Index of drugs

Tablets. Epilepsy: simple and complex partial seizures; generalized tonic-clonic seizures (especially secondary generalized), occurring during sleep and mixed-on seizures. Idiopathic neuralgia of the trigeminal nerve. Idiopathic neuralgia of the pharyngeal nerve. Pain in the course of diabetic neuropathy. Neuralgia of the trigeminal nerve in the course of multiple sclerosis. Prevention of seizures in the alcohol withdrawal syndrome in a hospital setting.Tablets with prolonged release. Epilepsy: simple and complex partial seizures; generalized tonic-clonic seizures (especially secondary generalized), occurring during sleep and mixed-on seizures. Idiopathic neuralgia of the trigeminal nerve. Idiopathic neuralgia of the pharyngeal nerve. Pain in the course of diabetic neuropathy. Neuralgia of the trigeminal nerve in the course of multiple sclerosis. Prevention of bipolar disorder in patients not responding to lithium treatment. Prevention of seizures in the alcohol withdrawal syndrome in a hospital setting. Note: if changing from an immediate release pharmaceutical form to prolonged release tablets, ensure that appropriate carbamazepine concentrations are obtained in the plasma.

1 tabl contains 200 mg carbamazepine. 1 tabl sustained release contains 200 mg or 400 mg carbamazepine.

Carbamazepine is a derivative of iminostilbene. The precise mechanism of action of carbamazepine is unknown. The therapeutic effect is first and foremost attributed to the blocking of synaptic conduction and, in this way, reduction in the conduction of convulsive discharges. At higher concentrations, carbamazepine decreases the suppressive tone of the response to the stimulus. The limitation of pain in trigeminal neuralgia is probably caused by the inhibition of the conduction of nerve impulses in the trigeminal nuclei. Carbamazepine is characterized by both anticonvulsant and psychotropic effects. Following oral administration, carbamazepine (depending on the pharmaceutical form) is absorbed relatively slowly and almost completely. The maximum concentration in the blood is reached after 4-16 h (very rarely after 35 h), and in children 4-6 h after a single oral dose. The blood levels of the prolonged-release tablets are smaller compared to regular tablets. Steady state is achieved after 2-8 days. Carbamazepine binds to 70-80% plasma proteins, the pharmacologically active metabolite - carbamazepine 10,11-epoxide is associated with plasma proteins in 48-53%. In the liver, carbamazepine is oxidized, deaminated, hydroxylated and partially esterified with glucuronic acid. The main metabolite is pharmacologically inactive. The active metabolite that exhibits anticonvulsant activity is carbamazepine 10,11-epoxide. Following a single oral dose of carbamazepine, the half-life in blood is approximately 36 hours (range: 18-65 h). During long-term treatment, the half-life is reduced due to enzyme induction by about 50%. The half-life of carbamazepine in blood is shorter during combination therapy (6-10 h) compared to monotherapy (11-13 h); it is shorter in children compared to adults and shorter in infants compared to newborns. About 72% of a single oral dose is excreted in the urine as metabolites; the remaining 28% are excreted in the faeces, partly in unchanged form. Only 2-3% of the dose is excreted in the urine as unchanged carbamazepine. Carbamazepine penetrates the placental barrier, reaches the fetus and is excreted in breast milk (approximately 58% of plasma concentration).

Hypersensitivity to carbamazepine or other components of the preparation and to medicines with a similar chemical structure (eg tricyclic antidepressants). Bone marrow dysfunction, history of bone marrow suppression. Atrioventricular block. acute porphyria interrupted. Concomitant use with MAO inhibitors, or within 14 days of discontinuing their administration. Co-administration with voriconazole as it interferes with carbamazepine.

