Valproic acid Altan 400 mg powder for solution for injection EFG: detailed information

Package leaflet: Information for the user

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 quicker detection of new safety information. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions is included at the end of section 4.

WARNING

Valproic Acid Altan, in the form of sodium valproate, may seriously harm the fetus when taken during pregnancy. If you are a woman of childbearing potential, you must use an effective method of contraception (birth control) continuously during treatment with Valproic Acid Altan. Your doctor will discuss this with you, but you should also follow the warning in section 2 of this leaflet.

Schedule an urgent appointment with your doctor if you wish to become pregnant or if you think you are pregnant.

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

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

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

Contents of the leaflet

What Valproic Acid Altan is and what it is used for
What you need to know before using Valproic Acid Altan
How to use Valproic Acid Altan
Possible adverse effects
How to store Valproic Acid Altan
Contents of the pack and other information

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

This medicine belongs to a group of medicines called antiepileptics. It is indicated in the treatment of generalized or partial epilepsies in adults and children.

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

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

Do not use Valproic Acid 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 inform your doctor. (listed in section 6)
You must not use Valproic Acid Altan if you are pregnant, unless no other treatment is effective.
If you are a woman of childbearing potential, you must 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 discussed this with your doctor. Your doctor will advise you (see below under “Pregnancy, breastfeeding and fertility – Important warning for women”).
If you currently have any liver or pancreas disease.
If you have previously had any liver disease.
If any of your close relatives have a history of serious liver disease (hepatitis), mainly caused by medications.
If there is a family history of death due to impaired liver function during treatment with sodium valproate.
If you have liver porphyria (a very rare type of metabolic disorder).
If you have a genetic disorder causing a mitochondrial disorder (e.g., Alpers-Huttenlocher syndrome).
If you have a known metabolic disorder, such as a urea cycle disorder.
If you have untreated carnitine deficiency (a very rare metabolic disease).

If you think you may have any of these problems or if you have any doubts, consult your doctor before taking 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 taking other antiepileptic medicines simultaneously, or in those with other neurological or metabolic disorders and severe forms of epilepsy.

Your doctor should check your liver function tests before starting treatment and periodically during the first 6 months, especially in at-risk patients.

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

If you or your child taking valproate develops problems with balance and coordination, feelings of lethargy or reduced alertness, or vomiting, inform your doctor immediately. This may be due to increased blood ammonia levels.

A small number of people who have been treated with antiepileptic medicines such as valproic acid have had thoughts of self-harm or suicide. If you have such thoughts at any time, contact your doctor immediately.

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

Before taking this medicine, consult your doctor

If you know or your doctor suspects a genetic disorder due to a mitochondrial disorder in your family, due to the risk of liver damage.
If a metabolic disorder is suspected, particularly inherited enzyme deficiencies such as a “urea cycle disorder,” due to the risk of increased blood ammonia levels.
If you have a rare disorder called “carnitine palmitoyl transferase type II deficiency,” because you are at higher risk of muscle disorders.
If you have an altered dietary intake of carnitine, found in meat and dairy products, especially in children under 10 years of age.
If you have carnitine deficiency and are taking carnitine supplements.
If you have impaired kidney function or hypoproteinemia (decreased levels of proteins in the blood). In this case, your doctor may wish to monitor your blood valproate levels or adjust the dose.
The concomitant administration of Valproic Acid Altan to children under 3 years of age with acetylsalicylic acid (aspirin) should be avoided.
If you have systemic lupus erythematosus.
If you have blood disorders (blood coagulation or thrombocytopenia). A blood test (complete blood count) is recommended before starting treatment, before any surgical procedure, and in cases of spontaneous bruising or bleeding.
If weight gain occurs at the beginning of treatment.
As with other antiepileptic medicines, seizures may worsen or occur more frequently while using this medicine. If this happens, contact your doctor immediately.
If you have ever developed a serious skin rash, peeling, blisters, and/or mouth sores after taking valproate.

