Package leaflet: Information for the user

ValproLEK 300, 300 mg, prolonged-release tablets
Natrii valproas
This medicinal product will be subject to additional monitoring. This will allow rapid
identification of new safety information. Users of this medicine can also help by reporting any
adverse reactions that occur after using the medicine. For information on how to report adverse
reactions – see section 4.
WARNING
ValproLEK 300 used during pregnancy can harm the unborn child. Women of childbearing potential
must use an effective method of birth control (contraception) continuously throughout the entire
treatment period with ValproLEK 300. The treating physician will discuss this with the patient,
but patients should also follow the recommendations provided in section 2 of this leaflet.
Patients should contact their doctor immediately if they are planning a pregnancy or suspect they
may be pregnant.
Do not stop taking ValproLEK 300 unless instructed by a doctor, as the patient's condition may worsen.
Please read all of this leaflet carefully before taking this medicine, as it contains important
information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm someone else, even if their symptoms are similar.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents:

What ValproLEK 300 is and what it is used for
Important information before taking ValproLEK 300
How to take ValproLEK 300
Possible adverse reactions
How to store ValproLEK 300
Contents of the pack and other information

1. What ValproLEK 300 is and what it is used for

ValproLEK 300 is a medicine used in the treatment of epilepsy and mania.
ValproLEK 300 is used in certain types of epilepsy, such as:
certain forms of brief loss of consciousness due to disturbances in brain function (petit mal),
sudden muscle jerks (myoclonic jerks),
rhythmic convulsive seizures associated with muscle rigidity (grand mal),
mixed forms of the above-mentioned disorders,
convulsive seizures without accompanying muscle rigidity (atonic seizures).
ValproLEK 300 may also be used in cases of epilepsy where other antiepileptic medicines have not been sufficiently effective, such as:
epilepsy occurring without convulsions or muscle rigidity,
epilepsy with symptoms affecting perception and symptoms involving voluntary movements.
ValproLEK 300 may be used as monotherapy or in combination with other antiepileptic medicines.
ValproLEK 300 is used in the treatment of mania – a condition in which the patient feels extremely excited, elated, stimulated, enthusiastic, or hyperactive. Mania occurs in the course of a disorder known as bipolar affective disorder. ValproLEK 300 may be used when lithium cannot be administered.

2. Important information before using ValproLEK 300

When not to use ValproLEK 300
if the patient is allergic (hypersensitive) to sodium valproate and/or valproic acid or to
any of the other ingredients of the medicine (listed in section 6);
if the patient has liver or pancreas function disorders;
if the patient has metabolic disorders (including urea cycle disorders);
if the patient or a family member previously had severe liver damage, especially related to
medication use;
if the patient has a disease caused by impaired production of blood pigment (porphyria);
if the patient has a tendency to bleed;
if the patient has a genetic disorder causing mitochondrial dysfunction (e.g. Alpers-Huttenlocher
syndrome).

Bipolar affective disorder

In bipolar affective disorder, ValproLEK 300 must not be used if the patient is pregnant.
In bipolar affective disorder, if the patient is of childbearing age, ValproLEK 300 must not be taken unless the patient uses an effective method of birth control (contraception) throughout the entire treatment period with ValproLEK 300. Do not stop taking ValproLEK 300 or contraception unless discussed with the doctor. The treating physician will provide further advice (see below "Pregnancy, breastfeeding and fertility – Important advice for women").

Epilepsy

In epilepsy, ValproLEK 300 must not be used if the patient is pregnant, unless no other therapy is effective.
In epilepsy, if the woman is of childbearing age, ValproLEK 300 must not be taken unless the patient uses an effective method of birth control (contraception) throughout the entire treatment period with ValproLEK 300. Do not stop taking ValproLEK 300 or contraception unless discussed with the doctor. The treating physician will provide further advice (see below "Pregnancy, breastfeeding and fertility – Important advice for women").

Warnings and precautions
SEE A DOCTOR IMMEDIATELY
Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug
reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme and angioedema,
have been reported during treatment with valproate.
If the patient experiences any of the symptoms associated with these severe skin reactions
described in section 4, they should contact a doctor immediately.

