics), such as epinephrine, norepinephrine, isoproterenol, or amphetamine. The action of sympathomimetic medicines 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 medicine may need to be reduced.
• medicines used to treat high blood pressure (called antihypertensive medicines): the action of the antihypertensive medicine 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 will adjust the dose of Xevoben XR and/or the dose of the antihypertensive medicine.

The following medicines may affect the action of Xevoben XR
Weakening of action by:

• certain painkillers (opioids);
• medicines used to treat high blood pressure that contain the active substance reserpine. In this case, Xevoben XR should not be taken (see above);
• certain medicines that lower mood (neuroleptics).

Enhancement of action and possible enhancement of side effects by:

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

Other possible interactions:

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

Concurrent use of Xevoben XR with other anti-parkinsonian medicines (e.g., dopamine agonists, amantadine, anticholinergic medicines, selegiline, bromocriptine) is allowed. However, it should be noted that not only the desired but also the undesired action of the medicine may be enhanced. The doctor may prescribe a reduced dose of Xevoben XR or another medicine. If adjunctive treatment is started with a medicine containing entacapone, it may also be necessary to reduce the dose of Xevoben XR. Concurrent administration of Xevoben XR with medicines that neutralize stomach acid may lead to reduced absorption of the active substances it contains.
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 heated);
• false-negative results for glucose in 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 levodopa/benserazide medicine should be discontinued 12-48 hours before the procedure, due to the risk of blood pressure fluctuations and/or arrhythmias.

Xevoben XR with food and drink

It is recommended to avoid eating protein-rich meals shortly before taking Xevoben XR, as this may weaken the action of the medicine.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before taking this medicine. Before starting treatment, it is recommended to perform a pregnancy test to rule out pregnancy. Xevoben XR 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 offspring of both active substances contained in Xevoben XR. Women of childbearing age should use effective contraception during treatment with Xevoben XR. If you become pregnant or think you may be pregnant, consult your doctor. The doctor will advise how to stop taking Xevoben XR.
During treatment with Xevoben XR, do not breastfeed. If treatment with Xevoben XR is necessary, breastfeeding should be discontinued.

Driving and using machines

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

3. How to take Xevoben XR

This medicine should always be taken as directed by your doctor. If you are unsure, consult your doctor or pharmacist. The number of Xevoben XR prolonged-release hard capsules taken depends on the severity of the disease and the patient's tolerance to Xevoben XR. The most optimal dose for the patient is determined by gradually increasing the daily dose. For this reason, the dose prescribed to you may differ from the dose prescribed to other patients. Do not change the dose determined by your doctor on your own.

Treatment of Parkinson's disease symptoms

Unless your doctor advises otherwise, the treatment regimen is as follows
The initial dose is the previous morning dose of Xevoben in the immediate-release form, and then Xevoben XR prolonged-release hard capsules are taken. The next dosing regimen must be determined by careful dose adjustment. If necessary, the dose of Xevoben XR prolonged-release hard capsules may be increased by about 50% compared to Xevoben in the standard form after 2-3 days, because Xevoben XR prolonged-release hard capsules cause lower levels of active substances in the blood.
If prolonged action of the medicine is to occur at night, an additional 1-2 Xevoben XR prolonged-release hard capsules should be taken, in addition to the established daily dosing regimen, before bedtime.
If the patient is taking another medicine for Parkinson's disease, they may also take Xevoben XR prolonged-release hard capsules. However, as soon as the patient's condition improves while taking Xevoben XR, the dose of the other medicine 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 XR is not necessary.
Use in children and adolescents
Xevoben XR should not be taken by children and adolescents under 25 years of age (see section 2).
Method of administration
Oral administration.
Xevoben XR should be taken 30 minutes before a meal or 1 hour after a meal, with a sufficient amount of liquid (preferably a glass of water) or with a small, protein-poor meal (e.g., biscuits, crackers, or similar). The prolonged-release hard capsules should always be swallowed whole.
Duration of treatment
Xevoben XR replaces the neurotransmitter dopamine, which is not produced in sufficient amounts by the body. Therefore, treatment with Xevoben XR is long-term. At least 3 months of treatment may be required for the doctor to assess the effectiveness of the therapy.

Treatment of restless legs syndrome symptoms

The number of Xevoben XR capsules 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 difficulty falling asleep
In patients who have difficulty falling asleep due to RLS, treatment with levodopa and benserazide in the immediate-release form should be used (e.g., Xevoben, 100 mg + 25 mg, tablets or Xevoben, 200 mg + 50 mg, tablets). The initial dose is 1 tablet of Xevoben, taken 1 hour before bedtime. If symptoms do not improve, the dose may be increased to 2 tablets.
RLS with difficulty falling asleep and sleep disturbances during the night
In patients with RLS who have both difficulty falling asleep and sleep disturbances during the night, a combination of Xevoben XR prolonged-release hard capsules and Xevoben, 100 mg + 25 mg or 200 mg + 50 mg, tablets should be used. Take 1 prolonged-release hard capsule with 1 tablet of Xevoben, 100 mg + 25 mg or 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 XR may be increased to 2 prolonged-release hard capsules.
Caution
The maximum daily dose should not exceed 200-300 mg of levodopa and 50-75 mg of benserazide per day (which corresponds to 2-3 Xevoben XR, 100 mg + 25 mg capsules) 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 essential not to increase the dose further. Instead, the doctor should consider additional treatment with a reduced dose of Xevoben XR or gradual discontinuation of Xevoben XR and replacement with another medicine.
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 XR is not necessary.
Use in children and adolescents
Xevoben XR should not be taken by children and adolescents under 25 years of age (see section 2).
Method of administration
Oral administration. Swallow the capsule whole, with a sufficient amount of liquid (preferably a glass of water) or with 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 XR to treat restless legs syndrome. The capsules are usually taken for a long time. The doctor will check at regular intervals whether it is necessary to continue taking Xevoben XR.
If the patient feels that the action of the medicine is too weak or too strong, they should consult their doctor or pharmacist.

