Package leaflet: Information for the user

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Depakine (Depakine I.V.)
400 mg (400 mg/4 ml), powder and solvent for solution for injection
Natrii valproas
Depakine and Depakine I.V. are different trade names for the same medicinal product.
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can also help by reporting any suspected adverse reactions that occur after using the medicine. For information on how to report adverse reactions – see section 4.
WARNING
The medicine Depakine (sodium valproate) used during pregnancy may seriously harm the unborn child. Women of childbearing potential must use effective contraception (birth control) continuously throughout the entire duration of treatment with Depakine. Your doctor will discuss this with you; you should also follow the recommendations provided in section 2 of this leaflet.
You must contact your doctor immediately if you are planning a pregnancy or if you suspect you may be pregnant.
Do not stop taking Depakine unless your doctor tells you to, because your condition may worsen.
Please read all of this leaflet carefully before using this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same as yours.
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet:

What Depakine is and what it is used for
Important information 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 for solution for injection and contains the active substance sodium valproate. Sodium valproate belongs to a group of medicines called antiepileptics. It has anticonvulsant activity in various types of epilepsy in humans.
Depakine is used:

in epileptic seizures when intravenous benzodiazepines are ineffective;
in status epilepticus;
for the treatment of convulsive seizures when oral treatment is temporarily impossible due to level of consciousness or inability to swallow, especially if the patient has previously been effectively treated orally with sodium valproate. This applies to generalized and partial seizures.
prophylactically in relation to 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),
if the patient has acute or chronic hepatitis,
if the patient has had severe hepatitis, especially drug-induced hepatitis, or if there is a family history of severe hepatitis,
if the patient has porphyria (a very rare metabolic disorder),
during concomitant use with mefloquine,
if the patient has a genetic disorder causing mitochondrial dysfunction (e.g. patients with Alpers-Huttenlocher syndrome),
if the patient has metabolic disorders, e.g. urea cycle disorders,
if 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 the entire treatment period with Depakine. Do not stop taking Depakine or contraception without first discussing it with your doctor. Your doctor 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.
YOU MUST IMMEDIATELY INFORM YOUR DOCTOR IF:

Any of the following symptoms occur suddenly: 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.
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 when Depakine is used 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.
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 patients taking antiepileptic medicines containing sodium valproate have had thoughts of harming themselves or committing suicide. If such thoughts occur, contact your doctor 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 potential must use effective contraception during treatment.
Before starting treatment, including prior to surgical procedures, and in case 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 impaired renal function. Your doctor may recommend a lower dose.
Depakine should be used with caution in patients with systemic lupus erythematosus.
If any metabolic disorder is suspected, 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 a rare disorder called "carnitine palmitoyltransferase II deficiency" due to increased risk of muscle disorders.
Concomitant use of carbapenem antibiotics with valproic acid is not recommended (see: Depakine and other medicines).
Sodium valproate is excreted mainly by the kidneys, partly in the form of ketone bodies; therefore, in diabetic patients, urine ketone tests may yield false-positive results.
If the patient has a family history of, or the doctor suspects, a genetic disorder caused by mitochondrial dysfunction, due to the risk of liver damage.
As with other antiepileptic drugs, seizures may worsen in severity or frequency during treatment. If seizures worsen, consult your doctor immediately.
If the patient has inadequate carnitine intake from meat and dairy products, especially in children under 10 years of age.
If the patient has carnitine deficiency and is taking carnitine supplements.

Depakine and 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 sodium 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 anticancer medicines containing pivampicillin (such as pivampicillin, adefovir dipivoxil);
methotrexate (used to treat cancer and inflammatory diseases);
zidovudine, ritonavir and lopinavir (used to treat HIV infection and AIDS);
mefloquine (used to treat and prevent malaria);
salicylates (acetylsalicylic acid);
anticoagulants;
cimetidine (used to treat gastric ulcers);
erythromycin, rifampicin;
carbapenems (antibiotics used to treat bacterial infections); cholestyramine (used to lower blood cholesterol levels);
propofol (used for general anaesthesia);
nimodipine;
medicines containing oestrogen (including certain contraceptives);
metamizole (used to treat pain and fever).

