Depakine 200 mg gastro-resistant tablets: detailed information

Patient Information Leaflet

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Depakine 200 mg enteric-coated tablets

sodium valproate

This medicine is subject to additional monitoring, which will allow quicker detection 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) without interruption 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 if you 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 you start taking this medicine, as it contains important information for you.

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

Contents of the leaflet

What Depakine 200 mg gastro-resistant tablets are and what they are used for.
What you need to know before taking Depakine 200 mg gastro-resistant tablets.
How to take Depakine 200 mg gastro-resistant tablets.
Possible adverse effects.
How to store Depakine 200 mg gastro-resistant tablets.
Contents of the pack and other information.

1. What Depakine 200 mg enteric-coated tablets are and what they are 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.

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

Do not take Depakine 200 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 must not use Depakine if you are pregnant, unless no other treatment has been effective.
If you are a woman of childbearing potential, you must not take Depakine unless you use an effective method of birth control (contraception) throughout your treatment with Depakine. Do not stop taking Depakine or your contraceptive until you have discussed this with your doctor. Your doctor will advise you (see below under “Pregnancy, breastfeeding and fertility – Important warning for women”).
If you currently have any liver or pancreas disease.
If you have previously had any liver disease.
If any of your close relatives have a history of severe liver disease (hepatitis), particularly caused by 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 disorder causing a mitochondrial disorder (e.g., Alpers-Huttenlocher syndrome).
If you have a known metabolic disorder, such as a urea cycle disorder.
If you have untreated carnitine deficiency (a very rare metabolic disease).

If you think you may have any of these problems or if you have any doubts, consult your doctor before 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 medicines simultaneously, or in those with other neurological or metabolic disorders and severe forms of epilepsy.

Your doctor should check 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 occurs during the first months of treatment and, in particular, if it includes repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, upper stomach pain, nausea, jaundice (yellowing of the skin or eyes), leg swelling, 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, feelings of lethargy or reduced alertness, or vomiting, inform your doctor immediately. This may be due to an increase in blood ammonia levels.

A small number of people who have taken 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 have been reported with valproate treatment, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), erythema multiforme, and angioedema. Seek immediate medical attention if you notice any symptoms related to these serious skin reactions described in section 4.

Before taking this medicine, consult your doctor:

If you know or your doctor suspects a genetic problem caused by a mitochondrial disorder in your family, due to the risk of liver damage.
If a metabolic disorder is suspected, particularly inherited enzyme deficiencies such as a “urea cycle disorder,” due to the risk of increased blood ammonia levels.
If you have a rare condition called “carnitine palmitoyltransferase 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 (full 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.

Use of Depakine 200 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 remedies, herbal medicines, and other health-related products, as it may be necessary to discontinue 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 developing a severe skin rash may increase when lamotrigine and valproic acid are taken together), carbamazepine, ethosuximide, felbamate, and topiramate. Concomitant administration of Depakine with topiramate has been associated with encephalopathy and/or hyperammonemia (a brain and nervous system disorder occurring as a complication of liver disorders with or without increased blood ammonia).
Zidovudine (a medicine used to treat HIV and AIDS infections).
Mefloquine (a medicine used to treat or prevent malaria).
Salicylates (aspirin). See also “Warnings and precautions – Children under 3 years of age”.
Anticoagulants (medicines used to prevent blood clots).
Cimetidine (a medicine used to treat stomach ulcers).
Erythromycin and rifampicin (antibiotics).
Rufinamide.
Acetazolamide.
Protease inhibitors, such as lopinavir, ritonavir (used in HIV treatment).
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-infective agents containing pivalate (e.g., pivampicillin, adefovir dipivoxil).

Clozapine (used to treat mental health disorders).

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

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

Taking Depakine 200 mg with food and drinks

Do not consume alcoholic beverages.

Pregnancy, breastfeeding and fertility

Pregnancy

Consult your doctor or pharmacist before using any medicine.

Important warning for women

You must not use Depakine if you are pregnant, unless no other treatment works.
If you are a woman of childbearing potential, you must not take Depakine unless you use an effective method of contraception (birth control) 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.

