Finlepsinum of the tab. of 200 mg No. 50

Pharmacological properties

Pharmacodynamics. as anticonvulsant: the range of activity of medicament Finlepsinum covers partial attacks (simple and complex) with secondary generalization and without it, generalized toniko-clonic convulsive attacks and also combinations of the specified types of attacks.

Mechanism of effect of carbamazepine, active agent of drug, is found out partially. Carbamazepine stabilizes membranes of the overexcited nerve fibrils, inhibits emergence of repeated neuronalny categories and reduces synoptic carrying out exciting impulses. It is quite possible that prevention of repeated formation of natriyzavisimy action potentials in the depolarized neurons by blockade of natrium channels which depends on duration of use and a voltage can be the main mechanism of effect of drug. While reduction of release of a glutamate and stabilization of membranes of neurons can explain anticonvulsant effect of drug, the anti-maniacal effect of carbamazepine can be caused by oppression of metabolism of a dopamine and noradrenaline.

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At use of carbamazepine as monotherapy at patients with epilepsy (especially at children and teenagers) noted the psychotropic effect of medicament which was partially shown by positive influence on symptoms of uneasiness and a depression and also decrease in irritability and aggression.

As neurotropic means Finlepsinum is effective in some neurologic diseases. So, for example, it prevents painful attacks in an idiopathic and secondary epileptiform neuralgia. Besides, medicament should be used for reduction of severity of a neurogenic pain at various states, including at tabes, posttraumatic paresthesias and post-herpetic neuralgia. At a syndrome of alcoholic abstinency medicament raises a threshold of convulsive readiness (which at this state is reduced) also the expressiveness of clinical manifestations of a syndrome, such as excitability, tremor, disturbance of gait reduces. At patients with not diabetes of the central genesis medicament reduces a diuresis and feeling of thirst.

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It is confirmed that as psychotropic medicament Finlepsinum is effective at affective disturbances, namely: for treatment of acute maniacal conditions, for the supporting treatment of bipolar affective (manic-depressive) disorders (as monotherapy, and in a combination with neuroleptics, antidepressants or medicaments of lithium).

Pharmacokinetics. After oral administration, carbamazepine is soaked up slowly and almost completely. The semi-absorption period = 8.5 h also is in the wide range (≈1.72-12 h). After single dose of the C _max carbamazepine in blood plasma at adults is reached in 4–16 h (very seldom — in 35 h), at children — in ≈4–6 h. Concentration of carbamazepine in blood plasma is not in linear dependence on a dose, and in case of use of higher doses the concentration curve in blood plasma has a plateau appearance.

Equilibrium concentration is reached by

in 2–8 days. The strong correlation between a dose of carbamazepine and equilibrium concentration in blood plasma is absent.

Rather therapeutic and toxic concentration of carbamazepine it is specified in blood plasma by p that disappearance of attacks is possible at concentration in blood plasma of 4-12 mkg/ml. The concentration of medicine in blood plasma exceeding 20 mkg/ml worsen a course of the disease.

In case concentration of active agent in blood plasma makes 5–18 mkg/ml, disappearance of pain in an epileptiform neuralgia is noted.

Linking of carbamazepine with proteins of blood plasma makes 70–80%. The percent untied with proteins at concentration of carbamazepine of 50 mkg/ml remains to constants.

Binding pharmacological of an active metabolite carbamazepine-10.11-epoxide with proteins of blood plasma makes 48–53%. Concentration of carbamazepine in SMZh makes 33% of its concentration in blood plasma.

Karbamazepin gets through a placental barrier, into breast milk.

carbamazepine is removed by

After single dose from blood plasma with T _½ =36 h. In case of long-term treatment of T _½ it is reduced by 50% in connection with induction of microsomal enzymes of a liver.

At healthy people the general plasma clearance of plasma of ≈19.8 ml/h/kg, at patients at monotherapy is ≈54.6 ml/h/kg, in case of the combined treatment of ≈113.3 ml/h/kg. After single dose of carbamazepine in 72% of a dose in the form of metabolites it is brought out of an organism by kidneys. Other 28% are removed with a stake, partially — in not changed look. Only 2–3% of the substance emitted with urine are a carbamazepine in not changed look.

