Carbamazepine - Darnitsa

General characteristics. Structure:

Active ingredient: carbamazepine;

1 tablet contains carbamazepine (in terms of 100% dry matter) 200 mg;

excipients: cellulose microcrystallic, potato starch, povidone, silicon dioxide colloid anhydrous, magnesium stearate.

Pharmacological properties:

Karbamazepin-Darnitsa possesses the expressed anticonvulsant (protivoepiletichesky) and moderate antidepressive (timoleptichesky) and normotimichesky influence. At epilepsy, along with positive dynamics of paroxysms, Karbamazepin-Darnitsa improves an emotional state and increases skill to communicate of patients with changes of the personality that promotes their social rehabilitation. Karbamazepin-Darnitsa has analgeziruyushchy effect at epileptiform neuralgias, prevents development of paroxysmal pain.
At not diabetes mellitus leads to bystry normalization (rekompensation) of hydrogen balance.
The mechanism of anticonvulsant action of Karbamazepin-Darnits is connected with restriction of spread of activation from certain zones of a cerebral cortex, with reduction of a post-tetanic potentsiirovaniye in a hrebetny brain, with reduction in the rate of carrying out on motor and sensory nerves, and also with nonspecific membrane stabilizing effect. Psychotropic action of Karbamazepin-Darnits is implemented due to changes in transport of ions through a cellular membrane thanks to increase in activity of Na+-K+-Atfazy and braking of tsAMF. At the same time inhibitory influence of Karbamazepin-Darnits on neurotransfer in limbic system is not excluded.

Pharmacokinetics. Karbamazepin-Darnitsa after hit in a stomach is rather slowly released from a tablet. Active ingredient in not changed form reaches peak concentration in a blood plasma in 4-24 hours after reception in a single dose. The limit of therapeutic concentration of Karbamazepin-Darnits in plasma is in an interval of 5-12 mkg/ml. 70-80% of Karbamazepin-Darnits contact proteins of plasma. Degree of bioavailability makes from 70 to 95%. The elimination half-life of not changed Karbamazepin-Darnits after reception in a single dose is in limits of 20-65 hours, averaging 36 hours. At long reception owing to an autoinduktion of microsomal enzymes of a liver time of semi-removal decreases till 16-24 o'clock. With urine in not changed look about 25% of the dose of drug getting into a stomach are removed. Karbamazepin-Darnitsa biotransformirutsya in a liver to 10, 11-epoxide, dihydrocarbamazepine and other metabolites. Epoxide possesses the antiepileptic action making 1/3 from inherent Karbamazepina-Darnitsa. Karbamazepin-Darnitsa and his active metabolite are had through a placenta. Karbamazepin-Darnits's metabolism is weakened at people of advanced age and children.
Control of Karbamazepin-Darnits's level is necessary with side effects, pregnancy and its simultaneous use with other anticonvulsant drugs and medicines of the accompanying therapy.

Indications to use:

Psychomotor epilepsy (at big and small attacks, a combination of big attacks with psychomotor manifestations, local forms of epilepsy). Primary and vtorichnogeneralizirovanny forms of attacks with a toniko-clonic component. As adjuvant together with the specific drugs appointed for therapy of generalizirovanny forms of attacks (absentia epileptica type).

Acute maniacal states and maintenance therapy of bipolar affective disorders for the purpose of prevention of aggravations or weakening of clinical manifestations of an aggravation.

The essential and caused by multiple sclerosis epileptiform neuralgia, essential glosofaringealny neuralgia. Diabetic neuropathy with a pain syndrome.

Abstinence syndrome at patients with an alcoholism (as a part of a combination therapy), not diabetes mellitus of the central genesis, a polydipsia and a polyuria of neurohormonal genesis.

Route of administration and doses:

Karbamazepin-Darnitsa accept inside during meal. At treatment of epilepsy by the adult at the beginning of a course to accept minimum effective dose –           100-200 mg, sick advanced age – on 100 mg of drug 1-2 times a day. Further the dose is gradually increased to 400 mg by 2-3 times a day, that is before achievement of an optimum daily dose within 800-1200 mg. In certain cases there can be necessary daily doses of 1600 mg or even 2000 mg. The daily dose of Karbamazepin-Darnits for children is established at the rate of 10-20 mg/kg of body weight.

