Valproic acid and sodium valproate EG

Package leaflet: Information for the user

Valproic Acid and Sodium Valproate EG 300 mg prolonged-release tablets, 500 mg prolonged-release tablets

Sodium valproate
Generic medicine
This medicinal product is subject to additional monitoring. This will allow rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
WARNING
Valproic Acid and Sodium Valproate EG may seriously harm the unborn baby if taken during pregnancy. If you are a woman of childbearing age, you must use an effective method of birth control (contraception) continuously throughout your treatment with Valproic Acid and Sodium Valproate EG. Your doctor will discuss this with you, but you must also follow the recommendations in section 2 of this leaflet.
If you are planning a pregnancy or think you might be pregnant, arrange an urgent appointment with your doctor.
Do not stop taking Valproic Acid and Sodium Valproate EG unless your doctor tells you to, because your condition could worsen.
Please read this leaflet carefully before taking this medicine because it contains important information for you.
Keep this leaflet. 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. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
Contents of this leaflet

1. What Valproic Acid and Sodium Valproate EG is and what it is used for
2. What you need to know before taking Valproic Acid and Sodium Valproate EG
3. How to take Valproic Acid and Sodium Valproate EG
4. Possible side effects
5. How to store Valproic Acid and Sodium Valproate EG
6. Contents of the pack and other information

1. What Acido Valproico e Sodio Valproato EG is and what it is used for

Acido Valproico e Sodio Valproato EG is a medicine used to treat epilepsy (antiepileptic) and to treat mania (abnormally elevated mood with increased activity).
Acido Valproico e Sodio Valproato EG is used to treat:

• Epileptic seizures involving both hemispheres of the brain (generalized epilepsy), such as absence seizures, myoclonic seizures, and tonic-clonic seizures;
• Epileptic seizures affecting a limited part of the brain (focal seizures) which, in some cases, spread to both sides of the brain (secondary generalized seizures).

Acido Valproico e Sodio Valproato EG may be administered together with other antiepileptic medicines for other seizure types, such as epileptic seizures with mixed (complex) symptoms, as well as seizures spreading from a limited area of the brain to both sides of the brain, when these seizure types do not respond to standard antiepileptic treatment.

• Mania, a condition in which a person may feel highly excited, euphoric, agitated, enthusiastic, or hyperactive. Mania occurs in a disorder called "bipolar disorder". Acido Valproico e Sodio Valproato EG may be used when lithium is not suitable.

Notes
When switching from previous dosage forms (non-extended release) to Acido Valproico e Sodio Valproato EG, care must be taken to ensure adequate serum levels of valproic acid.
In young children, Acido Valproico e Sodio Valproato EG may be chosen as first-line treatment only in exceptional cases. If used, Acido Valproico e Sodio Valproato EG should be administered with particular caution following careful assessment of the risk-benefit ratio and preferably not in combination with other antiepileptic medicines.

2. What you need to know before taking Acido Valproico e Sodio Valproato EG

Do not take Acido Valproico e Sodio Valproato EG

• if you are allergic to sodium valproate or valproic acid or to any of the other ingredients of this medicine (listed in section 6);
• if you or a member of your family has suffered from severe liver dysfunction, or if you currently suffer from severe liver or pancreatic dysfunction;
• if one of your siblings suffered from liver dysfunction that led to death during treatment with valproic acid;
• if you suffer from a congenital or acquired metabolic disorder of blood pigment (hepatic porphyria);
• if you have blood clotting problems;
• if you suffer from a genetic disorder causing mitochondrial disease (e.g., Alpers-Huttenlocher syndrome);
• if you suffer from a urea cycle disorder (a specific metabolic disorder);
• if you have untreated carnitine deficiency (a very rare metabolic disease).

Bipolar disorder

• For bipolar disorder, if you are pregnant, you must not use Acido Valproico e Sodio Valproato EG.
• For bipolar disorder, if you are a woman of childbearing age, you must not take Acido Valproico e Sodio Valproato EG unless you are using an effective method of birth control (contraception) throughout the entire treatment with Acido Valproico e Sodio Valproato EG. Do not stop taking Acido Valproico e Sodio Valproato EG or your contraceptive until you have discussed it with your doctor. Your doctor will advise you further (see below under “Pregnancy, breastfeeding and fertility – Important warning for women”).

Epilepsy

• For epilepsy, if you are pregnant, you must not use Acido Valproico e Sodio Valproato EG unless no other treatment has been effective for you.
• For epilepsy, if you are a woman of childbearing age, you must not take Acido Valproico e Sodio Valproato EG unless you are using an effective method of birth control (contraception) throughout the entire treatment with Acido Valproico e Sodio Valproato EG. Do not stop taking Acido Valproico e Sodio Valproato EG or your contraceptive until you have discussed it with your doctor. Your doctor will advise you further (see below under “Pregnancy, breastfeeding and fertility – Important warning for women”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Acido Valproico e Sodio Valproato EG.
Contact your doctor immediately

• Serious skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, and angioedema, have been reported in association with valproate treatment. Contact your doctor immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.
• If you experience symptoms of liver and/or pancreas damage (see below “Liver and/or pancreas damage”). The risk of liver damage is higher if Acido Valproico e Sodio Valproato EG is taken by children under 3 years of age, by people taking other antiepileptic medicines simultaneously, or by those with other neurological or metabolic disorders and severe forms of epilepsy.
• If you or your child being treated with Acido Valproico e Sodio Valproato EG develops problems with balance and coordination, a feeling of lethargy, or loss of alertness, vomiting, contact your doctor immediately. This could be due to increased ammonia levels in the blood.
• If your seizures worsen. As with other medicines used to treat epilepsy, worsening (increase) in frequency and severity of epileptic seizures may occur during treatment with Acido Valproico e Sodio Valproato EG. In this case, you must inform your doctor immediately.
• A small number of patients treated with antiepileptic medicines such as valproate have had thoughts of harming themselves or of suicide. If you have such thoughts at any time, contact your doctor immediately.

