Patient Information Leaflet

DEPAKINE
288.2 mg/5 ml, syrup
Sodium valproate
This medicinal product will be subject to additional monitoring. This will allow for rapid
identification of new safety information. Patients can help by reporting any side effects they
experience with this medicine. For information on how to report side effects – see section 4.
WARNING
Depakine (sodium valproate) used during pregnancy can seriously harm the unborn child. Women of childbearing potential must use an effective method of contraception (birth control) continuously throughout the entire duration of Depakine treatment. This will be discussed with the patient by her doctor, and the recommendations outlined in section 2 of this leaflet should also be followed. The patient should contact her doctor immediately if she is planning a pregnancy or suspects she may be pregnant.
Do not stop taking Depakine unless instructed by the doctor, as the patient's condition may worsen.
Please read this leaflet carefully before taking this medicine, as it contains important
information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not give it to others. It may harm them, even if their symptoms are similar.
If the patient experiences any side effects, including any not listed in this leaflet, inform the doctor or pharmacist. See section 4.

Table of contents:

What Depakine is and what it is used for
What you need to know before taking Depakine
How to take Depakine
Possible side effects
How to store Depakine
Contents of the pack and other information

1. What Depakine is and what it is used for

Depakine is available as a syrup and contains the active substance sodium valproate. Depakine belongs to a group of medicines called anticonvulsants and acts on the central nervous system. It has anticonvulsant activity in various forms of epilepsy in humans.
Depakine is used in adults and children 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;
for the treatment of partial seizures: partial seizures with or without secondary generalization.

2. Important information before using Depakine

When not to use Depakine
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, particularly drug-induced hepatitis, or if there is a family history of severe hepatitis,
the patient has porphyria (a very rare metabolic disorder),
concomitant 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 she uses an effective method of contraception throughout treatment with Depakine. Do not stop taking Depakine or contraception unless discussed with your doctor. Your doctor will provide further advice (see below "Pregnancy, breastfeeding and fertility – Important advice for women").

Warnings and precautions
Talk to your doctor before starting treatment with Depakine.
YOU MUST INFORM YOUR DOCTOR IMMEDIATELY IF:

There is sudden onset of the following symptoms: weakness, loss of appetite, drowsiness, recurrent vomiting and abdominal pain, jaundice (yellowing of the skin and whites of the eyes), or recurrence of seizures, especially during the first 6 months of treatment. Depakine may cause severe liver damage, sometimes resulting in 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 Depakine is used in children under 3 years of age, in patients taking other antiepileptic drugs, in patients with other neurological or metabolic disorders, or in patients with severe epilepsy. Sodium valproate should not be given concomitantly with salicylates in children under 3 years of age due to the risk of hepatotoxicity.
Severe abdominal pain occurs. Very rarely, Depakine may cause severe pancreatitis, sometimes leading to death.
The patient or their child taking Depakine 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 people taking antiepileptic medicines containing sodium valproate have had thoughts about harming or killing themselves. 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 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 using the medicine should be weighed against the risks before the first prescription or when a woman treated with valproate plans pregnancy. Women of childbearing potential must use effective contraception during treatment.
Before starting treatment, including prior to surgery, and in cases of bruising 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 impaired kidney function. Your doctor may recommend a lower dose.
The medicine should be used with caution in patients with systemic lupus erythematosus.
If any metabolic disorder is suspected in the patient, particularly 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 sodium valproate.
If the patient has a rare metabolic 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 "Depakine with other medicines").
Sodium valproate is excreted mainly via the kidneys, partly in the form of ketone bodies; therefore, in patients with diabetes, urine ketone tests may give false-positive results.
If there is a family history or the doctor suspects a genetic disorder due to mitochondrial dysfunction, due to the risk of liver damage.
As with other antiepileptic medicines, 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, 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.

Depakine with other medicines
Tell your doctor about all medicines the patient is currently taking or has 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:

neuroleptics, including quetiapine, olanzapine (used to treat psychotic disorders);
medicines used to treat depression, MAO inhibitors;
benzodiazepines, used to treat insomnia and anxiety disorders;
other medicines used to treat epilepsy, including phenobarbital, phenytoin, primidone, lamotrigine, carbamazepine, felbamate, topiramate, rufinamide;
cannabidiol (used to treat epilepsy and other conditions);
certain antimicrobial agents containing pivoxil (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), see also section "Exercise particular caution when using Depakine";
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 estrogen (including some contraceptives);
metamizole (used to treat pain and fever);
clozapine (used to treat psychiatric disorders).

