Convulex

Patient Information Leaflet

Convulex 150, 150 mg, soft capsules
Convulex 300, 300 mg, soft capsules
Convulex, 500 mg, soft capsules
Valproic acid

This medicinal product is subject to additional monitoring. This will allow rapid identification of

new safety information. You can help by reporting any side effects you experience while taking this medicine. For information on how to report side effects – see section 4.

WARNING
Convulex (valproate) taken during pregnancy can harm the unborn child. Women of childbearing potential must use an effective method of contraception (birth control) continuously throughout the entire duration of Convulex treatment. Your doctor will discuss this with you and you should also follow the recommendations given in section 2 of this leaflet.
You should contact your doctor immediately if you are planning a pregnancy or if you suspect you may be pregnant.
Do not stop taking Convulex unless your doctor tells you to, as your condition may worsen.

Please read 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 consult your doctor or pharmacist.
• 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.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

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

1. What Convulex is and what it is used for

Convulex contains the active substance valproic acid, which belongs to a group of medicines called antiepileptic drugs and acts on the central nervous system.
The medicine has anticonvulsant activity in various forms of epilepsy in humans.
Convulex is a medicine used in the treatment of epilepsy and mania.
Convulex is used to treat:

• epilepsy with generalized seizures:
  • myoclonic seizures,
  • tonic-clonic seizures,
  • atonic seizures,
• absence seizures, partial seizures:
• simple or complex partial seizures,
• secondarily generalized seizures,
• Lennox-Gastaut syndrome.
  • mania, a condition in which the patient feels extremely excited, elated, agitated, enthusiastic, or hyperactive. Mania occurs in a disorder known as bipolar affective disorder. Convulex may be used when lithium cannot be administered.

2. Important information before using Convulex

When not to use Convulex
Do not use this medicine if:

• the patient is allergic to the active substance, valproic acid, or to any of the other ingredients of this medicine (listed in section 6),
• the patient has acute or chronic hepatitis,
• the patient has had severe hepatitis, particularly drug-induced hepatitis, or if there is a family history of severe hepatitis,
• the patient has porphyria (a very rare metabolic disorder),
• concurrent use with mefloquine,
• the patient has a genetic disorder causing mitochondrial disorders (e.g. patients with Alpers-Huttenlocher syndrome),
• the patient has metabolic disorders, e.g. urea cycle disorders,
• the patient has carnitine deficiency (a very rare metabolic disorder) which is untreated,
• for treatment of bipolar affective disorder:
  • if the patient is pregnant,
  • if the patient is of childbearing age, unless she uses an effective method of contraception throughout the entire treatment period with Convulex. Do not stop taking Convulex or contraception without first discussing it with your doctor. Your doctor will provide further advice (see below "Pregnancy, breastfeeding and fertility – Important advice for women").
• for epilepsy:
  • if the patient is pregnant, unless no other therapy is effective,
  • if the patient is of childbearing age, unless she uses an effective method of contraception throughout the entire treatment period with Convulex. Do not stop taking Convulex or contraception without first discussing it with your doctor. Your doctor will provide further advice (see below "Pregnancy, breastfeeding and fertility – Important advice for women").

Warnings and precautions
Before starting treatment with Convulex, discuss this with your doctor.
YOU MUST IMMEDIATELY INFORM YOUR DOCTOR IF:

• Sudden onset of the following symptoms occurs: weakness, loss of appetite, drowsiness, recurrent vomiting and abdominal pain, jaundice (yellowing of the skin and whites of the eyes), or recurrence of epileptic seizures, especially during the first 6 months of treatment. Convulex may cause severe liver damage, sometimes leading to death. Liver function tests should be performed periodically before starting treatment and during the first 6 months of treatment.

The risk of liver damage increases if Convulex is used in children under 3 years of age, in patients taking other antiepileptic drugs simultaneously, in patients with other neurological or metabolic disorders, and in patients with severe epilepsy.

• Severe abdominal pain occurs. Convulex very rarely may cause severe pancreatitis, sometimes fatal.
• The patient or their child taking Convulex develops problems with balance and coordination, drowsiness or reduced alertness, or vomiting. This may be due to increased blood ammonia levels.
• A small number of patients taking antiepileptic medicines containing valproic acid have had thoughts of harming themselves or suicide. If such thoughts occur, contact your doctor immediately.
• Serious skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, and angioedema, have been reported with valproate treatment. If the patient notices any of the symptoms associated with these serious skin reactions described in section 4, they should seek medical advice immediately.