Use of Valproic Acid Altan with other medicines

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

Some medicines may alter the effect of 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 for sleep or to treat anxiety).
Olanzapine and quetiapine (medicines used to treat psychiatric disorders).
Other medicines used to treat epilepsy, including phenobarbital, phenytoin, primidone, lamotrigine (the risk of developing a serious skin rash may increase when lamotrigine and valproic acid are taken together), carbamazepine, ethosuximide, felbamate, and topiramate. Concomitant administration of Valproic Acid Altan with topiramate has been associated with encephalopathy and/or hyperammonemia (a brain and nervous system disorder occurring as a complication of liver disorders with or without increased blood ammonia).
Zidovudine (a medicine used to treat HIV and AIDS infections).
Mefloquine (a medicine used to treat or prevent malaria).
Salicylates (aspirin). See also “Warnings and precautions – Children under 3 years of age”.
Anticoagulants (medicines used to prevent blood clots).
Cimetidine (a medicine used to treat stomach ulcers).
Erythromycin and rifampicin (antibiotics).
Rufinamide.
Acetazolamide.
Protease inhibitors, such as lopinavir, ritonavir (used for the treatment of HIV).
Cholestyramine.
Propofol (an anesthetic).
Metamizole (a medicine used to treat pain and fever).
Cannabidiol (used to treat epilepsy and other conditions).
Methotrexate (used to treat cancer and inflammatory diseases).
Some anti-infectives containing pivalate (e.g., pivampicillin, adefovir dipivoxil).
Clozapine (for treating mental health conditions).

Valproic Acid Altan may increase the effects of nimodipine (a medicine used in the treatment of hypertension, angina pectoris, and blood vessel disorders).

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

Use of Valproic Acid Altan with food, drinks, and alcohol

Do not consume alcoholic beverages.

Pregnancy, breastfeeding and fertility

Pregnancy

Consult your doctor or pharmacist before using any medicine.

Important warning for women

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

Risks of valproate when taken during pregnancy:

Speak to your doctor immediately if you are planning to have a baby or if you are pregnant.
Valproate carries a risk when taken during pregnancy. With higher doses, the risk is greater, but all doses carry a risk, even when valproate is used in combination with other medicines to treat epilepsy.
It may cause serious birth defects and may affect how the child develops and grows. Reported birth defects include spina bifida (where the bones of the spine do not develop properly); malformations of the skull and face, heart, kidneys, urinary tract, genitals, limb defects, and multiple malformations affecting several organs and body parts. Birth defects may result in disabilities that can be severe.
Hearing problems or deafness have been reported in children exposed to valproate during pregnancy.
Ocular malformations have been reported in children exposed to valproate during pregnancy, often in association with other congenital malformations. These eye malformations may affect vision.
If you take valproate during pregnancy, you have a higher risk than other women of having a baby with birth defects requiring medical treatment. As valproate has been used for many years, it is known that approximately 10 out of every 100 babies born to women taking valproate will have birth defects. This compares with 2–3 out of every 100 babies born to women who do not have epilepsy.
It is estimated that up to 30–40% of preschool-aged children whose mothers took valproate during pregnancy may experience developmental problems in childhood. Affected children may speak and walk slowly, have lower intellectual capacity than other children, and experience language and memory difficulties.
Autism spectrum disorders are diagnosed more frequently in children exposed to valproate, and there is some evidence these children may develop symptoms of Attention Deficit Hyperactivity Disorder (ADHD).
Before prescribing this medicine, your doctor will have explained what could happen to your baby if you become pregnant while taking valproate. If you later decide you want to have a baby, you must not stop taking your medicine or your contraception until you have discussed it with your doctor.
If you are a parent or caregiver of a girl being treated with valproate, you should contact your doctor when the girl treated with valproate reaches menarche (first menstruation).
Some contraceptive pills (oral contraceptives containing oestrogen) may reduce blood levels of valproate. Be sure to discuss with your doctor the most appropriate contraceptive method (birth control) for you.
Consult your doctor about taking folic acid while trying to conceive. Folic acid may reduce the general risk of spina bifida and early miscarriage that exist in all pregnancies. However, it is unlikely to reduce the risk of birth defects associated with the use of valproate.

