Carbamazepine tillomed

Karbamazepina Tillomed, 200 mg, prolonged-release tablets
Karbamazepina Tillomed, 400 mg, prolonged-release tablets
Carbamazepinum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents

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

1. What Karbamazepina Tillomed is and what it is used for

Karbamazepina Tillomed contains the active substance called carbamazepine.
Karbamazepina Tillomed has been specially developed so that the active substance is released gradually.
Carbamazepine, the active substance of the medicine, may affect the body in several ways. It is an antiepileptic medicine (preventing epileptic seizures), it may also alter certain types of pain and control mood disorders.
Karbamazepina Tillomed is used:

• In the treatment of certain forms of epilepsy
• In the treatment of a painful facial condition called trigeminal neuralgia
• To control severe mood disorders when certain other medicines are ineffective.

2. Important information before taking Karbamazepina Tillomed

When not to use Karbamazepina Tillomed

• if the patient is allergic to carbamazepine, to medicines with a similar structure (e.g. tricyclic antidepressants, certain antidepressants), or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has previously experienced bone marrow damage or blood formation disorders in the bone marrow;
• if the patient has conduction disorders in the heart (atrioventricular block);
• if the patient has certain inherited metabolic disorders (acute intermittent porphyria, mixed porphyria, late cutaneous porphyria);
• if the patient has taken medicines called monoamine oxidase inhibitors (MAOIs), used to treat depression, within the last 14 days.

Warnings and precautions

• If the patient experiences episodes of unconsciousness (clouding of consciousness), carbamazepine should not be used, as this medicine may cause such epileptic seizures or worsen pre-existing seizures.
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported during carbamazepine treatment, which may be life-threatening. These appear on the trunk initially as reddish, target-like or circular spots (often with blisters in the center). The rash may lead to extensive blistering or peeling of the skin. Additional symptoms to watch for include open, painful lesions (ulcers) in the mouth, throat, nose, and genital organs, as well as redness and swelling of the eyes (conjunctivitis). These potentially life-threatening skin reactions are often accompanied by flu-like symptoms (headache, fever, and body aches).

The highest risk of these severe skin reactions occurs during the first few weeks of treatment. If the patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis related to carbamazepine use, the medicine must not be used again.
If a skin rash or any of the other skin-related symptoms listed above occur, seek medical help immediately. Inform the doctor that you are taking carbamazepine.
These severe skin reactions may occur more frequently in individuals from certain Asian countries. If the patient is of Han Chinese or Thai descent, the doctor may perform a blood test to determine whether the patient is at increased risk of these severe skin reactions. The doctor will inform the patient whether a blood test is necessary before starting carbamazepine.

Before taking Karbamazepina Tillomed, consult your doctor or pharmacist
If the patient has any of the following conditions:

• Blood-forming organ disorders (haematological disorders);
• Signs of unusual hypersensitivity (skin rash or other allergic symptoms) to oxcarbazepine or any other medicine. About 25% of patients allergic to carbamazepine may also be hypersensitive to oxcarbazepine;
• Sodium metabolism disorder;
• Heart, liver, or kidney disorders, even if they occurred in the past (see "What are the possible side effects?" and "How to take Karbamazepina Tillomed?");
• Increased intraocular pressure (glaucoma) or difficulty or pain during urination; in such cases, the patient's condition should be carefully monitored;
• Myotonic dystrophy (a degenerative muscle disease; conduction disorders in the heart are common in these patients).

If treatment with carbamazepine was previously discontinued.
If the doctor has diagnosed the patient with a psychiatric condition called psychosis, which may be accompanied by disorientation and excessive excitement.
If carbamazepine is used during pregnancy, there is a risk of harm to the unborn child. During treatment with carbamazepine and for two weeks after the last dose, women of childbearing potential should use effective contraception (see "Pregnancy and breastfeeding").
If the patient is taking a hormonal contraceptive medicine ("the pill"), be aware that carbamazepine may render it ineffective. A different or additional non-hormonal method of contraception should be used. This reduces the risk of unintended pregnancy.
Immediately inform the doctor if irregular bleeding or spotting from the vagina occurs.
Inform the doctor if the patient is pregnant or planning to become pregnant. The doctor will discuss the possible risks associated with using carbamazepine during pregnancy, as it may cause damage or congenital malformations in the unborn child (see section "Pregnancy").
A small number of people treated with antiepileptic medicines, such as Karbamazepina Tillomed, have had thoughts of self-harm or suicide. If such thoughts occur, contact your doctor immediately.
If any of the above situations apply to the patient, it is essential to discuss them with the doctor. In such cases, carbamazepine may only be taken if appropriate precautions are taken.
Due to the possibility of increased skin sensitivity to light (photosensitivity), protect yourself from strong sunlight during treatment with carbamazepine.

If any of the following situations apply to the patient, inform the doctor immediately:

• If the patient experiences symptoms such as fever, sore throat, allergic skin reactions such as rash with swollen lymph nodes and (or) flu-like symptoms, mouth ulcers, tendency to bruising, or pinpoint or extensive bleeding within the skin, seek medical advice immediately.
• If symptoms of an allergic reaction occur, which may include fever, skin rash, vasculitis, swollen lymph nodes, or joint pain, contact your doctor immediately or go to the emergency department of the nearest hospital (see "Other possible side effects").
• If the patient notices that epileptic seizures occur more frequently.
• If the patient develops symptoms of liver inflammation, such as fatigue, loss of appetite, nausea, yellowing of the skin and (or) eyes, or enlarged liver.
• If the patient has kidney problems related to low sodium levels in the blood or if the patient has kidney problems and is also taking medicines that reduce sodium levels in the blood (diuretics such as hydrochlorothiazide, furosemide).
• If the patient experiences symptoms such as dizziness, a feeling of emptiness in the head, drop in blood pressure, or confusion caused by taking carbamazepine, which may lead to falls.