Before starting treatment with this medicine, discuss the following with your doctor:

• Valproic acid should not be used in women with epilepsy who are planning pregnancy, except when other treatments are ineffective or not tolerated. The benefits of treatment should be weighed against the risks before first prescribing the medicine or when a woman treated with valproic acid is planning pregnancy. Women of childbearing age must use effective contraception during treatment.
• Before starting treatment, prior to surgery, or in case of bruises or spontaneous bleeding, laboratory tests are recommended (blood count with smear, including platelet count, bleeding time, and coagulation tests).
• Use with caution in patients with renal impairment. Your doctor may recommend a lower dose.
• Use with caution in patients with systemic lupus erythematosus.
• If any metabolic disorder is suspected in the patient, especially inherited enzyme deficiencies such as "urea cycle disorders," due to the risk of increased blood ammonia levels.
• Weight gain may occur in patients treated with valproic acid.
• If the patient has a rare disorder called "carnitine palmitoyltransferase II deficiency," due to increased risk of muscle disorders.
• Concomitant use of carbapenem antibiotics with valproic acid is not recommended (see section "Convulex and other medicines").
• Valproic acid is mainly excreted by the kidneys, partly in the form of ketone bodies, therefore in diabetic patients, tests for ketone bodies may give false positive results.
• If the patient has a family history or the doctor suspects a genetic disorder caused by mitochondrial dysfunction, due to the risk of liver damage.
• As with other antiepileptic drugs, seizures may worsen in frequency or severity during treatment. If seizures worsen, consult your doctor immediately.
• If the patient has inadequate intake of carnitine, found in meat and dairy products, particularly in children under 10 years of age,
• If the patient has carnitine deficiency and is taking carnitine supplements.
• If the patient has previously experienced severe skin rash, skin peeling, blistering and/or oral ulcers after taking valproate.

Children and adolescents
Children and adolescents under 18 years of age:
Convulex should not be used in children and adolescents under 18 years of age for the treatment of mania.

Convulex and other medicines
Tell your doctor about all medicines currently or recently taken, and any medicines you plan to take.
Some medicines may affect the action of valproic acid, and valproic acid may also affect the action of other medicines.
These include:

• neuroleptics, including quetiapine, olanzapine (used to treat psychotic disorders);
• antidepressants, including MAO inhibitors;
• benzodiazepines (used to treat insomnia and anxiety disorders);
• other antiepileptic medicines, including phenobarbital, phenytoin, primidone, lamotrigine, carbamazepine, felbamate, topiramate, rufinamide;
• cannabidiol (used to treat epilepsy and other conditions);
• certain anticancer medicines containing pivampicillin (such as pivampicillin, adefovir dipivoxil);
• methotrexate (used to treat cancer and inflammatory diseases);
• zidovudine, ritonavir and lopinavir (used to treat HIV infection and AIDS);
• mefloquine (used to treat and prevent malaria);
• salicylates (acetylsalicylic acid);
• anticoagulants;
• cimetidine (used to treat gastric ulcers);
• erythromycin, rifampicin;
• carbapenems (antibiotics used to treat bacterial infections);
• cholestyramine (used to lower blood cholesterol levels);
• propofol (used for general anaesthesia);
• nimodipine;
• medicines containing oestrogen (including some contraceptives);
• metamizole, used to treat pain and fever;
• clozapine (used to treat psychiatric disorders).

These medicines may affect the action of valproic acid and vice versa. It may be necessary to adjust the dose of these medicines or use alternative treatments. Your doctor will inform you of any changes in treatment.
Your doctor will also provide additional information about medicines that should be used with caution or avoided during treatment with Convulex.

Convulex with food, drink and alcohol
Convulex may be taken with or after food.
Alcohol consumption is not recommended during treatment with this medicine.

Pregnancy, breastfeeding and fertility
Pregnancy
Important advice for women
Bipolar affective disorder

• Do not use Convulex if the patient is pregnant.
• Women of childbearing age must not take Convulex unless they use an effective method of contraception (birth control) throughout the entire treatment period with Convulex. Do not stop taking Convulex or contraception without first discussing it with your doctor. Your doctor will provide further advice.

