Depakine 500 mg enteric-coated tablets: detailed information

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Depakine 500 mg gastro-resistant tablets

sodium valproate

This medicine is subject to additional monitoring, which will allow for rapid identification of new safety information. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions 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 others, even if they have the same symptoms as you, since it could 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 500 mg enteric-coated tablets are and what they are used for.
What you need to know before taking Depakine 500 mg enteric-coated tablets.
How to take Depakine 500 mg enteric-coated tablets.
Possible adverse effects.
How to store Depakine 500 mg enteric-coated tablets.
Contents of the pack and other information.

1. What Depakine 500 mg gastro-resistant tablets are and what they are used for

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

2. What you need to know before taking Depakine 500 mg gastro-resistant tablets.

Do not take Depakine 500 mg

If you are allergic (hypersensitive) to the active substance or to any of the other components of Depakine, or to any other medication, you must inform your doctor.
You should 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 birth control (contraception) throughout your 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 under “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 medications.
If there is a family history of death due to impaired liver function during treatment with sodium valproate.
If you have liver porphyria (a very rare metabolic disorder).
If you have a genetic condition 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 conditions 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 when 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 patients at risk.

If you, or your child, suddenly develop an illness, especially if it occurs during 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 stomach, nausea, jaundice (yellowing of the skin or eyes), swelling of the legs, worsening of epilepsy, or a general feeling of being unwell, 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, feels lethargic or less alert, or vomits, 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 condition 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 condition called “carnitine palmitoyl transferase type II deficiency,” because you are at 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 (low levels of proteins in the blood). In this case, your doctor may wish to monitor your blood levels of valproate or adjust the dose.
When administering Depakine to children under 3 years of age, concomitant use of acetylsalicylic acid (aspirin) should be 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, before any surgical procedure, 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 taking 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.

Taking Depakine 500 mg gastro-resistant tablets with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription, homeopathic medicines, herbal remedies, 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 levels).
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”.
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 (used to treat mental health disorders).

Depakine may enhance 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 you may need to take different medicines. Your doctor or pharmacist will advise you.

Taking Depakine 500 mg with food and drinks

Do not consume alcoholic beverages.

Pregnancy, lactation 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 works.
If you are a woman of childbearing potential, you must not take Depakine unless you use an effective method of birth control (contraception) throughout 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 to your doctor immediately if you are planning to have a baby or if you are pregnant.
Valproate carries a risk when taken during pregnancy. The risk is greater with higher doses, but all doses carry a risk, even when valproate is used in combination with other medicines to treat epilepsy.
It may cause serious birth defects and may 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); malformations of the skull and face, heart, kidneys, urinary tract, genitals, 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, 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 among women who take valproate, about 11 out of every 100 babies 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 experience developmental problems in childhood. Affected children may be slow to speak and walk, may have lower intellectual capacity than other children, and may have difficulties with language and memory.
In children exposed to valproate, autism spectrum disorders are diagnosed more frequently, and there is some evidence that these children have an increased risk of developing Attention Deficit Hyperactivity Disorder (ADHD).
If you take valproate during pregnancy, your baby may have a lower than expected weight for gestational age at birth. Among women taking valproate, about 11–15 out of every 100 babies may have a 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 should 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 have discussed it with your doctor.
If you are a parent or caregiver of a girl being treated with valproate, contact your doctor when the girl treated with valproate reaches menarche (first menstrual period).
Some oral contraceptives (contraceptive pills containing oestrogens) 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 below that apply to you:

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 contraceptive method continuously throughout your treatment with Depakine. Consult your doctor or family planning clinic if you need advice on contraception.

Important messages:

Pregnancy must be ruled out 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 contraceptive methods (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 treating epilepsy. During this visit, your doctor will ensure you understand all risks and warnings related to using valproate during pregnancy.
Inform your doctor if you wish to have a baby.
Contact 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 contraceptive method 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 treating epilepsy. During this visit, your doctor will ensure you understand all risks and warnings related to using valproate during pregnancy.
Inform your doctor if you wish to have a baby.
Contact 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 treating epilepsy so that alternative treatment options can be evaluated early. Your specialist may take several steps to ensure your pregnancy proceeds as safely as possible and risks to you and the fetus are minimized as much as possible.

