Absenor

Leaflet accompanying the packaging: information for the user

Absenor, 300 mg, prolonged-release tablets

Absenor, 500 mg, prolonged-release tablets

Sodium valproate
▼This medicinal product is subject to additional monitoring. This will allow for the quick identification of new safety information. The user of the medicinal product can also help by reporting any adverse reactions that occur after taking the medicinal product. To find out how to report adverse reactions, see section 4.

WARNING

Absenor (valproate) used during pregnancy may harm the unborn child. Women of childbearing age should use effective contraception (birth control) continuously throughout the entire treatment period with Absenor. The treating physician will discuss this with the patient, but the patient should also follow the recommendations presented in section 2 of this leaflet. The patient should contact the treating physician immediately if they plan to become pregnant or suspect they are pregnant. The patient should not stop taking Absenor unless the treating physician advises them to do so, as their condition may worsen.

It is essential to carefully read the contents of the leaflet before taking the medicinal product, as it contains important information for the patient.

• The patient should keep this leaflet to be able to read it again if necessary.
• In case of any doubts, the patient should consult their physician or pharmacist.
• This medicinal product has been prescribed specifically for the patient. The patient should not pass it on to others. The medicinal product may harm another person, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including those not listed in this leaflet, they should inform their physician or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Absenor and what is it used for

Absenor is a medicinal product used to treat epilepsy (as an antiepileptic) and manic episodes (abnormally elevated mood and increased activity). Absenor is used to treat:

• seizures affecting both sides of the brain (generalized seizures), such as absence seizures, myoclonic seizures, and tonic-clonic seizures;
• seizures starting in a specific part of the brain (focal seizures) that may spread to both sides of the brain (secondarily generalized seizures).

Absenor can also be used in combination with other antiepileptic medicinal products to treat other types of seizures, such as mixed (complex) seizures, as well as seizures that spread from a specific part of the brain to both sides of the brain, when these types of seizures do not respond to commonly used antiepileptic medicinal products.

• mania, when the patient feels very excited, elated, agitated, enthusiastic, or overactive. Mania occurs in a condition known as bipolar affective disorder. Absenor may be used when lithium cannot be used.

Notes:
If the patient is switching from previous treatment with sodium valproate (in the form of immediate release) to Absenor, it is essential to ensure that the appropriate serum concentration of the medicinal product is maintained. In young children, Absenor is a first-choice medicinal product only in exceptional cases. Absenor should be used with special caution, after careful consideration of the benefits and risks, and if possible, not in combination with other antiepileptic medicinal products.

2. Important information before taking Absenor

When not to take Absenor

• if the patient is allergic to sodium valproate, peanuts, or soy, or any of the other ingredients of this medicinal product (listed in section 6);
• if the patient or a family member has had severe liver disease in the past or currently has severe liver or pancreatic disorders;
• if any of the patient's siblings have had liver disorders leading to death during treatment with valproic acid;
• if the patient has a hereditary or acquired metabolic disorder of porphyrin (hepatic porphyria);
• if the patient has a blood coagulation disorder;
• if the patient has a genetic disorder causing mitochondrial disorders (e.g., Alpers-Huttenlocher syndrome);
• -if the patient has a urea cycle disorder (a type of metabolic disorder).

Bipolar affective disorder

• In the case of bipolar affective disorder, Absenor should not be used if the patient is pregnant.
• In the case of bipolar affective disorder, if the patient is of childbearing age, Absenor should not be taken unless the patient uses effective contraception (birth control) throughout the entire treatment period with Absenor. The patient should not stop taking Absenor or contraception until they have discussed it with their physician. The treating physician will provide further guidance (see "Pregnancy, breastfeeding, and fertility - Important note for women").

Epilepsy

• In the case of epilepsy, Absenor should not be used if the patient is pregnant, unless there is no alternative treatment.
• In the case of epilepsy, if the woman is of childbearing age, Absenor should not be taken unless the patient uses effective contraception (birth control) throughout the entire treatment period with Absenor. The patient should not stop taking Absenor or contraception until they have discussed it with their physician. The treating physician will provide further guidance (see "Pregnancy, breastfeeding, and fertility - Important note for women").

Warnings and precautions

The patient should discuss the following with their physician before taking this medicinal product:

• if the patient has ever experienced a severe skin rash or peeling of the skin after taking valproate.

