VALPROIC ACID ALTAN 400 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Valproic Acid Altan 400 mg Powder for Solution for Injection EFG

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Valproic Acid Altan and what is it used for
2. What you need to know before you use Valproic Acid Altan
3. How to use Valproic Acid Altan
4. Possible side effects
5. Storage of Valproic Acid Altan
6. Contents of the pack and further information

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

This medicinal product belongs to a group of medicines called antiepileptics. It is indicated for the treatment of epilepsy in adults and children, generalized or partial:

Valproic Acid Altan should be reserved for patients who are unconscious and other situations where oral administration is not possible temporarily, and should be replaced by the most suitable oral formulation as soon as possible. The injectable formulation may also be used in urgent situations where rapid therapeutic induction is required.

2. What you need to know before you use Valproic Acid Altan

Do not use Valproic Acid Altan:

• If you are allergic (hypersensitive) to valproic acid or any of the other components of valproic acid, or to any other medicine, you must inform your doctor. (listed in section 6)
• Do not use Valproic Acid Altan if you are pregnant, unless no other treatment works.
• If you are a woman of childbearing potential, do not take Valproic Acid Altan, unless you use an effective method of contraception (birth control) throughout treatment with Valproic Acid Altan. Do not stop taking Valproic Acid Altan or your contraceptive until you have spoken to your doctor. Your doctor will advise you (see below in “Pregnancy, breastfeeding, and fertility – Important warning for women”).
• If you currently have any liver or pancreatic disease.
• If you have previously had any liver disease.
• If any of your close relatives have a history of severe liver disease (hepatitis), mainly due to medication.
• If you have a history of a family member who died from liver function disorders during treatment with valproate.
• If you have hepatic porphyria (a very rare metabolic disorder).
• If you have a genetic problem that causes a mitochondrial disorder (e.g., Alpers-Huttenlocher syndrome).
• If you have a known metabolic disorder, such as a disorder of the urea cycle.
• If you have an untreated carnitine deficiency (a very rare metabolic disease).

If you think you may have any of these problems or if you have any doubts, consult your doctor before administering Valproic Acid Altan.

Warnings and precautions

CONSULT YOUR DOCTOR IMMEDIATELY:

The risk of liver damage increases if valproate is administered to children under 3 years of age, in people who take other antiepileptic medications at the same time, or who have other neurological or metabolic disorders and severe forms of epilepsy.

Your doctor must review your liver function tests before you start treatment and periodically during the first 6 months, especially in patients at risk.

If you or your child suddenly develop an illness, especially if it appears in the first few months of treatment and, in particular, if it includes repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, pain in the upper abdomen, nausea, jaundice (yellowing of the skin or eyes), swelling of the legs, or worsening of epilepsy or a feeling of general malaise. In this case, you must consult your doctor immediately. In a very small number of patients, Depakine can affect the liver or pancreas. The alteration of liver function along with pancreatic alteration increases the risk of fatal outcome.

If you or your child taking valproate develop problems with balance and coordination, a feeling of lethargy, or feeling less alert, vomit, inform your doctor immediately. This may be due to an increase in your blood ammonia level.

A small number of people who were being treated with antiepileptics like valproic acid have had thoughts of self-harm or suicide. If at any time you have these thoughts, contact your doctor immediately.

Severe 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 medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Before taking this medicine, consult your doctor

• If you know or your doctor suspects that there is a genetic problem in your family caused by a mitochondrial disorder, due to the risk of liver damage.
• If it is suspected that you have a metabolic disorder, particularly hereditary enzyme deficiency disorders, such as a “urea cycle disorder”, due to the risk of increased blood ammonia levels.
• If you have a rare disorder called “carnitine palmitoyltransferase type II deficiency”, because you have a higher risk of muscle disorders.
• If you have an altered dietary intake of carnitine, which is found in meat and dairy products, especially in children under 10 years of age.
• If you have a carnitine deficiency and are taking carnitine.
• If you suffer from kidney function impairment or hypoproteinemia (decreased protein levels in the blood). In this case, your doctor may want to monitor valproate blood levels or adjust the dose.
• If Valproic Acid Altan is administered to children under 3 years of age, the concomitant administration with acetylsalicylic acid (aspirin) should be avoided.
• If you have systemic lupus erythematosus.
• If you have blood disorders (blood clotting or thrombocytopenia). It is recommended to perform a blood test (complete blood count) before starting treatment or before surgery and in cases of spontaneous hematomas or bleeding.
• If you experience weight gain at the start of treatment.
• As with other antiepileptic medications, seizures may worsen or occur more frequently while using this medication. If this happens, contact your doctor immediately.
• If you have ever developed a severe skin rash or exfoliation, blisters, and/or ulcers in the mouth after taking valproate.

