DEPAKINE 100 mg/ml POWDER AND SOLVENT FOR INJECTABLE SOLUTION

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 for the quick identification of new safety information. You can help by reporting any side effects you may get. The last section of section 4 will tell you how to report side effects.

Read all of this package leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Depakine and what is it used for
2. What you need to know before you use Depakine
3. How to use Depakine
4. Possible side effects
5. Storage of Depakine
6. Contents of the pack and further information

1. What is Depakine and what is it used for

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

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

2. What you need to know before using Depakine

Do not use Depakine

• If you are allergic (hypersensitive) to the active ingredient or any of the other components of Depakine 100 mg/ml powder and solvent for injectable solution, or to any other medicine, you should inform your doctor.

• You must not use Depakine if you are pregnant, unless no other treatment works.

• If you are a woman of childbearing potential, you must not take Depakine, unless you use an effective method for 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 in "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 you have a history of a family member who died from liver function alteration during treatment with sodium valproate.
• If you have liver porphyria (a very rare metabolic disorder).
• If you have a genetic problem that produces a mitochondrial disorder (e.g., Alpers-Huttenlocher syndrome).
• If you have a known metabolic disorder, such as a disorder of the urea cycle.
• If you have an 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 administering Depakine.

Warnings and precautions

CONSULT YOUR DOCTOR IMMEDIATELY:

The risk of liver damage increases if valproate is administered to children under 3 years, to people taking other antiepileptic medications at the same time, or who have other neurological or metabolic diseases and severe forms of epilepsy.

Your doctor must review your liver function tests before you start treatment and periodically during the first 6 months, especially in patients at risk.

If you or your child suddenly develop an illness, especially if it appears in the first months of treatment and, in particular, if it includes repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, pain in the upper part of the stomach, nausea, jaundice (yellowing of the skin or eyes), swelling of the legs, or worsening of epilepsy or a feeling of generalized malaise. In this case, you should consult your doctor immediately. In a very small number of patients, Depakine can affect the liver or pancreas. The alteration of liver function along with pancreatic alteration increases the risk of fatal outcome.

If you or your child taking valproate develop problems with balance and coordination, a feeling of lethargy, or feeling less alert, vomit, inform your doctor immediately. This may be due to an increase in your blood ammonia levels.

A reduced number of people who were being treated with antiepileptics like valproic acid have had thoughts of self-harm or suicide. If at any time you have these thoughts, contact your doctor immediately.

Severe 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 medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Before taking this medication, consult your doctor

• If you know or your doctor suspects that there is a genetic problem caused by a mitochondrial disorder in your family, due to the risk of liver damage

• If it is suspected that you have a metabolic disorder, particularly hereditary enzyme deficiency disorders such as a "urea cycle disorder" due to the risk of an increase in blood ammonia levels.
• If you have a rare disorder called "carnitine palmitoyltransferase type II deficiency", because you have a higher risk of suffering from muscle disorders.
• If you have an altered dietary intake of carnitine, which is found in meat and dairy products, especially in children under 10 years.
• If you have a carnitine deficiency and are taking carnitine.
• If you suffer from kidney function impairment or hypoproteinemia (decrease in blood protein levels). In this case, your doctor may want to monitor your valproate blood levels or adjust the dose.
• If Depakine is administered to children under 3 years, the concomitant administration with acetylsalicylic acid (aspirin) should be especially avoided.
• If you have systemic lupus erythematosus.
• If you have blood disorders (blood clotting or thrombocytopenia). It is recommended to perform a blood test (complete blood count) before starting treatment or before surgery and in cases of spontaneous hematomas or bleeding.
• If you experience weight gain at the start of treatment.
• As with other antiepileptic medications, seizures can worsen or appear more frequently while using this medication. If this happens, contact your doctor immediately.
• If you have ever developed a severe skin rash or exfoliation, blisters, and/or ulcers in the mouth after taking valproate.

Using Depakine with other medications

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

Some medications can alter the effect of Depakine or vice versa. These medications include:

• Carbapenem agents (antibiotics used to treat bacterial infections).

