Valproic acid Aurovitas 500 mg prolonged-release tablets EFG: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

Valproic Acid Aurovitas 500 mg prolonged-release tablets EFG

sodium valproate/valproic acid

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is provided at the end of section 4.

WARNING

Valproic Acid Aurovitas, valproic acid, and sodium valproate may cause serious damage to the foetus 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 Valproic Acid Aurovitas. 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 might be pregnant.

Do not stop taking Valproic Acid Aurovitas unless your doctor tells you to, as your condition may worsen.

Read this 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, ask your doctor or pharmacist.
This medicine has been prescribed for you only and should not be given to other people, even if they have the same symptoms as you, since it could harm them.
If you experience any side effects, consult your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet Contents

What Valproic Acid Aurovitas is and what it is used for
What you need to know before taking Valproic Acid Aurovitas
How to take Valproic Acid Aurovitas
Possible side effects
How to store Valproic Acid Aurovitas
Contents of the pack and other information

1. What is Valproic Acid Aurovitas and what is it used for

Valproic acid belongs to a group of medicines used to treat epilepsy:

Partial or generalized epilepsy.
Primary generalized epilepsy: convulsive (clonic, tonic, tonic-clonic, myoclonic) and non-convulsive or absence seizures.
Partial epilepsy: simple and complex seizures.
Secondary generalized seizures.
Treatment of mixed and idiopathic generalized seizures and/or symptomatic generalized epilepsy (West and Lennox-Gastaut syndromes).

Valproic acid is a medicine used to treat mania, a condition in which you may feel extremely excited, euphoric, agitated, enthusiastic, or hyperactive. Mania occurs in an illness called "bipolar disorder." Valproic acid may be used when lithium cannot be used.

2. What you need to know before starting to take Valproic Acid Aurovitas

Do not take Valproic Acid Aurovitas

If you are allergic to valproic acid, sodium valproate, or any of the other ingredients of this medicine (listed in section 6).
If you currently have hepatitis or a liver disease.
If you have a disorder of liver or pancreatic function.
If you have a personal or family history of severe hepatitis, particularly caused by medications.
If you have hepatic porphyria (a 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 disorder).

Bipolar disorder

For bipolar disorder, you must not use valproic acid if you are pregnant.
For bipolar disorder, if you are a woman of childbearing potential, you must not take valproic acid unless you use an effective method of birth control (contraception) throughout treatment with valproic acid. Do not stop taking valproic acid 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 valproic acid if you are pregnant, unless no other treatment works.
For epilepsy, if you are a woman of childbearing potential, you must not take valproic acid unless you use an effective method of birth control (contraception) throughout treatment with valproic acid. Do not stop taking valproic acid 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 think you may have any of these conditions, or if you have any doubts, consult your doctor before taking valproic acid.

Warnings and precautions

CONSULT 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.
If you, or your child, suddenly develop an illness, especially if it occurs within the first 6 months of treatment and particularly if it repeatedly includes vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, stomach pain, nausea, jaundice (yellowing of the skin and eyes), swelling of the legs, worsening of epilepsy, or a general feeling of malaise. In such cases, you should consult your doctor immediately. In a small number of patients, valproic acid can affect the liver (and rarely the pancreas).
The risk of liver damage increases if valproic acid 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.
If you, or your child, experience problems with balance and coordination, feel lethargic or less alert, or have vomiting while taking valproic acid, inform your doctor immediately. This may be due to an increase in blood ammonia levels.
A small number of people receiving antiepileptic treatment such as sodium valproate/valproic acid have had thoughts of self-harm or suicide. If you have such thoughts at any time, contact your doctor immediately.
As with other antiepileptic medicines, seizures may worsen or occur more frequently while taking this medicine. If this happens, contact your doctor immediately.

Consult your doctor or pharmacist before taking Valproic Acid Aurovitas.

Especially in children under 3 years of age, valproic acid should not be administered together with other medicines containing acetylsalicylic acid (aspirin).
If you have systemic lupus erythematosus (a rare disease).
If you have any metabolic disorder, particularly hereditary enzyme deficiencies such as urea cycle disorders, as there is an increased risk of elevated blood ammonia levels.
If you have impaired kidney function. Your doctor may wish to monitor your blood levels of sodium valproate or adjust the dose.
If you experience weight gain due to increased appetite.
If you have carnitine palmitoyltransferase (CPT) type II deficiency, as you are at higher risk of developing muscle disorders.
If you know or your doctor suspects that there is a genetic disorder causing a mitochondrial disorder in your family, due to the risk of liver damage.
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 ever developed a severe skin rash, peeling, blisters, and/or mouth sores after taking valproate.