THE PATIENT SHOULD CONTACT THEIR PHYSICIAN IMMEDIATELY

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), polymorphic eruption, and angioedema, have been reported with valproate. If the patient notices any symptoms related to these severe skin reactions, as described in section 4, they should contact their physician immediately. During treatment with Absenor, special caution should be exercised in the following cases:

• previous bone marrow damage;
• systemic lupus erythematosus (an immune system reaction against the body's own connective tissue);
• metabolic disorders, particularly congenital enzyme deficiencies;
• increased ammonia levels in the blood (hyperammonemia) during treatment with valproic acid. The patient should contact their physician if they experience symptoms such as apathy, fatigue, vomiting, low blood pressure, or increased frequency of seizures. The physician will determine the ammonia and valproic acid levels in the blood and, if necessary, reduce the dose of Absenor;
• suspected urea cycle disorders; the physician will determine the ammonia level in the blood before starting treatment with valproic acid (see also section 2: "When not to take Absenor");
• mitochondrial metabolic disorder caused by a deficiency of the enzyme carnitine palmitoyltransferase II (CPT II) - the risk of rhabdomyolysis (muscle breakdown) increases during treatment with valproic acid;
• if there is a family history of mitochondrial disorders;
• renal impairment and/or low protein levels in the blood;
• before surgery or dental procedures (e.g., tooth extraction) and after injuries or spontaneous bleeding. Due to increased bleeding tendencies, the patient should inform their physician about taking Absenor so that they can order a blood coagulation test;
• concomitant use of anticoagulant medicinal products (e.g., vitamin K antagonists), as the risk of bleeding may increase. Therefore, regular blood coagulation tests should be performed;
• concomitant use of acetylsalicylic acid, as the valproic acid level in the blood may increase;
• increased frequency of seizures. Like other antiepileptic medicinal products, the frequency of seizures or their severity may increase during treatment with Absenor. In such cases, the patient should contact their physician immediately.

A small number of people taking antiepileptic medicinal products, including those containing sodium valproate, have had thoughts of harming themselves or suicide. If the patient ever has such thoughts, they should contact their physician immediately. Note: The glass bottle contains a desiccant. Do not swallow the desiccant.

Children and adolescents

Special caution should be exercised when using Absenor in:

• young children taking other antiepileptic medicinal products concomitantly;
• children and adolescents with multiple disabilities and severe epilepsy.

Sodium valproate should not be used in children and adolescents under 18 years of age for the treatment of mania. In infants and children during treatment of febrile diseases and in adolescents, Absenor and medicinal products containing acetylsalicylic acid should not be used concomitantly. Concomitant use is only allowed on special recommendation by the physician. Warning: Rarely, severe liver damage and, occasionally, pancreatic damage have been reported. The physician will monitor whether the patient, especially infants, young children, or older children, does not have symptoms of these conditions, particularly during the first six months of treatment. Liver and/or pancreatic damage may be preceded by sudden, non-specific symptoms such as recurrence or increased frequency or severity of seizures, impaired consciousness with disorientation, restlessness, motor disturbances, physical restlessness, and weakness, loss of appetite, aversion to usual foods, dislike of valproic acid, nausea, vomiting, upper gastrointestinal disorders, drowsiness, sleepiness, and increased bruising, jaundice (yellowing of the skin or whites of the eyes), nosebleeds, and localized or generalized edema (water retention). If these disorders persist or are severe, the patient should inform their physician so that they can determine whether to continue treatment with Absenor. Methods for early detection of liver and/or pancreatic damage Before starting treatment, the physician will conduct a thorough medical history and clinical and biochemical laboratory tests (with particular attention to metabolic disorders, liver or pancreatic disorders, blood morphology, and coagulation disorders). After four weeks of treatment, the physician will order another control biochemical laboratory test. In patients without clinical symptoms but with abnormally elevated test results, three additional control tests will be ordered at two-week intervals, and then once a month until six months of treatment. Parents and/or guardians should immediately, regardless of this schedule, inform the treating physician about any unusual changes in the patient's condition, including abnormalities found in test results. In adolescents (around 15 years of age and older) and adults, it is recommended to monitor the patient's clinical condition and laboratory test results monthly for the first six months and always before starting treatment. If the test results do not show any abnormalities after 12 months of treatment, it is sufficient to perform medical check-ups 2 to 3 times a year. Notes: At the beginning of treatment, weight gain may occur. The patient should regularly monitor their weight and discuss appropriate measures with their physician if necessary. Absenor should not be used for migraine prophylaxis (see also "Pregnancy, breastfeeding, and fertility").

Absenor and other medicinal products

The patient should tell their physician or pharmacist about all medicinal products they are currently taking or have recently taken, as well as any medicinal products they plan to take. Medicinal products that increase the effect of Absenor (and sometimes adverse reactions):

• felbamate (an antiepileptic medicinal product);
• cimetidine (a medicinal product for stomach ulcers);
• erythromycin (a medicinal product used for bacterial infections);
• acetylsalicylic acid (a medicinal product for pain and fever): acetylsalicylic acid reduces the binding of valproic acid to blood proteins. This may increase the harmful effect of valproic acid on the liver. See also "Children and adolescents" in section 2: "Important information before taking Absenor".

