Xevoben

Patient Information Leaflet

Xevoben, 50 mg + 12.5 mg, tablets
Levodopum + Benserazidum
Please read all of this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for a specific individual. 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 any not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

Xevoben is a medicine containing the active substances: levodopa and benserazide. The active substance levodopa is a precursor of dopamine, a substance naturally produced in the human body. Insufficient levels of dopamine in certain areas of the brain cause Parkinson's disease. This deficiency is compensated by conversion of levodopa into dopamine. The second active substance, benserazide, inhibits the breakdown of levodopa outside the brain and allows a lower dose of levodopa to be used.
Xevoben is used:

• in the treatment of Parkinson's disease (paralysis agitans, a disease characterized by tremor, slowness of movement and muscle stiffness);
• in the treatment of symptoms resembling Parkinson's disease, but resulting from poisoning, encephalitis or brain changes caused by cerebral arteriosclerosis (parkinsonism). An exception are symptoms resembling Parkinson's disease induced by certain medicines (drug-induced parkinsonism).

2. Important information before using Xevoben

When not to use Xevoben

• if the patient is allergic to levodopa, benserazide, or any of the other ingredients of this medicine (listed in section 6);
• in patients under 25 years of age (skeletal development must be complete);
• in patients with severe disorders of specific hormone-producing organs, such as hyperthyroidism or significantly elevated blood cortisol levels (Cushing's syndrome), or with an adrenal gland tumour;
• in patients with severe metabolic, liver, kidney, or bone marrow disorders;
• in patients with severe heart disease, such as serious problems with rapid heartbeat (tachycardia), severe cardiac arrhythmias, or heart failure;
• in patients with specific mental disorders (psychoses), whether or not of physical origin;
• in patients concurrently taking antihypertensive medicines containing the active substance reserpine (see "Xevoben with other medicines");
• in patients being treated concurrently with non-selective monoamine oxidase inhibitors (MAO inhibitors) (an antidepressant containing the active substance tranylcypromine) or with a combination of a selective MAO-A inhibitor (an antidepressant containing the active substance moclobemide) and a selective MAO-B inhibitor (a medicine used in the treatment of Parkinson's disease containing the active substance selegiline or rasagiline) (see "Xevoben with other medicines");
• in patients with high intraocular pressure (closed-angle glaucoma);
• in pregnant women;
• in women of childbearing age who are not using effective contraception (see "Pregnancy and breastfeeding").

Warnings and precautions
Before starting treatment with Xevoben, discuss this with your doctor, pharmacist, or nurse.
Hypersensitivity reactions may occur in predisposed individuals.
Caution should be exercised when using Xevoben in patients who experience excessive daytime sleepiness or sudden, unexpected episodes of sleep while being treated with Xevoben. If this applies to the patient, consult a doctor (see "Driving and using machines").
Inform the doctor if the patient or their close relatives notice unusual behaviours resulting from irresistible impulses, compulsions, or obsessive performance of certain activities, harmful to the patient or others. These behaviours are known as impulse control disorders and may include gambling addiction, compulsive overeating or spending, excessive sexual drive, or intensified sexual thoughts and feelings. It may be necessary for the doctor to reconsider the treatment regimen.
Regular medical monitoring is essential if:

• the patient has previously had a heart attack;
• the patient currently has irregular heartbeat, reduced blood flow to the coronary arteries, or heart failure;
• the patient has previously had gastrointestinal ulcers;
• the patient has reduced bone strength;
• the patient has open-angle glaucoma, as levodopa may theoretically increase intraocular pressure;
• the patient has diabetes.