These medicines may affect the action of sodium valproate and vice versa. The patient may require dose adjustments or alternative medicines. Your doctor will inform the patient about any such changes in treatment.
Your doctor will also provide additional information about medicines that should be used with caution or avoided during treatment with Depakine.

Depakine with food, drink and alcohol
The medicine should be taken during meals.
Alcohol consumption is not recommended during treatment with valproate.

Pregnancy, breastfeeding and fertility

Pregnancy
Important advice for women

Do not use Depakine if the patient is pregnant, unless no other therapy is effective.
If the patient is of childbearing potential, she must not take Depakine unless she uses an effective method of contraception (birth control) throughout treatment with Depakine. Do not stop taking Depakine or contraception unless discussed with your doctor. Your doctor will provide further advice.

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

Consult your doctor immediately if the patient is planning pregnancy or is pregnant.
Using valproate during pregnancy carries risks. The higher the dose, the greater the risk, but no dose is risk-free, even when valproate is used in combination with other epilepsy medicines.
Valproate may cause serious congenital malformations and affect the child's physical and mental development after birth.
The most common congenital malformations include: spina bifida (when the spinal bones do not develop properly); facial and skull 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 may 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 patients 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 11 out of 100 will have congenital malformations. For comparison, such malformations occur 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 valproate during pregnancy may have early developmental problems. Affected children may start walking and talking later, have lower intellectual abilities than other children, and may have language and memory problems.
Children exposed to valproate in utero are diagnosed more frequently with various autism spectrum disorders. Some evidence suggests an increased risk of developing symptoms of attention deficit (attention deficit hyperactivity disorder – ADHD).
In patients taking valproate during pregnancy, the child may have lower birth weight than expected for gestational age. In women taking valproate, about 11–15 out of every 100 children may have lower birth weight than expected for gestational age. For comparison, this affects about 5–10 out of every 100 children born to women in the general population.
Before prescribing this medicine, your doctor will explain to the patient the risks to the unborn child if she becomes pregnant while taking valproate. If a patient taking this medicine decides she wants to have a child, she should not stop taking the medicine or contraception without discussing it with her doctor.
Some contraceptives (oral contraceptives containing estrogen) may reduce the blood concentration of valproate. Discuss the most appropriate method of contraception (birth control) with your doctor.
Parents or guardians of girls treated with valproate should contact the doctor when menstruation begins in their child.
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 valproate treatment.

Choose the situation below that applies to the patient and read the information:
o STARTING TREATMENT WITH DEPAKINE
o CONTINUING TREATMENT WITH DEPAKINE WITHOUT PLANNING PREGNANCY
o CONTINUING TREATMENT WITH DEPAKINE WHILE PLANNING PREGNANCY
o BECOMING PREGNANT WHILE CONTINUING TREATMENT WITH DEPAKINE

STARTING TREATMENT WITH DEPAKINE
If Depakine is being prescribed for the first time, your doctor will explain the risks to the unborn child if the patient becomes pregnant. A woman of childbearing potential should ensure that she uses an effective method of contraception continuously throughout treatment with Depakine. If the patient needs advice on contraception, she should consult her doctor or a family planning clinic.
Important information

Before starting Depakine, the patient should confirm she is not pregnant with a pregnancy test, the result of which should be confirmed by her doctor.
The patient should use an effective method of contraception (birth control) throughout treatment with Depakine.
Discuss the appropriate method of contraception (birth control) with your doctor. Your doctor will provide information on pregnancy prevention and may refer the patient to a specialist for advice on contraception.
Visit a specialist experienced in treating epilepsy regularly (at least once a year). During this visit, the doctor will ensure the patient has been adequately informed and understands all risks and advice related to using valproate during pregnancy.
If the patient plans to have a child, she should inform her doctor.
If the patient is pregnant or suspects she may be pregnant, she should inform her doctor immediately.

CONTINUING TREATMENT WITH DEPAKINE WITHOUT PLANNING PREGNANCY
If the patient continues treatment with Depakine and does not plan pregnancy, she must be certain she uses an effective method of contraception continuously throughout treatment with Depakine. If the patient needs advice on contraception, she should consult her doctor or a family planning clinic.
Important information

The patient should use an effective method of contraception (birth control) throughout treatment with Depakine.
Discuss contraception (birth control method) with your doctor. Your doctor will provide information on pregnancy prevention and may refer the patient to a specialist for advice on contraception.
Visit a specialist experienced in treating epilepsy regularly (at least once a year). During this visit, the doctor will ensure the patient has been adequately informed and understands all risks and advice related to using valproate during pregnancy.
If the patient plans to have a child, she should inform her doctor.
If the patient is pregnant or suspects she may be pregnant, she should inform her doctor immediately.