Risks of valproate when taken during pregnancy

Speak with 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 higher with the highest dose, 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, genital organs, limb defects, and multiple 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.
Eye malformations have been reported in children exposed to valproate during pregnancy, often in association with other congenital malformations. These eye malformations may affect vision.
If you take valproate during pregnancy, you have a higher risk than other women of having a baby with birth defects requiring medical treatment. As valproate has been used for many years, it is known that 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 speak and walk slowly, may have lower intellectual capacity than other children, and may have language and memory difficulties.
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 at birth for their gestational age. Among women taking valproate, about 11–15 out of every 100 babies may have lower than expected birth weight. This compares with 5–10 out of every 100 babies born to women in the general population.
Before prescribing this medicine, your doctor 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 contraception until you have discussed it with your doctor.
If you are a parent or caregiver of a girl being treated with valproate, you should contact your doctor when the girl undergoing treatment with valproate reaches menarche (first menstruation).
Some oral contraceptives (birth control pills containing oestrogens) may reduce blood levels of valproate. Be sure to discuss with your doctor the most appropriate contraceptive method (birth control) for you.
Ask 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 the use of valproate.

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 should have explained the risks to the unborn baby if you become pregnant. Once you reach childbearing age, you must ensure you use an effective method of contraception continuously throughout your entire 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, as verified by your doctor.
You must use an effective method of birth control (contraception) throughout your entire treatment with Depakine.
You must discuss appropriate methods of birth control (contraception) with your doctor. Your doctor will provide information on how to prevent pregnancy and may refer you to a specialist for contraceptive advice.
You must have regular consultations (at least annually) with a specialist experienced in the treatment of epilepsy. During this visit, your doctor will ensure you understand all risks and warnings related to the use of 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 method of contraception continuously throughout your treatment with Depakine. Consult your doctor or family planning clinic if you need advice on contraception.

Important messages:

You must use an effective method of birth control (contraception) throughout your entire treatment with Depakine.
You must discuss contraception (birth control) with your doctor. Your doctor will provide information on how to prevent pregnancy and may refer you to a specialist for contraceptive advice.
You must have regular consultations (at least annually) with a specialist experienced in the treatment of epilepsy. During this visit, your doctor will ensure you understand all risks and warnings related to the use of 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, schedule an appointment with your doctor first.

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

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

Ask 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 the use of valproate.

Important messages:

Do not stop taking Depakine unless your doctor tells you to.
Do not stop using your contraceptive methods (birth control) before discussing it 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 the use of valproate during pregnancy.
Your doctor will aim to switch you to another medicine or discontinue Depakine well before conception.
Schedule an urgent appointment with your doctor if you are pregnant or think you may be pregnant.

I AM PREGNANT AND TAKING DEPAKINE

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

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

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

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

Ask 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 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.
Ensure you are referred to a specialist experienced in the treatment of 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 took Depakine during pregnancy also:

Bleeding disorders may occur due to partial or complete deficiency of one or more substances necessary for blood clotting. In the latter case, the condition may be fatal; therefore, blood tests and specific coagulation tests must be performed in the newborn.
Hypoglycaemia may occur in newborns of mothers who took 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, nervousness, hyperkinesia, muscle tone disorders, 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 regarding the advisability of continuing or discontinuing 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 associated with the use of valproate in the 3 months prior to conception

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, approximately 5 out of every 100 children exhibited 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 medications 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 new sperm production) 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 might 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 discontinuing contraception (birth control).
The possibility of using alternative treatments for your condition, depending on your individual circumstances.

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-month period before conception and you have any concerns, contact your doctor. Do not stop treatment without consulting your doctor. If you stop treatment, your symptoms may worsen.

You should 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 capability. 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 medication.

Important information about some of the components of Depakine 200mg

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

This medicine contains gluten-free corn starch.

3. How to take Depakine 200 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 to attend periodic check-ups with your doctor. This is very important, as the dose you are taking may require adjustments over time.

Depakine is prescribed individually and for a specific condition. You must strictly follow the treatment; 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 physician'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 people with kidney disease may require a reduced dose of Depakine.

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

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

Doses are always individually adjusted based on the patient's body weight. Doses with Depakine 200 mg may range from 1 to 3 tablets (200 mg–600 mg of sodium valproate) per day. For patients requiring higher daily doses due to greater body weight, other formulations are available.

Patients with renal 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 the effect of Depakine 200 mg is too strong or too weak, inform your doctor or pharmacist.

