Dipromal

LEAFLET INCLUDED IN THE PACKAGE: INFORMATION FOR THE PATIENT

Dipromal, 200 mg, coated tablets

Magnesium valproate

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. To learn how to report side effects, see point 4.

WARNING

Dipromal, magnesium valproate used during pregnancy can harm the unborn child. Women of childbearing age should use effective contraception (birth control) without interruption throughout the treatment period with Dipromal. The treating doctor will discuss this with the patient, but the patient should also follow the recommendations presented in section 2 of this leaflet.
Patients should contact their treating doctor immediately if they plan to become pregnant or suspect they are pregnant.
Dipromal should not be discontinued unless advised by a doctor, as the patient's condition may worsen.

It is necessary to carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• The leaflet should be kept in case it needs to be read again.
• In case of any doubts, the patient should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for the patient. It should not be passed on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or pharmacist. See point 4.

Table of contents of the leaflet

• 1. What is Dipromal and what is it used for
• 2. Important information before taking Dipromal
• 3. How to take Dipromal
• 4. Possible side effects
• 5. How to store Dipromal
• 6. Contents of the package and other information

1. WHAT IS DIPROMAL AND WHAT IS IT USED FOR

Dipromal is a medicine used to treat various forms of epilepsy (the exact mechanism of anticonvulsant action is not fully understood, but it is believed to be related to the increased concentration of one of the substances involved in the process of conducting stimuli in the brain - gamma-aminobutyric acid) and mania.
Dipromal is used to treat:

• various forms of epilepsy, in particular:
• epilepsy with primarily generalized seizures (petit mal, grand mal);
• myoclonic epilepsy;
• photosensitive epilepsy;
• other forms of epilepsy - as a second-line drug, also in combination with other antiepileptic drugs (except phenobarbital);
• mania, which is a state in which the patient feels very excited, elated, stimulated, enthusiastic, or overactive. Mania occurs in a disease called bipolar affective disorder. Dipromal may be used when lithium cannot be used.

2. IMPORTANT INFORMATION BEFORE TAKING DIPROMAL

When not to take Dipromal

• if the patient is allergic to magnesium valproate or any of the other ingredients of this medicine (listed in point 6),
• if the patient has porphyria,
• if the patient or a family member has currently or has had in the past liver disease and/or severe liver or pancreatic disorders,
• if a sibling of the patient died from liver failure during treatment with magnesium valproate,
• if the patient has a genetic disorder causing mitochondrial disorders (e.g., Alpers-Huttenlocher syndrome).

Bipolar affective disorder

• In the case of bipolar affective disorder, Dipromal should not be used if the patient is pregnant.
• In the case of bipolar affective disorder, if the patient is of childbearing age, Dipromal should not be taken unless the patient uses effective contraception (birth control) throughout the treatment period with Dipromal. Dipromal or contraception should not be discontinued until discussed with a doctor. The treating doctor will provide further guidance.

Epilepsy

• In the case of epilepsy, Dipromal should not be used if the patient is pregnant, unless no other therapy is effective.
• In the case of epilepsy, if the woman is of childbearing age, Dipromal should not be taken unless the patient uses effective contraception (birth control) throughout the treatment period with Dipromal. Dipromal or contraception should not be discontinued until the patient discusses this with a doctor. The treating doctor will provide further guidance.

Warnings and precautions

Before starting treatment with Dipromal, the patient should discuss the following with their doctor or pharmacist:

• if there is a family history of mitochondrial disorders,
• if the patient has had bone marrow damage or has a history of bone marrow damage,
• if the patient has bleeding disorders, thrombocytopenia (significant decrease in platelet count), inherited enzyme deficiencies, kidney failure, hypoproteinemia (decreased protein in the blood), lupus erythematosus, brain damage, developmental delay, and/or inherited metabolic disorders,
• if the patient is to undergo surgery or dental procedures (the doctor should be informed that Dipromal is being taken before the procedure),
• if the patient has diabetes (the medicine may affect the results of tests for ketone bodies).

Particular caution should be exercised when using Dipromal

• in infants or children, especially when multiple antiepileptic drugs are used simultaneously,
• in children with multiple disabilities or adolescents with severe epilepsy,
• in children and adolescents of the female sex, women of childbearing age, and pregnant women,
• when laboratory tests reveal abnormalities that may indicate severe liver or pancreatic disorders - triple increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activity, prolonged prothrombin time, increased alkaline phosphatase activity, and bilirubin concentration, changes in blood protein levels (it may be necessary to discontinue the medicine),
• if the patient experiences vomiting, loss of appetite, abdominal pain, malaise, increased frequency of seizures, nosebleeds, localized or generalized edema, lethargy, apathy, drowsiness, decreased blood pressure (it is necessary to consult a doctor, as these symptoms may indicate severe liver damage or increased ammonia levels in the blood),
• if the patient experiences unexpected bleeding from mucous membranes or increased tendency to bruise (it is necessary to consult a doctor).

