Depakine 100 mg/ml powder and solvent for solution for injection: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

DEPAKINE 100 mg/ml powder and solvent for solution for injection

Sodium valproate

This medicinal product is subject to additional monitoring, which will allow rapid identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

WARNING

Depakine, sodium valproate, can seriously harm the unborn baby when taken during pregnancy. If you are a woman of childbearing potential, you must use an effective method of contraception (birth control) continuously throughout treatment with Depakine. Your doctor will discuss this with you, but you should also follow the warning in section 2 of this leaflet.

Schedule an urgent appointment with your doctor if you wish to become pregnant or think you may be pregnant.

Do not stop taking Depakine unless your doctor tells you to, as your condition may worsen.

Read the entire leaflet carefully before starting to take this medicine, as it contains important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
- If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

What Depakine is and what it is used for
What you need to know before taking Depakine
How to take Depakine
Possible side effects
How to store Depakine
Contents of the pack and other information

1. What Depakine is and what it is used for

Depakine belongs to a group of medicines called antiepileptics. It is indicated for the treatment of various types of epilepsy in adults and children.

Depakine 100 mg/ml powder and solvent for injectable solution should be reserved for unconscious patients and other situations where oral administration is temporarily not possible, and should be replaced with the most appropriate oral formulation as soon as possible. The injectable formulation may also be used in urgent situations requiring rapid therapeutic initiation.

2. What you need to know before using Depakine

Do not use Depakine

If you are allergic (hypersensitive) to the active substance or to any of the other components of Depakine 100 mg/ml powder and solvent for injectable solution, or to any other medication, you must inform your doctor.
You must not use Depakine if you are pregnant, unless no other treatment is effective.
If you are a woman of childbearing potential, you must not take Depakine unless you use an effective method of birth control (contraception) throughout your treatment with Depakine. Do not stop taking Depakine or your contraceptive until you have discussed this with your doctor. Your doctor will advise you (see below under “Pregnancy, breastfeeding and fertility – Important warning for women”).
If you currently have any liver or pancreatic disease.
If you have previously had any liver disease.
If any of your close relatives have a history of severe liver disease (hepatitis), mainly due to medications.
If there is a family history of fatal liver function disorders during treatment with sodium valproate.
If you have hepatic porphyria (a very rare metabolic disorder).
If you have a genetic disorder causing a mitochondrial disorder (e.g., Alpers-Huttenlocher syndrome).
If you have a known metabolic disorder, such as a urea cycle disorder.
If you have untreated carnitine deficiency (a very rare metabolic disease).

If you think you may have any of these problems or if you have any doubts, consult your doctor before receiving Depakine.

Warnings and precautions

CONSULT YOUR DOCTOR IMMEDIATELY:

The risk of liver damage increases if valproate is administered to children under 3 years of age, in people taking other antiepileptic drugs simultaneously, or in those with other neurological or metabolic disorders and severe forms of epilepsy.

Your doctor should check your liver function tests before starting treatment and periodically during the first 6 months, especially in high-risk patients.

If you, or your child, suddenly develop an illness, particularly if it occurs in the first months of treatment and especially if it includes repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, upper abdominal pain, nausea, jaundice (yellowing of the skin or eyes), leg swelling, worsening of epilepsy, or a general feeling of malaise, you must consult your doctor immediately. In a very small number of patients, Depakine may affect the liver or pancreas. Impaired liver function together with pancreatic dysfunction increases the risk of fatal outcome.

If you or your child taking valproate develops problems with balance and coordination, feelings of lethargy or reduced alertness, or vomiting, inform your doctor immediately. This may be due to increased blood ammonia levels.

A small number of people treated with antiepileptic medicines such as valproic acid have had thoughts of self-harm or suicide. If at any time you have such thoughts, contact your doctor immediately.

Serious skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), erythema multiforme, and angioedema have been reported in association with valproate treatment. Seek immediate medical attention if you notice any symptoms related to these serious skin reactions described in section 4.

