Karbamazepin-FS

General characteristics. Structure:

Active ingredient: carbamazepine;

Excipients: cellulose microcrystallic, gelatin, sodium starch glikolit (type A), silicon dioxide colloid anhydrous, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Karbamazepin-FS shows anticonvulsant (antiepileptic) and moderate antidepressive (timoletichesky) and normotimichesky action.
The range of activity of carbamazepine as protivoeleptichesky medicine covers: partial attacks (simple and difficult) with secondary generalization and without it; generalizirovanny toniko-clonic convulsive attacks, and also combinations of the specified types of attacks. The mechanism of effect of carbamazepine - active agent of the drug Karbamazepin-FS - is found out partially. Carbamazepine stabilizes membranes of too excited nerve fibrils, inhibits emergence of repeated neyronalny 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 decrease in release of a glutamate and stabilization of membranes of neurons can explain prtivosudorozhny effect of drug, the anti-maniacal effect can be caused by oppression of metabolism of dopamine and noradrenaline.

Pharmacokinetics. Absorption. After oral use carbamazepine is soaked up almost completely, though rather slowly. After a single dose the maximum concentration in a blood plasma (Cmax) is reached in 12 hours. Clinically significant differences in extent of absorption of active agent after use of various dosage forms of drug for intake are not revealed. After a single dose in drug in a dose of 400 mg of carbamazepine average Cmax value of not changed active agent reaches about 4,5 mkg/ml.
Reception of food significantly does not influence the speed and extent of absorption of carbamazepine.
Equilibrium concentration of drug in a blood plasma are reached within 1-2 weeks that depends on specific features of metabolism (an autoinduktion of fermental systems of a liver carbamazepine, heteroinduction by other medicines applied at the same time), and also on a condition of the patient, a dose of drug and duration of treatment. Essential interindividual distinctions of values of equilibrium concentration in the therapeutic range are observed: at most of patients these values fluctuate from 4 to 12 mkg/ml (17-50 µmol/l). Concentration of carbamazepine-10,11-epoxide (pharmacological an active metabolite) reaches about 30% of concentration of carbamazepine.
Bioavailability of different drugs of carbamazepine can differ; such property allows to avoid change of a dosage form that can lead to decrease in effect at use of medicine or risk of emergence of epileptic attacks against the background of reception of medicine or to emergence of overshot side effects.

Distribution. Linkng of carbamazepine with proteins of a blood plasma reaches 70-80%. Concentration of not changed carbamazepine in cerebrospinal fluid and saliva is proportional to a share of the active agent which is not connected with blood proteins (20-30%).
Gets into breast milk (25-60% of level of carbamazepine in a blood plasma) and through a placental barrier. The conditional volume of distribution makes 0,8-1,9 l/kg.

Metabolism. Carbamazepine is metabolized in a liver, preferential epoxy way, with formation of several metabolites: 10,11-transdiolovy derivative and its conjugates with glucuronic acid, the monohydroxided derivatives, and also N-glucuronides. The main isoenzyme providing carbamazepine biotransformation in carbamazepine-10,11-epoxide is P450 3A4 cytochrome.

Removal. After a single dose of drug the elimination half-life of not changed carbamazepine (T1/2) averages about 36 hours, and after repeated administration of drug - on average 16-24 hours (owing to an autoinduktion of enzymes of metabolism) depending on treatment duration. At the patients accepting at the same time other drugs inducing the same fermental system of a liver (for example, Phenytoinum, phenobarbital), the elimination half-life of carbamazepine averages    9-10 hours. After a single dose in 400 mg of carbamazepine of 72% of the accepted dose also 28% - with a stake are removed with urine. About 2% of the accepted dose are removed with urine in the form of not changed carbamazepine, about 1% - in the form of pharmacological active         10,11-epoxy metabolite.

Features of pharmacokinetics in separate groups of patients.
At children owing to more bystry elimination of carbamazepine for maintenance of therapeutic concentration of drug use of higher doses of drug at the rate on body weight mg/kg in comparison with adults can be required.
Are absent this, testimonial that the pharmacokinetics of carbamazepine changes at patients of advanced age (in comparison with adult persons of young age).
Data on carbamazepine pharmacokinetics at patients with renal failures or a liver are absent.

Indications to use:

- Epilepsy:
- difficult or simple partial convulsive attacks (with loss or without loss of consciousness) with secondary generalization or without it;
- generalized toniko-clonic to the sudoroyena attacks;
- the mixed forms of convulsive attacks.

It is applied as monotherapy, and as a part of a combination therapy.
· Acute maniacal states; a maintenance therapy at bipolar affective disorders for the purpose of prevention of aggravations or for weakening of clinical manifestations of an aggravation.
· Syndrome of alcoholic abstinence.
· An idiopathic epileptiform neuralgia and an epileptiform neuralgia at multiple sclerosis (typical and atypical).
· Idiopathic neuralgia of a glossopharyngeal nerve.