For children at the age of 6-10 years the daily dose of drug makes 400-600 mg (for               2-3 receptions), for children at the age of 11-15 years – 600-1000 mg (for 2-3 receptions).

The specified doses usually divide into 2-3 receptions. To children 6 years are aged more senior treatment it is possible to begin with use of a dose 100 mg / to Dob; the dose is raised gradually – every week on 100 mg. Karbamazepin-Darnitsa is not recommended to apply to treatment of children under 6 years.

Diabetic neuropathy with a pain syndrome: the average dose of Karbamazepin-Darnits makes on 200 mg 2-4 times a day.

Acute maniacal states and maintenance therapy at bipolar affective disorders. Range of doses: from about 400 to 1600 mg a day; as a rule – from 400 to 600 mg a day divided into 2-3 separate receptions. At an acute maniacal state bystry increase in a dose is recommended, and within a maintenance therapy at bipolar disorders gradual increase by small doses is recommended.

At treatment of neuralgia and pain syndromes Karbamazepin-Darnitsa accept 200-400 mg which is divided into 2-3 receptions in a daily dose. In 2-3 days the dose is increased by 100-200 mg/days and in this dose accepted within 7-10 days. Further after improvement of a condition of the patient the dose is gradually reduced to supporting (the minimum effective) which accept a long time. At an abstinence syndrome the average dose of Karbamazepin-Darnits makes 200 mg 3 times a day. In hard cases within the first several days it is possible to raise a dose (400 mg         3 times a day) and to combine Karbamazepin-Darnits's reception with sedative and hypnotic drugs (клометиазол, chlordiazepoxide). After weakening of an acute form it is possible to continue treatment of Karbamazepinom-Darnitsa as the main therapeutic means – before the termination of pain. At use for treatment of not diabetes mellitus the average dose for adults makes 200 mg 2-3 times a day, for children – respectively it is less, depending on age and body weight.

Features of use:

Use during pregnancy or feeding by a breast.

Treatment by carbamazepine of pregnant women who have epilepsy has to be performed with special care. It is necessary to appoint a minimal effective dose of drug and to carry out monitoring of level of carbamazepine in a blood plasma.

To women of reproductive age carbamazepine is whenever possible applied as monotherapy, посколько the frequency of congenital anomalies of a fruit is in that case lower, than at the combined treatment by antiepileptic means.

If the woman accepting carbamazepine became pregnant or if the question of purpose of drug arises during pregnancy, it is necessary to compare carefully expected advantages of therapy and its possible complications, especially in the first three months of pregnancy.

It is known that children who are born at mothers having epilepsy are more often than others are inclined to emergence of disturbances of pre-natal development, including malformations, including a crack of a backbone and other congenital anomalies, for example, maxillofacial defects, cardiovascular anomalies of development, a hypospadias and anomalies of development of different systems of an organism. It was reported that carbamazepine, as well as all other antiepileptic drugs, is capable to increase risk of emergence of these disturbances though there is no final confirmation of it. Anyway carbamazepine is considered as choice drug at the women of reproductive age forced to accept anticonvulsants and also as the safest concerning a fruit. Patients should provide information on a possibility of increase in risk of anomalies of development and an opportunity to undergo antenatal diagnosis.

Several cases of spasms and/or respiratory depressions at newborns who connect with reception of carbamazepine and other anticonvulsant drugs by mother are known. Several cases of vomiting, diarrhea and/or small appetite at newborns who connect with carbamazepine reception by mother were noted. These reactions can be charged to an abstinence syndrome at newborns.

It is known that during pregnancy deficit of folic acid develops. It was reported that antiepileptic drugs increase this deficit. It can promote increase in frequency of inborn defects at the children born at women who accepted antiepileptic drugs. Therefore to and during pregnancy additional use of folic acid is recommended.

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 vitamin K.

Carbamazepine gets into breast milk therefore it is necessary to compare advantages and possible adverse effects on condition of therapy by carbamazepine. Mothers who accept carbamazepine can nurse the children, but on condition that for the child observation concerning development of possible side reactions will be established (for example, the expressed drowsiness, allergic skin reactions).

Children.

Children can have a need for use of high doses of drug in comparison with adults, at the rate on kilogram of body weight, owing to more bystry elimination of carbamazepine. Children can apply tablets aged 6 years are more senior.

