Depakine

Package Leaflet: Information for the User

DEPAKINE

288.2 mg/5 ml, syrup

Sodium valproate
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See section 4 for how to report side effects.

WARNING

Depakine (sodium valproate) can cause serious harm to the unborn child when taken during pregnancy. Women of childbearing potential must use effective contraception (birth control) without interruption during the entire treatment period with Depakine. The doctor will discuss this with the patient, and the patient should also follow the recommendations presented in section 2 of this leaflet.
Patients should immediately contact their doctor if they plan to become pregnant or if they suspect they are pregnant.
Depakine should not be discontinued without the advice of a doctor, as the patient's condition may worsen.

It is essential to carefully read the leaflet before taking the medicine, as it contains important information for the patient.

• The leaflet should be kept to be re-read if necessary.
• In case of any doubts, the patient should consult a doctor or pharmacist.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, 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 side effects
• 5. How to store Depakine
• 6. Contents of the pack and other information

1. What is Depakine and what is it used for

Depakine is a syrup that contains the active substance sodium valproate. It belongs to a group of antiepileptic medicines and acts on the central nervous system. It has antiepileptic effects in various forms of epilepsy in humans.
Depakine is used in adults and children for monotherapy or in combination with other antiepileptic medicines:

• for the treatment of generalized seizures such as: clonic seizures, tonic seizures, tonic-clonic seizures, absence seizures, myoclonic seizures, and atonic seizures;
• for the treatment of partial seizures: partial seizures that are or are not secondarily generalized.

2. Important information before taking Depakine

When not to take Depakine

Do not take the medicine if:

• the patient is allergic to the active substance sodium valproate or any of the other ingredients of this medicine (listed in section 6),
• the patient has acute or chronic hepatitis,
• the patient has had severe hepatitis, especially drug-induced or if the patient's family history indicates severe hepatitis,
• the patient has porphyria (a very rare metabolic disorder),
• the patient is taking mefloquine concurrently,
• the patient has a genetic disorder causing mitochondrial disorders (e.g., Alpers-Huttenlocher syndrome),
• the patient has metabolic disorders, such as disorders of the urea cycle,
• 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 potential, unless the patient uses effective contraception (birth control) throughout the treatment period with Depakine. Do not stop taking Depakine or contraception without discussing it with the doctor. The doctor will provide further guidance (see below "Pregnancy, breastfeeding, and fertility - Important advice for women").

Warnings and precautions

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

THE PATIENT MUST IMMEDIATELY INFORM THEIR DOCTOR:

• If the patient experiences any of the following symptoms: weakness, loss of appetite, sleepiness, recurring vomiting, and abdominal pain, jaundice (yellowing of the skin and whites of the eyes), or an increase in seizures, especially during the first 6 months of treatment. Depakine may cause severe liver damage, which can be life-threatening. Before starting treatment and during the first 6 months of treatment, the patient should have regular liver function tests. The risk of liver damage increases if Depakine is used in children under 3 years old, patients taking other antiepileptic medicines, or patients with other neurological or metabolic disorders.
• If the patient experiences severe abdominal pain, they should immediately inform their doctor. Depakine may rarely cause severe pancreatitis, which can be life-threatening.
• If the patient or their child taking Depakine experiences balance and coordination problems, drowsiness, or a feeling of reduced alertness, vomiting, they should immediately inform their doctor. This may be due to increased ammonia levels in the blood.
• A small number of people taking antiepileptic medicines, including those containing sodium valproate, have had thoughts of harming themselves or suicide. If the patient ever has such thoughts, they should immediately contact their doctor.
• Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS (drug reaction with eosinophilia and systemic symptoms), and angioedema, have been reported with valproate. If the patient notices any of the symptoms related to these severe skin reactions, they should immediately consult their doctor.