These medicines may affect the action of sodium valproate and vice versa. It may be necessary to adjust the dose of individual medicines or use alternative treatments. Your doctor will inform you of 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
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 potential, do not take Depakine unless she uses an effective method of contraception throughout the entire treatment period with Depakine. Do not stop taking Depakine or contraception until discussed with your doctor. Your doctor will provide further guidance.

Risk of using valproate during pregnancy (regardless of the condition for which valproate is used)

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 completely risk-free, even when valproate is used in combination with other antiepileptic drugs.
Valproate may cause serious congenital malformations and affect the child's physical and mental development after birth. The most commonly reported congenital malformations include: spina bifida (when the spinal bones are not properly formed); facial and cranial developmental defects; heart, kidney, urinary tract and genital organ malformations; limb malformations; and multiple associated developmental defects 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 observed 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 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, 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 an increased risk of attention deficit/hyperactivity disorder (ADHD) in these children.
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 on her own until she discusses it with her doctor.
Parents or guardians of girls treated with valproate should contact the doctor when their child starts menstruation.
Some contraceptive methods (oral contraceptives containing oestrogen) may reduce blood levels of valproate. Discuss with your doctor the most appropriate method of contraception.
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 will reduce 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:
o STARTING TREATMENT WITH DEPAKINE
o CONTINUING TREATMENT WITH DEPAKINE WITHOUT PLANNING PREGNANCY
o CONTINUING TREATMENT WITH DEPAKINE WHILE PLANNING PREGNANCY
o UNPLANNED PREGNANCY DURING CONTINUATION OF 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 the entire treatment period with Depakine. Consult your doctor or a family planning clinic if you need advice on contraception.
Important information:

Pregnancy must be ruled out before starting Depakine, using a pregnancy test confirmed by your doctor.
The patient must use an effective method of contraception throughout the entire treatment period with Depakine.
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 contraception advice.
Visit a specialist experienced in epilepsy treatment regularly (at least once a year). During this visit, your doctor will ensure that the patient has been adequately informed and understands all risks and advice related to valproate use during pregnancy.
Inform your doctor if the patient plans to have a child.
Inform your doctor immediately if the patient is pregnant or suspects she may be pregnant.

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

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

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 treatment with Depakine or contraception until this has been discussed with your doctor. Your doctor will provide further guidance.
Children born to mothers who took valproate are at serious risk of congenital malformations and developmental problems that may significantly impair the child. Your doctor will refer the patient to a specialist experienced in epilepsy treatment to assess alternative treatment options as early as possible. The specialist may take actions to ensure the best possible pregnancy outcome and minimise risks to both mother and unborn child.
The specialist may decide to change the dose of Depakine, switch to another medicine, or discontinue Depakine treatment 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 will reduce the risk of congenital malformations associated with valproate treatment.
Important information:

Do not stop treatment with Depakine unless your doctor decides to do so.
Do not stop using contraceptive methods before discussing with your doctor and jointly developing a management 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, your doctor will ensure that the patient has been adequately informed and understands all risks and advice related to valproate use during pregnancy.
Your doctor will attempt to switch to another medicine or discontinue Depakine treatment well before conception.
Schedule an urgent appointment with your doctor if the patient is pregnant or suspects she may be pregnant.

UNPLANNED PREGNANCY DURING CONTINUATION OF TREATMENT WITH DEPAKINE
Do not stop treatment with Depakine until this has been discussed with your doctor, as the patient's health condition may worsen. Schedule an urgent appointment with your doctor if the patient is pregnant or suspects she may be pregnant. Your doctor will provide further guidance.
Children born to mothers who took valproate are at serious risk of congenital malformations and developmental problems that may significantly impair the child. The patient will be referred to a specialist experienced in epilepsy treatment 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 the treatment of the underlying disease and the development of the foetus. The patient and her partner will receive counselling 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 will reduce the risk of congenital malformations associated with valproate treatment.
Important information:

Schedule an urgent appointment with your doctor if the patient is pregnant or suspects she may be pregnant.
Do not stop treatment with Depakine unless your doctor decides to do so.
The patient must be referred to a specialist experienced in epilepsy treatment to assess the need for alternative treatment options.
The patient must receive counselling on the risks of using Depakine during pregnancy, including its teratogenic effects (congenital malformations) and physical and mental developmental disorders in children.
The patient must be 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, hypoglycaemia, hypothyroidism, and withdrawal symptoms such as: agitation, irritability, hyperexcitability, muscle tremors, seizures, and feeding difficulties.
Please read the patient guide provided by your doctor.
Your doctor will discuss the annual risk acknowledgement 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 valproate use during pregnancy.