It is necessary to appoint carbamazepine only under medical observation. Carbamazepine it is necessary to appoint only after ratio assessment advantage/risk and on condition of careful monitoring of patients with cordial, hepatic or renal disturbances, side hematologic reactions to other drugs in the anamnesis, or patients with the interrupted therapy courses carbamazepine. Drug is usually inefficient at small attacks (petit mal, an absentia epileptica) and myoclonic attacks.

Hematologic effects. Using drug connect development of an agranulocytosis and aplastic anemia, however in view of extremely low frequency of cases of development of these states it is difficult to estimate significant risk at carbamazepine use. The general risk for people who did not receive therapy makes           4,7 persons / 1000000 in a year for development of an agranulocytosis and 2 persons / 1000000 in a year – for development of aplastic anemia.

Temporary or permanent decrease in quantity of thrombocytes or leukocytes of blood in connection with carbamazepine reception is periodically or often noted. However for the majority of these cases their temporality is confirmed, and they do not demonstrate development of aplastic anemia or an 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).

If the quantity of leukocytes or thrombocytes considerably decreases during therapy, the condition of the patient is subject to careful monitoring and continuous general blood test of the patient has to be carried out. Use of carbamazepine should be stopped at emergence of signs of oppression of function of marrow.

Patients need to be informed 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 heat, quinsy, skin rashes, ulcers in an oral cavity, bruises which easily arise, dot hemorrhages or a hemorrhagic purpura, it is necessary to see a doctor immediately.

Serious dermatological reactions. Serious dermatological reactions which include a toxic epidermal necrolysis (TEN or a Lyell's disease) and the Stephens-Johnson's syndrome (SJS) at use of carbamazepine arise very seldom. Patients with serious dermatological reactions can demand hospitalization as these states can threaten life and have fatal character. The majority of cases of development of SSD/TEN are noted for the first several months of treatment by carbamazepine. At development of the signs and symptoms testimonial of serious dermatological reactions (for example, SSD, a syndrome of Layella / TEN), reception of carbamazepine it is necessary to stop and appoint alternative therapy immediately.

Retrospective researches at Chinese patients of ethnic group of Khan showed the expressed correlation between the skin reactions of SSD/TEN connected with carbamazepine, and existence at these patients of human leukocytic antigen (HLA), alleles (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, Malaziya and Philippines) where among the population the allele (HLA) - B*1502 prevails. The number of carriers of this allele among the population of Asia makes more than 15% on Fillipinakh, in Thailand, Hong Kong and Malaziya, about 10% - on Taiwan, nearly 4% – in Northern China, approximately from 2% to 4% – in the Southern Asia (including India) and less than 1% – in Japan and Korea. Distribution of an allele (HLA) - B*1502 is insignificant among the European, African people, among indigenous people is America and the Latin American population.

At those patients who are considered per se that genetically belong to risk groups before an initiation of treatment carbamazepine 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 positive result, then use of carbamazepine should be avoided if only advantages of such treatment considerably do not exceed risks. The allele (HLA) - B*1502 can be risk factor of development of SSD/TEN in Chinese patients who receive other antiepileptic means which can be connected with emergence of SSD/TEN. Thus, it is necessary to avoid use of other drugs which can be connected with emergence of SSD/TEN, for patients who have an allele (HLA) - B*1502 if other, alternative therapy can be applied. As a rule, it is not recommended to carry out genetic screening of patients at whom among nationalities the coefficient of an allele (HLA) - B*1502 is low. As a rule, it is not recommended to carry out screening at persons who already receive carbamazepine as the risk of emergence of SSD/TEN is considerably limited the first several months, irrespective of presence at genes of the patient of an allele (HLA) - B*1502.

Results of genetic screening should not replace the corresponding clinical supervision and treatment of the patient at all. It is a lot of Asian patients who have a gene of an allele (HLA) - B*1502 and receive medical treatment for carbamazepine, have no SSD/TEN, and patients of any nationality who have no alleles (HLA) - B*1502 can get sick with SSD/TEN. A role in development and incidence of SSD/TEN of other possible reasons, such as, the level of dosing of antiepileptic drug, комплайнс, the accompanying drugs, influence of other diseases and level of monitoring of skin disturbances, were not investigated yet.