CONTINUING TREATMENT WITH DEPAKINE WHILE PLANNING PREGNANCY
If the patient plans to have a child, she should first schedule an appointment with her doctor. Do not stop taking Depakine or contraception until discussed with the 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 the patient to a specialist experienced in treating epilepsy to assess alternative treatment options as early as possible. The specialist may take steps to ensure the best possible pregnancy outcome and minimize risks to the mother and unborn child.
The treating specialist may decide to adjust the dose of Depakine, switch to another medicine, or discontinue Depakine treatment well before pregnancy 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 valproate treatment.
Important information

Do not stop treatment with Depakine unless advised by your doctor.
Do not stop using contraception methods (birth control) before talking to your doctor and jointly developing a plan that ensures control of the patient's condition and reduces risks to the child.
First, schedule an appointment with your doctor. During this visit, the doctor will ensure the patient has been adequately informed and understands all risks and advice related to using valproate during pregnancy.
Your doctor will attempt to switch to another medicine or discontinue Depakine treatment well before pregnancy.
If the patient is pregnant or suspects she may be pregnant, she should schedule an urgent appointment with her doctor.

BECOMING PREGNANT WHILE CONTINUING TREATMENT WITH DEPAKINE
Do not stop treatment with Depakine unless discussed with your doctor, as the patient's health condition may worsen. If the patient is pregnant or suspects she may be pregnant, she should schedule an urgent appointment with her 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. The patient will be referred to a specialist experienced in treating epilepsy to assess alternative treatment options.
In exceptional circumstances, when Depakine is the only available treatment option during pregnancy, the patient will be monitored very closely, both regarding treatment of the underlying condition and fetal development. The patient and her partner will receive advice 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

If the patient is pregnant or suspects she may be pregnant, she should schedule an urgent appointment with her doctor.
Do not stop treatment with Depakine unless advised by your doctor.
The patient should ensure she is referred to a specialist experienced in treating epilepsy to assess the need for alternative treatment methods.
The patient must receive advice on the risks of using Depakine during pregnancy, including its teratogenic effects (causing congenital malformations) and physical and mental developmental disorders in children.
The patient should ensure she is referred to a specialist in prenatal monitoring to detect possible developmental abnormalities.

Newborns of mothers who used Depakine during pregnancy may experience blood clotting disorders, hypoglycemia, hypothyroidism, and withdrawal symptoms such as: agitation, irritability, hyperactivity, tremors, seizures, and feeding difficulties.
Read the patient guide provided by your doctor.
Your doctor will discuss the annual risk acknowledgment form and ask the patient to sign and keep it. The patient will also receive a patient card from the pharmacist as a reminder of the risks of using valproate during pregnancy.

Important advice for male patients
Possible risk associated with taking valproate within 3 months before conception
A study suggests a possible risk of motor disorders and psychological developmental disorders (early childhood developmental problems) in children whose fathers were treated with valproate within 3 months before conception. In this study, about 5 out of 100 children whose fathers were treated with valproate had such disorders, compared to about 3 out of 100 children 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 (the time needed to produce new sperm) before conception is unknown. The study has limitations, so it is unclear whether the increased risk of motor and psychological developmental disorders suggested by this study is caused by valproate. The study was not large enough to determine the specific types of motor and psychological developmental disorders involved.
As a precaution, your doctor will discuss with the patient:

the possible risk in children whose fathers were treated with valproate;
the need to consider using effective contraception by the patient and his partner during treatment and for 3 months after its completion;
the need to consult a doctor when planning conception and before stopping contraception;
the possibility of using alternative treatment methods for the disease, depending on the patient's individual situation.

Do not donate semen while taking valproate and for 3 months after discontinuation.
If planning parenthood, discuss this with your doctor.
If the patient's partner becomes pregnant while the patient was taking valproate within 3 months before conception and the patient has questions, he should contact his doctor. Do not stop treatment without consulting a doctor. If the patient stops treatment, symptoms may worsen.
The patient should have regular visits with the doctor prescribing the medicine. During such visits, the doctor will discuss precautions related to using valproate and the possibility of alternative treatments for the patient's condition, depending on the patient's individual situation.
Read the patient guide provided by your doctor. The patient will also receive a patient card from the pharmacist as a reminder of the possible risks associated with using valproate.