Before using ValproLEK 300, discuss with a doctor or pharmacist if:
ValproLEK 300 is being used in infants or children under 3 years of age with severe epilepsy
(particularly in children with brain damage, intellectual disability, certain genetic disorders and/or
diagnosed metabolic disorders), as there is an increased risk of hepatotoxic effects during the first
6 months of treatment, especially in very young children. The risk is higher when treatment is
combined with other antiepileptic drugs.
the patient has kidney function disorders – the doctor may consider reducing the dose to lower
blood levels of valproic acid;
the patient has inflammatory-like skin or internal organ diseases (systemic lupus erythematosus),
as ValproLEK 300 may trigger or worsen the disease;
the patient has carnitine palmitoyltransferase (CPT) II deficiency-related encephalopathy, as
ValproLEK 300 increases the risk of muscle tissue breakdown with muscle cramps, fever and
reddish-brown urine (rhabdomyolysis);
the patient previously had bone marrow damage;
the patient’s family has a genetic disorder causing mitochondrial dysfunction;
if the patient ever developed severe skin rash, skin peeling, blistering and/or oral ulcers after
taking valproate.

Consult a doctor if any of the above warnings currently apply to the patient or applied in the past.
If during treatment with ValproLEK 300 the patient experiences symptoms such as physical or
mental weakness, loss of appetite (anorexia), apathy, drowsiness, repeated vomiting, abdominal
pain, recurrence or worsening of seizures and/or prolonged bleeding time, contact a doctor
immediately. These symptoms may be caused by liver or pancreas inflammation or increased blood
ammonia levels. For patients suspected of metabolic disorders, especially involving urea cycle
enzymes, the doctor will order appropriate tests before starting treatment.

Due to the possibility of prolonged bleeding from wounds, inform the doctor or dentist about taking
ValproLEK 300. If the patient is undergoing surgery or dental procedures, or experiences spontaneous
bruising or bleeding (see "Possible side effects"), the doctor will monitor blood cell counts.

If the patient taking ValproLEK 300 is undergoing a urine test for ketone bodies (substances formed
when the body burns fat instead of sugar), test results may be unreliable due to this medicine.

If the patient’s body weight increases, especially at the beginning of treatment, inform the doctor.
This may be a risk factor for polycystic ovary syndrome.
Weight gain may be due to increased appetite (see section 4 "Possible side effects"). Body weight
should be monitored and efforts made to minimize weight gain.

In a small number of people taking antiepileptic medicines such as ValproLEK 300, thoughts of self-harm or suicide have occurred. If such thoughts occur, contact a doctor immediately.

Note
The tablet skeleton of ValproLEK 300 may be excreted in faeces.

Children and adolescents
Children and adolescents under 18 years of age:
ValproLEK 300 must not be used in the treatment of mania in children and adolescents under 18 years of age.

ValproLEK 300 and other medicines
Inform the doctor about all medicines currently or recently taken, including those obtained without a prescription.

ValproLEK 300 and other medicines may affect each other’s action and side effects, so dose adjustments may sometimes be necessary. This includes, among others:
antipsychotics, monoamine oxidase inhibitors (MAO inhibitors), antidepressants and benzodiazepines (medicines used in psychiatric disorders). ValproLEK 300 may enhance the effects of these medicines;
phenobarbital (an antiepileptic medicine). Blood levels of phenobarbital may increase (especially in children);
primidone (an antiepileptic medicine). Increased levels of primidone and its side effects (such as mental dullness) are possible. This effect diminishes during long-term treatment;
phenytoin (an antiepileptic medicine). Increased blood levels (unbound form) of phenytoin and symptoms of overdose may occur. This may particularly affect simultaneous use of clonazepam (an antiepileptic medicine) and valproic acid in children;
carbamazepine (a medicine used in epilepsy and psychiatric disorders). Concurrent use of ValproLEK 300 may enhance the toxic effects of carbamazepine;
lamotrigine (an antiepileptic medicine). Combined treatment increases the risk of severe skin reactions, especially in children. Valproic acid may reduce lamotrigine metabolism in the body;
topiramate (an antiepileptic medicine);
zidovudine (a medicine used in HIV infections). Valproic acid may increase zidovudine blood levels;
other medicines used in seizures (antiepileptic medicines such as phenytoin, phenobarbital and carbamazepine). These may reduce blood levels of valproic acid;
rifampicin (a medicine used in bacterial infections). It may reduce blood levels of valproic acid;
felbamate (an antiepileptic medicine). Concurrent use may increase blood levels of valproic acid and felbamate;
mefloquine (a medicine used in prevention and treatment of malaria). Seizures may occur during simultaneous use with ValproLEK 300;
medicines that inhibit the activity of certain liver enzymes (such as cimetidine or erythromycin). These medicines may increase blood levels of valproic acid;
carbapenem antibiotics (used in bacterial infections). These may reduce blood levels of valproic acid;
medicines containing the active substance quetiapine, as concurrent use with ValproLEK 300 may increase the risk of abnormal blood cell counts;
acetylsalicylic acid (a medicine used to thin the blood or relieve pain). Valproic acid may enhance its effect. Concurrent use of both medicines is not recommended in children under 3 years of age due to the risk of liver damage;
valproate used with medicines such as acetylsalicylic acid, due to the possibility of increased valproate blood levels;
cholestyramine (a medicine that reduces cholesterol levels), as it reduces valproate absorption;
preparations containing estrogens (including certain oral contraceptives), as reduced valproate blood levels are possible; use of ValproLEK 300 should not affect the effectiveness of hormonal contraception ("the pill");
metamizole (a medicine used in pain and fever treatment);
clozapine (used in psychiatric disorders).