Other dermatological reactions. Development fast-passing and such which do not threaten health, easy dermatological reactions, for example, of the isolated macular or makulopapulezny dieback is possible. As a rule, they pass in several days or weeks both at constant dosing, and after a dose decline. At the same time, as precursory symptoms of more serious dermatological reactions can be very difficult otlichima from moderate fast-passing reactions, the patient has to be under careful supervision immediately to stop drug use if at its continuation reaction worsens.

Existence at the patient of an allele (HLA) - B*1502 is not risk factor of emergence at it less serious skin reactions to carbamazepine, such as hypersensitivity syndrome to anticonvulsant drugs or insignificant rashes (makulopapulezny rashes).

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 in other bodies, in total or separately within system reaction.

Patients with reactions of hypersensitivity to carbamazepine need to be informed that about 25-30% of such patients can also have reactions of hypersensitivity to an okskarbazepin.

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

In general at emergence of signs and symptoms which indicate hypersensitivity use of carbamazepine should be stopped immediately.

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

Increase in frequency of attacks can take place during transition from peroral forms of drug to suppositories.

Function of a liver. During therapy by drug it is necessary to carry out assessment of function of a liver at the leaving level and periodic estimates of this function throughout therapy, especially at patients with liver diseases in the anamnesis and at patients of old age. At an aggravation of abnormal liver functions or at patients with an active phase of a disease of a liver it is necessary to stop administration of drug immediately.

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

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

Mental effects. It is necessary to remember probability of activation of latent psychosis, and at patients of old age – confusion is consciousness or excitement.

Endocrine effects. Cases of breakthrough bleedings at women who received Carbamazepine in a combination with hormonal contraceptives were registered. As Karbamazepin can negatively affect efficiency of hormonal contraceptives, women of reproductive age should recommend to consider the possibility of use of alternative forms of contraception during drug use. In view of induction of enzymes of a liver Carbamazepine can become the reason of decrease in therapeutic effect of drugs of estrogen and/or progesterone (that is to interfere with effective contraception).

Monitoring of level of drug in a blood plasma. In spite of the fact that correlation between dosing and level of carbamazepine in a blood plasma, and also between carbamazepine level in a blood plasma and clinical performance and portability is doubtful, monitoring of level of drug in a blood plasma can be reasonable in such cases: at sudden increase in frequency of attacks, check of a komplayns of the patient, at pregnancy, at treatment of children and teenagers, at suspicion on absorption disturbances, at the suspected toxicity and at use more than one drug.

Dose decline and drug withdrawal. Sudden cancellation of carbamazepine can provoke attacks. In need of sudden cancellation of therapy by drug at patients with epilepsy, transition to new antiepileptic drug has to be carried out against the background of therapy by the corresponding medicine (for example, diazepam intravenously, rektalno or Phenytoinum intravenously).

Transfer of the patient from reception of tablets on reception of tablets ретард. Clinical experience demonstrates that some patients at use of tablets ретард can have a need for increase in a dose of drug.

Considering medicinal interactions and different pharmacokinetics of antiepileptic drugs, patients of old age of a dose of carbamazepine should select with care.

Ability to influence the speed of reactions at control of motor transport or work with other mechanisms.

Ability of the patient accepting carbamazepine to bystry reaction, especially in an initiation of treatment or during selection of a dose, can be broken owing to developing of dizziness and drowsiness. Therefore during treatment by drug it is necessary to abstain from control of motor transport or work with other mechanisms.

Side effects:

From the central nervous system and peripheral nervous system: headache, dizziness, drowsiness, ataxy, increased fatigue, involuntary reductions of muscles (tremor, dystonia, nervous tic), nystagmus, dyskinesia of face muscles, disturbance of movements by eyes, diction disturbance, peripheral neuropathy, paresthesias, muscular weakness, paresis, defatsialny dyskinesia, dysarthtia, choreoathetosis. Also psychotic reactions can be observed: hallucinations, a depression, the increased aggression, agitation, excitement, concern, confusion of consciousness, an exacerbation of psychosis, it is very rare – a malignant antipsychotic syndrome.

From sense bodys: disturbance of flavoring omissions, accommodation disturbance, diplopia, conjunctivitis, phacoscotasmus, increase in intraocular pressure, hearing disorder, sonitus, hyperacusia, gipoakuziya, disturbance of perception of height of tone.

From digestive tract: анорексія, dryness in a mouth, nausea, vomiting, diarrhea, a lock, abdominal pains, a glossitis, stomatitis, pancreatitis.