Children and adolescents

Children and adolescents under 18 years of age.

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

Other medicines and Valproic Acid Aurovitas

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Some medicines may alter the effect of valproic acid or vice versa. These include:

Antipsychotics (used to treat psychological disorders).
Medicines used to treat depression.
Benzodiazepines, used for sleep or to treat anxiety.
Lithium.
Rufinamide.
Acetazolamide.
Protease inhibitors, such as lopinavir, ritonavir (used for the treatment of HIV).
Cholestyramine.
Other medicines used to treat epilepsy, including phenobarbital, phenytoin, primidone, lamotrigine, carbamazepine, topiramate, felbamate.
Olanzapine and quetiapine (used to treat psychiatric disorders).
Clozapine (to treat mental health disorders).
Zidovudine (used to treat HIV infection or AIDS).
Mefloquine (used to prevent and treat malaria).
Salicylates (see also “Warnings and precautions – Children under 3 years of age”).
Anticoagulants (used to prevent blood clots).
Cimetidine (used to treat stomach ulcers).
Erythromycin and rifampicin.
Carbapenems such as imipenem, panipenem or meropenem (antibiotics used to treat bacterial infections). The combination of valproic acid and carbapenem antibiotics should be avoided, as it may reduce the effect of sodium valproate.
Propofol (an anaesthetic).
Metamizole, a medicine used to treat pain and fever.
Medicines containing estrogens (including some contraceptive pills).
Valproic acid may increase the effects of nimodipine (a medicine used to treat high blood pressure, angina, and blood vessel disorders).
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).

These and other medicines may be affected by valproic acid, or may affect how it works. It may be necessary to adjust the dose of your medicine, or to take different medicines. Your doctor or pharmacist can advise you and provide more information about medicines with which caution should be exercised or which should be avoided with valproic acid.

Taking Valproic Acid Aurovitas with food, drinks and alcohol

Valproic acid may be taken with food and/or drinks.

It is recommended not to consume alcohol during treatment.

Pregnancy, breastfeeding and fertility

Important warning for women

Bipolar disorder

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

Epilepsy

For epilepsy, you must not use valproic acid if you are pregnant, unless no other treatment works.
For epilepsy, if you are a woman of childbearing potential, you must not take valproic acid unless you use an effective method of birth control (contraception) throughout treatment with valproic acid. Do not stop taking valproic acid 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 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 higher 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 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 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 child with birth defects requiring medical treatment. As valproate has been used for many years, it is known that approximately 10 out of every 100 babies born to women taking valproate will have birth defects. In comparison, 2 to 3 out of every 100 babies born to women without epilepsy.
It is estimated that up to 30-40% of preschool-aged children whose mothers took valproate during pregnancy may have developmental problems in childhood. Affected children may be slow to speak and walk, may be less intellectually capable than other children, and may have language and memory difficulties.
Children exposed to valproate are diagnosed with autism spectrum disorders more frequently, and there is some evidence that these children may develop symptoms of Attention Deficit Hyperactivity Disorder (ADHD).
If you take valproate during pregnancy, your baby may have a lower than expected birth weight for gestational age. In women taking valproate, approximately 11-15 out of every 100 babies may have lower than expected birth weight. In comparison, 5 to 10 out of every 100 babies born to women in the general population.
Before prescribing this medicine, your doctor will 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 estrogen) 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 that apply to you from those described below:

I AM STARTING TREATMENT WITH VALPROIC ACID
I AM TAKING VALPROIC ACID AND DO NOT INTEND TO HAVE A BABY
I AM TAKING VALPROIC ACID AND INTEND TO HAVE A BABY
I AM PREGNANT AND TAKING VALPROIC ACID

I AM STARTING TREATMENT WITH VALPROIC ACID

If this is the first time you have been prescribed valproic acid, 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 method of contraception continuously throughout your treatment with valproic acid. Consult your doctor or family planning clinic if you need advice on contraception.