Other medicines that may affect ValproLEK 300 or whose effects may be altered by ValproLEK 300 include those containing the following active substances: protease inhibitors such as lopinavir and ritonavir (used in HIV infection treatment), nimodipine and propofol (used in anaesthesia).

ValproLEK 300 with food and drink
Food
Tablets may be taken 1 hour before a meal or during a meal (but always in the same way), taken with plain water (do not use carbonated drinks). Food does not significantly affect drug absorption.

Alcohol
Alcohol consumption is not recommended during treatment with ValproLEK 300 due to the risk of seizures and enhanced alcohol effects.

Pregnancy, breastfeeding and fertility
Pregnancy
Important advice for women

Bipolar affective disorder

In bipolar affective disorder, ValproLEK 300 must not be used if the patient is pregnant.
In bipolar affective disorder, if the patient is of childbearing age, ValproLEK 300 must not be taken unless the patient uses an effective method of birth control (contraception) throughout the entire treatment period with ValproLEK 300. Do not stop taking ValproLEK 300 or contraception unless discussed with the doctor. The treating physician will provide further advice.

Epilepsy

In epilepsy, ValproLEK 300 must not be used if the patient is pregnant, unless no other therapy is effective.
In epilepsy, if the woman is of childbearing age, ValproLEK 300 must not be taken unless the patient uses an effective method of birth control (contraception) throughout the entire treatment period with ValproLEK 300. Do not stop taking ValproLEK 300 or contraception unless discussed with the doctor. The treating physician will provide further advice.

Risk of taking valproate during pregnancy (regardless of the condition for which valproate is used)
Consult the treating doctor immediately if the patient plans pregnancy or is pregnant.
Taking valproate during pregnancy carries risks. The higher the dose, the greater the risk, but no dose is completely risk-free.

Valproate may cause serious congenital malformations and affect the child’s development. Most commonly reported congenital malformations include: spina bifida (when spinal bones do not develop properly); facial and skull developmental defects; heart, kidney, urinary tract and genital organ developmental defects; limb defects and multiple associated developmental defects affecting several organs and body parts. Congenital malformations may lead to disabilities, which may be significant.

Hearing disorders or deafness have been reported in children exposed to valproate in utero.
Developmental eye defects together with other congenital malformations have been observed in children exposed to valproate in utero. Eye developmental defects may affect vision.

The risk of giving birth to a child with congenital malformations requiring treatment is increased in patients taking valproate during pregnancy. Valproate has been used for many years, so it is known that in a group of children born to mothers taking valproate, about 10 out of 100 will have congenital malformations. For comparison, such malformations are found in 2-3 out of every 100 children born to women without epilepsy.

It is estimated that up to 30-40% of preschool-aged children whose mothers took valproate during pregnancy may have early developmental problems. Affected children may start walking and talking later, may be less intellectually capable than other children, and may have language and memory problems.