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

• Sodium valproate should not be used in women with epilepsy who are planning to become pregnant, unless 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 taking sodium valproate is planning to become pregnant. Women of childbearing potential must use effective contraception during treatment.
• Before starting treatment, the patient should have laboratory tests (blood morphology with smear, including platelet count, bleeding time, and coagulation tests), especially before surgery or in case of bruising or spontaneous bleeding.
• The medicine should be used with caution in patients with renal impairment. The doctor may recommend a lower dose.
• The medicine should be used with caution in patients with systemic lupus erythematosus.
• If the patient is suspected to have any metabolic disorder, especially inborn errors of metabolism, such as "urea cycle disorders", due to the risk of increased ammonia levels in the blood.
• Patients taking sodium valproate may experience weight gain.
• If the patient has a rare metabolic disorder called "carnitine palmitoyltransferase II deficiency", due to the increased risk of muscle disorders.
• It is not recommended to take antibiotics from the carbapenem group with valproic acid (see section "Depakine and other medicines").
• 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 medicines, the severity or frequency of seizures may increase during treatment with this medicine. If the patient experiences an increase in seizures, they should immediately consult their doctor.
• If the patient has inadequate carnitine intake, found in meat and dairy products, especially in children under 10 years old.
• If the patient has a carnitine deficiency and is taking carnitine.
• If the patient has ever experienced a severe skin rash or exfoliative dermatitis after taking sodium valproate.

Depakine and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Some medicines may affect the action of sodium valproate, and sodium valproate may 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;
• kanabidiol (used to treat epilepsy and other conditions);
• certain antibiotics that contain 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), see also section "Special warnings and precautions for use of Depakine";
• 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;
• estrogen-containing medicines (including some contraceptives);
• metamizole (used to treat pain and fever);
• clozapine (used to treat mental illnesses).

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

Depakine with food, drink, and alcohol

The medicine should be taken with meals.
It is not recommended to drink alcohol during treatment with sodium valproate.

Pregnancy, breastfeeding, and fertility

Pregnancy

Important advice for women

• Do not take Depakine if the patient is pregnant, unless no other therapy is effective.
• If the patient is of childbearing potential, they should not take Depakine unless they use effective contraception (birth control) throughout the treatment period with Depakine. Do not stop taking Depakine or contraception without discussing it with the doctor. The 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 doctor if they plan to become pregnant or if they suspect they are pregnant.
• Taking sodium valproate during pregnancy carries a risk. The higher the dose, the greater the risk, but no dose is completely safe, even when sodium valproate is used in combination with other antiepileptic medicines.
• 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; heart, kidney, urinary tract, and genital abnormalities; 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 abnormalities, often in combination with other birth defects. Eye abnormalities can affect vision.
• Women taking sodium valproate during pregnancy are at a higher risk of giving birth to a child with birth defects that require medical treatment. Sodium valproate has been used for many years, and it is known that about 11 out of 100 children born to mothers taking sodium valproate will have birth defects. For comparison, such defects are found in about 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 experience developmental problems. Children with the condition may start walking and talking later, be less intellectually able than other children, have language problems, and have memory difficulties.
• Children exposed to sodium valproate are more likely to be diagnosed with autism spectrum disorders. Some evidence suggests that these children may be at a higher risk of developing attention deficit hyperactivity disorder (ADHD).
• Before prescribing this medicine, the doctor will explain the risks to the patient, and the patient should not stop taking Depakine or contraception without discussing it with the doctor.
• Some contraceptives (estrogen-containing contraceptives) may decrease the level of sodium valproate in the blood. The patient should discuss their contraception method with their doctor.
• Parents or guardians of girls taking sodium valproate should contact the doctor when their child starts menstruating.
• The patient should ask their doctor about taking folic acid when 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 FOR A CHILD
about CONTINUING TREATMENT WITH DEPAKINE WHILE TRYING FOR A CHILD

TRYING FOR A CHILD

If the patient is planning to become pregnant, they should first make an appointment with their doctor. Do not stop taking Depakine or contraception without discussing it with the doctor. The doctor will provide further guidance.
Children born to mothers who took sodium valproate during pregnancy are at a higher risk of birth defects and developmental problems, which can significantly impair the child. The doctor will refer the patient to a specialist experienced in treating epilepsy to assess alternative treatment options. The specialist may take steps to ensure the best possible outcome for the pregnancy and minimize the risk to the mother and unborn child.
The patient should ask their doctor about taking folic acid when 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

• Do not stop taking Depakine unless the doctor decides to do so.
• Do not stop using contraception before discussing it with the doctor and developing a plan to ensure the patient's condition is controlled and the risks to the child are minimized.
• The patient should first make an appointment with their doctor. During this appointment, the doctor will ensure that the patient is well-informed and understands all the risks and advice related to taking sodium valproate during pregnancy.
• The doctor will try to switch the patient to another medicine or stop Depakine treatment well before the patient becomes pregnant.
• If the patient is pregnant or suspects they may be pregnant, they should make an urgent appointment with their doctor.