Breastfeeding
Valproate is excreted in small amounts in breast milk. Consult your doctor whether breastfeeding is possible during treatment.

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

Important information about some ingredients of Depakine
Depakine contains parahydroxybenzoates and may cause allergic reactions (possible delayed-type reactions).
Depakine contains sucrose and sorbitol.
The medicine contains 105 mg of sorbitol in 1 ml of syrup.
Sorbitol is a source of fructose. If fructose intolerance has previously been diagnosed in the patient (or their child) or hereditary fructose intolerance, a rare genetic disorder in which the patient's body does not break down fructose, the patient should contact their doctor before taking the medicine or giving it to the child.
Depakine contains sodium.
Depakine in doses above 170 mg contains more than 24 mg of sodium (the main component of table salt). This corresponds to 1.2% of the maximum recommended daily sodium intake in the diet for adults.
Depakine contains alcohol.
The medicine contains 0.00027 mg of alcohol (ethanol) in 1 ml of syrup. The small amount of alcohol in this medicine will not cause noticeable effects.

3. How to use Depakine

Depakine must always be used exactly as directed by the physician. If in doubt, consult your doctor.

Female patients of childbearing age
Treatment with Depakine should be initiated and supervised by a physician specialized in the treatment of epilepsy.

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

The usual recommended doses are:

infants and children: 30 mg/kg body weight per day,
adolescents and adults: 20 to 30 mg/kg body weight per day.

The medicine should be administered during meals:

in children under 1 year of age, in two divided doses;
in patients over 1 year of age, in three divided doses.

Initiating treatment with sodium valproate
In patients receiving other antiepileptic drugs, treatment with sodium valproate should be introduced gradually, reaching the optimal dose within 2 weeks. The doses of other antiepileptic drugs should then be gradually reduced, while monitoring disease symptoms.
In patients not receiving other antiepileptic drugs, the dose of sodium valproate should be increased every 2–3 days to achieve the optimal dose within approximately one week.

Method of administration
The medicine is administered using the syringe with marked graduations supplied with the package.
The syringe must not be used to administer other medicines, as the graduations on the syringe are specifically calibrated for Depakine syrup.

To administer the medicine using the syringe, perform the following steps:

ensure the plunger is fully depressed, then immerse the syringe into the bottle;
pull the plunger upwards and draw up the prescribed dose of the medicine; read the dose on the marked graduations;
place the tip of the syringe into the patient's mouth; slowly and gently press the plunger to administer the entire prescribed dose;
after administering the syrup, rinse the syringe 2 or 3 times with water.

The syringe should be stored in the box together with the bottle.
After first opening, the bottle may be stored for up to 1 month.

Duration of treatment
The medicine should be used for as long as directed by the physician.
If you feel that the effect of Depakine is too strong or too weak, consult your doctor.

Patients with renal impairment
The physician may decide that dose adjustment is necessary.

Overdose of Depakine
Clinical symptoms of severe overdose include: coma, decreased muscle tone, diminished tendon reflexes, constricted pupils, and respiratory disturbances. Metabolic acidosis, reduced arterial pressure, and acute circulatory failure may also occur.
Other symptoms may occur; seizures have been reported in cases of very high blood concentrations of valproate.
The presence of sodium in valproate medicinal formulations may lead to increased blood sodium levels in cases of overdose.

Hospital treatment of overdose is symptomatic and should include monitoring of cardiovascular and respiratory function.
In the most severe cases, hemodialysis or even exchange transfusion may be required.
In isolated cases, naloxone has been effective.
In case of overdose, seek immediate medical advice from a doctor or pharmacist.

Missed dose of Depakine
If a dose is missed, it should be taken as soon as possible, unless it is almost time for the next dose. Do not take a double dose or two doses in close succession. In case of doubt, consult your doctor.

Stopping treatment with Depakine
Do not discontinue treatment with Depakine or change the dose without consulting your doctor. Discontinuing treatment without medical supervision may worsen the patient's condition.