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

I AM STARTING TREATMENT WITH VALPROIC ACID ALTAN
I AM TAKING VALPROIC ACID ALTAN AND DO NOT INTEND TO HAVE A BABY
I AM TAKING VALPROIC ACID ALTAN AND INTEND TO HAVE A BABY
I AM PREGNANT AND 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 reach childbearing age, you will need to ensure uninterrupted use of an effective contraceptive method throughout your treatment with Valproic Acid Altan. Speak to your doctor or family planning clinic if you need advice on contraception.

Important messages:

Pregnancy must be ruled out before starting treatment with Valproic Acid Altan, confirmed by a pregnancy test result reviewed by your doctor.
You must use an effective method of birth control (contraception) throughout treatment with Valproic Acid Altan.
You must discuss appropriate birth control methods (contraception) with your doctor. Your doctor will provide information on how to prevent pregnancy and may refer you to a specialist for contraceptive advice.
You must have regular consultations (at least annually) with a specialist experienced in treating epilepsy. During this visit, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Inform your doctor if you wish to have a baby.
Contact your doctor immediately if you are pregnant or think you may be pregnant.

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

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

Important messages:

You must use a method of birth control (contraception) throughout treatment with Valproic Acid Altan.
You must discuss contraception (birth control) with your doctor. Your doctor will provide information on how to prevent pregnancy and may refer you to a specialist for contraceptive advice.
You must have regular consultations (at least annually) with a specialist experienced in treating epilepsy. During this visit, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Inform your doctor if you wish to have a baby.
Inform your doctor immediately if you are pregnant or think you may be pregnant.

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

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

Do not stop taking Valproic Acid Altan or your contraceptive method until you have discussed it with your doctor. Your doctor will advise you.

Babies born to mothers treated with valproate have significant risks of birth defects and developmental problems that may be severely disabling. Your doctor will refer you to a specialist experienced in treating epilepsy so that alternative treatment options can be evaluated from the outset. Your specialist may take several steps to ensure your pregnancy proceeds as safely as possible and that risks to you and the fetus are minimized.

Your specialist may decide to adjust the dose of Valproic Acid Altan, switch you to another medicine, or discontinue Valproic Acid Altan well before conception—to ensure your condition is stable.

Consult your doctor about taking folic acid when trying to conceive. Folic acid may reduce the general risk of spina bifida and early miscarriage that occur 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 contraceptive methods (contraception) before discussing it with your doctor and developing a plan together to ensure your condition is controlled and risks to your baby are minimized.
First, schedule an appointment with your doctor. During this visit, your doctor will ensure you understand all risks and warnings related to valproate use during pregnancy.
Your doctor will try to switch you to another medicine or discontinue Valproic Acid Altan well before conception.
Schedule an urgent appointment with your doctor if you are pregnant or think you may be pregnant.

I AM PREGNANT AND TAKING VALPROIC ACID ALTAN

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

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

Your doctor will refer you to a specialist experienced in treating epilepsy so that alternative treatment options can be evaluated.

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

Consult your doctor about taking folic acid. Folic acid may reduce the general risk of spina bifida and early miscarriage 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 Altan unless your doctor tells you to.
Ensure you are referred to a specialist experienced in treating epilepsy to evaluate the need for alternative treatment options.
You must receive counselling on the risks of Valproic Acid Altan during pregnancy, including teratogenicity and developmental effects in children.
Ensure you are referred to a specialist in prenatal monitoring to detect possible malformations.

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

In newborn babies of mothers who took Valproic Acid Altan during pregnancy also:

Bleeding disorders may occur due to partial or complete lack of certain blood clotting factors. In the latter case, the condition may be fatal; therefore, blood tests and specific coagulation tests should be performed in the newborn.
Hypoglycaemia may occur in newborns of mothers who took Valproic Acid Altan during pregnancy.
Cases of neonatal hypothyroidism have been reported in babies born to mothers who took valproate during pregnancy.
A withdrawal syndrome (including agitation, irritability, hyperexcitability, nervousness, hyperkinesia, muscle tone disorders, tremor, seizures, and feeding difficulties) may occur in neonates whose mothers took valproate during the last trimester of pregnancy.

Breastfeeding

Consult your doctor or pharmacist before using any medicine.

Sodium valproate 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 breastfeeding generally does not pose a risk to the infant and breastfeeding usually does not need to be discontinued. Nevertheless, you should consult your doctor on whether to continue or discontinue breastfeeding, taking into account the safety profile of Valproic Acid Altan, especially blood disorders (see section “Possible side effects”).