Route of administration and doses:

Karbamazepin-FS to appoint orally, to divide usually daily dose of drug into two-three receptions. It is possible to accept drug during food, after food or in intervals between receptions of food, washing down with a small amount of liquid.

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

Epilepsy.
To begin with use of a low daily dose which further slowly to raise (to adjust treatment taking into account need of each specific patient) before achievement of optimum effect.
In cases when it is possible, Karbamazepin-FS should appoint in the form of monotherapy, but in case of use with other medicines the mode of the same gradual increase in a dose of drug is recommended. If to add Karbamazepin-FS to already existing antiepileptic therapy, the dose of drug should be raised gradually, at the same time not to change a dose of the used drugs or if necessary to adjust.
Adults and children since 15 years. The recommended initial dose - 100-200 mg 1-2 times a day, then gradually to increase a dose before achievement of optimum effect; usually daily dose makes 800-1200 mg. The dose of Karbamazepina-FS reaching 1600 mg or even 2000 mg/days can be necessary for some patients.

Patients of advanced age. Considering medicinal interactions and different pharmacokinetics of antiepileptic drugs, patients of advanced age of a dose of Karbamazepina-FS should select with care.
Children since 5 years. Treatment it is possible to begin 100 mg/days with use; to raise a dose gradually - weekly on 100 mg.
Usually to carry out treatment by a dose of 10-20 mg/kg of body weight a day (in stages).
Children from 5 to 10 years - 400-600 mg/days (for 2-3 receptions).
Children from 10 to 15 years - 600-1000 mg/days (for 3-5 receptions).
Acute maniacal states and the supporting treatment of affective (bipolar) frustration.
Range of doses makes from 400 to 1600 mg/days. Usually therapy to carry out in a dose  400-600 mg/days to 2-3 receptions.
At treatment of acute maniacal states the dose of Karbamazepina-FS should be raised quickly enough. In case of a maintenance therapy of bipolar disorders for the purpose of ensuring optimum portability gradual increase is recommended by small doses.

Alcoholic abstinence syndrome.
The average dose makes on 200 mg 3 times a day. In hard cases during the first several days it is possible to raise a dose (for example, to a dose on 400 mg 3 times a day). At heavy manifestations of alcoholic abstinence to begin treatment with a combination of Karbamazepina-FS with sedative and somnolent drugs (for example, with klometiazoly, chlordiazepoxide), adhering to the above-stated recommendations concerning dosages. On end of an acute phase treatment of Karbamazepinom-FS can be continued in the form of monotherapy.

Idiopathic epileptiform neuralgia and epileptiform neuralgia at multiple sclerosis (typical and atypical). Idiopathic neuralgia of a glossopharyngeal nerve. 

The initial dose of Karbamazepina-FS makes 200-400 mg/days (100 mg 2 times a day for patients of advanced age). It is necessary to raise it slowly to disappearance of pain (usually to a dose on 200 mg 3-4 times a day). For most of patients the drug dose on 200 mg 3-4 times a day is sufficient for support of a painless state. Use of a daily dose of drug of 1600 mg can be in certain cases necessary. After the termination of pain gradually to lower a dose to the minimum supporting.

Features of use:

Use during pregnancy or feeding by a breast. Treatment of Karbamazepinom-FS of the pregnant women sick with epilepsy should be performed with extra care.
It is necessary to apply to women of reproductive age of Karbamazepin-FS, whenever possible, in the monotherapy mode as the frequency of congenital anomalies of a fruit at women to whom carried out kombinarovanny therapy by anti-epileptic means, above, than at those which received each of these means in the form of monotherapy.
It is necessary to appoint a minimal effective dose of Karbamazepina-FS. Regular control of level of active agent in a blood plasma is recommended.
If the woman receiving Karbamazepin-FS became pregnant, plans pregnancy or if the question of purpose of Karbamazepina-FS arises during pregnancy, it is necessary to weigh carefully expected advantages of therapy in comparison with possible risk, especially in the first three months of pregnancy.

During pregnancy it is not necessary to interrupt effective antiepileptic therapy as the exacerbation of a disease will threaten health, both mother, and a fruit.
Patients should be informed on a possibility of increase in risk of malformations and an opportunity to undergo antenatal diagnosis.
It is known that the children born at mothers sick with epilepsy are more often than others are subject to disturbances of pre-natal development, including malformations. Reported that carbamazepine, as well as all other anti-epileptic means, is capable to increase risk of emergence of these disturbances though final confirmation so far is absent. There are single messages on cases of inborn diseases and malformations, including splitting of a backbone (spina bifida) and other anomalies of development, such as the kraniofatsialny defects, cardiovascular malformation, hypospadias and anomalies of development of various systems of an organism associated using carbamazepine.