Medicinal products that decrease the effect of Absenor:

• phenobarbital, primidone, phenytoin, carbamazepine (other antiepileptic medicinal products);
• mefloquine (a medicinal product for malaria);
• rifampicin (a medicinal product for tuberculosis);
• carbapenems (antibiotics used to treat bacterial infections, such as imipenem, panipenem, and meropenem);
• The concomitant use of valproic acid and carbapenem should be avoided, as the efficacy of sodium valproate may decrease;
• protease inhibitors, such as lopinavir or ritonavir (a medicinal product for HIV infection);
• cholestyramine (a medicinal product that reduces the amount of fat in the blood);
• medicinal products containing estrogen (including some hormonal contraceptives);
• metamizole, a medicinal product used to treat pain and fever.

Medicinal products that increase or decrease the effects of Absenor:

• concomitant use of fluoxetine (an antidepressant medicinal product). The valproic acid level in the blood may increase, but also decrease.

Absenor increases the effects of, and sometimes the adverse reactions of:

• phenobarbital, primidone, phenytoin, carbamazepine, lamotrigine, felbamate (antiepileptic medicinal products);
• neuroleptic medicinal products (medicinal products used for psychiatric disorders), benzodiazepines (medicinal products used to alleviate anxiety and tension), barbiturates (sedative medicinal products), monoamine oxidase inhibitors (antidepressant medicinal products), and other antidepressant medicinal products;
• codeine (a cough medicinal product);
• zidovudine (a medicinal product for HIV);
• medicinal products that prevent blood clotting (e.g., vitamin K antagonists or acetylsalicylic acid), which may increase the risk of bleeding;
• rufinamide (an antiepileptic medicinal product) (caution should be exercised, especially in children);
• propofol (an anesthetic);
• nimodipine (a medicinal product used to treat cerebral disorders);
• clozapine (a medicinal product used to treat psychiatric disorders).

The level of phenytoin (another antiepileptic medicinal product) in the blood may increase in children when they are also taking clonazepam (a benzodiazepine, a medicinal product that alleviates anxiety and tension, and an antiepileptic medicinal product) and valproic acid. During concomitant use of valproic acid and clonazepam, cases of loss of consciousness (prolonged loss of consciousness) have been reported in patients with previous seizures with loss of consciousness (generalized tonic-clonic seizures). Catatonia (a state of rigidity with lack of response to stimuli) occurred in one patient with schizoaffective disorder (a psychiatric disorder) during concomitant use of valproic acid, sertraline (an antidepressant medicinal product), and risperidone (a neuroleptic medicinal product). Additional interactions

• Absenor does not affect the lithium level in the blood.
• The medicinal product does not reduce the effectiveness of hormonal contraceptives (oral contraceptives).
• In diabetic patients, false-positive test results for ketone bodies in the urine may occur, as valproic acid is partially metabolized to ketone bodies.
• The use of other medicinal products that burden liver metabolism may increase the risk of liver damage.
• Reports have been made of symptoms of brain disorder (encephalopathy) and/or increased ammonia levels in the blood (hyperammonemia) due to concomitant use of valproate and topiramate (an antiepileptic medicinal product).
• Concomitant use of Absenor with acetazolamide (a medicinal product for glaucoma) may lead to increased ammonia levels in the blood, with a risk of brain disorder (encephalopathy).
• Concomitant use of valproic acid and phenobarbital or phenytoin increases ammonia levels in the blood; therefore, the physician will closely monitor the patient's condition.
• Concomitant use of valproic acid and quetiapine (a medicinal product used to treat psychiatric disorders) may increase the risk of decreased white blood cell count (leukopenia, neutropenia).
• Absenor may decrease the olanzapine level in the blood (a medicinal product used to treat psychiatric disorders).

The physician will determine whether to stop concomitant use of medicinal products or continue treatment.

Absenor with food, drink, and alcohol

Concomitant consumption of alcohol may weaken or increase the effects of Absenor, as well as increase the risk of adverse reactions. Therefore, the patient should avoid consuming alcohol during treatment. Taking Absenor with food does not significantly affect the bioavailability of the medicinal product. If gastrointestinal irritation occurs at the beginning or during treatment, the tablets should be taken during or after meals.

Pregnancy, breastfeeding, and fertility

Important note for women

Bipolar affective disorder

• In the case of bipolar affective disorder, Absenor should not be used if the patient is pregnant.
• In the case of bipolar affective disorder, if the patient is of childbearing age, Absenor should not be taken unless the patient uses effective contraception (birth control) throughout the entire treatment period with Absenor. The patient should not stop taking Absenor or contraception until they have discussed it with their physician. The treating physician will provide further guidance.

