Prospect: information for the user

Ácido Valproico Altan 400 mg powder for injectable solution EFG

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You may contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, as it contains important information for you.

• Keep this prospect, as you may need to refer to it again.
• If you have any doubts, consult your doctor or nurse.
• This medicine has been prescribed only for you, and you must not give it to others who have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

1. What is Ácido Valproico Altan and for what it is used

2. What you need to know before starting to use Ácido Valproico Altan

3. How to use Ácido Valproico Altan

4. Possible adverse effects

5. Storage of Ácido Valproico Altan

6. Contents of the package and additional information

This medication belongs to the group of medications called antiepileptics. It is indicated for the treatment of adult and child epilepsy, generalized or partial:

Altan Valproic Acid should be reserved for unconscious patients and other situations in which oral administration is not possible temporarily, and should be replaced by the oral presentation as soon as possible. It may also be resorted to the injectable presentation in urgent situations in which a rapid therapeutic induction is required

No use Acido Valproico Altan:

- If you are allergic (hypersensitive) to valproic acid or to any of the other components of valproic acid, or to any other medicine, you must tell your doctor. (See section 6)

- Do not use valproic acid if you are pregnant, unless no other treatment works.

- If you are a woman of childbearing age, do not take valproic acid unless you use an effective method of birth control (contraception) throughout your treatment with valproic acid. Do not stop taking valproic acid or your contraceptive until you have talked to your doctor. Your doctor will advise you (see "Pregnancy, breastfeeding and fertility – Important warning for women").

- If you have any liver or pancreas disease currently.

- If you have had any liver disease in the past.

- If any of your close relatives have a history of severe liver disease (hepatitis), mainly caused by medication.

- If you have a family history of liver function disorder during treatment with sodium valproate.

- If you have porphyria of the liver (a rare metabolic disorder).

- If you have a genetic disorder that causes a mitochondrial disorder (e.g., Alpers-Huttenlocher syndrome).

- If you have a known metabolic disorder, such as a urea cycle disorder.

If you think you may have any of these problems or if you are unsure, consult your doctor before administering valproic acid.

Warnings and precautions

• If you know that there is a genetic disorder in your family that causes a mitochondrial disorder.
• Your doctor must review your liver function tests before you start treatment and periodically during the first 6 months, especially in high-risk patients.
• If you, or your child, suddenly develop a disease, 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, upper stomach pain, nausea, jaundice (yellowing of the skin or eyes), swelling of the legs, or worsening of epilepsy or generalised discomfort. In this case, you must consult your doctor immediately. In a very small number of patients, valproic acid can affect the liver or pancreas. Liver dysfunction combined with pancreatic dysfunction increases the risk of fatal outcome.
• If valproic acid is administered to children under 3 years old and in school age treated simultaneously with other antiepileptic drugs in addition to valproic acid, or who have another neurological or metabolic disease and severe forms of epilepsy.
• If valproic acid is administered to children under 3 years old, it should be especially avoided to administer it together with acetylsalicylic acid (aspirin).
• If you have systemic lupus erythematosus.
• If you suspect you have any metabolic disorder, particularly hereditary enzyme deficiency disorders, such as urea cycle disorders, as there is a higher risk of increased blood ammonia levels (see "Do not use valproic acid").
• If you have kidney dysfunction or hypoproteinemia (decreased blood protein levels). In this case, your doctor may want to monitor your valproate blood levels or adjust your dose.
• If you have blood disorders (coagulation disorders or thrombocytopenia). It is recommended to perform a blood test (complete blood count) before starting treatment or before surgery and in cases of spontaneous bleeding or bruising.
• If you experience weight gain at the start of treatment.
• If you have carnitine palmitoyltransferase type II deficiency due to the risk of rhabdomyolysis.
• A small number of people who have been treated with antiepileptic drugs such as valproic acid have had thoughts of self-harm or suicide. If you have these thoughts at any time, contact your doctor immediately.
• As with other antiepileptic drugs, seizures may worsen or occur more frequently while taking this medication. If this happens, contact your doctor immediately.

SEE YOUR DOCTOR IMMEDIATELY:

- Severe skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), multiform erythema, 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 medication, talk to your doctor

• If you have ever developed a severe skin rash or peeling, blisters, or mouth sores after taking valproate.

Use of Acido Valproico Altan with other medications

Inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription, homeopathic, herbal, or other health-related products, as it may be necessary to discontinue treatment or adjust the dose of one or more of them.