Your specialist may decide to adjust your Depakine dose, switch you to another medicine, or discontinue your Depakine treatment well in advance of 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 that exists 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 speaking 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 using valproate during pregnancy.
Your doctor will aim 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 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 treating epilepsy to evaluate alternative treatment options.

In exceptional circumstances where Depakine is the only treatment option during pregnancy, you will be closely monitored for management of your underlying condition and to assess fetal development. You and your partner may receive counselling 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 that exists 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 treating epilepsy to evaluate the need for alternative treatment options.
You must receive counselling 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 specialist in prenatal monitoring to detect possible malformations.

Make sure to read the Patient Guide provided by your doctor. Your doctor will discuss the Annual Risk Acknowledgement 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 newborn babies of mothers who have taken Depakine during pregnancy also:

Coagulation disorders may occur due to partial or complete deficiency of certain substances required for blood clotting. In severe cases, this problem may be fatal; therefore, specific blood tests and coagulation studies should be performed in the newborn.
Hypoglycemia may occur in newborns of mothers who have taken Depakine during pregnancy.
Cases of neonatal hypothyroidism have been reported in babies born to mothers who took valproate during pregnancy.
A withdrawal syndrome (such as agitation, irritability, hyperexcitability, restlessness, hyperkinesia, disturbances in muscle tone, tremor, seizures, and feeding difficulties) may occur in neonates whose mothers took valproate during the last trimester of pregnancy.

Breast-feeding

Consult your doctor or pharmacist before taking any medication.

Sodium valproate passes into breast milk. However, the amounts of sodium valproate excreted in breast milk are small and therefore, treatment with Depakine during the breast-feeding period generally does not pose a risk to the infant and discontinuation of breast-feeding is usually not necessary. Nevertheless, you should consult your doctor on whether or not to continue breast-feeding, taking into account the safety profile of Depakine, particularly blood disorders (see section “Possible side effects”).

Important information for male patients

Potential risks related to 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 during the 3 months prior to conception. In this study, approximately 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 may be used to treat your condition). The risk for children born to fathers who discontinued valproate treatment 3 months (the time required for the formation of 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 disorders that children may develop.

As a precautionary measure, 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 considering having a child.

If your female partner becomes pregnant while you were taking valproate within the 3 months prior to 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 attend regular appointments with your doctor. During these visits, your doctor will discuss with you the precautions associated with the use of valproate and the possibility of alternative treatments for your condition, depending on your individual situation.

You should make sure to read the patient guide you will receive from your doctor. You will also receive from your pharmacist a Patient Card to remind you of the potential risks of valproate.

Driving and use of machines

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

Important information about some of the components of Depakine 500 mg

This medicine contains 69.19 mg of sodium per tablet. This is equivalent to 3.5% of the maximum daily recommended sodium intake for an adult.

This medicine contains gluten-free maize starch.

3. How to take Depakine 500 mg gastro-resistant tablets

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

Remember to take your medication.

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.

Your doctor will inform you about the duration of your Depakine treatment. Do not stop treatment prematurely. Make sure you attend regular follow-up appointments with your doctor. This is very important, as the dose you are taking may need adjustments over time.

Depakine is prescribed individually and for a specific condition. You must strictly follow the treatment regimen and never stop it without consulting your doctor. The recommended doses in this leaflet are indicative only. Depakine doses are determined according to body weight, your individual condition, and the prescribing doctor's judgment.

Infants and children (28 days to 11 years): The recommended dose is 30 mg/kg body weight.
Adolescents (≥12 years) and adults (≥18 years): The recommended dose is 20–30 mg/kg body weight.
Elderly patients (≥65 years): 15–20 mg/kg body weight.
Patients with hepatic impairment: Depakine must not be administered to patients with severe liver disease.
Patients with renal impairment: Your doctor may have recommended doses lower than those indicated in this leaflet. This is because patients with kidney disease may require a reduced dose of Depakine.

Depakine is for oral use. Depakine tablets must be swallowed whole, without dividing, chewing, or crushing them, with a little water, preferably during meals.

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

Possible doses are always individually adjusted based on the patient's body weight. Doses with Depakine 500 mg may range between 2 and 6 tablets (1000 mg–3000 mg of sodium valproate) per day.

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.

If you think that the effect of Depakine 500 mg is too strong or too weak, inform your doctor or pharmacist.