Consult your doctor before taking this medicine

• If you have ever developed a severe skin rash or skin peeling, blisters and/or mouth ulcers after taking valproate.
• If you have ever had bone marrow damage.
• If you suffer from systemic lupus erythematosus (an autoimmune reaction against connective tissue in the body).
• If you suspect you have metabolic disorders, particularly inherited enzyme deficiencies such as a “urea cycle disorder,” due to the risk of increased ammonia levels in the blood.
• If you suffer from a rare disease known as “carnitine palmitoyltransferase deficiency type II,” as you are at higher risk of developing muscle disorders.
• If you know or your doctor suspects a genetic disorder in your family causing mitochondrial disease, due to the risk of liver damage.
• If you have a reduced 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 your kidney function is impaired or you have low blood protein levels.
• Before undergoing surgery or dental procedures (e.g., tooth extraction), or if you experience spontaneous injuries or bleeding. Since your tendency to bleed may increase, your doctor must be informed that you are taking Acido Valproico e Sodio Valproato EG so that blood coagulation can be monitored.
• If you are also taking medicines that prevent blood clotting (e.g., vitamin K antagonists); your tendency to bleed may increase. Blood coagulation should therefore be monitored regularly.
• If you are also taking acetylsalicylic acid (“ASA”), as blood concentrations of valproic acid (the active substance in Acido Valproico e Sodio Valproato EG) may increase.

Liver and/or pancreas damage
Severe liver damage has occasionally been observed, and pancreas damage rarely. Patients, particularly newborns, infants, and young children, must be closely monitored by a doctor in this regard, especially during the first six months of treatment.
Liver and/or pancreas damage may be preceded by non-specific signs that usually appear suddenly, such as recurrence of epileptic seizures, increased frequency or severity of seizures, disturbances in consciousness with confusion, restlessness, movement disorders, physical agitation and weakness, loss of appetite, aversion to usual foods, aversion to valproic acid, nausea, vomiting, upper abdominal discomfort, apathy, drowsiness, unusually frequent bruising (hematomas), jaundice (yellowing of the skin or whites of the eyes), nosebleeds, and fluid accumulation (edema) in certain parts of the body or throughout the body. If these symptoms are persistent or severe, you must inform your doctor to determine whether treatment with Acido Valproico e Sodio Valproato EG should continue.

Measures for early detection of liver and/or pancreas damage
Before starting treatment, your doctor should obtain a detailed medical history and perform a clinical examination and laboratory tests (particularly regarding metabolic disorders, liver or pancreas disorders, blood count, and blood coagulation disorders).
Four weeks after starting treatment, a further laboratory follow-up should be performed.
In patients without clinical signs but with abnormally high laboratory values at 4 weeks, follow-up tests should be performed three times at intervals of no more than two weeks, and subsequently at monthly intervals until the sixth month of treatment.
Parents/caregivers must immediately inform the treating doctor if any clinical abnormalities occur, regardless of this information.
In adolescents (from age 15) and adults, monthly monitoring of clinical findings and laboratory values is recommended during the first six months and always before starting therapy.
After 12 months of treatment without abnormal results, 2–3 additional medical follow-up checks per year are required.

Notes
Weight gain may occur at the beginning of treatment. You should regularly monitor your weight and, if necessary, discuss appropriate measures with your doctor.
Acido Valproico e Sodio Valproato EG must not be used for migraine prevention (see also section “Pregnancy, breastfeeding and fertility”).

Children and adolescents
Exercise particular caution when Acido Valproico e Sodio Valproato EG is administered to

• infants taking other antiepileptic medicines,
• children and adolescents with multiple disabilities and severe forms of epileptic seizures.

Acido Valproico e Sodio Valproato EG must not be used in children and adolescents under 18 years of age for the treatment of mania.
During febrile conditions, Acido Valproico e Sodio Valproato EG must not be taken simultaneously with acetylsalicylic acid in infants and children, or in adolescents, unless specifically instructed by a doctor.

Other medicines and Acido Valproico e Sodio Valproato EG
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effect and, in some cases, the side effects of Acido Valproico e Sodio Valproato EG are increased by

• felbamate (a medicine for treating epilepsy),
• cimetidine (a medicine for treating gastric ulcers),
• erythromycin (a medicine for treating bacterial infections),
• acetylsalicylic acid (a medicine for fever and pain): acetylsalicylic acid reduces the binding of valproic acid to blood proteins. This may increase the harmful effect of valproic acid on the liver. See also section “Children and adolescents” in section 2 “What you need to know before taking Acido Valproico e Sodio Valproato EG”.

The effect of Acido Valproico e Sodio Valproato EG is reduced by

• phenobarbital, primidone, phenytoin, carbamazepine (other medicines for epilepsy),
• mefloquine (a medicine for malaria),
• rifampicin (a medicine for tuberculosis),
• carbapenems (antibiotics for treating bacterial infections, such as imipenem, panipenem, and meropenem). Avoid using valproic acid simultaneously with carbapenems, as this could reduce the effectiveness of valproic acid;
• protease inhibitors such as lopinavir or ritonavir (medicines for treating HIV infections),
• colestyramine (medicines for lowering blood fats),
• estrogen-containing products (including some hormonal contraceptives),
• metamizole (a medicine for treating pain and fever),
• methotrexate (used to treat cancer or inflammatory diseases).

The effect of Acido Valproico e Sodio Valproato EG may be increased or reduced by:

• co-administration of fluoxetine (an antidepressant). Serum concentrations of valproic acid (the active substance in Acido Valproico e Sodio Valproato EG) may increase, but cases of decreased concentrations have also been reported.

Acido Valproico e Sodio Valproato EG increases the effect and, in some cases, the side effects of

• phenobarbital, primidone, phenytoin, carbamazepine, lamotrigine, felbamate (medicines for epilepsy),
• neuroleptics (medicines for treating mental disorders), benzodiazepines (medicines for relieving anxiety and tension), barbiturates (sedatives), MAO inhibitors (antidepressants), and other medicines for depression,
• codeine (a medicine for cough),
• zidovudine (a medicine for treating HIV infections),
• medicines that prevent blood clotting (e.g., vitamin K antagonists or acetylsalicylic acid). Increased tendency to bleed may occur;
• rufinamide (a medicine for epilepsy) (caution is required, especially in children),
• propofol (an anaesthetic),
• nimodipine (a medicine for treating cerebral function disorders).

