Xevoben

Package Leaflet: Information for the Patient

Xevoben, 50 mg + 12.5 mg, Tablets

Levodopa + Benserazide

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medication has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your 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 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 cause Parkinson's disease. 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:

• in the treatment of Parkinson's disease (paralytic tremor, a disease characterized by tremors, slowed movements, and muscle stiffness);
• in the treatment of 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). Exceptions are symptoms similar to Parkinson's disease caused by certain medications (treatment-induced parkinsonism).

2. Important information before taking Xevoben

When not to take Xevoben

• if you are 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 development 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 heart disease, such as serious rapid heartbeat (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 and other medications");
• in patients being treated with non-selective monoamine oxidase inhibitors (MAOIs) (antidepressant medications containing the active substance tranylcypromine) or a combination of selective MAOI-A (antidepressant medication containing the active substance moclobemide) with selective MAOI-B (medication used to treat Parkinson's disease, which contains the active substance selegiline or rasagiline) (see "Xevoben and other medications");
• in patients with high intraocular pressure (glaucoma with closed-angle filtration);
• 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, discuss it with your 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 you, consult your doctor (see "Driving and using machines"). You should inform 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 spending money, excessive sexual drive, or increased sexual thoughts and feelings. It may be necessary to re-evaluate the treatment being taken by your doctor. Regular medical check-ups are necessary if:

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

Additionally, 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 you are elderly or taking medications for high blood pressure or other medications that may lower blood pressure, or if you have circulation problems due to low blood pressure, your doctor will closely monitor you, especially at the beginning of treatment or when increasing the dose. Therefore, regular visits scheduled by your 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, muscle protein excretion in the urine (myoglobinuria), muscle fiber breakdown (rhabdomyolysis), acute kidney failure, or complete paralysis may occur. These symptoms are potentially life-threatening. In such a case, you should immediately contact your doctor! If you are scheduled to undergo surgery under general anesthesia, you should take the medication containing levodopa/benserazide for as long as possible before the operation, except when using halothane anesthesia. When using halothane anesthesia, you should stop taking the medication containing levodopa/benserazide 12-48 hours before the procedure, due to the risk 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. WarningEspecially 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 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 when taking 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 unclear 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. When taking Xevoben, patients should regularly examine their skin for suspicious changes and undergo periodic skin examinations by a suitable specialist (e.g., dermatologist). Warning to people around the patientTreatment with Xevoben may lead to the development of abnormally low mood (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. Therefore, patients should be closely monitored for psychological changes to detect depression at an early stage. In such a case, you should contact your doctor.

Xevoben and other medications

Tell your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you 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 heartbeat, medications that induce labor, medications used to treat spasms of the lower airways (called sympathomimetics), such as epinephrine, norepinephrine, isoproterenol, or amphetamine. The action of sympathomimetic medications may be enhanced. For this reason, 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.

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 will adjust the dose of Xevoben and/or the dose of the antihypertensive medication.

The following medications may affect the action of XevobenWeakening of action by:

• certain pain medications (opioids);
• medications used to treat high blood pressure that contain the active substance reserpine. In this case, Xevoben should not be taken (see above);
• certain medications that lower 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). For this reason, 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 use may increase the risk of arrhythmias.

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 testsChanges may occur in the following laboratory tests:

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

General anesthesia with halothaneIn the case of general anesthesia when halothane is used, the medication containing levodopa/benserazide should be stopped 12-48 hours before the procedure, due to the risk of blood pressure fluctuations and/or arrhythmias.

Xevoben with food and drink

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

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 medication. Before starting treatment, it is recommended to perform a pregnancy test to rule out pregnancy. You should not take Xevoben 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 in Xevoben. Women of childbearing age should use effective contraception during treatment with Xevoben. If you become pregnant or think you may be pregnant, consult your doctor. The doctor will advise you on how to stop taking Xevoben. You should not breastfeed during treatment with Xevoben. If Xevoben treatment is necessary, you should stop breastfeeding.

Driving and using machines

Xevoben may have a major impact on your ability to drive and use machines. In rare cases, taking Xevoben may cause excessive daytime 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 the excessive daytime sleepiness or sudden sleep attacks have stopped.

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

Always take this medication exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist. The number of Xevoben tablets you take depends on the severity of your disease and your tolerance to Xevoben. The most optimal dose for you will be determined by gradually increasing the daily dose. For this reason, the dose prescribed for you may differ from the dose prescribed for other patients. Do not change the dose determined by your doctor yourself. If your doctor does not recommend otherwise, the treatment regimen is as followsTreatment 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. Do not take more than 800 mg of levodopa and 200 mg of benserazide per day. 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 regimen 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 you are taking another medication for Parkinson's disease, you can also take Xevoben. However, as soon as your condition improves while taking Xevoben, the dose of the other medication should be re-evaluated and reduced, and then, if necessary, gradually stopped. Patients with liver or kidney function disordersIn 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 adolescentsXevoben should not be used in children and adolescents under 25 years of age (see section 2). Method of administrationOral administration. Xevoben should be taken 30 minutes before a meal or 1 hour after a meal, drinking a liquid (preferably a glass of water) or taking a small, protein-poor meal (e.g., biscuits, crackers, or similar). Duration of treatmentXevoben replaces a neurotransmitter in the body - 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 administrationInitially, 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 hard capsules.

Taking a higher dose of Xevoben than recommended

If you accidentally take a double dose, it will not affect further treatment, and you should continue with the treatment regimen. If you take a significantly higher dose of Xevoben, the side effects listed in section 4 "Possible side effects" may occur. If life-threatening symptoms occur, you should immediately contact your doctor! Treatment involves the use of general procedures for overdose, with particular attention to monitoring cardiovascular parameters.

Missing a dose of Xevoben

Do not take a double dose to make up for a missed tablet. If you miss a dose of Xevoben only once, continue with the treatment regimen. However, keep in mind that the action of Xevoben is effective only when the medication is taken according to the treatment regimen established by your doctor.

Stopping treatment with Xevoben

Consult your doctor if you experience any side effects. The doctor will discuss other available treatment options with you and whether other methods of treatment are available. Do not stop taking Xevoben yourself, as the symptoms may recur. If you have any further questions about taking this medication, consult your 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, abnormally low mood (depression), which may be one of the clinical symptoms of Parkinson's disease (see section 2 "Warning to people around the patient"), inner restlessness, anxiety, sleep disorders, sensory illusions, delusions, disturbed sense of time.
• You may experience an inability to resist impulses, temptations, or urges to perform actions that may be harmful to you 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 you 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). You should inform your doctor if you exhibit any of these behaviors to discuss ways to control or limit these symptoms.
• Lack of taste, taste disorders, involuntary movements resulting from long-term treatment and/or high doses of Xevoben (see section 2), significant coordination disorders after prolonged treatment, 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 mucous membranes of the mouth.
• 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 standing).

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.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform 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 medication.

5. How to store Xevoben

Keep this medication out of the sight and reach of children. Do not use 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 precautions for this medication. Keep the bottle tightly closed to protect from moisture. Medications should not be disposed of via wastewater or household waste. Ask your 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 50 mg of levodopa + 12.5 mg of benserazide (in the form of hydrochloride).
• The other ingredients are: sodium docusate, 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 7.5 mm. Xevoben is available in an HDPE bottle containing a desiccant, closed with a white, child-resistant PE cap, containing 20, 50, 60, 100, or 200 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 medication is authorized in the Member States of the European Economic Area:

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