Depakine Chrono 300 mg prolonged-release tablets: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

Depakine Chrono 300 mg prolonged-release tablets

sodium valproate/valproic acid

This medicine is subject to additional monitoring, which will allow rapid 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 Chrono, valproic acid and sodium valproate, can seriously harm the fetus 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 Chrono. 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 Chrono 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, as it may harm them.
- If you experience any adverse effects, consult your doctor or pharmacist, even if these adverse effects are not listed in this leaflet. See section 4.

Contents of the leaflet

What Depakine Chrono 300 mg is and what it is used for
What you need to know before taking Depakine Chrono 300 mg
How to take Depakine Chrono 300 mg
Possible adverse effects
Storage of Depakine Chrono 300 mg
Contents of the pack and other information
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1. What is Depakine Crono 300 mg and what is it used for

Depakine Crono is a medication used for the treatment of epilepsy and mania.

Depakine Crono is used in the treatment of:

Various types of epilepsy in adults and children.
Mania, a disorder in which you may feel extremely excited, euphoric, agitated, enthusiastic, or hyperactive. Mania occurs in a condition called "bipolar disorder". Depakine Crono 300 mg may be taken when lithium cannot be used.

2. What you need to know before taking Depakine Chrono 300 mg

Do not take Depakine Chrono 300 mg

If you are allergic (hypersensitive) to the active substance or to any of the other components of Depakine Chrono, or to any other medicine, you must inform your doctor.
Bipolar disorder
For bipolar disorder, you must not use Depakine Chrono if you are pregnant.
For bipolar disorder, if you are a woman of childbearing potential, you must not take Depakine Chrono unless you use an effective method of birth control (contraception) throughout treatment with Depakine Chrono. Do not stop taking Depakine Chrono 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”).
Epilepsy
For epilepsy, you must not use Depakine Chrono if you are pregnant, unless no other treatment works.
For epilepsy, if you are a woman of childbearing potential, you must not take Depakine Chrono unless you use an effective method of birth control (contraception) throughout treatment with Depakine Chrono. Do not stop taking Depakine Chrono or your contraceptive until you have discussed this with your doctor. Your doctor will advise you (see below under “Pregnancy, breastfeeding and fertility – Important warning for women”).
If you currently have any liver or pancreatic disease.
If you have previously had any liver disease.
If any of your close relatives have a history of severe liver disease (hepatitis), mainly due to medicines.
If you have a family history of a relative who died from 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 problems or if you have any doubts, consult your doctor before taking Depakine Chrono.

Warnings and precautions

CONSULT YOUR DOCTOR IMMEDIATELY:

The risk of liver damage increases if valproate is administered to children under 3 years of age, in people taking other antiepileptic medicines at the same time, 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 develops 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 abdomen, 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 Chrono 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 an increase in 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 you have such thoughts at any time, contact your doctor immediately.

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

Before taking this medicine, consult your doctor

If you know or your doctor suspects a genetic problem caused by a mitochondrial disorder in your family, due to the risk of liver damage. If a metabolic disorder is suspected, particularly inherited enzyme deficiencies such as a “urea cycle disorder,” due to the risk of increased blood ammonia levels.
If you have a rare 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 suffer from impaired kidney function or hypoproteinemia (decreased levels of proteins in the blood). In this case, your doctor may wish to monitor valproate blood levels or adjust the dose.
Concomitant administration of Depakine Chrono with acetylsalicylic acid (aspirin) should be especially avoided in children under 3 years of age.
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 or before a surgical procedure, and in cases of spontaneous bruising or bleeding. If weight gain occurs 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 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 interrupt treatment or adjust the dose of one of them.

Some medicines may alter the effect of Depakine Chrono 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 to help 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 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 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 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 Chrono, or they may directly affect the activity of Depakine Chrono. You may need different doses of medicine or may need to take different medicines. Your doctor or pharmacist will advise you.

Taking Depakine Chrono 300 mg with food and drinks

Do not consume alcoholic beverages.

