Package leaflet: Information for the user

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
DEPAKINE
400 mg (400 mg/4 ml), powder and solvent for solution for injection
Natrii valproas
▼ 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
adverse reactions that occur after using the medicine. To find out how to report adverse
reactions – 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 birth control (contraception) continuously throughout the entire duration of treatment with Depakine. Your doctor will discuss this with you; please also follow the recommendations provided in section 2 of this leaflet.
You must contact your doctor immediately if you are planning a pregnancy or suspect you may be pregnant.
Do not stop taking Depakine unless your doctor advises you to do so, as your condition may worsen.
Please read this leaflet carefully before using 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 someone else, even if their symptoms are the same as yours.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

What Depakine is and what it is used for
What you need to know before using Depakine
How to use 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 a powder and solvent for solution for injection, containing the active substance: sodium valproate. Sodium valproate belongs to a group of medicines called antiepileptics. It has anticonvulsant effects in various types of epilepsy in humans.
Depakine is used:

in epileptic conditions where intravenous benzodiazepines are ineffective;
in cluster seizures;
for the treatment of convulsive seizures when oral treatment is temporarily impossible due to the patient's state of consciousness or inability to swallow, particularly if the patient has previously been effectively treated orally with sodium valproate. This applies to generalized and partial seizures;
prophylactically in connection with neurosurgical procedures of the head, when there is a risk of occurrence of epileptic seizure(s).

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 had 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),
when used concomitantly 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:
the patient is pregnant, unless no other therapy is effective,
the patient is of childbearing age, unless she uses an effective method of contraception throughout the entire treatment period with Depakine. Do not discontinue treatment with Depakine or contraception without first discussing it with your doctor. Your treating physician will provide further guidance (see below "Pregnancy, breastfeeding and effects on fertility – Important advice for women").

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

Sudden onset of symptoms such as 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, occurs. Contact your doctor immediately.
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 in children under 3 years of age, in patients taking other antiepileptic drugs, in patients with other neurological or metabolic disorders, and in patients with severe epilepsy. Sodium valproate should not be administered 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 fatal.
Problems with balance and coordination, drowsiness or reduced alertness, or vomiting occur in the patient or in a child taking Depakine. This may be due to increased blood ammonia levels.
The patient has ever had thoughts of self-harm or suicide while taking antiepileptic medicines containing sodium valproate. If such thoughts occur, contact your doctor immediately.
Serious skin reactions have been reported during treatment with valproate, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, and angioedema. 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 the first prescription or when a woman treated with valproate plans pregnancy. Women of childbearing age must use effective contraception during treatment.
Before starting treatment, including prior to surgical procedures and in cases of bruising or spontaneous bleeding, laboratory tests should be performed (complete 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 sodium valproate.
If the patient has the rare condition known as "carnitine palmitoyltransferase II deficiency," due to increased risk of muscle disorders.
Concomitant use of carbapenem antibiotics with valproic acid is not recommended (see: Depakine and other medicines).
Sodium valproate is excreted mainly by the kidneys, partly in the form of ketone bodies; therefore, urine ketone tests may yield false-positive results in diabetic patients.
If the patient has 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 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, particularly in children under 10 years of age.
If the patient has carnitine deficiency and is taking carnitine supplements.
If the patient has ever experienced severe skin rash, skin peeling, blistering, and/or oral ulcers after taking valproate.

Depakine and other medicines
Inform your doctor about all medicines currently 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:

neuroleptics, 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 in the treatment of epilepsy and other indications);
certain antimicrobial agents containing pivoxil (such as pivampicillin, adefovir dipivoxil);
methotrexate (used in cancer and inflammatory diseases);
zidovudine, ritonavir, and lopinavir (used in the treatment of 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 certain 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. Dose adjustments or alternative treatments may be necessary. 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 Depakine.

Depakine with food, drink, and alcohol
Alcohol consumption is not recommended during treatment with valproate.

Pregnancy, breastfeeding and effects on 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 age, she must not take Depakine unless she uses an effective method of contraception throughout the entire treatment period with Depakine. Do not discontinue treatment with Depakine or contraception without first discussing it with your doctor. Your treating physician will provide further guidance.