If you take more Depakine 200 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 number: 91 562 04 20, indicating the medication and the amount taken.

An overdose of Depakine can be dangerous. Symptoms of intoxication include confusion, sedation, or even coma with hypotonia, muscle weakness, and loss 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. Fatal outcomes have occurred after massive overdoses; however, a favorable outcome is more common.

Nevertheless, symptoms may vary, and seizures have been reported with very high plasma levels. Cases of intracranial hypertension associated with cerebral edema have been reported.

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

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

If you forget to take Depakine 200 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 directed by your doctor. If you have missed several doses, contact your doctor immediately.

If you stop taking Depakine 200 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 using this product, ask your doctor or pharmacist.

4. Possible adverse effects

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

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

Drowsiness, change in level of consciousness (including coma), confusion, slow or abnormal behavior, and memory loss, with or without increased frequency or severity of seizures, particularly if you are taking phenobarbital or topiramate (medicines used to treat seizures) at the same time, or if the dose of Depakine has been increased suddenly.
Confusion that may be caused by a decrease in blood sodium levels or by a condition called Syndrome of Inappropriate Secretion of Antidiuretic Hormone (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 number and severity of seizures.
Repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, severe pain in the upper abdomen, nausea, jaundice (yellowing of the skin or whites of the eyes), swelling of the legs, worsening of epilepsy, or feeling generally unwell. These may be symptoms of serious liver or 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 hives (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 bruising 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 presenting with 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.
Agitation (tremor), uncontrollable muscle contractions, unsteadiness when walking (parkinsonism, extrapyramidal disorder, ataxia).
Muscle pain and muscle weakness (rhabdomyolysis).
Sedation, extrapyramidal disorders.
Uncommon: difficulty breathing, chest pain or pressure (especially when inhaling), difficulty breathing and dry cough due to fluid accumulation around the lungs (pleural effusion).
Kidney disease (renal failure, tubulointerstitial nephritis) that may present as reduced urine output.

Contact your doctor or pharmacist if any of the following adverse effects worsen or persist for more than a few days; you may require 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 red blood cells (anemia) and reduction in platelet count (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, confusion has been reported, which improves after discontinuation or dose reduction.
Renal and urinary disorders: urinary incontinence.
Ear disorders: hearing problems or deafness.
Gastrointestinal disorders: vomiting, gum problems (mainly hypertrophy), pain and swelling in the mouth, 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 resolve within a few days without stopping treatment.
Skin and subcutaneous tissue disorders: nail and nail bed abnormalities, hypersensitivity, hair loss (transient and/or dose-related).
Metabolism and nutrition disorders: decreased blood sodium (hyponatremia), weight gain.
Vascular disorders: bleeding.
Hepatobiliary disorders: liver injury.
Reproductive system disorders: painful menstruation (dysmenorrhea).
Psychiatric disorders: confusion, seeing, feeling or hearing things that are not there (hallucinations), aggression*, agitation*, attention disorders* (* mainly observed in children).

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

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

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

Blood disorders: bone marrow failure including pure red cell aplasia (halted or reduced production of red blood cells, leading to severe anemia, with symptoms such as unusual tiredness and lack of energy), agranulocytosis (decreased number of white blood cells), decreased number of red blood cells with larger than normal size (macrocytic anemia, macrocytosis).
Additional 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, which may be 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.
Additional investigations: false positive results in urine ketone tests may occur in diabetic patients.
Decreased levels of carnitine (detected in blood or muscle biopsy).
Skin and subcutaneous tissue disorders: darkened areas of 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, pancreas inflammation (pancreatitis), aggression, agitation, attention disorders, abnormal behavior, hyperactivity, and learning disorders.

Reporting of adverse effects

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

5. Storage of Depakine 200 mg gastro-resistant tablets

Keep the container tightly closed to protect it from moisture. Depakine tablets may soften if exposed to atmospheric 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 packaging. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Unused medicines and their containers should be returned to the SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of medicines and containers you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of Depakine 200 mg enteric-coated tablets

The active substance 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 corn starch, titanium dioxide, diethyl phthalate and cellulose acetate phthalate.

Appearance of the product and contents of the pack

Depakine 200 mg is presented as enteric-coated tablets. The tablets are white and round. Each pack contains 40 or 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 (GERONA), Spain

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/48827

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/