BECOMING PREGNANT WHILE CONTINUING TREATMENT WITH DEPAKINE

Do not stop taking Depakine without discussing it with the doctor, as the patient's condition may worsen. If the patient is pregnant or suspects they may be pregnant, they should make an urgent appointment with their doctor. The doctor will provide further guidance.
Children born to mothers who took sodium valproate during pregnancy are at a higher 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 and sodium valproate exposure.
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 make an urgent appointment with their doctor.
• Do not stop taking Depakine unless the doctor decides to do so.
• The patient should ensure they are referred to a specialist experienced in treating epilepsy to assess the need for alternative treatment options.
• The patient must receive counseling about 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 they are referred to a specialist for prenatal monitoring to detect any developmental abnormalities.

Newborns whose mothers 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 doctor.

The doctor will discuss and ask the patient to sign and keep the annual confirmation form regarding the risks and benefits of sodium valproate treatment. The patient will also receive a patient card from the pharmacist to remind them of the risks associated with sodium valproate treatment during pregnancy.

Important advice for male patients

Possible risk associated with taking sodium valproate in the 3 months before conception
A study suggests a possible risk of developmental disorders (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 whose fathers were treated with lamotrigine or levetiracetam (other medicines that may be used to treat the patient's condition). The risk to children whose fathers stopped taking sodium valproate at least 3 months (the time needed to produce new sperm) before conception is not known. The study has limitations, and it is not clear whether the suggested increased risk of developmental disorders is caused by sodium valproate. The study was not large enough to show what specific types of developmental disorders are associated with this risk.
As a precaution, the doctor will discuss with the patient:

• the possible risk to children whose fathers were treated with sodium valproate;
• the need for the patient and their partner to use effective contraception during treatment and for 3 months after stopping treatment;
• the need to consult the doctor when planning to conceive and before stopping contraception;
• the possibility of using alternative treatments for the patient's condition, depending on their individual situation.

Do not donate sperm while taking sodium valproate and for 3 months after stopping treatment.
If the patient is planning 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, they should contact their doctor. Do not stop taking Depakine without consulting the doctor, as the patient's condition may worsen.
The patient should regularly visit their doctor. During such a visit, the doctor will discuss the precautions associated with sodium valproate treatment and the possibility of using alternative treatments for the patient's condition, depending on their individual situation.
The patient should read the patient guide provided by their doctor. The patient will also receive a patient card from the pharmacist to remind them of the possible risk associated with sodium valproate treatment.
Breastfeeding
Sodium valproate is excreted in small amounts into breast milk. The patient should consult their doctor about whether they can breastfeed during treatment.

Driving and using machines

Some patients may experience drowsiness during treatment, especially when taking several antiepileptic medicines or when taking benzodiazepines concurrently. Before driving or operating machinery, the patient should make sure they know how they react to the treatment.

Important information about some ingredients of Depakine

Depakine contains parahydroxybenzoates and may cause allergic reactions (possible late reactions).

Depakine contains sucrose and sorbitol.

The medicine contains 105 mg of sorbitol per 1 ml of syrup.
Sorbitol is a source of fructose. If the patient (or their child) has been diagnosed with intolerance to some sugars or has been diagnosed with hereditary fructose intolerance, a rare genetic disorder in which the patient's body does not break down fructose, the patient should contact their doctor before taking the medicine or giving it to their child.

Depakine contains sodium.

Depakine in a dose above 170 mg contains more than 24 mg of sodium (the main component of common salt). This corresponds to 1.2% of the maximum recommended daily intake of sodium in the diet for adults.

Depakine contains alcohol.

The medicine contains 0.00027 mg of alcohol (ethanol) per 1 ml of syrup. The small amount of alcohol in this medicine will not have noticeable effects.

3. How to take Depakine

Depakine should always be taken as directed by the doctor. If the patient has any doubts, they should consult their doctor.
Girls and women of childbearing potential
Treatment with Depakine should be started and supervised by a doctor specializing in epilepsy.
Male patients
It is recommended that treatment with Depakine be started and supervised by a specialist with experience in treating epilepsy - see section 2 "Important advice for male patients".
Recommended doses are usually:

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

The medicine should be taken with meals:

• in children under 1 year of age, in 2 divided doses;
• in patients over 1 year of age, in 3 divided doses.