• Products containing estrogens (including some birth control pills).
• Neuroleptics (medications used to treat psychological disorders).
• Medications used to treat depression.
• Benzodiazepines (medications used to sleep or treat anxiety).
• Olanzapine and quetiapine (medications used to treat psychiatric disorders).
• Other medications used to treat epilepsy, including phenobarbital, phenytoin, primidone, lamotrigine (the risk of severe skin rash may increase when lamotrigine and valproic acid are administered together), carbamazepine, ethosuximide, felbamate, and topiramate. The concomitant administration of Depakine with topiramate has been associated with encephalopathy and/or hyperammonemia (a condition of the brain and nervous system that occurs as a complication of liver disorders with or without an increase in blood ammonia levels).
• Zidovudine (a medication used to treat HIV and AIDS).
• Mefloquine (a medication used to treat or prevent malaria).
• Salicylates (aspirin). See also "Warnings and precautions - Children under 3 years".
• Anticoagulants (medications used to prevent blood clot formation).
• Cimetidine (a medication used to treat stomach ulcers).
• Erythromycin and rifampicin (antibiotics).
• Rufinamide.
• Acetazolamide.
• Protease inhibitors, such as lopinavir, ritonavir (used for HIV treatment).
• Colestyramine.
• Propofol (anesthetic).
• Metamizole (a medication used to treat pain and fever).
• Cannabidiol (used to treat epilepsy and other diseases).
• Methotrexate (used to treat cancer and inflammatory diseases).
• Some anti-infectives that contain pivalate (e.g., pivampicillin, adefovir dipivoxil).
• Clozapine (for treating mental health disorders).

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

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

Using Depakine with food and beverages

Do not consume alcoholic beverages.

Pregnancy, breastfeeding, and fertility

Pregnancy

Consult your doctor or pharmacist before using any medication.

Important warning for women

• You must not use Depakine if you are pregnant, unless no other treatment works.
• If you are a woman of childbearing potential, you must not take Depakine, unless you use an effective method for 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

• Talk to your doctor immediately if you are planning to have a baby or are pregnant.
• Valproate carries a risk when taken during pregnancy. With the highest dose, the risk is greater, but all doses have a risk, even when valproate is used in combination with other medications to treat epilepsy.
• It can cause serious birth defects and can affect the physical and mental development of the child and how it grows after birth. The most frequently reported birth defects include spina bifida(where the bones of the spine do not develop properly); malformations of the skull and face, heart, kidney, urinary tract, genital organs, and limb defects, as well as multiple malformations that affect several organs and parts of the body. Birth defects can 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 in association with other congenital malformations. These ocular malformations can affect vision.
• If you take valproate during pregnancy, you have a higher risk than other women of having a child with birth defects that require medical treatment. As valproate has been used for many years, it is known that of the women who take valproate, around 11 babies out of 100 will have birth defects. In comparison with 2 to 3 babies out of 100 born to women who do not have epilepsy.
• It is estimated that up to 30-40% of children in preschool age whose mothers took valproate during pregnancy may have developmental problems in childhood. The affected children may speak and walk slowly, be less intellectually capable than other children, and have difficulties with language and memory.
• In children exposed to valproate, autistic spectrum disorders are more frequently diagnosed, and there is some evidence that these children have a higher risk of developing Attention Deficit Hyperactivity Disorder (ADHD).
• Before prescribing this medication, your doctor will have explained what can happen to your baby if you become pregnant while taking valproate. If you later decide that you want to have a baby, do not stop taking your medication or your contraceptive until you have discussed this with your doctor.
• If you are a parent or caregiver of a girl being treated with valproate, you should contact your doctor when your daughter being treated with valproate has her menarche (first menstruation).
• Some birth control pills (birth control pills that contain estrogens) can decrease valproate blood levels. Make sure to talk to your doctor about the most suitable birth control method (contraception) for you.
• Consult your doctor about taking folic acid when trying to have a baby. Folic acid can reduce the overall risk of spina bifidaand early abortion that exists during all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with the use of valproate.

Choose and read the situations that apply to you from the following:

• 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 are of childbearing age, you will need to ensure that you use an effective contraceptive method without interruption throughout your treatment with Depakine. Consult your doctor or family planning clinic if you need advice on contraception.

Important messages:

• Pregnancy should be ruled out before starting treatment with Depakine, through the result of a pregnancy test, confirmed by your doctor.
• You must use an effective method for birth control (contraception) throughout your treatment with Depakine.
• You should talk to your doctor about suitable methods for birth control (contraception). Your doctor will give you information on how to prevent pregnancy and may refer you to a specialist for birth control advice.
• You should have regular check-ups (at least annual) with a specialist experienced in the treatment of epilepsy. During this visit, your doctor will ensure that you know and have understood all the risks and warnings related to the use of valproate during pregnancy.
• Inform your doctor if you want 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, make sure to use an effective contraceptive method without interruption 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 for birth control (contraception) throughout your treatment with Depakine.
• You should talk to your doctor about contraception (birth control). Your doctor will give you information on how to prevent pregnancy and may refer you to a specialist for birth control advice.
• You should have regular check-ups (at least annual) with a specialist experienced in the treatment of epilepsy. During this visit, your doctor will ensure that you know and have understood all the risks and warnings related to the use of valproate during pregnancy.
• Inform your doctor if you want 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 until you have discussed this 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 can be severely debilitating. Your doctor will refer you to a specialist with experience in the treatment of epilepsy, so that alternative treatment options can be evaluated from the start. Your specialist may take several actions to ensure that your pregnancy develops in the best possible way and the risks to you and the fetus are reduced as much as possible.