Karbamazepina Tillomed and other medicines

Tell your doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines the patient plans to take, including over-the-counter medicines and herbal remedies.
Treatment with MAO inhibitors (medicines used to treat depression) must be discontinued at least 2 weeks before starting carbamazepine treatment.
Be aware that the following information may also apply to recently used medicines.

Effect of carbamazepine on plasma concentrations of other medicines
Carbamazepine may increase the activity of certain liver enzymes and thereby reduce the plasma concentration of other medicines.
The effect of some other medicines taken simultaneously, which are metabolized in the same way as carbamazepine, may thus be weakened or even reversed.
If carbamazepine is administered simultaneously, dose adjustment of the following active substances with various therapeutic areas may be necessary, depending on clinical needs:

• Analgesics, anti-inflammatory medicines: buprenorphine, fentanyl, methadone, paracetamol (long-term use of carbamazepine and paracetamol [acetaminophen] may cause hepatotoxicity), phenazone, tramadol
• Antiparasitic medicines: praziquantel, albendazole
• Anticoagulants: warfarin, phenprocoumon, dicoumarol, acenocoumarol, rivaroxaban, dabigatran, apixaban, edoxaban
• Medicines used to treat depression: bupropion, citalopram, mianserin, nefazodone, sertraline, trazodone (but appears to enhance the antidepressant effect)
• Other antidepressants (so-called tricyclic antidepressants): imipramine, amitriptyline, nortriptyline, clomipramine
• Medicines for nausea and vomiting: aprepitant
• Antiepileptic medicines, other medicines used to treat epileptic seizures: clonazepam, ethosuximide, felbamate, eslicarbazepine, oxcarbazepine, primidone, lamotrigine, tiagabine, topiramate, valproic acid, zonisamide, phenytoin (plasma concentration of phenytoin may be increased or decreased)
• Medicines used to treat (systemic) fungal infections: caspofungin, antifungal azoles: e.g. itraconazole, voriconazole. In patients treated with voriconazole or itraconazole, alternative antiepileptic medicines are recommended.
• Medicines for viral infections/HIV: e.g. indinavir, ritonavir, saquinavir
• Anxiolytics: alprazolam, midazolam, clobazam
• Medicines used to treat respiratory diseases: theophylline
• Medicines used to treat heart diseases: digoxin, simvastatin, atorvastatin, lovastatin, cerivastatin, ivabradine
• Immunosuppressive medicines used to prevent organ transplant rejection: cyclosporine, tacrolimus, sirolimus, everolimus
• Calcium antagonists (medicines used to treat dizziness, migraine, high blood pressure): felodipine, flunarizine
• Medicines for contraception: hormonal contraceptives
• Corticosteroids: e.g. prednisolone, dexamethasone
• Medicines used to treat psychiatric disorders: haloperidol, bromperidol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, zotepine (accelerated metabolism), aripiprazole, paliperidone
• Thyroid hormones: levothyroxine
• Antibiotics: rifabutin, tetracyclines e.g. doxycycline
• Medicines used to treat cancer: imatinib, cyclophosphamide, lapatinib, temsirolimus
• Others: quinidine (used to treat cardiac arrhythmias), estrogens (hormones), methylphenidate (a psychostimulant and medicine used to treat attention disorders), progesterone derivatives (hormones), propranolol (beta-blocker, antihypertensive medicine)
• Medicines used to treat erectile dysfunction: tadalafil

Hormonal contraceptives, e.g. pills, patches, injections, or implants.
Carbamazepine may affect the action of hormonal contraceptives and reduce their effectiveness in preventing pregnancy. During carbamazepine treatment, discuss with your doctor the most appropriate type of contraception.
Carbamazepine may reduce plasma concentrations of bupropion (a medicine to help quit smoking) and increase concentrations of its metabolite hydroxybupropion, thereby reducing the clinical efficacy and safety of bupropion.

Reduced plasma concentration of carbamazepine caused by other medicines
Plasma concentration of carbamazepine may be reduced by:

• Antiepileptic medicines, other medicines used to treat epileptic seizures: felbamate, methsuximide, oxcarbazepine, phenobarbital, phenytoin, fosphenytoin, primidone, gabapentin, and probably (data partially conflicting) clonazepam, valproic acid, valpromide
• Antituberculosis medicine: rifampicin
• Medicines used to treat respiratory diseases, antiasthmatics: theophylline, aminophylline
• Medicines used for skin diseases: isotretinoin
• Medicines used to treat cancer: cisplatin, doxorubicin
• Others: St. John's wort (Hypericum perforatum), a herbal product used to treat depressive mood

On the other hand, valproic acid and primidone may increase plasma concentrations of the pharmacologically active metabolite of carbamazepine (10,11-epoxide of carbamazepine).
Concomitant administration of felbamate may reduce plasma concentrations of carbamazepine and increase concentrations of 10,11-epoxide of carbamazepine, while decreasing plasma concentrations of felbamate.
Due to mutual interactions, especially when multiple antiepileptic medicines are used simultaneously, monitoring of plasma carbamazepine concentrations is recommended, and dose adjustment may be necessary.