Children and adolescents

Children and adolescents under 18 years of age.

Depakine Chrono must not be used in children and adolescents under 18 years of age for the treatment of mania.

Pregnancy, breastfeeding and fertility

Pregnancy

Consult your doctor or pharmacist before using any medicine.

Important warning for women

Bipolar disorder

For bipolar disorder, you must not use Depakine Chrono if you are pregnant.
For bipolar disorder, if you are a woman of childbearing potential, you must not take Depakine Chrono unless you use an effective method of birth control (contraception) throughout treatment with Depakine Chrono. Do not stop taking Depakine Chrono or your contraceptive, until you have discussed this with your doctor. Your doctor will advise you.

Epilepsy

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

Risks of valproate when taken during pregnancy (regardless of the condition for which it is used)

Speak with your doctor immediately if you are planning to have a baby or 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, kidney, urinary tract, genitals, 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.
Ocular malformations have been reported in children exposed to valproate during pregnancy, often associated 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 child with birth defects requiring medical treatment. As valproate has been used for many years, it is known that among women taking valproate, approximately 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, have lower intellectual capacity than other children, and experience 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 birth weight. In women taking valproate, approximately 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, you should contact your doctor when the girl undergoing treatment with valproate reaches menarche (first menstruation).
Some contraceptive pills (contraceptive pills containing estrogens) may reduce valproate blood levels. Be sure to discuss with your doctor the most appropriate contraceptive method (birth control) for you.
Consult your doctor about taking folic acid 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.

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

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

I AM STARTING TREATMENT WITH DEPAKINE CHRONO

If this is the first time you have been prescribed Depakine Chrono, your doctor should have explained the risks to the fetus if you become pregnant. Once you reach childbearing age, you must ensure that you use an effective contraceptive method continuously throughout your treatment with Depakine Chrono. 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 Chrono, confirmed by a pregnancy test result reviewed by your doctor.
You must use an effective method of birth control (contraception) throughout treatment with Depakine Chrono.
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 bipolar disorder or epilepsy. During these visits, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Inform your doctor if you wish to have a baby.
Consult your doctor immediately if you are pregnant or think you may be pregnant.

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

If you continue treatment with Depakine Chrono but do not plan to have a baby, ensure you use an effective contraceptive method continuously throughout your treatment with Depakine Chrono. 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 treatment with Depakine Chrono.
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 bipolar disorder or epilepsy. During these visits, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Inform your doctor if you wish to have a baby.
Consult your doctor immediately if you are pregnant or think you may be pregnant.

I AM TAKING DEPAKINE CHRONO 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 Chrono 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 bipolar disorder or epilepsy so that alternative treatment options can be evaluated from the outset. Your specialist may take several steps to ensure your pregnancy proceeds as safely as possible and risks to you and the fetus are minimized.

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

Consult your doctor about taking folic acid when trying to conceive. Folic acid may reduce the general risk of spina bifida and early miscarriage present 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 Chrono unless your doctor tells you to.
Do not stop using your contraceptive methods (contraception) before discussing with your doctor and developing a plan together to ensure your condition is controlled and risks to your baby are minimized.
First, schedule an appointment with your doctor. During this visit, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Your doctor will aim to switch you to another medicine or discontinue Depakine Chrono 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 CHRONO

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

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

Your doctor will refer you to a specialist experienced in treating bipolar disorder or epilepsy to evaluate alternative treatment options.

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

Consult your doctor about taking folic acid. Folic acid may reduce the general risk of spina bifida and early miscarriage present 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 Chrono unless your doctor tells you to.
Ensure you are referred to a specialist experienced in treating epilepsy or bipolar disorder to evaluate the need for alternative treatment options.
You must receive counseling on the risks of Depakine Chrono 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.

Be sure to read the Patient Guide provided by your doctor. Your doctor will discuss the Annual Risk Acknowledgement 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 taken during pregnancy.

