Depakine

Leaflet accompanying the packaging: information for the user

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 quick identification of new safety information. The user of the medicinal product can also help by reporting any adverse reactions that occur after taking the medicinal product. 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 age should use effective contraception (birth control) without interruption throughout the entire period of treatment with Depakine. The treating doctor will discuss this with the patient, and the patient should also follow the recommendations presented in section 2 of this leaflet.
Patients should contact their treating doctor immediately if they plan to become pregnant or if they suspect they are pregnant.
Depakine should not be discontinued unless advised by a doctor, as the patient's condition may worsen.

It is necessary to carefully read the contents of the leaflet before taking the medicinal product, as it contains important information for the patient.

• The leaflet should be kept so that it can be re-read if necessary.
• In case of any doubts, the patient should consult a doctor or pharmacist.
• This medicinal product has been prescribed specifically for one person. It should not be passed on to others. The medicinal product may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any adverse reactions, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Depakine and what is it used for
• 2. Important information before taking Depakine
• 3. How to take Depakine
• 4. Possible adverse reactions
• 5. How to store Depakine
• 6. Contents of the packaging and other information

1. What is Depakine and what is it used for

Depakine is a powder for solution for injection containing the active substance sodium valproate. Sodium valproate belongs to a group of antiepileptic medicinal products. It has antiepileptic effects in various types of epilepsy in humans.
Depakine is used:

• in epileptic states where benzodiazepines administered intravenously are ineffective;
• in generalized seizures;
• in the treatment of seizure attacks when oral treatment is temporarily impossible due to the state of consciousness or inability to swallow, especially if the patient was previously

successfully treated orally with sodium valproate. This applies to generalized and partial seizures;

• prophylactically in connection with neurosurgical head operations, when there is a risk of seizure(s) occurring.

2. Important information before taking Depakine

When not to take Depakine:

Depakine should not be taken in the following cases:

• if the patient is allergic to the active substance sodium valproate or any of the other ingredients of this medicinal product (listed in section 6),
• if the patient has acute and chronic hepatitis,
• if the patient has had severe hepatitis, especially drug-induced or if the patient's family history indicates severe hepatitis,
• if the patient has porphyria (a very rare metabolic disorder),
• in combination with mefloquine.
• if the patient has a genetic disorder causing mitochondrial disorders (e.g., Alpers-Huttenlocher syndrome),
• if the patient has metabolic disorders, such as disorders of the urea cycle,
• if the patient has a carnitine deficiency (a very rare metabolic disorder) that is not being treated.
• epilepsy:
• if the patient is pregnant, unless no other therapy is effective,
• if the patient is of childbearing age, unless the patient uses effective contraception (birth control) throughout the entire treatment period with Depakine. Depakine should not be discontinued or contraception stopped without consulting a doctor. The treating doctor will provide further guidance (see below "Pregnancy, breastfeeding, and fertility - Important note for women").

Warnings and precautions

Before starting to take Depakine, the patient should discuss it with their doctor.

THE PATIENT SHOULD IMMEDIATELY INFORM THEIR TREATING DOCTOR:

• In case of sudden onset of the following symptoms: weakness, loss of appetite, drowsiness, recurring vomiting, and abdominal pain, jaundice (yellowing of the skin and whites of the eyes) or recurrence of seizures, especially during the first 6 months of treatment, the patient should immediately inform their treating doctor.
• Depakine may cause severe liver damage, sometimes resulting in death. Before starting treatment and during the first 6 months of treatment, liver function tests should be performed periodically. The risk of liver damage increases if Depakine is used in children under 3 years of age, people taking other antiepileptic medicinal products, or those with other neurological or metabolic disorders, as well as in people with severe epilepsy. Children under 3 years of age should not be given sodium valproate in combination with salicylates due to the risk of toxic effects on the liver.
• In case of acute abdominal pain, the patient should immediately inform their treating doctor. Depakine may rarely cause severe pancreatitis, sometimes resulting in death.
• If the patient or their child taking Depakine experiences balance and coordination problems, drowsiness, or decreased alertness, vomiting, they should immediately inform their treating doctor. This may be caused by increased ammonia levels in the blood.
• A small number of people taking antiepileptic medicinal products containing sodium valproate have thought about harming or killing themselves. If such thoughts occur, the patient should immediately contact their treating doctor.
• In connection with the treatment with sodium valproate, severe skin reactions have been reported, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and erythema multiforme. If the patient notices any symptoms related to these severe skin reactions, as described in section 4, they should immediately consult a doctor.