Before taking this medicine, consult your doctor

If you know or your doctor suspects a genetic problem caused by a mitochondrial disorder in your family, due to the risk of liver damage.
If a metabolic disorder is suspected, particularly inherited enzyme deficiencies such as a “urea cycle disorder,” due to the risk of increased blood ammonia levels.
If you have a rare disorder called “palmitoyl-coenzyme A transferase type II deficiency,” because you have a higher risk of developing muscle disorders.
If you have an altered dietary intake of carnitine, found in meat and dairy products, especially in children under 10 years of age.
If you have carnitine deficiency and are taking carnitine supplements.
If you have impaired kidney function or hypoproteinemia (decreased levels of proteins in the blood). In this case, your doctor may wish to monitor your blood valproate levels or adjust the dose.
When Depakine is administered to children under 3 years of age, concomitant administration with acetylsalicylic acid (aspirin) should be especially avoided.
If you have systemic lupus erythematosus.
If you have blood disorders (blood coagulation or thrombocytopenia). A blood test (complete blood count) is recommended before starting treatment or before surgery, and in cases of spontaneous bruising or bleeding.
If you experience weight gain at the beginning of treatment.
As with other antiepileptic medicines, seizures may worsen or occur more frequently while using this medicine. If this happens, contact your doctor immediately.
If you have ever developed a severe skin rash, peeling, blisters, and/or mouth sores after taking valproate.

Use of Depakine with other medicines

Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription, homeopathic remedies, herbal medicines, and other health-related products, as it may be necessary to interrupt treatment or adjust the dose of one or more of them.

Some medicines may alter the effect of Depakine or vice versa. These include:

Carbapenem agents (antibiotics used to treat bacterial infections).
Products containing estrogens (including some birth control pills).
Neuroleptics (medicines used to treat psychological disorders).
Medicines used to treat depression.
Benzodiazepines (medicines used for sleep or to treat anxiety).
Olanzapine and quetiapine (medicines used to treat psychiatric disorders).
Other medicines used to treat epilepsy, including phenobarbital, phenytoin, primidone, lamotrigine (the risk of severe skin rash may increase when lamotrigine and valproic acid are taken together), carbamazepine, ethosuximide, felbamate, and topiramate. Concomitant administration of Depakine with topiramate has been associated with encephalopathy and/or hyperammonemia (a brain and nervous system disorder occurring as a complication of liver disorders with or without increased blood ammonia).
Zidovudine (a medicine used to treat HIV and AIDS infections).
Mefloquine (a medicine used to treat or prevent malaria).
Salicylates (aspirin). See also “Warnings and precautions – Children under 3 years of age”.
Anticoagulants (medicines used to prevent blood clots).
Cimetidine (a medicine used to treat stomach ulcers).
Erythromycin and rifampicin (antibiotics).
Rufinamide.
Acetazolamide.
Protease inhibitors, such as lopinavir, ritonavir (used in the treatment of HIV).
Cholestyramine.
Propofol (an anesthetic).
Metamizole (a medicine used to treat pain and fever).
Cannabidiol (used to treat epilepsy and other conditions).
Methotrexate (used to treat cancer and inflammatory diseases).
Some anti-infectives containing pivalate (e.g., pivampicillin, adefovir dipivoxil).
Clozapine (for treating mental health conditions).

Depakine may increase the effects of Nimodipine (a medicine used in the treatment of hypertension, angina pectoris, and blood vessel disorders).

The activity of these and other medicines may be affected by Depakine, or they may directly affect the activity of Depakine. You may need different doses of medicine or may need to take different medicines. Your doctor or pharmacist will advise you.

Use of Depakine with food and drinks

Do not consume alcoholic beverages.

Pregnancy, breastfeeding and fertility

Pregnancy

Consult your doctor or pharmacist before using any medicine.

Important warning for women

You must not use Depakine if you are pregnant, unless no other treatment is effective.
If you are a woman of childbearing potential, you must not take Depakine unless you use an effective method of birth control (contraception) throughout your treatment with Depakine. Do not stop taking Depakine or your contraceptive until you have discussed this with your doctor. Your doctor will advise you.