Indication

Epilepsy:

• difficult or simple partial convulsive attacks (with a loss of consciousness or without) with secondary generalization or without it;
• generalized toniko-clonic convulsive attacks;
• mixed forms of convulsive attacks.

Monoterapiya's

or as a part of combination therapy:

• acute maniacal conditions; maintenance therapy in bipolar affective disorders for the purpose of prevention of aggravations or for reduction of expressiveness of clinical manifestations of aggravation;
• syndrome of alcoholic abstinency;
• an idiopathic epileptiform neuralgia and an epileptiform neuralgia in multiple sclerosis (typical and atypical);
• idiopathic neuralgia of a glossopharyngeal nerve.

Use

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Finlepsinum is appointed orally, usually daily dose should be distributed on 2–3 receptions. it is possible to take the medicament at meal time, after a meal or in intervals between meals, washing down with a small amount of liquid. the tablet of Finlepsinum can be divided into equal half.

Before an initiation of treatment the patients belonging to the Chinese ethnic group of Khan or patients of the Thai origin have to undergo, as far as possible, inspection on existence of HLA-B*1502 as this the allele can provoke development of a heavy karbamazepinassotsiirovanny syndrome of Stephens — Johnson.

Epilepsy. Treatment begins with use of a low daily dose which is slowly raised further (to be adjusted, considering needs of each specific patient) before achievement of optimum effect.

should appoint Finlepsinum by

In cases when it is possible, in the form of monotherapy, but at use with other medicines recommend the mode of the same gradual increase in a dose of drug. If to add Finlepsinum to already existing antiepileptic therapy, the dose of medicament should be raised gradually, at the same time doses of the used medicaments do not change or in case of need adjust.

Adults and children are aged more senior than 15 years. The recommended initial dose — 100–200 mg 1–2 times a day, then gradually raise a dose to achievement of optimum effect; usually daily dose = 800–1200 mg. Finlepsinum dose which reaches 1600 mg or even 2000 mg/days

Patients of advanced age can be required by some patients. Considering medicinal interactions and various pharmacokinetics of antiepileptic drugs, patients of advanced age of a dose of Finlepsin should select with care.

Children aged from 5 years. Treatment it is possible to begin 100 mg/days with use of a dose, the dose is increased gradually — every week by 100 mg.

Usually treatment should carry out by

in a dose 10–20 mg/kg of body weight a day (in stages).

Children at the age of 5–10 years — 400–600 mg/days (for 2–3 receptions).

Children at the age of 10–15 years — 600–1000 mg/days (for 3–5 receptions).

Acute maniacal conditions and the supporting treatment of affective (bipolar) disorders. Range of doses is 400–1600 mg/days. Usually therapy carry out in a dose 400–600 mg/days for 2–3 receptions. At treatment of acute maniacal conditions the medicament dose Finlepsinum should be raised pretty fast. At maintenance therapy of bipolar disorders for ensuring optimum shipping the gradual increase is recommended by low doses.

Alcoholic abstinence syndrome. The average dose makes 200 mg 3 times a day. In hard cases during the first several days the dose can be raised (for example to 400 mg 3 times a day). At heavy manifestations of alcoholic abstinency the treatment is begun with a medicament Finlepsinum combination with sedative and somnolent medicaments (for example with klometiazoly, chlordiazepoxide), adhering to the above-stated instructions on a dosage.

Finlepsinum medicament treatment can be continued by

After end of a sharp phase in the form of monotherapy.

Idiopathic epileptiform neuralgia and an epileptiform neuralgia in multiple sclerosis (typical and atypical). Idiopathic neuralgia of a glossopharyngeal nerve. The initial dose of the medicament Finlepsinum makes 200–400 mg/days (100 mg 2 times a day for patients of advanced age). It should be raised slowly to disappearance of pain (usually to a dose of 200 mg 3–4 times a day). In certain cases the daily dose of medicament of 1600 mg can be required. After the termination of pain the dose should be reduced to the minimum supporting gradually.