Do not use in patients with type epileptic seizuresabsences, mixed seizures (typical or unusual seizures) and patients in the Chinese and Thai populations with the HLA-B * 1502 allele. Use after a thorough risk / benefit assessment and after taking the necessary precautions in patients with existing or past haematological diseases and haematological reactions with other medications, a history, disturbed sodium metabolism, heart, liver and kidney disorders and with myotonic dystrophy. Treatment should be discontinued in the event of severe allergic reactions, hypersensitivity reactions, leucopenia (mainly neutropenia), thrombocytopenia and worsening of seizures, as well as in cases of petechia or purpura bleeding, hepatic insufficiency, reductions in erythrocytes below 4 million / mm³, hematocrit reduction less than 32%, hemoglobin decrease below 11 g%, decrease in the number of leukocytes below 2000 / mm³ and granulocytes below 1000 / mm, respectively³ or thrombocytes less than 80,000 / mm³ and symptomatic hemopoetic disorder. Changing the form of the drug from oral to rectal can be associated with an increased risk of epilepsy. If it is necessary to reduce the dose or change carbamazepine to another anticonvulsant in patients with epilepsy, stop the sudden discontinuation of the drug and reduce the dose gradually. If abrupt discontinuation of carbamazepine is necessary, conversion to another antiepileptic drug should be made with the appropriate medication (eg diazepam in rectal or intravenous administration or phenytoin in intravenous administration). Carefully monitor for signs of suicidal ideation or suicidal behavior and, if necessary, consider appropriate treatment. Table. about release: it is not recommended to use this form of preparation in children under 6 years of age; in case of change from the table about immediate release on the tabl. about release, it must be ensured that appropriate concentrations of carbamazepine are obtained in the plasma. 

Carbamazepine can be used during pregnancy and lactation only after careful consideration of the therapeutic benefit of the risk. Women of childbearing age should be informed about the need for planning and increased medical control of pregnancy. During pregnancy, carbamazepine should be used as monotherapy, due to the increased risk of developing congenital defects in combination with other antiepileptic drugs. In the first trimester (especially between 20 and 40 days after fertilization) the lowest effective dose should be used. It is recommended to regularly determine the concentration of the drug in plasma and keep them in the lowest therapeutic range. Under no circumstances should you stop treatment without consulting your doctor, because fits can harm your baby. Antiepileptic drugs can lead to folic acid deficiency - folic acid is recommended both before and during pregnancy. Newborns have been diagnosed with coagulation disorders due to antiepileptic drugs, therefore, in the last weeks of pregnancy and in a newborn baby, prophylactic vitamin K should be given. Several cases of convulsions and / or depression of the neonatal respiratory center and vomiting, diarrhea and / or reduced food intake in connection with taking the preparation. They can also be symptoms of withdrawal syndrome in newborns. Carbamazepine and its active matabolites are excreted in breast milk. The preparation can be used during breastfeeding, however, the child should be observed for side effects. Withdrawal from the breast is recommended when the lack of proper weight gain, the child is excessively calm or lethargic. Carbamazepine may weaken the effectiveness of hormonal contraceptives - women of childbearing age should use non-hormonal contraception during treatment with the product.

The occurrence of side effects is greater in the case of combination therapy than monotherapy. Very common: leukopenia, increased γ-glutamyl transpeptidase, allergic dermatitis, urticaria, dizziness, drowsiness, ataxia, malaise, vomiting. Common: thrombocytopenia, eosinophilia, hyponatremia (which causes fluid retention, edema, weight gain and decreased plasma osmolarity), headache, diplopia, accommodation disorders (blurred vision), dry mouth, lack of appetite, increased alkaline phosphatase .Uncommon: involuntary movements (flutter tremors, dystonia, tics), nystagmus, diarrhea, constipation, increased transaminase levels, exfoliative dermatitis, erythroderma. Rare: leukocytosis, lymphadenopathy, folic acid deficiency, acoustic and visual hallucinations, depression, phobia, aggressive behavior, agitation, confusion, thinking disorders, speech disorders, orofacial dyskinesia, choreoathetosis, peripheral neuritis, paresthesia, limb paresis, motion disorders eyeball, conduction abnormalities, hypertension, hypotension, abdominal pain, cholestatic or hepatocellular carcinoma or mixed type hepatitis, jaundice, systemic lupus erythematosus, pruritus, muscle weakness, late type hypersensitivity with fever, skin rash, vasculitis, swollen lymph nodes, pain arthritis, leukocyte count, eosinophilia, hepatomegaly, or changes in liver function tests, as well as effects on other organs, ie lungs, kidneys, pancreas, myocardium and colon. Very rare: agranulocytosis, aplastic anemia, pancytopenia, bone marrow aplasia, anemia, megaloblastic anemia, porphyria, reticulocytosis, hemolytic anemia, aseptic meningitis with clonic seizures and eosinophilia, anaphylactic reactions, angioneurotic edema, increased prolactin levels with symptoms (or asymptomatic) mlekotoku, gynecomastia, thyroid dysfunction (decrease in FT4, T3, T4) and increase in TSH, bone metabolism disorders, osteoporosis / osteomalacia, increase in cholesterol, HDL and triglycerides, activation of latent psychotic syndrome, taste disorders, neuroleptic malignant syndrome, loss of lens transparency, conjunctivitis, increased intraocular pressure, impaired hearing (tinnitus, increased or decreased auditory sensitivity, changes in tone perception), bradycardia, arrhythmia, atrio-ventricular block sometimes with loss of consciousness cysts, collapse, congestive heart failure, exacerbation of coronary heart disease, thrombophlebitis, thromboembolic episodes, hypersensitivity reactions of the lungs with fever, dyspnoea, also inflammation or pulmonary fibrosis (treatment should be discontinued), stomatitis, gums, tongue, pancreatitis, granulomatous hepatitis, hepatic failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, hypersensitivity to light, erythema multiforme and nodular, changes in skin pigmentation, purpura, alopecia, profuse sweating, acne, hirsutism, joint pain , muscle pain, muscle spasms, interstitial nephritis, renal failure, proteinuria, hematuria, oliguria, increased blood urea nitrogen, frequent urination, urinary retention, spermiogenesis disorders (decreased sperm count and / or decreased motility), impaired fertility men, disorders libido, impotence. Isolated cases: reduction of folic acid, vitamin B₁₂ and homocysteine ​​in blood serum. There have been reports of exacerbation of MS symptoms. Carbamazepine may increase the frequency of epileptic seizures, type epileptic seizuresabsences they can be intensified or triggered. There have also been cases of suicidal thoughts and behaviors. There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients using carbamazepine in long-term therapy.

