Index of drugs

Epilepsy: simple partial seizures, partial complex seizures, generalized tonic-clonic seizures (grand mal), mixed forms of epilepsy. Neuralgia of the trigeminal nerve. Spontaneous neuralgia of the pharyngeal nerve. Prevention of seizures in the alcohol withdrawal syndrome in hospitalized patients. Prevention of bipolar disorder, especially in patients who do not respond to lithium therapy.

5 ml of the suspension contains 100 mg of carbamazepine. 1 tabl contains 200 mg. 1 tabl sustained release contains 150 mg carbamazepine.

Antiepileptic medicine. The main mechanism of action of carbamazepine is the change in the ability of the neuron to induce high frequency action potentials. It limits the persistent, repetitive, high-frequency action potentials of sodium-dependent channels through the inactivation of sodium channels, resulting in functional and potential-dependent block of sodium channels. In addition, it inhibits synaptic conduction by acting on presynaptic sodium channels, thereby reducing the activity of potential Calcium dependent channels. At higher concentrations, carbamazepine modifies the metabolism of gamma-aminobutyric acid and presumably also catecholamine transmission. Therefore, this drug has psychotropic properties. The analgesic effect in trigeminal neuralgia is probably the result of inhibition of synaptic conduction in the trigeminal core. It is relatively slow and almost completely absorbed from the gastrointestinal tract. After a single dose of C_max in adults it is achieved depending on the form of the drug between 4 and 16 h (in very rare cases after 35 h); in children after 4-6 h. Steady state is achieved after 2-8 days of treatment. Carbamazepine is 70-80% bound to plasma proteins and its pharmacologically active metabolite (carbamazepine 10,11-epoxide) is 48-53%. The concentration of carbamazepine in the cerebrospinal fluid is approximately 33% of the concentration in the blood. The concentration in the saliva corresponds to the concentration of the free substance and remains in good correlation with the concentration in the blood - about 20-30% (the value of the concentration in saliva after multiplication by 4 can be used to estimate the concentration in the blood). Carbamazepine passes the placental barrier and into breast milk (the milk concentration is approximately 58% in the blood). It is metabolized in the liver to 10,11-epoxide, which has antiepileptic activity, and other metabolites. T_0,5 carbamazepine is about 36 h after a single dose, in long-term treatment is shorter - 10-20 h due to enzymatic induction. The half-lives when used with another antiepileptic medicine are shorter than in monotherapy. In children, they are shorter than in adults, in newborns longer than in infants. After a single oral administration, 72% of the dose is excreted in the urine in the form of metabolites (only 2-3% in the unchanged form), 28% in the faeces, including a small part in the unchanged form.

Hypersensitivity to carbamazepine or drugs with a similar chemical structure (eg tricyclic antidepressants) or to any of the excipients. History of bone marrow dysfunction. Atrioventricular conduction disorders (atrioventricular block). acute porphyria interrupted in an interview. NO Cancer - carbamazepine may induce or enhance unconscious seizures. Concomitant use of MAO inhibitors (they should be discontinued at least 14 days before the start of carbamazepine treatment).

Particularly with caution (after considering the risk-benefit ratio), patients should be treated with hematological disorders, water and electrolysis disorders (disorders of sodium metabolism) and disorders of the heart, liver or kidneys. Caution should be exercised in patients with glaucoma (regular intraocular pressure measurements are indicated), in patients with hypersensitivity to oxcarbazepine or phenytoin (cross-overkill with carbamazepine may occur) and in the elderly.Caution for use in patients of the yellow race, originating in Southeast Asia, due to the risk of severe skin reactions. Studies have shown a correlation between skin reactions and the presence of the HLA-B * 1502 allele in these patients. Before beginning treatment with carbamazepine in patients of the aforementioned origin in genetic risk populations, testing for the HLA-B * 1502 allele is recommended; in patients with a positive test result, carbamazepine should be avoided. Due to the possibility of suicidal thoughts and behaviors, all patients taking the preparation should be closely monitored for signs of psychiatric disturbances. If fever, sore throat, flu-like symptoms or allergic skin reactions (rash with enlarged lymph nodes) occur during treatment with carbamazepine, blood counts should be performed. Treatment with carbamazepine should be discontinued in case of petechiae, reduction in erythrocytes below 4 million / mm³, hematocrit reduction less than 32%, hemoglobin decrease below 11 g%, decrease in the number of leukocytes below 2000 / mm³granulocytes below 1000 / mm³ or thrombocytes less than 80,000 / mm³as well as in case of severe allergic reactions, exacerbating rash or severe skin reactions (ie Stevens-Johnson syndrome, toxic epidermal necrolysis). Before and during treatment, the blood picture should be checked and the liver and kidney function tests should be performed (in the first month of treatment every week, then every month, and after 6 months of therapy - 2-4 times in a year). It is recommended to monitor the concentration of carbamazepine in the blood, especially in polytherapy (range of therapeutic concentrations 4-12 μg / ml). The oral suspension contains p-hydroxybenzoates that can cause allergic reactions (including those of late type). The prolonged-release tablets should not be used in children and adolescents (no clinical trials).