Additionally, liver and kidney function, as well as cardiovascular function and blood count, should be monitored periodically.
Treatment with Xevoben may cause circulatory problems due to excessively low blood pressure (see section 4). These symptoms usually resolve or improve after reducing the dose of Xevoben. If the patient is elderly, or if they are concurrently taking medicines for high blood pressure or other medicines that may lower blood pressure, or if the patient has circulatory problems due to low blood pressure, the doctor will closely monitor the patient, especially at the beginning of treatment or during dose increases. Therefore, regular visits as scheduled by the doctor are essential.
Warning
In a small number of patients with Parkinson's disease, cognitive and behavioural disorders may occur, which may be related to taking Xevoben in significantly higher doses than required for the treatment of motor disorders, contrary to the doctor's instructions.
After many years of therapy with a medicine containing the same active substances as Xevoben, abrupt discontinuation of Xevoben may lead to withdrawal symptoms (known as the malignant withdrawal syndrome of levodopa). Symptoms include very high fever, muscle rigidity, and mental changes. In severe cases, excretion of muscle proteins in the urine (myoglobinuria), breakdown of muscle fibres (rhabdomyolysis), acute kidney failure, or complete immobility may occur. These symptoms are potentially life-threatening. In such a case, contact a doctor immediately!
If the patient has a planned surgical procedure under general anaesthesia, treatment with a levodopa/benserazide-containing medicine should be continued as long as possible before surgery, except when using halothane. For general anaesthesia with halothane, levodopa/benserazide-containing medicine should be discontinued 12–48 hours before the procedure due to the risk of blood pressure fluctuations and/or cardiac arrhythmias in patients concurrently receiving levodopa/benserazide and halothane. After the procedure, treatment can be resumed, gradually increasing the dose until the previously used dose is reached.
Note
Gastrointestinal disturbances such as dry mouth, nausea, vomiting, or diarrhoea may occur especially at the beginning of treatment (see section 4). These can be significantly reduced or eliminated by taking Xevoben with a small, low-protein meal (e.g., biscuits, crackers, or similar), taking the medicine with fluid, or by gradually increasing the dose.
During long-term treatment and/or when using high doses, involuntary movements may occur (see section 4). These symptoms usually resolve or become less bothersome after dose reduction.
Patients with Parkinson's disease have an increased risk of developing melanoma compared to the general population. It is unclear whether this increased risk is due to Parkinson's disease itself or other factors, such as the use of levodopa in the treatment of Parkinson's disease. While taking Xevoben, patients should regularly examine their skin for suspicious changes and undergo periodic skin examinations by an appropriate specialist (e.g., dermatologist).
Note for people around the patient
Treatment with Xevoben may lead to abnormally low mood (depression), especially if there are previous predispositions to such symptoms (see section 4). However, depression may also 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, contact the doctor.
Xevoben with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Concurrent use of Xevoben with the following active substances or medicines may affect their action

• medicines used to treat low blood pressure, circulatory disorders, irregular heartbeat, labour-inducing medicines, or medicines used to treat bronchospasm (called sympathomimetics), e.g., epinephrine, norepinephrine, isoproterenol, or amphetamine. The effect 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 antihypertensives): the effect of antihypertensive medicines may be enhanced, thereby increasing the risk of low blood pressure. Therefore, blood pressure should be monitored regularly (see above). If necessary, the doctor will adjust the dose of Xevoben and/or the antihypertensive medicine.

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

• certain painkillers (opioids);
• medicines used to treat high blood pressure containing the active substance reserpine. In this case, Xevoben should not be used (see above);
• certain mood-lowering medicines (neuroleptics).

Enhancement of effect and possible increase in adverse effects by:

• medicines containing the active substance selegiline (used in the treatment of Parkinson's disease).

Other possible interactions:

• certain antidepressants (called MAO inhibitors): concurrent use of Xevoben 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 should not be used at that time (see above). Therefore, a 2-week interval should be maintained between stopping tranylcypromine and starting Xevoben treatment. On the other hand, concurrent use of Xevoben with moclobemide, selegiline, and rasagiline is considered safe.
• concurrent use of Xevoben with domperidone may lead to increased blood levels of levodopa. Concurrent administration may increase the risk of cardiac arrhythmias.