A small number of patients taking antiepileptic drugs containing magnesium valproate have thought about harming or killing themselves. If such thoughts occur, the patient should immediately contact their treating doctor.
Both before starting treatment with Dipromal and regularly during treatment (in children, every month for the first 6 months, every 3 months for the next 6 months, and every 4-6 months after 12 months of treatment), the patient should undergo medical examinations and blood tests.
Blood tests performed before starting treatment should include: complete blood count (including platelet count), coagulation parameters (prothrombin time, fibrinogen concentration), amylase activity in serum, AST, ALT, alkaline phosphatase, total bilirubin, protein, blood glucose, while tests during treatment, when there are no clinical abnormalities, complete blood count (including platelet count) and determination of liver aminotransferase activity, and every other test, coagulation tests.
In the case of a child, during the period between tests, parents/guardians should remain in regular telephone contact with the treating doctor - this will enable early detection of any adverse effects of treatment.
Treatment of mania in children and adolescents under 18 years of age:
Dipromal should not be used in children and adolescents under 18 years of age for the treatment of mania.

Other medicines and Dipromal

The patient should inform their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
It is particularly important to inform the doctor if the following medicines are taken simultaneously with Dipromal:

• other antiepileptic drugs;
• phenobarbital;
• phenytoin;
• primidone;
• medicines that may be toxic to the liver (e.g., paracetamol, antiviral drugs);
• medicines containing lithium;
• medicines that reduce blood clotting (e.g., acenocoumarol, warfarin);
• acetylsalicylic acid and its derivatives;
• mefloquine;
• cimetidine;
• erythromycin;
• carbamazepine;
• nimodipine;
• lamotrigine;
• zidovudine;
• codeine;
• ethosuximide;
• felbamate;
• barbiturate derivatives (e.g., allobarbital, cyclobarbital);
• benzodiazepine derivatives (e.g., diazepam, lorazepam);
• neuroleptic drugs (e.g., chlorpromazine, fluphenazine);
• antidepressant drugs (e.g., amitriptyline, fluoxetine);
• carbapenem antibiotics (used to treat bacterial infections): it is recommended to avoid simultaneous use of valproic acid and carbapenem antibiotics, as this may reduce the effectiveness of valproate.

Dipromal with food, drink, and alcohol

Dipromal should be taken with meals.
Alcohol should not be consumed during treatment.

Pregnancy, breastfeeding, and fertility

Pregnancy and breastfeeding: before using this medicine, the patient should consult a doctor.

Important advice for women

Bipolar affective disorder

• In the case of bipolar affective disorder, Dipromal should not be used if the patient is pregnant.
• In the case of bipolar affective disorder, if the patient is of childbearing age, Dipromal should not be taken unless the patient uses effective contraception (birth control) throughout the treatment period with Dipromal. Dipromal or contraception should not be discontinued until discussed with a doctor. The treating doctor will provide further guidance.

Epilepsy

• In the case of epilepsy, Dipromal should not be used if the patient is pregnant, unless no other therapy is effective.
• In the case of epilepsy, if the woman is of childbearing age, Dipromal should not be taken unless the patient uses effective contraception (birth control) throughout the treatment period with Dipromal. Dipromal or contraception should not be discontinued until the patient discusses this with a doctor. The treating doctor will provide further guidance.

Risk of taking valproate during pregnancy (regardless of the disease for which valproate is used)

• The patient should immediately consult their treating doctor if they plan to become pregnant or are pregnant.
• Taking valproate during pregnancy carries a risk. The higher the dose, the greater the risk, but no dose is risk-free.
• Valproate may cause serious birth defects and affect the development of the child. Reported birth defects include: spina bifida (when the bones of the spine are not properly developed); developmental abnormalities of the face and skull; developmental abnormalities of the heart, kidneys, urinary tract, and genital organs; limb abnormalities.
• In patients taking valproate during pregnancy, there is an increased risk of birth defects requiring treatment. Valproate has been used for many years, and it is known that in a group of children born to mothers taking valproate, about 10 children out of 100 will have birth defects. For comparison, such defects are found in 2-3 children out of every 100 born to women without epilepsy.