Risks of valproate when taken during pregnancy

Speak with your doctor immediately if you are planning to have a baby or are pregnant.
Valproate carries a risk when taken during pregnancy. At higher doses, the risk is greater, but all doses carry a risk, even when valproate is used in combination with other medicines to treat epilepsy.
It can cause serious birth defects and can affect the child's physical and mental development and growth after birth. The most frequently reported birth defects include spina bifida (where the bones of the spine do not develop properly); craniofacial malformations, heart, kidney, urinary tract, genital organs, limb defects, and multiple associated malformations affecting several organs and body parts. Birth defects may result in disabilities that can be severe.
Hearing problems or deafness have been reported in children exposed to valproate during pregnancy.
Ocular malformations have been reported in children exposed to valproate during pregnancy, often in association with other congenital malformations. These eye malformations may affect vision.
If you take valproate during pregnancy, you have a higher risk than other women of having a baby with birth defects requiring medical treatment. As valproate has been used for many years, it is known that approximately 11 out of every 100 babies born to women taking valproate will have birth defects. This compares with 2 to 3 out of every 100 babies born to women who do not have epilepsy.
It is estimated that up to 30–40% of preschool-aged children whose mothers took valproate during pregnancy may have developmental problems in childhood. Affected children may speak and walk slowly, have lower intellectual capacity than other children, and experience language and memory difficulties.
Children exposed to valproate are diagnosed more frequently with autism spectrum disorders, and there is some evidence that these children have a higher risk of developing Attention Deficit Hyperactivity Disorder (ADHD).
If you take valproate during pregnancy, your baby may have a lower than expected weight at birth. In women taking valproate, approximately 11–15 out of every 100 babies may have lower than expected birth weight. This compares with 5–10 out of every 100 babies born to women in the general population.
Before prescribing this medicine, your doctor will have explained what could happen to your baby if you become pregnant while taking valproate. If you later decide you want to have a baby, do not stop taking your medicine or your contraceptive method until you discuss it with your doctor.
If you are a parent or caregiver of a girl being treated with valproate, contact your doctor when the girl undergoing treatment with valproate reaches menarche (first menstruation).
Some contraceptive pills (contraceptive pills containing estrogens) may reduce valproate blood levels. Be sure to discuss with your doctor the most appropriate contraceptive method (birth control) for you.
Consult your doctor about taking folic acid while trying to conceive. Folic acid may reduce the general risk of spina bifida and early miscarriage that exists in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.

Choose and read the situations that apply to you from those described below:

I am starting treatment with DEPAKINE
I am taking Depakine and do not intend to have a baby
I am taking Depakine and intend to have a baby
I am pregnant and taking Depakine

I AM STARTING TREATMENT WITH DEPAKINE

If this is the first time you have been prescribed Depakine, your doctor will have explained the risks to the fetus if you become pregnant. Once you reach childbearing age, you will need to ensure you use an effective method of contraception continuously throughout your treatment with Depakine. Consult your doctor or family planning clinic if you need advice on contraception.

Important messages:

Pregnancy must be excluded before starting treatment with Depakine, confirmed by a pregnancy test result reviewed by your doctor.
You must use an effective method of birth control (contraception) throughout your treatment with Depakine.
You must discuss appropriate methods of birth control (contraception) with your doctor. Your doctor will provide information on how to prevent pregnancy and may refer you to a specialist for contraceptive advice.
You must have regular consultations (at least annually) with a specialist experienced in the treatment of epilepsy. During this visit, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Inform your doctor if you wish to have a baby.
Consult your doctor immediately if you are pregnant or think you may be pregnant.

I AM TAKING DEPAKINE AND DO NOT INTEND TO HAVE A BABY

If you continue treatment with Depakine but do not plan to have a baby, ensure you use an effective method of contraception continuously throughout your treatment with Depakine. Consult your doctor or family planning clinic if you need advice on contraception.

