Convulex

Package leaflet: Information for the user

Convulex
50 mg/mL, syrup
Valproic acid sodium salt
This medicinal product will be subject to additional monitoring. This will allow for rapid identification of

new safety information. Users of this medicine can also help by reporting any side effects that occur after starting treatment. For information on how to report side effects – see section 4.
WARNING
The use of Convulex (sodium valproate) during pregnancy can cause serious harm to the unborn child. Women of childbearing potential must use an effective method of contraception (birth control) continuously throughout the entire period of treatment with Convulex. Your doctor will discuss this with you and you should also follow the advice provided in section 2 of this leaflet.
You must contact your doctor immediately if you are planning a pregnancy or suspect that you may be pregnant.
Do not stop taking Convulex unless instructed by your doctor, as your condition may worsen.
You should read this leaflet carefully before taking the medicine, because 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 you personally. Do not pass it on to others. It may harm someone else, even if their symptoms are similar to yours.
• 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 pack and other information

1. What Convulex is and what it is used for

Convulex is a syrup containing the active substance sodium valproate. It belongs to a group of medicines called antiepileptics, which act on the central nervous system.
It has antiepileptic activity in various forms of epilepsy in humans.
Convulex is used in adults and children, either as monotherapy or in combination with other antiepileptic medicines, for the treatment of:

• generalized seizures such as clonic, tonic, tonic-clonic seizures, absence seizures, myoclonic seizures, and atonic seizures;
• partial seizures: partial seizures with or without secondary generalization.

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 sodium valproate or to any of the other ingredients of this medicine (listed in section 6),
• the patient has acute or chronic hepatitis,
• the patient has previously experienced severe hepatitis, especially 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 dysfunction (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) that is untreated,
• epilepsy:
  • if the patient is pregnant, unless no other therapy is effective,
  • if the patient is of childbearing potential, unless the patient 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. Inform your doctor immediately. 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. Sodium valproate should not be administered concurrently with salicylates in children under 3 years of age due to the risk of hepatotoxic effects.
• Severe abdominal pain occurs. Inform your doctor immediately. Very rarely, Convulex 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. Inform your doctor immediately. This may be due to increased blood ammonia levels.
• A small number of people taking antiepileptic medicines containing sodium valproate have had thoughts of harming themselves or committing 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 symptoms related to 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:

• Valproate 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 prescribing the medicine for the first time or when a woman treated with valproate is planning pregnancy. Women of childbearing potential must use effective contraception during treatment.
• Before starting treatment, as well as before surgery and in cases of bruising or spontaneous bleeding, laboratory tests should be performed (complete blood count with blood 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 disorder," due to the risk of increased blood ammonia levels.
• Weight gain may occur in patients treated with sodium valproate. This is particularly relevant in patients with a rare metabolic disorder called "carnitine palmitoyltransferase II deficiency" due to increased risk of muscle disorders.
• Concurrent use of carbapenem antibiotics with valproic acid is not recommended (see section "Convulex and other medicines"). Sodium valproate is excreted mainly by the kidneys, partly in the form of ketone bodies; therefore, in patients with diabetes, testing for ketone bodies may give false-positive results.
• If there is a family history of, or if 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 severity or frequency during treatment. If seizures worsen, consult your doctor immediately.
• If the patient has inadequate intake of carnitine, found in meat and dairy products, especially in children under 10 years of age.
• If the patient has carnitine deficiency and is taking carnitine supplements.
• If the patient previously developed a severe skin rash, skin peeling, blistering, and/or oral ulcers after taking valproate.

Information for patients with diabetes
Convulex 50 mg/mL syrup contains artificial sweeteners and therefore may be used by patients with diabetes. However, the carbohydrate content should be considered – 0.05 bread units (BU) per 1 mL of syrup.