Starting treatment with sodium valproate
Treatment with sodium valproate in patients taking other antiepileptic medicines should be introduced gradually, reaching the optimal dose of the medicine within 2 weeks, and then gradually reducing the doses of other antiepileptic medicines while controlling the symptoms of the disease.
In patients not taking other antiepileptic medicines, the dose of sodium valproate should be increased every 2-3 days to reach the optimal dose of the medicine within about 1 week.
Method of administration
The medicine is administered using a syringe with a marked scale, included in the packaging.
The syringes should not be used to administer other medicines, as the marked scale on the syringe is specifically designed for Depakine syrup.
To administer the medicine using the syringe, the patient should:

• make sure the syringe plunger is pushed all the way in, then insert the syringe into the bottle
• pull the plunger up and draw the prescribed dose of the medicine into the syringe. The drawn dose should be read on the marked scale
• place the end of the syringe in the patient's mouth. Press the plunger slowly and gently to administer the entire prescribed dose of the medicine
• after administering the syrup, rinse the syringe with water 2 or 3 times

The syringe should be stored in the box with the bottle.
After the first opening of the bottle, the medicine can be stored for 1 month.
Duration of treatment
The medicine should be taken for as long as the doctor recommends.
If the patient feels that the effect of Depakine is too strong or too weak, they should consult their doctor.
Patients with renal impairment
The doctor may decide to adjust the dose.

Taking a higher dose of Depakine than recommended

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

Missing a dose of Depakine

If the patient misses a dose, they should take it as soon as possible, unless it is almost time for the next dose. Do not take two doses of the medicine at the same time or in a short period. If the patient has any doubts, they should consult their doctor.

Stopping treatment with Depakine

Do not stop taking Depakine without consulting the doctor, as the patient's condition may worsen.

4. Possible side effects

Like all medicines, Depakine can cause side effects, although not everybody gets them. Patients may need appropriate treatment for some side effects.

If the patient experiences any of the following serious side effects, they should immediately contact their doctor, as they may need urgent medical attention:

• Coma, encephalopathy (brain damage), lethargy (a 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 taking phenobarbital or when rapidly increasing the dose 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
• Balance and coordination problems, drowsiness, or a feeling of reduced alertness, accompanied by vomiting. This may be due to increased ammonia levels in the blood (hyperammonemia)
• Increased number and severity of seizures
• Extreme fatigue, weakness, loss of appetite, sleepiness, recurring vomiting, and abdominal pain, severe abdominal pain, nausea, jaundice (yellowing of the skin and whites of the eyes), or an increase in seizures. These symptoms may indicate liver or pancreas damage
• Allergic reactions, which may manifest as: blisters with skin peeling (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" or drug reaction with eosinophilia and systemic symptoms (DRESS) or erythema multiforme or angioedema
• Blood coagulation disorders, 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, coordination disorders (parkinsonism, extrapyramidal disorders, ataxia)
• Muscle pain and weakness (rhabdomyolysis - breakdown of striated muscle)
• Difficulty breathing, chest pain or a 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 (renal failure, interstitial nephritis), which may manifest as decreased urine output

5. How to store Depakine

Store in a dry place, protected from light. The medicinal product should be stored in a place inaccessible and invisible to children. Do not use the medicinal product after the expiry date stated on the packaging. Medicines should not be disposed of via wastewater or household waste containers. 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

100 ml of syrup contains:
active substance:
sodium valproate
5.764 g
excipients:
methyl p-hydroxybenzoate
0.10 g
propyl p-hydroxybenzoate
0.02 g
sucrose
60.0 g
sorbitol (70% solution)
15.0 g
glycerol
15.0 g
cherry flavor (contains ethanol)
0.03 g
hydrochloric acid or
sodium hydroxide
to pH 7.3-7.7
purified water
to 100 ml
5 ml of syrup contains 288.2 mg of sodium valproate.

What Depakine looks like and what the package contains

The package contains 150 ml of syrup.
A plastic measuring syringe with a capacity of 6 ml and a scale every 10 mg is attached to the package.

Marketing authorization holder and manufacturer

Marketing authorization holder
Sanofi Winthrop Industrie
82, Avenue Raspail
94250 Gentilly
France
Manufacturer:
Unither Liquid Manufacturing
1-3 Allée de la Neste
Z.I. d‘en Sigal
31770 Colomiers
France
Manufacturer/Importer:
Sanofi Winthrop Industrie
30-36 Avenue Gustave Eiffel,
37100 Tours
France
To obtain more detailed information about 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 update of the leaflet:December 2024

Other sources of information

Detailed and up-to-date information about this medicinal product is available by scanning the QR code on the leaflet and the outer packaging using a smartphone. The same information is also available on the website: www.qr.walproinianija.pl