Increased plasma concentration of carbamazepine caused by other medicines
The following active substances may increase plasma concentrations of carbamazepine:

• Analgesics, anti-inflammatory medicines: dextropropoxyphene/propoxyphene, ibuprofen
• Gonadotropin inhibitors: danazol
• Antibiotics, medicines used to treat bacterial infections: macrolide antibiotics (e.g. erythromycin, troleandomycin, josamycin, clarithromycin, ciprofloxacin)
• Medicines used to treat depression: fluoxetine, fluvoxamine, nefazodone, paroxetine, trazodone, vilazodone, and probably also desipramine
• Antiepileptic medicines, other medicines used to treat epileptic seizures: stiripentol, vigabatrin
• Medicines used to treat (systemic) fungal infections, antifungal azoles such as e.g. itraconazole, ketoconazole, fluconazole, voriconazole. In patients treated with voriconazole or itraconazole, alternative antiepileptic medicines are recommended
• Medicines used to treat allergic reactions: loratadine, terfenadine
• Medicines used to treat tuberculosis: isoniazid
• Medicines used to treat viral diseases/HIV, e.g. ritonavir
• Medicines used to treat glaucoma: acetazolamide
• Calcium antagonists (active substances used to treat cardiovascular diseases): diltiazem, verapamil
• Medicines used to relax muscles (muscle relaxants): oxybutynin, dantrolene
• Medicines used to treat psychiatric disorders: loxapine, olanzapine, quetiapine
• Anticoagulants: ticlopidine
• Medicines used to treat stomach and intestinal ulcers: omeprazole, probably also cimetidine
• Others: grapefruit juice, nicotinamide (a B-group vitamin, in high doses)

Increased plasma concentration of carbamazepine may lead to symptoms listed in section 4 "Possible side effects" (e.g. dizziness, fatigue, unsteady gait, double vision). If such symptoms occur, speak to your doctor; the doctor will then check the plasma concentration of carbamazepine and adjust the dose if necessary.

Other interactions
Concomitant use of carbamazepine with loxapine, quetiapine (medicines used to treat psychiatric disorders), primidone, gabapentin, valproic acid, valnoctamide, valpromide, and brivaracetam (antiepileptic medicines, other medicines used to treat epileptic seizures) may lead to increased plasma concentrations of the active metabolite 10,11-epoxide of carbamazepine, and thus to the same adverse effects as an overdose of carbamazepine.
Concomitant use of carbamazepine and levetiracetam may enhance the toxicity of carbamazepine.
Carbamazepine may enhance liver damage caused by isoniazid (a medicine used to treat tuberculosis).
Concomitant use of carbamazepine and lithium (a medicine used to treat psychiatric disorders), metoclopramide (a medicine used to treat gastrointestinal disorders), or neuroleptics (haloperidol, thioridazine: medicines used to treat psychiatric disorders) may promote neurological adverse effects.
On the other hand, in patients treated with antipsychotic medicines, carbamazepine may reduce plasma concentrations of these medicines, leading to worsening of the clinical condition. Therefore, the doctor may also consider increasing the dose of the neuroleptic.
Note that particularly concomitant use of lithium (a medicine used to treat and prevent certain psychiatric and emotional disorders) and carbamazepine may enhance the harmful effects of both active substances on the nervous system. Therefore, careful monitoring of blood levels of both medicines is necessary. Previous treatment with neuroleptics should have occurred more than 8 weeks earlier, not simultaneously. Be alert for the following symptoms: unsteady gait (ataxia), eye tremor or nystagmus (horizontal nystagmus), exaggerated muscle reflexes, muscle twitching (fasciculations).
Concomitant administration of carbamazepine and certain diuretics (hydrochlorothiazide, furosemide) may lead to decreased serum sodium concentration.
Carbamazepine may reduce the effectiveness of certain medicines used during anesthesia to relax muscles (non-depolarizing muscle relaxants such as pancuronium). This may lead to faster reversal of neuromuscular blockade. Patients treated with muscle relaxants should be monitored accordingly, and their doses may need to be increased if necessary.
Concomitant administration of carbamazepine and direct oral anticoagulants (rivaroxaban, dabigatran, apixaban, and edoxaban) may lead to reduced plasma concentrations of direct oral anticoagulants.
Further information is provided in the table below:

There are reports in the literature that in patients previously treated with neuroleptics,
additional administration of carbamazepine may increase the risk of developing the so-called
neuroleptic malignant syndrome (a potentially life-threatening condition characterized by elevated
body temperature and muscle rigidity) or Stevens-Johnson syndrome (a severe skin reaction).
When isotretinoin (an active substance used in the treatment of acne) is administered concomitantly
with carbamazepine, the plasma concentration of carbamazepine should be monitored.
Concomitant administration of carbamazepine and paracetamol (an analgesic and antipyretic)
may reduce the bioavailability, and thus the efficacy, of paracetamol.
Carbamazepine appears to increase the excretion (elimination) of thyroid hormones and increases
the requirement for these hormones in patients with hypothyroidism. Therefore, in patients receiving
thyroid hormone replacement therapy, thyroid function parameters should be assessed at the beginning
and at the end of treatment with carbamazepine. If necessary, the dose of thyroid hormone-containing
medicinal products should be adjusted.
Concomitant administration of antidepressants belonging to the serotonin reuptake inhibitors group
(antidepressants such as fluoxetine) may lead to serotonin toxicity syndrome.
The concomitant use of carbamazepine with nefazodone (an antidepressant) is not recommended,
because carbamazepine may significantly reduce the plasma concentration of nefazodone, leading
to loss of its efficacy. Moreover, when nefazodone and carbamazepine are taken concomitantly,
the plasma concentration of carbamazepine increases, while the concentration of its active metabolite,
10,11-epoxy-carbamazepine, decreases.
Concomitant administration of carbamazepine and other medicinal products that may cause
cardiac conduction disturbances (arrhythmias), such as antiarrhythmics (medicinal products used
in cardiac arrhythmias), cyclic antidepressants (antidepressants), or erythromycin (an antibiotic),
increases the risk of cardiac conduction disturbances.
Use of Karbamazepina Tillomed with food, drink, and alcohol

• Alcohol consumption may have a stronger effect on the patient than usual. The patient should discuss with the doctor whether alcohol consumption should be discontinued.
• Consumption of grapefruit or grapefruit juice may increase the likelihood of adverse reactions in the patient.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child,
she should consult her doctor or pharmacist before using this medicinal product.
Pregnancy
Karbamazepina Tillomed may cause serious congenital malformations. When carbamazepine is taken
during pregnancy, the risk of congenital malformations in the child is up to three times higher than in women
not taking antiepileptic medicinal products. The main congenital malformations reported include neural
tube defects (spina bifida), facial birth defects such as cleft lip and palate, cranial malformations, heart defects,
genital malformations involving the urethral opening (hypospadias), and digital malformations. When
Karbamazepina Tillomed is taken during pregnancy, the unborn child should be closely monitored.
In children born to mothers who used Karbamazepina Tillomed during pregnancy, developmental
problems of the nervous system (brain development) have been reported. Some studies have shown
that carbamazepine negatively affects the development of the nervous system in children exposed
to carbamazepine in utero, while other studies have not demonstrated such an effect. The influence
of the medicinal product on nervous system development cannot be ruled out.
Women of childbearing potential who do not plan pregnancy should use effective contraceptive
medicinal products during treatment with carbamazepine. Karbamazepina Tillomed may affect
the efficacy of hormonal contraceptives such as oral contraceptives, reducing their effectiveness
in preventing pregnancy. Intermenstrual bleeding or spotting may occur. While taking Karbamazepina
Tillomed, the patient should discuss with her doctor the most appropriate type of contraception.
After discontinuation of Karbamazepina Tillomed, effective contraception should be continued
for 2 weeks.
If a woman of childbearing potential is planning pregnancy, she should consult her doctor about changing
her treatment to another medicinal product before stopping contraception and becoming pregnant,
in order to avoid exposing the unborn child to carbamazepine.
If the patient is pregnant or suspects she may be pregnant, she should immediately inform her doctor.
She should not discontinue the medicinal product without discussing this with her doctor. Discontinuing
the medicinal product without medical advice may trigger a seizure, which could be dangerous for both
the patient and her unborn child. The doctor may decide to change the treatment.
If the patient takes Karbamazepina Tillomed during pregnancy, her newborn child may also be at risk
of bleeding shortly after birth. The doctor may administer a medicinal product to both the mother and
the child to prevent this.
Breastfeeding
Carbamazepine passes into breast milk. The benefits of breastfeeding should be weighed against
the low risk of adverse reactions in the breastfed infant. Infants breastfed by mothers treated with
carbamazepine should be closely monitored for adverse reactions such as poor weight gain, excessive
drowsiness, or allergic skin reactions.
Fertility
Isolated cases of sexual dysfunction, such as impotence or decreased libido, have been reported.
Reduced fertility in men and (or) abnormal semen production have been reported very rarely.
Driving and operating machinery
Karbamazepina Tillomed may cause dizziness or drowsiness, blurred vision, double vision, or lack
of muscular coordination, especially at the beginning of treatment or after a dose adjustment. If the patient
experiences such adverse effects or visual disturbances, he or she should not drive or operate machinery.
Karbamazepina Tillomed contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should
consult his or her doctor before taking this medicinal product.

3. How to take Karbamazepina Tillomed

This medicine should always be taken exactly as directed by the physician or pharmacist. In case of doubts,
consult your doctor or pharmacist.
Dosage will be individually determined and monitored by a physician (specialist), aiming to control seizures
with the lowest possible dose, especially during pregnancy.
Do not make any changes to the treatment or dosage without first consulting your doctor, to avoid
jeopardizing the success of therapy.
It is recommended to gradually (slowly) increase the dose to the optimal, effective level.
The daily dose is usually administered in 1 or 2 divided doses.
The general daily dosage range of carbamazepine is 400 to 1200 mg.
In general, the total daily dose of carbamazepine should not exceed 1600 mg, as higher doses are associated
with an increased incidence of adverse effects.
Therapeutic dosage, particularly in combination therapy, should be based on plasma carbamazepine
concentrations and clinical response. Experience has shown that the therapeutic range for carbamazepine
lies between 4 and 12 micrograms/ml.
In individual cases, the required dose may differ significantly from the initial or maintenance dose
(e.g. due to accelerated metabolism caused by enzyme induction or drug interactions when taking other
medicines concomitantly).
In the treatment of epilepsy, carbamazepine is best used as monotherapy. Treatment should be supervised
by a specialist physician experienced in managing epilepsy.
When switching from another antiepileptic drug to carbamazepine, the dose of the drug being discontinued
should be gradually reduced.
For the treatment of epileptic seizures, the following general dosing regimen is recommended:

  Children* <br/>
  From 6 to 10 years of age: 200 mg in the evening <br/> (1 prolonged-release tablet) <br/>
  From 200 to 400 mg in the evening <br/> (1 or 2 prolonged-release tablets) <br/><br/>

  15 years: 200 mg in the evening <br/> (1 prolonged-release tablet) <br/>
  From 200 to 400 mg in the morning <br/> (from 1 to 2 prolonged-release tablets) <br/>
  From 400 to 600 mg in the evening <br/> (2 or 3 prolonged-release tablets) <br/><br/>

  > 15 years of age: Dosing as for adults
</td>

* Note:
For children under 6 years of age, dosage forms with non-extended release (suspension or tablets) are available for use as initial and maintenance dosing. The use of extended-release tablets is not recommended due to insufficient data.
Maximum recommended dose:
From age 6 to 15: 1000 mg/day
Over age 15: 1200 mg/day

Seizures (epilepsy):
In adults, the usual initial dose is 1 or 2 extended-release carbamazepine tablets (corresponding to 200–400 mg of carbamazepine per day), which should be gradually increased to a maintenance dose of 4 to 6 extended-release carbamazepine tablets (corresponding to 800–1200 mg of carbamazepine per day).
In children, the average maintenance dose is usually 10–20 mg of carbamazepine/kg body weight/day.
See dosage recommendations above.

Trigeminal neuralgia (facial pain):
The usual dose is 600–800 mg per day.
The maximum dose is 1200 mg per day.
Elderly patients may require a lower dose.

Prophylaxis of manic-depressive episodes:
The initial dose, which is usually also sufficient as the maintenance dose, is 1 or 2 200 mg extended-release carbamazepine tablets (corresponding to 200–400 mg of carbamazepine) per day.
If necessary, the dose may be increased to 2 200 mg extended-release carbamazepine tablets (corresponding to 800 mg of carbamazepine) twice daily.

Note:
Lower doses are recommended for patients with severe cardiovascular, hepatic, or renal disease and for elderly patients.

Instructions for use
Extended-release tablets must be swallowed whole and should not be chewed or crushed.
Extended-release tablets should be taken during or after a meal, with sufficient fluid (e.g., 1 glass of water, 200 ml).
In some cases, dividing the daily dose into 4 to 5 single doses has proven particularly effective. In such cases, immediate-release carbamazepine formulations are more suitable than extended-release forms.

Duration of treatment
The duration of treatment depends on the indication and the individual patient's response and is determined by the treating physician.
Antiepileptic therapy is generally long-term.
The decision to initiate, continue, or discontinue carbamazepine therapy in individual cases should be made by a specialist experienced in epilepsy management.
Dose reduction and discontinuation of the drug should generally be considered no earlier than two or three years after seizure cessation.
Discontinuation of the drug should be carried out by gradually reducing the dose over one or two years; in children, instead of adjusting the dose according to age, the dose may be maintained at the same level, reducing the dose per kilogram of body weight as body weight increases, and deterioration in EEG results must not occur.

In the treatment of neuralgia, continuing therapy for several weeks at a maintenance dose sufficient to relieve pain has proven beneficial. The dose should be reduced cautiously to determine whether spontaneous remission has occurred during treatment. In case of recurrence of pain attacks, the original maintenance dose should be continued.

Prophylaxis of manic-depressive episodes constitutes long-term treatment.

If you feel that the effect of carbamazepine is too strong or too weak, consult your doctor or pharmacist.

Missed dose of Karbamazepina Tillomed
Do not take a double dose to make up for a missed dose. Continue taking the medication as directed.

Overdose of Karbamazepina Tillomed
If too many tablets are accidentally taken, contact your doctor or the nearest hospital emergency department immediately.
In case of carbamazepine overdose, the adverse effects listed in section 4 "Possible side effects" may intensify.

Central nervous system
Nervous system depression, disturbances of consciousness (drowsiness, lethargy), rigidity (stupor), coma, dizziness, disorientation, restlessness, agitation, confusion, sensation of warmth (hot flushes), hallucinations, blurred vision, slurred or indistinct speech, eye tremors (nystagmus), unsteady gait (ataxia), disturbances in motor sequences or abnormal motor sequences (dyskinesias), reflex disturbances (initially increased, then decreased reflexes), seizures (tonic-clonic convulsions), psychomotor disturbances, muscle twitching (myoclonus), opisthotonus, involuntary movements, tremor, low body temperature (hypothermia), dilated pupils, EEG abnormalities.

Respiratory system
Breathing disturbances (respiratory depression), pulmonary edema (fluid in the lungs), bluish discoloration of the face (cyanosis), respiratory arrest.

Cardiovascular system
Increased heart rate (tachycardia), usually reduced (hypotensive) blood pressure, hypertension may also occur, disturbances in cardiac conduction (changes in ECG, cardiac arrhythmias, atrioventricular block), loss of consciousness, cardiac arrest, intense flushing with sensation of warmth (hot flushes).