4. Possible adverse effects

Like all medicines, Depakine may cause adverse effects, although not everyone experiences them.
However, patients may require appropriate treatment if certain adverse effects occur.
If any of the following severe adverse effects occur in a patient, contact a doctor immediately,
as the patient may urgently require medical assistance:

Coma, encephalopathy (brain damage), lethargy (a state of inertia and lack of response to stimuli), changes in behaviour with or without an increased frequency or severity of epileptic seizures, especially when phenobarbital is used concomitantly or during a sudden increase in the dose of Depakine
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 inappropriate antidiuretic hormone secretion syndrome
Problems with balance and coordination, drowsiness or reduced alertness, combined with vomiting. This may be due to increased ammonia levels in the blood (hyperammonaemia)
Increase in 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, 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”
o Skin rash or skin changes with a red/pink ring and pale centre, 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 Swelling caused by allergy with painful, itchy swellings (most commonly 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” or drug reaction with eosinophilia and systemic symptoms
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 confirmed by 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, disturbances in 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 adverse effects worsen or persist for more than a few days, inform the
doctor or pharmacist; treatment may be necessary.
Adverse effects are listed according to the following frequency classification:
Very common (may occur in more than 1 in 10 people):

tremor
nausea

Common (may occur in 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, headache, nystagmus (rapid, uncontrolled eye movements), dizziness
hearing impairment
vomiting, stomach pain, diarrhoea (frequent in some patients at the beginning of treatment), usually resolving after a few days without the need to discontinue treatment
gum disorders (mainly gum overgrowth), oral inflammation
transient and/or dose-dependent hair loss, nail and nail bed disorders
weight gain, which should be monitored as it is associated with polycystic ovary syndrome
irregular menstrual cycles
confusion (disorientation), hallucinations, aggression, agitation, attention disturbances
urinary incontinence

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

leucopenia (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 and numbness in hands or feet
rash, hair disorders (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 Depakine therapy
hyperandrogenism (excessive male-pattern hair growth, virilisation, acne, male-pattern baldness and/or elevated androgen levels)
vasculitis
low body temperature, mild oedema of feet and legs
absence of menstruation

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

macrocytic anaemia (low number of red blood cells), macrocytosis (abnormal increase in size of red blood cells)
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 reversible after dose reduction. Do not discontinue treatment without prior consultation with a doctor
polycystic ovary syndrome
unusual behaviour, psychomotor hyperactivity, learning disorders (observed in children and adolescents)
transient dementia associated with transient brain atrophy, cognitive disturbances, double vision

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

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

Additional adverse effects in children
Some adverse effects of valproate 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 disorders.
Reporting adverse effects
If any adverse symptoms occur, including any adverse effects not listed in this leaflet, inform the doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw,
Tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting adverse effects helps to collect more information on the safety of the medicine.

5. How to store the medicine Depakine

Store in a dry place, protected from light.
Keep the medicine out of the reach and sight of children.
Do not use this medicine after the expiry date stated on the packaging.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What the medicine Depakine contains
100 ml of syrup contains:
Active substance:
Sodium valproate 5.764 g
Excipients:
Methyl p-hydroxybenzoate 0.10 g
Propyl p-hydroxybenzoate 0.02 g
Sucrose 60.0 g
Sorbitol (70% solution) 15.0 g
Glycerol 15.0 g
Cherry flavour (contains ethanol) 0.03 g
Hydrochloric acid, concentrated or
Sodium hydroxide to adjust pH to 7.3–7.7
Purified water up to 100 ml
5 ml of syrup contains 288.2 mg of sodium valproate.

What Depakine looks like and contents of the pack
The pack contains 150 ml of syrup.
A plastic dosing syringe with a capacity of 6 ml and graduations every 10 mg is included in the pack.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Sanofi Winthrop Industrie
82, Avenue Raspail
94250 Gentilly
France

Manufacturer:
Unither Liquid Manufacturing
1-3 Allée de la Neste
Z.I. d’en Sigal
31770 Colomiers
France

Manufacturer/Importer:
Sanofi Winthrop Industrie
30-36 Avenue Gustave Eiffel
37100 Tours
France

For further information about this medicine, please contact the representative of the Marketing Authorisation Holder in Poland:
Sanofi Sp. z o.o.
ul. Marcina Kasprzaka 6
01-211 Warsaw
Tel.: +48 22 280 00 00

Other sources of information
Detailed and up-to-date information about this medicine is available by scanning, with a smartphone, the QR code located on the leaflet and on the outer packaging. The same information is also available on the website: www.qr.walproinianija.pl