Important information for male patients

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

One study suggests a possible risk of motor and mental developmental disorders (problems with childhood development) in children born to fathers treated with valproate in the 3 months before conception. In this study, about 5 out of every 100 children had such disorders when born to fathers treated with valproate, compared to about 3 out of every 100 children when born to fathers treated with lamotrigine or levetiracetam (other medicines that may be used to treat your condition). The risk for children born to fathers who stopped valproate treatment 3 months (the time needed to form new sperm) or more before conception is unknown. The study has limitations, so it is unclear whether the increased risk of motor and mental developmental disorders suggested by this study is caused by valproate. The study was not large enough to determine the specific type of motor and mental developmental disorders the children might develop.

As a precautionary measure, your doctor will discuss with you:

The potential risk in children born to fathers treated with valproate.
The need to consider effective contraceptive methods (birth control) for you and your female partner during treatment and for 3 months after stopping treatment.
The need to consult your doctor when planning to conceive a child and before stopping contraception (birth control).
The possibility of using alternative treatments for your condition, depending on your individual situation.

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

Talk to your doctor if you are considering having a child.

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

You should attend regular appointments with your doctor. During these visits, your doctor will discuss precautions associated with valproate use and the possibility of alternative treatments for your condition, depending on your individual situation.

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

Driving and use of machines:

Valproic acid may cause symptoms such as drowsiness, dizziness or visual disturbances, and may reduce reaction ability. These effects, as well as the disease itself, may impair your ability to drive or operate machinery. Therefore, do not drive, operate machinery, or engage in other activities requiring special attention until your doctor has assessed your response to this medicine.

Important information about some of the components of Valproic Acid Altan

Patients on low-sodium diets should be aware that this medicine contains 55.33 mg (2.41 mmol) of sodium per vial. This corresponds 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 physician specialized in the treatment of epilepsy.

Male patients

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

Follow exactly the instructions for administration of the medicine provided in this leaflet or those given by your doctor or nurse. If in doubt, ask your doctor or nurse.

Valproic Acid Altan must be administered under medical supervision. It is usually administered by a doctor or nurse (under medical supervision).

Your doctor will determine the most appropriate dose of Valproic Acid Altan. Make sure to attend your scheduled periodic check-ups with your doctor.

Valproic Acid Altan is prescribed individually and for a specific condition. The recommended doses in this leaflet are only guidelines. Doses of Valproic Acid Altan are established according to body weight, your individual condition, and the prescribing physician's judgment.

? 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 already receiving oral treatment, Valproic Acid Altan will be administered as a continuous infusion, 4 to 6 hours after the oral dose, following the same established dosing regimen, at an infusion rate between 0.5 and 1 mg/kg/h. In all other patients, administer the preparation as a slow injection (3–5 minutes) at a dose of 15 mg/kg of body weight, followed 30 minutes later by 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 impairment: Valproic Acid Altan must not be administered to patients with severe liver disease.

? Patients with renal impairment: Lower doses may be required in these patients.

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.

Patients with renal problems

Your doctor may decide to adjust your dose.

UNDER NO CIRCUMSTANCES SHOULD THIS MEDICINE BE ADMINISTERED BY ANY ROUTE OTHER THAN INTRAVENOUS.

The dose is always adjusted individually, depending on each patient's response.

If you use more Valproic Acid Altan than you should

If this medicine is administered by a doctor or nurse (under medical supervision), it is unlikely that you will receive more than you should. They will monitor your progress. Always ask if you are unsure why you are receiving a particular dose.

An overdose of Valproic Acid can be dangerous. Symptoms of poisoning include confusion, sedation, or even coma with hypotonia, muscle weakness, and absent reflexes. Therefore, go immediately to the nearest hospital, where your symptoms will be treated and cardiorespiratory monitoring will be performed. In some cases, hypotension, miosis, cardiovascular and respiratory disturbances, circulatory collapse/shock, metabolic acidosis, hypocalcemia, and hypernatremia have also been observed. Fatal outcomes have occurred after massive overdoses; however, a favorable outcome is more common.