Epilepsy

• Do not use Convulex if the patient is pregnant, unless no other therapy is effective.
• Women of childbearing age must not take Convulex unless they use an effective method of contraception throughout the entire treatment period with Convulex. Do not stop taking Convulex or contraception without first discussing it with your doctor. Your doctor will provide further advice.

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

• Consult your doctor immediately if you are planning pregnancy or are pregnant.
• Taking valproic acid during pregnancy carries risks. The higher the dose, the greater the risk, but no dose is completely risk-free, even when valproic acid is used in combination with other antiepileptic drugs.
• Valproic acid may cause serious congenital malformations and affect the physical and mental development of the child after birth. The most common congenital malformations include: spina bifida (when the spinal bones do not develop properly); facial and cranial developmental defects; heart, kidney, urinary tract and genital organ malformations; limb defects and multiple associated developmental defects affecting several organs and body parts. Congenital malformations may lead to disability, which may be significant.
• Hearing problems or deafness have been reported in children exposed to valproic acid in utero.
• Eye developmental defects together with other congenital malformations have been reported in children exposed to valproate in utero. Eye developmental defects may affect vision.
• Pregnant women taking valproic acid have an increased risk of giving birth to a child with congenital malformations requiring treatment. Valproic acid has been used for many years, so it is known that in the group of children born to mothers taking valproic acid, about 11 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 30-40% of preschool-aged children whose mothers took valproic acid 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.
• Autism spectrum disorders are more frequently diagnosed in children exposed to valproic acid in utero. Some evidence suggests an increased risk of attention deficit/hyperactivity disorder (ADHD) in these children.
• Before prescribing this medicine, your doctor will explain the risks to the unborn child if you become pregnant while taking valproic acid. If you are taking this medicine and decide you want to have a child, do not stop taking the medicine or contraception on your own; discuss it with your doctor first.
• Some contraceptives (oral contraceptives containing oestrogen) may reduce blood levels of valproic acid. Discuss with your doctor the most appropriate method of contraception for you.
• Parents or guardians of girls treated with valproic acid should contact the treating doctor when their child starts menstruation.
• Ask your doctor about taking folic acid when planning pregnancy. Folic acid may reduce the general risk of spina bifida and early miscarriage, which affects all pregnancies. However, it is unlikely that folic acid supplementation reduces the risk of congenital malformations associated with valproic acid treatment.

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

• STARTING TREATMENT WITH CONVULEX
• CONTINUING TREATMENT WITH CONVULEX WITHOUT PLANNING PREGNANCY
• CONTINUING TREATMENT WITH CONVULEX WHILE PLANNING PREGNANCY
• BECOMING PREGNANT DURING CONTINUATION OF TREATMENT WITH CONVULEX

STARTING TREATMENT WITH CONVULEX
If Convulex is being prescribed for the first time, your doctor will explain the risks to the unborn child if you become pregnant. Women of childbearing age should ensure they use an effective method of contraception continuously throughout the entire treatment period with Convulex. If you need advice on contraception, consult your doctor or a family planning clinic.
Important information:

• Before starting Convulex, the patient should confirm she is not pregnant using a pregnancy test, the result of which should be confirmed by the treating doctor.
• The patient should use an effective method of contraception throughout the entire treatment period with Convulex.
• Discuss with your doctor the appropriate method of contraception. Your doctor will provide information on pregnancy prevention and may refer you to a specialist for contraception advice.
• You should have regular visits (at least once a year) with the specialist treating your bipolar disorder or epilepsy. During this visit, the doctor will ensure you have been adequately informed and understand all risks and advice related to valproic acid use during pregnancy.
• If you are planning to have a child, inform your doctor.
• If you are pregnant or suspect you may be pregnant, inform your doctor immediately.