Contraindication

should not appoint Finlepsinum:

• at the established hypersensitivity to carbamazepine or similar medicines (tricyclic antidepressants) in the chemical plan, or other components of drug;
• at AV blockade;
• to patients with oppression of function of marrow in the anamnesis;
• to patients with a hepatic porphyria (for example the sharp intermittent porphyria mixed by a porphyria, a late porphyria of skin) in the anamnesis;
• in a combination with MAO inhibitors;
• in combination with vorikonazoly as treatment can be inefficient.

Side effects

Side effects arose at the combined treatment more often, than at monotherapy. depending on a dose and generally in an initiation of treatment there can be certain side effects. in general they disappear independently in 8–14 days or after a temporary dose decline.

from blood and lymphatic system: a leukocytosis, an eosinophilia, a leukopenia, thrombocytopenia, deficiency of folic acid, an agranulocytosis, aplastic anemia, a pancytopenia, an erythrocyte aplasia, anemia, megaloblastny anemia, the sharp alternating porphyria, the mixed porphyria, a late skin porphyria, a reticulocytosis, hemolytic anemia, insufficiency of marrow is possible.

from the immune system: medicamentous rash with an eosinophilia and system symptoms (DRESS), multiorgan hypersensitivity of the slowed-down type with fever, skin rash, a vasculitis, a lymphadenopathy; the signs reminding a lymphoma; an arthralgia, a leukopenia, an eosinophilia, a gepatosplenomegaliya, abnormal results of hepatic tests and a syndrome of disappearance of bile ducts (destruction and disappearance of intra hepatic bile ducts), arising in different combinations; aseptic meningitis with a myoclonus and a peripheral eosinophilia, anaphylactic reaction, a Quincke's disease, a hypogammaglobulinemia. There can be disturbances from other bodies (for example a liver, lungs, kidneys, a pancreas, a myocardium, a large intestine).

from an endocrine system: hypostases, a liquid delay, increase in body weight, a hyponatremia and decrease in osmolarity of blood plasma because of effect of the carbamazepine similar to effect of antidiuretic hormone that sometimes leads to an overhydratation which is followed by a lethargy, vomiting, a headache, confusion of consciousness and neurologic disorders, increase in level of prolactin with or without clinical symptoms, such as galactorrhoea and gynecomastia; abnormal results of tests of function of a thyroid gland: decrease in level of L-thyroxine (FT ₄ , T ₄ , T ₃ ) and increase in TSH which usually takes place without clinical manifestations, disturbances of indicators of bone metabolism (decrease in level of calcium in blood plasma and 25 hydroxycholecalciferols in blood plasma which attracts osteomalacy/osteoporosis, increase in level XC, including the XC LPVP and TG. Carbamazepine can reduce the level of folic acid in blood plasma. Also it was reported about decrease under the influence of carbamazepine of level of _{12 vitamin B} in blood plasma and increase in level of a gomotsistein.

from a metabolism and disturbance of food: insufficiency of folates, a loss of appetite, a sharp porphyria (the sharp intermittent and mixed porphyria), a chronic porphyria (late porphyria of skin).

from mentality: hallucinations (visual or acoustical), depression, loss of appetite, concern, agressive behavior, agitation, nervous arousing, confusion of consciousness, activization of latent psychosis, change of mood, such as depressive or maniacal mood swings, phobias, lack of motivation, involuntary movements, such, as asterixis.

from nervous system: the general weakness, dizziness, an ataxy, drowsiness, sedation, increased fatigue, a headache, abnormal involuntary movements (for example a tremor, a krupnorazmashisty tremor, dystonia, a tic), a nystagmus, orofatsialny dyskinesia, the slowed-down thinking, speech disorders (for example a dysarthtia or the muffled speech), a choreoathetosis, peripheral neuropathy, paresthesias, muscle weakness and paresis, disturbance of taste, a malignant antipsychotic syndrome, a memory impairment, atactic and cerebellar disorders which sometimes are followed by a headache.