Observation and prevention. It is known that during pregnancy deficit of folic acid develops. Antiepileptic means can increase this deficit. It can promote increase in frequency of inborn defects at the children who were born at the women accepting antiepileptic means. Therefore to and during pregnancy additional use of folic acid is recommended.

Newborns. For the purpose of prevention of the raised bleeding at newborns to women in recent weeks of pregnancy, and also the newborn recommends to appoint K1 vitamin.
Several cases of convulsive attacks and/or respiratory depressions at newborns whose mothers accepted carbamazepine and other anticonvulsant drugs are described. Besides, in connection with carbamazepine administration of drugs by mothers, it was reported also seldom about cases of vomiting, diarrhea and/or reduced appetite of newborns. Perhaps, these reactions are manifestation at newborns of a withdrawal.

Feeding by a breast. Carbamazepine gets into breast milk (25-60% of concentration in a blood plasma). Therefore it is necessary to compare advantages and possible undesirable effects of chest feeding at therapy of Karbamazepinom-FS. Mothers accepting Karbamazepin-FS can nurse the children, but provided that for the child observation concerning development of possible side reactions will be established (for example, excessive drowsiness, allergic skin reactions).

Children. At children owing to more bystry elimination of carbamazepine use of higher doses of drug (in terms of kilogram of body weight) in comparison with adults can be required. Karbamazepin-FS children can apply from 5 years.  

Karbamazepin-FS it is necessary to apply only on condition of ensuring medical observation and only after the careful analysis of a ratio advantage/risk, and also when ensuring attentive and regular monitoring of patients who in the anamnesis have data on a heart disease, a liver, kidneys, side hematologic reactions on other medicines or about cancellation of the treatment which is carried out early Karbamazepinom-FS.

Karbamazepin-FS it is usually inefficient at small attacks (petit mal, an absentia epileptica) and myoclonic attacks. Separate cases demonstrate that strengthening of attacks can arise at patients with atypical absentias epileptica.

It is necessary to apply with care Karbamazepin-FS to treatment of patients with the mixed forms of convulsive attacks, including absentias epileptica (typical and atypical). Under such circumstances Karbamazepin-FS can provoke attacks. If it happens, drug needs to be cancelled.

Increase in frequency of attacks can take place during transition from peroral forms of drug to suppositories.
Hematologic effects. Using carbamazepine connect development of an agranulocytosis and aplastic anemia. However because such states arise very seldom, it is heavy to estimate the importance of risk. It is known that the total risk of development of an agranulocytosis in the general population which did not receive treatment by carbamazepine reached 4,7 cases on 1 million population a year, and aplastichny anemia -   2 cases on 1 million population a year.

During use of carbamazepine with a different frequency swift-flowing or permanent decrease in quantity of thrombocytes or leukocytes is noted. However in most cases these by-effects passing and usually are not harbingers of the beginning of aplastichny anemia or an agranulocytosis. Nevertheless, before an initiation of treatment, and also periodically in the course of treatment it is necessary to carry out clinical blood tests, including calculation of quantity of thrombocytes and, perhaps, reticulocytes, and also to determine iron level in blood serum.

If during treatment the low level of quantity of leukocytes or thrombocytes (or the tendency to their decrease takes place) is noted, it is necessary to watch a condition of the patient and indicators of the developed clinical blood test attentively. Treatment by the drug Karbamazepin-FS 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 a pharyngalgia. If signs of considerable oppression of marrow are revealed, Karbamazepin-FS should be cancelled.

Patients have to be informed on the precursory symptoms of toxicity inherent to possible hematologic disturbances, and also about symptoms from integuments and a liver and are warned about need to see immediately a doctor in case of such undesirable reactions as fever, a pharyngalgia, a rash, ulcers in oral cavities, causeless developing of bruises, hemorrhages in the form of petechias or a purpura.

Serious dermatological reactions.
Serious dermatological reactions, including the Stephens-Johnson's syndrome (SJS) or a Lyell's disease, at use of carbamazepine arise very seldom. Hospitalization as these states can threaten life can be required by patients with serious dermatological reactions and have lethal character. The majority of cases of development of SSD or Lyell's disease are noted within the first several months of treatment by carbamazepine. At development of the signs and symptoms testimonial of serious dermatological reactions (for example, SSD or a Lyell's disease), administration of drug of Karbamazepin-FS it is necessary to stop and nazanachit alternative therapy immediately.

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

Communication with (HLA) - B*1502. Retrospective researches at Chinese patients of ethnic group of Khan showed the expressed correlation between skin reactions by SSD or a Lyell's disease connected with carbamazepine, and existence at these patients of human leukocytic antigen (HLA), an allele (HLA) - B*1502. Big frequency of messages on development of SSD (rather seldom, than very seldom) is characteristic of some countries of Asia (for example, Taiwan, Malaysia and Philippines) where among the population the allele (HLA) - B*1502 prevails.