In children, serum levels of phenytoin (another medicine for epilepsy) may increase when co-administered with clonazepam (a benzodiazepine, a medicine for relieving anxiety and tension and for epilepsy) and valproic acid.
During combined treatment with medicines containing valproic acid and clonazepam (a medicine for epilepsy), absence status (a prolonged state of semiconsciousness) has occurred in patients with a history of absence seizures (a specific type of epileptic seizure involving both brain hemispheres).
One patient with schizoaffective disorder (a mental disorder) developed catatonia (a state of rigidity unresponsive to external stimuli) when treated simultaneously with valproic acid, sertraline (an antidepressant), and risperidone (a neuroleptic).
Some medicines can affect the effects of valproate and vice versa. These include:

• clozapine (for treating mental health problems).

Other interactions

• Acido Valproico e Sodio Valproato EG has no effect on serum lithium levels.
• The effect of hormonal contraceptive preparations (the “pill”) is not reduced.
• In patients with diabetes, false positives may occur in urine ketone tests, as valproic acid itself is partially metabolized into ketone bodies.
• Other medicines that overload hepatic metabolism may increase the risk of liver damage, such as cannabidiol (used to treat epilepsy and other conditions).
• When valproic acid has been administered simultaneously with topiramate (a medicine for epilepsy), signs of brain damage (encephalopathy) and/or increased blood ammonia levels (hyperammonaemia) have been reported.
• If Acido Valproico e Sodio Valproato EG is administered together with acetazolamide (a medicine used to treat glaucoma), increased blood ammonia levels may occur, with risk of brain damage (encephalopathy).
• If valproic acid is used simultaneously with phenobarbital or phenytoin, blood ammonia levels may increase. Your doctor will closely monitor you for this.
• When used simultaneously, valproic acid and quetiapine (a medicine used to treat psychiatric disorders) may increase the risk of reduced white blood cell count (leukopenia, neutropenia).
• Acido Valproico e Sodio Valproato EG may reduce plasma concentrations of olanzapine (a medicine for treating psychiatric disorders).
• Some antimicrobial agents containing pivalate (e.g., pivampicillin, adefovir dipivoxil) may increase the risk of carnitine deficiency if used concomitantly with valproate.

Your doctor will determine whether it is necessary to stop taking other medicines you are using or whether treatment can continue.

Acido Valproico e Sodio Valproato EG with food, drinks and alcohol
Concomitant consumption of alcohol may reduce or increase the effect of Acido Valproico e Sodio Valproato EG, as well as increase its side effects. You must therefore avoid alcohol consumption during treatment.
The bioavailability of Acido Valproico e Sodio Valproato EG is not affected by concomitant food intake.

Pregnancy, breastfeeding and fertility
Important warning for women

Bipolar disorder

• If you are pregnant, you must not use Acido Valproico e Sodio Valproato EG for bipolar disorder.
• For bipolar disorder, if you are a woman of childbearing age, you must not take Acido Valproico e Sodio Valproato EG unless you are using an effective method of birth control (contraception) throughout the entire treatment with Acido Valproico e Sodio Valproato EG. Do not stop taking Acido Valproico e Sodio Valproato EG or your contraceptive unless you have discussed it with your doctor. Your doctor will advise you further.

Epilepsy

• For epilepsy, if you are pregnant, you must not use Acido Valproico e Sodio Valproato EG unless no other treatment has been effective for you.
• For epilepsy, if you are a woman of childbearing age, you must not take Acido Valproico e Sodio Valproato EG unless you are using an effective method of birth control (contraception) throughout the entire treatment with Acido Valproico e Sodio Valproato EG. Do not stop taking Acido Valproico e Sodio Valproato EG or your contraceptive unless you have discussed it with your doctor. Your doctor will advise you further.

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

• Speak immediately with your doctor if you are planning to have a child or if you are pregnant.
• Valproate poses risks if taken during pregnancy. The risk is higher at higher doses, but all doses carry a risk, including the use of valproate in combination with other medicines for treating epilepsy.
• This medicine can cause serious birth defects and can have consequences on the child's physical and mental development and growth after birth. The most frequently reported birth defects include: spina bifida (incomplete development of some spinal bones); facial and skull malformations; heart, kidney, urinary tract, and genital organ malformations; limb defects; and multiple associated malformations affecting various organs and body parts. Birth defects may lead to disabilities that can be severe.
• Hearing problems or deafness have been reported in children exposed to valproate during pregnancy.
• Eye malformations associated with other congenital malformations have been reported in children exposed to valproate during pregnancy. 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. Because valproate has been used for many years, we know that about 11 out of 100 babies born to women taking valproate have birth defects, compared to 2–3 out of 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 early childhood. These children may start walking and talking later, may be less intellectually capable than other children, and may have language and memory difficulties.
• Autism spectrum disorders are more frequently diagnosed in children exposed to valproate, and there is some evidence that children exposed to valproate during pregnancy have a higher risk of developing symptoms of attention deficit hyperactivity disorder (ADHD).
• Before prescribing this medicine, your doctor will explain what could happen to your child if you become pregnant while taking valproate. If at a later time you decide you want to have a child, do not stop taking the medicine or your contraceptive method before discussing it with your doctor.
• If you are the parent or caregiver of a girl treated with valproate, you must contact the doctor as soon as the girl has her first menstrual period.
• Some hormonal contraceptives (oral contraceptives containing estrogens) may decrease valproate levels in the blood. Make sure to discuss with your doctor the most suitable method of contraception (birth control) for you.
• Consult your doctor about taking folic acid while trying to become pregnant. Folic acid can reduce the general risk of spina bifida and early miscarriage, which are possible in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.
• If you have taken medicines containing valproic acid during pregnancy, blood coagulation values (platelets, fibrinogen) and coagulation factors should be checked, and coagulation tests performed in the newborn, due to possible blood coagulation disorders.
• Withdrawal symptoms (such as restlessness, excessive motor activity, tremors, cramps, and sucking difficulties) may occur in newborns whose mothers were treated with medicines containing valproic acid during the last three months of pregnancy.
• Cases of low blood sugar have been reported in newborns whose mothers took valproate during the last three months of pregnancy.
• Cases of hypothyroidism have been described in newborns whose mothers with epilepsy took valproate during pregnancy.