Various autistic disorders are more frequently diagnosed in children exposed to valproate in utero, and some evidence suggests that children exposed to the drug during pregnancy may be more prone to developing symptoms of attention deficit/hyperactivity disorder (ADHD).

In exceptional cases, children of mothers treated with sodium valproate during pregnancy have blood clotting disorders.

A doctor may prescribe valproate to a woman capable of becoming pregnant only if no other treatment helps.

Before prescribing this medicine, the treating doctor will explain to the patient what risks the child may face if she becomes pregnant while taking valproate. If the patient taking this medicine decides to have a child, she should not stop taking the medicine or contraception independently until discussed with the treating doctor.

Parents or guardians of girls treated with valproate should contact the treating doctor when menstruation begins in their child.

Ask the doctor about taking folic acid during attempts to conceive. Folic acid may reduce the general risk of spina bifida and early miscarriage, which affect all pregnancies. However, it is unlikely that folic acid use will reduce the risk of congenital malformations associated with valproate treatment.

Please select from the situations described below that applies to the patient and read the information:

STARTING TREATMENT WITH ValproLEK 300
CONTINUING TREATMENT WITH ValproLEK 300 WITHOUT PLANNING PREGNANCY
CONTINUING TREATMENT WITH ValproLEK 300 WHILE PLANNING PREGNANCY
UNPLANNED PREGNANCY DURING CONTINUATION OF TREATMENT WITH ValproLEK 300

STARTING TREATMENT WITH ValproLEK 300
If ValproLEK 300 is prescribed for the first time, the treating doctor will explain the risks to the unborn child if the patient becomes pregnant. A woman of childbearing age should ensure that she continuously uses an effective method of contraception throughout the entire treatment period with ValproLEK 300. Consult the treating doctor or a family planning clinic if advice on contraception is needed.

Important information:
Pregnancy must be excluded with a pregnancy test before starting ValproLEK 300, with results confirmed by the treating doctor.
The patient should use an effective method of birth control (contraception) throughout the entire treatment period with ValproLEK 300.
Discuss the appropriate method of birth control (contraception) with the treating doctor. The treating doctor will provide information on pregnancy prevention and may refer the patient to a specialist for contraception advice.
Regular visits (at least once a year) to a specialist experienced in treating bipolar affective disorder or epilepsy should be scheduled. During these visits, the treating doctor will ensure that the patient has been adequately informed and understands all risks and advice related to valproate use during pregnancy.
Inform the doctor if the patient plans to have a child.
Inform the doctor immediately if the patient is pregnant or suspects she may be pregnant.

CONTINUING TREATMENT WITH ValproLEK 300 WITHOUT PLANNING PREGNANCY
If the patient continues treatment with ValproLEK 300 and does not plan pregnancy, she must ensure continuous use of an effective method of contraception throughout the entire treatment period with ValproLEK 300. Consult the doctor or a family planning clinic if advice on contraception is needed.

Important information:
The patient should use an effective method of birth control (contraception) throughout the entire treatment period with ValproLEK 300.
Discuss contraception (birth control method) with the treating doctor. The treating doctor will provide information on pregnancy prevention and may refer the patient to a specialist for contraception advice.
Regular visits (at least once a year) to a specialist experienced in treating bipolar affective disorder or epilepsy should be scheduled. During these visits, the treating doctor will ensure that the patient has been adequately informed and understands all risks and advice related to valproate use during pregnancy.
Inform the doctor if the patient plans to have a child.
Inform the doctor immediately if the patient is pregnant or suspects she may be pregnant.

CONTINUING TREATMENT WITH ValproLEK 300 WHILE PLANNING PREGNANCY
If the patient plans to have a child, she should first schedule an appointment with the treating doctor. Do not stop treatment with ValproLEK 300 or contraception until discussed with the treating doctor. The treating doctor will provide further advice.
Children born to mothers who took valproate are seriously at risk of congenital malformations and developmental problems that may significantly impair the child.
The treating doctor will refer the patient to a specialist experienced in treating bipolar affective disorder or epilepsy to appropriately assess alternative treatment options. The specialist may take actions to ensure the best possible pregnancy course and minimize risks for mother and unborn child.
The treating specialist may decide to change the dose of ValproLEK 300, switch to another medicine, or discontinue ValproLEK 300 treatment well before conception to ensure the disease is stable.
Ask the doctor about taking folic acid during attempts to conceive. Folic acid may reduce the general risk of spina bifida and early miscarriage, which affect all pregnancies. However, it is unlikely that folic acid use will reduce the risk of congenital malformations associated with valproate treatment.