At patients who are considered per se that genetically belong to risk groups before an initiation of treatment of Karbamazepinom-FS it is necessary to hold testing for presence of an allele (HLA) - B*1502. If the analysis of the patient on presence of an allele (HLA) - B*1502 yields a positive take, then use of the drug Karbamazepin-FS it is necessary to avoid if only advantages of such treatment do not exceed risks. Patients who underwent inspection and received a negative take on existence (HLA) - B*1502 have the low level of development of SSD though very much seldom such reactions can meet.

At present due to the lack of data it is precisely unknown whether everything persons of a southeast Asian origin have this risk.
The allele (HLA) - B*1502 can be risk factor of development of SSD or Lyell's disease in Chinese patients who receive other antiepileptic means and who can be connected with emergence of such syndromes. Thus, it is necessary to avoid use of other drugs which can be connected with emergence of SSD or Lyell's disease, for the patients having an allele (HLA) - B*1502 if it is possible to apply other, alternative therapy. Usually it is not recommended to carry out genetic screening of patients who have among nationalities a low coefficient of an allele (HLA) - B*1502, and also at persons who already receive Karbamazepin-FS as the risk of emergence of SSD or Lyell's disease is considerably limited by the first several months, irrespective of presence at genes of the patient of an allele (HLA) - B*1502.

Patients of Caucasian race have an interrelation between an allele (HLA) - B*1502 and emergence of SSD is absent.
Communication with (HLA) - A*3101. Leukocytic antigen of the person (HLA) - A*3101 can be risk factor of development of side reactions from skin, such as SSD, Lyell's disease, medicamentous rash with an eosinophilia and system symptoms (DRESS), acute generalized exanthematous пустулез, makulopapulezny rash. Therefore at detection of existence of an allele (HLA) - A*3101 should refrain from use of drug.

Results of genetic screening should not replace the corresponding clinical observation and management of treatment of patients.
The role of other possible factors, such as dosing of antiepileptic means, observance of the mode of therapy, the accompanying therapy, influence of other diseases in emergence of these heavy side reactions from skin and monitoring of skin disturbances were not studied.

Other dermatological reactions. Perhaps also development fast-passing and such that do not threaten health of easy dermatological reactions, for example, the isolated macular or makullopapulezny dieback. Usually these reactions take place within several days or weeks even at continuation of treatment or after a drug dose decline. As can be very difficult to distinguish precursory symptoms of more serious dermatological reactions from the easy fast-taking place reactions, the patient has to be under careful medical observation at this time immediately to stop administration of drug if with continuation of its use reaction worsens.

Existence at the patient of an allele (HLA) - A*3101 is risk factor of emergence at it less serious skin reactions to carbamazepine, such as hypersensitivity syndrome to anticonvulsants or insignificant rashes (makulopapulezny rash). However it was not established that existence at the patient of an allele (HLA) - B*1502 can be risk factor of emergence at it the above-stated skin reactions.

Hypersensitivity. Carbamazepine can provoke development of reactions of hypersensitivity, including multiple reactions of hypersensitivity, with localization in skin, a liver, the hemopoietic bodies and lymphatic system or other bodies, in total or separately, within system reaction (see the section "Side reactions").

Patients with reactions of hypersensitivity to carbamazepine should be informed that about 25-30% of such patients can also have reactions of hypersensitivity on окскарбазепин.

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

Generally, at emergence of the signs and symptoms indicating hypersensitivity, administration of drug of Karbamazepin-FS should be stopped immediately.

Function of a liver. Before purpose of Karbamazepina-FS and in the course of treatment the research of function of a liver, especially at patients in whose anamnesis there are data on liver diseases, and also at patients of advanced age is necessary. In case of an aggravation of the existing abnormal liver functions or at manifestation of an active phase of a disease of a liver of Karbamazepin-FS it is necessary to cancel immediately.

Some indicators of laboratory analyses by means of which estimate a functional condition of a liver at patients who accept carbamazepine, can go beyond norms, in particular gamma glutaminetransferase (GGT). It probably happens because of induction of liver enzymes. Induction of enzymes can lead to moderate increase in level of an alkaline phosphatase also. Such increase in functional activity of hepatic metabolism is not an indicator for carbamazepine cancellation.

Heavy reactions from a liver because of use of carbamazepine happen very seldom. In case of signs and symptoms of hepatic dysfunction or an active disease of a liver it is necessary to inspect urgently the patient, and to suspend treatment of Karbamazepinom-FS before obtaining results of inspection.

Functions of kidneys. Before an initiation of treatment of Karbamazepinom-FS and periodically in the course of therapy it is recommended to estimate functions of kidneys and carrying out the general analysis of urine and determination of level of urea at blood.