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

• Products containing estrogens (including some birth control pills).
• Neuroleptics (medications used to treat mental disorders).
• Medications used to treat depression.
• Benzodiazepines (medications used to sleep or treat anxiety).
• Olanzapine and quetiapine (medications used to treat mental disorders).
• Other medications 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 with topiramate has been associated with encephalopathy and/or hyperammonemia (brain and nervous system disorder that occurs as a complication of liver disorders with or without increased blood ammonia levels).
• Zidovudine (medication used to treat HIV and AIDS).
• Mefloquine (medication used to treat or prevent malaria).
• Salicylates (aspirin). See also "Warnings and precautions – Children under 3 years old".
• Anticoagulants (medications used to prevent blood clotting).
• Cimetidine (medication used to treat stomach ulcers).
• Erythromycin and rifampicin (antibiotics).
• Rufinamide.
• Acetazolamide.
• Inhibitors of protease, such as lopinavir, ritonavir (used to treat HIV).
• Colestiramine.
• Propofol (anesthetic).
• Metamizol (medication used to treat pain and fever).
• Clozapine (for treating mental health disorders)

Valproic acid may increase the effects of Nimodipino (medication used to treat hypertension, angina, and vascular disorders).

The activity of these and other medications may be affected by valproic acid, or they may directly affect the activity of valproic acid. You may need different doses of medication or take different medications. Your doctor or pharmacist will advise you.

Inform your doctor or nurse if you are using any of the following medications:

Carbapenem agents (antibiotics used to treat bacterial infections). The combination of valproic acid and carbapenem antibiotics should be avoided because it reduces the effect of valproic acid.

Use of Ácido Valproico Altan with food, drinks, and alcohol

Do not consume alcoholic beverages.

Pregnancy, breastfeeding, and fertility

Pregnancy

Consult your doctor or pharmacist before using any medication.

Important warning for women

• Do not use valproic acid if you are pregnant, unless no other treatment works.
• If you are a woman of childbearing age, do not take valproic acid unless you use an effective method of birth control (contraception) throughout your treatment with valproic acid. Do not stop taking valproic acid or your contraceptive until you have talked to 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. The higher the dose, the greater the risk, but all doses have a risk, even when valproate is used in combination with other medications to treat epilepsy.
• It may cause severe birth defects and may affect how the child develops and grows. Notified birth defects includespina bifida(where the spinal vertebrae do not develop properly); malformations of the skull and face, heart, kidney, urinary system, reproductive organs, and limb defects.There have been reports of hearing or deafness problems in children exposed to valproate during pregnancy.
• 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 taking valproate, about 10 out of 100 babies will have birth defects. In comparison, 2-3 out of 100 babies born to women without epilepsy will have birth defects.
• It is estimated that up to 30-40% of preschool children whose mothers took valproate during pregnancy may have developmental problems in childhood. Affected children may speak and walk slowly, be intellectually less capable than other children, and have language and memory difficulties.
• Children exposed to valproate are more likely to be diagnosed with autism spectrum disorders and there is some evidence that these children may develop symptoms ofAttention Deficit Hyperactivity Disorder (ADHD)
• Before prescribing this medication, your doctor will have explained to you that your baby may be affected if you become pregnant while taking valproate. If you decide later that you want to have a baby, do not stop taking your medication or your contraceptive until you have talked to your doctor.
• If you are a father or caregiver of a girl being treated with valproate, contact your doctor when your daughter in treatment with valproate reaches menarche (first menstruation).
• Some birth control pills (birth control pills containing estrogens) may decrease valproate blood levels. Make sure to talk to your doctor about the best birth control method for you.
• Consult your doctor about taking folic acid while trying to have a baby. Folic acid may reduce the risk ofspina bifidaand early miscarriage that exist in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.

Choose and read the situations that affect you from the following:

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

I AM STARTING TREATMENT WITH VALPROIC ACID

If this is the first time you have been prescribed valproic acid, your doctor will have explained the risks to your baby if you become pregnant. Once you are of childbearing age, you will need to ensure the use of an effective method of birth control (contraception) without interruption throughout your treatment with valproic acid. Consult your doctor or family planning clinic if you need advice on contraception.

Important messages:

• You must exclude pregnancy before starting treatment with valproic acid, by the result of a pregnancy test, confirmed by your doctor.
• You must use an effective method of birth control (contraception) throughout your treatment with valproic acid.
• You must talk to your doctor about the best birth control method (contraception). Your doctor will give you information on how to prevent pregnancy and may refer you to a specialist to advise you on birth control.
• You must have regular consultations (at least annually) with a specialist experienced in treating epilepsy. During this visit, your doctor will ensure that you know and understand all the risks and warnings related to the use of valproate during pregnancy.
• Inform your doctor if you want to have a baby.
• Inform your doctor immediately if you are pregnant or think you may be pregnant.