Carbamazepine can be used during pregnancy only after considering the benefits of administering the preparation against the risk of fetal malformation. Women of childbearing age should be advised to plan their pregnancy and to monitor their pregnancy in a special way. Since the risk of fetal malformations is increased in combination therapy, in women of childbearing age and in pregnant women, whenever possible carbamazepine should be administered as monotherapy. If starting a therapy with a pregnant woman or continuing treatment of a woman who became pregnant during carbamazepine treatment, the lowest dose should be used to prevent seizures, especially between the 20th and 40th day of pregnancy. The reason for the developmental defects are probably the maximum concentration of the drug in the blood, so the daily dose should be divided into several smaller single doses, distributed over a 24-hour period. It is recommended to monitor the concentration of the drug in the blood and keep it in the lower therapeutic range (3-7 μg / ml). Due to the action of carbamazepine inducing microsomal enzymes of the liver, it is beneficial to give folic acid to women before and during pregnancy. It is also recommended to administer vitamin K to a pregnant woman in the last weeks of pregnancy and a newborn baby. Carbamazepine and its active metabolite are excreted in human milk, but in small amounts. Only after finding a reduction in the weight gain of the newborn or increased drowsiness, breastfeeding should be discontinued.

Disorders o.u.n. - drowsiness, sedation, impaired motor coordination (irregularity), headache and, especially in the elderly, confusion and agitation were commonly observed; rarely: involuntary movements (eg thick-fluttering fluttering hands, tics and nystagmus); in individual cases: speech disorders, sensation, muscle weakness, peripheral nerve inflammation, paraparesis, taste disturbances, aggressive behaviors, depressive states, difficulties in logical thinking, weakening of the drive, hallucinations and tinnitus. Carbamazepine may activate latent psychotic disorders. In addition, elderly people and patients with brain damage may experience facial dyskinesias (involuntary movements of the muscles around the mouth, grimaces, distortion of facial features), and choreoathetosis.Disorders of the digestive system - lack of appetite, dryness of the oral mucosa, nausea and vomiting, and less frequently diarrhea or constipation; uncommon: changes in the results of liver function tests; rarely: jaundice; in individual cases: hepatitis (cholestatic, granulomatous, mixed parenchyma) and abdominal pain, inflammation of the lining of the mouth and throat (inflammation of the gums, tongue). Pancreatitis may occur.Disorders of the circulatory system - rarely: atrioventricular block, in individual cases with fainting; very rare (especially in elderly patients or with a history of heart disease): bradycardia, arrhythmia and exacerbation of ischemic heart disease; there may also be: increase or decrease in blood pressure and thromboembolic disorders (thrombophlebitis, thromboembolism and thrombosis).Disorders of the hematopoietic system- leukocytosis, eosinophilia or leukopenia, thrombocytopenia. In the light of the literature, the most common is benign leukopenia, which is transient in 10% of cases and persistent, resistant in 2%; in individual cases: life-threatening disorders, i.e.: aplastic anemia, agranulocytosis, hemolytic anemia or megaloblastic anemia. Enlargement of lymph nodes or spleen may occur.Disorders of the genitourinary system - renal dysfunction, partly due to the antidiuretic effect of carbamazepine, i.e. proteinuria, hematuria, oliguria, renal insufficiency and incontinence (painful, frequent urination, urinary retention); in individual cases: impotence and decreased sex drive.Skin and mucous membrane and vascular system disorders - skin allergic reactions with or without fever, i.e. urticaria, pruritus, hypersensitivity to sunlight; in individual cases: exfoliative dermatitis, erythroderma, toxic epidermal necrolysis, exudative erythema multiforme and erythema nodosum, Stevens-Johnson syndrome, disseminated lupus erythematosus, alopecia, sweating, vasculitis.Eye disorders - conjunctivitis, transient visual disturbances (accommodation disorder, double vision); isolated cases of clouding of the eye lens.Respiratory system disorders - isolated cases of allergic reactions associated with fever, dyspnea, pneumonia or pulmonary fibrosis.Musculoskeletal disorders - pain in the joints, muscles, muscle contraction.Metabolism, water-electrolyte and endocrine disorders - hyponatremia with vomiting, headache, confusion has been observed occasionally due to the antidiuretic effect of carbamazepine; isolated cases of edema and weight gain. Carbamazepine may reduce the level of calcium in the blood by accelerating the metabolism of 25-hydroxy-cholecalciferol - this leads in individual cases to osteomalacia (softening the bones). Gynecomastia and mycotoxicity may occur. Thyroid parameters: T₃, T₄, TSH and FT₄ they may change, especially during combination therapy. In two cases there was a sharp interrupted porphyry.Hypersensitivity reactions - rarely: late-type allergic reactions with fever, skin rash, vasculitis, lymphadenopathy, joint pain, leukopenia, eosinophilia, hepatosplenomegaly, and altered liver function parameters. These symptoms can occur in various combinations and also affect other organs (lungs, kidneys, pancreas, myocardium); very rare: severe generalized allergic reactions with aseptic meningitis, myoclonus, eosinophilia.