Important messages:

You must use an effective method of birth control (contraception) throughout your treatment with Depakine.
You must discuss contraception (birth control) with your doctor. Your doctor will provide information on how to prevent pregnancy and may refer you to a specialist for contraceptive advice.
You must have regular consultations (at least annually) with a specialist experienced in the treatment of epilepsy. During this visit, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Inform your doctor if you wish to have a baby.
Consult your doctor immediately if you are pregnant or think you may be pregnant.

I AM TAKING DEPAKINE AND INTEND TO HAVE A BABY

If you are planning to have a baby, first schedule an appointment with your doctor.

Do not stop taking Depakine or your contraceptive method until you have discussed it with your doctor. Your doctor will advise you.

Babies born to mothers who have been treated with valproate have significant risks of birth defects and developmental problems that may be severely disabling. Your doctor will refer you to a specialist experienced in the treatment of epilepsy so that alternative treatment options can be evaluated from the outset. Your specialist may take several steps to ensure your pregnancy proceeds as safely as possible and risks to you and the fetus are minimized.

Your specialist may decide to change your Depakine dose, switch you to another medicine, or discontinue your Depakine treatment well before conception—to ensure your condition is stable.

Consult your doctor about taking folic acid when trying to conceive. Folic acid may reduce the general risk of spina bifida and early miscarriage in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.

Important messages:

Do not stop taking Depakine unless your doctor tells you to.
Do not stop using your contraceptive methods (contraception) before discussing with your doctor and working together on a plan to ensure your condition is controlled and risks to your baby are minimized.
First schedule an appointment with your doctor. During this visit, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Your doctor will attempt to switch you to another medicine or discontinue Depakine treatment well before conception.
Schedule an urgent appointment with your doctor if you are pregnant or think you may be pregnant.

I AM PREGNANT AND TAKING DEPAKINE

Do not stop taking Depakine unless your doctor tells you to, as your condition may worsen. Schedule an urgent appointment with your doctor if you are pregnant or think you may be pregnant. Your doctor will advise you.

Babies born to mothers who have been treated with valproate have significant risks of birth defects and developmental problems that may be severely disabling.

Your doctor will refer you to a specialist experienced in the treatment of epilepsy to evaluate alternative treatment options.

In exceptional circumstances where Depakine is the only treatment option during pregnancy, you will be closely monitored for both your underlying condition and fetal development. You and your partner may receive counseling and support regarding pregnancy with valproate exposure.

Consult your doctor about taking folic acid. Folic acid may reduce the general risk of spina bifida and early miscarriage in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.

Important messages:

Schedule an urgent appointment with your doctor if you are pregnant or think you may be pregnant.
Do not stop taking Depakine unless your doctor tells you to.
Ensure you are referred to a specialist experienced in the treatment of epilepsy to evaluate the need for alternative treatment options.
You must receive counseling on the risks of Depakine during pregnancy, including teratogenicity (birth defects) and physical and mental developmental disorders in children.
Ensure you are referred to a prenatal monitoring specialist to detect possible malformations.

Make sure to read the Patient Guide provided by your doctor. Your doctor will discuss the Annual Risk Acknowledgment Form with you and ask you to sign and keep it. Your pharmacist will also provide you with a Patient Card to remind you of the risks of valproate if taken during pregnancy.

In newborns of mothers who took Depakine during pregnancy also:

Coagulation problems may occur due to partial or complete lack of substances necessary for blood clotting. In the latter case, the problem may be fatal, so specific blood tests and coagulation tests should be performed in the newborn.
Hypoglycemia may occur in newborns of mothers who took Depakine during pregnancy.
Cases of neonatal hypothyroidism have been reported in newborns of mothers who took valproate during pregnancy.
A withdrawal syndrome (such as agitation, irritability, hyperexcitability, restlessness, hyperkinesia, muscle tone disorders, tremor, seizures, and feeding difficulties) may occur in neonates whose mothers took valproate during the last trimester of pregnancy.

Breastfeeding

Consult your doctor or pharmacist before using any medicine.