Important information:
Do not stop treatment with ValproLEK 300 unless advised by the doctor.
Do not stop using birth control methods (contraception) before discussing with the treating doctor and jointly developing a management plan that ensures control of the patient’s condition and reduces risks to the child.
First, schedule an appointment with the treating doctor. During this visit, the treating doctor will ensure that the patient has been adequately informed and understands all risks and advice related to valproate use during pregnancy.
The treating doctor will attempt to switch to another medicine or discontinue ValproLEK 300 treatment well before conception.
Schedule an urgent visit to the treating doctor if the patient is pregnant or suspects she may be pregnant.

UNPLANNED PREGNANCY DURING CONTINUATION OF TREATMENT WITH ValproLEK 300
Do not stop treatment with ValproLEK 300 unless discussed with the treating doctor, as the patient’s health condition may worsen. Schedule an urgent appointment with the doctor if the patient is pregnant or suspects she may be pregnant. The treating doctor will provide further advice.
Children born to mothers who took valproate are seriously at risk of congenital malformations and developmental problems that may significantly impair the child.
The patient will be referred to a specialist experienced in treating bipolar affective disorder or epilepsy to assess alternative treatment options.
In exceptional circumstances when ValproLEK 300 is the only available treatment option during pregnancy, the patient will be closely monitored regarding both the treatment of the underlying disease and the child’s development. The patient and her partner will receive advice and support regarding valproate-exposed pregnancy.
Ask the doctor about taking folic acid. Folic acid may reduce the general risk of spina bifida and early miscarriage, which affect all pregnancies. However, it is unlikely that folic acid use will reduce the risk of congenital malformations associated with valproate treatment.

Important information:
Schedule an urgent visit to the treating doctor if the patient is pregnant or suspects she may be pregnant.
Do not stop taking ValproLEK 300 unless decided by the doctor.
The patient must be referred to a specialist experienced in treating epilepsy or bipolar affective disorder to assess the need for alternative treatment options.
The patient must receive advice on the risks of using ValproLEK 300 during pregnancy, including teratogenic effects and impact on child development.
The patient must be referred to a specialist in prenatal monitoring to detect possible developmental abnormalities.
Read the patient information leaflet received from the treating doctor. The treating doctor will discuss the annual risk acknowledgment form and ask the patient to sign and keep it. The patient will also receive a Patient Card from the pharmacist as a reminder of the risks of valproate use during pregnancy.

Important advice for male patients
Possible risk associated with taking valproate within 3 months before conception
A study suggests a possible risk of motor disorders and psychological developmental disorders (early childhood developmental problems) in children whose fathers were treated with valproate within 3 months before conception. In this study, about 5 out of 100 children whose fathers were treated with valproate had such disorders, compared to about 3 out of 100 children of men treated with lamotrigine or levetiracetam (other medicines that may be used in the treatment of the patient’s condition). The risk in children whose fathers discontinued valproate treatment at least 3 months (the time needed for new sperm production) before conception is unknown. The study has limitations, so it is unclear whether the increased risk of motor and psychological developmental disorders suggested by this study is caused by valproate. The study was not large enough to show exactly what types of motor and psychological developmental disorders in children are involved.

As a precaution, the doctor will discuss with the patient:
the possible risk in children whose fathers were treated with valproate;
the need to consider using effective birth control (contraception) by the patient and his partner during treatment and for 3 months after discontinuation;
the need to consult a doctor when planning conception and before stopping contraception;
the possibility of using other treatment methods for the disease, depending on the individual situation.
Do not donate sperm while taking valproate and for 3 months after discontinuation.
If planning parenthood, discuss this with the doctor.
If the patient’s partner becomes pregnant while the patient is taking valproate within 3 months before conception and the patient has related questions, he should contact the doctor. Do not stop treatment without consulting the doctor. If the patient stops treatment, symptoms may worsen.
The patient should have regular visits with the prescribing doctor. During such visits, the doctor will discuss precautions related to valproate use and the possibility of using other treatment methods for the patient’s condition, depending on the individual situation.
Read the patient guide received from the treating doctor. The patient will also receive a Patient Card from the pharmacist as a reminder of the possible risks associated with valproate use.

