DEPAKINE 200 mg GASTRO-RESISTANT TABLETS

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Depakine 200 mg gastro-resistant tablets

valproate sodium

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

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

• Keep this package leaflet, 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. It may harm them, even if their symptoms are the same as yours.
• 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 Depakine 200 mg gastro-resistant tablets are and what they are used for.
2. What you need to know before you take Depakine 200 mg gastro-resistant tablets.
3. How to take Depakine 200 mg gastro-resistant tablets.
4. Possible side effects.
5. Storage of Depakine 200 mg gastro-resistant tablets.
6. Contents of the pack and other information.

1. What Depakine 200 mg gastro-resistant tablets are and what they are 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.

2. What you need to know before you take Depakine 200 mg gastro-resistant tablets

Do not take Depakine 200 mg

• If you are allergic (hypersensitive) to the active substance or any of the other ingredients of Depakine, or to any other medicine, you must 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 of contraception (birth control) during the entire 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 pancreas 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 medicines.
• If you have a history of a family member who died from liver function disorder during treatment with valproate sodium.
• 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 taking 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 medicines 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 few 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 general malaise. In this case, you must consult your doctor immediately. In a very small number of patients, Depakine can affect the liver or pancreas. The alteration of liver function together with the alteration of the pancreas increases the risk of fatal outcome.

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

A small number of people who were being treated with antiepileptics such as 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 medicine, 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 increased blood ammonia levels.

• If you have a rare disorder called “carnitine palmitoyltransferase type II deficiency”, because you have a higher risk of 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 (decreased protein levels in the blood). In this case, your doctor may want to monitor 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 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 medicines, seizures may worsen or appear more frequently while taking this medicine. If this happens, contact your doctor immediately.

• If you have ever developed a severe skin rash or peeling, blisters, and/or sores in the mouth after taking valproate.

Using Depakine 200 mg gastro-resistant tablets with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, 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 medicines may alter the effect of Depakine or vice versa. These medicines 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 to sleep or 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 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 increased ammonia levels in the blood).

• Zidovudine (a medicine used to treat HIV and AIDS).

• Mefloquine (a medicine used to treat or prevent malaria).

• Salicylates (aspirin). See also “Warnings and precautions - Children under 3 years”.

• Anticoagulants (medicines used to prevent blood clot formation).

• Cimetidine (a medicine used to treat stomach ulcers).

• Erythromycin and rifampicin (antibiotics).

• Rufinamide.

• Acetazolamide.

• Protease inhibitors, such as lopinavir, ritonavir (used to treat HIV).

• Colestyramine.

• Propofol (an anesthetic).

• Metamizole (a medicine 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 diseases).

Depakine may increase the effects of Nimodipine (a medicine used to treat hypertension, angina pectoris, and vascular disorders).

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

Taking Depakine 200 mg with food and drinks

Do not drink alcoholic beverages.

Pregnancy, breastfeeding, and fertility

Pregnancy

Consult your doctor or pharmacist before using any medication.

Important warning for women

• You should not use Depakine if you are pregnant, unless no other treatment works.
• If you are a woman of childbearing potential, you should 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

• 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 may affect the physical and mental development of the child and how they grow 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 defects of the limbs and multiple malformations associated with 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 language and memory difficulties.
• In children exposed to valproate, autism 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. Your doctor will advise you.
• If you are a father 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 oral contraceptives (contraceptive pills containing estrogens) may decrease valproate levels in the blood. Make sure to talk to your doctor about the most suitable contraceptive method (birth control) for you.
• Consult your doctor about taking folic acid when trying to have a baby. Folic acid may decrease the overall risk of spina bifidaand early abortion that exists in 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 excluded before starting treatment with Depakine, through the result of a pregnancy test, confirmed by your doctor.
• You should use an effective method of birth control (contraception) throughout your treatment with Depakine.
• You should talk to your doctor about suitable methods of 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.
• Tell 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 should use an effective method of birth control (contraception) throughout your treatment with Depakine.
• You should talk to your doctor about 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.
• Tell 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 switch to another medication, or stop 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 may decrease the overall risk of spina bifidaand early abortion that exists in 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 discussing with your doctor and working 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 switch you to another medication or stop 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 may decrease the overall risk of spina bifidaand early abortion that exists in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with the use of valproate.

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.
• Make sure you are referred to a specialist with experience in the treatment of epilepsy to evaluate the need for alternative treatment options.
• You should have counseling about the risks of Depakine during pregnancy, including teratogenicity (birth defects) and physical and mental developmental disorders in children.
• Make sure you are referred to a prenatal monitoring specialist to detect possible malformations.