It is estimated that up to 30-40% of preschool-age children whose mothers took valproate during pregnancy may exhibit early developmental problems. Affected children may start walking and talking later, be less intellectually agile than other children, have language problems, and memory difficulties.

• Children exposed to valproate are more likely to be diagnosed with various autistic disorders, and some evidence suggests that these children may be more prone to developing symptoms of attention deficit hyperactivity disorder (ADHD).
• Before prescribing this medicine, the treating doctor will explain to the patient what may threaten the child if the patient becomes pregnant while taking valproate. If a patient taking this medicine decides to have a child, they should not stop taking the medicine or contraception without discussing it with their treating doctor.
• Parents or guardians of girls treated with valproate should contact the treating doctor when their child starts menstruating.
• The patient should ask their doctor about taking folic acid when trying to conceive. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with valproate treatment.

Please select the situation that applies to the patient and read the information:

ABOUT STARTING TREATMENT WITH DIPROMAL
ABOUT CONTINUING TREATMENT WITH DIPROMAL WITHOUT TRYING TO CONCEIVE
ABOUT CONTINUING TREATMENT WITH DIPROMAL WHILE TRYING TO CONCEIVE
ABOUT UNPLANNED PREGNANCY DURING CONTINUING TREATMENT WITH DIPROMAL

STARTING TREATMENT WITH DIPROMAL

If Dipromal is prescribed for the first time, the treating doctor will explain the risks to the unborn child if the patient becomes pregnant. Women of childbearing age should ensure that they use effective contraception (birth control) without interruption throughout the treatment period with Dipromal. The patient should consult their treating doctor or a family planning clinic if they need advice on contraception.
Important information:

• Before starting treatment with Dipromal, pregnancy should be ruled out using a pregnancy test, the results of which should be confirmed by the treating doctor.
• The patient should use effective contraception (birth control) throughout the treatment period with Dipromal.
• The patient should discuss the appropriate contraception method with their treating doctor. The treating doctor will provide information on pregnancy prevention and may refer the patient to a specialist for contraception advice.
• The patient should have a regular check-up (at least once a year) with a specialist experienced in treating bipolar affective disorder or epilepsy. During this visit, the treating doctor will ensure that the patient has been well-informed and understands all the risks and advice related to taking valproate during pregnancy.
• The patient should inform their doctor if they plan to have a child.
• The patient should immediately inform their doctor if they are pregnant or suspect they may be pregnant.

CONTINUING TREATMENT WITH DIPROMAL WITHOUT TRYING TO CONCEIVE

If the patient continues treatment with Dipromal and does not plan to become pregnant, they must ensure that they use effective contraception (birth control) without interruption throughout the treatment period with Dipromal.
The patient should consult their doctor or a family planning clinic if they need advice on contraception.

Important information:

• The patient should use effective contraception (birth control) throughout the treatment period with Dipromal.
• The patient should discuss contraception (birth control) with their treating doctor. The treating doctor will provide information on pregnancy prevention and may refer the patient to a specialist for contraception advice.
• The patient should have a regular check-up (at least once a year) with a specialist experienced in treating bipolar affective disorder or epilepsy. During this visit, the treating doctor will ensure that the patient has been well-informed and understands all the risks and advice related to taking valproate during pregnancy.
• The patient should inform their doctor if they plan to have a child.
• The patient should immediately inform their doctor if they are pregnant or suspect they may be pregnant.

CONTINUING TREATMENT WITH DIPROMAL WHILE TRYING TO CONCEIVE

TO CONCEIVE

If the patient plans to have a child, they should first schedule a visit with their treating doctor.
Dipromal should not be discontinued, nor should contraception be stopped, until this has been discussed with the treating doctor. The treating doctor will provide further guidance.
Children born to mothers who took valproate are at serious risk of birth defects and developmental problems, which can significantly impair the child.
The treating doctor will refer the patient to a specialist experienced in treating bipolar affective disorder or epilepsy to assess alternative treatment options. The specialist may take steps to ensure the best possible course of pregnancy and minimize the risk to the mother and unborn child.
The treating doctor may decide to change the dose of Dipromal or switch to another medicine, or discontinue Dipromal treatment long before the patient becomes pregnant - to ensure that the disease is stable.
The patient should ask their doctor about taking folic acid when trying to conceive. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with valproate treatment.

