Index of drugs

Treatment of partial epileptic seizures with or without secondary generalized tonic-clonic seizures. The drug is indicated for use as monotherapy or in combination therapy in adults and children aged 6 years and older.

1 tabl powl. contains 150 mg, 300 mg or 600 mg of oxcarbazepine (and 1.23 mg, 2.46 mg or 4.92 mg lactose, respectively).

Antiepileptic medicine. The mechanism of action of oxcarbazepine and its active metabolite (monohydroxy derivative - MHD) is based mainly on the blockade of voltage-sensitive sodium channels, which leads to stabilization of overly stimulated membranes of nerve cells, inhibition of recurrent neuronal discharges and reduction of synaptic impulses. In addition, increased potassium conductivity and modulation of voltage-dependent Calcium channels may also contribute to the anticonvulsive effect of the drug. After oral administration, oxcarbazepine is completely absorbed and extensively metabolised to the active metabolite (MHD). MHD is further transformed by conjugation with glucuronic acid. Small amounts (4% of the dose) are oxidized to a pharmacologically inactive metabolite (DHD). About 40% of MHD is bound to plasma proteins. Oxcarbazepine is excreted mainly as metabolites. Over 95% of the dose is excreted in the urine. T_0,5 oxcarbazepine is 1.3-2.3 h, while for MHD it is 9.3 +/- 1.8 h. In patients with impaired renal function, the half-life of MHD is increased by 60-90% (16-19 h) , The AUC increases twice. In children, the drug is eliminated faster. In the elderly, the maximum MHD concentration in blood and AUC are higher. No change in the pharmacokinetics of oxcarbazepine was observed in patients with mild or moderate hepatic impairment.

Hypersensitivity to the active substance or any of the excipients.

The use of oxcarbazepine is associated with the risk of serious skin reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), usually occurring in the first 3 weeks of treatment. In patients who develop a rash, if there is no other cause for this complication, the medicine should be discontinued immediately. There are no data on the use of the preparation in patients with severe hepatic impairment - caution should be exercised in determining the posology of this medicine in this patient group. The preparation should be used with caution in patients at risk of hyponatraemia (especially in the elderly) - in patients with a history of hyponatraemia associated with kidney disease, in patients receiving concomitant medications that reduce serum sodium (eg diuretics, desmopressin), as well as NSAIDs (e.g. indomethacin); in these patients, serum sodium should be measured before starting treatment, this should be repeated after approximately 2 weeks, followed by monthly intervals, for the first 3 months of treatment or if necessary. All patients with cardiac dysfunction or secondary heart failure should undergo regular body weight measurements to determine fluid retention - in the event of fluid retention or worsening of heart failure, serum sodium should be checked. Patients with a history of conduct disorder (eg atrioventricular block, arrhythmia) should undergo careful medical observation. If liver dysfunction is suspected, discontinuation should be considered. Due to the lactose content, the preparation should not be used in patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

In children of women with epilepsy, the incidence of malformations is 2-3 times higher than in the general population. Clinical data on exposure during pregnancy are still insufficient to assess the possible teratogenic effects of oxcarbazepine. If a woman taking oxcarbazepine becomes pregnant or plans to become pregnant, the use of this medicine should be carefully re-evaluated.The lowest effective dose should be used, and if possible, monotherapy should be preferred, at least in the first 3 months of pregnancy. Patients should be informed about the increased risk of malformations and provide them with the possibility of prenatal testing. During pregnancy, effective antiepileptic treatment with oxcarbazepine must not be interrupted, as exacerbation of the disease is harmful for both the mother and the fetus. Antiepileptic drugs may contribute to a deficiency of folic acid, which may cause fetal abnormalities. Folic acid supplementation is recommended before and during pregnancy. Due to the fact that the effectiveness of such supplementation has not been proven, a special prenatal diagnosis can also be offered to women who use folic acid supplementation. Results from a limited number of women indicate that plasma concentrations of the active metabolite oxcarbazepine (MHD) may gradually decrease during pregnancy. Women who take oxcarbazepine during pregnancy are advised to carefully monitor the clinical response to ensure that adequate seizure control is maintained. A study of changes in plasma MHD concentrations should be considered. If the dose is increased during pregnancy, monitoring of postnatal MHD levels may also be considered. Newborns have been diagnosed with coagulation disorders due to antiepileptic drugs. In the last weeks of pregnancy and in a newborn baby, caution should be given to vitamin K1 as a precautionary measure. Oxcarbazepine and its active metabolite (MHD) are excreted in human milk. For both compounds, the ratio of milk concentration to plasma concentration is 0.5. The effect on the child exposed to oxcarbazepine in this way is unknown. Therefore, oxcarbazepine should not be used during breastfeeding.