from an organ of sight: conjunctivitis, accommodation disturbance (diplopia, misting of sight), increase in intraocular pressure, cataract, retinotoksichnost, oculomotor disturbances.

from an organ of hearing and a vestibular mechanism: hearing disorder, sonitus, a ring in ears, a hyperacusia, a gipoakuziya, disturbance of perception of height of a sound.

from a cardiovascular system: disturbances of intracardial conductivity, bradycardia, arrhythmia, deterioration in an ischemic heart disease, stagnant heart failure, circulator collapse, AV blockade with a syncope, AG or hypotension, a vasculitis, thrombophlebitis, a thrombembolia (for example a vascular embolism of lungs).

from a respiratory system: reactions of hypersensitivity from lungs which is characterized by fervescence, short wind, a pulmonitis or pneumonia. In case of such hypersensitivity reactions the administration of medicament needs to be stopped.

from digestive system: a loss of appetite, dryness in a mouth, nausea, vomiting, diarrhea, a constipation, an abdominal pain, stomatitis, an ulitis, a glossitis, pancreatitis, colitis.

Gepatobiliarny disturbances: changes of indicators of functional trial of a liver (increase in level gamma glutamiltransferazy, increase in the SF level, transaminases), jaundice, various forms of hepatitis (cholestatic, hepatocellular, granulematozny, mixed), a life-threatening acute hepatitis, a liver failure.

from skin and hypodermic fatty tissue: allergic dermatitis, a small tortoiseshell, an itching, exfoliative dermatitis, an erythrosis, a toxic epidermal necrolysis (Lyell's disease), a photosensitization, erubescence with polymorphic rash in the form of spots and formation of nodes, with hemorrhages (an exudative poliformny erythema, a poliformny knotty erythema, Stephens's syndrome — Johnson), petekhialny hemorrhages in skin, a system lupus erythematosus, an alopecia, diaforez, changes of xanthopathy, an acne, a hirsutism, a vasculitis, a purpura, the increased sweating, sharp generalized exanthematous pustulez (AGEP), a lichenoid keratosis, onikhomadezis.

from a musculoskeletal system: arthralgia, myalgia, myotonia, muscular pain, fractures, decrease in bone mineral density.

from kidneys and urinary tract: a renal failure (for example a proteinuria, a hamaturia, an oliguria, increase in level of urea in a blood/azotemia), tubulointerstitsialny nephrite, a renal failure, an ischuria, the speeded-up urination.

from a reproductive system and mammary glands: disturbance of a spermatogenesis (with reduction of quantity and/or mobility of spermatozoa), erectile dysfunction, impotence, decrease in sexual desire.

Infection and invasion: reactivation of a virus of herpes of the person of the VI type.

General disturbances: general weakness.

Deviation of results of laboratory researches: hypogammaglobulinemia.

Special instructions

Carbamazepine should appoint by

only under medical observation, only after ratio assessment advantage/risk and on condition of careful monitoring of patients with warm, hepatic or renal disturbances, side hematologic reactions to other medicaments in the anamnesis, or patients with the interrupted therapy courses carbamazepine.

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recommends carrying out the general analysis of urine and determination of level of urea nitrogen in blood at the beginning and with a certain frequency during therapy.

Karbamazepin shows light anticholinergic activity therefore patients with the increased intraocular pressure should be warned about it and to consult rather possible risk factors.

Should remember

possible activation of the latent psychoses, and concerning patients of advanced age — possible activation of confusion of consciousness and development of disturbing excitement.

Drug is usually inefficient

at absentias epileptica (small epileptic seizures) and myoclonic attacks. Separate cases demonstrate that strengthening of attacks can arise at patients with atypical absentias epileptica.