Take more than the recommended dose of Xevoben XR

If the patient accidentally takes a double dose, it does not affect further treatment; they should continue with the treatment regimen.
If the patient takes a significantly higher dose of Xevoben XR, 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 the use of general procedures for overdose, with particular attention to monitoring cardiovascular parameters.
If the patient takes a significantly higher dose of Xevoben XR prolonged-release hard capsules, the onset of symptoms may be delayed due to the later absorption of active substances from the gastrointestinal tract.
Additionally, in the case of taking the prolonged-release form, it is necessary to prevent further absorption of the medicine by using appropriate methods.

Miss a dose of Xevoben XR

In Parkinson's disease
Do not take a double dose to make up for a missed capsule. If the patient misses taking a Xevoben XR capsule only once, they should continue with the treatment regimen.
However, remember that the action of Xevoben XR is effective only when the medicine is taken according to the treatment regimen established by the doctor.
In restless legs syndrome
Do not take a double dose to make up for a missed dose. If the patient misses taking a Xevoben XR capsule only once, they should continue with the treatment regimen.
However, remember that the action of Xevoben XR is effective only when the medicine is taken according to the treatment regimen established by the doctor.

Stop taking Xevoben XR

Consult your doctor if you experience any side effects. The doctor will discuss other available treatment options and whether other treatment methods are available. Do not stop taking Xevoben XR on your own, as symptoms may worsen.
In case of further doubts about taking this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Xevoben XR can cause side effects, although not everybody gets them. The frequency of side effects during treatment with Xevoben XR 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-than-recommended doses of Xevoben XR (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 people around the patient"), inner restlessness, anxiety, sensory illusions, delusions, disturbed sense of time.
• The patient may experience an inability to resist impulses, urges, or compulsions to perform actions that may be harmful to themselves or others, which may include:
• addiction to gambling, despite significant personal or family consequences,
• changed or increased sexual interests and behaviors of great importance to the patient or others, e.g., actions related to increased sexual drive,
• compulsive, uncontrolled spending or compulsive shopping,
• binge eating (consuming large amounts of food in a short time) or compulsive eating (consuming more food than normal and more than needed to satisfy hunger).

Tell your doctor if you experience 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 the medicine (see section 2), fatigue, excessive daytime sleepiness, sudden sleep attacks (see section 2 "Warnings and precautions"), dizziness, headache, dry mouth.
• Irregular heartbeat.
• 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 the color of saliva, tongue, teeth, and oral mucosa.
• Increased activity of transaminases, increased activity of alkaline phosphatase, increased activity of gamma-glutamyltransferase.
• Skin allergic 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 disturbances, sensory illusions, delusions, disturbed sense of time, which occur especially in elderly patients or patients who have had previous predispositions to such disorders.

Additional side effects in patients with Parkinson's disease

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

Additional side effects in patients with restless legs syndrome

• worsening or shifting of symptoms to the afternoon or early evening in case of prolonged treatment and/or high doses of the medicine (see section 3, "Caution");
• sleep disturbances unrelated to restless legs syndrome.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, 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, you can help gather more information on the safety of this medicine.

5. How to store Xevoben XR

Keep the medicine out of sight and reach of children. Do not use this medicine after the expiry date stated on the label or carton after: EXP. The expiry date refers to the last day of the month. There are no special storage instructions for the medicine. Keep the bottle tightly closed to protect it from moisture. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Xevoben XR contains

• The active substances of Xevoben XR are levodopa and benserazide. One prolonged-release hard capsule contains 100 mg of levodopa + 25 mg of benserazide (in the form of hydrochloride).
• Other ingredients are: capsule contents: hypromellose, hydrogenated vegetable oil (derived from cotton), calcium hydrogen phosphate, povidone K30, mannitol, talc, magnesium stearate. Capsule shell: gelatin (E 141), titanium dioxide (E 171), yellow iron oxide (E 172), indigo carmine (E 132).

What Xevoben XR looks like and contents of the pack

Hard, opaque gelatin capsules, size "1", with a dark green cap and light blue body, filled with a white to off-white fine powder. Xevoben XR is available in an orange, type III glass bottle with a PE cap containing a desiccant, containing 20, 30, 50, 60, or 100 prolonged-release hard capsules in a cardboard box.

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: biuro@farmakinternational.pl

Manufacturer/Importer

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

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

Poland: Xevoben XR
Date of last revision of the leaflet:May 2025