From gepatobiliarny system: cholestatic hepatitis, increase in concentration of an alkaline phosphatase in blood, increase in level of transaminases, parenchymatous and cholestatic hepatitis, granulematozny hepatitis, jaundice, a liver failure. Increase in level of a gammaglutamiltransferaza (a liver enzyme induction vstedstviye) is very often observed, but as a rule has no clinical value.

From endocrine system: hypostases, a liquid delay, increase in body weight, a hyponatremia and decrease in osmolarity of a blood plasma under the influence of an antidiuretic goromon that in rare instances leads to a cultivation hyponatremia that is followed by vomiting, a lethargy, a headache, confusion of consciousness, neurologic disturbances. Also increases in level of prolactin of blood with manifestation of the following symptoms can be observed: galactorrhoea, gynecomastia, pathological results of researches of a thyroid gland; decrease in level            of L-thyroxine (free thyroxine, thyroxine, triiodothyronine) and increase in concentration in blood of hormones of stimulators of a thyroid gland, disturbance of metabolism in bones (decrease in concentration of calcium in a blood plasma and                        25 hydrocalciferols in blood) that leads to osteomalacy, osteoporosis, increase in level of cholesterol in blood, including lipoproteids of high density and triglycerides.

From cardiovascular system: hypostases, disturbances of endocardiac conductivity, arterial hypertension, arterial hypotension, bradycardia, arrhythmia, atrioventricular block, syncope, circulator collapse, congestive heart failure, exacerbation of coronary heart disease, thrombophlebitis, thrombembolia (for example, embolism of pulmonary vessels).

From system of blood: a leukopenia, thrombocytopenia, a leukocytosis, deficit of folic acid, an agranulocytosis, aplastic anemia, a lymphadenopathy, a pancytopenia, an aplasia of red blood cells, anemia, megaloblastny anemia, an acute intermittent porphyria, the mixed porphyria, a late skin porphyria, a reticulocytosis, hemolitic anemia.

From respiratory system: hypersensitivity reactions (fever, диспноэ, pneumonitis, pneumonia).

From a musculoskeletal system: arthralgias, muscle pains, spasms of muscles.

From a reproductive system: gynecomastia, pathological spermatogenesis, sexual dysfunction, impotence.

From an urinary system: intersticial nephrite, renal failure, renal failure (proteinuria, albuminuria, hamaturia, oliguria, azotemia), frequent urinations, ischuria.

From immune system: multiorgan reactions of hypersensitivity of the slowed-down type with the following manifestations: fervescence, skin rashes, inflows, a vasculitis, a lymphadenopathy, a pseudo-lymphoma, a leukopenia, an eosinophilia, a gepatosplenomegaliya and the changed indicators of function of a liver (the specified manifestations meet in different combinations). Also can be observed: aseptic meningitis (with a myoclonia and a peripheral eosinophilia), anaphylactic reactions, a Quincke's disease.

Dermatological disturbances: rashes, allergic dermatitis, an itch, a small tortoiseshell, exfoliative dermatitis, an erythrosis, a volchanochnopodobny syndrome, Stephens-Johnson's syndrome, a toxic epidermal necrolysis, reactions of a photosensitization, a multiformny nodular erythema, a nodose erythema, alterations on skin, disturbance of a xanthopathy, purple, eels, a hyperhidrosis, loss of hair, a hirsutism.

Deviations of results of laboratory researches: hypogammaglobulinemia.

Interaction with other medicines:

P450 3A4 cytochrome (CYP3A4) is the main enzyme catalyzing formation of an active metabolite of carbamazepine-10,11-epoxide. Simultaneous use of CYP3A4 inhibitors can cause increase in concentration of carbamazepine in a blood plasma that, in turn, can lead to development of side reactions. Simultaneous use of the inductors CYP3A4 can strengthen carbamazepine metabolism that leads to potential decrease in concentration of carbamazepine in blood serum and therapeutic effect. In this way 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 ІІ 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 carbamazepine-10,11-epoxides........................ Co-administration of inhibitors human microsomal can lead epoxide-hydrolase to increase in concentration of carbamazepine-10,11-epoxide in a blood plasma.

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 undesirable reactions (for example, dizziness, drowsiness, an ataxy, a diplopia), dosing of carbamazepine it is necessary to korrigirovat and/or control respectively its levels in a blood plasma at simultaneous use with such drugs:

analgetics, antiinflammatory drugs: dextropropoxyphene, ibuprofen.