Nevertheless, symptoms may vary, and seizures have been reported in the presence of very high plasma levels. Cases of intracranial hypertension associated with cerebral edema have been reported.

The presence of sodium in formulations containing valproate may lead to hypernatremia in cases of overdose.

It is recommended to bring the medicine packaging and leaflet to the healthcare professional.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately, or call the Toxicology Information Service at: 91.562.04.20, indicating the medicine 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 stop using Valproic Acid Altan

Abruptly stopping treatment with Valproic Acid without explicit instruction from your doctor may be harmful to you, as it could trigger seizure episodes with serious consequences.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Immediately inform your doctor if any of the following serious adverse reactions occur, as you may require urgent medical attention:

? Drowsiness, change in level of consciousness (including coma), confusion, slow or abnormal behavior, and memory loss, with or without increased frequency or severity of seizures, particularly if you are taking phenobarbital or topiramate (medicines used to treat seizures) at the same time, or if the dose of Valproic Acid Altan has been increased suddenly.

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

? Problems with balance and coordination, feeling lethargic or less alert, associated with vomiting. This may be due to 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 abdomen, nausea, jaundice (yellowing of the skin or whites of the eyes), swelling of the legs, worsening of epilepsy, or feeling generally unwell. These may be symptoms of serious liver or pancreatic disorders.

? Allergic reactions that may present as:

Blisters with skin peeling (blisters, skin shedding, or bleeding on any part of the skin (including lips, eyes, mouth, nose, genitals, hands or feet), with or without rash, sometimes accompanied by flu-like symptoms such as fever, chills, or muscle pain – these may be signs of conditions called 'toxic epidermal necrolysis' or 'Stevens-Johnson syndrome').
Allergic swelling with painful, itchy hives (often around the eyes, lips, throat, and sometimes hands and feet) – these may be symptoms of “angioedema”.
A syndrome involving skin rash, fever, swollen lymph nodes, and possible failure of other organs – these may be signs of a condition called “DRESS” (Drug Reaction with Eosinophilia and Systemic Symptoms) or drug-induced rash with eosinophilia and systemic symptoms.

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

? Severe decrease in white blood cells or bone marrow failure detected in blood tests, sometimes presenting with fever and breathing difficulties.

? Underactive thyroid gland, which may cause tiredness or weight gain (hypothyroidism).

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

? Agitation (tremor), uncontrollable muscle contractions, unsteadiness when walking (parkinsonism, extrapyramidal disorder, ataxia).

? Muscle pain and muscle weakness (rhabdomyolysis).

? Sedation, extrapyramidal disorders.

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

? Kidney disease (renal failure, tubulointerstitial nephritis, and Fanconi syndrome), which may present as reduced urine output.

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

The very common adverse effects, which may affect more than 1 in 10 patients, are:

? Nervous system disorders: tremor.

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

The common adverse effects, which may affect up to 1 in 10 patients, are:

? Blood disorders: reduction in red blood cells (anemia) and reduction in platelet count (thrombocytopenia).

? Nervous system disorders: involuntary movements (extrapyramidal disorders), stupor, drowsiness, seizures, memory impairment, headache, rapid and uncontrollable eye movements (nystagmus). Dizziness may occur a few minutes after intravenous injection and resolves spontaneously within a few minutes. In isolated cases or associated with increased seizure frequency during treatment, confusion has been reported, which improves after discontinuation or dose reduction.

? Renal and urinary disorders: urinary incontinence.

? Ear disorders: hearing problems or deafness.

? Gastrointestinal disorders: vomiting, gum problems (mainly hypertrophy), pain and swelling in the mouth, mouth ulcers and burning sensation in the mouth (stomatitis), upper abdominal pain and diarrhea. These commonly occur in some patients at the beginning of treatment and usually resolve within a few days without discontinuing treatment.

? Skin and subcutaneous tissue disorders: nail and nail bed abnormalities, hypersensitivity, hair loss (transient and/or dose-related).

? Metabolism and nutrition disorders: decreased blood sodium (hyponatremia), weight gain.

? Vascular disorders: bleeding.

? Hepatobiliary disorders: liver injury.

? Reproductive system disorders: painful menstruation (dysmenorrhea).