Using Valproic Acid Altan with other medicines

Tell your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription, homeopathic medicines, herbal remedies, and other health-related products, as it may be necessary to interrupt treatment or adjust the dose of one of them.

Some medicines may alter the effect of Valproic Acid Altan or vice versa. These include:

• Carbapenem agents (antibiotics used to treat bacterial infections).
• Products containing estrogens (including some birth control pills).
• Neuroleptics (medicines used to treat psychological disorders).
• Medicines used to treat depression.
• Benzodiazepines (medicines used to sleep or treat anxiety).
• Olanzapine and quetiapine (medicines used to treat psychiatric disorders).
• Other medicines used to treat epilepsy, including phenobarbital, phenytoin, primidone, lamotrigine (the risk of severe skin rash may increase when lamotrigine and valproic acid are administered together), carbamazepine, ethosuximide, felbamate, and topiramate. The concomitant administration of Valproic Acid Altan with topiramate has been associated with encephalopathy and/or hyperammonemia (a condition of the brain and nervous system that presents as a complication of liver disorders with or without increased ammonia levels in the blood).
• Zidovudine (a medicine used to treat HIV and AIDS).
• Mefloquine (a medicine used to treat or prevent malaria).
• Salicylates (aspirin). See also “Warnings and precautions – Children under 3 years”.
• Anticoagulants (medicines used to prevent blood clot formation).
• Cimetidine (a medicine used to treat stomach ulcers).
• Erythromycin and rifampicin (antibiotics).
• Rufinamide.
• Acetazolamide.
• Protease inhibitors, such as lopinavir, ritonavir (used to treat HIV).
• Colestyramine.
• Propofol (anesthetic).
• Metamizole (a medicine used to treat pain and fever).
• Cannabidiol (used to treat epilepsy and other diseases).
• Methotrexate (used to treat cancer and inflammatory diseases).
• Some anti-infectives that contain pivalate (e.g., pivampicillin, adefovir dipivoxil).
• Clozapine (for treating mental health diseases)

Valproic Acid Altan may increase the effects of Nimodipine (a medicine used to treat hypertension, angina pectoris, and vascular disorders).

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

Using Valproic Acid Altan with food, drinks, and alcohol

Do not drink alcoholic beverages.

Pregnancy, Breastfeeding, and Fertility

Pregnancy

Consult your doctor or pharmacist before using any medication.

Important Warning for Women

• You should not use Valproic Acid Altan if you are pregnant, unless no other treatment works.
• If you are a woman of childbearing potential, you should not take Valproic Acid Altan unless you use an effective method of birth control (contraception) throughout your treatment with Valproic Acid Altan. Do not stop taking Valproic Acid Altan or your contraceptive until you have spoken with your doctor. Your doctor will advise you.

Risks of valproate when taken during pregnancy:

• Talk to your doctor immediately if you are planning to have a baby or are pregnant.
• Valproate carries a risk when taken during pregnancy. With the highest dose, the risk is greater, but all doses have a risk, even when valproate is used in combination with other medications to treat epilepsy.
• It can cause serious birth defects and may affect the way the child develops and grows. The reported birth defects include spina bifida(where the bones of the spine do not develop properly); malformations of the skull and face, heart, kidney, urinary tract, sexual organs, and limb defects, as well as multiple malformations that affect several organs and parts of the body. Birth defects can result in disabilities that can be severe.
• Hearing problems or deafness have been reported in children exposed to valproate during pregnancy.
• Ocular malformations have been reported in children exposed to valproate during pregnancy, in association with other congenital malformations. These ocular malformations can affect vision.
• If you take valproate during pregnancy, you have a higher risk than other women of having a child with birth defects that require medical treatment. As valproate has been used for many years, it is known that of the women who take valproate, around 10 babies out of 100 will have birth defects. In comparison, 2-3 babies out of 100 born to women who do not have epilepsy will have birth defects.
• It is estimated that up to 30-40% of children in preschool age whose mothers took valproate during pregnancy may have developmental problems in childhood. The affected children may speak and walk slowly, be less intellectually capable than other children, and have language and memory difficulties.
• In children exposed to valproate, autism spectrum disorders are more frequently diagnosed, and there is some evidence that these children may develop symptoms of Attention Deficit Hyperactivity Disorder (ADHD).
• Before prescribing this medication, your doctor will have explained that your baby may be at risk if you become pregnant while taking valproate. If you later decide that you want to have a baby, do not stop taking your medication or your contraceptive until you have spoken with your doctor. Your doctor will advise you.
• If you are a father or caregiver of a girl being treated with valproate, you should contact your doctor when your daughter being treated with valproate has her menarche (first menstruation).
• Some oral contraceptives (contraceptive pills containing estrogens) may decrease valproate levels in the blood. Make sure to talk to your doctor about the most suitable contraceptive method (birth control) for you.
• Consult your doctor about taking folic acid when trying to have a baby. Folic acid may decrease the overall risk of spina bifidaand early abortion 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 the Following:

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

I AM STARTING TREATMENT WITH VALPROIC ACID ALTAN

If this is the first time you have been prescribed Valproic Acid Altan, your doctor will have explained the risks to the fetus if you become pregnant. Once you are of childbearing age, you will need to ensure the use of an effective contraceptive method without interruption throughout your treatment with Valproic Acid Altan. Consult your doctor or family planning clinic if you need advice on contraception.

Important Messages:

• Pregnancy should be excluded before starting treatment with Valproic Acid Altan, by means of a pregnancy test result confirmed by your doctor.
• You should use an effective method of birth control (contraception) throughout your treatment with Valproic Acid Altan.
• You should talk to your doctor about suitable methods of birth control (contraception). Your doctor will give you information on how to prevent pregnancy and may refer you to a specialist for birth control advice.
• You should have regular check-ups (at least annual) with a specialist experienced in the treatment of epilepsy. During this visit, your doctor will ensure that you know and have understood all the risks and warnings related to the use of valproate during pregnancy.
• Tell your doctor if you want to have a baby.
• Consult your doctor immediately if you are pregnant or think you may be pregnant.

I AM TAKING VALPROIC ACID ALTAN AND I DO NOT PLAN TO HAVE A BABY

If you continue treatment with Valproic Acid Altan but do not plan to have a baby, make sure to use an effective contraceptive method without interruption throughout your treatment with Valproic Acid Altan. Consult your doctor or family planning clinic if you need advice on contraception.

Important Messages:

• You should use a method of birth control (contraception) throughout your treatment with Valproic Acid Altan.
• You should talk to your doctor about birth control (contraception). Your doctor will give you information on how to prevent pregnancy and may refer you to a specialist for birth control advice.
• You should have regular check-ups (at least annual) with a specialist experienced in the treatment of epilepsy. During this visit, your doctor will ensure that you know and have understood all the risks and warnings related to the use of valproate during pregnancy.
• Tell your doctor if you want to have a baby.
• Tell your doctor immediately if you are pregnant or think you may be pregnant.

I AM TAKING VALPROIC ACID ALTAN AND I PLAN TO HAVE A BABY

If you are planning to have a baby, first schedule an appointment with your doctor.

Do not stop taking Valproic Acid Altan or your contraceptive until you have spoken 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 can be severely debilitating.

Your doctor will refer you to a specialist with experience in the treatment of epilepsy, so that alternative treatment options can be evaluated from the start. Your specialist may take several actions to ensure that your pregnancy develops as well as possible and the risks to you and the fetus are reduced as much as possible.

Your specialist may decide to change the dose of Valproic Acid Altan or switch to another medication, or stop treatment with Valproic Acid Altan long before you become pregnant – to ensure that your disease is stable.

Consult your doctor about taking folic acid when trying to have a baby. Folic acid may decrease the overall risk of spina bifidaand early abortion that exists in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.