Androgens: даназол.

Antibiotics: makrolidny antibiotics (for example, erythromycin, тролеандомицин, йозамицин, кларитромицин).

Antidepressants: perhaps, desipramine, fluoxetine, флувоксамин, нефазодон, пароксетин, Trazodonum, вилоксазин.

Antiepileptic: стирипентол, вигабатрин.

Antifungal means: azoles (for example, итраконазол, кетоконазол, флуконазол, вориконазол).

Antihistaminic drugs: лоратадин, терфенадин.

Antipsychotic drugs: olanzapine.

Antitubercular drugs: isoniazid.

Antiviral drugs: protease inhibitors for HIV (for example, ритонавир).

Karboangidraza inhibitors: acetazoleamide.

Cardiovascular drugs: diltiazem, verapamil.

Drugs for treatment of gastrointestinal diseases: perhaps, Cimetidinum, омепразол.

Muscle relaxants: оксибутинин, дантролен.

Antiagregantny drugs: тиклопидин.

Other substances: grapefruit juice, niacinamide (at adults, only in high doses).

Drugs which can increase the level of an active metabolite of carbamazepine-10,11-epoxide in a blood plasma.

As the increased level of an active metabolite of carbamazepine-10,11-epoxide in a blood plasma can cause development of side reactions (for example, dizziness, drowsiness, an ataxy, a diplopia), dosing of carbamazepine it is necessary to adjust and/or control respectively drug level in a blood plasma if carbamazepine is accepted along with such drugs: локсапин, кветиапин, Primidonum, прогабид, valproic acid, валноктамид and валпромид.

Drugs which can reduce carbamazepine level in a blood plasma.

There can be a need for dose adjustment of carbamazepine at simultaneous use with such drugs:

antiepileptic drugs: фелбамат, метсуксимид, окскарбазепин, Phenobarbitonum, фенсуксимид, Phenytoinum and фосфенитоин, Primidonum and clonazepam (though data on it are contradictory).

Antineoplastic drugs: Cisplatinum or doxorubicine.

Antitubercular drugs: rifampicin.

Bronkhodilyatatora or antiasthmatic drugs: theophylline, Aminophyllinum.

Dermatological drugs: изотретиноин.

Interaction with other substances: drugs of officinal herbs which contain a St. John's Wort (Hypericum perforatum).

Influence of carbamazepine on level in a blood plasma of at the same time appointed drugs.

Carbamazepine can reduce the level of some drugs in a blood plasma and reduce or level their effects. Emergence of need for correction of dosing of the included below drugs according to clinical requirements is possible.

Analgetics, antiinflammatory drugs: methadone, paracetamol, phenazone (antipyrine), трамадол.

Antibiotics: doxycycline.

Anticoagulants: peroral anticoagulants (for example, warfarin, фенпрокоумон, дикумарол and аценокумарол).

Antidepressants: бупропион, to tsitalopra, нефазодон, Trazodonum, tricyclic antidepressants (for example, Imipraminum, amitriptyline, нортриптилин, кломипрамин). Carbamazepine is not recommended to be applied along with monoamine oxidase inhibitors (MAO); before use of drug it is necessary to stop MAO inhibitor reception (at least in two weeks or earlier if it clinical circumstances allow).

Antiepileptic drugs: to klobaza, clonazepam, Ethosuximidum, фелбамат, ламотриджин, окскарбазепин, Primidonum, тиагабин, топирамат, valproic acid, зонисамид. It was reported as about increase in level of Phenytoinum in a blood plasma owing to effect of carbamazepine, and about its decrease and about single cases of increase in level of Mephenytoinum in a blood plasma.

Antifungal drugs: итраконазол.

Anthelmintic drugs: praziquantel.

Antineoplastic drugs: иматиниб.

Antipsychotic drugs: clozapine, haloperidol and бромперидол, olanzapine, кветиапин, рисперидон, зипразидон.

Antiviral drugs: inhibitors of proteases for treatment of HIV (for example, индинавир, ритонавир, саквинавир).

Anxiolytics: to alprazola, midazolam.

Bronkhodilyatatora or antiasthmatic drugs: theophylline.

Contraceptive drugs: hormonal contraceptives (it is necessary to consider the possibility of use of alternative methods of contraception).