Your specialist may decide to change the dose of Depakine or change to another medication, or stop your treatment with Depakine long before you become pregnant - to ensure that your disease is stable.

Consult your doctor about taking folic acid when trying to have a baby. Folic acid can reduce the overall risk of spina bifidaand early abortion that exists during all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with the use of valproate.

Important messages:

• Do not stop taking Depakine unless your doctor tells you to.
• Do not stop using your contraceptive methods (contraception) before you have discussed this with your doctor and worked together on a plan to ensure that your disease is controlled and the risks to your baby are reduced.
• First, schedule an appointment with your doctor. During this visit, your doctor will ensure that you know and have understood all the risks and warnings related to the use of valproate during pregnancy.
• Your doctor will try to change you to another medication or stop your treatment with Depakine long before you become pregnant.
• 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 disease 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 can be severely debilitating.

Your doctor will refer you to a specialist with experience in the treatment of epilepsy, so that alternative treatment options can be evaluated.

In exceptional circumstances, when Depakine is the only treatment option during pregnancy, it will be closely monitored, both for the management of your underlying disease and to check how the fetus is developing. You and your partner may receive counseling and support related to pregnancy with valproate exposure.

Consult your doctor about taking folic acid. Folic acid can reduce the overall risk of spina bifidaand early abortion that exists during all pregnancies.

3. How to use Depakine

Girls and women of childbearing age

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

Male patients

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

Depakine should be administered under medical supervision. It is usually administered by a doctor or nurse (under medical supervision).

Your doctor will decide the most convenient dose of Depakine. Make sure to attend regular check-ups with your doctor.

Depakine is prescribed individually and for a specific situation. The recommended doses in this prospectus are indicative. The doses of Depakine are established according to body weight, your specific situation, and the doctor's criterion.

• Infants and children (28 days to 11 years): The recommended dose is 20-30 mg/kg of body weight.
• Adolescents (≥12 years) and adults (≥18 years): In patients with established oral treatment, Depakine 100 mg/ml powder and solvent for solution for injection will be administered in continuous perfusion, 4 to 6 hours after oral intake, following the same posology already established, at a perfusion rate between 0.5 and 1 mg/kg/h. In the rest of the patients, the preparation will be administered in the form of slow injection (3-5 minutes), at a rate of 15 mg/kg of body weight, to continue after 30 minutes with continuous perfusion at 1 mg/kg/h up to a maximum of 25 mg/kg/day.
• Elderly patients (≥65 years): 15-20 mg/kg of body weight.
• Patients with hepatic insufficiency: Depakine should not be administered to patients with severe liver disease.
• Patients with renal insufficiency: It may be necessary to administer lower doses to this type of patient.

The usual daily dose is 0.2 – 0.3 ml (equivalent to 20-30 mg of valproate sodium) per kilogram of body weight, administered by intravenous perfusion. Oral therapy should replace intravenous therapy as soon as possible.

Patients with kidney problems

Your doctor may decide to adjust your dose.

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

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

The dose is always adjusted individually, according to the response of each patient.

If you use more Depakine than you should

If this medication is administered by a doctor or nurse (under medical supervision), it is unlikely that you will be administered more than you should. They will monitor your progress. Always ask if you are not sure why you are being administered a dose of medication.

An overdose of Depakine can be dangerous. Among the symptoms of intoxication, confusion, sedation, or even coma with hypotonia, muscle weakness, and lack of reflexes stand out. Therefore, go to the nearest hospital where you will be treated for the symptoms and undergo cardio-respiratory monitoring. In some cases, hypotension, miosis, cardiovascular and respiratory alterations, circulatory collapse/shock, metabolic acidosis, hypocalcemia, and hypernatremia have also been observed. There have been cases of death after massive overdose; however, the usual outcome is favorable.

However, the symptoms may be variable, and convulsions have been reported in the presence of very high plasma levels. Cases of intracranial hypertension associated with cerebral edema have been reported.

The presence of sodium in the presentations with valproate may lead to hypernatremia in the event of an overdose.