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

Consult your doctor immediately if you are planning pregnancy or are already pregnant.
Taking 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 antiepileptic drugs.
Valproate 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 abnormalities; limb defects; and multiple associated developmental defects 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 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 among 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 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, have lower intellectual abilities than other children, and may have language and memory problems.
Various autism spectrum disorders are more frequently diagnosed in children exposed to valproate in utero. Some evidence suggests an increased risk of attention deficit (attention deficit hyperactivity disorder – ADHD) in these children.
Babies born to women taking valproate during pregnancy may have lower birth weight than expected for gestational age. In women taking valproate, about 11–15 out of every 100 babies may have lower than expected birth weight. For comparison, this affects about 5–10 out of every 100 babies born to women in the general population.
Before prescribing this medicine, your doctor will explain to you 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 without first discussing it with your doctor.
Some contraceptive methods (oral contraceptives containing estrogen) may reduce blood levels of valproate. Discuss with your doctor the most appropriate method of contraception for you.
Parents or guardians of girls treated with valproate should contact the treating doctor when menstruation begins in their child.
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 from the situations described below the one that applies to the patient and read the information:

STARTING TREATMENT WITH DEPAKINE
CONTINUING TREATMENT WITH DEPAKINE WITHOUT PLANNING PREGNANCY
CONTINUING TREATMENT WITH DEPAKINE WHILE PLANNING PREGNANCY
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 you become pregnant. Women of childbearing age should ensure they use an effective method of contraception continuously throughout the entire treatment period with Depakine. If you need advice on contraception, consult your doctor or a family planning clinic.
Important information

Before starting Depakine, ensure you are not pregnant by taking a pregnancy test confirmed by your doctor.
You must use an effective method of contraception (birth control) throughout the entire treatment period with Depakine.
Discuss with your doctor the appropriate method of contraception. Your doctor will provide information on preventing pregnancy and may refer you to a specialist for contraception advice.
Visit a specialist experienced in treating epilepsy regularly (at least once a year). During this visit, your doctor will ensure you have been adequately informed and understand all risks and advice related to using valproate during pregnancy.
If you plan to have a child, inform your doctor.
If you are pregnant or suspect you may be pregnant, inform your doctor immediately.

CONTINUING TREATMENT WITH DEPAKINE WITHOUT PLANNING PREGNANCY
If you continue treatment with Depakine and do not plan pregnancy, you must be certain that you continuously use an effective method of contraception throughout the entire treatment period with Depakine. If you need advice on contraception, consult your doctor or a family planning clinic.
Important information

You must use an effective method of contraception (birth control) throughout the entire treatment period with Depakine.
Discuss contraception (birth control method) with your doctor. Your doctor will provide information on preventing pregnancy and may refer you to a specialist for contraception advice.
Visit a specialist experienced in treating epilepsy regularly (at least once a year). During this visit, your doctor will ensure you have been adequately informed and understand all risks and advice related to using valproate during pregnancy.
If you plan to have a child, inform your doctor.
If you are pregnant or suspect you may be pregnant, inform your doctor immediately.

CONTINUING TREATMENT WITH DEPAKINE WHILE PLANNING PREGNANCY
If you plan to have a child, schedule an appointment with your doctor first. Do not discontinue treatment with Depakine or contraception until you have discussed it with your doctor. Your doctor will provide further guidance.
Children born to mothers who took valproate have a high risk of congenital malformations and developmental problems that may significantly impair the child. Your doctor will refer you 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 specialist may decide to adjust the dose of Depakine, switch to another medicine, or discontinue Depakine treatment well before conception to ensure the disease is 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 discontinue treatment with Depakine unless your doctor advises it.
Do not discontinue contraception methods before discussing with 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, your doctor will ensure you have been adequately informed and understand 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 conception.
If you are pregnant or suspect you may be pregnant, schedule an urgent appointment with your doctor.

BECOMING PREGNANT WHILE CONTINUING TREATMENT WITH DEPAKINE
Do not discontinue treatment with Depakine until you have discussed 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 guidance.
Children born to mothers who took valproate have a high risk of congenital malformations and developmental problems that may significantly impair the child.
You will be referred to a specialist experienced in treating epilepsy to evaluate alternative treatment options.
In exceptional circumstances, when Depakine 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 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

If you are pregnant or suspect you may be pregnant, schedule an urgent appointment with your doctor.
Do not discontinue treatment with Depakine unless your doctor advises it.
Ensure you are referred to a specialist experienced in treating epilepsy to evaluate the need for alternative treatment methods.
You must receive counseling on the risks of using Depakine 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 Depakine during pregnancy may experience bleeding disorders, hypoglycemia, hypothyroidism, and withdrawal symptoms such as: agitation, irritability, hyperactivity, tremors, seizures, and feeding difficulties.