Concurrent use of Xevoben with other anti-Parkinson medicines (e.g., dopamine agonists, amantadine, anticholinergics, selegiline, bromocriptine) is permitted.
However, it should be noted that not only the desired but also the undesirable effects of the medicine may be enhanced. The doctor may prescribe a reduced dose of Xevoben or the other medicine. If adjunctive treatment is initiated with a medicine containing entacapone, a reduction in the dose of Xevoben may also be necessary.
Changes in diagnostic laboratory tests
The following laboratory tests may be affected:

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

General anaesthesia with halothane
In the case of general anaesthesia requiring the use of halothane, levodopa/benserazide-containing medicine should be discontinued 12–48 hours before the procedure due to the risk of blood pressure fluctuations and/or arrhythmias.
Xevoben with food and drink
Avoid eating high-protein meals immediately before taking Xevoben, as this may reduce the medicine's effectiveness.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.
A pregnancy test is recommended before starting treatment to rule out pregnancy.
Xevoben must not be used during pregnancy, as there are no available studies in pregnant women, and animal studies have shown harmful effects on the unborn offspring of both active substances in Xevoben. Women of childbearing age must use an effective method of contraception during treatment with Xevoben. If the patient becomes pregnant despite this, or suspects she may be pregnant, she should consult a doctor. The doctor will advise on how to discontinue treatment with Xevoben.
Breastfeeding must not be continued during treatment with Xevoben. If treatment with Xevoben is required, breastfeeding must be discontinued.
Driving and using machines
Xevoben may have a major influence on the ability to drive and use machines. In rare cases, treatment with Xevoben may cause excessive tiredness or sudden sleep attacks. If this applies to the patient, driving and using machines should be avoided to prevent the risk of serious injury to the patient or others until excessive tiredness or sudden sleep attacks have resolved.
Xevoben contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Xevoben

This medicine should always be taken exactly as directed by the doctor. If in doubt, consult the doctor or pharmacist.
The number of Xevoben tablets to take depends on the severity of the disease and the patient's tolerance to Xevoben. The most optimal dose for each patient is determined by gradually increasing the daily dose. For this reason, the dose prescribed to one patient may differ from that prescribed to others. Do not change the dose prescribed by the doctor without medical advice.

If the doctor has not advised otherwise, the treatment schedule is as follows:
Treatment starts with low doses, which are then gradually increased to minimize the occurrence of adverse effects and to maintain the likelihood of achieving a therapeutic effect.

In patients who have not previously been treated for Parkinson's disease, treatment starts with 100–200 mg of levodopa and 25–50 mg of benserazide per day. Every 3rd to 7th day, the doctor may increase the daily dose by 50 mg levodopa + 12.5 mg benserazide or by 100 mg levodopa + 25 mg benserazide.

Do not take more than 800 mg of levodopa and 200 mg of benserazide per day.

Summary of dosing in tabular form:

If adverse reactions occur (see section 4 "Possible adverse reactions"), the doctor may reduce the dose of the medicine. Any subsequent dose increase will then be slower.
If the treatment regimen is changed from a medicine containing levodopa alone to Xevoben (a combination of levodopa and benserazide), a similar therapeutic effect can be achieved by administering only 20% of the previous levodopa dose. When making such a switch, a 12-hour interval must be maintained between taking the previous and the new medicine.
If a patient is using another medicine for Parkinson's disease, Xevoben may additionally be administered. However, as soon as the patient's condition improves with Xevoben, the dose of the other medicine should be re-evaluated, reduced, and then, if necessary, gradually discontinued.

Patients with impaired liver or kidney function
Dosage adjustment of Xevoben is not required in patients with moderate impairment of liver function or mild to moderate impairment of kidney function (creatinine clearance ≥30 mL/min).

Use in children and adolescents
Xevoben must not be used in children and adolescents under 25 years of age (see section 2).

Method of administration
Oral administration.
Whenever possible, Xevoben should be taken 30 minutes before a meal or 1 hour after a meal, swallowing the tablet(s) with an adequate amount of liquid (preferably a glass of water), or taken with a small, low-protein meal (e.g., biscuits, rusks, or similar).

Duration of treatment
Xevoben replaces the neurotransmitter dopamine, which is insufficiently produced in the body. Therefore, treatment with Xevoben is long-term. At least three months of treatment may be required before the doctor can assess the therapy's effectiveness.