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

If you continue treatment with valproic acid but do not plan to have a baby, make sure to use an effective method of birth control (contraception) without interruption throughout your treatment with valproic acid. Consult your doctor or family planning clinic if you need advice on contraception.

Important messages:

• You must use an effective method of birth control (contraception) throughout your treatment with valproic acid.
• You must 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 to advise you on birth control.
• You must have regular consultations (at least annually) with a specialist experienced in treating epilepsy. During this visit, your doctor will ensure that you know and understand all the risks and warnings related to the use of valproate during pregnancy.
• Inform your doctor if you want to have a baby.
• Inform your doctor immediately if you are pregnant or think you may be pregnant.

I AM TAKING VALPROIC ACID AND INTEND TO HAVE A BABY

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

Do not stop takingvalproic acidor your contraceptive until you have talked to 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 experienced in treating epilepsy to evaluate alternative treatment options.

Your specialist may decide to change your valproic acid dose or switch to another medication, or stop your treatment with valproic acid well before you become pregnant – to ensure that your underlying disease is stable.

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

Important messages:

• Do not stop taking valproic acid unless your doctor tells you to.
• Do not stop using your contraceptive methods until you have talked to your doctor and worked 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 understand 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 your treatment with valproic acid well 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 TAKING VALPROIC ACID

• Do not stop taking valproic acid 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 experienced in treating epilepsy to evaluate alternative treatment options.

In exceptional circumstances, when valproic acid is the only treatment option during pregnancy, it will be closely monitored, both for the management of your underlying disease and for checking how the fetus is developing. You and your partner may receive counseling and support regarding pregnancy exposure to valproate.

Consult your doctor about taking folic acid. Folic acid may reduce the general risk ofspina bifidaand early miscarriage that exist in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with valproate use.

Important messages:

• Schedule an urgent appointment with your doctor if you are pregnant or think you may be pregnant.
• Do not stop taking valproic acid unless your doctor tells you to.
• Make sure you are referred to a specialist in prenatal monitoring to detect possible malformations.
• Make sure you receive counseling about the risks of valproate during pregnancy, including teratogenicity and developmental effects in children.

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

Important information for male patients

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

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

As a precaution, your doctor will talk to you:

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

or The need to consider effective contraceptive methods for you and your female partner during treatment and for 3 months after stopping treatment.

or The need to consult your doctor when planning to conceive a child and before stopping contraception.

or The possibility of using other treatments to treat your disease, 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 female partner becomes pregnant while you were taking valproate in the 3 months before 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 must have regular appointments with your doctor. During this visit, your doctor will talk to you about the precautions associated with valproate use 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. You will also receive a Patient Card from your pharmacist to remind you of the potential risks of valproate.

In babies born to mothers who have taken valproic acid during pregnancy, there may also be:

• Problems with blood clotting due to partial or complete lack of some substances necessary for blood clotting. In the latter case, the problem can be fatal, so in the newborn, specific blood tests and coagulation tests should be performed.
• Low blood sugar in newborns of mothers who took valproic acid during pregnancy.
• There have been reports of hypothyroidism in newborns of mothers who took valproate during pregnancy.
• A withdrawal syndrome (such as agitation, irritability, hyperexcitability, nervousness, hyperkinesia, muscle tone disorders, tremors, seizures, and feeding disorders) may appear in newborns whose mothers took valproate during the last trimester of pregnancy.

Breastfeeding

Consult your doctor or pharmacist before using any medication.

Valproate passes into breast milk. However, the amounts of valproate that pass into breast milk are small, and therefore, treatment with valproic acid during breastfeeding does not generally pose a risk to the infant, and it is usually not necessary to stop breastfeeding. However, you should consult your doctor about the advisability of continuing or stopping breastfeeding, taking into account the safety profile of valproic acid, especially blood disorders (see "Possible side effects").

Driving and operating machinery:

Valproic acid may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may decrease your reaction time. These effects, as well as your underlying disease, may impair your ability to drive vehicles or operate machinery. Therefore, do not drive, operate machinery, or engage in other activities that require special attention until your doctor assesses your response to this medication.

Important information about some of the components of Acido Valproico 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 daily sodium intake recommended for an adult.

Girls and women of childbearing age

The treatment withAltan Valproic Acidshould be initiated and supervised by a specialized doctor in the treatment of epilepsy.