Gastrointestinal tract
Nausea, vomiting, delayed gastric emptying, reduced intestinal motility.

Urinary tract, genital organs
Urinary retention, decreased urine production or anuria, fluid retention in the body.

Laboratory findings
Low serum sodium concentration (hyponatremia), possible blood acidification, possible increase in blood glucose (hyperglycemia), increased creatine phosphokinase activity in muscles, increased or decreased white blood cell count (leukocytosis, leukopenia, neutropenia), glucose in urine (glucosuria), increased concentration of a specific metabolite in urine (acetonuria).

In case of any error in treatment, inform your doctor immediately.
In case of ingestion of large doses, emergency measures must be taken (hospitalization).
There is currently no specific antidote for acute carbamazepine poisoning. Treatment of carbamazepine overdose depends on the symptoms present and usually requires hospitalization.

Discontinuation of Karbamazepina Tillomed
Under no circumstances should carbamazepine treatment be interrupted or discontinued prematurely on your own initiative. This may jeopardize treatment success and lead to recurrence of epileptic seizures. If intolerance occurs or clinical condition changes, consult your doctor.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The frequency of adverse reactions is based on the following categories:
Very common: may occur in more than 1 in 10 people
Common: may occur in up to 1 in 10 people
Uncommon: may occur in up to 1 in 100 people
Rare: may occur in up to 1 in 1,000 people
Very rare: may occur in up to 1 in 10,000 people
Not known: frequency cannot be estimated from the available data

The following adverse reactions may have serious consequences:
You must immediately contact a doctor if the patient experiences any of the following adverse reactions. These may be early signs of serious damage to the blood, liver, kidneys, or other organs, which may require urgent medical attention.

• If the patient develops flu-like symptoms, fever, sore throat, skin rash, mouth ulcers, swollen lymph nodes, or increased susceptibility to infections (signs of certain blood abnormalities, particularly reduced number of white blood cells)
• If the patient develops fatigue, headache, shortness of breath during physical exertion, dizziness, pallor, frequent infections leading to fever, chills, sore throat, mouth ulcers, easier bruising than usual, nosebleeds (signs of certain blood abnormalities, particularly pancytopenia)
• If the patient develops a red, blotchy rash, mainly on the face, and simultaneous exhaustion, fever, nausea, loss of appetite (signs of systemic lupus erythematosus)
• If the patient develops yellowing of the skin or whites of the eyes (signs of hepatitis)
• If the patient develops dark-coloured urine (signs of porphyria or hepatitis)
• If the patient develops reduced urine output due to kidney failure and presence of blood in the urine
• If the patient develops severe upper abdominal pain, vomiting, loss of appetite (signs of pancreatitis)
• If the patient develops skin rash, redness of the skin, blisters on the lips, eyes or in the mouth, skin peeling, and simultaneous fever, chills, headache, cough, body aches (signs of severe skin reactions)
• If the patient develops swelling of the face, eyes or tongue, difficulty swallowing, wheezing, hives or itching of the whole body, skin rash, fever, abdominal cramps, discomfort or tightness in the chest, difficulty breathing, loss of consciousness (signs of angioedema or severe allergic reactions)
• If the patient feels drowsy, confused, has muscle tremors, or seizures worsen (symptoms which may be related to low blood sodium levels)
• If the patient develops fever, nausea, vomiting, headache, neck stiffness, and extreme sensitivity to light (signs of meningitis)
• If the patient develops muscle rigidity, high fever, altered mental status, high blood pressure, excessive salivation (signs of neuroleptic malignant syndrome)
• If the patient develops irregular heartbeat and chest pain
• If the patient develops altered consciousness and fainting
• If the patient develops diarrhoea, abdominal pain and fever (signs of colitis). The frequency of this adverse reaction is not known*
• If the patient experiences falls due to dizziness, drowsiness, low blood pressure, or disorientation

Other possible adverse reactions:
Observed adverse reactions occur less frequently when carbamazepine is used alone (monotherapy) than when used concomitantly with other antiepileptic drugs (combination therapy).
Some adverse reactions are dose-dependent, especially at the beginning of treatment if the initial dose is too high or in elderly patients, such as disorders of the central nervous system (dizziness, headache, gait disturbances, drowsiness, sedation, fatigue, double vision, accommodation disorders such as blurred vision), gastrointestinal disorders (nausea, vomiting), and allergic skin reactions.
Dose-dependent adverse reactions usually resolve spontaneously within a few days or after a temporary dose reduction. Therefore, if possible, carbamazepine should be titrated gradually. Central nervous system disorders may indicate relative overdose or large fluctuations in plasma concentration; therefore, in such cases, determination of carbamazepine plasma concentration is recommended.

Infections and parasitic diseases
The frequency of herpes virus reactivation is not known (this may be a serious condition if the immune system is weakened).*

Blood and lymphatic system disorders
Very commonly: changes in blood morphology such as reduced number of white blood cells (leukopenia). According to the literature, mild leukopenia is most commonly observed, transient in about 10% of cases and chronic in 2%. Mild leukopenia occurs mainly within the first four months of treatment.
Commonly: increased number of certain white blood cells (eosinophilia) or reduced number of platelets (thrombocytopenia).
Uncommonly: increased number of other white blood cells (leukocytosis) or swollen lymph nodes, as well as folic acid deficiency.
Very rarely: sometimes life-threatening damage to blood cells such as agranulocytosis, aplastic anaemia, pancytopenia, red cell aplasia, and other forms of anaemia (megaloblastic, possibly haemolytic), reticulocytosis, and various forms of porphyria (acute intermittent porphyria, erythropoietic porphyria, porphyria cutanea tarda). Splenomegaly has been very rarely reported.