Before taking this medicinal product, the patient should discuss it with their doctor:

• Sodium valproate should not be used in women with epilepsy planning to become pregnant, unless other treatments are ineffective or not tolerated. The benefits of using the medicinal product should be weighed against the risks before the first prescription or when a woman treated with sodium valproate plans to become pregnant. Women of childbearing age must use effective contraception during treatment.
• Before starting treatment, including before surgery and in case of bruising or spontaneous bleeding, laboratory tests are recommended (blood morphology test, including platelet count, bleeding time, and coagulation tests).
• Depakine should be used with caution in patients with impaired renal function. The doctor may recommend a lower dose of the medicinal product.
• The medicinal product should be used with caution in patients with systemic lupus erythematosus.
• If the patient is suspected to have any metabolic disorder, especially congenital enzyme deficiencies, such as "urea cycle disorders", due to the risk of increased ammonia levels in the blood.
• Weight gain may occur in patients treated with sodium valproate.
• If the patient has a rare disorder called "carnitine palmitoyltransferase II deficiency" due to the increased risk of muscle disorders.
• The concomitant use of carbapenem antibiotics with valproic acid is not recommended (see "Depakine and other medicinal products").
• Sodium valproate is mainly excreted by the kidneys, partly in the form of ketone bodies, so in diabetic patients, the test for ketone bodies may give a false positive result.
• If there is a family history of mitochondrial disorders or if the doctor suspects such a disorder, due to the risk of liver damage.
• As with other antiepileptic medicinal products, the severity or frequency of seizures may increase during treatment with this medicinal product. If the seizures worsen, the patient should immediately consult a doctor.
• If the patient has inadequate carnitine intake, found in meat and dairy products, especially in children under 10 years of age.
• If the patient has a carnitine deficiency and is taking carnitine.
• If the patient has ever experienced a severe skin rash or exfoliation after taking sodium valproate.

Depakine and other medicinal products

The patient should tell their doctor about all medicinal products they are currently taking or have recently taken, as well as any medicinal products they plan to take.
Some medicinal products may affect the action of sodium valproate, and sodium valproate may affect the action of other medicinal products.
These include:

• neuroleptics, including quetiapine, olanzapine (used to treat psychotic disorders);
• medicinal products used to treat depression, MAO inhibitors;
• benzodiazepines, used to treat insomnia and anxiety disorders;
• other medicinal products used to treat epilepsy, including phenobarbital, phenytoin, primidone, lamotrigine, carbamazepine, felbamate, topiramate, rufinamide;
• kanabidiol (used to treat epilepsy and other indications);
• certain antibacterial medicinal products containing pivampicillin (such as pivampicillin, adefovir dipivoxil);
• methotrexate (used to treat cancer and inflammatory diseases);
• zydovudine, 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 stomach ulcers);
• erythromycin, rifampicin;
• carbapenems (antibiotics used to treat bacterial infections); cholestyramine (used to lower cholesterol levels in the blood);
• propofol (used for general anesthesia);
• nimodipine
• medicinal products containing estrogen (including some contraceptive medicinal products);
• metamizole (used to treat pain and fever);
• clozapine (used to treat mental illnesses).

These medicinal products may affect the action of sodium valproate and vice versa. The patient may need to adjust the dose of individual medicinal products or use other medicinal products. The doctor will inform the patient about these changes in treatment.
The doctor will also provide additional information about medicinal products that should be used with caution or avoided during treatment with Depakine.

Depakine with food, drink, and alcohol

It is not recommended to drink alcohol during treatment with sodium valproate.

Pregnancy, breastfeeding, and fertility

Pregnancy

Important note for women

• Depakine should not be taken if the patient is pregnant, unless no other therapy is effective.
• If the patient is of childbearing age, they should not take Depakine unless they use effective contraception (birth control) throughout the entire treatment period with Depakine. The patient should not stop taking Depakine or contraception without consulting their doctor. The treating doctor will provide further guidance.