Make sure to read the Patient Guide that your doctor will provide. Your doctor will discuss the Annual Risk Awareness Form 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 you take it during pregnancy.

In newborn babies of mothers who have taken Depakine during pregnancy, the following may also occur:

• Coagulation problems may occur due to partial or total lack of some of the substances necessary for blood coagulation. In the latter case, the problem can be fatal, so specific analytics and coagulation tests should be performed on the newborn.

• Hypoglycemia may occur in newborns of mothers who have taken Depakine during pregnancy.

• Cases of hypothyroidism have been reported in neonates of mothers who have taken valproate during pregnancy.

• A withdrawal syndrome (such as agitation, irritability, hyperexcitability, nervousness, hyperkinesia, tonicity disorders, tremors, convulsions, and feeding disorders) may occur in newborns whose mothers have taken valproate during the last trimester of pregnancy.

Breastfeeding

Consult your doctor or pharmacist before taking any medication.

Valproate sodium passes into breast milk. However, the amounts of valproate sodium that pass into breast milk are small, and therefore, treatment with Depakine during the breastfeeding period does not generally pose a risk to the infant, and it is not usually necessary to stop breastfeeding. Nevertheless, you should consult your doctor about the convenience of maintaining or not maintaining breastfeeding, taking into account the safety profile of Depakine, especially blood disorders (see section “Possible adverse effects”).

Important information for male patients

Potential risks associated with the use of valproate in the 3 months prior to conception of a child

A study suggests a possible risk of movement and mental development disorders (problems with childhood development) in children born to fathers treated with valproate in the 3 months prior to conception. In this study, around 5 out of 100 children presented with these disorders when born to fathers treated with valproate, compared to 3 out of 100 children when born to fathers treated with lamotrigine or levetiracetam (other medications that can be used to treat your disease). The risk to children born to fathers who stopped treatment with valproate 3 months (the time needed to form new sperm) or more before conception is unknown. The study has limitations, and therefore, it is not clear if the higher risk of movement and mental development disorders suggested by this study is caused by valproate. The study was not extensive enough to demonstrate what specific type of movement and mental development disorder children may develop.

As a precautionary measure, your doctor will talk to you about:

• 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 during the 3 months following discontinuation.
• The need to consult your doctor when planning to conceive a child and before stopping contraception (birth control).
• The possibility of using other treatments to treat your disease, depending on your individual situation.

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

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

If your female partner becomes pregnant while you were taking valproate in the 3 months prior to conception and you have any doubts, 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 this visit, your doctor will talk to you about the precautions associated with the use of valproate and the possibility of other treatments that can be used to treat your disease, depending on your individual situation.

Make sure to read the patient guide that your doctor will provide. 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 vision changes, and may decrease your reaction ability. These effects, as well as your underlying disease, may impair your ability to drive vehicles or operate machines. Therefore, do not drive, operate machines, or engage in other activities that require special attention until your doctor assesses your response to this medication.

Important information about some of the components of Depakine 200mg

This medication contains 27.68mg of sodium in each tablet. This is equivalent to 1.4% of the maximum daily recommended sodium intake for an adult.

This medication contains gluten-free cornstarch.

3. How to take Depakine 200 mg enteric-coated tablets

Follow the administration instructions for Depakine indicated by your doctor exactly. Consult your doctor or pharmacist if you have any doubts.

Remember to take your medication.

Girls and women of childbearing age

Treatment with Depakine should be initiated and supervised by a doctor specializing 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.

Your doctor will indicate the duration of your treatment with Depakine. Do not suspend treatment beforehand. Make sure to have regular check-ups with your doctor. This is very important, as the dose you are taking may need to be modified over time.

Depakine is prescribed individually and for a specific situation. You must strictly follow the treatment, never stop it without consulting your doctor. 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 30 mg/kg of body weight.
• Adolescents (≥12 years) and adults (≥18 years): The recommended dose is 20-30 mg/kg of body weight.
• Older adults (≥65 years): 15-20 mg/kg of body weight.
• Patient with hepatic insufficiency: Depakine should not be administered to patients with severe liver disease.
• Patient with renal insufficiency: It is possible that your doctor has recommended lower doses than those indicated in this prospectus. This is because people who suffer from kidney disease may need to decrease the dose of Depakine.

Depakine is for oral administration. The Depakine tablets should be swallowed whole, without fractioning, chewing, or crushing with the help of a little water, preferably during meals.

Try to take the tablets every day at the same time.

The possible doses are always adjusted individually, based on the patient's body weight. The doses with Depakine 200 mg can vary between 1 to 3 tablets (200 mg-600 mg of sodium valproate) per day. For those patients who need higher daily doses, since body weight is greater, other presentations are available.