Important Messages:

• Do not stop taking Valproic Acid Altan unless your doctor tells you to.
• Do not stop using your contraceptives (contraception) before talking to your doctor and working together on a plan to ensure that your disease is controlled and the risks to your baby are reduced.
• First, schedule an appointment with your doctor. During this visit, your doctor will ensure that you know and have understood all the risks and warnings related to the use of valproate during pregnancy.
• Your doctor will try to switch you to another medication or stop treatment with Valproic Acid Altan long before you become pregnant.
• Schedule an urgent appointment with your doctor if you are pregnant or think you may be pregnant.

I AM PREGNANT AND I AM TAKING VALPROIC ACID ALTAN

• Do not stop taking Valproic Acid Altan unless your doctor tells you to, as your disease 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 can be severely debilitating.

Your doctor will refer you to a specialist with experience in the treatment of epilepsy, so that alternative treatment options can be evaluated.

In exceptional circumstances, when Valproic Acid Altan is the only treatment option during pregnancy, you will be closely monitored, both for the management of your underlying disease and to check how the fetus is developing. You and your partner may receive counseling and support related to pregnancy with valproate exposure.

Consult your doctor about taking folic acid. Folic acid may decrease the overall risk of spina bifidaand early abortion that exists in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.

Important Messages:

• Schedule an urgent appointment with your doctor if you are pregnant or think you may be pregnant.
• Do not stop taking Valproic Acid Altan unless your doctor tells you to.
• Make sure you are referred to a specialist with experience in the treatment of epilepsy, to evaluate the need for alternative treatment options.
• You should receive counseling about the risks of Valproic Acid Altan during pregnancy, including teratogenicity and developmental effects in children.
• Make sure you are referred to a prenatal monitoring specialist to detect possible malformations.

Make sure to read the Patient Guide that your doctor will provide. Your doctor will discuss the Annual Risk Knowledge Form and ask you to sign and keep it. Your pharmacist will also provide you with a Patient Card to remind you of the risks of valproate if you take it during pregnancy.

In newborn babies of mothers who have taken Valproic Acid Altan during pregnancy, the following may also occur:

• Coagulation problems may occur due to partial or total lack of some of the substances necessary for blood coagulation. In the latter case, the problem can be fatal, so specific analytics and coagulation tests should be performed on the newborn.

• Hypoglycemia may occur in newborns of mothers who have taken Valproic Acid Altan during pregnancy.

• Cases of hypothyroidism have been reported in neonates of mothers who have taken valproate during pregnancy.

• A withdrawal syndrome (such as agitation, irritability, hyperexcitability, nervousness, hyperkinesia, tone disorders, tremors, convulsions, and feeding disorders) may occur in newborns whose mothers have taken valproate during the last trimester of pregnancy.

Breastfeeding

Consult your doctor or pharmacist before using any medication.

Valproate sodium passes into breast milk. However, the amounts of valproate sodium that pass into breast milk are small, and therefore, treatment with Valproic Acid Altan during the breastfeeding period does not generally pose a risk to the infant, and it is not usually necessary to stop breastfeeding. Nevertheless, you should consult your doctor about the convenience of maintaining or not maintaining breastfeeding, taking into account the safety profile of Valproic Acid Altan, especially blood disorders (see section "Possible adverse effects").

Important Information for Male Patients

Potential risks associated with the use of valproate in the 3 months prior to conception of a child

A study suggests a possible risk of movement and mental development disorders (problems with childhood development) in children born to fathers treated with valproate in the 3 months prior to conception. In this study, around 5 out of 100 children presented with these disorders when born to fathers treated with valproate, compared to 3 out of 100 children when born to fathers treated with lamotrigine or levetiracetam (other medications that can be used to treat your disease). The risk to children born to fathers who stopped treatment with valproate 3 months (the time necessary to form new sperm) or more before conception is unknown. The study has limitations, and therefore, it is not clear whether the higher risk of movement and mental development disorders suggested by this study is caused by valproate. The study was not extensive enough to demonstrate what specific type of movement and mental development disorder children may develop.

As a precautionary measure, your doctor will talk to you about:

o The potential risk in children born to fathers treated with valproate.

o The need to consider effective birth control methods (contraception) for you and your female partner during treatment and for 3 months after stopping treatment.

o The need to consult your doctor when planning to conceive a child and before stopping contraception (birth control).

o The possibility of using other treatments to treat your disease, depending on your individual situation.