Risk of taking sodium valproate during pregnancy (regardless of the disease being treated with sodium valproate)

• The patient should immediately consult their treating doctor if they plan to become pregnant or if they are pregnant.
• Taking sodium valproate during pregnancy carries a risk. The higher the dose, the greater the risk, but no dose is risk-free, even when sodium valproate is used in combination with other antiepileptic medicinal products.
• Sodium valproate may cause serious birth defects and affect the physical and mental development of the child after birth.
• The most common birth defects include: spina bifida (when the bones of the spine are not properly developed); developmental abnormalities of the face and skull; developmental abnormalities of the heart, kidneys, urinary tract, and genital organs; limb abnormalities; and many related developmental abnormalities affecting several organs and body parts. Birth defects can cause disability, which can be significant.
• Children exposed to sodium valproate in the womb have been reported to have hearing problems or deafness.
• Children exposed to sodium valproate in the womb have been reported to have eye developmental abnormalities, often in combination with other birth defects. Eye developmental abnormalities can affect vision.
• In children born to mothers taking sodium valproate, about 11 out of 100 children will have birth defects. For comparison, such defects are found in 2-3 out of 100 children born to women without epilepsy.
• It is estimated that up to 30-40% of preschool-age children whose mothers took sodium valproate during pregnancy may exhibit early developmental problems. Affected children may start walking and talking later, be less intellectually able, have language problems, and have memory difficulties.
• Children exposed to sodium valproate in the womb are more likely to be diagnosed with various autism spectrum disorders. Some evidence suggests that these children may have an increased risk of developing attention deficit hyperactivity disorder (ADHD).
• Before prescribing this medicinal product, the treating doctor will explain to the patient what may threaten the child if the patient becomes pregnant while taking sodium valproate. If the patient taking this medicinal product decides to have a child, they should not stop taking Depakine or contraception without consulting their treating doctor.
• Some contraceptive medicinal products (estrogen-containing oral contraceptives) may decrease sodium valproate levels in the blood. The patient should discuss their contraception method with their doctor.
• Parents or guardians of girls treated with sodium valproate should contact the treating doctor when their child starts menstruating.
• The patient should ask their doctor about taking folic acid while trying to conceive. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with sodium valproate treatment.

Choose the situation that applies to the patient and read the information:

about STARTING TREATMENT WITH DEPAKINE
about CONTINUING TREATMENT WITH DEPAKINE WITHOUT TRYING TO CONCEIVE
about CONTINUING TREATMENT WITH DEPAKINE WHILE TRYING TO CONCEIVE

STARTING TREATMENT WITH DEPAKINE

If Depakine is prescribed for the first time, the treating doctor will explain the risks to the unborn child if the patient becomes pregnant. Women of childbearing age should ensure that they use effective contraception throughout the entire treatment period with Depakine.
If the patient needs advice on contraception, they should consult their doctor or a family planning clinic.

Important information

• The patient should use effective contraception (birth control) throughout the entire treatment period with Depakine.
• The patient should discuss their contraception method with their treating doctor. The treating doctor will provide information on pregnancy prevention and may refer the patient to a specialist for advice on contraception.
• The patient should have regular check-ups (at least once a year) with a specialist experienced in treating epilepsy. During this check-up, the treating doctor will ensure that the patient has been well-informed and understands all the risks and advice related to taking sodium valproate during pregnancy.
• If the patient plans to become pregnant, they should inform their doctor.
• If the patient is pregnant or suspects they may be pregnant, they should immediately inform their doctor.

CONTINUING TREATMENT WITH DEPAKINE WITHOUT TRYING TO CONCEIVE

If the patient continues treatment with Depakine and does not plan to become pregnant, they must ensure that they use effective contraception throughout the entire treatment period with Depakine.
If the patient needs advice on contraception, they should consult their doctor or a family planning clinic.

Important information

• The patient should use effective contraception (birth control) throughout the entire treatment period with Depakine.
• The patient should discuss their contraception method with their treating doctor. The treating doctor will provide information on pregnancy prevention and may refer the patient to a specialist for advice on contraception.
• The patient should have regular check-ups (at least once a year) with a specialist experienced in treating epilepsy. During this check-up, the treating doctor will ensure that the patient has been well-informed and understands all the risks and advice related to taking sodium valproate during pregnancy.
• If the patient plans to become pregnant, they should inform their doctor.
• If the patient is pregnant or suspects they may be pregnant, they should immediately inform their doctor.

CONTINUING TREATMENT WITH DEPAKINE WHILE TRYING TO CONCEIVE

TRYING TO CONCEIVE

If the patient plans to become pregnant, they should first schedule a consultation with their treating doctor.
The patient should not stop taking Depakine or contraception without discussing it with their treating doctor. The treating doctor will provide further guidance.
Children born to mothers who took sodium valproate during pregnancy are at high risk of birth defects and developmental problems, which can significantly impair the child. The treating doctor will refer the patient to a specialist experienced in treating epilepsy to assess alternative treatment options. The specialist may take actions to ensure the best possible outcome of the pregnancy and minimize the risk to the mother and unborn child.
The specialist may decide to change the dose of Depakine, switch to another medicinal product, or discontinue Depakine treatment long before becoming pregnant - to ensure that the disease is stable.
The patient should ask their doctor about taking folic acid while trying to conceive. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with sodium valproate treatment.