Hyponatremia. Cases of development of a hyponatremia at carbamazepine use are known. At patients with already existing renal failure or at patients with the accompanying use of the medicines reducing sodium level (for example, the diuretics, medicines associated with inadequate secretion of antidiuretic hormone), before treatment it is necessary to measure sodium level in blood. Further it is necessary to measure each two weeks, then at an interval of one month for the first three months of treatment or according to clinical need. It concerns first of all patients of advanced age. It is necessary to limit amount of the used water in this case.

Anticholinergic effects. Carbamazepine shows moderate anticholinergic activity. Therefore patients with the increased intraocular pressure and an ischuria in case of use of drug have to be under fixed supervision.

Mental effects. It is necessary to take a possibility of activation of latent psychosis into account, and patients of advanced age have a confusion of consciousness or excitement.

There are separate data on suicide thoughts and behavior of the patients receiving antiepileptic drugs. Meta-analysis of these placebos - controlled researches of antiepileptic drugs showed small increase in risk of suicide thoughts and behavior. The mechanism of this risk is unknown, and the available data do not exclude a possibility of the increased risk of suicide thoughts and behavior for carbamazepine. Therefore patients it is necessary to check for existence of suicide thoughts and behavior and, if necessary, to appoint the corresponding treatment. Patients (and to trustees of patients) should recommend to see a doctor if signs of suicide thoughts or behavior appear.

Endocrine effects. Karbamazepin-FS can become the reason of decrease in therapeutic effect of drugs of estrogen and/or progesterone. It can make negative impact on reliability of peroral contraceptive drugs, lead to a recurrence of symptoms or breakthrough bleedings, or bloody allocations. The patients accepting carbamazepine and for which hormonal contraception is necessary have to receive the drug containing not less than 50 mkg of estrogen, or women of reproductive age during treatment of Karbamazepinom-FS need to use alternative methods of contraception.

There are separate messages on disturbance of male fertility and/or disturbance of a spermatogenesis.
Hypothyroidism. 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 at patients with a hypothyroidism is necessary.

Monitoring of level of drug in a blood plasma. Though the interrelation between the size of a dose of drug and level of carbamazepine in a blood plasma, and also between carbamazepine level in a blood plasma and its clinical performance or portability very weak, regular determination of level of carbamazepine can be useful in such situations: at sharp increase in frequency of attacks; to check of a komplayens of the patient; during pregnancy; at treatment of children and teenagers; at suspicion about drug absorption disturbance; at suspicion about development of toxic reactions if the patient accepts several medicines.

Dose decline and drug withdrawal. The sudden termination of reception of Karbamazepina-FS can provoke convulsive attacks. In need of sharp cancellation of treatment of Karbamazepinom-FS of patients epilepsy transition to other antiepileptic means needs to be carried out against the background of the drug shown in such cases (for example, diazepam which is entered intravenously or rektalno, or Phenytoinum entered intravenously).

Ability to influence speed of response at control of motor transport or work with other mechanisms. Ability of the patient accepting Karbamazepin-FS to bystry reaction, especially at the beginning of therapy or during selection of a dose, can be broken owing to developing of dizziness and drowsiness. Therefore during the driving or work with mechanisms the patient needs to be careful or to abstain from this type of activity.

Side effects:

Certain types of undesirable reactions, for example, from the central nervous system (CNS) (dizziness, a headache, an ataxy, drowsiness, the general weakness, a diplopia), the alimentary system (nausea, vomiting) or allergic skin reactions, arise very often or often, especially in an initiation of treatment carbamazepine, at use of too high initial dose or at treatment of patients of advanced age.
Dozozavisimy side reactions usually take place within several days as it is spontaneous, and after a temporary dose decline of carbamazepine. Development of side reactions from TsNS can be a consequence of relative overdose of drug or considerable fluctuations of concentration of active agent in a blood plasma. In such cases it is recommended to control the level of active agent in a blood plasma or to divide a daily dose into smaller (for example, on 3-4) separate doses.
From a nervous system: dizziness, an ataxy, sedation, drowsiness, the general weakness, a headache, a diplopia, sight accommodation disturbance (for example, sight opacification), the abnormal spontaneous movements (for example, a tremor, the "flitting" tremor, dystonia, a tic), a nystagmus, orofatsialny dyskinesia, disturbance of the movement of eyes, alalias (for example, a dysarthtia or the illegible speech), a memory impairment, choreoathetoid frustration, a peripheral neuropathy, paresthesias, muscular weakness and symptoms of paresis, disturbance of flavoring feelings, a malignant antipsychotic syndrome.
Mental disorders: hallucinations (visual or acoustical), depression, appetite loss, concern, agressive behavior, agitation, confusion of consciousness,  activation of psychosis.
From skin and hypodermic cellulose: allergic dermatitis, a small tortoiseshell, sometimes in a severe form, exfoliative dermatitis, an erythrosis, a system lupus erythematosus, an itch, Stephens-Johnson's syndrome, a toxic epidermal necrolysis, photosensitivity, a multiformny and nodular erythema, disturbance of a xanthopathy, purple, an acne, the increased perspiration, a hair loss, a hirsutism, acute generalized exanthematous пустулез, a lichenoid keratosis, онихомадезис.
From system of a hemopoiesis: insufficiency of marrow, a leukopenia, thrombocytopenia, an eosinophilia, a leukocytosis, a lymphadenopathy, deficit of folic acid, an agranulocytosis, aplastic anemia, a pancytopenia, a true erythrocyte aplasia, anemia, megaloblastny anemia, an acute intermittent porphyria, the mixed porphyria, a late porphyria of skin, a reticulocytosis and, perhaps, hemolitic anemia.
From gepatobiliarny system: increase in level gamma глутамилтрансферазы (owing to induction of this enzyme in a liver) that, as a rule, has no clinical value; increase in level of an alkaline phosphatase of blood, increase in level of transaminases, hepatitis cholestatic, the parenchymatous (hepatocellular) or mixed types, jaundice, granulematozny hepatitis, a liver failure.
From the alimentary system: nausea, vomiting, dryness in a mouth, diarrhea or a lock, an abdominal pain, a glossitis, stomatitis, pancreatitis, colitis.
From immune system: medicamentous rash with an eosinophilia and system symptoms (DRESS), multiorgan hypersensitivity of the slowed-down type with fever, skin rashes, a vasculitis, lymphadenopathy; with the signs reminding a lymphoma; arthralgias, a leukopenia, an eosinophilia, a gepatosplenomegaliya and the changed indicators of function of a liver and a syndrome of disappearance of bilious channels (destruction and disappearance of intra hepatic bilious channels) (the specified manifestations meet in different combinations). There can also be disturbances from other bodies (for example, lungs, kidneys, a pancreas, a myocardium, a large intestine) aseptic meningitis with a myoclonus and a peripheral eosinophilia, anaphylactic reaction, a Quincke's disease.
From cardiovascular system: disturbance of endocardiac conductivity, arterial hypertension or hypotension, bradycardia, arrhythmias, AV blockade with a loss of consciousness, a circulator collapse, congestive heart failure, an exacerbation of an ischemic disease, thrombophlebitis, a thrombembolia (for example, a vascular embolism of lungs).
From endocrine system and a metabolism: hypostases, a liquid delay, increase in body weight, a hyponatremia and decrease in osmolarity of plasma owing to effect, similar to effect of antidiuretic hormone that seldom leads to the overhydratation which is followed by a lethargy, vomiting, a headache, confusion of consciousness and neurologic disturbances, the increase in level of prolactin which is followed or not followed by such manifestations as a galactorrhoea, a gynecomastia; changes of indicators of function of a thyroid gland - decrease in level of L-thyroxine (FT4, T4, T3) and increase in level of tireostimuliruyushchy hormone that, as a rule, is not followed by clinical manifestations; disturbance of metabolism of a bone tissue (decrease in level of calcium and 25-IT-cholecalciferol in a blood plasma) that decrease in mineral density of a bone tissue leads to osteomalacy/osteoporosis; in some cases - increase in concentration of cholesterol, including cholesterol of lipoproteids of high density and triglycerides.
From urinogenital system: intersticial nephrite, a renal failure, a renal failure (for example, an albuminuria, a hamaturia, an oliguria, increase in level an urea/azotemia), a frequent urination, an ischuria, sexual dysfunction / impotence, disturbance of a spermatogenesis (with decrease in quantity/mobility of spermatozoa).
From organs of sight: cataract, conjunctivitis, increase in intraocular pressure.
From hearing and balance: disorders of hearing, including a noise/ring in ears, a hyperacusia, a gipoakuziya, change of perception of height of a sound. 
From a musculoskeletal system: arthralgias, muscular pain or spasms of muscles, changes.
From a respiratory organs: the reactions of hypersensitivity from lungs which are characterized by fever, an otdyshka, a pneumonitis or pneumonia.
Infections and invasions: reactivation of a virus of herpes of the person of the VI type.
General disturbances: fatigue.
Laboratory researches: hypogammaglobulinemia.