Male patients

It is recommended that Altan Valproic Acidbe initiated and supervised by an experienced specialist in the treatment of epilepsy - see section 2 Important information for male patients

Follow exactly the medication administration instructions contained in this leaflet or those indicated by your doctor or nurse. If in doubt, ask your doctor or nurse.

Altan Valproic Acid should be administered under the supervision of a doctor. Normally, it will be administered by a doctor or a nurse (under medical supervision).

Your doctor will decide on the most suitable dose of Altan Valproic Acid. Make sure to perform regular check-ups with your doctor.

Altan Valproic Acid is prescribed on an individual basis and for a specific situation. The doses recommended in this leaflet are indicative. The doses ofAltan Valproic Acid are established according to body weight, your specific situation, and the doctor's prescription 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 oral treatment initiated, Altan Valproic Acid will be administered in continuous infusion, 4 to 6 hours after oral intake, following the same established dosing regimen, at a rate of infusion between0.5 and 1 mg/kg/h. In the rest of 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 liver insufficiency: Altan Valproic Acid 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 body weight, administered by intravenous infusion. Oral therapy should replace intravenous therapy as soon as possible.

IN NO CASE WILL THIS MEDICINE BE ADMINISTERED BY ANY OTHER ROUTE THAN INTRAVENOUS.

The dose is always adjusted individually, according to the response of each patient.

If you use more Altan Valproic Acid than you should

If this medicine 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 unsure why you are being given a dose of medicine.

A overdose of Altan Valproic Acid can be dangerous. Among the symptoms of intoxication 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 cardio-respiratory monitoring will be performed. In some cases, hypotension, miosis, cardiovascular and respiratory alterations, circulatory collapse/shock, metabolic acidosis, hypocalcemia, and hypernatremia have also been observed. Cases of death after massive overdose have been reported; however, a favorable outcome is usually the case.

However, symptoms may 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 the presentations with valproate may lead to hypernatremia in the event of an overdose.

It is recommended to bring the packaging and the leaflet of the medicine 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 medicine and the amount ingested.

If you forgot to use Altan Valproic Acid

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment withAltan Valproic Acid

Stopping treatment with Altan Valproic Acid without explicit indication from your doctor may be harmful to you, as seizures may be triggered with severe consequences.

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

Like all medications, this medication may cause side effects, although not everyone will experience them.

Inform your doctor immediately if any of the following severe side effects occur, as you may need urgent medical attention:

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

? Confusion caused by a decrease in blood sodium levels or a condition called Syndrome of Inadequate Antidiuretic Hormone Secretion (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 stomach, nausea, ictericia (yellowing of the skin or white of the eyes), swelling of the legs or worsening of epilepsy or general feeling of discomfort. These may be symptoms of severe liver and pancreas disorders.

? Allergic reactions that may manifest as:

•Blisters with skin detachment (blisters, peeling, or bleeding in any part of the skin, including lips, eyes, mouth, nose, genitals, hands, or feet) with or without rash, with symptoms sometimes similar to the flu such as fever, chills, or muscle pain - these may 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 in some cases, hands, and feet) - these may be symptoms of 'angioedema'.

•Syndrome involving rash on the skin, fever, enlargement of lymph nodes, and possible failure of other organs - these may be signs of a condition called 'DRESS' or 'drug reaction with eosinophilia and systemic symptoms'.

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

? Blisters with skin detachment.

? Severe decrease in white blood cells or bone marrow insufficiency that appears in blood tests, which may manifest with fever and difficulty breathing.

? Hypoactive thyroid gland, which may cause fatigue or weight gain (hypothyroidism).

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

? Agitation (tremor), uncontrollable muscle contractions, instability while walking (parkinsonism, extrapyramidal disorder, ataxia).

? Muscle pain and muscle weakness (rhabdomyolysis).

? Kidney disease (renal insufficiency, tubulointerstitial nephritis, and Fanconi syndrome) that may manifest as reduced urine output.

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

The very common side effects that may affect more than 1 in 10 patients are:

?Nervous system disorders: tremor.

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

The common side effects that may affect up to 1 in 10 patients are:

?Blood and lymphatic system disorders: reduction in red blood cells (anemia) and reduction in platelets (thrombocytopenia).

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

?Renal and urinary disorders: incontinence.

?Auditory disorders: hearing problems or deafness.

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

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

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

?Vascular disorders: hemorrhage.

?Hepatobiliary disorders: liver damage.