Choose and read the situations applicable to you from those described below:

• I AM STARTING TREATMENT WITH ACIDO VALPROICO E SODIO VALPROATO EG
• I AM TAKING ACIDO VALPROICO E SODIO VALPROATO EG AND DO NOT PLAN TO HAVE A CHILD
• I AM TAKING ACIDO VALPROICO E SODIO VALPROATO EG AND PLAN TO HAVE A CHILD
• I AM PREGNANT AND TAKING ACIDO VALPROICO E SODIO VALPROATO EG

I AM STARTING TREATMENT WITH ACIDO VALPROICO E SODIO VALPROATO EG
If Acido Valproico e Sodio Valproato EG is prescribed to you for the first time, your doctor will explain the risks to the fetus in case of pregnancy. If you are of childbearing age, you must ensure you use an effective contraceptive method continuously throughout the entire treatment with Acido Valproico e Sodio Valproato EG. Talk to your doctor or visit a family planning clinic if you need advice on contraception.
Key messages:

• Before starting treatment with Acido Valproico e Sodio Valproato EG, pregnancy must be ruled out through a pregnancy test confirmed by your doctor.
• During the entire treatment with Acido Valproico e Sodio Valproato EG, you must use an effective method of birth control (contraception).
• You must discuss appropriate methods of birth control (contraceptives) with your doctor. Your doctor will explain how to prevent pregnancy and can refer you to a specialist for advice on birth control.
• You must schedule regular appointments (at least once a year) with a specialist experienced in managing bipolar disorder or epilepsy. During this visit, your doctor will ensure you are fully aware and understand all risks and advice related to valproate use during pregnancy.
• Inform your doctor if you wish to have a child.
• Inform your doctor immediately if you are pregnant or think you might be.

I AM TAKING ACIDO VALPROICO E SODIO VALPROATO EG AND DO NOT PLAN TO HAVE A CHILD
If you are continuing treatment with Acido Valproico e Sodio Valproato EG but do not plan to have a child, ensure you use an effective contraceptive method continuously throughout the entire treatment with Acido Valproico e Sodio Valproato EG. Talk to your doctor or a family planning clinic if you need advice on contraception.
Key messages:

• You must use an effective method of birth control (contraception) throughout the entire treatment with Acido Valproico e Sodio Valproato EG.
• You must discuss contraception (birth control) with your doctor. Your doctor will explain how to prevent pregnancy and can refer you to a specialist for advice on birth control.
• You must schedule regular appointments (at least once a year) with a specialist experienced in managing bipolar disorder or epilepsy. During this visit, your doctor will ensure you are fully aware and understand all risks and advice related to valproate use during pregnancy.
• Inform your doctor if you wish to have a child.
• Inform your doctor immediately if you are pregnant or think you might be.

I AM TAKING ACIDO VALPROICO E SODIO VALPROATO EG AND PLAN TO HAVE A CHILD
If you are planning to have a child, schedule an appointment with your doctor first.
Do not stop taking Acido Valproico e Sodio Valproato EG or your contraceptive until you have discussed it with your doctor. Your doctor will advise you further.
Children born to mothers treated with valproate have a high risk of birth defects and developmental problems that may be severely disabling. Your doctor will refer you to a specialist experienced in managing bipolar disorder or epilepsy to evaluate alternative treatment options as soon as possible. The specialist may take various measures to facilitate the pregnancy as much as possible and reduce risks for you and your unborn child.
The specialist may decide to adjust the dose of Acido Valproico e Sodio Valproato EG, switch to another medicine, or discontinue treatment with Acido Valproico e Sodio Valproato EG well before pregnancy to ensure the disease is stable.
Ask your doctor about taking folic acid when planning to have a child. Folic acid can reduce the general risk of spina bifida and early miscarriage, which are possible in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.
Key messages:

• Do not stop taking Acido Valproico e Sodio Valproato EG unless your doctor tells you to.
• Do not stop using birth control methods (contraceptives) before discussing it with your doctor and agreeing on a plan to ensure disease control and reduce risks for the child.
• Schedule an appointment with your doctor first. During this visit, your doctor will ensure you are fully aware and understand all risks and advice related to valproate use during pregnancy.
• Your doctor will try to switch your medication or discontinue treatment with Acido Valproico e Sodio Valproato EG well before pregnancy.
• Request an urgent appointment with your doctor if you are pregnant or think you might be pregnant.

I AM PREGNANT AND TAKING ACIDO VALPROICO E SODIO VALPROATO EG
Do not stop taking Acido Valproico e Sodio Valproato EG unless instructed by your doctor, as your condition may worsen. Request an urgent appointment with your doctor if you are pregnant or think you might be pregnant. Your doctor will advise you further.
Children born to mothers treated with valproate have a high risk of birth defects and developmental problems that may be severely disabling.
You will be referred to a specialist experienced in managing bipolar disorder or epilepsy to evaluate alternative treatment options.
In exceptional circumstances, if Acido Valproico e Sodio Valproato EG is the only available treatment option during pregnancy, you will be closely monitored for management of your underlying condition and fetal development. You and your partner may receive counselling and support regarding valproate exposure during pregnancy.
Ask your doctor about taking folic acid. Folic acid can reduce the general risk of spina bifida and miscarriage, which are possible in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.
Key messages:

• Request an urgent appointment with your doctor if you are pregnant or think you might be pregnant.
• Do not stop taking Acido Valproico e Sodio Valproato EG 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 detailed counselling regarding the risks of Acido Valproico e Sodio Valproato EG during pregnancy, including teratogenicity and effects on physical and mental development in children.
• Ensure you are referred to a specialist in prenatal monitoring to identify possible cases of malformation.

Make sure to read the patient guide you will receive from your doctor. Your doctor will discuss the Annual Risk Acknowledgement Form with you and ask you to sign and keep it. You will also receive from the pharmacist the Patient Alert Card to remind you of the risks of valproate during pregnancy.