Sodium valproate passes into breast milk. However, the amounts of sodium valproate in breast milk are small, and therefore, treatment with Depakine during breastfeeding generally does not pose a risk to the infant and breastfeeding usually does not need to be discontinued. Nevertheless, you should consult your doctor about whether to continue or discontinue breastfeeding, taking into account the safety profile of Depakine, especially blood disorders (see section “Possible side effects”).

Important information for male patients

Potential risks related to valproate use in the 3 months before conception

A study suggests a possible risk of movement and mental development disorders (childhood development problems) in children born to fathers treated with valproate in the 3 months before conception. In this study, about 5 out of every 100 children had such disorders when born to fathers treated with valproate, compared to about 3 out of every 100 children when born to fathers treated with lamotrigine or levetiracetam (other medicines that can be used to treat your condition). The risk for children born to fathers who discontinued valproate treatment 3 months (the time required to form new sperm) or more before conception is unknown. The study has limitations, and therefore, it is unclear whether the increased risk of movement and mental development disorders suggested by this study is caused by valproate. The study was not large enough to determine the specific type of movement and mental development disorder that children may develop.

As a precaution, your doctor will discuss with you:

The potential risk in children born to fathers treated with valproate.
The need to consider effective contraceptive methods (birth control) for you and your female partner during treatment and for 3 months after stopping treatment.
The need to consult your doctor when planning to conceive a child and before stopping contraception (birth control).
The possibility of using other treatments for your condition, depending on your individual situation.

Do not donate sperm while taking valproate and for 3 months after stopping valproate.

Talk to your doctor if you are thinking about having a child.

If your female partner becomes pregnant while you were taking valproate in the 3 months before conception and you have any concerns, contact your doctor. Do not stop treatment without consulting your doctor. If you stop treatment, your symptoms may worsen.

You should have regular appointments with your doctor. During these visits, your doctor will discuss with you the precautions associated with valproate use and the possibility of other treatments for your condition, depending on your individual situation.

You must read the Patient Guide you will receive from your doctor. You will also receive a Patient Card from your pharmacist to remind you of the potential risks of valproate.

Driving and using machines

Depakine may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may reduce reaction ability. These effects, as well as the disease itself, may impair your ability to drive or operate machinery. Therefore, do not drive or operate machinery or engage in other activities requiring special attention until your doctor evaluates your response to this medicine.

Important information about some of the components of Depakine This medicine contains 55.35 mg of sodium per vial. This corresponds to 2.8% of the maximum daily sodium intake recommended for an adult.

3. How Depakine is administered

Girls and women of childbearing age

Treatment with Depakine must be initiated and supervised by a physician specialized in the treatment of epilepsy.

Male patients

It is recommended that Depakine be initiated and supervised by a specialist experienced in the treatment of epilepsy – see section 2 Important information for male patients.

A doctor or nurse will always administer Depakine to you or your child, as it must be given as a slow injection or infusion into a vein (intravenous). If you are unsure why Depakine is being administered to you or your child, or have any questions about the amount being given, consult your doctor or nurse.

How much Depakine is administered

Your doctor will decide the dose to be given to you or your child depending on the condition being treated. The dose you or your child receive will depend on age and body weight. Your doctor will determine and monitor the daily dose, frequency, and timing of administration. The duration of treatment will be determined by your doctor.

If you or your child have been taking Depakine by mouth, your doctor may decide to administer the same dose of Depakine 6 hours after the last oral dose, either as a continuous or repeated infusion.

If you or your child have not previously taken Depakine:

In adults, adolescents, and children older than 10 years, the recommended dose is usually 15 mg/kg, administered by slow intravenous injection over 3–5 minutes, followed by continuous or repeated infusion.
In children up to 10 years of age, the recommended dose is usually 20–30 mg/kg, administered by slow intravenous injection, followed by continuous or repeated infusion. For children under 3 years of age, see Section 2.

Patients with kidney problems

Your doctor may decide to adjust your dose.

In children under 11 years of age, administration of Depakine 200 mg/ml oral solution is considered more appropriate.