Breastfeeding
Sodium valproate partially passes into breast milk. If the patient wishes to breastfeed, the doctor will consider the benefits of breastfeeding against the risk of adverse effects in the child. Breastfeeding is possible if the child is carefully monitored for adverse effects (such as drowsiness, feeding difficulties, vomiting, skin rashes).
Before taking any medicine, consult a doctor or pharmacist.

Driving and operating machinery
ValproLEK 300 may cause side effects (such as dizziness, sluggishness and drowsiness) that impair reaction ability. This should be considered when driving or operating machinery.
Epilepsy itself also requires caution during these activities, especially in patients who have not been seizure-free for a long time. Consult a doctor beforehand.
Taking multiple antiepileptic medicines or medicines with sedative, hypnotic and/or muscle-relaxing effects (benzodiazepines) may enhance these effects.

Important information about some ingredients of ValproLEK 300
This medicine contains 29.7 mg of sodium (a main component of table salt) in each tablet. This corresponds to 1.5% of the maximum recommended daily sodium intake in the diet for adults. Consult a doctor or pharmacist if the patient needs to take 14 or more tablets per day for a prolonged period, especially if on a low-salt (low-sodium) diet.

3. How to use ValproLEK 300

Girls and women of childbearing age
Treatment with ValproLEK 300 should be initiated and supervised by a physician specialized in the treatment of epilepsy or bipolar affective disorder.

Male patients
It is recommended that treatment be initiated and supervised by a specialist experienced in the treatment of epilepsy or bipolar affective disorder – see section 2 Important advice for male patients.

ValproLEK 300 must always be taken exactly as prescribed by the doctor.
If in doubt, consult your doctor or pharmacist.

The tablets (or their halves) should be swallowed whole without chewing, with water (not with carbonated drinks such as soft drinks). If gastrointestinal irritation occurs at the beginning or during treatment, the tablets should be taken during or after meals.

ValproLEK 300 tablets may be divided into equal doses.

The doctor determines the dose of the medicine for each patient.

Treatment usually starts with a low dose of ValproLEK 300, which is gradually increased until the appropriate dose for the patient is reached.

Typical dosing:
Epilepsy
Adults and children
Initial dose of sodium valproate: 10 to 20 mg/kg body weight per day. This dose should be taken in two or more divided doses, preferably during meals.
(Example: a patient weighing 75 kg has been prescribed the medicine at a dose of 10 mg/kg body weight (milligrams per kilogram of body weight) per day, i.e. 2½ extended-release tablets of ValproLEK 300 per day).

If necessary, the doctor may increase the dose weekly by 5 to 10 mg/kg body weight per day until the desired therapeutic effect is achieved.

Maintenance dose of sodium valproate: usually 20 to 30 mg/kg body weight per day.
Adults: 9 to 35 mg/kg body weight per day.
Children: 15 to 60 mg/kg body weight per day.

The optimal maintenance daily dose is usually taken with meals, in one or two divided doses.

The maximum dose of sodium valproate, i.e. 60 mg/kg body weight per day, should not be exceeded.

Children with body weight less than 20 kg
In this patient group, sodium valproate should be administered in another pharmaceutical form due to the need for precise dose adjustment.

Mania
The daily dose should be determined and monitored by the treating physician.

Initial dose
The recommended initial daily dose is 750 mg.

Average daily dose
Recommended daily doses usually range from 1000 mg to 2000 mg.

If you feel that the effect of ValproLEK 300 is too strong or too weak, consult your doctor or pharmacist.

Elderly patients
The doctor may decide to modify the dose.

Patients with renal function impairment
The doctor may decide to modify the dose.

Duration of treatment
Your doctor will inform you how long you need to take ValproLEK 300. Do not discontinue treatment prematurely, as symptoms of the disease may recur.

Taking more ValproLEK 300 than prescribed
If you take more ValproLEK 300 than prescribed, seek immediate medical advice from your doctor or pharmacist. Symptoms of overdose may include: coma with reduced muscle tone, diminished reflexes, constricted pupils, low blood pressure, drowsiness, metabolic acidosis, increased blood sodium levels, and impaired respiratory or cardiac function.