Epilepsy

• In the case of epilepsy, Absenor should not be used if the patient is pregnant, unless there is no alternative treatment.
• In the case of epilepsy, if the woman is of childbearing age, Absenor should not be taken unless the patient uses effective contraception (birth control) throughout the entire treatment period with Absenor. The patient should not stop taking Absenor or contraception until they have discussed it with their physician. The treating physician will provide further guidance.

Risk of taking valproate during pregnancy (regardless of the condition being treated with valproate)

• The patient should immediately consult their physician if they plan to become pregnant or are pregnant.
• Taking valproate during pregnancy carries a risk. The higher the dose, the greater the risk, but no dose is risk-free, even when valproate is used in combination with other antiepileptic medicinal products.
• Valproate may cause severe birth defects and affect the physical and mental development of the child after birth. The most commonly reported birth defects include: spina bifida (when the bones of the spine are not properly developed); developmental abnormalities of the face and skull; developmental abnormalities of the heart, kidneys, urinary tract, and genital organs, limb abnormalities, and many related developmental abnormalities affecting multiple organs and body parts. Birth defects may cause disability, which can be significant.
• Children exposed to valproate in the womb have reported hearing problems or deafness.
• Children exposed to valproate in the womb have reported eye abnormalities, often in combination with other birth defects. Eye abnormalities may affect vision.
• In a group of children born to mothers taking valproate, about 11 out of 100 children will have birth defects. For comparison, birth defects occur in about 2-3 out of 100 children born to women without epilepsy.
• It is estimated that up to 30-40% of children in preschool age, whose mothers took valproate during pregnancy, may exhibit early developmental problems. Children with the condition may start walking and talking later, be less intellectually capable than other children, have language problems, and memory difficulties.
• Children exposed to valproate are more likely to be diagnosed with various autistic disorders. Some evidence suggests that children exposed to valproate may be more likely to develop attention deficit hyperactivity disorder (ADHD).
• Before prescribing this medicinal product, the physician will explain to the patient what may threaten the child if the patient becomes pregnant while taking valproate. If the patient taking this medicinal product decides later that they want to have a child, they should not stop taking Absenor or contraception without discussing it with their physician.
• Parents or guardians of girls treated with valproate should contact the treating physician when their child starts menstruating.
• Some hormonal contraceptives (oral contraceptives containing estrogens) may decrease the valproate level in the blood. The patient should discuss with their physician which contraceptive method is most suitable for them.
• The patient should ask their physician about taking folic acid when trying to become pregnant. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with valproate treatment.
• If the patient took a valproate-containing medicinal product during pregnancy, they should have their blood coagulation parameters (platelets, fibrinogen) and coagulation factors tested, as well as have coagulation tests performed on their newborn, due to possible coagulation disorders.
• Newborns whose mothers took valproate-containing medicinal products during the last three months of pregnancy may experience withdrawal symptoms (such as restlessness, hyperactivity, tremors, convulsions, and feeding disorders).
• Reports have been made of low blood sugar levels in newborns whose mothers took valproate during the last three months of pregnancy.
• Reports have been made of hypothyroidism in newborns whose mothers took valproate for the treatment of epilepsy during pregnancy.

Please select the situation that applies to the patient from the options below and read the relevant information:

• STARTING TREATMENT WITH ABSENOR
• CONTINUING TREATMENT WITH ABSENOR WITHOUT PLANNING PREGNANCY
• CONTINUING TREATMENT WITH ABSENOR WITH PLANNED PREGNANCY
• UNPLANNED PREGNANCY DURING CONTINUING TREATMENT WITH ABSENOR

STARTING TREATMENT WITH ABSENOR

If Absenor is prescribed for the first time, the treating physician will explain the risks to the unborn child if the patient becomes pregnant. Women of childbearing age should ensure that they use effective contraception (birth control) continuously throughout the entire treatment period with Absenor. The patient should consult their physician or a family planning clinic if they need advice on a suitable contraceptive method. Important information:

• Before starting Absenor, the patient should rule out pregnancy using a pregnancy test, the results of which should be confirmed by the treating physician.
• The patient should use effective contraception (birth control) throughout the entire treatment period with Absenor.
• The patient should discuss contraception with their treating physician. The treating physician will provide information on pregnancy prevention and may refer the patient to a specialist for advice on contraception.
• The patient should regularly (at least once a year) visit a specialist experienced in the treatment of bipolar affective disorder or epilepsy. During this visit, the treating physician will ensure that the patient has been well-informed and understands all the risks and advice related to taking valproate during pregnancy.
• The patient should inform their physician if they plan to become pregnant.
• The patient should immediately inform their physician if they are pregnant or suspect they may be pregnant.