CONTINUING TREATMENT WITH CONVULEX WITHOUT PLANNING PREGNANCY
If the patient continues treatment with Convulex and does not plan pregnancy, she must be certain she uses an effective method of contraception continuously throughout the entire treatment period with Convulex. If you need advice on contraception, consult your doctor or a family planning clinic.
Important information:

• The patient should use an effective method of contraception throughout the entire treatment period with Convulex.
• Discuss contraception (birth control method) with your doctor. Your doctor will provide information on pregnancy prevention and may refer you to a specialist for contraception advice.
• You should have regular visits (at least once a year) with the specialist treating your bipolar disorder or epilepsy. During this visit, the doctor will ensure you have been adequately informed and understand all risks and advice related to valproic acid use during pregnancy.
• If you are planning to have a child, inform your doctor.
• If you are pregnant or suspect you may be pregnant, inform your doctor immediately.

CONTINUING TREATMENT WITH CONVULEX WHILE PLANNING PREGNANCY
If you are planning to have a child, you should first schedule an appointment with your doctor.
Do not stop taking Convulex or contraception until you have discussed it with your doctor. Your doctor will provide further advice.
Children born to mothers who took valproate have a high risk of congenital malformations and developmental problems, which may significantly impair the child. Your doctor will refer you to a specialist experienced in treating bipolar disorder or epilepsy to appropriately evaluate alternative treatment options. The specialist may take steps to ensure the best possible pregnancy outcome and minimise risks to mother and unborn child.
The treating specialist may decide to change the dose of Convulex, switch to another medicine, or discontinue Convulex treatment well before conception to ensure the disease is stable.
Ask your doctor about taking folic acid when planning pregnancy. Folic acid may reduce the general risk of spina bifida and early miscarriage, which affects all pregnancies. However, it is unlikely that folic acid supplementation reduces the risk of congenital malformations associated with valproic acid treatment.
Important information:

• Do not stop treatment with Convulex unless your doctor advises it.
• Do not stop using contraception methods before talking to your doctor and jointly developing a management plan that ensures control of your condition and reduces risks to the child.
• First, schedule an appointment with your doctor. During this visit, the doctor will ensure you have been adequately informed and understand all risks and advice related to valproic acid use during pregnancy.
• Your doctor will try switching to another medicine or discontinuing Convulex treatment well before conception.
• If you are pregnant or suspect you may be pregnant, schedule an urgent appointment with your doctor.

BECOMING PREGNANT DURING CONTINUATION OF TREATMENT WITH CONVULEX
Do not stop treatment with Convulex without first discussing it with your doctor, as your health condition may worsen. If you are pregnant or suspect you may be pregnant, schedule an urgent appointment with your doctor. Your doctor will provide further advice.
Children born to mothers who took valproic acid have a high risk of congenital malformations and developmental problems, which may significantly impair the child.
You will be referred to a specialist experienced in treating bipolar disorder or epilepsy to evaluate alternative treatment options.
In exceptional circumstances, when Convulex is the only available treatment option during pregnancy, you will be closely monitored for both your underlying condition and fetal development. You and your partner will receive counselling and support regarding valproic acid-exposed pregnancy.
Ask your doctor about taking folic acid. Folic acid may reduce the general risk of spina bifida and early miscarriage, which affects every pregnancy. However, it is unlikely that folic acid supplementation reduces the risk of congenital malformations associated with valproic acid treatment.
Important information:

• If you are pregnant or suspect you may be pregnant, schedule an urgent appointment with your doctor.
• Do not stop treatment with Convulex unless your doctor advises it.
• Ensure you are referred to a specialist experienced in treating epilepsy or bipolar disorder to evaluate the need for alternative treatment methods.
• You must receive counselling on the risks of using Convulex during pregnancy, including its teratogenic effects (causing congenital malformations) and physical and mental developmental disorders in children.
• Ensure you are referred to a specialist in prenatal monitoring to detect possible developmental abnormalities.

Newborns of mothers who took Convulex during pregnancy may experience bleeding disorders, hypoglycaemia, hypothyroidism, and withdrawal symptoms such as irritability, restlessness, tremors, seizures, and feeding difficulties.
You should read the patient guide provided by your doctor. Your doctor will discuss the annual risk acknowledgement form and ask you to sign and keep it. You will also receive a patient card from the pharmacist as a reminder of the risks associated with valproic acid use during pregnancy.