Important information

• The patient should not stop taking Depakine unless advised by their doctor.
• The patient should not stop using contraception before discussing it with their treating doctor and developing a plan to ensure control of their condition and minimize risks to the child.
• First, the patient should schedule a consultation with their treating doctor. During this consultation, the treating doctor will ensure that the patient has been well-informed and understands all the risks and advice related to taking sodium valproate during pregnancy.
• The treating doctor may consider switching to another medicinal product or discontinuing Depakine treatment.
• If the patient is pregnant or suspects they may be pregnant, they should schedule an urgent consultation with their treating doctor.

BEING PREGNANT WHILE CONTINUING TREATMENT WITH DEPAKINE

The patient should not stop taking Depakine unless advised by their treating doctor, as their condition may worsen.
If the patient is pregnant or suspects they may be pregnant, they should schedule an urgent consultation with their treating doctor. The treating doctor will provide further guidance.
Children born to mothers who took sodium valproate during pregnancy are at high risk of birth defects and developmental problems, which can significantly impair the child.
The patient will be referred to a specialist experienced in treating epilepsy to assess alternative treatment options.
In exceptional circumstances, when Depakine is the only available treatment option during pregnancy, the patient will be closely monitored, both in terms of the underlying disease and fetal development. The patient and their partner will receive counseling and support regarding the pregnancy exposed to sodium valproate.
The patient should ask their doctor about taking folic acid. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with sodium valproate treatment.

Important information

• If the patient is pregnant or suspects they may be pregnant, they should schedule an urgent consultation with their treating doctor.
• The patient should not stop taking Depakine unless advised by their doctor.
• The patient should ensure that they have been referred to a specialist experienced in treating epilepsy to assess the need for alternative treatment options.
• The patient must receive counseling on the risks of taking Depakine during pregnancy, including its teratogenic effects (causing birth defects) and physical and mental developmental disorders in children.
• The patient should ensure that they have been referred to a specialist for prenatal monitoring to detect any developmental abnormalities.

Newborns of mothers who took Depakine during pregnancy may experience coagulation disorders, hypoglycemia, hypothyroidism, and withdrawal symptoms such as: irritability, restlessness, hyperactivity, tremors, seizures, and feeding problems.

The patient should read the patient guide provided by their treating doctor.

The treating doctor will discuss the annual confirmation form regarding the risk and ask the patient to sign and keep it. The patient will also receive a patient card from the pharmacist to remind them of the risk of taking sodium valproate during pregnancy.

Important note for male patients

Possible risk associated with taking sodium valproate in the 3 months before conception
A study suggests a possible risk of motor disorders and developmental delays (problems with development in early childhood) in children whose fathers were treated with sodium valproate in the 3 months before conception. In this study, such disorders occurred in about 5 out of 100 children whose fathers were treated with sodium valproate, compared to about 3 out of 100 children of men treated with lamotrigine or levetiracetam (other medicinal products that may be used to treat the patient's disease). The risk to children whose fathers stopped taking sodium valproate at least 3 months (the time needed to produce new sperm) before conception is unknown. The study has limitations, and it is not clear whether the suggested increased risk of developmental delays is caused by sodium valproate. The study was not large enough to show what specific types of motor disorders and developmental delays are involved.

• The doctor will discuss with the patient:
• the possible risk to children whose fathers were treated with sodium valproate;
• the need to consider using effective contraception (birth control) by the patient and their partner during treatment and for 3 months after its completion;
• the need to consult a doctor when planning to conceive and before stopping contraception;
• the possibility of using other treatment options for the patient's disease, depending on their individual situation.

The patient should not donate sperm while taking sodium valproate and for 3 months after stopping it.
If the patient plans to have children, they should discuss it with their doctor.
If the patient's partner becomes pregnant while the patient is taking sodium valproate in the 3 months before conception and the patient has questions about it, they should contact their doctor. The patient should not stop taking Depakine without consulting their doctor. If the patient stops taking Depakine, their symptoms may worsen.
The patient should regularly visit their doctor. During such a visit, the doctor will discuss with the patient the precautions related to taking sodium valproate and the possibility of using other treatment options for their disease, depending on their individual situation.
The patient should read the patient guide provided by their treating doctor. The patient will also receive a patient card from the pharmacist to remind them of the possible risk associated with taking sodium valproate.