Do not donate sperm when taking valproate and for 3 months after stopping valproate.

Talk to your doctor if you are thinking of having a child.

If your female partner becomes pregnant while you were taking valproate in the 3 months prior to conception and you have any doubts, contact your doctor. Do not stop treatment without consulting your doctor. If you stop treatment, your symptoms may worsen.

You should have regular appointments with your doctor. During this visit, your doctor will talk to you about the precautions associated with the use of valproate and the possibility of other treatments that can be used to treat your disease, depending on your individual situation.

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

Driving and Using Machines:

Valproic acid may produce symptoms such as drowsiness, dizziness, or vision changes, and may decrease your reaction ability. These effects, as well as the disease itself, may impair your ability to drive vehicles or operate machines. Therefore, do not drive, operate machines, or engage in other activities that require special attention until your doctor assesses your response to this medication.

Important Information about Some Components of Valproic Acid Altan

Patients with low-sodium diets should note that this medication contains 55.33 mg (2.41 mmol) of sodium per vial. This is equivalent to 2.8% of the maximum recommended daily sodium intake for an adult.

3. How to use Valproic Acid Altan.

Girls and women of childbearing age

Treatment with Valproic Acid Altan should be initiated and supervised by a doctor specializing in the treatment of epilepsy.

Male patients

It is recommended that Valproic Acid Altan be initiated and supervised by a specialist with experience in the treatment of epilepsy - see section 2 Important information for male patients

Follow the administration instructions for the medication contained in this prospectus or as indicated by your doctor or nurse. In case of doubt, ask your doctor or nurse.

Valproic Acid Altan should be administered under medical supervision. It will normally be administered by a doctor or nurse (under medical supervision).

Your doctor will decide the most convenient dose of Valproic Acid Altan. Make sure to perform periodic reviews with your doctor.

Valproic Acid Altan is prescribed individually and for a specific situation. The recommended doses in this prospectus are indicative. The doses of Valproic Acid Altan are established according to body weight, specific situation, and the prescribing doctor's criteria.

? Infants and children (28 days to 11 years): The recommended dose is 20-30 mg/kg of body weight.

? Adolescents (≥12 years) and adults (≥18 years): In patients with established oral treatment, Valproic Acid Altan will be administered in continuous infusion, 4 to 6 hours after oral intake, following the same established dosage, at an infusion rate between 0.5 and 1 mg/kg/h. In the rest of the patients, administer the preparation in the form of slow injection (3-5 minutes), at a rate of 15 mg/kg of body weight, to continue after 30 minutes with a continuous infusion at 1 mg/kg/h up to a maximum of 25 mg/kg/day.

? Elderly patients (≥65 years): 15-20 mg/kg of body weight.

? Patients with hepatic insufficiency: Valproic Acid Altan should not be administered to patients with severe liver disease.

? Patients with renal insufficiency: It may be necessary to administer lower doses to this type of patient.

The usual daily dose is 0.2 – 0.3 ml (equivalent to 20-30 mg of sodium valproate) per kilogram of weight, administered by intravenous infusion. Oral therapy should replace intravenous therapy as soon as possible.

Patients with kidney problems

Your doctor may decide to adjust your dose.

IN NO CASE SHOULD THIS MEDICINE BE ADMINISTERED BY A ROUTE OTHER THAN INTRAVENOUS.

The dose is always adjusted individually, according to each patient's response.

If you use more Valproic Acid Altan than you should

If this medication is administered by a doctor or nurse (under medical supervision), it is unlikely that you will be given more than you should. They will monitor your progress. Always ask if you are not sure why you are being given a dose of medication.

An overdose of Valproic Acid can be dangerous. Among the symptoms of poisoning are confusion, sedation, or even coma with hypotonia, muscle weakness, and lack of reflexes. Therefore, go to the nearest hospital where you will be treated for symptoms and undergo cardio-respiratory monitoring. In some cases, hypotension, miosis, cardiovascular and respiratory alterations, circulatory collapse/shock, metabolic acidosis, hypocalcemia, and hypernatremia have also been observed. There have been cases of death after massive overdose; however, the usual outcome is favorable.

However, the symptoms can be variable, and seizures have been reported in the presence of very high plasma levels. Cases of intracranial hypertension associated with cerebral edema have been reported.

