Depakine

Leaflet attached to the packaging: information for the user

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

Depakine (Depakine I.V.)

400 mg (400 mg/4 ml), powder and solvent for solution for injection
Sodium valproate
Depakine and Depakine I.V. are different trade names for the same medicine.
▼ This medicinal product is subject to additional monitoring. This will allow for quick
identification of new safety information. The user of the medicine can also help by
reporting any adverse reactions that occur after taking the medicine. To learn how to
report adverse reactions, see section 4.

WARNING

Depakine medicine (sodium valproate) used during pregnancy can seriously harm the
unborn child. Women of childbearing age should use effective birth control (contraception) continuously throughout the entire period of taking Depakine medicine. The doctor
will discuss this with the patient, and the patient should also follow the recommendations presented in
section 2 of this leaflet.
It is necessary to immediately contact the attending physician if the patient plans to become pregnant or
if she suspects that she is pregnant.
Depakine medicine should not be discontinued unless the doctor recommends it, as the patient's condition may worsen.

It is necessary to carefully read the contents of the leaflet before taking the medicine, 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, you should consult a doctor or pharmacist.
• This medicine has been prescribed for a specific person. It should not be passed on to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. What is Depakine medicine and what is it used for

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

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

When not to take Depakine medicine

Depakine medicine 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 medicine (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),
• with concurrent use of mefloquine,
• if the patient has a genetic disorder causing mitochondrial disorders (e.g., patients with 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 birth control (contraception) throughout the entire treatment period with Depakine medicine. Depakine medicine and contraception should not be discontinued unless discussed with a doctor. The attending physician will provide further guidance (see below "Pregnancy, breastfeeding, and fertility - Important note for women").

Warnings and precautions

Before starting to take Depakine medicine, it is necessary to discuss it with a doctor.

THE ATTENDING PHYSICIAN MUST BE IMMEDIATELY INFORMED:

• In case of sudden occurrence 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 seizure attacks, especially during the first 6 months of treatment, the attending physician must be immediately informed.
• Depakine medicine may cause severe liver damage, sometimes resulting in death. Before starting treatment and during the first 6 months of treatment, periodic laboratory tests of liver function should be performed. The risk of liver damage increases if Depakine medicine is used in children under 3 years of age, people taking other antiepileptic medicines, or people 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 concurrently with salicylates due to the risk of toxic effects on the liver.
• In case of acute abdominal pain, the attending physician must be immediately informed. Very rarely, Depakine medicine may cause severe pancreatitis, sometimes resulting in death.
• If the patient or their child taking Depakine medicine experiences balance and coordination problems, drowsiness, or a feeling of reduced alertness, vomiting, the attending physician must be immediately informed. This may be caused by an increased amount of ammonia in the blood.
• A small number of people taking antiepileptic medicines containing sodium valproate have thought about harming or killing themselves. If such thoughts ever occur to the patient, they should immediately contact their attending physician.

Before taking this medicine, it is necessary to discuss it with a doctor:

• 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 risk before the medicine is first prescribed or when the woman taking valproate plans to become pregnant. Women of childbearing age must use effective contraception during treatment.
• Before starting treatment, as well as before surgery and in case of bruising or spontaneous bleeding, it is recommended to perform laboratory tests (blood morphology test with smear, including platelet count, bleeding time, and coagulation tests).
• The medicine should be used with caution in patients with impaired renal function. The doctor may recommend a lower dose of the medicine.
• The medicine 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.
• Patients treated with sodium valproate may experience weight gain.
• If the patient has a rare disorder called "carnitine palmitoyltransferase II deficiency" due to the increased risk of muscle disorders.
• Concomitant use of carbapenem antibiotics with valproic acid is not recommended (see: Depakine medicine 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 that such a disorder exists, due to the risk of liver damage.
• As with other antiepileptic medicines, the severity or frequency of seizure attacks may increase during treatment with this medicine. In case of increased severity of seizure attacks, it is necessary to immediately consult a doctor.
• If the patient has insufficient 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.

Depakine medicine and other medicines

The doctor should be informed about all medicines currently being taken by the patient or
recently taken, as well as about medicines that the patient plans to take.
Some medicines may affect the action of sodium valproate, and valproate may affect the action of other medicines.
These include the following medicines:

• 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 indications);
• certain antibacterial medicines 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);
• anticoagulant medicines;
• 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;
• medicines containing estrogen (including some contraceptive measures);
• metamizole (used to treat pain and fever).

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 medicine.

Depakine medicine with food, drink, and alcohol

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

Pregnancy, breastfeeding, and fertility

Pregnancy

Important note for women

• Depakine medicine should not be taken if the patient is pregnant, unless no other therapy is effective.
• If the woman is of childbearing age, she should not take Depakine medicine unless she uses effective birth control (contraception) throughout the entire treatment period with Depakine medicine. Depakine medicine and contraception should not be discontinued unless discussed with a doctor. The attending physician will provide further guidance.