Important warning for male patients
Potential risk associated with valproate use in the 3 months before conception
One study suggests a possible risk of movement and mental development disorders (problems affecting early childhood development) in children born to fathers treated with valproate in the 3 months before conception. In this study, about 5 out of 100 children had such disorders when born to fathers treated with valproate, compared to about 3 out of 100 children born to fathers treated with lamotrigine or levetiracetam (other medicines that may be used to treat your condition). The risk for children born to fathers who discontinued valproate treatment 3 months (the time required to form new sperm) or longer before conception is unknown. The study has limitations, so it is not entirely clear 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 show which particular type of movement and mental development disorder the children may be at risk of developing.
As a precautionary measure, your doctor will discuss with you:

• The potential risk for children born to fathers taking valproate.
• The need to consider effective contraception (birth control) for you and your partner during treatment and for 3 months after stopping therapy.
• The need to consult a specialist if you are planning to conceive a child and before stopping contraception (birth control).
• The possibility of other treatments that may be used to treat 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 thinking of having a child.
If your partner becomes pregnant while you have taken valproate in the 3 months before conception and you have questions, contact your doctor. Do not stop treatment without discussing it with your doctor. If you stop treatment, your symptoms may worsen.
You should plan regular appointments with your prescribing doctor. During this visit, your doctor will discuss with you the precautions associated with valproate use and the possibility of other treatments that may be used to treat your condition, depending on your individual situation.
Make sure to read the patient guide you will receive from your doctor. You will also receive from the pharmacist the Patient Alert Card to remind you of the potential risks of valproate.

Breastfeeding
Small amounts of valproic acid are excreted in breast milk. Ask your doctor for advice before taking this medicine if you are breastfeeding.

Fertility
This medicine may impair your ability to have a child. Clinical cases have shown that these effects are generally reversible upon discontinuation of the active substance or after dose reduction. Do not stop treatment without first consulting your doctor.

Driving and using machines
Do not drive or operate machinery without first consulting your doctor.
At the beginning of treatment with Acido Valproico e Sodio Valproato EG, at higher doses, or when taken simultaneously with other medicines acting on the central nervous system, central nervous system effects such as drowsiness or confusion may impair your reaction ability to such an extent that, regardless of the effect of the underlying condition being treated, your ability to drive or use machinery may be compromised. This is especially true in case of interaction with alcohol.

Acido Valproico e Sodio Valproato EG contains sodium
Acido Valproico e Sodio Valproato EG 300 mg
This medicine contains up to 29.1 mg of sodium (the main component of table salt) per prolonged-release tablet. This corresponds to 1.5% of the maximum daily dietary intake recommended for an adult.
Acido Valproico e Sodio Valproato EG 500 mg
This medicine contains up to 48.5 mg of sodium (the main component of table salt) per prolonged-release tablet. This corresponds to 2.4% of the maximum daily dietary intake recommended for an adult.

3. How to take Acido Valproico e Sodio Valproato EG

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. Do not change the treatment or dosage without first consulting your doctor.

Girls and women of childbearing age
Treatment with Acido Valproico e Sodio Valproato EG must be initiated and supervised by a specialist doctor experienced in the treatment of epilepsy or bipolar disorder.

Male patients
It is recommended that treatment with Acido Valproico e Sodio Valproato EG be initiated and supervised by a specialist experienced in managing epilepsy or bipolar disorder – see section 2 Important warning for male patients.

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

Initial dose
The recommended starting dose is 750 mg. The dose should be increased as rapidly as possible to reach the lowest effective dose that produces the desired clinical effect.

Average daily dose
The recommended daily dose generally ranges between 1,000 mg and 2,000 mg (equivalent to 3½–6½ prolonged-release tablets of Acido Valproico e Sodio Valproato EG 300 mg or 2–4 prolonged-release tablets of Acido Valproico e Sodio Valproato EG 500 mg). The dose must be individually adjusted according to your clinical condition.
Treatment of mania should be individually tailored using the lowest effective dose.

Epilepsy
Dosage will be determined and monitored individually by the specialist doctor, aiming to achieve a seizure-free state using the lowest possible dose, especially during pregnancy.

Dosing
A gradual increase in dosage is recommended until the optimal effective dose is reached. Acido Valproico e Sodio Valproato EG prolonged-release tablets may be split to allow individual dose adjustment.

When valproic acid is administered alone (monotherapy), the usual initial dose is 5–10 mg of valproic acid/kg body weight. The daily dose is then gradually increased every 4–7 days by approximately 5 mg of valproic acid/kg body weight until the dose required to control seizures is reached.

In some cases, the full effect may only become apparent after 4–6 weeks. Daily doses should therefore not be increased above average levels too early.

The usual average daily dose during long-term treatment corresponds to:

• 30 mg of valproic acid/kg body weight/day for children,
• 25 mg of valproic acid/kg body weight/day for adolescents,
• 20 mg of valproic acid/kg body weight/day for adults and elderly patients.

Therefore, the following daily doses are recommended as guidelines:

Acido Valproico e Sodio Valproato EG 300 mg

| Age | Body weight [kg] | Average dose¹ (mg/day) | Number of prolonged-release tablets | |-----|------------------|------------------------|-------------------------------------| | Adults | from ca. 60 | 1,200 – 2,100 | 4 – 7 | | Adolescents from age 14 | ca. 40 – 60 | 1,000 – 1,500 | 3½ – 5 | | Children² | | | | | 3–6 months | ca. 5.5 – 7.5 | 150 | See Notes | | 6–12 months | ca. 7.5 – 10 | 150 – 300 | See Notes | | 1–3 years | ca. 10 – 15 | 300 – 450 | See Notes | | 3–6 years | ca. 15 – 25 | 450 – 750 | 1½ – 2½ | | 7–14 years | ca. 25 – 40 | 750 – 1,200 | 2½ – 4 |

Acido Valproico e Sodio Valproato EG 500 mg

| Age | Body weight [kg] | Average dose¹ (mg/day) | Number of prolonged-release tablets | |-----|------------------|------------------------|-------------------------------------| | Adults | from ca. 60 | 1,200 – 2,100 | 2½ – 4 | | Adolescents from age 14 | ca. 40 – 60 | 1,000 – 1,500 | 2 – 3 | | Children² | | | | | 3–6 months | ca. 5.5 – 7.5 | 150 | See Notes | | 6–12 months | ca. 7.5 – 10 | 150 – 300 | See Notes | | 1–3 years | ca. 10 – 15 | 300 – 450 | See Notes | | 3–6 years | ca. 15 – 25 | 450 – 750 | See Notes | | 7–14 years | ca. 25 – 40 | 750 – 1,200 | 1½ – 2 |

Details refer to mg of sodium valproate.