Important messages:

Pregnancy must be ruled out before starting treatment with valproic acid, confirmed by a pregnancy test result reviewed by your doctor.
You must use an effective method of birth control (contraception) throughout treatment with valproic acid.
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 treating bipolar disorder or epilepsy. During this visit, 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 VALPROIC ACID AND DO NOT INTEND TO HAVE A BABY

If you continue treatment with valproic acid but do not plan to have a baby, ensure you use an effective method of contraception continuously throughout your treatment with valproic acid. 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 valproic acid.
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 this visit, 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 VALPROIC ACID 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 valproic acid 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 to reduce risks to you and the fetus as much as possible.

Your specialist may decide to adjust your valproic acid dose, switch you to another medicine, or discontinue your valproic acid 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 in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.

Important messages:

Do not stop taking valproic acid unless your doctor tells you to.
Do not stop using your contraceptive methods (contraception) before discussing with your doctor and working together on a plan to ensure 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 try to switch you to another medicine or discontinue valproic acid 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 VALPROIC ACID

Do not stop taking valproic acid 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 valproic acid is the only treatment option during pregnancy, you will be closely monitored for management of your underlying condition and 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 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 valproic acid 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 valproic acid 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 review 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.

Important information for male patients

Potential risks related to valproate use in the 3 months before conception

A study suggests a possible risk of movement and mental development disorders (developmental problems in childhood) in children born to fathers treated with valproate in the 3 months before conception. In this study, about 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 needed to form 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 in the 3 months 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 valproate use and the possibility of other treatments for your condition, depending on your individual situation.

You must read the Patient Guide provided by your doctor. You will also receive a Patient Card from your pharmacist to remind you of the potential risks of valproate.

Breastfeeding

Since only small amounts of valproic acid pass into breast milk, there is generally no risk to the baby and breastfeeding usually does not need to be discontinued. However, you should consult your doctor about whether continuing breastfeeding is advisable.

Driving and using machines

Valproic acid may cause drowsiness or dizziness in some people, especially at the beginning of treatment or when taken with other antiepileptic medicines or benzodiazepines. Make sure you know how you react to valproic acid before driving, operating tools or machinery, or engaging in other activities that could be dangerous if you are drowsy or dizzy.

Valproic Acid Aurovitas contains sodium

This medicine contains 46.2 mg of sodium (a main component of cooking/table salt) per tablet. This is equivalent to 2.31% of the maximum daily intake of sodium recommended for an adult.

3. How to take Valproic Acid Aurovitas

Follow exactly the instructions for use of this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Girls and women of childbearing age

Treatment with valproic acid should be initiated and supervised by a physician specialized in the treatment of epilepsy or bipolar disorder.

Male patients

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

Ensure that you attend regular follow-up appointments with your doctor. This is very important, as the dose you are taking may need adjustments over time.

The daily dose of valproic acid is determined by the physician according to age and body weight; however, significant inter-individual variations in sensitivity to valproate must be taken into account. The optimal dose is primarily established based on clinical response. Measurement of serum levels may be considered to complement clinical monitoring if seizure control is inadequate or if adverse effects are suspected. The effective therapeutic range for serum levels of valproic acid is generally 40–100 mg/liter (300–700 micromoles/liter).

Initiation of valproic acid treatment (oral administration)

If you are not taking another antiepileptic medicine, the ideal approach is to increase valproic acid gradually by administering successive doses at intervals of 2 to 3 days, reaching the optimal dose after one week.
If you are already taking another antiepileptic medicine, valproic acid should be increased gradually over approximately 2 weeks to reach the optimal dose, while the other treatment should be gradually reduced until completely discontinued.
If combination therapy with other antiepileptic medicines is required, these should be adjusted slowly (see section 2 “Other medicines and Valproic Acid Aurovitas”).

Practical administration: administration of valproic acid (oral)

Dosage:

The dose should start at 10–15 mg/kg daily, with gradual increases until the ideal dose is achieved (see section “Initiation of valproic acid treatment (oral use)”). Generally, this dose is between 20 and 30 mg/kg.

However, when seizure control is not achieved within this range, the dose may be further increased; patients should be closely monitored (this is why follow-up appointments are important) when daily doses exceed 50 mg/kg (see section 2).

In children, the normal dose is approximately 30 mg/kg per day.
In adults, the usual dose is within the range of 20–30 mg/kg per day.
Although pharmacokinetic parameters are altered in elderly individuals, these changes have not been considered clinically significant; therefore, the dose should be determined based on clinical response (seizure control).