Please 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 within 3 months before conception
A study suggests a possible risk of motor disorders and psychological development 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 required for new sperm production) before conception is unknown. The study has limitations, so it is unclear whether the suggested increased risk of motor and psychological developmental disorders 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 you:

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

Do not donate semen while taking valproate and for 3 months after stopping it.
If planning a family, discuss this with your doctor.
If your partner becomes pregnant while you were taking valproate within 3 months before conception and you have questions, contact your doctor. Do not discontinue treatment without consulting your doctor, as symptoms may worsen.
You should have regular check-ups with the doctor prescribing the medicine. During these visits, the doctor will discuss precautions related to valproate use and the possibility of alternative treatments for your condition, depending on your individual situation.
Please 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. Discuss with 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 concomitant benzodiazepines. Before driving or operating machinery, patients should ensure they know how they react to the treatment.

Depakine contains sodium
Depakine contains 55.35 mg of sodium (the main component of table salt) in 400 mg of sodium valproate. This corresponds to 2.8% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Depakine

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor.
Girls and women of childbearing age
Treatment with Depakine should be initiated and supervised by a doctor 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".
Depakine is administered to the patient only by a doctor or nurse, as it requires slow intravenous injection or infusion (intravenous administration). If the patient is unsure why Depakine has been prescribed or has any questions regarding the administered dose of Depakine, they should discuss this with their doctor or nurse.
Dose of Depakine to be administered
The doctor will decide the appropriate dose of Depakine for the patient, depending on the type of disease. The dose administered depends on age and body weight. The daily dose, frequency, and timing of administration are determined and monitored by the doctor. The doctor will also decide on the duration of treatment.
Epilepsy:
If the patient has previously taken Depakine orally, the doctor may decide to administer the same dose of Depakine as a continuous or repeated infusion, starting 6 hours after the last oral dose.
If the patient has not previously taken Depakine:

In adults, adolescents, and children above 10 years of age, the usual recommended dose is 15 mg/kg, administered as a slow intravenous injection over 3-5 minutes, followed by continuous or repeated infusion.
In children up to 10 years of age, the usual recommended dose is 20-30 mg/kg, administered as a slow intravenous injection, followed by continuous or repeated infusion. For children under 3 years of age, see section 2.

Different forms of epileptic status:

In adults, the recommended initial dose is 10-20 mg/kg, administered as a slow intravenous injection over 5-10 minutes, followed by continuous infusion.
In children, the recommended initial dose is 15-40 mg/kg, administered as a slow intravenous injection, followed by continuous infusion.

Patients with impaired kidney function
The doctor may decide that dose adjustment is necessary.
Administration of a higher than recommended dose of Depakine
Clinical symptoms of severe overdose include: coma, decreased muscle tone, diminished tendon reflexes, constricted pupils, and respiratory disturbances. Metabolic acidosis, reduced arterial blood pressure, and acute circulatory failure may also occur. Other symptoms may appear; seizures have been reported in cases of very high valproate blood concentration.
The presence of sodium in valproate pharmaceutical forms may lead to increased serum sodium concentration in case 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.
If a higher than recommended dose has been administered, seek immediate medical advice from a doctor or pharmacist.
Missed dose of Depakine
Do not administer two doses at the same time or in close succession. Continue taking the medicine as prescribed by the doctor.
If several doses have been missed, contact the doctor immediately.
Stopping treatment with Depakine
Do not discontinue treatment with Depakine or change the dose without consulting your doctor. Discontinuation of treatment without medical advice may worsen the patient's condition.

4. Possible adverse effects

Like any medicine, Depakine can 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 inactivity and lack of response to stimuli), changes in behaviour with or without an increase in the frequency or severity of epileptic seizures, especially when Depakine is taken concomitantly with phenobarbital or when the dose of Depakine is rapidly increased
Confusion, weakness, dizziness, nausea, vomiting, which may be caused by low sodium levels in the blood or a condition called "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 caused by increased levels of ammonia in the blood (hyperammonaemia)
Increase in 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 manifest as:
Blisters with skin peeling (formation of blisters, skin peeling or bleeding from various parts of the body 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"
Skin rash or skin lesions with a pink/red ring and pale centre, which may be itchy, peeling or fluid-filled. The rash may appear especially on the palms or soles. These may be symptoms of a disease called "erythema multiforme"
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"
Syndrome with skin rash, fever, enlarged 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
Marked decrease in white blood cell count or bone marrow failure confirmed by blood tests, sometimes presenting with fever and difficulty breathing
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 feeling of pressure in the chest (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, nystagmus (rapid, uncontrolled eye movements), dizziness (may occur within minutes after intravenous administration and usually resolve spontaneously within minutes)
hearing impairment
vomiting, stomach pain, diarrhoea (common in some patients at the beginning of treatment) usually resolving after a few days without the need to discontinue treatment
abnormalities of the gums (mainly gingival hyperplasia), stomatitis (inflammation of the mouth)
transient and/or dose-dependent hair loss, nail and nail bed disorders
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 up to 1 in 100 people):