?Reproductive system and breast 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 uncommon side effects that may affect up to 1 in 100 patients are:

?Blood and lymphatic system disorders: pancytopenia (scarcity of blood components) and decrease in white blood cells in blood (leucopenia).

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

?Respiratory disorders: accumulation of fluid between the layers of tissue that cover the lungs and the thoracic cavity (pleural effusion).

?Renal and urinary disorders: renal insufficiency.

?Gastrointestinal disorders: pancreatitis that may 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: bone alterations, including osteopenia and osteoporosis (bone decalcification) and fractures. Consult your doctor or pharmacist if you are on long-term antiepileptic treatment, have a history of osteoporosis, or take steroids.

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

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

?General disorders: peripheral edema (non-serious swelling of ankles, feet, and legs), low body temperature.

?Reproductive system and breast disorders: irregular menstruation or absence of menstruation (amenorrhea).

?Difficulty breathing, chest pain (especially when inhaling), difficulty breathing, and dry cough due to fluid accumulation around the lungs (pleural effusion)

The rare side effects that may affect up to 1 in 1,000 patients are:

?Blood and lymphatic system disorders: bone marrow insufficiency including pure red cell aplasia (cessation or reduction of red blood cell production. This causes severe anemia, among whose symptoms are unusual fatigue and lack of energy), agranulocytosis (decrease in white blood cells), decrease in red blood cells with larger-than-normal size (macrocyclic anemia, macrocytosis).

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

?Nervous system disorders: worsening of mental function causing confusion and changes in intellect or reasoning (reversible dementia), disorder of knowledge, double vision.

?Renal disorders: involuntary urination (enuresis), tubulointerstitial nephritis, excessive elimination of certain compounds through urine (Fanconi syndrome) leading to dehydration due to urinating more frequently.

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

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

?Endocrine disorders: hypothyroidism.

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

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

?Reproductive system and breast 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 side effects of unknown frequency (cannot be estimated from available data) are:

?Genetic and congenital disorders: autism spectrum disorders, congenital malformations, and developmental disorders.

?Investigations: false positives in urine ketone elimination test in diabetic patients.

?Darker skin areas and mucous membranes (hyperpigmentation)

Side effects in children

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

Reporting of side effects

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

Keep this medication out of the 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°Cwithin 24 hours.

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

Medicines should not be disposed of through drains or in the trash.Ask your pharmacist how to dispose ofthe packaging and the medications you no longerneed.This will help protect the environment.

Composition of Valproic Acid Altan

-The active ingredient is sodium valproate.

Aspect of the product and contents of the package

Valproic Acid Altan contains 1 vial of lyophilized powder.

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

Once the powder is reconstituted, the solution contains a concentration of 95 mg/ml.

Holder of the marketing authorization and responsible for manufacturing:

Holder of the marketing authorization

Altan Pharmaceuticals, S.A.

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

Edificio Prisma

28230 - Las Rozas (Madrid)

Spain

Responsible for manufacturing:

Altan Pharmaceuticals, S.A

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

45950 - Casarrubios del Monte (Toledo)

Spain

Last review date of this leaflet: January 2025

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es

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This information is intended solely for doctors or healthcare professionals:

The daily dose should be adjusted according to age and body weight; while also taking into account the wide individual variability of sensitivity to valproic acid.

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

The recommended daily dose to administer valproic acid is:

Adolescents (≥ 12 years) and adults (≥ 18 years): In patients treated orally, Altan Valproic Acid will be administered in continuous perfusion, 4 to 6 hours after oral intake, following the same established dosing regimen, at a perfusion rate of 0.5 to 1 mg/kg/h. In the rest of 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 perfusion 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.

Patients over 65 years old: 15-20 mg/kg.

Patients with renal insufficiency

In patients with renal insufficiency, it may be necessary to reduce 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 monitored by an experienced specialist in the management of epilepsy. Altan Valproic Acid should not be used in girls or women of childbearing age, unless other treatments are ineffective or not tolerated.

Valproate should be prescribed and dispensed in accordance with the Valproate 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 WILL ALTAN VALPROIC ACID BE ADMINISTERED BY A ROUTE OTHER THAN INTRAVENOUS.

The preparation should be reconstituted by injecting the solvent into the vial, waiting for it to dissolve, and then extracting the desired amount.

Given the displacement of the solvent by valproic acid, the concentration of the reconstituted preparation will be 95 mg/ml.

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

Altan Valproic Acid should be administered by slow intravenous injection (3 min) or by perfusion. If other substances are being administered by perfusion, do not use the same route.