The presence of sodium in valproate presentations may lead to hypernatremia in the event of an overdose.

It is recommended to take the packaging and prospectus of the medication to the healthcare professional.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91.562.04.20, indicating the medication and the amount ingested.

If you forget to use Valproic Acid Altan

Do not take a double dose to make up for forgotten doses.

If you interrupt treatment withValproic Acid Altan

The sudden suspension of treatment with Valproic Acid without explicit indication from your doctor can be harmful to you, as it may trigger episodes with seizures with serious consequences.

If you have any other doubts about the use of this medication, ask your doctor or nurse.

4. Possible adverse effects

Like all medications, this medication can have adverse effects, although not all people suffer from them.

Inform your doctor immediately if any of the following serious adverse reactions appear, as you may need urgent medical attention:

? Drowsiness, change in level of consciousness (including coma), confusion, slow or abnormal behavior, and memory loss associated or not with an increased frequency or severity of convulsive attacks, particularly if you are taking phenobarbital or topiramate (medications used to treat convulsions) at the same time or if the dose of Valproic Acid Altan has been suddenly increased.

? Confusion that may be caused by a decrease in sodium levels in the blood or by a condition called Syndrome of Inadequate Secretion of Antidiuretic Hormone (SIADH).

? Problems with balance and coordination, feeling of lethargy or loss of alertness, associated with vomiting. This may be due to an increase in blood ammonia levels.

? Increase in the number and severity of seizures.

? Repeated vomiting, extreme fatigue, abdominal pain, drowsiness, weakness, loss of appetite, severe pain in the upper part of the stomach, nausea, jaundice (yellowing of the skin or the whites of the eyes), swelling of the legs, or worsening of epilepsy or general feeling of discomfort. These can be symptoms of serious liver and pancreas disorders.

? Allergic reactions that can manifest as:

• Blisters with skin peeling (blisters, peeling, or bleeding on any part of the skin (including lips, eyes, mouth, nose, genitals, hands, or feet) with or without rash, with symptoms sometimes similar to those of the flu such as fever, chills, or muscle pain - these can be signs of conditions called 'toxic epidermal necrolysis' or 'Stevens-Johnson syndrome').
• Allergic inflammation with painful hives that cause itching (frequently around the eyes, lips, throat, and sometimes on hands and feet) – these can be symptoms of “angioedema”.
• Syndrome that involves skin rash, fever, swelling of lymph nodes, and possible failure of other organs – these can be signs of a condition called “DRESS” or drug rash with eosinophilia and systemic symptoms.

? Spontaneous appearance of bruises or bleeding due to blood coagulation problems that appear in blood tests.

? Severe decrease in white blood cells or bone marrow failure that appears in blood tests, which sometimes manifests with fever and difficulty breathing.

? Underactive thyroid gland, which can cause fatigue or weight gain (hypothyroidism).

? Joint pain, fever, fatigue, rash. These can be signs of systemic lupus erythematosus.

? Agitation (tremor), uncontrolled muscle contractions, instability when walking (parkinsonism, extrapyramidal disorder, ataxia).

? Muscle pain and muscle weakness (rhabdomyolysis).

? Sedation, extrapyramidal disorders.

? Infrequent: difficulty breathing, pain or pressure in the chest (especially when inhaling), difficulty breathing, and dry cough due to fluid accumulation around the lungs (pleural effusion).

? Kidney disease (renal failure, tubulointerstitial nephritis, and Fanconi syndrome) that can manifest as a reduction in diuresis.

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

The very frequent adverse effects that can affect more than 1 in 10 patients are:

? Nervous system disorders: tremor.

? Gastrointestinal disorders: nausea (also observed a few minutes after intravenous injection and resolving spontaneously in a few minutes).

The frequent adverse effects that can affect up to 1 in 10 patients are:

? Blood disorders: reduction in the number of red blood cells (anemia) and reduction in the number of platelets (thrombocytopenia).

? Nervous system disorders: involuntary movement (extrapyramidal disorders), stupor, drowsiness, seizures, memory failure, headache, rapid and uncontrolled eye movements (nistagmus), dizziness may appear a few minutes after intravenous injection that disappears spontaneously in a few minutes. In isolated cases or associated with an increase in convulsive attacks during treatment, cases of confusion have been described that decrease after suspension of treatment and dose reduction.