In newborns of mothers who took Depakine Chrono 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 should be performed in the newborn.
Hypoglycemia may occur in newborns of mothers who took Depakine Chrono during pregnancy.
Cases of neonatal hypothyroidism have been reported in newborns of mothers who took valproate during pregnancy.
A withdrawal syndrome (such as agitation, irritability, hyperexcitability, restlessness, hyperkinesia, muscle tone disorders, tremor, seizures, and feeding difficulties) may occur in neonates whose mothers took valproate during the last trimester of pregnancy.

Breastfeeding

Consult your doctor or pharmacist before taking any medication.

Sodium valproate is excreted in breast milk. However, the amounts of sodium valproate transferred into breast milk are small, and therefore treatment with Depakine Chrono during breastfeeding generally does not pose a risk to the infant and discontinuation of breastfeeding is usually not necessary. Nevertheless, you should consult your doctor regarding the advisability of continuing or discontinuing breastfeeding, taking into account the safety profile of Depakine Chrono, 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 motor and mental developmental 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 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 to form) or more before conception is unknown. The study has limitations, and therefore it is unclear whether the increased risk of motor and mental developmental disorders suggested by this study is caused by valproate. The study was not large enough to determine the specific type of motor and mental developmental 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 stopping contraception (birth control).
The possibility of using alternative 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-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 other treatments that may be used to treat your condition, depending on your individual situation.

You should ensure you 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 Chrono may cause symptoms such as drowsiness, dizziness, or visual disturbances and may reduce reaction time. These effects, as well as the underlying 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 Chrono 300 mg

This medicine contains 27.65 mg of sodium per tablet. This corresponds to 1.4% of the maximum daily recommended sodium intake for an adult.

3. How to take Depakine Chrono 300 mg

Follow exactly the administration instructions for Depakine Chrono provided 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 Chrono should be initiated and supervised by a physician specialized in the treatment of epilepsy or bipolar disorder.

Male patients

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

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

Recommended indicative doses for the treatment of epilepsy

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.
Elderly patients (≥65 years): 15–20 mg/kg of body weight.
Patients with hepatic impairment: Depakine Chrono 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 individuals with kidney disease may require a reduced dose of Depakine Chrono.

Possible doses are always individually adjusted based on the patient's body weight. Doses with Depakine Chrono 300 mg may range from 1 to 3 tablets (300 mg – 900 mg of sodium valproate) per day. For patients requiring higher daily doses due to higher body weight, other available presentations are available.

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

Mania

The daily dose must be individually established and monitored by your doctor.

Initial dose

The recommended initial daily dose is 750 mg.

Average daily dose

The recommended daily dose usually ranges between 1,000 mg and 2,000 mg.

Depakine Chrono is for oral use. Depakine Chrono 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 every day.

Patients with renal problems

Your doctor may decide to adjust your dose.

If you feel that the effect of Depakine Chrono is too strong or too weak, inform your doctor or pharmacist.

If you take more Depakine Chrono 300 mg than you should

If you have taken more Depakine Chrono 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 amount taken.

An overdose of Depakine Chrono can be dangerous. Symptoms of intoxication include confusion, sedation, or even coma with hypotonia, muscle weakness, and lack of reflexes. You should go 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 overdose; however, a favorable outcome is more common.

However, 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 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 Chrono 300 mg

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

If you stop taking Depakine Chrono 300 mg

Abruptly stopping treatment with Depakine Chrono without explicit instruction from your doctor may be harmful, as it could trigger seizure episodes with serious consequences. Do not stop or alter the dose of Depakine 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 Chrono can cause adverse effects, although not everyone experiences them.