Interaction with other medicines:

P450 3A4 cytochrome (CYP3A4) is the main enzyme providing formation of an active metabolite of carbamazepine-10,11-epoxide. Simultaneous use with Karbamazepinom-FS of CYP3A4 inhibitors can lead to increase in concentration of carbamazepine in a blood plasma that, in turn, can cause emergence of side reactions. Combined use of the inductors CYP3A4 can lead to acceleration of metabolism of carbamazepine and, thus, to possible decrease in concentration of carbamazepine in a blood plasma and to reduction of expressiveness of therapeutic effect.
Similarly the termination of reception of the inductor CYP3A4 can reduce carbamazepine metabolism speed that leads to increase in level of carbamazepine in a blood plasma.
Carbamazepine is the powerful inductor CYP3A4 and other fermental systems of a phase І and phases II in a liver therefore can reduce concentration of other drugs in a blood plasma which are preferential metabolized by CYP3A4 by induction of their metabolism.
Human microsomal epoxide-hydrolase represents the enzyme responsible for education 10,11 from carbamazepine-10,11-epoxide. Co-administration of inhibitors human microsomal can lead epoxide-hydrolase to increase in concentration of carbamazepine-10,11-epoxide in a blood plasma.
As Karbamazepin-FS has structural similarity to tricyclic antidepressants, it is not necessary to appoint it in a combination with MAO inhibitors; before purpose of Karbamazepina-FS MAO inhibitors need to be cancelled at least in 2 weeks or if the clinical situation, even for bigger term allows.

Drugs which can increase carbamazepine level in a blood plasma.
As increase in level of carbamazepine in a blood plasma can lead to emergence of side reactions (for example, dizziness, drowsiness, an ataxy, a diplopia), in such cases it is necessary to adjust a dose of Karbamazepina-FS and/or to control carbamazepine level in a blood plasma at simultaneous use with such drugs: verapamil, diltiazem, dextropropoxyphene, ibuprofen, Cimetidinum, омепразол, desipramine, вилоксазин, fluoxetine, флувоксамин; Trazodonum, пароксетин; acetazoleamide, даназол, niacinamide (at adults, only in high doses); нефазодон, makrolidny antibiotics (for example, erythromycin, тролеандомицин, джозамицин, кларитромицин), ciprofloxacin; azoles (for example, итраконазол, кетоконазол, флуконазол, вориконазол); терфенадин, лоратадин, inhibitors of proteases, ритонавир, стирипентол, вигабатрин, olanzapine, isoniazid, оксибутинин, дантролен, тиклопидин, grapefruit juice.

Alternative antiepileptic means can be recommended to patients who receive treatment vorikonazoly or itrakonazoly.
Drugs which can increase the level of an active metabolite of carbamazepine-10,11-epoxide in a blood plasma.

As increase in level of an active metabolite of carbamazepine-10,11-epoxide in a blood plasma can lead to emergence of side reactions, dosing of Karbamazepina-FS it is necessary to adjust and/or control respectively drug level in a blood plasma if to accept Karbamazepin-FS along with such drugs: локсапин, кветиапин, Primidonum, прогабид, валноктамид, valproic acid, вальпромид.

Drugs which can reduce carbamazepine level in a blood plasma: phenobarbital, метсуксимид, фенсуксимид, окскарбазепин, Phenytoinum (for avoidance of intoxication Phenytoinum and subtherapeutic concentration of carbamazepine it is recommended          to correct concentration of Phenytoinum in        a blood plasma to 13 micrograms/ml before a carbamazepine initiation of treatment), фосфенитоин, Primidonum, clonazepam (though data on it are contradictory), theophylline, Aminophyllinum, rifampicin, Cisplatinum or doxorubicine, изотретиноин, drugs of the officinal herbs containing a St. John's Wort (Hypericum perforatum).

Meflokhin can show antagonistic properties concerning antiepileptic effect of carbamazepine. Respectively the dose of the drug Karbamazepin-FS needs to be modified.

At simultaneous use with felbamaty the reduction of concentration of carbamazepine in blood serum connected with increase in concentration carbamazepine-epoxide at the same time is possible decrease in concentration in serum of a felbamat is possible.

Izotretinoin changes bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide; in this case monitoring of concentration of carbamazepine in a blood plasma is necessary.

Influence of Karbamazepina-FS on concentration in a blood plasma of at the same time used drugs.
Carbamazepine can reduce concentration in a blood plasma or reduce and even completely to level effects of some drugs. Correction of doses of such drugs can be required: to klobaza, clonazepam, Ethosuximidum, фелбамат, Primidonum, окскарбазепин, ламотриджин, зонисамид, тиагабин, топирамат, valproic acid; to alprazola, midazolam; corticosteroids (for example, Prednisolonum, dexamethasone); cyclosporine, эверолимус, такролимус, сиролимус; doxycycline, рифабутин; methadone, paracetamol, phenazone (antipyrine), трамадол; theophylline; peroral anticoagulants (warfarin, фенпрокумон, дикумарол, аценокумарол); бупропион, to tsitalopra, нефазодон, Trazodonum, tricyclic antidepressants (for example, Imipraminum, amitriptyline, нортриптиллин, кломипрамин); clozapine, haloperidol, бромперидол, olanzapine, кветиапин, рисперидон, арипипразол, палиперидон, зипразидон; protease inhibitors at antiviral therapy (индинавир, ритонавир, саквинавир); blockers of calcium channels (group of dihydropyridine - фелодипин, исрадипин), digoxin, аторвастатин, ловастатин, церивастатин, ивабрадин; итраконазол, вориконазол, an aprepitant, a praziquantel, albendazole, иматиниб, cyclophosphamide, лапатиниб, терсиролимус, the left thyroxine, products incorporating estrogen and/or progesterona (selection of alternative methods of contraception is necessary); tadalafit, buprenorphine, гестринон, тиболон, торемифен, миансерин, sertraline.