Important information:

• Dipromal should not be discontinued until the treating doctor decides to do so.
• Contraception should not be stopped before discussing it with the treating doctor and developing a plan to ensure control of the patient's condition and minimize the risks to the child.
• The patient should first schedule a visit with their treating doctor. During this visit, the treating doctor will ensure that the patient has been well-informed and understands all the risks and advice related to taking valproate during pregnancy.
• The treating doctor will try to switch to another medicine or discontinue Dipromal treatment long before the patient becomes pregnant.
• The patient should schedule an urgent visit with their treating doctor if they are pregnant or suspect they may be pregnant.

UNPLANNED PREGNANCY DURING CONTINUING TREATMENT WITH DIPROMAL

Dipromal should not be discontinued until this has been discussed with the treating doctor, as the patient's condition may worsen. The patient should schedule an urgent visit with their doctor if they are pregnant or suspect they may be pregnant. The treating doctor will provide further guidance.
Children born to mothers who took valproate are at serious risk of birth defects and developmental problems, which can significantly impair the child.
The patient will be referred to a specialist experienced in treating bipolar affective disorder or epilepsy to assess alternative treatment options.
In exceptional circumstances, when Dipromal is the only available treatment option during pregnancy, the patient will be closely monitored, both in terms of the underlying disease and fetal development. The patient and their partner will receive counseling and support regarding valproate-exposed pregnancy.
The patient should ask their doctor about taking folic acid. Folic acid may reduce the overall risk of spina bifida and early miscarriage, which applies to all pregnancies. However, it is unlikely that taking folic acid will reduce the risk of birth defects associated with valproate treatment.

Important information:

• The patient should schedule an urgent visit with their treating doctor if they are pregnant or suspect they may be pregnant.
• Dipromal should not be discontinued unless the treating doctor decides to do so.
• The patient must be referred to a specialist experienced in treating epilepsy, bipolar affective disorder, to assess the need for alternative treatment options.
• The patient must receive counseling on the risks of taking Dipromal during pregnancy, including teratogenic effects and the impact on child development.
• The patient must be referred to a specialist for prenatal monitoring to detect possible developmental abnormalities.

The patient should read the patient guide provided by their treating doctor.

The treating doctor will discuss the annual confirmation form and ask the patient to sign and keep it. The patient will also receive a Patient Card from the pharmacist to remind them of the risks of taking valproate during pregnancy.

Driving and operating machinery

The patient should not drive or operate machinery, as the medicine may affect reaction time.
Additionally, people whose epilepsy is not effectively controlled should not drive or operate machinery.

3. HOW TO TAKE DIPROMAL

Dipromal should always be taken as directed by the doctor.
In case of doubts, the patient should consult their doctor.
Treatment with Dipromal should be started and supervised by a doctor specializing in the treatment of epilepsy or bipolar affective disorder.
Epilepsy
Usual doseof Dipromal: orally, 20 to 30 mg/kg body weight per day, in 2 to 4 divided doses, with meals.
Elderly
In elderly patients, the doses that allow optimal clinical effect are usually lower than in younger patients, but they are also determined based on the assessment of efficacy and tolerance of treatment.
Patients with renal impairment
In cases of mild and moderate renal impairment, lower doses should be used, while in patients with severe renal impairment, dosing should be based on the concentration of free valproic acid in the blood.
Patients with liver impairment
Contraindicated.
Therapeutic concentration of valproate in serum is between 40 and 100 μg/ml (280 to 700 μmol/l).
Mania
The daily dose should be determined and checked individually by the treating doctor.
Initial dose
The recommended initial daily dose is 750 mg.
Average daily dose
The average daily dose is usually between 1000 mg and 2000 mg.

Taking a higher dose of Dipromal than recommended

After an overdose, symptoms such as excessive drowsiness, heart block, deep coma, muscle weakness, decreased or absent reflexes, hypotension, miosis, circulatory and respiratory disorders, brain edema, metabolic acidosis, decreased calcium levels, and increased sodium levels in the blood, behavioral changes may occur.
In case of an overdose, an attempt should be made to remove the medicine from the stomach by inducing vomiting (if the person who took the overdose is conscious) and immediate contact with a doctor, who will start appropriate treatment.
Dipromal should not be used interchangeably with other medicines containing magnesium valproate.

Missing a dose of Dipromal

If the next dose of Dipromal is missed, it should be taken as soon as possible. However, if the time for the next dose is approaching, the missed dose should be skipped.
A double dose should not be taken to make up for a missed dose.