Patient with kidney problems

Your doctor may decide to adjust your dose.

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

If you think the action of Depakine 200 mg is too strong or too weak, tell your doctor or pharmacist.

If you take more Depakine 200 mg than you should

If you have taken more Depakine than you should, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20 indicating the medication and the amount taken.

An overdose of Depakine can be dangerous. Among the symptoms of poisoning are confusion, sedation, or even coma with hypotonia, muscle weakness, and lack of reflexes. Therefore, go to the nearest hospital where you will be treated for the symptoms and cardio-respiratory monitoring will be performed. In some cases, hypotension, miosis, cardiovascular and respiratory disorders, 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 can be variable, and seizures 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 valproate presentations may lead to hypernatremia when there is an overdose.

It is recommended to take the package and the prospectus of the medication to the healthcare professional.

If you forget to take Depakine 200 mg

In case of forgetting a dose, wait for the next one. Do not take a double dose to make up for the forgotten doses. Continue taking the treatment according to your doctor's instructions. If you have forgotten several doses, contact your doctor immediately.

If you interrupt treatment with Depakine 200 mg

The sudden suspension of treatment with Depakine without explicit indication from your doctor can be harmful to you, as it could trigger episodes with seizures with serious consequences. Do not suspend or alter the dose of Depakine without consulting your doctor beforehand.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

4. Possible adverse effects

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

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

• Somnolence, change in level of consciousness (including coma), confusion, slow or abnormal behavior, and memory loss associated or not with 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 sodium levels in the blood 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 can be due to an increase in the amount of ammonia in the blood.
• Increased number and severity of seizures.
• Repeated vomiting, extreme fatigue, abdominal pain, somnolence, 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 general feeling of discomfort. These can be symptoms of serious liver and pancreas disorders.
• Allergic reactions that can 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 rash, with symptoms sometimes similar to those of the flu such as fever, chills, or muscle pain - these can be signs of conditions called 'toxic epidermal necrolysis' or 'Stevens-Johnson syndrome').
• Inflammatory allergic reaction with painful hives that cause itching (frequently around the eyes, lips, throat, and sometimes on hands and feet) – these can be symptoms of “angioedema”.
• Syndrome that involves skin rash, fever, lymph node enlargement, and possible failure of other organs – these can 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 sometimes manifests with fever and difficulty breathing.
• Underactive thyroid gland, which can cause fatigue or weight gain (hypothyroidism)
• Pain in the joints, fever, fatigue, rash. These can 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.
• Less frequently: 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, interstitial nephritis) that can manifest as a reduction in urine output.

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

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

• Nervous system disorders: tremor.
• Gastrointestinal disorders: nausea.

The frequent adverse effects that can 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, somnolence, seizures, memory failure, headache, rapid and uncontrolled eye movements (nystagmus), dizziness. In isolated cases or associated with an increase in seizures during treatment, cases of confusion that decrease after suspension of treatment and dose reduction have been described.
• 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 (transitory and/or related to the dose).
• Metabolism and nutrition disorders: decrease in sodium levels 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 infrequent adverse effects that can 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 hands or feet (paresthesia), worsening of seizures.

• 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 and connective tissue disorders: alterations in the bones, including osteopenia and osteoporosis (decalcification of the bones) and fractures. Consult your doctor or pharmacist if you are on long-term 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 rare adverse effects that can 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. This 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), interstitial 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 and 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 your 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 the 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 of 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 200 mg enteric-coated tablets

Keep the package perfectly closed to protect it from moisture. Depakine tablets, in contact with environmental humidity, can soften, but the medication remains effective.

Store below 25°C.

Keep out of sight and reach of children.

Do not use Depakine after the expiration date that appears on the package. The expiration date is the last day of the month indicated.

Medications should not be thrown away through the sewers or in the trash. Deposit the packages and medications you no longer need in the SIGRE Point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packages and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Depakine 200 mg enteric-coated tablets

The active principle is sodium valproate. Each enteric-coated tablet contains 200 mg of sodium valproate.

The other components are: povidone, calcium silicate, magnesium stearate, talc, macrogol 400, gluten-free cornstarch, titanium dioxide, diethyl phthalate, and cellulose acetophthalate.

Appearance of the product and package contents

Depakine 200 mg is presented in the form of enteric-coated tablets. The tablets are round and white. Each package contains 40 and 100 tablets for oral administration.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Sanofi-aventis, S.A.

C/ Rosselló i Porcel, 21

08016 Barcelona

Spain

Manufacturer:

sanofi-aventis, S.A.

Ctra. La Batlloria a Hostalrich, Km.63,09

17404 – Riells i Viabrea (Girona), Spain

This prospectus was approved inJanuary 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/48827

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/