Breastfeeding

Sodium valproate is excreted in small amounts into breast milk. The patient should consult their doctor about whether they can breastfeed while taking Depakine.

Driving and using machines

Some patients may experience drowsiness during treatment, especially when taking several antiepileptic medicinal products or when taking benzodiazepines concomitantly. Before driving or using machines, the patient should make sure how they react to the treatment.

Depakine contains sodium

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

3. How to take Depakine

The medicinal product should always be taken as directed by the doctor. In case of doubts, the patient should consult their doctor.
Girls and women of childbearing age
Treatment with Depakine should be started and supervised by a doctor specializing in the treatment of epilepsy.
Male patients
It is recommended that the use of Depakine be started and supervised by a specialist with experience in the treatment of epilepsy - see section 2 "Important note for male patients".
Patients who have been successfully treated with oral Depakine can be given the current dose in a continuous intravenous infusion or multiple injections; for example, if the patient was taking 25 mg/kg body weight per day, treatment can be continued for 2-3 days with a continuous infusion at a rate of 1 mg/kg body weight per hour. The dose and duration of administration are interdependent.

Other patients can be given the medicinal product initially in a slow intravenous injection (over 3 minutes), usually 15 mg/kg body weight, and then continued as an intravenous infusion at a rate usually of 1 to 2 mg/kg body weight per hour, adjusted according to clinical response.

Studies have shown that the results are not dependent on sex, injection time, prior use of another antiepileptic medicinal product, or previously used dose of valproic acid within the range of 5.3 - 28 mg/kg body weight per day.

General notes

The daily dose is determined based on age and body weight, but individual sensitivity should be taken into account.
The optimal dose is determined based on the clinical response to treatment; determination of valproic acid levels in serum should be considered as an additional element of monitoring, necessary only when clinical control of seizures is inadequate or adverse reactions have occurred. The average effective concentration is usually 50 - 120 mg/l (375 - 840 µmol/l).
Depakine can be administered intravenously through direct slow injection or as a continuous infusion. If other medicinal products are administered concomitantly, Depakine should be given through a separate catheter.
When possible, treatment should be continued with the oral preparation in the generally recommended doses.
Duration of treatment
The medicinal product should be taken for as long as directed by the doctor.
If the patient feels that the effect of Depakine is too strong or too weak, they should consult their doctor.
Patients with impaired renal function
The doctor may decide to modify the dose in the patient.

Taking a higher than recommended dose of Depakine

Clinical symptoms of severe overdose include: coma, decreased muscle tone, decreased reflexes, pinpoint pupils, and respiratory disorders. Metabolic acidosis, decreased blood pressure, and acute cardiovascular failure may also occur. Other symptoms may occur; seizures have been reported in cases of very high valproate levels in the blood.
The presence of sodium in valproate formulations may lead to increased sodium levels in the blood in case of overdose of the medicinal product.
Hospital treatment of overdose is symptomatic; it should involve monitoring of cardiovascular and respiratory function.
In severe cases, hemodialysis or even exchange transfusion may be necessary.
In individual cases, the use of naloxone has been effective.
If the patient has taken a higher dose of Depakine than recommended, they should immediately consult their doctor or pharmacist.

Missing a dose of Depakine

The patient should not take two doses of the medicinal product at the same time or at short intervals. The patient should continue taking the medicinal product as directed by their doctor.
In case of missing several doses of the medicinal product, the patient should immediately contact their doctor.

Stopping treatment with Depakine

Without consulting their doctor, the patient should not stop taking Depakine or change the dose of the medicinal product. If the patient stops taking Depakine without consulting their doctor, their condition may worsen.

4. Possible adverse reactions

Like all medicinal products, Depakine can cause adverse reactions, although not everybody gets them. Patients may need appropriate treatment in case of some adverse reactions.