Important advice for male patients
Possible risks associated with taking valproate during the 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 during the 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 whose fathers were treated with lamotrigine or levetiracetam (other medicines that may be used to treat the patient's condition). The risk in children whose fathers discontinued valproate treatment at least 3 months before conception (the time required for new sperm production) is unknown. The study has limitations, and therefore 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 associated with this risk.
As a precaution, your doctor will discuss with you:

• the possible risks for children whose fathers were treated with valproate;
• the need to consider using effective contraception (birth control) by both the patient and his partner during treatment and for 3 months after stopping treatment;
• the need to consult your doctor when planning conception and before stopping contraception;
• the possibility of using alternative treatment methods for the disease, depending on individual circumstances.

Do not donate sperm while taking valproate and for 3 months after stopping it.
If planning parenthood, discuss this with your doctor.
If your partner becomes pregnant while you are taking valproate during the 3 months before conception and you have questions, contact your doctor. Do not stop treatment without consulting your doctor, as symptoms may worsen.
You should have regular visits with the doctor who prescribed the medicine. During these visits, the doctor will discuss precautions related to valproate use and the possibility of alternative treatment methods for your condition, depending on your individual situation.
You should read the patient guide provided by your doctor. You will also receive a patient card from the pharmacist as a reminder of the possible risks associated with valproate use.

Breastfeeding
Valproic acid passes into breast milk in small amounts. Consult your doctor whether breastfeeding is possible during treatment.

Driving and operating machinery
Some patients may experience drowsiness during treatment, especially when taking several antiepileptic medicines or when benzodiazepines are used concomitantly. Before driving or operating machinery, the patient should ensure how they react to the treatment.

Convulex contains sorbitol
Convulex 150 contains up to 5.3 mg of sorbitol per capsule.
Convulex 300 contains up to 8.7 mg of sorbitol per capsule.
Convulex 500 mg contains up to 14.3 mg of sorbitol per capsule.

3. How to use Convulex

Convulex must always be used as directed by the physician. If in doubt, consult your doctor.
Girls and women of childbearing age
Treatment with Convulex 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 with Convulex 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.
This medicine should always be used according to the doctor's instructions. If in doubt, consult your doctor or pharmacist.
The dosage and duration of treatment will be determined by the doctor.
Other strengths and pharmaceutical forms of Convulex are also available, which may be important when adjusting the dose.
This formulation is not suitable for children under 6 years of age (risk of choking).
If indicated, Convulex 150 or Convulex 300, or Convulex capsules, may be used in children with body weight above 17 kg, provided they are able to swallow capsules.
The capsules should be swallowed whole with sufficient fluid, with or after a meal.

Epilepsy
Treatment usually starts with a low dose, which is gradually increased by the doctor until the optimal dose is reached.
The daily dose is usually divided into several doses. However, if valproic acid is used as monotherapy, the doctor may recommend taking a single daily dose in the evening.

Monotherapy
Adults: The initial dose is 5 to 10 mg/kg body weight per day. The dose is then increased by 5 mg of valproic acid per kg of body weight every 3 to 7 days until seizure control is achieved. This is usually achieved at a dose of 20 to 30 mg/kg body weight per day. If the desired effect is not achieved with this dose, it may be increased up to 2500 mg of valproic acid per day.

Use in children and adolescents
Children with body weight above 20 kg: In children, treatment starts with a daily dose of 10 to 20 mg of valproic acid per kg of body weight, which is then increased to 20–30 mg of valproic acid per kg of body weight per day.
Children with body weight below 20 kg: Other pharmaceutical forms of Convulex are available for use in children with body weight below 20 kg (e.g. drops or syrup).
The table below serves as a general dosing guideline.