Under no circumstances should Depakine 100 mg/ml powder and solvent for injectable solution be administered by any route other than intravenous.

If you use more Depakine than you should

If this medicine is administered by a doctor or nurse (under medical supervision), it is unlikely that you will receive more than you should. They will monitor your progress. Always ask if you are unsure why a dose of medicine is being administered.

An overdose of Depakine can be dangerous. Symptoms of poisoning may include confusion, sedation, or even coma with hypotonia, muscle weakness, and lack of reflexes. Therefore, go to the nearest hospital where symptoms will be treated and cardio-respiratory monitoring will be performed. In some cases, hypotension, miosis, cardiovascular and respiratory disturbances, circulatory collapse/shock, metabolic acidosis, hypocalcemia, and hypernatremia may also occur. Deaths have been reported following massive overdoses; however, a favorable outcome is more common.

Nevertheless, symptoms may vary, and seizures have been reported in the presence of very high plasma levels. Cases of increased intracranial pressure associated with cerebral edema have been reported.

The presence of sodium in valproate-containing formulations may lead to hypernatremia in cases of overdose.

It is recommended to bring the medicine packaging and patient information leaflet to the healthcare professional.

If you stop treatment with Depakine

It is important that you continue receiving Depakine injections until your doctor decides to discontinue them. If you stop, your seizures may return.

4. Possible adverse effects

Like all medicines, Depakine may produce adverse effects, although not everyone experiences them.

Contact your doctor immediately if any of the following serious adverse effects occur. You may require urgent medical attention:

Drowsiness, change in level of consciousness (including coma), confusion, slow or abnormal behavior, and memory loss, with or without increased frequency or severity of seizures, particularly if you are taking phenobarbital or topiramate (medicines used to treat seizures) at the same time, or if the dose of Depakine has been increased suddenly.
Confusion that may be caused by a decrease in blood sodium levels or by a condition called Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).
Problems with balance and coordination, feeling lethargic or less alert, associated with vomiting. This may be due to increased blood ammonia levels.
Increase in the number and severity of seizures.
Repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, severe pain in the upper abdomen, nausea, jaundice (yellowing of the skin or whites of the eyes), swelling of the legs, worsening of epilepsy, or a general feeling of being unwell. These may be symptoms of serious liver and pancreas disorders.
Allergic reactions that may manifest as:
Blisters with skin peeling (blisters, skin shedding, or bleeding in any part of the skin (including lips, eyes, mouth, nose, genitals, hands, or feet), with or without rash, sometimes accompanied by flu-like symptoms such as fever, chills, or muscle pain—these may be signs of conditions called 'toxic epidermal necrolysis' or 'Stevens-Johnson syndrome').
Allergic swelling with painful, itchy hives (often around the eyes, lips, throat, and sometimes hands and feet)—these may be symptoms of “angioedema”.
Syndrome involving skin rash, fever, swollen lymph nodes, and possible failure of other organs—these may be signs of a condition called “DRESS” (Drug Reaction with Eosinophilia and Systemic Symptoms).
Spontaneous bruising or bleeding due to blood clotting problems detected in blood tests.
Severe reduction in white blood cells or bone marrow failure detected in blood tests, sometimes manifesting as fever and breathing difficulties.
Underactive thyroid gland, which may cause fatigue or weight gain (hypothyroidism).
Joint pain, fever, fatigue, rash. These may be signs of systemic lupus erythematosus.
Agitation (tremor), uncontrollable muscle contractions, unsteadiness when walking (parkinsonism, extrapyramidal disorder, ataxia). Muscle pain and muscle weakness (rhabdomyolysis). Sedation, extrapyramidal disorders.
Uncommon: difficulty breathing, chest pain or pressure (especially when inhaling), difficulty breathing and dry cough due to fluid accumulation around the lungs (pleural effusion).
Kidney disease (renal failure, tubulointerstitial nephritis) that may manifest as reduced urine output.