If the patient experiences any of the following serious adverse reactions, they should immediately consult their doctor, as they may need urgent medical attention:

• Coma, encephalopathy (brain damage), lethargy (state of indifference and lack of reaction to stimuli), changes in behavior related or unrelated to increased frequency of seizures or their severity, especially when phenobarbital is used concomitantly or during rapid dose increase of Depakine
• Confusion, weakness, dizziness, nausea, vomiting, which may be caused by low sodium levels in the blood or a condition called "SIADH" (Syndrome of Inappropriate Secretion of ADH) or inappropriate antidiuretic hormone secretion syndrome
• Balance and coordination problems, drowsiness, or decreased alertness, accompanied by vomiting. This may be caused by increased ammonia levels in the blood (hyperammonemia)
• Increased number and severity of seizures
• Extreme fatigue, weakness, loss of appetite, drowsiness, recurring vomiting, and abdominal pain, severe abdominal pain, nausea, jaundice (yellowing of the skin and whites of the eyes), or increased frequency of seizures, or general malaise - these symptoms may indicate liver or pancreas damage
• Allergic reactions, which may manifest as: o Blisters with skin exfoliation (formation of blisters, peeling, or bleeding from various parts of the body, including the lips, eyes, mouth, nose, genitals, hands, or feet) with or without rash, sometimes with flu-like symptoms, such as fever, chills, or muscle pain - these may be symptoms of conditions called "toxic epidermal necrolysis" or "Stevens-Johnson syndrome" o Skin rash or skin changes with a pink/red ring and pale center, which may be itchy, peeling, or fluid-filled. The rash may appear especially on the palms or soles. These may be symptoms of a condition called "erythema multiforme" o Swelling caused by an allergic reaction with painful, itchy, and swollen areas (most often around the eyes, lips, throat, and sometimes hands and feet) - these may be symptoms of "angioedema"

o
A syndrome with skin rash, fever, lymph node enlargement, and possible liver damage - these may be symptoms of a condition called "DRESS" or drug reaction with eosinophilia and systemic symptoms

• Blood coagulation disorders confirmed by laboratory tests, which may cause spontaneous bruising and bleeding
• Significant decrease in white blood cell count or bone marrow failure (myelodysplastic syndrome) shown in blood tests, sometimes accompanied by fever and breathing difficulties
• Hypothyroidism, which may cause fatigue or weight gain
• Arthralgia, fever, fatigue, rash. These may be symptoms of systemic lupus erythematosus
• Tremors, gait disturbances, muscle stiffness, movement coordination disorders (parkinsonism, extrapyramidal disorders, ataxia)
• Muscle pain and weakness (rhabdomyolysis - breakdown of striated muscle)
• Breathing difficulties, chest pain or feeling of pressure in the chest (especially when inhaling), shortness of breath, and dry cough due to fluid accumulation around the lungs (pleural effusion)
• Kidney disease (kidney failure, interstitial nephritis), which may manifest as decreased urine output

If the patient experiences any adverse reactions, including those not listed in this leaflet, they should inform their doctor or pharmacist.

5. How to store Depakine

The medicinal product should be stored in a place inaccessible and invisible to children. The medicinal product should not be used after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month. Unopened vial with powder: no special storage precautions. After reconstitution: the solution should be used immediately. Medicines should not be disposed of via wastewater or household waste containers. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Package contents 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 what the pack contains

Depakine is a white powder. The solvent is a clear, colorless 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.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder: Sanofi Winthrop Industrie, 82, Avenue Raspail, 94250 Gentilly, France. Manufacturer: Sanofi S.r.l., Via Valcanello 4, 03012 Anagni, Italy. For more detailed information on this medicinal product, please contact the representative of the marketing authorization holder in Poland: Sanofi Sp. z o.o., ul. Marcina Kasprzaka 6, 01-211 Warsaw, tel.: +48 22 280 00 00. Date of last revision of the leaflet:February 2025

Other sources of information

Detailed and up-to-date information on this medicinal product is available by scanning the QR code on the leaflet using a smartphone. The same information is also available on the website: www.qr.walproinianija.pl
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Information intended for healthcare professionals only
The vial and ampoule contain an overfill to allow for the withdrawal of the specified amount:

• Vial: 415 mg of lyophilized sodium valproate powder (overfill 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 into the vial of lyophilized powder.
• Allow to dissolve completely.
• The total volume of the reconstituted solution is 4.15 ml with a concentration of 100 mg/ml.
• 4 ml of the reconstituted solution for injection (100 mg/ml) can be withdrawn from the vial.

The reconstituted solution is clear and almost colorless. Preparation of the intravenous form of Depakine should occur immediately before use, and the solution should be used within 24 hours. The solution for infusion can be administered from a container made of polyvinyl chloride, polyethylene, or glass. Physicochemical compatibility has been demonstrated with the following solutions: sodium chloride 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 the intravenous form of Depakine in 500 ml of each of the above solutions (except trometamol: 250 ml).