? Renal and urinary disorders: urinary incontinence.

? Ear disorders: hearing problems or deafness.

? Gastrointestinal disorders: vomiting, gum problems (mainly hypertrophy), pain and swelling in the mouth, ulcers, and burning sensation in the mouth (stomatitis), pain in the upper part of the abdomen, and diarrhea, frequently appear in some patients at the beginning of treatment and normally disappear within a few days without interrupting treatment.

? Skin and subcutaneous tissue disorders: alteration of the nail and the skin under the nail, hypersensitivity, hair loss (transitory and/or related to the dose).

? Metabolism and nutrition disorders: decrease in sodium levels in the blood (hyponatremia), weight gain.

? Vascular disorders: bleeding.

? Hepatobiliary disorders: liver damage.

? Reproductive system disorders: painful menstruation (dysmenorrhea).

? Psychiatric disorders: confusion, seeing, feeling, or hearing things that do not exist (hallucinations), aggression*, agitation*, attention disorders* (*mainly observed in children).

The infrequent adverse effects that can affect up to 1 in 100 patients are:

? Blood disorders: scarcity of blood components (pancytopenia) and decrease in the number of white blood cells in the blood (leukopenia).

? Nervous system disorders: coma, encephalopathy, lethargy, disorder characterized by tremor, difficulty walking, movement, and coordination (reversible parkinsonism), incoordination of movements (ataxia), numbness or tingling in the feet or hands (paresthesia), worsening of seizures.

? Renal and urinary disorders: renal failure.

? Gastrointestinal disorders: pancreatitis that can be fatal.

? Skin and subcutaneous tissue disorders: inflammation of feet, hands, throat, lips, and respiratory tract (angioedema) and rash, abnormal growth and texture of hair, and changes in hair color.

? Musculoskeletal and connective tissue disorders: alterations in bones, including osteopenia and osteoporosis (decalcification of bones) and fractures. Consult your doctor or pharmacist if you are undergoing prolonged treatment with antiepileptics, have a history of osteoporosis, or take steroids.

? Endocrine disorders: Syndrome of Inadequate Secretion of Antidiuretic Hormone, (fluid retention and decrease in certain electrolyte levels in the blood), hyperandrogenism (increased hair, virilization, acne, male-pattern baldness, and/or increased androgens).

? Vascular disorders: inflammation of small blood vessels (vasculitis).

? General disorders: swelling of ankles, feet, and legs due to fluid accumulation (non-severe peripheral edema), decrease in body temperature.

? Reproductive system disorders: irregular or absent menstruation (amenorrhea).

The rare adverse effects that can affect up to 1 in 1,000 patients are:

? Blood disorders: bone marrow failure including pure red cell aplasia (stop or decrease in the production of red blood cells. This causes severe anemia, whose symptoms include unusual fatigue and lack of energy), agranulocytosis (decrease in the number of white blood cells), decrease in the number of red blood cells with a larger than normal size (macrocytic anemia, macrocytosis).

? Complementary tests: decrease in coagulation factors, biotin/biotinidase deficiency (low levels of vitamin B8).

? Nervous system disorders: reversible dementia, mental function impairment causing confusion and changes in intellect or reasoning, double vision.

? Kidney disorders: involuntary urination (enuresis), tubulointerstitial nephritis, and Fanconi syndrome, which can manifest as frequent urination and thirst.

? Skin and subcutaneous tissue disorders: skin lesions with red spots, blisters, and even peeling that can be severe (Stevens-Johnson Syndrome), DRESS Syndrome (severe skin lesion characterized by generalized rash, fever, lymph node inflammation, blood alterations, and internal organ involvement).

? Musculoskeletal and connective tissue disorders: systemic lupus erythematosus, rhabdomyolysis (muscle pain and weakness).

? Endocrine disorders: hypothyroidism.

? Metabolism and nutrition disorders: obesity and increased ammonia levels in the blood (hyperammonemia).

? Neoplasms: myelodysplastic syndrome (disease in which the bone marrow does not function normally).

? Reproductive system disorders: male infertility (may be reversible after dose reduction or discontinuation), polycystic ovaries.

? Psychiatric disorders: abnormal behavior*, hyperactivity*, learning disorders* (*mainly observed in children).