Use in patients with kidney and (or) liver disease
The physician may decide whether dose adjustment is necessary in a patient.
Combination therapy
If Convulex is added to an already ongoing antiepileptic treatment, the physician's instructions must be followed very carefully.
Bipolar disorder (manic-depressive illness) (adult patients only):
The initial dose is 600 to 900 mg per day, divided into several doses. Depending on the severity of symptoms, the physician may recommend a dose of up to 1500 mg per day. The physician may increase the dose based on blood levels of the active substance. The recommended daily maintenance dose is 1000 to 2000 mg.
Mania
The daily dose should be individually determined and monitored by the treating physician.
Initial dose
The recommended initial daily dose is 750 mg.
Average daily dose
The average daily dose usually ranges from 1000 mg to 2000 mg.
Use of higher than recommended doses of Convulex
Symptoms of acute overdose include: nausea, vomiting, dizziness, and sometimes serious adverse effects on the central nervous system and breathing difficulties. In severe cases, immediate medical assistance is required.
Information for physicians:
In case of overdose, hospital management should include induction of vomiting, gastric lavage, respiratory support, and other life-sustaining measures.
In the most severe cases, hemodialysis or even exchange transfusion may be necessary. In individual cases, naloxone has been effective.
Missed dose of Convulex
If a dose is missed, do not take a double dose to make up for the missed dose; instead, continue treatment according to the physician's instructions.
Discontinuation of Convulex treatment
Do not change the dose of the medication without consulting the physician.
Do not discontinue treatment without prior consultation with the physician, otherwise the therapeutic progress achieved may be lost and disease relapses may occur.

4. Possible side effects

Like all medicines, Convulex may cause side effects, although not everyone gets them.
However, patients may require appropriate treatment if certain side effects occur.
If any of the following serious side effects occur, contact a doctor immediately, as the patient may urgently require medical assistance:

• Seizures, encephalopathy (brain damage), lethargy (a state of inertia and lack of response to stimuli), changes in behaviour with or without association, increased frequency or severity of epileptic seizures, especially when used concomitantly with phenobarbital or during abrupt dose reduction of Convulex
• Confusion, weakness, dizziness, nausea, vomiting, which may be caused by low sodium levels in the blood or a condition called "SIADH" (Syndrome of Inappropriate Secretion of ADH) or inappropriate antidiuretic hormone secretion syndrome
• Problems with balance and coordination, drowsiness or reduced alertness, combined with vomiting. This may be due to increased blood ammonia levels (hyperammonemia)
• Increased number and severity of seizures
• Extreme fatigue, weakness, loss of appetite, drowsiness, recurrent vomiting and abdominal pain, severe upper abdominal pain, nausea, jaundice (yellowing of the skin and whites of the eyes), leg swelling or increased frequency of epileptic seizures, or general malaise – these symptoms may indicate liver or pancreas damage
• Allergic reactions, which may manifest as:
  o Skin blistering with peeling (formation of blisters, skin peeling or bleeding from various body parts including lips, eyes, mouth, nose, genital organs, palms or soles), with or without rash, sometimes accompanied by flu-like symptoms such as fever, chills or muscle pain – these may be symptoms of conditions known as "toxic epidermal necrolysis" or "Stevens-Johnson syndrome"
  o Skin rash or skin changes with red/rose-coloured rings and pale centres, which may be itchy, peeling or fluid-filled. The rash may appear especially on palms or soles. These may be symptoms of a disease called "erythema multiforme"
  o Allergy-induced swelling with painful, itchy swellings (most often around the eyes, lips, throat, and sometimes hands and feet) – these may be symptoms of "angioedema"
  o Syndrome with skin rash, fever, swollen lymph nodes and possible damage to other organs – these may be symptoms of a condition known as "DRESS" (Drug Reaction with Eosinophilia and Systemic Symptoms) or drug-induced hypersensitivity syndrome
• Blood clotting disorders confirmed by laboratory tests, which may cause spontaneous bruising and bleeding
• Significant decrease in white blood cells or bone marrow failure (myelodysplastic syndrome) shown in blood tests, sometimes presenting with fever and breathing difficulties
• Hypothyroidism, which may cause fatigue or weight gain
• Joint pain, fever, fatigue, rash. These may be symptoms of systemic lupus erythematosus
• Tremors, gait disturbances, muscle stiffness, impaired body coordination (parkinsonism, extrapyramidal disorders, ataxia)
• Muscle pain and weakness (rhabdomyolysis – breakdown of striated muscles)
• Breathing difficulties, chest pain or pressure (especially during inhalation), shortness of breath and dry cough due to fluid accumulation around the lungs (pleural effusion)
• Kidney disease (renal failure, interstitial nephritis), which may present as reduced urine output

If any of the following side effects worsen or persist for more than several days, inform your doctor or pharmacist; treatment may be necessary.
The side effects are listed according to the following frequency classification:

Very common (may affect more than 1 in 10 people):