Frequency of administration
Initially, the daily dose is divided into 2 to 4 individual doses; at higher doses, at least 4 individual doses are recommended.
Patients experiencing significant fluctuations in motor function during the day (the so-called “on-off” phenomenon) should receive smaller doses of Xevoben more frequently throughout the day. If necessary, the doctor may switch treatment to Xevoben prolonged-release hard capsules.

Use of a higher than recommended dose of Xevoben
If a patient accidentally takes a single dose twice, this will not affect further treatment; continue with the prescribed regimen.
If a patient takes a significantly higher dose of Xevoben, symptoms listed in section 4 "Possible adverse reactions" may occur. If life-threatening symptoms occur, contact the nearest doctor immediately!
Treatment consists of general procedures used in cases of overdose, with special attention to monitoring cardiovascular parameters.

Missed dose of Xevoben
Do not take a double dose to make up for a missed tablet. If a patient misses a single dose of Xevoben, continue with the prescribed regimen.
However, it should be remembered that Xevoben is effective only when taken according to the treatment schedule prescribed by the doctor.

Discontinuation of Xevoben
Consult a doctor if any adverse reactions occur. The doctor will discuss with the patient other available treatment options and whether alternative therapies are available.
Do not discontinue Xevoben independently, as symptoms may recur.
If you have any further doubts regarding the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The frequency of adverse effects with Xevoben is unknown.

Possible adverse effects:

• Cold, bronchitis, febrile infections.
• Decreased number of platelets, white and red blood cells.
• Decreased appetite.
• Cognitive disturbances and behavioural disorders after taking higher than recommended doses of the medicine (see section 2).
• Confusion, pathologically low mood (depression), which may be one of the clinical symptoms of Parkinson's disease (see section 2 "Note for people around the patient"), inner restlessness, anxiety, sleep disorders, sensory hallucinations, delusions, distorted sense of time.
• The patient may experience inability to resist impulses, urges or compulsions to perform actions that may be harmful to the patient or others, which may include:
• Gambling addiction, despite serious personal or family consequences,
• Changed or increased sexual interests and behaviours of significance to the patient or others, e.g. activities 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 (eating more food than normal and more than needed to satisfy hunger). Inform the doctor if the patient exhibits any of these behaviours, so ways to control or reduce these symptoms can be discussed.
• Loss of taste sensation, taste disturbances, involuntary movements resulting from long-term treatment and (or) high doses of the medicine (see section 2), significant motor coordination disturbances after prolonged treatment, fatigue, excessive daytime tiredness, sudden sleep attacks (see section 2 "Warnings and precautions"), dizziness, headache, dry mouth.
• Irregular heartbeat.
• Low blood pressure causing dizziness and fainting (see section 2).
• Nausea, vomiting, diarrhoea, especially at the beginning of treatment (see section 2), change in colouration of saliva, tongue, teeth and oral mucosa.
• Increased transaminase activity, increased alkaline phosphatase activity, increased gamma-glutamyl transferase activity.
• Skin hypersensitivity reactions such as itching and rash.
• Increased blood urea concentration, change in urine colour (urine usually turns red and darkens upon standing).

Psychiatric disorders such as inner restlessness, anxiety, sleep disturbances, sensory hallucinations,
delusions, and distorted sense of time occur especially in elderly patients or in patients who have
previously had a predisposition to such disorders.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed
in this leaflet, tell your doctor, pharmacist, or nurse. Adverse effects
can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 adverse effects, more information on the safety of this medicine can be collected.

5. How to store Xevoben

Keep this 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 stated month.
There are no special requirements regarding the storage temperature of the medicine. Keep the bottle
tightly closed to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Xevoben contains

• The active substances in this medicine are levodopa and benserazide. Each tablet contains 50 mg levodopa + 12.5 mg benserazide (as hydrochloride).
• Other components are: sodium docosate, iron oxide red (E172), ethylcellulose 20 cps, colloidal anhydrous 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, light red tablets approximately 7.5 mm in diameter.
Xevoben is available in HDPE bottles containing a desiccant, closed with a white child-resistant polyethylene cap, packed in a cardboard box containing 20, 50, 60, 100 or 200 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation 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 medicine is authorised for sale in the European Economic Area countries:
Poland: Xevoben