It is recommended to bring the packaging and prospectus of the medication to the healthcare professional.

If you forget to use Depakine

This does not apply.

If you stop treatment with Depakine

Suddenly stopping treatment with Depakine without your doctor's explicit indication can be harmful to you, as it may trigger episodes with convulsions with serious consequences.

4. Possible Adverse Effects

Like all medications, Depakine can produce adverse effects, although not all people suffer from them.

Inform your doctor immediately if any of the following serious adverse effects appear. You may need urgent medical attention:

• Drowsiness, change in level of consciousness (including coma), confusion, slow or abnormal behavior, and memory loss associated or not with an increased frequency or severity of convulsive attacks, particularly if you are taking phenobarbital or topiramate (medications used to treat convulsions) at the same time or if the dose of Depakine has been suddenly increased.
• Confusion that may be caused by a decrease in blood sodium levels or by a condition called Syndrome of Inadequate Secretion of the Antidiuretic Hormone (SIADH).
• Problems with balance and coordination, feeling of lethargy or being less alert, associated with vomiting. This may be due to an increase in your blood ammonia levels.
• Increased number and severity of convulsions.
• Repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, severe pain in the upper part of the stomach, nausea, jaundice (yellowing of the skin or the whites of the eyes), swelling of the legs, or worsening of epilepsy or generalized feeling of discomfort. These may be symptoms of serious liver and pancreas disorders.
• Allergic reactions that may manifest as:

• Blisters with skin peeling (blisters, peeling, or bleeding on any part of the skin, including lips, eyes, mouth, nose, genitals, hands, or feet) with or without a rash, with symptoms sometimes similar to those of the flu, such as fever, chills, or muscle pain - these may be signs of conditions called 'toxic epidermal necrolysis' or 'Stevens-Johnson syndrome'.
• Allergic inflammation with painful hives that cause itching (frequently around the eyes, lips, throat, and sometimes on hands and feet) – these may be symptoms of “angioedema”.
• Syndrome that involves skin rash, fever, lymph node enlargement, and possible failure of other organs – these may be signs of a condition called “DRESS” or drug rash with eosinophilia and systemic symptoms.

• Sudden appearance of bruises or bleeding due to blood coagulation problems that appear in blood tests.
• Severe decrease in white blood cells or bone marrow failure that appears in blood tests, which may manifest with fever and difficulty breathing.
• Underactive thyroid gland, which can cause fatigue or weight gain (hypothyroidism).
• Pain in the joints, fever, fatigue, rash. These may be signs of systemic lupus erythematosus.
• Agitation (tremor), uncontrolled muscle contractions, instability when walking (parkinsonism, extrapyramidal disorder, ataxia). Muscle pain and muscle weakness (rhabdomyolysis). Sedation, extrapyramidal disorders.
• Rarely: difficulty breathing, pain or pressure in the chest (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 a reduction in urine output.

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

The very frequent adverse effects that may affect more than 1 in 10 patients are:

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

The frequent adverse effects that may affect up to 1 in 10 patients are:

• Blood disorders: reduction in the number of red blood cells (anemia) and reduction in the number of platelets (thrombocytopenia).
• Nervous system disorders: involuntary movement (extrapyramidal disorders), stupor, drowsiness, convulsions, memory failure, headache, rapid and uncontrolled eye movements (nystagmus), dizziness may appear a few minutes after intravenous injection and disappear spontaneously in a few minutes. In isolated cases or associated with an increase in convulsive crises during treatment, cases of confusion have been described that decrease after discontinuation of treatment and 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, ulcers, and burning sensation in the mouth (stomatitis), pain in the upper part of the abdomen, and diarrhea, which frequently appear in some patients at the beginning of treatment and usually disappear within a few days without interrupting treatment.
• Skin and subcutaneous tissue disorders: alteration of the nail and the skin under the nail, hypersensitivity, hair loss (transient and/or related to the dose).
• Metabolism and nutrition disorders: decreased sodium in the blood (hyponatremia), weight gain.
• Vascular disorders: bleeding.
• Hepatobiliary disorders: liver damage.
• Reproductive system disorders: painful menstruation (dysmenorrhea).
• Psychiatric disorders: confusion, seeing, feeling, or hearing things that do not exist (hallucinations), aggression*, agitation*, attention disorders* (*mainly observed in children).

The adverse effects that may affect up to 1 in 100 patients are:

• Blood disorders: scarcity of blood components (pancytopenia) and decrease in the number of white blood cells in the blood (leukopenia).
• Nervous system disorders: coma, encephalopathy, lethargy, disorder characterized by tremor, difficulty walking, movement, and coordination (reversible parkinsonism), lack of coordination (ataxia), numbness or tingling in the feet or hands (paresthesia), worsening of convulsions.