CONTINUING TREATMENT WITH ABSENOR WITHOUT PLANNING PREGNANCY

If the patient continues treatment with Absenor and does not plan to become pregnant, they must ensure that they use effective contraception (birth control) continuously throughout the entire treatment period with Absenor. The patient should consult their physician or a family planning clinic if they need advice on contraception.

Important information:

• The patient should use effective contraception (birth control) throughout the entire treatment period with Absenor.
• The patient should discuss contraception with their treating physician. The treating physician will provide information on pregnancy prevention and may refer the patient to a specialist for advice on contraception.
• The patient should regularly (at least once a year) visit a specialist experienced in the treatment of bipolar affective disorder or epilepsy. During this visit, the treating physician will ensure that the patient has been well-informed and understands all the risks and advice related to taking valproate during pregnancy.
• The patient should inform their physician if they plan to become pregnant.
• The patient should immediately inform their physician if they are pregnant or suspect they may be pregnant.

CONTINUING TREATMENT WITH ABSENOR WITH PLANNED PREGNANCY

PREGNANCY

If the patient plans to become pregnant, they should first schedule a visit with their treating physician. The patient should not stop taking Absenor or contraception until they have discussed it with their treating physician. The treating physician will provide further guidance. Children born to mothers who took valproate are at serious risk of birth defects and developmental problems, which can significantly impair the child. The treating physician will refer the patient to a specialist experienced in the treatment of bipolar affective disorder or epilepsy to assess alternative treatment options. The specialist may take actions to ensure the best possible course of pregnancy and minimize the risk to the mother and unborn child. The specialist may decide to change the Absenor dose or switch to another medicinal product, or stop Absenor treatment long before the patient becomes pregnant - to ensure that the condition is stable. The patient should ask their physician about taking folic acid when trying to become pregnant. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with valproate treatment. Important information:

• The patient should not stop taking Absenor unless their physician decides to do so.
• The patient should not stop using contraception before discussing it with their physician and developing a plan of action that ensures control of their condition and minimizes the risks to the child.
• First, the patient should schedule a visit with their treating physician. During this visit, the treating physician will ensure that the patient has been well-informed and understands all the risks and advice related to taking valproate during pregnancy.
• The treating physician will try to switch to another medicinal product or stop Absenor treatment long before the patient becomes pregnant.
• The patient should schedule an urgent visit with their treating physician if they are pregnant or suspect they may be pregnant.

UNPLANNED PREGNANCY DURING CONTINUING TREATMENT WITH ABSENOR

The patient should not stop taking Absenor unless their physician advises them to do so, as their condition may worsen. The patient should schedule an urgent visit with their physician if they are pregnant or suspect they may be pregnant. The treating physician will provide the patient with further guidance. Children born to mothers who took valproate are at serious risk of birth defects and developmental problems, which can significantly impair the child. The patient will be referred to a specialist experienced in the treatment of bipolar affective disorder or epilepsy to assess alternative treatment options. In exceptional cases, when Absenor is the only suitable treatment option during pregnancy, the patient will be closely monitored, both in terms of the underlying condition and fetal development. The patient and their partner will receive counseling and support regarding valproate-exposed pregnancy. The patient should ask their physician about taking folic acid when trying to become pregnant. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with valproate treatment. Important information:

• The patient should schedule an urgent visit with their treating physician if they are pregnant or suspect they may be pregnant.
• The patient should not stop taking Absenor unless their physician advises them to do so.
• The patient must be referred to a specialist experienced in the treatment of epilepsy or bipolar affective disorder to assess the need for alternative treatment options.
• The patient must receive counseling on the risks associated with taking Absenor during pregnancy, including its teratogenic effects (birth defects) and physical and mental developmental disorders in children.
• The patient must be referred to a specialist for prenatal monitoring to detect possible developmental abnormalities.

The patient should read the patient guide provided by their physician.

The treating physician will discuss the annual confirmation form regarding the risks and ask the patient to sign and keep it. The patient will also receive a Patient Card from the pharmacist to remind them of the risks associated with taking valproate during pregnancy.

Breastfeeding Valproic acid passes into breast milk in small amounts. If the patient is breastfeeding, they should consult their physician before taking Absenor. Fertility This medicinal product may affect fertility. Individual case reports have indicated that this effect is usually reversible after discontinuation of treatment and may be dose-dependent. The patient should not stop taking Absenor without consulting their physician. Important note for male patients Possible risk associated with taking valproate during the 3 months before conceptionA study suggests a possible risk of motor disorders and developmental disorders (problems with early childhood development) in children whose fathers were treated with valproate during the 3 months before conception. In this study, such disorders occurred in about 5 out of 100 children whose fathers were treated with valproate, compared to about 3 out of 100 children whose fathers were treated with lamotrigine or levetiracetam (other medicinal products that may be used to treat the patient's condition). The risk to children whose fathers stopped taking valproate at least 3 months (the time needed to produce new sperm) before conception is unknown. The study has limitations, and therefore, it is not clear whether the suggested increased risk of developmental disorders is caused by valproate. The study was not large enough to show what specific types of motor disorders and developmental disorders in children are associated with this risk. As a precaution, the physician will discuss with the patient:

• The possible risk to children whose fathers were treated with valproate
• The need to consider using effective contraception (birth control) during treatment and for 3 months after discontinuation
• The need to consult with the physician when planning to conceive and before stopping contraception
• The possibility of using other treatment methods for the condition, depending on the individual situation

The patient should not donate sperm while taking valproate and for 3 months after discontinuation. If the patient is planning to have children, they should discuss this with their physician. If the patient's partner becomes pregnant while the patient is taking valproate during the 3 months before conception, and the patient has questions about this, they should contact their physician. The patient should not stop taking Absenor without consulting their physician. If the patient stops taking Absenor, their symptoms may worsen. The patient should regularly visit their physician. During such a visit, the physician will discuss with the patient the precautions associated with taking valproate and the possibility of using other treatment methods for their condition, depending on their individual situation. The patient should read the patient guide provided by their physician. The patient will also receive a Patient Card from the pharmacist to remind them of the possible risk associated with taking valproate.

Driving and using machines

The patient should not drive or operate machinery without consulting their physician. At the beginning of treatment with Absenor, especially when taking a higher dose and/or in combination with medicinal products that affect the central nervous system (CNS), symptoms such as drowsiness and/or disorientation have occurred, which, regardless of the underlying condition being treated, may impair the patient's ability to actively participate in traffic or operate machinery. This is especially true when consuming alcohol. The patient should not drive or operate machinery if they experience such symptoms.

Absenor contains sodium and soy lecithin

Absenor 300 mg prolonged-release tablets contain 42 mg of sodium(a major component of table salt) per tablet. This corresponds to 2.1% of the WHO-recommended maximum daily intake of sodium for adults. Absenor 500 mg prolonged-release tablets contain 69 mg of sodium(a major component of table salt) per tablet. This corresponds to 3.5% of the WHO-recommended maximum daily intake of sodium for adults. Absenor 300 mg prolonged-release tablets contain 2.1 mg of soy lecithin(E 322) per tablet. The patient should not take Absenor if they are hypersensitive to peanuts or soy. Absenor 500 mg prolonged-release tablets contain 2.9 mg of soy lecithin(E 322) per tablet. The patient should not take Absenor if they are hypersensitive to peanuts or soy.

3. How to take Absenor

The patient should always take this medicinal product exactly as their physician has told them. If the patient is unsure, they should consult their physician or pharmacist. The patient should not change their medicinal product or dosage without consulting their physician.

Girls and women of childbearing age

Treatment with Absenor should be initiated and supervised by a physician specializing in the treatment of epilepsy or bipolar affective disorder.

Male patients

It is recommended that treatment with Absenor be initiated and supervised by a specialist with experience in the treatment of epilepsy or bipolar affective disorder - see section 2 "Important note for male patients".

Manic episodes:

The daily dose should be determined and checked individually by the treating physician. Initial dose: The recommended initial dose is 750 mg. The dose should be increased as quickly as possible to achieve the smallest effective concentration that provides the desired clinical effect. Average daily dose: The recommended daily doses usually range from 1,000 mg to 2,000 mg. The dose should be adjusted individually according to the clinical picture. Continuation of treatment for mania in bipolar affective disorder should be individually adjusted, using the smallest effective dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequency of side effects is defined as follows:
Very common:
may occur in more than 1 in 10 people
Common:
may occur in up to 1 in 10 people
Uncommon:
may occur in up to 1 in 100 people
Rare:
may occur in up to 1 in 1,000 people
Very rare:
may occur in up to 1 in 10,000 people
Frequency not known:
frequency cannot be estimated from the available data

If the patient experiences any of the following serious side effects, they should immediately contact a doctor, as the patient may urgently need medical attention:

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

If any of the following side effects worsen or persist for more than a few days, the patient should tell their doctor or pharmacist; treatment may need to be instituted:

Frequency not known: darker areas of skin and mucous membranes (hyperpigmentation).

Other side effects

Benign, malignant, and unspecified tumors (including cysts and polyps)

Rare: bone marrow precursor cell disorder (myelodysplastic syndrome, shown in blood tests).

Blood and lymphatic system disorders

Common: reduced red blood cell count (anemia), platelet count (thrombocytopenia), or significantly reduced white blood cell count (leukopenia).
Uncommon: significantly reduced count of all blood cells (pancytopenia).
Rare: bone marrow dysfunction with reduced white blood cell count (lymphopenia, neutropenia), significantly reduced count of certain white blood cells (agranulocytosis), with a lack of red blood cells (aplasia), or enlarged red blood cells (macrocytosis) at their normal or reduced count (macrocytic anemia). This is visible in blood morphology and sometimes causes symptoms such as fever and breathing difficulties.