Additionally, high doses in adults and children may cause neurological disturbances such as increased tendency to seizures and behavioral changes.

Missing a dose of ValproLEK 300
Do not take a double dose to make up for a missed dose.
If you forget to take your medicine, take it as soon as possible, unless it is almost time for your next dose. In that case, take the medicine according to your regular schedule.

Stopping ValproLEK 300
Do not stop taking this medicine without consulting your doctor.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.
If any of the following serious adverse reactions occur, seek medical advice immediately – urgent treatment may be required:

Common (may affect up to 1 in 10 people)
Liver damage. This can be very serious, especially in children, and usually occurs within the first 6 months of treatment. Early recognition is important. Sometimes symptoms occur together with drowsiness and high blood ammonia levels (which may be recognised by an ammonia-like odour of urine). For more information, see section “Warnings and precautions”.

Spontaneous bruising or bleeding due to reduced platelet count (thrombocytopenia). This occurs more frequently in women and elderly people.

Extrapyramidal disorders, which may be irreversible (movement disorders such as stiffness, tremor, or abnormal involuntary movements of the mouth and tongue).

Lethargy and immobility with reduced response to stimuli (stupor), marked drowsiness and sleepiness, followed by transient disturbances in consciousness. Sometimes increased frequency of seizures may also occur. These symptoms usually occur after sudden intake of a higher dose or when the patient is taking several antiepileptic medicines simultaneously (especially phenobarbital or topiramate).

Uncommon (may affect up to 1 in 100 people)
Pancreatitis, which may be severe and associated with nausea, vomiting and severe abdominal pain radiating to the back.

Severe allergic reaction causing swelling of the face or throat (angioedema).

Reduction in white blood cell count with increased susceptibility to infections (leucopenia).

Excessive fluid accumulation in the body due to excessive release of antidiuretic hormone. This leads to reduced sodium levels in the blood; confusion may occur.

Kidney failure.

Worsening of epileptic seizures.

Breathing difficulties, pain or pressure in the chest (especially during inhalation), shortness of breath and dry cough due to fluid accumulation around the lungs (pleural effusion).

Rare (may affect up to 1 in 1,000 people)
Severe hypersensitivity reaction with (high) fever, red skin rashes, skin blisters and skin peeling, joint pain and (or) eye inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Drug-induced hypersensitivity reaction, known as DRESS syndrome, with skin rash, fever, swollen lymph nodes and possible involvement of other organs.

Bone marrow suppression, which may lead to serious changes in blood cell counts such as red blood cell aplasia and white blood cell deficiency with sudden high fever, severe sore throat and mouth ulcers (agranulocytosis).

Hypothyroidism (reduced thyroid function, which may cause fatigue or weight gain).

Autoimmune disease with skin rash and joint inflammation (systemic lupus erythematosus).

Unusual muscle breakdown, which may lead to kidney damage (rhabdomyolysis).

Seek medical advice if any of the following adverse reactions worsen or persist for more than a few days:

Very common (may affect more than 1 in 10 people)
Uncontrolled tremor
Nausea (frequent at the beginning of treatment and usually resolves within a few days)

Common (may affect up to 1 in 10 people):
Anaemia
Low blood sodium levels
Hypersensitivity (allergic reaction)
Confusion
Aggressive behaviour, restlessness, attention disorders (these adverse reactions occur mainly in children)
Seeing or hearing things that are not there (hallucinations)
Dizziness
Seizure attacks
Headache
Drowsiness
Memory disturbances
Uncontrolled rapid eye movements (nystagmus)
Hearing loss (temporary or permanent)
Bleeding
Pain in the upper abdomen, diarrhoea, vomiting
Swelling or inflammation of the gums, inflammation of the oral mucosa
Hair loss
Nail and nail bed disorders
Irregular menstruation, painful menstruation
Weight gain (see also section “How to take ValproLEK 300”), weight loss
Urinary incontinence