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

? Congenital, familial, and genetic disorders: autism spectrum disorders, congenital malformations, and developmental disorders.

? Complementary tests: false positives may appear in the urine ketone elimination test in diabetic patients.

? Decrease in carnitine levels (detected in blood or muscle test).

? Skin and subcutaneous tissue disorders: darker areas of the skin and mucous membranes (hyperpigmentation)

Additional adverse effects in children

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Valproic Acid Altan.

Keep this medication out of sight and reach of children.

No special storage conditions are required.

If stored at room temperature (25°C), the reconstituted product must be used within 8 hours, and if stored at 2-8°C, within 24 hours.

Do not use Valproic Acid Altan after the expiration date shown on the packaging. The expiration date is the last day of the month indicated.

Medications should not be thrown down the drain or into the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Composition of Valproic Acid Altan

• The active ingredient is sodium valproate.

Appearance of the Product and Container Content

Valproic Acid Altan contains 1 vial of lyophilized powder.

Each vial of powder for injectable solution contains as active ingredient sodium valproate 400 mg.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder

Altan Pharmaceuticals, S.A.

C/ Cólquide nº 6. Portal 2, 1ª planta, oficina F

Edificio Prisma

28230 - Las Rozas (Madrid)

Spain

Manufacturer:

Altan Pharmaceuticals, S.A

Avd. Constitución nº 198- 199, Pol. Industrial Monte Boyal

45950 - Casarrubios del Monte (Toledo)

Spain

Date of the Last Revision of this Prospectus: May 2025

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

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This information is intended only for doctors or healthcare professionals:

The daily dose should be adjusted according to age and body weight; however, the wide individual variability in sensitivity to valproic acid should also be taken into account.

Since a satisfactory correlation has not been established between the daily dose, serum concentration, and therapeutic effect, the optimal dose should be determined mainly based on clinical response. When sufficient control of seizures is not achieved or adverse effects are suspected, in addition to clinical monitoring, the determination of valproic acid plasma concentrations may be considered. The reported efficacy range usually fluctuates between 50-125 μg/ml (300-752 μmol/l).

The recommended average daily dose of valproic acid to be administered is:

Adolescents (≥ 12 years) and adults (≥ 18 years): In patients with established oral treatment, Valproic Acid Altan will be administered in continuous infusion, 4 to 6 hours after oral intake, following the same established posology, at an infusion rate between 0.5 and 1 mg/kg/h. In the rest of the patients, administer the preparation in the form of slow injection (3-5 minutes), at a rate of 15 mg/kg of body weight, to continue after 30 minutes with a continuous infusion at 1 mg/kg/h up to a maximum of 25 mg/kg.

Infants and children (28 days to 11 years): 20-30 mg/kg.

Elderly patients (≥ 65 years): 15-20 mg/kg.

Patients with renal insufficiency

In patients with renal insufficiency, it may be necessary to decrease the dose or increase the dose in patients undergoing hemodialysis. Valproate is dialyzable (see section 4.9). The dose should be modified according to clinical monitoring of the patient (see section 4.4).

Girls and women of childbearing age: Valproate should be initiated and supervised by a specialist with experience in the management of epilepsy. Valproic Acid Altan should not be used in girls or women of childbearing age, unless other treatments are not effective or tolerated.

Valproate is prescribed and dispensed according to the Valproate Pregnancy Prevention Plan (see sections 4.3 and 4.4).

Valproate should be prescribed preferably as monotherapy and at the lowest effective dose, if possible as prolonged-release formulations. The daily dose should be divided into at least two individual doses (see section 4.6).

Oral therapy should replace intravenous therapy as soon as possible.

UNDER NO CIRCUMSTANCES SHOULD VALPROIC ACID ALTAN BE ADMINISTERED BY ANY ROUTE OTHER THAN INTRAVENOUSLY.

Reconstitute the preparation by injecting 4 mL of water for injectable preparations into the vial of powder, wait for it to dissolve, and then extract the desired amount.

The preparation should be reconstituted immediately before use, and the infusion solutions containing valproic acid should be used within the next 24 hours. If the entirety of the initial preparation is not used, the remaining fraction of the product should not be reused.

Valproic Acid Altan will be administered by slow intravenous injection (3 min) or infusion. In case other substances are being administered by infusion, do not use the same route.