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

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

Depakine contains sodium
Depakine contains 55 mg of sodium (the main component of table salt) in 4 ml. This corresponds to 2.7% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Depakine

The medicine should always be used as directed by the physician. In case of doubt, consult your doctor.
Treatment with Depakine should be initiated and supervised by a physician specialized in the treatment of epilepsy.
In patients who have previously been successfully treated with oral Depakine, the current dose may be administered as a continuous intravenous infusion or repeated intravenous injections; for example, if the patient was taking 25 mg/kg body weight per day, treatment may be continued over 2–3 days as a continuous infusion at a rate of 1 mg/kg body weight/hour. The dose and duration of administration are interdependent.
For other patients, the medicine may initially be given as a slow intravenous injection (over at least 3 minutes), usually 15 mg/kg body weight, followed by continuation as an intravenous infusion at a rate usually of 1 to 2 mg/kg body weight/hour, adjusted according to clinical response.
Studies show that outcomes do not depend on gender, duration of injection, prior use of other antiepileptic drugs, or previously administered dose of valproic acid within the range of 5.3–28 mg/kg body weight/day.
General notes
The daily dose is determined according to age and body weight; however, individual sensitivity should also be taken into account.
The optimal dose is established based on the clinical response to treatment; serum valproic acid concentration measurements should be considered an additional monitoring tool, necessary only when seizure control is inadequate or adverse effects occur. The average effective serum concentration is usually 50–120 mg/litre (375–840 μmol/l).
Depakine may be administered intravenously either by slow direct intravenous injection or as a continuous infusion. If other medicines are administered simultaneously, Depakine should be given through a separate catheter.
When feasible, treatment should be continued with the oral formulation at the generally recommended doses.
Duration of treatment
The medicine should be used for as long as directed by the physician.
If you feel the effect of Depakine is too strong or too weak, consult your doctor.
Patients with renal impairment
The physician may decide whether dose adjustment is necessary.
Use of a higher than recommended dose of Depakine
Clinical symptoms of severe overdose include: coma, decreased muscle tone, diminished tendon reflexes, pupillary constriction, and respiratory disturbances. Metabolic acidosis, reduced arterial blood pressure, and acute circulatory failure may also occur.
Other symptoms may also appear; seizures have been reported in cases of very high blood valproate concentrations.
The presence of sodium in valproate pharmaceutical forms may lead to increased blood sodium concentration 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 administration of a higher than recommended dose, seek immediate medical advice from a physician or pharmacist.
Missed dose of Depakine
Do not administer two doses at the same time or in close succession. Continue taking the medicine as directed by your physician.
If several doses have been missed, contact your 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 consultation may worsen the patient's condition.

4. Possible adverse reactions

Like any medicine, Depakine may cause adverse reactions, although not everyone experiences them. However, patients may require appropriate treatment if certain adverse reactions occur.

Seek immediate medical advice from your doctor if any of the following serious adverse reactions occur, as urgent medical intervention may be necessary:

Coma, encephalopathy (brain damage), lethargy (a state of inertia 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 following a sudden increase in the dose of Depakine
Confusion, weakness, dizziness, nausea, vomiting, which may be caused by low blood sodium levels or a condition called "SIADH" (SIADH, Syndrome of Inappropriate Secretion of ADH) or syndrome of inappropriate antidiuretic hormone secretion
Problems with balance and coordination, drowsiness or reduced alertness, associated with vomiting. This may be due to increased blood ammonia levels (hyperammonaemia)
Increase in the number and severity of seizures
Extreme tiredness, 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), swelling of the legs, 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 shedding or bleeding from various body parts including lips, eyes, mouth, nose, genital organs, palms or soles), with or without rash, sometimes accompanied by flu-like symptoms such as fever, chills or muscle pain – these may be symptoms of conditions known as "toxic epidermal necrolysis" or "Stevens-Johnson syndrome"
- Skin rash or skin lesions with a pink/red ring and pale centre, which may be itchy, scaly or filled with fluid. The rash may appear especially on the palms or soles. These may be symptoms of a disease called "erythema multiforme"
- Swelling due to 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, 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
Marked decrease in white blood cells or bone marrow failure (myelodysplastic syndrome) shown in blood tests, sometimes presenting with fever and breathing difficulties
Hypothyroidism, which may cause fatigue or weight gain
Joint pain, fever, fatigue, rash. These may be symptoms of systemic lupus erythematosus
Tremors, gait disturbances, muscle rigidity, impaired body coordination (parkinsonism, extrapyramidal disorders, ataxia)
Muscle pain and weakness (rhabdomyolysis – breakdown of striated muscles)
Breathing difficulties and pain due to pleuritis (pleural effusion)
Kidney disease (renal failure, interstitial nephritis), which may present as reduced urine output.

Other adverse reactions are listed below according to the following frequency classification:

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

tremor,
nausea.

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

anaemia (reduced number of red blood cells), thrombocytopenia (reduced number of platelets, increasing the risk of bleeding and bruising),
stupor, drowsiness, seizures, memory disturbances, headache, nystagmus (rapid, uncontrolled eye movements), dizziness (may occur within minutes after intravenous administration and usually resolves spontaneously within a few minutes),
hearing impairment,
vomiting, stomach pain, diarrhoea (frequent in some patients at the beginning of treatment, usually transient and resolves within a few days without the need to discontinue treatment),
gum disorders (mainly gum overgrowth), stomatitis (inflammation of the mouth),
transient and/or dose-dependent hair loss, nail disorders 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 affect up to 1 in 100 people):

leucopenia (marked decrease in white blood cells), pancytopenia (marked 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 (inflammation of blood vessels),
low body temperature, mild oedema of feet and legs,
absence of menstruation.

Rare (may affect fewer 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 stop treatment without consulting your doctor first,
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, familial and/or genetic diseases,
decreased carnitine levels (detectable in blood and muscle tests).

Additional adverse reactions in children
Some adverse reactions 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 of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of 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 reactions helps to provide more information on the safety of this medicine.

5. How to store Depakine

There are no special requirements for storing this medicine.
The solution should be stored at 2-8°C and used within 24 hours.
Keep the medicine out of the 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 month indicated.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such practices help protect the environment.

6. Contents of the packaging and other information

What Depakine contains
1 vial of powder contains the active substance sodium valproate 400 mg.
1 ampoule contains the solvent - 4 ml of water for injections.
What Depakine looks like and contents of the packaging
Pack sizes: 1 vial of powder and 1 ampoule of solvent 4 ml.
For more detailed information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Belgium, country of export:
Sanofi Belgium
Leonardo Da Vincilaan 19
1831 Diegem
Belgium
Manufacturer:
Sanofi S.r.l.
Via Valcanello 4
03012 Anagni
Italy
Parallel importer:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Marketing authorisation number in Belgium, country of export: BE163134
Parallel import authorisation number: 166/24
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 package leaflet. The same information is also available on the website:
https://sirpl.org/walproinian
[QR code]

Information intended exclusively for medical professionals:

Instructions for use – reconstitution and administration
To prepare the solution, inject the provided solvent, wait until dissolution is complete, and withdraw the appropriate dose.
The concentration of the prepared solution is 100 mg/ml, due to volume increase caused by sodium valproate.
Preparation of the intravenous form of Depakine should be performed immediately before use, and the solution should be used within 24 hours.
The intravenous 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 physiological solution: 0.9 g in 100 ml
Glucose: 5 g in 100 ml
Glucose: 10 g in 100 ml
Glucose: 20 g in 100 ml
Glucose: 30 g in 100 ml
Glucose: 2.55 g + NaCl: 0.45 g in 100 ml
Sodium bicarbonate: 0.14 g in 100 ml
Trometamol (THAM): 3.66 g + NaCl: 0.172 g in 100 ml, with 400 mg of intravenous Depakine formulation in 500 ml of each of the above solutions (except for trometamol: 250 ml).