Package leaflet: Information for the user

Warning! Please keep this leaflet. The information on the immediate packaging is in a foreign language.
Depakine
400 mg (400 mg/4 ml), powder and solvent for solution for injection
Sodium valproate
▼ This medicinal product is subject to additional monitoring. This will allow rapid identification
of new safety information. You can also help by reporting any side effects you experience after using
this medicine. For information on how to report side effects – see section 4.
WARNING
The use of Depakine (sodium valproate) 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. Your doctor will discuss this
with you. Please also follow the recommendations provided in section 2 of this leaflet.
Contact your doctor immediately if you are planning a pregnancy or suspect you may be pregnant.
Do not stop taking Depakine unless your doctor tells you to, 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 questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm someone else, even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

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 for solution for injection and contains the active substance sodium valproate.
Sodium valproate belongs to a group of medicines called anticonvulsants. It has anticonvulsant
effects in various types of epilepsy in humans.
Depakine is used:

in epileptic conditions when 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, especially if the patient has previously been effectively treated orally with sodium valproate. This applies to both 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 liver inflammation,
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),
when mefloquine is being used concomitantly,
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 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 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, you must inform your doctor immediately.
Depakine may cause severe liver damage, sometimes leading to death. Laboratory 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 forms of epilepsy. Sodium valproate should not be given concomitantly with salicylates in children under 3 years of age due to the risk of hepatotoxic effects.
In case of sudden severe abdominal pain, you must inform your doctor immediately. Very rarely, Depakine may cause severe pancreatitis, sometimes fatal.
If the patient or their child taking Depakine develops problems with balance and coordination, drowsiness or reduced alertness, or vomiting, you must inform your doctor immediately. This may be due to increased blood ammonia levels.
A small number of people taking antiepileptic medicines containing sodium valproate have had thoughts about harming or killing themselves. If such thoughts ever 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 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 before any surgical procedure, and in case of bruises or spontaneous bleeding, laboratory tests should be performed (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 cautiously 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 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 mainly excreted by the kidneys, partly in the form of ketone bodies; therefore, in diabetic patients, ketone body 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 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.

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

neuroleptic medicines, 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 indications),
certain anti-infective medicines 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),
anticoagulant medicines,
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 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 medicines. Your doctor will inform you 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
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 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.

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 pregnant.
Taking valproate during pregnancy carries risks. The higher the dose, the greater the risk, but no dose is completely risk-free, even when valproate is used in combination with other 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 are not properly developed); facial and skull developmental defects; heart, kidney, urinary tract and genital organ defects; limb defects; and many associated developmental defects affecting multiple 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.
Eye developmental defects, together with other congenital malformations, have been reported in children exposed to valproate in utero. Eye developmental defects may affect vision.
Pregnant women taking valproate have an increased risk of giving birth to a child with congenital malformations requiring treatment. Valproate has been used for many years, and it is known that in a group of children whose mothers took valproate during pregnancy, 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 indicates an increased risk of attention deficit (attention deficit hyperactivity disorder - ADHD) in these children.
Before prescribing this medicine, your doctor will explain the risks to the unborn child if you become pregnant while taking valproate. If you are taking this medicine and decide you want to have a child, do not stop taking the medicine or contraception on your own; discuss it with your doctor first.
Some contraceptive methods (contraceptive pills containing estrogen) may reduce the blood concentration of valproate. Discuss with your doctor the most appropriate method of contraception for you.
Parents or caregivers of girls treated with valproate should contact the doctor when their child starts menstruation.
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 the situation below that applies to the patient and read the relevant information:
o STARTING TREATMENT WITH DEPAKINE
o CONTINUING TREATMENT WITH DEPAKINE WITHOUT TRYING FOR A CHILD
o CONTINUING TREATMENT WITH DEPAKINE WHILE PLANNING TO CONCEIVE
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 you become pregnant. A woman of childbearing potential should ensure that she uses an effective method of contraception continuously throughout the entire Depakine treatment period. If you need advice on contraception, consult your 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 the treating doctor.
The patient should use an effective method of contraception (birth control) throughout the entire Depakine treatment period.
Discuss with your treating doctor the appropriate method of contraception (birth control). Your doctor will provide information on pregnancy prevention and may refer you to a specialist for contraception advice.
You should have regular visits (at least once a year) with a specialist experienced in treating epilepsy. During these visits, your doctor will ensure you have been adequately informed and understand all risks and advice related to valproate use 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 TRYING FOR A CHILD
If the patient continues treatment with Depakine and does not plan pregnancy, she must be certain that she uses an effective method of contraception continuously throughout the entire Depakine treatment period. If you need advice on contraception, consult your doctor or a family planning clinic.
Important information:

The patient should use an effective method of contraception (birth control) throughout the entire Depakine treatment period.
Discuss contraception (birth control method) with your treating doctor. Your doctor will provide information on pregnancy prevention and may refer you to a specialist for contraception advice.
You should have regular visits (at least once a year) with a specialist experienced in treating epilepsy. During these visits, your doctor will ensure you have been adequately informed and understand all risks and advice related to valproate use 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 TO CONCEIVE
If the patient plans to have a child, she should first schedule an appointment with her treating doctor. Do not stop taking Depakine or contraception until this has been discussed with your treating 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 appropriately assess alternative treatment options early. The specialist may take actions to ensure the best possible pregnancy outcome and minimize risks to both mother and unborn child.
The treating specialist may decide to change 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 will reduce the risk of congenital malformations associated with valproate treatment.
Important information:

Do not stop treatment with Depakine unless your doctor decides so.
Do not stop using contraception methods before talking to your treating 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 treating doctor. During this visit, your doctor will ensure you have been adequately informed and understand all risks and advice related to valproate use during pregnancy.
Your treating 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 treating doctor.

BECOMING PREGNANT WHILE CONTINUING TREATMENT WITH DEPAKINE
Do not stop treatment with Depakine until this has been discussed with your treating doctor, as your health condition may worsen. If you are pregnant or suspect you may be pregnant, schedule an urgent appointment with your treating 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 assess alternative treatment options.
In exceptional circumstances, when Depakine is the only available treatment option during pregnancy, you will be closely monitored, both regarding treatment of the 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 will reduce 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 treating doctor.
Do not stop treatment with Depakine unless your doctor decides so.
You should ensure you have been referred to a specialist experienced in treating epilepsy to assess 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.
You should ensure you have been referred to a specialist specializing 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, feeding difficulties.
Please read the patient guide provided by your treating 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 risk 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 during the 3 months before conception. In this study, about 5 out of 100 children whose fathers were treated with valproate had such disorders, compared to about 3 out of 100 children whose fathers were treated with lamotrigine or levetiracetam (other medicines that may be used to treat the patient's condition). The risk in children whose fathers discontinued valproate treatment at least 3 months (the time required for new sperm production) before conception is unknown. The study has limitations, and therefore 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 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 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 during valproate treatment and for 3 months after discontinuation.
If planning parenthood, discuss this with your doctor.
If your partner becomes pregnant while you are taking valproate within the 3 months before conception and you have questions, contact your doctor. Do not stop treatment without consulting your doctor, as symptoms may worsen if you discontinue treatment.
You should have regular visits with the doctor who prescribed the medicine. During these visits, your doctor will discuss precautions related to valproate use and the possibility of alternative treatment methods for your condition, depending on your individual situation.
Please read the patient guide provided by your treating 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
Drowsiness may occur in some patients 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.

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

The medicine should always be used as directed by the physician. In case of doubt, consult your doctor.

Female patients and women of childbearing potential
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.

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 for 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 more than 3 minutes), usually at 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 have shown that outcomes do not depend on gender, duration of injection, prior use of other antiepileptic drugs, or previously administered doses of valproic acid within the range of 5.3–28 mg/kg body weight/day.

General notes
The daily dose should be determined according to age and body weight; however, individual sensitivity should also be taken into account.

The optimal dose is determined based on the clinical response to treatment; serum valproic acid concentration measurements should be considered an additional monitoring tool, necessary only when clinical 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 as a direct slow intravenous injection or as a continuous infusion. If other medicines are being administered simultaneously, Depakine should be given through a separate catheter.