Stopping treatment with Dipromal

Stopping treatment with Dipromal may cause the symptoms of epilepsy to worsen. It should not be stopped abruptly or without consulting a doctor.
In case of any further doubts regarding the use of this medicine, the patient should consult their doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Dipromal can cause side effects, although not everybody gets them.
The most common side effects associated with valproate are gastrointestinal disorders (occurring in about 20% of patients). Severe liver damage, which can be fatal, occurs mainly in children taking valproate in high doses or in combination with other antiepileptic drugs.
Valproate taken during pregnancy may cause birth defects and developmental problems in the child.

Very common (may affect more than 1 in 10 people)

• abdominal pain, nausea, vomiting

Common (may affect up to 1 in 10 people)

• thrombocytopenia (significant decrease in platelet count), leukopenia (significant decrease in white blood cell count)
• increased ammonia levels in the blood, increased or decreased appetite
• increased or decreased body weight, changes in liver function test results
• drowsiness, tremors, paresthesia (tingling sensation)
• temporary hair loss, changes in hair pigmentation and curl, nail disorders, and nail bed disorders
• amenorrhea

Uncommon (may affect up to 1 in 100 people)

• bleeding
• transient coma, in some cases with increased frequency of seizures

Rare (may affect up to 1 in 1,000 people)

• allergic reactions
• vasculitis
• lupus erythematosus
• hyperandrogenism (excessive production of male sex hormones)
• hyperinsulinism (increased insulin levels in the blood), edema, obesity
• low levels of insulin-like growth factor-binding protein type 1
• hypothermia (low body temperature)
• irritability, hallucinations, confusion
• headache, hyperactivity, muscle stiffness, lack of coordination, stupor
• diarrhea, pancreatitis, excessive salivation
• severe liver damage
• rash, erythema multiforme (red, blistering rash on the skin and mucous membranes)
• polycystic ovary syndrome (when hormonal disorders cause menstrual irregularities and excessive hair growth)
• diplopia (double vision)

Very rare (may affect up to 1 in 10,000 people)

bone marrow disorders, lymphopenia (significant decrease in lymphocyte count), neutropenia (significant decrease in neutrophil count), pancytopenia (significant decrease in all blood cell types), anemia

• decreased fibrinogen and/or factor VIII levels, impaired platelet aggregation, prolonged bleeding time, abnormal thyroid function test results (of unknown clinical significance)
• encephalopathy (a type of brain damage), dementia associated with brain atrophy, (reversible) parkinsonian syndrome
• hearing impairment, tinnitus
• Stevens-Johnson syndrome, Lyell syndrome (diseases characterized by blistering of the skin and mucous membranes, ulcers, and scarring)
• Fanconi syndrome (a disorder affecting the kidneys' ability to reabsorb water and various compounds), bedwetting in children

Frequency not known(frequency cannot be estimated from available data)

• sedation, extrapyramidal symptoms, i.e., muscle stiffness, involuntary movements, slowed movement

Additional side effects in children and adolescents:

Some side effects of valproate may occur more frequently in children and adolescents or be more severe than in adults. These include: liver damage, pancreatitis, aggression, hyperactivity, concentration disorders, abnormal behavior, hyperactivity, and learning difficulties.

Reporting side effects

If side effects occur, including any not listed in this leaflet, the patient should inform their doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Post-Marketing Surveillance of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C, 02-222 Warsaw
phone: +48 22 49 21 301
fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of this medicine.

5. HOW TO STORE DIPROMAL

Store in a temperature below 25°C. Store in the original package.
Store out of sight and reach of children.
Do not use this medicine after the expiry date stated on the package.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Dipromal contains

• The active substance of the medicine is magnesium valproate (200 mg per tablet).
• The other ingredients of the medicine are: in the core of the tablet: potato starch, microcrystalline cellulose, crospovidone, talc, magnesium stearate, in the coating: acetylated cellulose phthalate, macrogol 6000, propylene glycol.

What Dipromal looks like and contents of the package

Aluminum/PVC foil blisters in a cardboard box.
40 coated tablets (2 blisters of 20 each).

Marketing authorization holder

Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus
Dublin 24, D24PPT3
Ireland

Manufacturer

ICN Polfa Rzeszów S.A.
Przemysłowa Street 2
35-959 Rzeszów
Bausch Health Poland sp. z o.o.
Przemysłowa Street 2
35-959 Rzeszów

Date of last update of the leaflet:

Other sources of information

Detailed and up-to-date information on the use of this product is available by scanning the QR code on the leaflet using a smartphone. The same information is also available on the website: www.walproiniany.pl.
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