There are messages that against the background of carbamazepine reception Phenytoinum level in a blood plasma can, both to raise, and to decrease, and Mephenytoinum level - to increase (in some cases).
Combinations which should be taken into account.
Simultaneous use of carbamazepine and levetiratsetam can lead to strengthening of toxicity of carbamazepine.

At combined use of carbamazepine and paracetamol (acetaminophen) decrease in bioavailability of the last is possible. Prolonged use of carbamazepine with paracetamol (acetaminophen) can lead to development of a hepatotoxic.

Simultaneous use of carbamazepine and isoniazid can lead to strengthening of a hepatotoxic of an isoniazid.
The combined use of carbamazepine and drugs of lithium or Metoclopramidum, and also carbamazepine and neuroleptics (haloperidol, thioridazine) can lead to increase in frequency of undesirable neurologic reactions (in case of the last combination - even at therapeutic concentration of active agents in a blood plasma).

Simultaneous use of carbamazepine with some diuretic means (a hydrochlorothiazide, furosemide) can lead to the hyponatremia which is followed by clinical manifestations.

Carbamazepine can counteract effects of not depolarizing muscular relaxants (for example, a pankuroniya). In case of use of such combination of medicines there can be a need of increase in a dose of the specified muscle relaxants; it is necessary to watch patients as perhaps more bystry, than was expected, cancellation of muscle relaxants attentively. Karbamazepin-FS, as well as other psychotropic drugs, portability of alcohol can reduce. In this regard the patient is recommended to refuse alcohol intake.

Influence on serological researches. Carbamazepine can yield a false positive take of VEZhH of the analysis for definition of concentration of a perfenazon. Carbamazepine and carbamazepine-10,11-epoxide can yield false positive result of immunoassay on a technique of the polarized fluorescence for definition of concentration of tricyclic antidepressants.

Contraindications:

Hypersensitivity to carbamazepine or to similar medicines in the chemical relation (for example, to tricyclic antidepressants), or to any other component of drug;
atrioventricular block;
existence in the anamnesis of episodes of oppression of marrow;
hepatic porphyria (for example, an acute intermittent porphyria, the mixed porphyria, a late porphyria of skin) in the anamnesis.
in a combination with inhibitors of a monoaminooxidase (MAO).

Overdose:

Symptoms
The symptoms and complaints arising at overdose usually reflect defeat central nervous, cardiovascular and respiratory systems.

Central nervous system: oppression of functions of the central nervous system; disorientation, oppressed level of consciousness, drowsiness, excitement, hallucinations, coma; sight opacification, the illegible speech, a dysarthtia, a nystagmus, an ataxy, dyskinesia, a hyperreflexia (at the beginning), a hyporeflexia (later); spasms, psychomotor frustration, myoclonus, hypothermia, mydriasis.

Respiratory system: respiratory depression, fluid lungs.

Cardiovascular system: tachycardia, hypotension, sometimes hypertensia, disturbance of conductivity with expansion of the QRS complex; the cardiac standstill which is followed by a loss of consciousness.

Alimentary system: vomiting, a delay of passing of food from a stomach, decrease in motility of a large intestine.

Skeletal and muscular system: рабдомиолиз that is connected with toxic influence of carbamazepine.

Urinary system: ischuria, oliguria or anury; liquid delay; the cultivation hyponatremia caused by effect of carbamazepine, similar with effect of antidiuretic hormone.

Changes from laboratory indicators: hyponatremia, possible metabolic acidosis, hyperglycemia, increase in muscular fraction of a kreatininfosfokinaza.

Treatment.
The specific antidote is absent. In the beginning treatment has to be based on a clinical condition of the patient; hospitalization is shown. To carry out definition of concentration of carbamazepine in a blood plasma for confirmation of poisoning with this means and assessment of extent of overdose.

To carry out evacuation of contents of a stomach, a gastric lavage, use of absorbent carbon. Late evacuation of gastric contents can lead to otstrochenny absorption and repeated emergence of symptoms of intoxication during recovery. To apply the symptomatic supporting treatment in intensive care unit, monitoring of functions of heart, attentive correction of electrolytic frustration.

Storage conditions:

To store in original packaging in the place unavailable to children, at a temperature below 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister; on 5 blisters in a pack cardboard.