Contact your doctor immediately if any of the following serious adverse effects occur. Urgent medical attention may be required:

Drowsiness, changes in consciousness level (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 Chrono has been increased suddenly.
Confusion that may be caused by low blood sodium levels or by a condition called Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).
Problems with balance and coordination, feeling lethargic or less alert, associated with vomiting. This may be due to increased blood ammonia levels.
Increase in the number and severity of seizures.
Repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, severe upper stomach pain, nausea, jaundice (yellowing of the skin or whites of the eyes), leg swelling, or worsening of epilepsy or general malaise. These may be symptoms of serious liver or pancreas disorders.
Allergic reactions that may manifest as:
Blisters with skin peeling (blisters, skin shedding, 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 known as '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 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.
Tremor (shakiness), 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), which may present as reduced urine output.

Inform your doctor or pharmacist if any of the following adverse effects worsen or persist beyond a few days; medical treatment may be needed:

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

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

Blood disorders: deficiency of blood components (pancytopenia) and decreased number of white blood cells in blood (leukopenia).
Nervous system disorders: coma, encephalopathy, lethargy, a disorder characterized by tremor, difficulty walking, movement, and coordination (reversible parkinsonism), incoordination of movements (ataxia), numbness or tingling in feet or hands (paresthesia), worsening of seizures.
Renal and urinary disorders: renal failure.
Gastrointestinal disorders: pancreatitis, which may be fatal.
Skin and subcutaneous tissue disorders: swelling of feet, hands, throat, lips, and airways (angioedema) and rash, abnormal hair growth and texture, and changes in hair color.
Musculoskeletal disorders: bone abnormalities have been reported, including osteopenia and osteoporosis (bone demineralization) and fractures. Consult your doctor or pharmacist if you are on long-term antiepileptic treatment, have a history of osteoporosis, or take steroids.
Endocrine disorders: Syndrome of Inappropriate Antidiuretic Hormone Secretion (fluid retention and decreased levels of certain electrolytes in blood), hyperandrogenism (increased hair growth, virilization, acne, male-pattern baldness, 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, causing 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 tests: decreased coagulation factors, biotin/biotinidase deficiency (low levels of vitamin B8).
Nervous system disorders: worsening of mental function causing confusion and changes in intellect or reasoning (reversible dementia), cognitive disorder, double vision.
Kidney disorders: involuntary urination (enuresis), tubulointerstitial nephritis, increased frequency of urination and thirst (Fanconi syndrome).
Skin and subcutaneous tissue disorders: skin lesions with red spots, blisters, and even peeling that may become severe (Stevens-Johnson syndrome), DRESS syndrome (severe skin reaction characterized by 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 condition 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 treatment without consulting your doctor first), polycystic ovaries.
Psychiatric disorders: abnormal behavior*, psychomotor hyperactivity*, learning disorders* (* mainly observed in children).

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

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

Additional adverse effects in children

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

Reporting of adverse effects

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

5. Storage of Depakine Chrono 300 mg

This medicine does not require any special storage conditions.

Keep the tablets in the original container until the time of use. Depakine Chrono tablets may soften when exposed to ambient moisture, but the medicine remains effective.

Keep out of the sight and reach of children.

Do not use Depakine Chrono 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 medicines and their containers at the SIGRE collection point at your pharmacy. If you are in doubt, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Depakine Chrono 300 mg

Each Depakine Chrono 300 mg prolonged-release tablet contains 200 mg of sodium valproate and 87 mg of valproic acid, equivalent to 300 mg of sodium valproate. The other components are: acrylic and methacrylic acid copolymer ester, ethylcellulose, colloidal hydrated silica, hypromellose, macrogol 6000, talc, titanium dioxide and polycrylate.

Appearance of the product and contents of the pack

Depakine Chrono 300 mg is presented as prolonged-release tablets. The tablets are white and oblong. Each pack contains 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 Winthrop Industrie

1, rue de la Vierge, Ambarès et Lagrave,

F-33565 Carbon Blanc cedex, France

sanofi-aventis S.A.

Ctra. C-35 La Batllòria-Hostalric, Km. 63.09

17404 Riells i Viabrea (Girona)

Spain

This summary of product characteristics was approved in October 2025

You can access detailed and up-to-date information on 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/60351.

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/