Cardiovascular drugs: blockers of calcium channels (group of dihydropyridine), for example, фелодипин, digoxin.

Corticosteroids: for example, Prednisolonum, dexamethasone.

Immunodepressants: cyclosporine, эверолимус.

Thyroid drugs: left thyroxine.

Interaction with other drugs: the drugs containing estrogen and/or progesterona.

Combinations of drugs which demand separate consideration.

Simultaneous use of carbamazepine and levetiratsetam can lead to strengthening of toxicity of carbamazepine.

Simultaneous use of carbamazepine and isoniazid can lead to strengthening of a hepatotoxic of an isoniazid.

Simultaneous use of carbamazepine and drugs of lithium or Metoclopramidum, and also carbamazepine and neuroleptics (haloperidol, thioridazine) can lead to strengthening of side neurologic effects (in case of the last combination – even on condition of therapeutic levels in a blood plasma).

The combination therapy carbamazepine and some diuretics (Hydrochlorthiazidum, furosemide) can lead to emergence of a symptomatic hyponatremia.

Carbamazepine can antagonizirovat effects of not depolarizing muscular relaxants (for example, a pankuroniya). There can be a need of increase in doses of these drugs, and patients demand careful monitoring in view of a possibility of more bystry, than it is expected, end to a neyromysha

Contraindications:

Hypersensitivity to carbamazepine or to similar drugs in the chemical relation (for example, to tricyclic antidepressants) or to any other component of drug; atrioventricular block; marrow diseases; hematologic diseases; acute porphyria; heavy abnormal liver functions, kidneys, cordial activity, sodium exchange; glaucoma; prostatitis; a concomitant use with monoamine oxidase inhibitors (MAO).

Overdose:

Poisoning with carbamazepine is characterized by disturbances from TsNS, cardiovascular system and systems of a respiratory organs.

From the central and peripheral nervous system: TsNS function oppression, disorientation, drowsiness, hallucinations, hypothermia, dyskinesia, dysarthtia, hyperreflexia (in the beginning), hyporeflexia (later), myoclonus, diction disturbances, psychomotor excitement, dizziness, ataxy, catalepsy, stupor, concern, tremor, involuntary movements, spasms, coma, psychomotor frustration.

From sense bodys: accommodation disturbance, mydriasis, nystagmus, sight opacification.

From cardiovascular system: arterial hypo - or hypertensia, tachycardia, disturbance of cordial conductivity with expansion of a QRS complex, syncopes, a cardiac standstill that is followed by a loss of consciousness.

From system of a respiratory organs: oppression of a respiratory center, fluid lungs.

From digestive tract: nausea, vomiting, decrease in motility of a stomach, disturbance of evacuation function of a stomach, decrease in motility of a large intestine.

From an urinary system: an ischuria, an oliguria, an anury, a liquid delay an organism, a cultivation hyponatremia thanks to effect of carbamazepine similar to effect of antidiuretic hormone.

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

Dermatological disturbances: erubescence of the person and neck with a burning sensation.

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

Evacuation of contents of a stomach, gastric lavage, use of absorbent carbon is made. Late evacuation of gastric contents can lead to the delayed absorption and repeated emergence of symptoms of intoxication during recovery. The symptomatic supporting treatment in intensive care unit, monitoring of function of heart, careful correction of electrolytic frustration is applied.

Special recommendations. At development of arterial hypotension intravenous administration of a dopamine or Dobutaminum is shown; at development of disturbances of a heart rhythm treatment is selected individually; at development of spasms – administration of benzodiazepines (for example, diazepam) or other anticonvulsants, for example, phenobarbital (with care in view of the increased risk of development of respiratory depression) or paraldehyde; at development of a hyponatremia (water intoxication) – restriction of administration of liquid, slow, careful intravenous infusion of 0,9% of solution of sodium of chloride. These actions can be useful to prevention of wet brain.

Carrying out hemosorption on coal sorbents is recommended. It was reported about inefficiency of an artificial diuresis, hemodialysis and peritoneal dialysis.

It is necessary to expect a possibility of repeated strengthening of symptoms of overdose for the 2nd and 3rd day after its beginning that is caused by drug absorption delay.

Storage conditions:

Store in the dry, protected from light place. The period of validity is specified on packaging.

Issue conditions:

According to the recipe

Packaging:

 On 0,2 g in tablets on 10 pieces in a blister strip packaging.