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

The uncommon adverse effects, which may affect up to 1 in 100 patients, are:

? Blood disorders: deficiency of blood components (pancytopenia) and decreased number of white blood cells in blood (leukopenia).

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

? Renal and urinary disorders: renal failure.

? Gastrointestinal disorders: pancreatitis, which may be fatal.

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

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

? Endocrine disorders: Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) (fluid retention and decreased levels of certain electrolytes in blood), hyperandrogenism (excessive hair growth, virilization, acne, male-pattern baldness, and/or increased androgens).

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

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

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

The rare adverse effects, which may affect up to 1 in 1,000 patients, are:

? Blood disorders: bone marrow failure including pure red cell aplasia (cessation or reduction in red blood cell production, leading to severe anemia with symptoms such as unusual tiredness and lack of energy), agranulocytosis (decreased number of white blood cells), decreased number of red blood cells with larger than normal size (macrocytic anemia, macrocytosis).

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

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

? Kidney disorders: involuntary urination (enuresis), tubulointerstitial nephritis, increased frequency of urination and thirst (Fanconi syndrome).

? Skin and subcutaneous tissue disorders: skin lesions with red spots, blisters, and even peeling, which may be severe (Stevens-Johnson syndrome), DRESS syndrome (severe skin reaction characterized by generalized rash, fever, swollen lymph nodes, blood abnormalities, and internal organ involvement).

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

? Endocrine disorders: hypothyroidism.

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

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

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

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

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

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

? Investigations: false positive results in urine ketone tests in diabetic patients.

? Decreased levels of carnitine (detected in blood or muscle tests).

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

Additional adverse effects in children

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

Reporting of adverse effects

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

5. Storage of Valproic Acid Altan.

Keep this medicine 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; if stored at 2–8°C, it must be used within 24 hours.

Do not use Valproic Acid Altan after the expiry date stated on the container. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their containers. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Valproic Acid Altan

The active substance is sodium valproate.

Appearance 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 400 mg of sodium valproate as the active substance.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder

Altan Pharmaceuticals, S.A.
C/ Cólquide no. 6. Portal 2, 1st floor, office 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 most recent review of this package leaflet: May 2025

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

This information is intended solely for 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 between daily dose, serum concentration, and therapeutic effect has not been established, the optimal dose should be determined primarily based on clinical response. When adequate seizure control is not achieved or adverse effects are suspected, in addition to clinical monitoring, measurement of plasma concentrations of valproic acid may be considered. The reported effective range is typically between 50–125 μg/ml (300–752 μmol/l).

The recommended daily dosage regimen for valproic acid is as follows:

Adolescents (≥12 years) and adults (≥18 years): In patients already receiving oral therapy, Valproic Acid Altan should be administered as a continuous infusion over 4 to 6 hours following the oral dose, following the same dosing schedule already established, at an infusion rate between 0.5 and 1 mg/kg/h. In all other patients, administer the preparation as a slow injection (3–5 minutes) at a dose of 15 mg/kg body weight, followed 30 minutes later by 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 impairment

In patients with renal impairment, dose reduction may be necessary, or dose adjustment may be required in patients undergoing hemodialysis. Valproate is dialyzable (see section 4.9). Dose adjustments should be made according to clinical monitoring of the patient (see section 4.4).

Girls and women of childbearing potential: Valproate should be initiated and supervised by a specialist experienced in the management of epilepsy. Valproic Acid Altan must not be used in girls or women of childbearing potential unless other treatments are ineffective or not tolerated.

Valproate must be prescribed and dispensed in accordance with the Valproate Pregnancy Prevention Programme (see sections 4.3 and 4.4).

Valproate should preferably be prescribed as monotherapy and at the lowest effective dose, ideally using prolonged-release formulations when possible. 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.

IN NO CASE SHOULD VALPROIC ACID ALTAN BE ADMINISTERED BY ANY ROUTE OTHER THAN INTRAVENOUS.

Reconstitute the preparation by injecting 4 mL of water for injections into the vial of powder, wait until dissolved, and then withdraw the desired amount.

The preparation must be reconstituted immediately before use, and infusion solutions containing valproic acid must be used within 24 hours. If the entire initial preparation is not used, the remaining portion must not be reused.

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