Hematologic ﾚeffekty. Using medicament connect development of an agranulocytosis and aplastic anemia; however because of extremely low frequency of cases of development of these states it is difficult to estimate significant risk at intake of carbamazepine.

should inform

Patients on precursory symptoms of toxicity and symptoms of possible hematologic disturbances and also on symptoms of dermatological and hepatic reactions. The patient should be warned that in case of such reactions as fever, a tonsillitis, skin rash, ulcers in oral cavities, bruises which easily arise dot hemorrhages or a hemorrhagic purpura, it is necessary to see a doctor immediately.

If the quantity of leukocytes or thrombocytes considerably decreases during therapy, the condition of the patient is subject to careful monitoring, it is also necessary to carry out continuous general blood test of the patient. Treatment by carbamazepine needs to be stopped if at the patient the leukopenia which is serious develops, progressing or is followed by clinical manifestations, for example fever or sore throat. Use of carbamazepine should be stopped at emergence of signs of oppression of function of marrow.

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Periodically or often note temporary or steady decrease in quantity of thrombocytes or leukocytes in connection with intake of carbamazepine. However for the majority of these cases their temporariness is confirmed and they do not demonstrate development of aplastic anemia or agranulocytosis. Prior to therapy and periodically during its carrying out it is necessary to carry out blood test, including determination of quantity of thrombocytes (and also, perhaps, quantities of reticulocytes and level of hemoglobin).

Serious dermatological reactions. The serious dermatological reactions including the toxic epidermal necrolysis (TEN) or a Lyell's disease, the Stephens's syndrome — Johnson (SSJ) at use of carbamazepine arise very seldom. Hospitalization as these states can threaten life can be required by patients with serious dermatological reactions and come to an end with a lethal outcome. The majority of cases of development of SSD/TEN note within the first several months of treatment by carbamazepine. At development of the signs and symptoms demonstrating serious dermatological reactions (SSD, a syndrome of Layella / TEN), intake of carbamazepine it is necessary to stop and appoint alternative therapy immediately.

Pharmacogenomics. There are more and more certificates on influence of various alleles of HLA on tendency of the patient to emergence of the side reactions connected with the immune system.

Communication with (HLA)-B*1502. Retrospective researches at patients — Chinese of ethnic group of Khan showed the significant correlation between skin reactions by SSD/TEN connected with carbamazepine and existence at these patients of human leucocyte antigen (HLA), allelya (HLA)-B*1502. Big frequency of messages about development of SSD (rather seldom, than very seldom) is characteristic of some countries of Asia (for example the islands of Taiwan, Malaysia and Philippines) where among the population the allele (HLA)-B*1502 prevails. The number of carriers of it allelya among the population of Asia is 15% on Philippines, in Thailand, Hong Kong and Malaysia, ≈10% — on the island of Taiwan, nearly 4% — in Northern China, ≈2–4% — in the Southern Asia (including India) and 1% — in Japan and Korea. Distribution allelya is insignificant (HLA)-B*1502 among the European, African people, among indigenous people is America and the Latin American population.

At patients who are considered as genetically belonging to risk groups before an initiation of treatment carbamazepine should hold testing for existence allelya (HLA)-B*1502. If the analysis on existence allelya (HLA)-B*1502 yields positive take, then treatment by carbamazepine should not be begun unless there are no other options of therapeutic treatment. At patients who underwent inspection and received negative take on (HLA)-B*1502, note low risk of development of SSD though very much seldom such reactions can develop.

in view of lack of data does precisely not know Now to

whether for all persons of southeast Asian origin there are risks.

Allele (HLA)-B*1502 can be risk factor of development of SSD/TEN at the Chinese patients receiving other antiepileptic means which can be connected with emergence of SSD/TEN. Thus, it is necessary to avoid use of other medicaments which can be connected with emergence of SSD/TEN, for patients with alleles is (HLA)-B*1502 if other, alternative therapy can be performed. Usually it is not recommended to carry out genetic screening of patients of whose nationalities the low coefficient allelya is characteristic (HLA)-B*1502. Usually it is not recommended to carry out screening at the persons who are already receiving carbamazepine as the risk of emergence of SSD/TEN is considerably limited the first several months irrespective of existence in the patient's genes allelya (HLA)-B*1502.