Convulex and other medicines
Tell your doctor about all medicines currently taken or recently taken, as well as any medicines the patient plans to take.
Some medicines may affect the action of sodium valproate, and valproate may also affect the action of other medicines. These include:

• neuroleptic drugs, including quetiapine, olanzapine (used to treat psychotic disorders);
• antidepressants, including MAO inhibitors;
• benzodiazepines, used to treat insomnia and anxiety disorders;
• other antiepileptic drugs, including phenobarbital, phenytoin, primidone, lamotrigine, carbamazepine, felbamate, topiramate, rufinamide;
• cannabidiol (used to treat epilepsy and other conditions);
• certain anticancer drugs containing pivampicillin or 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 anesthesia);
• nimodipine;
• medicines containing estrogen (including some contraceptives);
• metamizole, a medicine used to treat pain and fever, which may reduce the effectiveness of sodium valproate;
• clozapine (used to treat psychiatric disorders).

These medicines may affect the action of sodium valproate and vice versa. Dose adjustments of individual medicines or use of alternative medicines may be necessary. Your doctor will inform you about 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 syrup is intended for oral use and should be taken during or after a meal. A dosing device with graduations and a plunger is included in the package for accurate dosing.
Alcohol consumption is not recommended during treatment with valproate.

Pregnancy, breastfeeding and fertility
Pregnancy
Important advice for women

• Do not use Convulex if the patient is pregnant, unless no other therapy is effective.
• Do not take Convulex if the patient is of childbearing potential, 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.

Risks of taking valproate during pregnancy (regardless of the condition for which valproate is used)

• Consult your doctor immediately if you are planning pregnancy or become pregnant.
• Taking valproate during pregnancy carries risks. The higher the dose, the greater the risk, but no dose is completely risk-free, even when valproate is used in combination with other antiepileptic drugs.
• Valproate may cause serious congenital malformations and affect the development of the growing fetus. The most commonly reported 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 developmental abnormalities affecting several organs and body parts. Congenital malformations may lead to disabilities, which can be significant.
• Hearing problems or deafness have been reported in children exposed to valproate in utero.
• Developmental eye 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 valproate have an increased risk of giving birth to a child with congenital malformations requiring treatment. Valproate has been used for many years, so it is known that in the group of children born to mothers taking valproate, about 10 out of 100 will have congenital malformations. For comparison, such malformations are observed 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 have lower intellectual abilities than other children, and may have language and memory problems.
• Autism spectrum disorders are more frequently diagnosed in children exposed to valproate. Some evidence suggests these children may be at higher risk of developing symptoms of attention deficit/hyperactivity disorder (ADHD).
• Before prescribing this medicine, your doctor will explain the risks to the unborn child if you become pregnant while taking valproate. 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 without first discussing it with your doctor.
• Parents or guardians of girls treated with valproate should contact the treating doctor when menstruation (periods) begins.
• Some contraceptives (oral contraceptives containing estrogen) may reduce blood levels of valproate. Discuss the most appropriate method of contraception with your doctor.
• Ask your doctor about taking folic acid when trying to conceive. 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 valproate treatment.

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

• STARTING TREATMENT WITH CONVULEX
• CONTINUING TREATMENT WITH CONVULEX WITHOUT PLANNING PREGNANCY
• CONTINUING TREATMENT WITH CONVULEX WHILE PLANNING PREGNANCY
• BECOMING PREGNANT DURING CONTINUOUS 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 potential should ensure they use an effective method of contraception continuously throughout the entire treatment period with Convulex. Consult your doctor or a family planning clinic if you need advice on contraception.
Important information:

• Before starting Convulex, pregnancy should be ruled out with a pregnancy test confirmed by your doctor.
• The patient should use an effective method of contraception throughout the entire treatment period with Convulex.
• Discuss the appropriate method of contraception with your doctor. Your doctor will provide information on pregnancy prevention and may refer you to a specialist for advice on contraception.
• Regular visits (at least once a year) to a specialist experienced in treating epilepsy are recommended. During these visits, the doctor will ensure the patient has been adequately informed and understands all risks and advice related to valproate use during pregnancy.
• Inform your doctor if you plan to have a child.
• Inform your doctor immediately if you are pregnant or suspect you may be pregnant.