Hypersensitivity reactions
Delayed hypersensitivity reactions involving multiple organs, including fever, skin rash, vasculitis, swollen lymph nodes, pseudolymphoma, joint pain, altered white blood cell count (leukopenia, eosinophilia), hepatosplenomegaly, abnormal liver function tests, and liver disease with damage and atrophy of intrahepatic bile ducts, occur sporadically. These phenomena may occur in various combinations and affect other organs such as the lungs, kidneys, pancreas, heart muscle, and large intestine.
Very rarely: acute systemic allergic reaction and aseptic (not caused by bacteria or viruses) meningitis with muscle jerks (myoclonus) and increased number of certain white blood cells (eosinophilia), anaphylactic reactions (shock), and skin and mucous membrane swelling (angioedema).
The frequency of skin rash with blood morphology changes and systemic symptoms (drug rash with eosinophilia and systemic symptoms – DRESS) is not known.*

Metabolism (water-electrolyte balance), hormonal status
Commonly: fluid retention in tissues (oedema), reduced fluid excretion, weight gain, hyponatraemia (reduced sodium concentration in blood serum), and reduced plasma osmolality, which rarely may lead to water intoxication with lethargy, vomiting, headache, confusion, and other neurological disturbances.
Very rarely: increased prolactin concentration with or without clinical symptoms such as breast enlargement in men (gynaecomastia) or milk secretion (galactorrhoea). Thyroid function parameters T3, T4, TSH, and FT4 may change, especially during concomitant use with other antiepileptic drugs. Clinical symptoms usually do not occur.
Carbamazepine may reduce serum calcium levels by accelerating the breakdown of 25-OH-cholecalciferol. Very rarely, this may lead to osteomalacia (softening of bones).
Elevated cholesterol levels, including HDL cholesterol and triglycerides, may occur very rarely, as well as increased free cortisol concentration in serum.
Carbamazepine may reduce serum folate levels. There is also evidence of reduced vitamin B12 levels and increased homocysteine levels in serum during carbamazepine treatment. The frequency of high blood ammonia levels (hyperammonaemia) is not known. Symptoms of hyperammonaemia may include irritability, disorientation, vomiting, loss of appetite, and drowsiness.

Psychiatric disorders
In elderly patients: very commonly: lethargy, dizziness, fatigue, drowsiness, gait and movement disorders, sometimes headache, disorientation, and restlessness (agitation).
Uncommonly: sensory illusions (visual and auditory hallucinations), mood changes such as depression, depressive or manic moods (associated with elevated mood, aggression), loss of appetite, anxiety, aggressive behaviour, confusion, and restlessness (agitation).
Very rarely: phobic disorders (anxiety disorders), difficulty thinking, and lack of motivation. Latent psychoses (subclinical mental disorders) may be activated during carbamazepine treatment.

Nervous system
Very commonly: lethargy, dizziness, fatigue, drowsiness, gait and movement disorders, and exhaustion.
Commonly: headaches, double vision, and accommodation disorders (e.g. blurred vision), sporadically: eye movement disorders with accompanying nystagmus (involuntary eye movement), involuntary movements (e.g. tremor, twitching, tics, dystonia).
Additionally: movement disorders, e.g. involuntary movements around the mouth and face such as grimacing (orofacial dyskinesia), facial twisting movements (choreoathetosis), and speech disorders (dysarthria, slurred speech), discomfort, muscle weakness, nerve diseases (polyneuropathy), nerve inflammation (peripheral neuropathy), and paralysis symptoms (paresis).
Very rarely: taste disturbances or neuroleptic malignant syndrome.
The frequency of memory loss is not known.*
There is evidence that carbamazepine may exacerbate symptoms of multiple sclerosis.
As with other antiepileptic drugs, carbamazepine may exacerbate seizures; in particular, absence seizures (specific types of seizures originating from both brain hemispheres) may occur more frequently or recur.

Eyes
Very rarely: conjunctivitis, lens opacities, and increased intraocular pressure.
Retinotoxicity (retinal damage) has been reported in two patients associated with long-term carbamazepine therapy, which resolved after discontinuation of carbamazepine.

Ears and vestibular system
Hearing disorders such as ringing in the ears (tinnitus), increased or decreased hearing sensitivity (hyperacusis or hypoacusis), and changes in pitch perception occur very rarely.

Heart and circulatory system
Sporadically: cardiac conduction disorders (atrioventricular block), in single cases with loss of consciousness, as well as high or low blood pressure.
Sporadically or uncommonly: slow heart rate (bradycardia) and arrhythmias, circulatory collapse, heart failure, and worsening of pre-existing coronary artery disease.
Phlebitis (thrombophlebitis) and blood clots (thromboembolic disease) have also been observed.

Respiratory system
In the scientific literature, very rare cases of lung hypersensitivity reactions with fever, shortness of breath, pneumonia (pneumonitis, alveolitis), and single cases of pulmonary fibrosis have been described.