Endocrine disorders

Uncommon: increased levels of antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH), excessive hair growth on the body in women, appearance of male characteristics in women, acne, male pattern baldness, and (or) increased androgen levels.
Rare: hypothyroidism, which can cause feelings of fatigue or weight gain.

Metabolic and nutritional disorders

Very common: isolated, moderate increase in blood ammonia levels (hyperammonemia) without changes in liver function test results, but sometimes with symptoms from the central nervous system, such as balance and coordination problems, drowsiness, or decreased alertness, with accompanying vomiting (see also section 2 "Warnings and precautions").
Common: weight gain (a risk factor for the development of ovarian cysts) or weight loss, increased appetite or loss of appetite, decreased sodium levels in the blood (hyponatremia), which can cause disorientation.
Rare: obesity.

Psychiatric disorders

Common: confusion, hallucinations (seeing, feeling, or hearing things that do not actually exist), aggression, restlessness, attention disorders.
Uncommon: irritability, hyperactivity.
Rare: atypical behavior, learning disorders, psychomotor hyperactivity. These side effects were mainly observed in children.

Nervous system disorders

Very common: tremors.
Common: extrapyramidal disorders (movement disorders related to brain function, such as uncontrolled muscle movements; partially irreversible), stupor, drowsiness, seizures (convulsions), memory disorders, headaches, involuntary eye movements (nystagmus), dizziness, tingling, and sensation of non-existent sensations (paresthesia).
Uncommon: coma, brain function disorders (encephalopathy), lethargy, parkinsonism that disappears after discontinuation of valproic acid treatment, increased muscle tension (spasticity), coordination disorders (ataxia), e.g., gait instability, worsening of seizures (see also section 2 "Warnings and precautions"). Symptoms of brain function disorders (encephalopathy) were observed shortly after the administration of valproic acid-containing drugs. These symptoms disappeared after the drug was discontinued. Sometimes they were associated with increased ammonia levels and phenobarbital in combination therapy with phenobarbital.
Rare: double vision, clear cognitive impairment (dementia), which is transient after treatment discontinuation and may be transient after dose reduction; slight cognitive impairment (cognitive disorder).
Rarely, cases of brain diseases (chronic encephalopathy) with brain function and mental performance disorders, especially after the use of higher doses or in combination with other antiepileptic drugs, have been reported.
Frequency not known: sedation.
Cases of stupor and lethargy progressing to transient coma or brain function disorders (encephalopathy) have been reported. Sometimes they were associated with an increased frequency of seizures. These cases occurred especially during concomitant use of phenobarbital or topiramate or after rapid dose escalation. Symptoms disappeared after dose reduction or treatment discontinuation.
After long-term treatment with Absenor, especially when administered with phenytoin (another antiepileptic drug), symptoms of brain function disorders (encephalopathy) may occur: increased seizures, apathy, stupor, decreased muscle tone (hypotonia), and serious general changes in brain function (EEG).

Ear and labyrinth disorders

Common: hearing loss (partially irreversible).
Frequency not known: ringing in the ears (tinnitus).

Vascular disorders

Common: spontaneous bruising or bleeding (see also "Warnings and precautions" and "Pregnancy, breastfeeding, and fertility").
Uncommon: vasculitis.

Gastrointestinal disorders

Very common: nausea.
Common: vomiting, gum disorders (mainly gum hypertrophy), inflammation of the oral mucosa (pain, swelling, ulcers, and burning in the mouth), diarrhea, especially at the beginning of treatment, discomfort in the upper abdomen that usually disappears within a few days despite continued treatment.
Uncommon: pancreatic damage, sometimes leading to death (see also "Warning" in section 2 "Warnings and precautions"), excessive saliva production (especially at the beginning of treatment).

Hepatobiliary disorders

Common: dose-dependent, severe (sometimes fatal) liver damage (see also "Warning" in section 2 "Warnings and precautions").

Skin and subcutaneous tissue disorders

Common: hypersensitivity, transient and (or) dose-dependent hair loss, nail disorders, and nail bed disorders.
Uncommon: edema (angioedema) with painful, itchy blisters, usually involving the eyes, lips, throat, and sometimes hands, feet, and genitals, rash, hair changes (e.g., changes in hair structure, hair color change, abnormal hair growth).
Rare: severe skin reactions: blistering, peeling, or bleeding from various parts of the body (including lips, eyes, mouth, nose, genitals, hands, or feet) with or without rash, sometimes with flu-like symptoms such as fever, chills, or muscle pain (Stevens-Johnson syndrome or toxic epidermal necrolysis or Lyell's syndrome), skin rash (especially on hands or soles) or skin changes with a pink/red ring and a pale center, which may be itchy, peeling, or fluid-filled (erythema multiforme), drug-induced rash with fever and lymph node swelling, and possible dysfunction of other organs (DRESS syndrome).