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. Consult your doctor or a family planning clinic if you need advice on contraception.
Important information:

• The patient should use an effective method of contraception throughout the entire treatment period with Convulex.
• Discuss contraception (method of birth control) with your doctor. Your doctor will provide information on pregnancy prevention and may refer you to a specialist for advice on contraception.
• Regular visits (at least once a year) to a specialist experienced in treating epilepsy are recommended. During these visits, the doctor will ensure the patient has been adequately informed and understands all risks and advice related to valproate use during pregnancy.
• Inform your doctor if you plan to have a child.
• Inform your doctor immediately if you are pregnant or suspect you may be pregnant.

CONTINUING TREATMENT WITH CONVULEX WHILE PLANNING PREGNANCY
If the patient plans to have a child, she should first schedule an appointment with her doctor. Do not stop treatment with Convulex or contraception until this has been discussed with your doctor. Your 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. Your doctor will refer the patient to a specialist experienced in treating epilepsy to evaluate alternative treatment options as early as possible. The specialist may take steps to ensure the best possible pregnancy outcome and minimize risks to both mother and unborn child. The treating specialist may decide to adjust the dose of Convulex, switch to another medicine, or discontinue Convulex well before conception to ensure the disease remains stable.
Ask your doctor about taking folic acid when trying to conceive. 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 valproate treatment.
Important information:

• Do not stop treatment with Convulex unless your doctor advises it.
• Do not stop using contraception methods before speaking with your doctor and jointly developing a management plan that ensures control of the patient's condition and reduces risks to the child.
• Schedule an appointment with your doctor first. During this visit, the doctor will ensure the patient has been adequately informed and understands all risks and advice related to valproate use during pregnancy.
• Your doctor may try switching to another medicine or discontinuing Convulex well before conception.
• Schedule an urgent appointment with your doctor if you are pregnant or suspect you may be pregnant.

BECOMING PREGNANT DURING CONTINUOUS TREATMENT WITH CONVULEX
Do not stop treatment with Convulex without first discussing it with your doctor, as your health condition may worsen. Schedule an urgent appointment with your doctor if you are pregnant or suspect you may be pregnant. Your 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 epilepsy to evaluate alternative treatment options.
In exceptional circumstances, when Convulex is the only available treatment option during pregnancy, the patient will be closely monitored for both the underlying disease and fetal development. The patient and her partner will receive counseling and support regarding valproate-exposed pregnancy.
Ask your doctor about taking folic acid. 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 valproate treatment.
Important information:

• Schedule an urgent appointment with your doctor if you are pregnant or suspect you may be pregnant.
• Do not stop treatment with Convulex unless advised by your doctor.
• The patient should ensure she has been referred to a specialist experienced in treating epilepsy to evaluate the need for alternative treatment options.
• The patient must receive counseling on the risks of using Convulex during pregnancy, including its teratogenic effects and impact on child development.
• The patient should ensure she has been referred to a specialist in prenatal monitoring to detect possible developmental abnormalities.

Newborns of mothers who took Convulex during pregnancy may experience bleeding disorders, hypoglycemia, hypothyroidism, and withdrawal symptoms such as agitation, irritability, hyperexcitability, tremors, seizures, and feeding difficulties.
You should read the patient guide provided by your doctor. Your doctor will discuss the annual risk acknowledgment 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 valproate use during pregnancy.

Important advice for male patients
Possible risks associated with taking valproate during the 3 months before conception
Studies suggest a possible risk of motor disorders and neurodevelopmental 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 neurodevelopmental disorders suggested by this study is caused by valproate. The study was not large enough to determine the specific types of motor and neurodevelopmental disorders involved.
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 discontinuation;
• 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 the individual situation.

Do not donate sperm while taking valproate and for 3 months after stopping it.
If you are planning a child, discuss this with your doctor.
If your partner becomes pregnant while you are taking valproate during the 3 months before conception and you have any concerns, contact your doctor. Do not stop treatment without consulting your doctor. If you stop treatment, symptoms may worsen.
You should have regular check-ups 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 options, 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
Valproate is excreted in small amounts in breast milk. Consult your doctor whether breastfeeding is possible during treatment.