If you take more Depakine 500 mg than you should

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

An overdose of Depakine can be dangerous. Symptoms of poisoning include confusion, sedation, or even coma with hypotonia, muscle weakness, and absence of reflexes. Therefore, go immediately to the nearest hospital, where symptoms will be treated and cardiorespiratory monitoring will be performed. In some cases, hypotension, miosis, cardiovascular and respiratory disturbances, circulatory collapse/shock, metabolic acidosis, hypocalcemia, and hypernatremia have also been observed. Fatalities have occurred after 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 intracranial hypertension associated with cerebral edema have been reported.

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

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

If you forget to take Depakine 500 mg

If you miss a dose, wait until the next scheduled dose. Do not take a double dose to make up for the missed dose. Continue taking the medication as instructed by your doctor. If you have missed several doses, contact your doctor immediately.

If you stop taking Depakine 500 mg

Abruptly stopping Depakine treatment without explicit instruction from your doctor may be harmful, as it could trigger seizure episodes with serious consequences. Do not stop or alter your Depakine dose without first consulting your doctor.

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

4. Possible adverse effects

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

Tell your doctor immediately if any of the following serious adverse effects occur. You may need 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 decreased sodium levels in the blood 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, or 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 peeling, or bleeding on 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 rashes (often around the eyes, lips, throat, and sometimes hands and feet)—these may be symptoms of “angioedema”.
A 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 appearance of bruises or bleeding due to blood clotting problems detected in blood tests.
Severe decrease in white blood cells or bone marrow failure detected in blood tests, sometimes manifested by fever and breathing difficulties.
Underactive thyroid gland, which may cause tiredness or weight gain (hypothyroidism).
Joint pain, fever, fatigue, rash. These may be signs of systemic lupus erythematosus.
Tremor, uncontrollable muscle contractions, unsteadiness when walking (parkinsonism, extrapyramidal disorder, ataxia).
Muscle pain and muscle weakness (rhabdomyolysis).
Sedation, extrapyramidal disorders.
Uncommon: 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 reduced 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:

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

Nervous system disorders: tremor.
Gastrointestinal disorders: nausea.

Common adverse effects (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 movements (extrapyramidal disorders), stupor, drowsiness, seizures, memory impairment, headache, rapid and uncontrollable eye movements (nystagmus), dizziness. In isolated cases or associated with increased seizure frequency during treatment, cases of confusion have been reported, which improve 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), upper abdominal pain and diarrhea, which frequently occur in some patients at the beginning of treatment and usually disappear within a few days without interrupting treatment.
Skin and subcutaneous tissue disorders: nail and nail bed abnormalities, hypersensitivity, hair loss (transient and/or dose-related).
Metabolism and nutrition disorders: decreased sodium in blood (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 there (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 (leucopenia).
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 (paraesthesia), 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 decalcification) 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 alopecia, 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. This causes severe anemia, symptoms of which include unusual tiredness and lack of energy), agranulocytosis (decreased number of white blood cells), decreased number of red blood cells with abnormally large size (macrocytic anemia, macrocytosis).
Investigations: 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 widespread 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.
Investigations: false positive results in urine ketone elimination tests may occur 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, talk to 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 500 mg enteric-coated tablets

Keep the container tightly closed to protect it from moisture. Depakine tablets may soften if exposed to environmental moisture, but the medicinal product remains effective.

Store below 25°C.

Keep out of the sight and reach of children.

Do not use Depakine after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused containers and medicines at the SIGRE collection point at your pharmacy. If you are unsure how to dispose of unused containers and medicines, ask your pharmacist. This will help protect the environment.

6. Contents of the pack and other information

Composition of Depakine 500 mg gastro-resistant tablets

The active substance is sodium valproate. Each gastro-resistant tablet contains 500 mg of sodium valproate.

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

Appearance of the product and contents of the pack

Depakine 500 mg is presented as gastro-resistant tablets. The tablets are round and yellow in colour. Each pack contains 20 or 100 tablets for oral administration.

Marketing Authorisation Holder and Manufacturer:

Marketing Authorisation 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 (GERONA) Spain

Sanofi Winthrop Industrie

1, rue de la Vierge

Ambarès et Lagrave

33565 Carbon Blanc CEDEX

France

This leaflet was approved in October 2025

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 leaflet. You can also access this information at the following internet address: https://cima.aemps.es/info/54470

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