leucopenia (marked decrease in white blood cell count), pancytopenia (marked decrease in blood cell counts, 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 Depakine treatment
hyperandrogenism (excessive male-pattern hair growth, virilisation, acne, male-pattern baldness and/or elevated androgen levels)
vasculitis (inflammation of blood vessels)
low body temperature, mild to moderate swelling 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 the 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 stop treatment without first consulting a doctor
polycystic ovary syndrome
unusual behaviour, psychomotor hyperactivity, learning difficulties (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 hereditary 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 difficulties.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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.
Reporting adverse effects helps to collect more information on the safety of the medicine.

5. How to store the medicine Depakine

Keep the medicine out of sight and reach of children.
Do not use the medicine after the expiry date stated on the container. The expiry date refers to the last day of the stated month.
Unopened vial of powder: no special storage conditions required.
After reconstitution: the solution should be stored at 2–8°C and used within 24 hours.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Depakine contains
Each vial of powder contains 400 mg of sodium valproate.
After reconstitution, each 1 ml of solution contains 100 mg of sodium valproate.
What Depakine looks like and contents of the pack
Depakine is a white to off-white powder. The solvent is a clear, colourless liquid.
Depakine is available in packs containing:

1 vial of powder and 1 ampoule of solvent (4 ml),
4 vials of powder and 4 ampoules of solvent (4 ml each).

For further information about this medicinal product, please contact the Marketing Authorisation Holder or the Parallel Importer.
Marketing Authorisation Holder in Bulgaria, the country of export:
Sanofi Winthrop Industrie, 82 avenue Raspail, 94250 Gentilly, France
Manufacturer:
Sanofi S.r.l, Via Valcanello 4, 03012 Anagni, Italy
Parallel Importer:
InPharm Sp. z o.o., ul. Strumykowa 28/11, 03-138 Warsaw
Repackaged by:
InPharm Sp. z o.o. Services sp. k., ul. Chełmżyńska 249, 04-458 Warsaw
Marketing Authorisation Number in Bulgaria, the country of export: 9600303
Parallel Import Licence Number: 93/21
Patient Information Leaflet for women and Patient Information Leaflet for men are available by scanning the QR code located on the package leaflet using a smartphone. The same information is also available at the website https://inpharm.pl/narzedzia-edukacyjne/#walproiniany
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Information intended exclusively for healthcare professionals

The vial and ampoule contain an overage to allow for withdrawal of the specified amount:

Vial: 415 mg of lyophilized sodium valproate powder (displacement factor: 8.65%).
Ampoule: 4.25 ml of solvent (water for injections).

Reconstitution

Using a graduated syringe, withdraw 3.8 ml of solvent (water for injections) from the ampoule and inject it into the vial containing the lyophilized powder.
Allow sufficient time for complete dissolution.
The total volume of the reconstituted solution is 4.15 ml with a concentration of 100 mg/ml.
4 ml of the reconstituted injection solution (100 mg/ml) can be withdrawn from the vial.

The reconstituted solution is clear and almost colorless.
Preparation of intravenous Depakine should be performed immediately before use, and the solution should be used within 24 hours.
The infusion solution may be administered from containers made of polyvinyl chloride, polyethylene, or glass.
Physicochemical compatibility has been demonstrated with the following solutions:

Sodium chloride 0.9% (0.9 g in 100 ml)
Glucose 5% (5 g in 100 ml)
Glucose 10% (10 g in 100 ml)
Glucose 20% (20 g in 100 ml)
Glucose 30% (30 g in 100 ml)
Glucose 2.55% + NaCl 0.45% (2.55 g + 0.45 g in 100 ml)
Sodium bicarbonate 0.14% (0.14 g in 100 ml)
Trometamol (THAM) 3.66% + NaCl 0.172% (3.66 g + 0.172 g in 100 ml), using 400 mg of intravenous Depakine in 500 ml of each of the above solutions (except for trometamol: 250 ml).