Orally. Treatment should be started with a low daily dose, slowly increasing until optimal performance. Do not exceed the dose of 1600 mg / day.Tablets and suspension. Adults in epilepsy initially 200-400 mg per day, then the dose is gradually increased to a maintenance dose of 600-1200 mg per day. Children in epilepsy - children up to 1 year of age: starting dose of 100 mg per day, maintenance dose 100-200 mg per day; children 1-5 years: initial dose 100-200 mg daily, maintenance dose 200-400 mg per day; children 6-10 years: initial dose 200 mg daily, maintenance dose 400-600 mg per day; children 11-15 years: initial dose 200-300 mg per day, maintenance dose 600-1000 mg per day.Children under 4 years of age are advised to gradually start the initial dose, starting at 20-60 mg daily and increasing it every other day by 20-60 mg until the recommended therapeutic dose is reached. For children over 4 years, the initial dose may be 100 mg per day and may be increased by 100 mg every other day or once a week until the therapeutic dose is reached. The average maintenance dose in children is 10-20 mg / kg / day. Children under 6 years of age should receive the preparation as an oral suspension, enabling the precise administration of small doses. In neuralgia, initially 200-400 mg per day in 1-2 divided doses (initial dose for elderly patients is 200 mg per day in 2 divided doses), then the dose is increased to the lowest effective analgesic, ie usually up to 400-800 mg daily for 2-4 divided doses. In some patients, it is possible to continue treatment with a maintenance dose of 400 mg daily for 2 divided doses. In the prevention of epileptic seizures in patients hospitalized in alcohol withdrawal syndrome, usually 600 mg per day in 3 divided doses; in severe cases, it is administered in the first days of treatment up to 1200 mg per day in 3 doses. For the prophylaxis of bipolar disorder, initially 200-400 mg per day in 1-2 divided doses, if necessary, the dose is increased to 800 mg per day in 2-4 divided doses.Tablets with prolonged release. In epilepsy, adults initially receive 300 mg once a day, then the dose is increased to 600-1200 mg per day in 1-2 divided doses. Children: conventional and direct-release carbamazepine (tablets or oral suspension) are used in the initial and maintenance treatment of children and adolescents. In nerve pain, initially 150-300 mg per day in 1-2 divided doses (the starting dose for elderly patients is 150 mg once a day), then the dose is increased to the lowest effective analgesic, i.e. typically up to 300-900 mg per day 1-2 divided doses. In some patients, it is possible to continue treatment with a maintenance dose of 300-450 mg daily for 1-2 divided doses. In the prevention of epileptic seizures in patients hospitalized in the alcohol withdrawal syndrome, usually 600 mg daily in 2 divided doses, in severe cases administered in the first days of treatment 1200 mg per day. For the prophylaxis of bipolar disorder, initially 300 mg per day in 1-2 divided doses, if necessary, the dose is increased to 300-450 mg per day in 2 divided doses.
Lower doses are recommended in patients with cardiovascular disease, kidney or liver problems, and the elderly.
In epilepsy, the use of carbamazepine monotherapy is recommended. When changing another antiepileptic medicine to carbamazepine, the dose of the previous drug should be gradually reduced. Anti-epileptic therapy is long-term. When the seizure control is achieved, the dose should not be changed without significant need due to the low therapeutic index of carbamazepine - even slight fluctuations in the blood levels of the drug may lead to recurrence of seizures or side effects. The decision to terminate treatment can be made at the earliest after a two- or three-year period without seizures. The drug should be discontinued gradually reducing the dose within 1-2 years. Treatment of neuralgia lasts for several weeks. The lowest dose with analgesic effect should be used. The therapeutic dose should be gradually reduced to determine if spontaneous remission has occurred. If the pain recurs, return to the initial therapeutic dose. The administration of carbamazepine in the prophylaxis of seizures in the alcohol withdrawal syndrome in hospitalized patients should be completed after 7-10 days by a gradual reduction of the dose. In delirium t Remens, concomitant administration of carbamazepine and sedative hypnotics is not recommended. However, when the clinical situation so requires, it is possible to simultaneously use carbamazepine with other drugs to control the symptoms of the alcohol withdrawal syndrome. Prevention of recurrences of bipolar disorder is a long-term treatment.
The preparation should be used during meals or after meals, drink with a small amount of liquid or take after pouring the tablets with water (tablets will form a suspension in water). The delayed absorption of the drug in the case of prolonged release tablets is also maintained after the aqueous suspension has been prepared from the tablet.In some cases, dividing the daily dose into 4-5 single doses distributed throughout the day is associated with greater effectiveness of the drug. In the above dosing schedule, conventional forms with direct release of carbamazepine are applicable.