• Renal and urinary disorders: renal failure.
• Gastrointestinal disorders: pancreatitis that can be fatal.
• Skin and subcutaneous tissue disorders: inflammation of the feet, hands, throat, lips, and respiratory tract (angioedema) and rash, growth, and abnormal texture of the hair, and changes in hair color.
• Musculoskeletal disorders: bone alterations, including osteopenia and osteoporosis (decalcification of bones), and fractures. Consult your doctor or pharmacist if you are undergoing prolonged treatment with antiepileptics, have a history of osteoporosis, or take steroids.
• Endocrine disorders: Syndrome of Inadequate Secretion of the Antidiuretic Hormone (fluid retention and decrease in certain electrolyte levels in the blood), hyperandrogenism (increased hair, virilization, acne, male-pattern baldness, and/or increased androgens).
• Vascular disorders: inflammation of small blood vessels (vasculitis).
• General disorders: swelling of the ankles, feet, and legs due to fluid accumulation (non-severe peripheral edema), decrease in body temperature.
• Reproductive system disorders: irregular or absent menstruation (amenorrhea).

The adverse effects that may affect up to 1 in 1,000 patients are:

• Blood disorders: bone marrow failure, including pure red cell aplasia (stop or decrease in the production of red blood cells, which causes severe anemia, whose symptoms include unusual fatigue and lack of energy), agranulocytosis (decrease in the number of white blood cells), decrease in the number of red blood cells with a larger than normal size (macrocytic anemia, macrocytosis).
• Complementary tests: decrease in coagulation factors, biotin/biotinidase deficiency (low levels of vitamin B8).

• Nervous system disorders: reversible dementia, mental function impairment causing confusion and changes in intellect or reasoning, disorder of consciousness, double vision.
• Kidney disorders: involuntary urination (enuresis), tubulointerstitial nephritis, frequent urination, and thirst (Fanconi syndrome).
• Skin and subcutaneous tissue disorders: skin lesions with red spots, blisters, and even peeling that can be severe (Stevens-Johnson syndrome), DRESS syndrome (severe skin lesion characterized by generalized rash, fever, lymph node inflammation, blood alterations, and involvement of internal organs).
• Musculoskeletal and connective tissue disorders: systemic lupus erythematosus, rhabdomyolysis (muscle pain and weakness).
• Endocrine disorders: hypothyroidism.
• Metabolism and nutrition disorders: obesity, increased ammonia in the blood (hyperammonemia).
• Neoplasms: myelodysplastic syndrome (disease in which the bone marrow does not function normally).
• Reproductive system disorders: male infertility (usually reversible after discontinuation of treatment and may be reversible after dose reduction; do not stop treatment without consulting your doctor first), polycystic ovaries.
• Psychiatric disorders: abnormal behavior*, hyperactivity*, learning disorders* (*mainly observed in children).

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

• Congenital, familial, and genetic disorders: autism spectrum disorders, congenital malformations, and developmental disorders.
• Complementary tests: false positives may appear in the urine ketone elimination test in diabetic patients.
• Decrease in carnitine levels (detected in blood or muscle test).
• 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 in children or are more severe compared to adults. These include liver damage, pancreatitis, aggression, agitation, attention disorders, abnormal behavior, hyperactivity, and learning disorders.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medications: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Depakine

Keep the solvent ampoule and the vial with the lyophilized powder in the original packaging until use.

No special storage conditions are required.

Keep out of sight and reach of children.

Do not use Depakine after the expiration date that appears on the packaging and on the labels of the vial and ampoule. The expiration date is the last day of the month indicated.

Medications should not be thrown down the drain or into the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help the environment.

6. Package Contents and Additional Information

Composition of Depakine 100 mg/ml Powder and Solvent for Injectable Solution

The active principle is sodium valproate. Each vial contains 400 mg of sodium valproate.

The other components are water for injectable preparations.

Appearance of the Product and Package Contents

Depakine 100 mg/ml powder and solvent for injectable solution is presented in packages containing 1 vial and 1 ampoule. Each ampoule contains 4 ml of water for injectable preparations.

Marketing Authorization Holder and Manufacturer

Marketing Authorization 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 prospectus was approved in January 2025

You can access detailed and updated information about this medication by scanning the QR code included in the prospectus with your smartphone. You can also access this information at the following internet address:https://cima.aemps.es/info/60352.

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