Uncommon (may affect up to 1 in 100 people)
Reduction in all types of blood cells (pancytopenia)
Increased levels of male hormones, leading to excessive growth of body and facial hair (hirsutism), male-like appearance in women (virilisation), acne, hair loss
Fatigue, lack of energy
Coma
Brain disorder characterised by seizures and loss of consciousness (encephalopathy)
Transient symptoms of Parkinson’s disease (tremor, movement disorders, so-called mask-like face, etc.)
Coordination disorders (ataxia), e.g. unsteady gait
Tingling or numbness (paraesthesia)
Inflammation of blood vessels in the skin (vasculitis)
Hair disorders (including abnormal hair structure, hair colour changes, abnormal hair growth)
Skin rash
Absence of menstruation
Fluid accumulation in hands and feet (peripheral oedema)
Low body temperature

Rare (may affect up to 1 in 1,000 people)
Deficiency of blood coagulation factor VIII
Disease caused by impaired production of haem pigment (porphyria)
Increased blood ammonia levels (hyperammonaemia)
Obesity
Abnormal behaviour, hyperkinesia/excessive activity, learning disorders (these adverse reactions occur mainly in children)
Transient mental disturbances associated with temporary brain shrinkage, cognitive disorders
Double vision
Skin rash with red (moist), irregular patches (erythema multiforme)
Bedwetting
Fanconi syndrome
Kidney inflammation
Polycystic ovary syndrome
Male infertility

Very rare (may affect up to 1 in 10,000 people)
Breast enlargement in men (gynaecomastia)

Frequency not known (cannot be estimated from available data):
Excessive number of white blood cells in blood (lymphocytosis)
Prolonged bleeding time due to impaired blood clotting and (or) disorders affecting platelets (deficiency of factor VIII/von Willebrand factor)
Gastrointestinal disorders (usually transient, occurring at the beginning of treatment)
Constipation
Increased or decreased appetite
Apathy (in case of concomitant treatment with other antiepileptic drugs)
Sedation
Congenital malformations and developmental disorders in children of mothers who took this medicine during pregnancy. More information is provided in section 2 “Pregnancy, breastfeeding and fertility”.
Darker areas of skin and mucous membranes (hyperpigmentation)

There have been reports of bone disorders, including bone thinning (osteopenia, osteoporosis) and bone fractures. Consult your doctor if the patient has been taking antiepileptic medicine for a long time, has a history of osteoporosis or is taking steroids.

If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur, consult a doctor or pharmacist.

Additional adverse reactions in children
Some adverse reactions of valproate occur more frequently or are more severe in children than in adults. These include liver damage, pancreatitis, aggression, restlessness, attention disorders, unusual behaviour, hyperactivity and learning disorders.

Reporting of adverse reactions
If any adverse symptoms occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store ValproLEK 300

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What ValproLEK 300 contains
The active substances in this medicinal product are sodium valproate and valproic acid.
Each prolonged-release tablet contains 200 mg of sodium valproate and 87 mg of valproic acid, which together correspond to 300 mg of sodium valproate.
Other ingredients are: colloidal anhydrous silica, colloidal hydrated silica, ethylcellulose, hypromellose, sodium saccharin (E954), macrogol 6000, copolymer of methacrylic acid and ethyl acrylate (1:1), 30% dispersion, talc, titanium dioxide (E171).

What ValproLEK 300 looks like and contents of the pack
ValproLEK 300 prolonged-release tablets are white, bean-shaped, with a score line on both sides to facilitate breaking.
The prolonged-release tablets are packed in blisters made of aluminium/aluminium foil and placed in a cardboard box.
Pack sizes:
30, 50 prolonged-release tablets

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

Manufacturer
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben, Germany
Lek S.A.
ul. Domaniewska 50 C
02-672 Warsaw, Poland
Lek Pharmaceuticals d.d.
Verovškova 57
1526 Ljubljana, Slovenia

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Belgium: Valproate Sandoz 300 mg tabletten met verlengde afgifte
Czech Republic: Valproat Chrono Sandoz
Germany: Valproat - 1 A Pharma 300 mg Retardtabletten
Finland: Valproat Sandoz 300 mg depottabletti
Netherlands: Natriumvalproaat Sandoz Chrono 300, tabletten met verlengde afgifte 300 mg
Poland: VALPROLEK 300, 300 MG, TABLETKI O PRZEDŁUŻONYM UWALNIANIU

For further information about this medicinal product, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw, Poland
tel. 22 209 70 00

Valprolek 300