Notes:
For children up to 3 years of age, pharmaceutical forms with lower active substance content (e.g. solution) should preferably be used.
For children up to 6 years of age, pharmaceutical forms with lower active ingredient content are particularly suitable [e.g. solution or 150 mg tablets (½ tablet of Acido Valproico e Sodio Valproato EG 300 mg)].

Patients with renal problems
Your doctor may decide to adjust the dosage.

Patients with protein deficiency in the blood
If you suffer from protein deficiency in the blood, blood levels of the active substance (valproic acid) in Acido Valproico e Sodio Valproato EG may increase. Your doctor may need to adjust your daily dose, possibly reducing it.

Notes on switching from another treatment
If you need to switch from another antiepileptic medicine with the same active substance or from an antiepileptic with a different active substance to treatment with Acido Valproico e Sodio Valproato EG, this switch must be carried out as directed by your doctor.

In most patients previously treated with non-prolonged-release formulations, switching to the prolonged-release formulation can be done immediately or within a few days. In this case, the previously administered dose should be maintained. A dose reduction may be possible once seizures have decreased.

If Acido Valproico e Sodio Valproato EG is taken together with other antiepileptic drugs, the dose of the antiepileptics previously taken, especially phenobarbital, should be immediately reduced. If the previously used medicinal product is discontinued, this must be done gradually.

Other antiepileptic medicines accelerate the breakdown of valproic acid. If treatment with these medicines is stopped, the blood concentration of valproic acid will slowly increase; therefore, serum valproic acid concentration should be monitored for a period of 4–6 weeks after discontinuation of the concomitant treatment. The daily dose of Acido Valproico e Sodio Valproato EG should be reduced as necessary.

The serum concentration (measured just before the first daily dose) should not exceed 100 mg/L. Treatment success is not directly correlated with the daily dose or serum concentration of the active substance. The dose should therefore be based primarily on seizure control.

The daily dose of Acido Valproico e Sodio Valproato EG may be divided into 1–2 single administrations.

Method of administration
Prolonged-release tablets should preferably be taken 1 hour before meals (in the morning on an empty stomach) and must be swallowed whole (or split in half), not chewed, and taken with a sufficient amount of liquid (e.g. a glass of water). Carbonated beverages such as mineral water or similar should not be used to take the prolonged-release tablets.

Duration of treatment
Treatment of epilepsy and mania are long-term therapies. A specialist doctor must individually decide on the duration of treatment and on discontinuation of therapy with Acido Valproico e Sodio Valproato EG. Gradual dose reduction or discontinuation of this medicine in the treatment of epilepsy may usually be considered only after at least two to three years without seizures. Gradual dose reduction or discontinuation should be performed by slowly decreasing the daily dose over a period of one to two years.

Experience with long-term use of valproic acid is limited, especially in children under 6 years of age.

If you feel that the effect of Acido Valproico e Sodio Valproato EG is too strong or too weak, consult your doctor.

Occasionally, components of the prolonged-release tablets may be found as white residue in the stool. However, this does not mean that the medicine’s effect has been compromised, as the active substance is released from the tablet structure (matrix) during intestinal transit.

If you take more Acido Valproico e Sodio Valproato EG than you should
Inform a doctor immediately so that appropriate measures can be taken if necessary. The adverse effects listed under “Side effects” may occur more intensely, such as increased tendency to seizures and behavioral disturbances, in both adults and children. Isolated deaths have occurred following massive overdose.

If you forget to take Acido Valproico e Sodio Valproato EG
Do not take a double dose to make up for the missed tablet. Continue taking the medicine as prescribed.

If you stop taking Acido Valproico e Sodio Valproato EG
Do not alter, interrupt, or prematurely discontinue treatment with Acido Valproico e Sodio Valproato EG without authorization. First consult your doctor if you experience intolerance or changes in your clinical condition. Otherwise, you may jeopardize the success of treatment and trigger new epileptic seizures.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The following frequency data have been used to assess the side effects:
Very common: more than 1 in 10 patients treated
Common: 1 to 10 in 100 patients treated
Uncommon: 1 to 10 in 1,000 patients treated
Rare: 1 to 10 in 10,000 patients treated
Very rare: less than 1 in 10,000 patients treated
Not known: frequency cannot be estimated from the available data

Contact your doctor immediately if you notice any of the following serious side effects.
You may need urgent medical treatment:
Uncommon (may affect up to 1 in 100 people)

• Breathing difficulties, pain or pressure in the chest (especially during inhalation), shortness of breath, and dry cough due to fluid accumulation around the lungs (pleural effusion).

Inform your doctor or pharmacist if any of the following side effects worsen or last longer than a few days; you may need medical treatment:
Not known (frequency cannot be estimated from the available data)

• Darker areas of the skin and mucous membranes (hyperpigmentation).

Inform your doctor or pharmacist if any of the following side effects worsen or last longer than a few days; you may need to receive medical treatment:

Benign, malignant and unspecified tumours (including cysts and polyps)
Rare: Abnormal development of red blood cell precursors in the bone marrow (myelodysplastic syndrome, as shown by blood count).

Disorders of the haemolymphopoietic system
Common: Reduced number of red blood cells (anaemia), platelets (thrombocytopenia), or markedly reduced number of white blood cells (leucopenia).
Uncommon: Markedly reduced number of all blood cells (pancytopenia).
Rare: Impaired bone marrow function with reduced number of white blood cells (lymphopenia, neutropenia), markedly reduced number of certain white blood cells (agranulocytosis), failure of red blood cell formation (aplasia), or formation of enlarged red blood cells in normal or reduced numbers (macrocytosis) or reduced numbers (macrocytic anaemia). This is indicated in blood tests and may sometimes present with symptoms such as fever and breathing difficulties.