Treatment of mania associated with bipolar disorders

Your doctor must individually establish and monitor your daily dosage.

Initial dose:

The recommended initial daily dose is 750 mg.

The dose should be increased as rapidly as possible to reach the lowest therapeutic dose producing the desired clinical effect.

Average daily dose:

Recommended daily doses usually range between 1,000 mg and 2,000 mg. In exceptional cases, the dose may subsequently be increased up to 3,000 mg/day. The dose should be adjusted according to individual clinical response.

Patients with renal impairment

Your doctor may decide to adjust your dose.

Follow exactly the instructions for use of this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Method of administration:

Oral use.

The daily dose may be taken in two divided doses.

Take the medicine for as long as your doctor considers necessary and for the duration prescribed.

If you think the effect of valproic acid is too strong or too weak, consult your doctor or pharmacist.

If you take more Valproic Acid Aurovitas than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medicine and the amount ingested.

An overdose of valproic acid can be dangerous. Inform your doctor or go immediately to the nearest hospital. Signs of acute intoxication typically present as coma, with muscle hypotonia, hyporeflexia, miosis, respiratory dysfunction, or metabolic acidosis.

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. Hospital treatment of overdose should be symptomatic: gastric lavage, which may be useful up to 10–12 hours after ingestion, and monitoring of cardiopulmonary function. Naloxone has been successfully used in a few isolated cases.

If you forget to take Valproic Acid Aurovitas

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

If you stop taking Valproic Acid Aurovitas

Do not stop or alter the dose of valproic acid without consulting your doctor. Your condition may worsen if you discontinue treatment with valproic acid without prior consultation with your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. These effects are usually mild or moderate.

Adverse effects may be rare (serious), but in most cases they are not. They are often reversible, but some may require medical treatment:

Vomiting, nausea, stomach pain, and diarrhoea, especially at the beginning of treatment.
Headache.
Tremor, drowsiness, sedation, unsteadiness when walking.
Aggression, agitation, attention disorders, abnormal behaviour, and hyperactivity.
Dizziness.
Tingling in hands and feet.
Seeing, feeling, or hearing things that do not exist (hallucinations).
Skin reactions such as rash.
Temporary hair loss, abnormal hair growth, abnormal hair texture, change in hair colour.
Increased hair growth, especially in women, virilization, acne (hyperandrogenism).
Nail disorders and skin disorders under the nail (frequent).
Irregular or absent menstruation, menstrual pain, ovarian cysts (polycystic ovaries).
Hearing problems or deafness.
Gingival (gum) disorders (particularly hyperplasia).
Mouth pain, mouth swelling, mouth ulcers, and burning sensation in the mouth (stomatitis).
Rapid, uncontrollable eye movements.
Double vision.
Allergic reactions.
Swelling of feet and legs (oedema).
Weight gain.
Obesity (rare).
Kidney problems, enuresis (urinary incontinence during sleep), or increased need to urinate.
Frequent urination and feeling thirsty (Fanconi syndrome) (rare).
Decreased body temperature.
Male infertility is usually reversible after stopping treatment and may be reversible after dose reduction. Do not stop your treatment without first consulting your doctor.
Memory loss and cognitive disorders.
Learning disorders.
Darker areas of the skin and mucous membranes (hyperpigmentation) (frequency not known).
Decreased levels of carnitine (detected in blood or muscle tests) (frequency not known).
Inflammation of small blood vessels (vasculitis).
Reduced levels of vitamin B8 (biotin deficiency).

Bone abnormalities, including osteopenia and osteoporosis (bone demineralization), have been reported. Consult your doctor or pharmacist if you are on long-term treatment with antiepileptic drugs, have a history of osteoporosis, or are taking steroids.