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

Important information about some ingredients of Convulex
The medicine contains methyl and propyl parahydroxybenzoate. It may cause allergic reactions (delayed-type reactions possible).

3. How to use Convulex

Convulex must always be used exactly as directed by the physician. In case of 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.

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

The dosage and duration of treatment will be determined by the physician.
Other strengths and pharmaceutical forms of Convulex are also available, which may be relevant when adjusting the dose.

Convulex syrup is intended for oral use and should be administered during or after a meal. For accurate dosing, an oral dosing device with graduated markings and a plunger is included in the package.

The syrup contains liquid maltitol, a sugar substitute, and therefore does not cause or promote dental caries.

The total daily dose is usually divided into several doses. During monotherapy with sodium valproate, the total daily dose may also be administered as a single evening dose (up to 15 mg/kg body weight per day).

The daily dose depends on the patient's age and body weight.

Dosage
Monotherapy
Children: The initial dose is 10–20 mg/kg body weight of valproic acid per day, gradually increased by 5–10 mg/kg body weight at intervals of 3–7 days until seizure control is achieved. This is usually achieved at a dose within the range of 20–30 mg/kg body weight per day (see also dosing table). If seizure control is not achieved with this dosage, the dose may be increased up to 35 mg/kg body weight per day. In individual cases, doses exceeding 40 mg/kg body weight per day may be considered.

In children requiring doses higher than 40 mg/kg body weight per day, regular laboratory monitoring should be performed.

Children with body weight above 20 kg: The usual recommended initial dose is generally 300 mg per day.

Recommended daily doses for sodium valproate
(guideline table)

Patients with impaired renal function
The physician may decide whether dose adjustment is necessary for the patient.
Combination therapy
If Convulex is added to an already ongoing antiepileptic treatment, it is essential to follow the physician's instructions precisely.
Method of administration
Instructions for using the dosing device with piston:

1. Press the piston fully down and insert the dosing device into the bottle.
2. Pull the piston up to the level corresponding to the prescribed dose (marked in mL or mg). Repeat this procedure as necessary until the complete required dose of syrup has been drawn into the dosing device.
3. Empty the contents of the dosing device directly into the child's mouth or onto a spoon. Ensure that the entire prescribed dose of the medicine is administered.
4. After each use, close the bottle and rinse the dosing device carefully with water.

The bottle and dosing device should be stored in the box.
Use of a higher than recommended dose of Convulex
Clinical symptoms of severe overdose include: somnolence, reduced muscle tone, diminished tendon reflexes, miosis, and respiratory disturbances. Metabolic acidosis, decreased arterial pressure, and acute circulatory failure may also occur.

Other symptoms may appear as well; seizures have been reported in cases of very high blood concentrations of valproate.

The presence of sodium in valproate pharmaceutical formulations may lead to increased blood sodium concentration in case of overdose.

Hospital treatment of overdose is symptomatic and should involve monitoring of cardiovascular and respiratory function.

In the most severe cases, hemodialysis or even exchange transfusion may be necessary. In isolated cases, naloxone has proven effective.

If a higher than recommended dose of the medicine has been taken, seek immediate medical advice from a doctor or pharmacist.

Missed dose of Convulex
If a dose is missed, do not take a double dose to make up for the missed dose; continue treatment as directed by the physician.

Discontinuation of Convulex treatment
Do not discontinue treatment with Convulex or alter the dose without consulting a physician. Discontinuing treatment without medical consultation may worsen the patient's condition.