Orally. Treatment should be started with small doses, selected individually depending on the clinical condition of the patient. The dose is then gradually increased until the optimal maintenance dose is obtained. The therapeutic dose, especially in combination therapy, should be determined based on the concentration of the drug in the blood. The therapeutic concentrations of carbamazepine are 4-12 μg / ml. Typically, doses of 400-1200 mg per day are used in 1, 2 or several individual doses. The maximum daily dose (in exceptional cases) should not exceed 1600 mg, due to the significant increase in side effects at higher doses. In individual cases, the required dose may significantly differ from the initial and maintenance doses given (e.g., due to the increased or reduced breakdown of the drug due to the action of inducing or inhibiting enzymes in combination therapy).If other anti-epileptic preparations are replaced with carbamazepine preparations, the dose of the drug withdrawn should be reduced gradually. If possible, you should be treated with one antiepileptic medicine.
Epilepsy. Table. 200 mg. Adults: starting dose - 100-400 mg per day, maintenance dose - 600-1200 mg per day. Children: a maintenance dose of 10-20 mg / kg / day; 3-5 years (if they are able to swallow the tablet) - the starting dose is 100-200 mg per day, maintenance dose 200-400 mg per day; 6-10 years - initial dose 200 mg daily, maintenance dose 600 mg per day; 11-15 years - initial dose 200-300 mg per day, maintenance dose 600-1200 mg per day. Table. about release. Adults: initial dose - 100-400 mg in the evening, maintenance dose - 600-1200 mg per day. Children: a maintenance dose of 10-20 mg / kg / day; 6-10 years - initial dose of 100 mg in the evening, maintenance dose 400-600 mg per day; 11-15 years - initial dose of 100 mg in the evening, maintenance dose 600-1000 mg per day.Neuralgia of the trigeminal nerve, neuralgia of the pharyngeal nerve: usually 200-400 mg per day, the dose is increased until the relief of pain usually reaches 400-800 per day in 1 or 2 divided doses; in some cases, treatment can be continued with a reduced maintenance dose of 400 mg per day; after the pain has disappeared, reduce the dose gradually and use a maintenance dose if pain returns. in particularly sensitive or elderly patients, the recommended starting dose is 100-200 mg per day.Pain in diabetic neuropathy: normally 600 mg per day, in exceptional cases 1200 mg per day.Neuralgia of the trigeminal nerve in multiple sclerosis: usually 400-800 mg per day.Prevention of seizures in the alcohol withdrawal syndrome in a hospital setting: usually 600 mg per day, in severe cases 1200 mg per day; combination with sedative and hypnotics is not recommended; in patients with severe cardiovascular disease, liver disease or kidney failure, and in the elderly, a reduced dose may be present.Prevention of bipolar disorder. Table. about release: initial dose 200-400 mg per day, maintenance dose up to 800 mg per day. In patients with severe cardiovascular disease, liver disease or kidney failure, and the elderly, a reduced dose may be sufficient.
The tablets are divisible, they should be taken during or after a meal in divided doses. A good efficacy of a daily dose divided into 4-5 doses has been demonstrated. Table. about release can be dissolved in water.