Musculoskeletal and connective tissue disorders

Reports of cases have been made from decreased bone density (osteopenia and osteoporosis) to bone fractures.
A doctor or pharmacist should be consulted if the patient has been taking antiepileptic drugs for a long time, has osteoporosis, or is taking corticosteroids or other steroids at the same time.
Rare: an immune system reaction against the body's own connective tissue with symptoms such as joint pain, fever, fatigue, and rash (systemic lupus erythematosus, see also "Warnings and precautions"), severe muscle breakdown with accompanying pain and muscle weakness (rhabdomyolysis).

Renal and urinary disorders

Common: urinary incontinence (involuntary urination).
Uncommon: kidney failure, which may manifest as reduced urine excretion.
Rare: bedwetting or increased need to urinate, kidney inflammation (tubulointerstitial nephritis), kidney function disorders (Fanconi syndrome) with excretion of phosphate, glucose, and some proteins, and excessive acidity in the body (metabolic acidosis).

Reproductive system and breast disorders

Common: painful menstruation.
Uncommon: irregular menstruation or absence of menstruation.
Rare: infertility in men, usually transient after treatment discontinuation and may be transient after dose reduction. Treatment should not be discontinued without prior consultation with a doctor. Increased testosterone levels in the blood, ovarian cysts (polycystic ovary syndrome).

Congenital, familial, and genetic disorders

(see section "Pregnancy, breastfeeding, and fertility").

General disorders and administration site conditions

Uncommon: low body temperature (hypothermia), fluid retention in the upper and (or) lower limbs (peripheral edema).

Investigations

Rare: blood coagulation disorders, identified based on changes in laboratory test results for blood coagulation (see also sections "Warnings and precautions" and "Pregnancy, breastfeeding, and fertility"). Decreased levels of vitamin B7 in the body (biotin deficiency).

Additional information

If dose-independent side effects occur, such as symptoms of liver or pancreas damage (see also the warning in section 2: "Important information before using Absenor"), the doctor should be informed immediately. The doctor will decide whether to continue treatment with Absenor.

Additional side effects in children and adolescents

Some side effects of valproate occur more frequently in children or have a more severe course than in adults. These include liver damage, pancreatitis, aggression, excitement, attention disorders, atypical behavior, psychomotor hyperactivity, and learning disorders.

Reporting side effects

If any side effects occur, including any side effects not listed in this leaflet, the doctor or pharmacist should be informed. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, more information can be collected on the safety of the drug.

5. How to store Absenor

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of the month.
Store at a temperature below 25°C.
Tablets can be stored in a tablet box for a week at a temperature below 25°C.
Store the bottle tightly closed to protect from moisture.
Medicines should not be disposed of via wastewater or household waste. A pharmacist should be asked 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 Absenor contains

• The active substance of the drug is sodium valproate.
• Absenor, 300 mg: one tablet contains 300 mg of sodium valproate.
• Absenor, 500 mg: one tablet contains 500 mg of sodium valproate.
• Other ingredients of the tablet core are: copovidone, hypromellose, colloidal silica, anhydrous, magnesium stearate.
• Coating ingredients: polyvinyl alcohol, titanium dioxide (E 171), talc, soy lecithin (E 322), xanthan gum.

What Absenor looks like and contents of the pack

Absenor, 300 mg: white or almost white, round, convex, prolonged-release tablets, 12.5 mm in diameter.
Absenor, 500 mg: white or almost white, capsule-shaped, prolonged-release tablets, 9.8 x 20.7 mm in size.
Pack size: 100 tablets.

Marketing authorization holder

Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland

Manufacturer

Orion Corporation, Orion Pharma
Orionintie 1
FI-02200 Espoo
Finland
Orion Corporation Orion Pharma
Joensuunkatu 7
FI-24100 Salo
Finland
To obtain more detailed information about this medicinal product, please contact the local representative of the marketing authorization holder:
Orion Pharma Poland Sp. z o.o.
kontakt@orionpharma.info.pl

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

Lithuania, Latvia, Poland: Absenor
Germany: Valproat Orion 300 mg Retardtabletten, Valproat Orion 500 mg Retardtabletten
Date of last revision of the leaflet:02.2025
Detailed and up-to-date information on the use of this product is available by scanning the QR code on the patient leaflet with a smartphone. The same information is available on the website: qr.orionproductsafety.com/valproate/PL
QR code to the website: qr.orionproductsafety.com/valproate/PL