At patients of Caucasian race the communication between a gene (HLA)-B*1502 and emergence of SSD is absent.

Communication with (HLA)-A*3101. Human leucocyte antigen can be risk factor of development of skin side reactions, such as SSD, TEN, medicamentous rash with an eosinophilia and system symptoms (DRESS), sharp generalized exanthematous pustulez (AGEP), makulopapulezny rash. If the analysis reveals existence allelya HLA-A*3101, then it is necessary to refrain from use of carbamazepine.

Restriction of genetic screening. Results of genetic screening should not replace the corresponding clinical observation and treatment of patients. A role in emergence of these heavy skin side reactions is played by other possible factors, such as dosage of antiepileptic means, observance of the mode of therapy, the accompanying therapy. Influence of other diseases and level of monitoring of skin disturbances did not study.

Other dermatological reactions. Development of the passing and not menacing to health easy dermatological reactions, for example the isolated macular or makulopapulezny dieback is possible. Usually they take place in several days or weeks both at constant dosing, and after a medicament dose decline. As can be very difficult to distinguish precursory symptoms of more serious dermatological reactions from the fast-proceeding easy reactions, the patient has to be under observation immediately to stop medicament use if with its continuation the reaction worsens.

Existence at the patient allelya (HLA)-B*1502 is not risk factor of emergence at it less serious undesirable reactions to carbamazepine from skin, such as hypersensitivity syndrome to anticonvulsants or insignificant rashes (makulopapulezny rash). However it was not established that existence (HLA)-B*1502 can demonstrate risk of emergence of above-mentioned reactions.

Hypersensitivity. Carbamazepine can provoke development of reactions of hypersensitivity, including medicamentous rash with an eosinophilia and system symptoms (DRESS), multiple delayed-type hypersensitivity reactions with fever, rash, a vasculitis, a lymphadenopathy, a pseudo-lymphoma, an arthralgia, a leukopenia, an eosinophilia, a gepatosplenomegaliya, change of indicators of function of a liver and a syndrome of disappearance of bile ducts (including destruction and disappearance of intra hepatic bile ducts). Influence on other bodies (lungs, kidneys, a pancreas, a myocardium, a large intestine) is also possible.

Existence at the patient allelya HLA-A*3101 is connected by

with emergence of less serious undesirable reactions to carbamazepine from skin, such as hypersensitivity syndrome to anticonvulsants or insignificant rashes (makulopapulezny rash).

Patients with reactions of hypersensitivity to carbamazepine have to be informed by

that they at about 25-30% of such patients can also note reactions of hypersensitivity on okskarbazepin.

At use of carbamazepine and Phenytoinum the development of cross hypersensitivity is possible

.

in general at emergence of the signs and symptoms indicating hypersensitivity, use of carbamazepine it is necessary to stop immediately.

Attacks. Carbamazepine should be applied with care at patients with the mixed attacks which include absentias epileptica (typical or atypical). Under such circumstances medicament can provoke attacks. In case of provoking of attacks the use of carbamazepine should be stopped immediately.

Increase in frequency of attacks can be noted upon transition from oral forms of medicament to suppositories.

Function of a liver. During therapy by medicament it is necessary to carry out the assessment of function of a liver at the initial level and periodic assessment of this function during therapy, especially at patients with liver diseases in the anamnesis and at elderly people. At exacerbation of abnormal liver functions or at patients with an active phase of a disease of a liver it is necessary to stop administration of medicament immediately.

Some indicators of laboratory analyses by means of which estimate a functional condition of a liver at the patients accepting carbamazepine can go beyond norm, in particular gamma glutamiltransferazy. It probably happens because of induction of liver enzymes. Induction of enzymes can lead to moderate increase in the SF level also. Such increase in functional activity of hepatic metabolism is not the indication for carbamazepine cancellation.