Very common: drowsiness, pain and dizziness, diplopia, nausea, vomiting, fatigue. Common: hyponatraemia, confusion, depression, apathy, muscle agitation, nystagmus, attention deficit disorder, amnesia, blurred vision, blurred vision, diarrhoeas, diarrhea, constipation, abdominal pain, rash, alopecia, acne, weakness. Uncommon: leukopenia, urticaria, increased liver enzymes, increased ALP activity in the blood. Very rare: thrombocytopenia, hypersensitivity [including multi-organ hypersensitivity; characterized by symptoms such as a rash, fever; reactions may affect other organs or systems, such as the lymphatic system (e.g., eosinophilia, thrombocytopenia, leukopenia, lymphadenopathy), splenomegaly; liver (eg abnormal liver function tests, hepatitis), muscles and joints (eg swollen joints, muscle aches, joint pain), nervous system (eg hepatic encephalopathy), kidneys (eg proteinuria, interstitial nephritis, insufficiency) kidneys), lungs (eg dyspnoea, pulmonary edema, asthma, bronchospasm, interstitial lung disease), hyponatremia (associated with signs and symptoms such as convulsions, confusion, disturbances of consciousness, encephalopathy, blurred vision, vomiting) , nausea), arrhythmia, atrioventricular block, pancreatitis and / or lipase and / or amylase elevation, hepatitis, angioneurotic edema, Stevens-Johnson syndrome, necrotizing toxic epidermolysis, erythema multiforme, systemic lupus erythematosus. Not known: bone marrow depression, aplastic anemia, agronulocytosis, pancytopenia, neutropenia, anaphylactic reactions; hypothyroidism, hypertension, decreased T4 concentration, there are reports indicating a decrease in bone mineral density, osteopenia, osteoporosis and fractures in patients using long-term oxcarbazepine therapy.

Orally. In monotherapy and in combination therapy, treatment starts with a clinically effective dose administered in two divided doses. The dose can be increased depending on the patient's clinical response. If other antiepileptic drugs are being replaced with oxcarbazepine, the dose of the anti-epileptic medicine (s) used should be gradually reduced after starting oxcarbazepine treatment.In combination therapy, because the total patient load of antiepileptic drugs is increased, the dose of the antiepileptic drug (s) used and / or the slower increase in the oxcarbazepine dose may need to be reduced. There is no need to monitor the plasma concentration of the drug to ensure optimal treatment with oxcarbazepine.Adults.monotherapy. Treatment should be started at a dose of 600 mg daily (8-10 mg / kg body weight daily) given in two divided doses. If there are clinical indications, the dose may be increased by a maximum of 600 mg per day in approximately one week. intervals, starting with the initial dose, to achieve the desired clinical response. Therapeutic effects are observed at doses ranging from 600 mg to 2400 mg per day. A controlled study with the monotherapy drug in patients not currently treated with antiepileptic drugs showed that 1200 mg a day was effective; in more refractory patients, switched from other anti-epileptic drugs to monotherapy, the effective dose of 2400 mg per day has been demonstrated. Under controlled hospital conditions, an increase in the dose to 2400 mg per day was achieved within 48 hours.Treatment associated. Treatment should be started at a dose of 600 mg daily (8-10 mg / kg body weight daily) given in two divided doses. If there are clinical indications, the dose may be increased by a maximum of 600 mg per day in approximately one week. intervals, starting with the initial dose, to achieve the desired clinical response. Therapeutic response is observed at doses ranging from 600 mg to 2,400 mg per day. Doses of 600 mg to 2,400 mg per day are effective, although most patients did not tolerate a dose of 2,400 mg per day without reducing the dosage of other concomitant anti-epileptic drugs, mainly due to side effects from the CNS. Daily doses above 2400 mg / day have not been systematically evaluated in clinical trials.Children and adolescents aged 6 and more.In monotherapy and combination therapy, treatment should start at a dose of 8-10 mg / kg. daily administered in two divided doses. In combination treatment, the therapeutic effect was observed after an average maintenance dose of approx. 30 mg / kg. per day. If there are clinical indications, the dose may be increased by a maximum of 10 mg / kg. daily in approx. 1-week intervals, starting from the initial dose, up to a maximum dose of 46 mg / kg. daily to get the desired clinical response. The drug is not recommended for use in children under the age of 6, because the effectiveness and safety of treatment have not been adequately confirmed.Special groups of patients. No dosage adjustment is necessary for patients with mild or moderate hepatic impairment. The use of the drug has not been evaluated in patients with severe hepatic impairment and therefore caution should be used when setting the dose in patients with severe hepatic impairment. In patients with impaired renal function (creatinine clearance less than 30 ml / min), treatment should be initiated at half the usual starting dose (300 mg / day). The dose should be increased at intervals of at least one week to achieve the desired clinical response. Increasing the dose in patients with renal function requires more careful observation.Method of administration.It can be taken with or without food. The tablets have a dividing groove and can be broken in half to facilitate swallowing of the tablet by the patient. For children who can not swallow tablets and for patients in whom the required dose can not be administered using tablets, other pharmaceutical forms are available.