4. Possible side effects

Like all medicines, Convulex may cause side effects, although not everyone experiences them.
They are rarely serious and usually temporary. However, patients may require appropriate treatment
if certain side effects occur.
If the patient experiences any of the following severe side effects, seek medical advice immediately,
as urgent medical help may be needed:

• 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 a rapid increase in the dose of Convulex
• Confusion, weakness, dizziness, nausea, vomiting, which may be caused by low sodium levels in the blood or a condition known as "SIADH" (SIADH, Syndrome of Inappropriate Secretion of ADH) or syndrome of inappropriate antidiuretic hormone secretion
• Problems with balance and coordination, drowsiness or reduced alertness, accompanied by vomiting. This may be due to increased levels of ammonia in the blood (hyperammonaemia)
• Increased frequency 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 present as:
  • Blisters with skin peeling (formation of blisters, skin sloughing or bleeding from various parts of the body including lips, eyes, mouth, nose, genitals, 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"
  • Skin rash or skin changes with red/rose-coloured rings and pale centres, which may be itchy, peeling or filled with fluid. Rashes may appear especially on palms or soles. These may be symptoms of a disease called "erythema multiforme"
  • Swelling caused by allergy with painful, itchy swellings (most commonly around eyes, lips, throat, and sometimes hands and feet) – these may be symptoms of "angioedema"
  • 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 cell count 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 a few days, inform your doctor or pharmacist; treatment may be necessary.
The side effects are listed according to the following frequency classification:
Very common (may occur in more than 1 in 10 patients):

• Tremor
• Nausea

Common (may occur in less than 1 in 10 patients):

• 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 resolves within a few days without the need to discontinue treatment)
• Gum abnormalities (mainly gum overgrowth), oral inflammation
• Transient and/or dose-dependent hair loss, nail disorders and nail bed changes
• Weight gain, which should be monitored as it may be associated with polycystic ovary syndrome
• Irregular menstrual cycles
• Confusion (disorientation), hallucinations, aggression, agitation, attention disturbances
• Urinary incontinence

Uncommon (may occur in less than 1 in 100 patients):

• Leukopenia (significant decrease in white blood cell count), pancytopenia (significant decrease in blood cells, which may cause weakness, easy bruising or increased susceptibility to infections)
• Tingling or numbness in hands or feet
• Skin 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
• Low body temperature, mild peripheral oedema
• Absence of menstruation

Rare (may occur in less than 1 in 1000 patients):

• Macrocytic anaemia (low number of red blood cells), macrocytosis (abnormal enlargement of red blood cell size)
• Biotin deficiency / biotinidase deficiency
• Excessive urination and thirst (Fanconi syndrome)
• Involuntary urination (nocturnal enuresis)
• Obesity
• Male infertility, which is usually reversible after discontinuation of treatment and may be transient
• Polycystic ovary syndrome
• Unusual behaviour, psychomotor hyperactivity, learning difficulties (observed in children and adolescents)
• Transient cognitive dulling associated with transient brain atrophy, cognitive disturbances
• Double vision

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

• Congenital disorders and 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 disturbances, abnormal behaviour, hyperactivity and learning difficulties.

Reporting of side effects
If any adverse symptoms occur, including any 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 marketing authorization holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Convulex

Keep this 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 25°C. Protect from light.
Shelf life after first opening: 6 months.
Medicines must not be disposed of via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer in use.
This helps protect the environment.

6. Contents of the pack and other information

What Convulex contains
The active substance is 50 mg of sodium valproate per 1 mL of syrup. Sodium valproate is obtained from valproic acid and sodium hydroxide.
The other ingredients are: liquid maltitol (800 mg/mL, a sugar substitute), methyl parahydroxybenzoate (1.0 mg/mL), propyl parahydroxybenzoate (0.4 mg/mL), sodium saccharin (1.0 mg/mL), sodium cyclamate (3.0 mg/mL), sodium chloride, raspberry flavour, peach flavour, purified water.

What Convulex looks like and contents of the pack
Syrup.
A colourless to slightly yellowish solution in a 100 mL amber glass bottle, contained in a cardboard box.

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

For further information about this medicinal product, 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 medicine is available by scanning the QR code on the leaflet using a smartphone. The same information is also available on the website:
www.walproiniany.pl