• tremor
• nausea

Common (may affect up to 1 in 10 people):

• anaemia (reduced number of red blood cells), thrombocytopenia (reduced number of platelets, increasing the risk of bleeding and bruising)
• stupor, drowsiness, seizures, memory disturbances, nystagmus (rapid, uncontrolled eye movements), dizziness
• hearing impairment
• vomiting, stomach pain, diarrhoea (frequent at the beginning of treatment in some patients), usually transient and resolving after a few days without the need to discontinue treatment
• abnormalities affecting the gums (mainly gingival hyperplasia), stomatitis (inflammation of the mouth)
• transient and/or dose-dependent hair loss, nail disorders and nail bed abnormalities
• weight gain, which should be monitored as it may be associated with polycystic ovary syndrome
• irregular menstrual cycles
• confusion, hallucinations, aggression, agitation, attention disorders
• urinary incontinence

Uncommon (may affect up to 1 in 100 people):

• leukopenia (significant decrease in white blood cells), pancytopenia (significant decrease in blood cells, which may cause weakness, easy bruising or increased susceptibility to infections)
• tingling and numbness in hands or feet
• rash, hair abnormalities (such as abnormal hair structure, changes in hair colour, abnormal hair growth)
• decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term Convulex therapy
• hyperandrogenism (excessive male-pattern hair growth, virilization, acne, male-pattern baldness and/or elevated androgen levels)
• vasculitis (inflammation of blood vessels)
• decreased body temperature, mild oedema of feet and legs
• absence of menstruation

Rare (may affect up to 1 in 1000 people):

• macrocytic anaemia (low number of red blood cells), macrocytosis (abnormal enlargement of red blood cells)
• biotin deficiency / biotinidase deficiency
• excessive urination and thirst (Fanconi syndrome)
• involuntary urination (nocturnal enuresis)
• obesity
• male infertility, which is usually transient after discontinuation of treatment and may be transient
• polycystic ovary syndrome
• unusual behaviour, psychomotor hyperactivity, learning difficulties (observed in children and adolescents)
• transient obtundation associated with transient brain atrophy, cognitive disturbances
• double vision

Frequency not known (frequency cannot be estimated from available data):

• congenital disorders, familial and/or genetic diseases
• decreased carnitine levels (visible in blood and muscle tests)
• darker areas of skin and mucous membranes (hyperpigmentation)

Additional side effects in children
Some valproate-related side effects occur more frequently or are more severe in children than in adults. These include liver damage, pancreatitis, aggression, agitation, attention disorders, abnormal behaviour, hyperactivity and learning difficulties.

Reporting of side effects
If any undesirable symptoms occur, including any side effects not listed in this leaflet, inform your doctor or pharmacist. Side effects 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 181 C
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 responsible entity.
By reporting side effects, more information on the safety of this medicine can be collected.

5. How to store Convulex

Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton.
The expiry date refers to the last day of the stated month.
Store below 30°C.
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 package and other information

What Convulex contains
The active substance is valproic acid. Each capsule contains 150 mg or 300 mg or 500 mg of valproic acid.
The other components are carion 83, glycerol 85%, gelatin, titanium dioxide (E171), iron oxide red (E172), hydrochloric acid 25%; coating: copolymer of methacrylic acid and ethyl acrylate (1:1) dispersion 30%, triethyl citrate, macrogol 6000, glycerol monostearate 44-55 Type II.

What Convulex looks like and contents of the pack
Convulex 150, 150 mg capsules and Convulex 300, 300 mg capsules: Pink oval gelatin capsules.
Convulex 500 mg capsules: Pink elongated gelatin capsules.
Pack contains 30 or 100 capsules.

Marketing Authorisation Holder and Manufacturer
G.L. Pharma GmbH
Schloßplatz 1
A-8502 Lannach
Austria

For further information, please contact the representative of the Marketing Authorisation Holder:
G.L. PHARMA POLAND Sp. z o.o.
Sienna Street 75; 00-833 Warsaw, Poland
Tel: 022/ 636 52 23; 636 53 02
[email protected]

Other sources of information
Detailed and up-to-date information about this medicinal product is available by scanning with a smartphone the QR code located on the package leaflet. The same information is also available on the website:
www.walproiniany.pl
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