Heavy reactions from a liver at use of carbamazepine note

very seldom. In case of signs and symptoms of hepatic dysfunction or an active disease of a liver it is necessary to examine urgently the patient, and carbamazepine to suspend treatment before obtaining results of inspection.

Function of kidneys. It is recommended to carry out the assessment of function of kidneys and determination of level of urea nitrogen of blood at the beginning and periodically during a therapy course.

Hyponatremia. Cases of development of a hyponatremia at carbamazepine use are known. At patients with already existing renal failure which is connected with the reduced level of sodium or at patients with the accompanying treatment by medicines which reduce sodium level (such as diuretics, medicines which are associated with inadequate secretion of antidiuretic hormone), before treatment it is necessary to determine sodium level in blood. Further this indicator should be measured each 2 weeks, then — at an interval of 1 month within the first 3 months of treatment or according to clinical need. It concerns first of all patients of advanced age. In this case it is necessary to limit amount of the used water.

Gipotireoidizm. Carbamazepine can reduce concentration of hormones of a thyroid gland, in this regard increase in a dose of replacement therapy by hormones of a thyroid gland is necessary for patients with a hypothyroidism.

Anticholinergic effects. Carbamazepine shows moderate anticholinergic activity. Thus, patients with the increased intraocular pressure have to be under observation during therapy.

Psychotic effects. It is necessary to remember the probability of activization of latent psychosis and at patients of advanced age — confusion is consciousness or excitement.

Suicide thoughts and behavior. Several messages about suicide thoughts and behavior at the patients receiving antiepileptic medicaments are registered. The metaanalysis of the data obtained during placebo - controlled researches of antiepileptic drugs, also confirms small increase in risk of emergence of suicide thoughts and behavior. The origins of such risk are unknown, and available data do not exclude increase in risk of emergence of suicide thoughts and behavior for carbamazepine. Therefore patients need to be examined on existence of suicide thoughts and behavior and if it is required, to appoint the corresponding treatment. Patients (and to the persons who are looking after patients) should recommend to see a doctor in case of signs of suicide thoughts and behavior.

Endocrine effects. In view of induction of enzymes of a liver carbamazepine can become the reason of decrease in therapeutic effect of medicaments of estrogen and/or progesterone. It can lead to decrease in efficiency of contraception, a recurrence of symptoms to either breakthrough bleedings or bloody discharges. The patients accepting carbamazepine and for which hormonal contraception is necessary have to receive the medicament containing not less than 50 mkg of estrogen or for them it is necessary to consider the possibility of use of alternative non-hormonal methods of contraception.

Monitoring of level of medicament in blood plasma. In spite of the fact that the correlation between a dose and level of carbamazepine in blood plasma and also between carbamazepine level in blood plasma and clinical performance and shipping is doubtful, monitoring of level of medicament in blood plasma can be reasonable in the following cases: at sudden increase in frequency of attacks, check of compliance of the patient, during pregnancy, at treatment of children and teenagers; at suspicion on absorption disturbance, at the suspected toxicity and use more than one drug.

Dose decline and withdrawal of drug. Sudden medicament withdrawal can provoke attacks therefore carbamazepine should be cancelled gradually within 6 months. In need of immediate medicament withdrawal at patients with epilepsy the transition to new antiepileptic medicament should be carried out against the background of therapy by the corresponding medicines.

Use during pregnancy and feeding by a breast. Treatment by carbamazepine of pregnant women with epilepsy should be performed with extra care.

oral administration of carbamazepine caused development of defects In animals.

At children at whose mothers note epilepsy reveal tendency to disturbances of pre-natal development, including congenital malformations. It was reported about the probability that carbamazepine, as well as the majority of antiepileptic means, increases the frequency of these disturbances, however convincing proofs within the controlled researches of monotherapy by carbamazepine are absent. At the same time it was reported about the disturbances of pre-natal development and congenital malformations associated with carbamazepine use, including about a crevice of a backbone and other congenital anomalies, press