Whenever possible, treatment should be continued with the oral formulation at generally recommended doses.

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.

Use of a higher than recommended dose of Depakine
Clinical symptoms of severe overdose include: coma, reduced muscle tone, diminished tendon reflexes, miosis (pupillary constriction), and respiratory disturbances. Metabolic acidosis, hypotension, 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 medicinal formulations 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.

In case of administration of a higher than recommended dose of the medicine, 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 directed by your doctor.

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.
Contact your doctor immediately if any of the following severe 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 increased frequency or worsening of epileptic seizures, especially when phenobarbital is used concomitantly or when the dose of Depakine is rapidly increased
Confusion, weakness, dizziness, nausea, vomiting, which may be due to 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 caused by increased blood ammonia levels (hyperammonemia)
Increased frequency and severity of seizures
Extreme fatigue, weakness, loss of appetite, drowsiness, recurrent vomiting and abdominal pain, severe upper abdominal pain, nausea, jaundice (yellowing of the skin and whites of the eyes), leg swelling, or increased frequency of seizures, or general malaise – these symptoms may indicate liver or pancreas damage
Allergic reactions, which may manifest as:
o Skin blistering with 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"
o Skin rash or skin lesions with pink/red rings and pale centres, which may be itchy, peeling or fluid-filled. The rash may appear especially on palms or soles. These may be symptoms of a disease called "erythema multiforme"
o Allergy-induced swelling with painful, itchy oedema (most commonly around the eyes, lips, throat, and sometimes hands and feet) – these may be symptoms of "angioedema"
o 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
Impaired blood coagulation confirmed by laboratory tests, which may lead to spontaneous bruising and bleeding
Marked decrease in white blood cell count or bone marrow failure (myelodysplastic syndrome) shown in blood tests, sometimes accompanied by 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 manifest as reduced urine output.

Other adverse reactions 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 no more than 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, convulsions, memory disturbances, 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 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 may be associated with polycystic ovary syndrome,
irregular menstrual cycles,
confusion (disorientation), hallucinations, aggression, agitation, attention disturbances,
urinary incontinence.

Uncommon (may occur in no more than 1 in 100 people):

leukopenia (marked decrease in white blood cell count), 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, virilization, acne, male-pattern baldness and/or elevated androgen levels),
vasculitis,
lowered body temperature, mild oedema of feet and legs,
absence of menstruation.

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

macrocytic anaemia (low number of red blood cells), macrocytosis (abnormal enlargement of red blood cells),
biotin deficiency/biotinidase deficiency,
excessive urine output 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/or hereditary or genetic diseases,
decreased carnitine levels (visible 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 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
Reporting adverse reactions helps to collect more information on the safety of the medicine.

5. How to store Depakine

No special storage requirements apply.
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 packaging. The expiry date refers to the last day of the stated month.
Medicines should 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 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 pack
Pack sizes:

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

For more detailed information, please contact the responsible party or parallel importer.

Marketing Authorisation Holder in Bulgaria, country of export:
Sanofi Winthrop Industrie
82 avenue Raspail, 94250 Gentilly, France

Manufacturer:
Sanofi S.r.l
Via Valcanello 4
03012 Anagni (FR), Italy

Parallel Importer:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź, Poland

Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź, Poland

Marketing Authorisation Number in Bulgaria, country of export: 9600303
Parallel Import Licence Number: 204/17

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 healthcare professionals:

Instructions for use – reconstitution and administration
To prepare the solution, inject the provided solvent, wait until
dissolution is complete, and then withdraw the appropriate dose.
The concentration of the prepared solution is 100 mg/ml, resulting from the volume increase caused by sodium valproate.
The intravenous formulation of Depakine should be prepared 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 0.9% 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,
Tromethamine (THAM): 3.66 g + NaCl: 0.172 g in 100 ml,
when 400 mg of intravenous Depakine is added to 500 ml of each of the above solutions (except for tromethamine: 250 ml).