Risk of taking valproate during pregnancy (regardless of the disease for which valproate is used)

• The attending physician should be immediately consulted if the patient plans to become pregnant or is pregnant.
• Taking valproate during pregnancy carries a risk. The higher the dose, the greater the risk, but no dose is risk-free, even when valproate is used in combination with other antiepileptic medicines.
• Valproate may cause serious birth defects and affect the physical and mental development of the child after birth. The most common birth defects reported 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 valproate in utero have reported hearing problems or deafness.
• Children exposed to valproate in utero have reported eye developmental abnormalities, often in combination with other birth defects. Eye developmental abnormalities can affect vision.
• In women taking valproate during pregnancy, there is an increased risk of giving birth to a child with birth defects that require treatment. Valproate has been used for many years, and it is known that in a group of children born to mothers taking valproate, about 11 children out of 100 will have birth defects. For comparison, such defects are found in 2-3 children out of every 100 born to women without epilepsy.
• It is estimated that up to 30-40% of preschool-age children whose mothers took valproate during pregnancy may exhibit early developmental problems. Children with the disease may later start walking and talking, be less intellectually agile than other children, may have language problems, and memory problems.

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

Please read the patient guide provided by the attending physician.

The attending physician will discuss the annual confirmation form regarding awareness of 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 valproate during pregnancy.

Breastfeeding
Valproate is excreted in small amounts into breast milk. It is necessary to consult a doctor about whether it is possible to breastfeed during treatment.

Driving and operating machinery

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

Depakine medicine contains sodium

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

3. How to take Depakine medicine

The medicine should always be taken according to the doctor's recommendations. In case of doubts, the doctor should be consulted.
Treatment with Depakine medicine should be started and supervised by a doctor specializing in the treatment of epilepsy.
In patients who have been successfully treated with oral Depakine medicine, the current dose can be used in 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 a period of 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 medicine 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 of usually 1 to 2 mg/kg body weight per hour, adjusting it to the clinical response.
Studies have shown that the results are not dependent on sex, injection time, previous use of another antiepileptic medicine, 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; determining the concentration of valproic acid in serum should be treated as an additional monitoring element, necessary only when clinical control of seizures is insufficient or adverse reactions have occurred. The average effective concentration is usually 50 - 120 mg/liter (375 - 840 μmol/l).
Depakine medicine can be administered intravenously through direct slow intravenous injection or as a continuous infusion. If other medicines are used concurrently, Depakine medicine should be administered through a separate catheter.
When possible, treatment should be continued with the oral preparation in the generally recommended doses.
Duration of treatment
The medicine should be used for as long as the doctor recommends.
In case of a feeling that the effect of Depakine medicine is too strong or too weak, the doctor should be consulted.
Patients with renal impairment
The doctor may decide to modify the dose in the patient.

Using a higher dose of Depakine medicine than recommended

Clinical symptoms of severe overdose are: coma, decreased muscle tone, decreased reflexes, pupil constriction, 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.
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.
In case of taking a higher dose of the medicine than recommended, the doctor or pharmacist should be immediately consulted.

Missing a dose of Depakine medicine

A double dose of the medicine should not be taken at the same time or at short intervals. The dosing of the medicine should be continued according to the doctor's recommendations.
In case of missing several doses of the medicine, the doctor should be immediately consulted.

Discontinuing Depakine medicine

Without consulting a doctor, treatment with Depakine medicine should not be discontinued, nor should the dose of the medicine be changed. If treatment is discontinued without consulting a doctor, the patient's condition may worsen.

4. Possible adverse reactions

Like any medicine, Depakine medicine can cause adverse reactions, although not everyone will experience them. Patients may need appropriate treatment in case of certain adverse reactions.
The attending physician should be immediately contacted in case of any of the following serious adverse reactions, as urgent medical attention may be necessary:

• Coma, encephalopathy (brain damage), lethargy (state of indifference and lack of reaction to stimuli), changes in behavior related or unrelated to increased frequency of seizure attacks or their severity, especially in case of concurrent use of phenobarbital or during rapid increase in Depakine medicine dose
• Confusion, weakness, dizziness, nausea, vomiting, which may be caused by decreased 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 a feeling of reduced alertness, combined with 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 seizure attacks, or general poor health - these symptoms may indicate liver or pancreas damage
• Allergic reactions, which may manifest as: o Blisters with skin exfoliation (formation of blisters, exfoliation, or bleeding from various parts of the body, including the lips, eyes, mouth, nose, genital organs, 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 a pale center, which may be itchy, exfoliating, or fluid-filled. The rash may appear especially on the hands or soles of the feet. These may be symptoms of a disease 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 a skin rash, fever, lymph node enlargement, and possible damage to other organs - these may be symptoms of a condition called "DRESS" or drug rash with eosinophilia and systemic symptoms
• Blood coagulation disorders confirmed by 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 manifested 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 stiffness, movement coordination disorder (parkinsonism, extrapyramidal disorders, ataxia)
• Muscle pain and weakness (rhabdomyolysis - breakdown of striated muscle)
• Breathing difficulties and pain due to inflammation of the pleura (pleural effusion)
• Kidney disease (kidney failure, interstitial nephritis), which may manifest as decreased urine output.