Endocrine disorders
Uncommon: Increased levels of antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH), excessive hair growth on the body in women, development of male characteristics in women, acne, male-pattern hair loss, and/or increased androgen levels.
Rare: Underactive thyroid gland (hypothyroidism), which may cause fatigue or weight gain.

Metabolism and nutrition disorders
Very common: Isolated, moderate increase in blood ammonia levels (hyperammonaemia) without changes in liver function tests, but with central nervous system symptoms in isolated cases, such as imbalance and coordination disorders, fatigue or reduced alertness, associated with vomiting. If you experience these symptoms, inform your doctor immediately. You may need urgent medical treatment (see also section 2 “Warnings and precautions”).
Common: Weight gain (a risk factor for the development of ovarian cysts) or weight loss, increased appetite or loss of appetite; reduced sodium concentration in the blood (hyponatraemia), which may lead to confusion.
Rare: Obesity.
Not known: Reduced carnitine concentrations (detected in blood or muscle tests).

Psychiatric disorders
Common: Confusional states, hallucinations (seeing, perceiving or hearing things that are not present), aggression, restlessness, attention disorders.
Uncommon: Irritability, hyperactivity.
Rare: Abnormal behaviour, learning disorder, mental and physical hyperactivity (psychomotor).

Nervous system disorders
Very common: Tremor (trembling).
Common: Extrapyramidal disorders (movement disorders affecting muscle activity regulated by the brain, such as uncontrollable muscle contractions; sometimes permanent disorders), stupor, drowsiness, epileptic seizures (convulsions), memory impairment, headache, involuntary eye movements (nystagmus), dizziness, and tingling or abnormal sensations on the skin (paraesthesiae).
Uncommon: Coma, brain damage (encephalopathy), apathy (lethargy), parkinsonism (which resolves rapidly after discontinuation of valproic acid), increased muscle tone (spasticity), impaired coordination of movements (ataxia), such as unsteady gait, worsening of epileptic seizures (see also section 2 “Warnings and precautions”).
Shortly after using medicines containing valproic acid, signs of brain damage (encephalopathy) have been reported, which resolved after discontinuation of the medicine. In some cases, these were associated with increased ammonia levels, as well as increased phenobarbital levels when used in combination therapy with phenobarbital.
Rare: Double vision, marked deterioration in mental performance (dementia) that improves upon discontinuation of treatment, sometimes associated with loss of brain tissue; mild decline in mental performance (cognitive disorder).
Rarely, brain disorders (chronic encephalopathy) with disturbances in brain function and mental performance have been reported, particularly with higher doses or when taken concurrently with other antiepileptic medicines.
Not known: Drowsiness.
During long-term treatment with Valproic Acid and Sodium Valproate EG, especially when taken concurrently with phenytoin (another medicine for epilepsy), signs of brain damage (encephalopathy) may occur: increased frequency of epileptic seizures, lethargy, stupor, reduced muscle tone (muscular hypotonia), and severe general abnormalities in brain wave recordings (electroencephalogram, EEG).

Ear and labyrinth disorders
Common: Hearing loss (sometimes permanent).
Not known: Tinnitus (ringing or buzzing in the ear).

Vascular disorders
Common: Bruising or spontaneous bleeding (see also section 2 “Warnings and precautions” and “Pregnancy, breastfeeding and fertility”).
Uncommon: Inflammation of blood vessels (vasculitis).

Respiratory, thoracic and mediastinal disorders
Uncommon: Breathing difficulties and pain due to pleuritis/fluid accumulation between the lungs and chest (pleural effusion).

Gastrointestinal disorders
Very common: Nausea.
Common: Vomiting, gum disorders (mainly excessive gum growth), inflammation of the oral mucosa (sores, swelling, ulcers and burning sensation in the mouth), diarrhoea, especially at the beginning of treatment, as well as upper abdominal discomfort, which usually resolves after a few days without discontinuation of treatment.
Uncommon: Pancreatic damage, sometimes fatal (see also section 2 “Warnings and precautions”), increased salivation (especially at the beginning of treatment).

Hepatobiliary disorders
Common: Severe liver damage (sometimes fatal), dose-independent (see also section 2 “Warnings and precautions”).

Skin and subcutaneous tissue disorders
Common: Hypersensitivity, transient and/or dose-dependent hair loss, nail and nail bed disorders.
Uncommon: Swelling (angioedema) with painful, itchy swellings, usually around the eyes, lips, throat and larynx, and sometimes hands, feet and genital area; skin rash, hair changes (e.g. altered hair structure, change in hair colour, abnormal hair or hair growth).
Rare: Severe skin reactions: blisters, skin peeling or bleeding (including lips, eyes, mouth, nose, genitals, hands or feet), with or without rash, sometimes with flu-like symptoms such as fever, chills or muscle pain (Stevens-Johnson syndrome or toxic epidermal necrolysis or Lyell’s syndrome); skin rash (especially on palms and soles) or skin lesions with a pink/red ring and a pale centre that may be itchy, scaly or filled with fluid (erythema multiforme); drug-induced rash, fever, swollen lymph nodes, increased numbers of certain white blood cells (eosinophilia), and possible involvement of other organs (DRESS syndrome).

Musculoskeletal and connective tissue disorders
Cases of decreased bone density (osteopenia and osteoporosis) and even bone fractures have been reported. Consult your doctor or pharmacist if you have been taking antiepileptic medicines for a long time, if you have been diagnosed with osteoporosis, or if you are also taking cortisone or other steroid hormones.
Rare: Immune system reactions against connective tissue, with symptoms such as joint pain, exhaustion/fatigue and skin rash (systemic lupus erythematosus, see also section 2 “Warnings and precautions”), severe muscle breakdown accompanied by muscle weakness and pain (rhabdomyolysis).

Renal and urinary disorders
Common: Urinary incontinence (involuntary urination).
Uncommon: Kidney failure with signs such as reduced urine output. Inform your doctor immediately if this serious side effect occurs. Urgent medical assistance may be required.
Rare: Enuresis (weak bladder) or increased urinary urgency, inflammatory kidney disease (tubulo-interstitial nephritis), excessive urine production and thirst (Fanconi syndrome) with excretion of phosphate, glucose and certain protein components, and excess acid in the body (metabolic acidosis).