Contact your doctor or pharmacist if any of the following adverse effects worsen or last longer than a few days; you may need medical treatment:

Very common adverse effects (may affect more than 1 in 10 patients) are:

Nervous system disorders: tremor.
Gastrointestinal disorders: nausea (also observed a few minutes after intravenous injection, resolving spontaneously within a few minutes).

Common adverse effects (may affect up to 1 in 10 patients) are:

Blood disorders: reduction in red blood cells (anemia) and reduction in platelets (thrombocytopenia).
Nervous system disorders: involuntary movements (extrapyramidal disorders), stupor, drowsiness, seizures, memory impairment, headache, rapid and uncontrollable eye movements (nystagmus). Dizziness may occur a few minutes after intravenous injection and resolves spontaneously within a few minutes. In isolated cases or associated with increased seizure frequency during treatment, confusion has been reported, which improves after discontinuation or dose reduction.
Renal and urinary disorders: urinary incontinence.
Ear disorders: hearing problems or deafness.
Gastrointestinal disorders: vomiting, gum problems (mainly hypertrophy), pain and swelling in the mouth, mouth ulcers and burning sensation in the mouth (stomatitis), upper abdominal pain, and diarrhea. These commonly occur in some patients at the beginning of treatment and usually resolve within a few days without interrupting treatment.
Skin and subcutaneous tissue disorders: nail and skin changes under the nail, hypersensitivity, hair loss (transient and/or dose-related).
Metabolism and nutrition disorders: decreased blood sodium (hyponatremia), weight gain.
Vascular disorders: bleeding.
Hepatobiliary disorders: liver injury.
Reproductive system disorders: painful menstruation (dysmenorrhea).
Psychiatric disorders: confusion, seeing, feeling, or hearing things that are not real (hallucinations), aggressiveness*, agitation*, attention disorders* (* mainly observed in children).

Uncommon adverse effects (may affect up to 1 in 100 patients) are:

Blood disorders: deficiency of blood components (pancytopenia) and decreased number of white blood cells in blood (leukopenia).
Nervous system disorders: coma, encephalopathy, lethargy, disorder characterized by tremor, difficulty walking, movement, and coordination (reversible parkinsonism), incoordination of movements (ataxia), numbness or tingling in feet or hands (paresthesia), worsening of seizures.
Renal and urinary disorders: renal failure.
Gastrointestinal disorders: pancreatitis, which may be fatal.
Skin and subcutaneous tissue disorders: swelling of feet, hands, throat, lips, and airways (angioedema) and rash, abnormal hair growth and texture, and changes in hair color.
Musculoskeletal disorders: bone abnormalities have been reported, including osteopenia and osteoporosis (bone demineralization) and fractures. Consult your doctor or pharmacist if you are on long-term antiepileptic treatment, have a history of osteoporosis, or take steroids.
Endocrine disorders: Syndrome of Inappropriate Antidiuretic Hormone Secretion (fluid retention and decreased levels of certain electrolytes in blood), hyperandrogenism (excessive hair growth, virilization, acne, male-pattern hair loss, and/or increased androgens).
Vascular disorders: inflammation of small blood vessels (vasculitis).
General disorders: swelling of ankles, feet, and legs due to fluid accumulation (non-severe peripheral edema), decreased body temperature.
Reproductive system disorders: irregular menstruation or absence of menstruation (amenorrhea).

Rare adverse effects (may affect up to 1 in 1,000 patients) are:

Blood disorders: bone marrow failure including pure red cell aplasia (halted or reduced production of red blood cells, leading to severe anemia, with symptoms such as unusual fatigue and lack of energy), agranulocytosis (decreased number of white blood cells), decreased number of red blood cells with larger than normal size (macrocytic anemia, macrocytosis).
Additional tests: decreased coagulation factors, biotin/biotinidase deficiency (low levels of vitamin B8).
Nervous system disorders: worsening of mental function causing confusion and changes in intellect or reasoning (reversible dementia), cognitive disorder, double vision.
Kidney disorders: involuntary urination (enuresis), tubulointerstitial nephritis, increased frequency of urination and thirst (Fanconi syndrome).
Skin and subcutaneous tissue disorders: skin lesions with red spots, blisters, and even peeling that may become severe (Stevens-Johnson syndrome), DRESS syndrome (severe skin reaction characterized by generalized rash, fever, swollen lymph nodes, blood abnormalities, and internal organ involvement).
Musculoskeletal and connective tissue disorders: systemic lupus erythematosus, rhabdomyolysis (muscle pain and weakness).
Endocrine disorders: hypothyroidism.
Metabolism and nutrition disorders: obesity and increased blood ammonia (hyperammonemia).
Neoplasms: myelodysplastic syndrome (a disease in which the bone marrow does not function properly).
Reproductive system disorders: male infertility (usually reversible after discontinuation of treatment and may be reversible after dose reduction. Do not stop your treatment without first consulting your doctor), polycystic ovaries.
Psychiatric disorders: abnormal behavior*, psychomotor hyperactivity*, learning disorders* (* mainly observed in children).

Other adverse effects with unknown frequency (cannot be estimated from available data) are:

Congenital, familial, and genetic disorders: autism spectrum disorders, congenital malformations, and developmental disorders.
Additional tests: false positive results in urine ketone elimination tests in diabetic patients.
Decreased levels of carnitine (detected in blood or muscle tests).
Skin and subcutaneous tissue disorders: darker areas of the skin and mucous membranes (hyperpigmentation).

Additional adverse effects in children

Some adverse effects of valproate occur more frequently or are more severe in children compared to adults. These include liver damage, inflammation of the pancreas (pancreatitis), aggressiveness, agitation, attention disorders, abnormal behavior, hyperactivity, and learning disorders.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Depakine

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging, vial, and ampoule, following the label "EXP". The expiry date refers to the last day of the month indicated.

Unopened powder vial: no special storage conditions are required.

After reconstitution: immediate use is recommended.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Depakine 100 mg/ml powder and solvent for injectable solution

Each vial of powder contains 400 mg of sodium valproate. After reconstitution, each ml of solution contains 100 mg of sodium valproate. The other components are water for injectable preparations.

Appearance of the product and contents of the pack

Depakine 100 mg/ml powder and solvent for injectable solution and for infusion is a white to off-white powder. The solvent is a clear, colourless liquid.

Depakine powder and solvent for injectable solution and for infusion is supplied in a pack containing 1 vial of powder and 1 ampoule of solvent.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Sanofi-aventis, S.A
C/ Rosselló i Porcel, 21
08016 Barcelona
Spain

Manufacturer:

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

This patient information leaflet was last approved in October 2025

The following information is intended for healthcare professionals

The vial and ampoule contain an overfill to allow extraction of the declared amount:

Vial: 415 mg of lyophilized sodium valproate powder (displacement factor: 8.65%).
Ampoule: 4.25 ml of solvent, water for injectable preparations.

Reconstitution

Use a graduated syringe to withdraw 3.8 ml of water for injectable preparations (solvent) from the ampoule and inject it into the vial of lyophilized powder.
Allow it 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 injectable solution (100 mg/ml) can be withdrawn from the vial.

The reconstituted solution is clear and almost colourless.

Dilution

Withdraw the required amount of reconstituted solution and dilute in 500 ml of any of the following infusion solutions (250 ml is used only for tromethamine):

Sodium chloride 0.9 g/100 ml
Glucose 5 g/100 ml, 10 g/100 ml, 20 g/100 ml, 30 g/100 ml
Glucose 2.5 g + 0.45 g sodium chloride per 100 ml
Sodium bicarbonate 0.14 g/100 ml
Tromethamine 3.66 g + sodium chloride 0.172 g per 100 ml.

The intravenous solution is suitable for infusion in PVC, polyethylene or glass containers.

Depakine must be reconstituted immediately before use. Infusion solutions containing the medicinal product should be used within 24 hours.

You can access detailed and up-to-date information about this medicine by scanning with your mobile phone (smartphone) the QR code included in the package leaflet. You can also access this information at the following internet address: https://cima.aemps.es/info/60352.

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/