Other adverse reactions are presented according to the following frequency classification:
Very common(may occur in more than 1 in 10 people):

• tremors,
• nausea.

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

• anemia (decreased red blood cell count), thrombocytopenia (decreased platelet count, which increases the risk of bleeding and bruising),
• stupor (state of indifference and lack of reaction to stimuli), drowsiness, seizures, memory disorders, headache, nystagmus (rapid, uncontrolled eye movements), dizziness (which may occur within a few minutes after intravenous administration and usually resolve spontaneously after a few minutes),
• hearing loss,
• vomiting, stomach pain, diarrhea (frequent in some patients at the beginning of treatment) usually resolving spontaneously after a few days without the need to discontinue treatment,
• abnormalities of the gums (mainly gum hypertrophy), oral inflammation,
• temporary and (or) dose-dependent hair loss, nail disorders, and nail bed disorders,
• weight gain, which should be monitored as it is associated with polycystic ovary syndrome,
• irregular menstrual cycles,
• confusion (disorientation), hallucinations, aggression, agitation, attention disorders,
• urinary incontinence.

Uncommon(may occur in up to 1 in 100 people):

• leukopenia (significant decrease in white blood cell count), pancytopenia (significant decrease in blood cell count, which may cause weakness, easy bruising, or increased risk of infection),
• feeling of tingling and numbness in hands or feet,
• skin rash, hair abnormalities (such as abnormal hair structure, hair color changes, abnormal hair growth),
• decreased bone mineral density, osteopenia, osteoporosis, and fractures in patients taking Depakine medicine for a long time,
• hyperandrogenism (excessive male-type hair growth, virilization, acne, male-type baldness, and (or) elevated androgen levels),
• vasculitis (inflammation of blood vessels),
• hypothermia (low body temperature), swelling of feet and legs of moderate severity,
• amenorrhea (absence of menstruation).

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

• macrocytic anemia (low red blood cell count), macrocytosis (abnormal increase in red blood cell size),
• biotin deficiency/biotinidase deficiency,
• excessive urine production and thirst (Fanconi syndrome),
• nocturnal enuresis (bedwetting),
• obesity,
• male infertility is usually temporary after discontinuation of treatment and may be temporary after dose reduction. Treatment should not be discontinued without prior consultation with a doctor,
• polycystic ovary syndrome,
• abnormal behavior, hyperactivity, learning disorders (observed in children and adolescents),
• transient dementia, related to transient brain atrophy, cognitive disorders, double vision.

Frequency not known(frequency cannot be determined based on available data):

• congenital disorders and hereditary or genetic diseases,
• decreased carnitine levels (visible in blood and muscle tests).

Additional adverse reactions in children

Certain adverse reactions of valproate occur more frequently or are more severe in children than in adults. These include liver damage, pancreatitis, aggression, agitation, attention disorders, abnormal behavior, hyperactivity, and learning disorders.

Reporting adverse reactions

If any adverse reactions occur, including any adverse reactions not listed in the leaflet, the doctor, pharmacist, or nurse should be informed. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products 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
By reporting adverse reactions, more information can be collected on the safety of using the medicine.

5. How to store Depakine medicine

There are no special recommendations for storing the medicine.
The solution should be stored in a refrigerator at 2-8°C, used within 24 hours.
The medicine should be stored out of sight and reach of children.
The medicine should not be used after the expiration date stated on the packaging. The expiration date indicates the last day of the specified month.
Medicines should not be disposed of in the sewage system or household waste containers. The pharmacist should be asked how to dispose of unused medicines. This will help protect the environment.

6. Package contents and other information

What Depakine medicine 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 medicine looks like and what the package contains

Package sizes: 1 vial of powder and 1 ampoule with 4 ml of solvent.
For more detailed information, the marketing authorization holder or parallel importer should be contacted.

Marketing authorization holder in Belgium, the country of export:

Sanofi Belgium
Leonardo Da Vincilaan 19
1831 Diegem
Belgium

Manufacturer:

Sanofi S.r.l.
Via Valcanello 4
03012 Anagni
Italy

Parallel importer:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Belgian marketing authorization number, the country of export: BE163134

Parallel import authorization number: 166/24

Date of leaflet approval: 24.04.2024

Other sources of information

Detailed and up-to-date information about this medicine is available by scanning the QR code on the leaflet using a smartphone. The same information is also available on the website: https://sirpl.org/walproinian
[Information about the trademark]
[QR code]
---------------------------------------------------------------------------
Information intended only for healthcare professionals:

Instructions for use – reconstitution and administration

To prepare the solution, the enclosed solvent should be injected, waited for until dissolution, and the proper dose taken.
The concentration of the prepared solution is 100 mg/ml, which results from the increase in the volume of the solvent by sodium valproate.
Preparation of the intravenous form of the Depakine drug should take place immediately before use, and this solution should be used within 24 hours.
The solution for intravenous infusion can be administered from a container made of polyvinyl chloride, polyethylene, or glass.
Physicochemical compatibility has been found with the following solutions:

• physiological 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 at a dose of 400 mg of the intravenous form of the Depakine drug in 500 ml of each of the above solutions (except for trometamol: 250 ml).