Reproductive and breast disorders
Common: Painful menstrual periods (dysmenorrhoea).
Uncommon: Irregular or absent menstruation (amenorrhoea).
Rare: Male infertility, which usually resolves after discontinuation of treatment or may resolve after dose reduction. Do not stop treatment without first consulting your doctor.
Increased levels of testosterone (a sex hormone) in the blood and ovarian cysts (polycystic ovaries).

Congenital, familial and genetic disorders
(see section “Pregnancy, breastfeeding and fertility”).

General disorders and administration site conditions
Uncommon: Decreased body temperature (hypothermia), fluid retention in arms and/or legs (peripheral oedema).

Investigations
Rare: Blood coagulation disorders, detectable by abnormal laboratory results in blood coagulation tests (see also section 2 “Warnings and precautions” and “Pregnancy, breastfeeding and fertility”). Reduced levels of vitamin B7 in the body (biotin deficiency).

Other
If you experience dose-independent side effects or possible signs of liver or pancreas damage (see also section 2 “What you need to know before taking Valproic Acid and Sodium Valproate EG”), inform your doctor immediately, who will decide whether to continue treatment with Valproic Acid and Sodium Valproate EG.

Other side effects in children
Some side effects of valproate occur more frequently or are more severe in children than in adults. These include liver damage, pancreas inflammation (pancreatitis), aggression, restlessness, attention disorders, abnormal behaviour, mental and physical hyperactivity (psychomotor), and learning disorders.
These adverse reactions have been observed mainly in children.
Cases of stupor and apathy have been reported, which may progress to a transient coma or brain damage (encephalopathy), sometimes associated with increased frequency of epileptic seizures, particularly when administered concomitantly with phenobarbital or topiramate, or when the dose was increased rapidly. These symptoms resolved after dose reduction or discontinuation of treatment.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Valproic Acid and Sodium Valproate EG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the wording
{EXP}. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Acido Valproico e Sodio Valproato EG 300 mg contains
The active substance is sodium valproate.
Each 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: acesulfame potassium, basic butyl methacrylate copolymer, dibutyl sebacate,
hypromellose, sodium lauryl sulfate, magnesium stearate, hydrated colloidal silica, titanium dioxide (E171).

Description of the appearance of Acido Valproico e Sodio Valproato EG 300 mg and contents of the pack
The prolonged-release tablets of Acido Valproico e Sodio Valproato EG 300 mg are white, elongated, with a score line on both sides. The tablet can be divided into equal doses.
Brown glass bottle with plastic cap containing 50, 100, 200 and 500 prolonged-release tablets.
Al/Al blister packs containing 7, 10, 20, 30, 50, 84, 90, 100, 120, 150, 200, 2 x 100 and 500 prolonged-release tablets.
Not all pack sizes may be marketed.

What Acido Valproico e Sodio Valproato EG 500 mg contains
The active substance is sodium valproate.
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: acesulfame potassium, basic butyl methacrylate copolymer, dibutyl sebacate,
hypromellose, sodium lauryl sulfate, magnesium stearate, hydrated colloidal silica, titanium dioxide (E171).

Description of the appearance of Acido Valproico e Sodio Valproato EG 500 mg and contents of the pack
The prolonged-release tablets of Acido Valproico e Sodio Valproato EG 500 mg are white, elongated, with a score line on both sides. The tablet can be divided into equal doses.
Brown glass bottle with plastic cap containing 50, 100, 200 and 500 prolonged-release tablets.
Al/Al blister packs containing 7, 10, 20, 30, 50, 84, 90, 100, 120, 150, 200, 2 x 100 and 500 prolonged-release tablets.
Polypropylene container with closure and desiccant (silicon dioxide) containing 30, 50, 100, 200 and 500 prolonged-release tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
EG S.p.A. Via Pavia, 6 - 20136 Milan, Italy

Manufacturer
STADA Arzneimittel AG, Stadastrasse 2–18, 61118 Bad Vilbel - Germany
Centrafarm Services B.V., Van de Reijtstraat 31-E, 4814 NE Breda - Netherlands
Eurogenerics N.V., Heizel Esplanade B22, 1020 Brussels - Belgium

This medicinal product is authorized in the European Economic Area countries under the following names:
Belgium: Valproat(e) Retard EG 300 mg tabletten met verlengde afgifte
Germany: Valproat STADA 300 mg Retardtabletten
Italy: Acido Valproico e Sodio Valproato EG 300 mg compresse a rilascio prolungato
Luxembourg: Co-Valproat(e) EG 300 mg Tabs PR (prolonged release)
Netherlands: Natriumvalproaat Chrono CF 300 mg, tabletten met gereguleerde afgifte

Belgium: Valproat(e) Retard EG 500 mg tabletten met verlengde afgifte
Germany: Valproat STADA 500 mg Retardtabletten
Italy: Acido Valproico e Sodio Valproato EG 500 mg compresse a rilascio prolungato
Luxembourg: Co-Valproat(e) EG 500 mg Tabs PR (prolonged release)
Netherlands: Natriumvalproaat Chrono CF 500 mg, tabletten met gereguleerde afgifte

The complete approved educational material is available on the AIFA website. The following documents can be downloaded:

• Patient Guide for male patients: https://www.aifa.gov.it/documents/20142/2208912/Valproato_Guida_per_pazienti_sesso_maschile_aprile- 2024.pdf/3690edfe-0920-7dd6-aef9-a266c20aa537?t=1713877465409

• Patient Alert Card (PAC), single version for female and male patients: https://www.aifa.gov.it/documents/20142/2208912/Valproato_Carta_paziente_F-M_aprile- 2024.pdf/51698567-a3d4-6ad6-9840-82ce22277990?t=1713877465966

• Guide for female patients: https://www.aifa.gov.it/documents/20142/2208912/Valproato_Guida_per_le_pazienti_gen2024.pdf/889a045 7-5f75-ccda-21b3-5f75d6a84533?t=1705059431849