Gastrointestinal tract
Very commonly: nausea and vomiting; commonly: loss of appetite, dry mouth; sometimes: diarrhoea or constipation. Uncommonly: abdominal pain; very rarely: inflammation of the mucous membranes of the mouth and throat (stomatitis, gingivitis, glossitis) or pancreatitis.

Liver and biliary system
Changes (increases) in liver function test values are very common for gamma-glutamyltransferase, common for alkaline phosphatase, sporadic for aminotransferases, and rare for jaundice or hepatitis (hepatitis in various forms: cholestatic, hepatocellular, granulomatous, mixed) and liver diseases with destruction and atrophy of intrahepatic bile ducts. Life-threatening acute hepatitis or liver failure may occur rarely, especially in the first months of treatment.

Skin, mucous membranes, vascular system
Very commonly reported: allergic skin reactions, including severe reactions, occurring with or without fever and urticaria, sometimes manifesting as skin inflammation with peeling of the skin or mucous membranes (exfoliative dermatitis), inflammatory redness and peeling of the entire body skin (erythroderma), rarely severe and potentially life-threatening skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) (see section 2), itching (pruritus), or systemic lupus erythematosus (an autoimmune disease with vasculitis).
Very rarely: photosensitivity (light sensitivity), skin redness with target-like or nodular lesions and bleeding (erythema multiforme and nodular), small petechial skin haemorrhages (purpura), hair loss, increased sweating, skin pigmentation changes, acne, hirsutism (excessive male-pattern hair growth in women), vasculitis (inflammation of blood vessels). The frequency of acute generalized skin rash (acute generalized exanthematous pustulosis), appearance of purplish to reddish-purple macular skin lesions which may itch, and nail loss is not known.*

Musculoskeletal system:
Uncommonly: muscle weakness; very rarely: joint pain, muscle pain, and muscle cramps. These symptoms resolved after discontinuation of carbamazepine treatment.
Cases of reduced bone density (from osteoporosis to fractures) have been reported. If a patient has been taking antiepileptic drugs for a long time, has been diagnosed with osteoporosis, or is simultaneously taking cortisone or other steroid hormones, consult a doctor or pharmacist.

Urinary and reproductive system
Sporadically: kidney function disorders, e.g. protein in urine (albuminuria), blood in urine (haematuria), reduced urine production (oliguria), or increased blood urea nitrogen (azotemia); very rarely: interstitial nephritis (inflammation of kidney tissue), kidney failure, or other urinary system problems (frequent urination, painful urination, frequent urge to urinate without increased urine output (pollakiuria), urinary retention).
Additionally, very rarely: sexual disorders, e.g. impotence, reduced libido, reduced fertility in men and (or) altered sperm production (reduced number and (or) motility of sperm).

Laboratory tests
Very rarely: reduced gamma-globulin concentration in blood (hypogammaglobulinaemia) has been observed.
* Spontaneous reports and cases of adverse reactions described in the literature (frequency cannot be estimated from the available data).
In post-marketing experience, adverse reactions have been identified based on spontaneous reports and literature. Since the reports were voluntary and from an unknown population size, the frequency cannot be estimated from the available data.

If the patient notices one or more of the adverse reactions listed above, they should immediately inform the doctor so that the severity and any necessary measures can be assessed.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to gather more information on the safety of the medicine.
Adverse reactions can also be reported to the marketing authorisation holder or its representative in Poland.

5. How to store Karbamazepina Tillomed

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
No special precautions regarding storage of the medicinal product are required.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Karbamazepina Tillomed contains
Each prolonged-release tablet contains 200 mg of carbamazepine.
Each prolonged-release tablet contains 400 mg of carbamazepine.
Other ingredients are: ammonium methacrylate copolymer type B, triethyl citrate, talc, microcrystalline cellulose, monohydrate lactose, corn starch, sodium carboxymethyl starch type A, magnesium stearate.
What Karbamazepina Tillomed looks like and contents of the pack
Karbamazepina Tillomed 200 mg prolonged-release tablets: White or almost white, round, biconvex tablets, embossed with the code "297" on one side and "HP" on the other side.
Karbamazepina Tillomed 400 mg prolonged-release tablets: White or almost white, round, biconvex tablets, embossed with the code "298" on one side and "HP" on the other side.
Tablets are available in blister packs containing 30, 50, 56, 100 and 200 tablets, packed in a cardboard carton. Not all pack sizes may be marketed.
Marketing authorisation holder and manufacturer
Marketing authorisation holder
Tillomed Pharma GmbH
Mittelstrasse 5/5a
12529 Schönefeld
Germany
Importer
MIAS Pharma Limited
Suite 2, Stafford House
Strand Road
Portmarnock, Co. Dublin
Ireland
Tillomed Malta Ltd.
Malta Life Sciences Park
LS2.01.06 Industrial Estate
San Gwann, SGN 3000
Malta
This medicinal product is authorised for marketing in the Member States of the European Economic Area under the following names:
Croatia Karbamazepin Tillomed 200 mg i 400 mg tableta s produljenim Oslobađanjem
Netherlands Carbamazepine Tillomed 200 mg en 400 mg tabletten met verlengde afgifte
Germany Carbamazepin Tillomed 200 mg und 400 mg Retardtabletten
Poland Karbamazepina Tillomed
Sweden Carbamazepine Tillomed
Italy Carbamazepina Zentiva