Inform your doctor immediately if you experience any of the following adverse effects (which are considered serious). You may require urgent medical attention:

Numbness, change in level of consciousness (including coma), lethargic (strange) behaviour, memory loss with or without increased frequency or severity of seizures, disorientation, especially if taken simultaneously with medicines containing phenobarbital and topiramate or if the dose of valproic acid has been suddenly increased.
Problems with balance and coordination, feeling lethargic or less alert, associated with vomiting. This may be due to increased levels of ammonia in the blood.
Repeated vomiting, extreme tiredness, abdominal pain, drowsiness, weakness, loss of appetite, severe stomach pain, nausea, jaundice (yellowing of the skin and/or eyes), swollen legs, or worsening of epilepsy or a general feeling of malaise. These may be signs of serious liver or pancreas disorders (consult a doctor immediately to assess possible pancreatitis. If pancreatitis is confirmed, sodium valproate must be discontinued).
Blood clotting problems, which appear in blood tests.
Spontaneous appearance of bruises or bleeding.
You have an allergic reaction which may present as:
- Blisters with skin peeling (blisters, skin peeling or bleeding from 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".
- Rash or skin lesions with a pink/red ring and a pale centre that may cause itching, peeling, or be filled with fluid. The rash may appear especially on the palms or soles of the feet. These may be signs of a condition called "erythema multiforme".
- Allergic swelling with painful, itchy hives (frequently around the eyes, lips, throat, and sometimes hands and feet). These may be signs of "angioedema".
- Drug-induced syndrome characterized by rash, fever, enlarged lymph nodes, and possible failure of other organs. These may be signs of a condition called "drug reaction with eosinophilia and systemic symptoms (DRESS)".
Severe decrease in white blood cells (leukocytes) or bone marrow failure, sometimes manifested by fever and breathing difficulties.
Confusion, which may be caused by low sodium levels in the blood or by a condition called Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).
Underactive thyroid gland, which may cause tiredness or weight gain (hypothyroidism).
Allergic reaction causing joint pain, fatigue, rash, and fever (systemic lupus erythematosus).
- Extrapyramidal disorder (movement disorders).
Difficulty breathing, chest pain or pressure (especially when inhaling), difficulty breathing, and dry cough due to fluid accumulation around the lungs (pleural effusion) (uncommon).
Muscle pain and muscle weakness (rhabdomyolysis).
Kidney disease; urinary incontinence (involuntary loss of urine).
Kidney disease (renal failure, tubulointerstitial nephritis) which may present as reduced urine output.
Increase in number and severity of seizures.
Agitation (tremor), uncontrollable muscle contractions, unsteadiness when walking (parkinsonism, extrapyramidal disorder, ataxia).

Valproic acid may also cause a reduction in platelet or red blood cell count, an abnormal increase in the size of red blood cells, and bone marrow disorders.

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 infection (pancreatitis), aggression, agitation, attention disturbances, abnormal behaviour, 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: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Valproic Acid Aurovitas

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the blister, packaging, or bottle, after "EXP". The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. Ask your pharmacist how to dispose of containers and medicines you no longer need. This helps protect the environment.

6. Package contents and other information

Composition of Valproic Acid Aurovitas

The active substances are sodium valproate and valproic acid. Each prolonged-release tablet contains 333 mg of sodium valproate and 145 mg of valproic acid (equivalent to 500 mg of sodium valproate).
The other components are:

Tablet core: anhydrous colloidal silica, hypromellose type 2208 (15000 cps), hypromellose type 2910 (4000 cps), and acesulfame potassium.

Tablet coating: sodium lauryl sulfate, dibutyl sebacate, basic butylated methacrylate copolymer, magnesium stearate, and titanium dioxide (E171).

Appearance of the medicinal product and contents of the pack

Film-coated tablets, white or almost white, oval-shaped, biconvex, with a score line on both sides. The tablet may be divided into equal doses.

Valproic Acid Aurovitas prolonged-release tablets are available in blister packs (triple cold-forming foil (Al-Al)) and in bottles (opaque white high-density polyethylene bottle and opaque white polypropylene bottle, closed with an opaque white polypropylene cap containing silica gel as desiccant).

Blister pack sizes:

500 mg: 30, 40, 50, 60, 90 and 100 prolonged-release tablets.

Bottle pack sizes:

28 prolonged-release tablets.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Generis Farmacêutica, S.A.

Rua João de Deus, 19

2700-487 Amadora

Portugal

This medicinal product is authorized in the European Economic Area member states under the following names:

Spain: Valproic Acid Aurovitas 500 mg prolonged-release tablets EFG

Netherlands: Natriumvalproaat Chrono Aurobindo 500 mg, tabletten met verlengde afgifte

Portugal: Ácido Valpróico Generis Phar

Date of the most recent revision of this leaflet: February 2026.

Other sources of information

You can access detailed and up-to-date information about this medicinal product 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/84516.

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