Carbamazepine таб. 200 mg, No. 50 Comte. cell. (in a pack)

General characteristics. Structure:

Active agent: 200 mg of carbamazepine; excipients – лудипресс (lactoses monohydrate, povidone, кросповидон), magnesium stearate, calcium monohydrate, potato starch.

Pharmacological properties:

Pharmacodynamics. The antiepileptic means derivative of dibenzazepine having normotimichesky, anti-maniacal and analgetic effect. Activates the central brake GAMK-ergichesky system. Blocks potential - dependent natrium channels of membranes of nervous cells that leads to functional stabilization of neurons, reduces activity of exciting neuromediator acids (a glutamate, aspartate), interacts with the central adenosine receptors (adenylatecyclase activation suppression). Raises a convulsive threshold, adjusts epileptic changes of the personality. At not diabetes mellitus reduces a diuresis and feeling of thirst (due to antidiuretic effect).

Pharmacokinetics.  Absorption – slow, but rather full (meal does not influence the speed and extent of absorption). After a single dose the maximum concentration (Cmax) is reached in 12 hours. Equilibrium concentration of drug in plasma are reached in 1-2 weeks. Concentration carbamazepine – 10,11 – epoxide (pharmacological an active metabolite) make about 30% of concentration of carbamazepine. Communication with proteins of plasma children – 55 – 59%, at adults have 70 – 80%. In cerebrospinal fluid (further SMZh) and saliva create concentration in proportion to amount of active agent, untied with proteins (20 – 30%). Gets through a placental barrier. Concentration in breast milk makes 25 – 60% of that in plasma. It is metabolized in a liver, it is preferential on an epoxy way with formation of the main metabolites: active – carbamazepine-10, 11 epoxides and an inactive conjugate with glucuronic acid. A low-active metabolite 9-hydroxy-methyl-10 карбамоилакридан is formed as well. Can induce own metabolism. Concentration of carbamazepine-10,11-epoxide makes 30% of concentration of carbamazepine. An elimination half-life (T1/2) of one-time reception of 25-65 h (on average about 36 h), after repeated reception – 12-24 h. At the patients receiving in addition other anticonvulsant drugs T1/2 on average of 9-10 h. It is removed in the form of inactive metabolites with urine (70%) and a stake (30%). There are no data that the pharmacokinetics of carbamazepine changes at patients of advanced age. Patients with renal failures or a liver have still not enough data on carbamazepine pharmacokinetics.

Indications to use:

Epilepsy (excepting absentias epileptica, myoclonic or sluggish attacks) – partial attacks with difficult and simple symptomatology, initially and for the second time generalized forms of attacks with tonikoklonichesky spasms, the mixed forms of attacks (monotherapy or in combination with other antiepileptic drugs); an idiopathic epileptiform neuralgia, an epileptiform neuralgia at multiple sclerosis, idiopathic glossopalatine neuralgia, an alcoholic abstinence syndrome, treatment of affective frustration, a polydipsia and a polyuria at not diabetes mellitus, a pain syndrome at diabetic polyneuropathy.            

Prevention of faznoprotekayushchy affective disturbances (maniac-depressive psychosis, schizoaffective disorders, etc.).

Route of administration and doses:

Inside, regardless of meal with a small amount of liquid.           

At epilepsy: whenever possible, it is necessary to appoint carbamazepine in the form of monotherapy. Treatment is begun with a small daily dose which in the subsequent is slowly raised to achievement of optimum effect. Accession of carbamazepine to already carried out antiepileptic therapy should be carried out gradually.            

For adults an initial dose of 100-200 mg 1-2 times a day. Then the dose is slowly raised to 400 mg by 2-3 times a day. Maximum daily dose of 1600 - 2000 mg.            

For children the average daily dose is defined at the rate of 10-20 mg/kg of body weight a day and makes: for children aged from 4 months till 1 year – 100-200 mg a day, from 1 year to 5 years – 200-400 mg (for 1-2 receptions),  from 6 to 10 years – 400-600 mg (for 2-3 receptions), for 11-15 years – 600-1000 mg (for 2-3 receptions).  

At an epileptiform neuralgia and a neurogenic pain syndrome: 100-200 mg 2 times a day, then gradually raise a dose no more than on 200 mg a day up to the termination of pains (on average, to 600-800 mg), then reduce to a minimal effective dose. The effect occurs usually in 1 – 3 day after an initiation of treatment.            

Appoint drug it is long: at premature drug withdrawal of pain can renew. At treatment of patients of advanced age an initial dose of 100 mg 2 times a day.            

Alcoholic abstinence syndrome: an average dose – 200 mg 3 times a day. In hard cases, in the first days it is possible to raise a dose to 400 mg 3 times a day. In an initiation of treatment at the heavy phenomena of abstinence it is appointed in combination with disintoxication therapy and sedative and somnolent drugs.           Not diabetes mellitus: an average dose for adults – 200 mg 2 – 3 times a day. The diabetic neuropathy which is followed by pains: 200 mg 2 – 4 times a day.            

For prevention of affective disturbances: in the first week a daily dose of 200 - 400 mg. In the subsequent the dose is increased by 200 mg a week, bringing it to 1 g/days. The daily dose is evenly divided into 3-4 receptions.            

Transition to treatment by carbamazepine has to be gradual, with reduction of a dose of the previous drug. It is necessary to stop treatment gradually. Duration of treatment is established by the doctor.

Features of use:

Before an initiation of treatment it is necessary to carry out the general blood test (including calculation of thrombocytes, reticulocytes), the general analysis of urine, to determine the level of iron, concentration of electrolytes and urea in blood serum. Afterwards these indicators should be controlled within the first month of treatment weekly, and then – monthly. At appointment its periodic control is necessary for patients with the increased intraocular pressure. Not progressing symptomless leukopenia does not demand cancellation, however, treatment should be stopped at emergence of the progressing leukopenia or the leukopenia which is followed by clinical symptoms of an infectious disease. The sudden termination of reception of carbamazepine can provoke epileptic attacks. Before purpose of carbamazepine and in the course of treatment the research of function of a liver is necessary. In case of strengthening of already being available abnormal liver functions or at emergence of an active disease of a liver drug should be cancelled immediately. It is necessary to take into account a possibility of activation latentno of the proceeding psychoses, and patients of advanced age have a possibility of development of a disorientation or excitement.            

 During treatment it is necessary to abstain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. It is recommended to refuse alcohol intake.

Side effects:

From the central nervous system: dizziness, ataxy, drowsiness, general weakness, headache, accommodation paresis, tremor, tics, nystagmus, orofatsialny dyskinesia, oculomotor disturbances, dysarthtia, choreoathetoid frustration, peripheral neuritis, paresthesias, muscular weakness and paresis.            
From the mental sphere: hallucinations, depression, appetite loss, concern, agressive behavior, excitement, disorientation, activation of psychosis.            
Allergic reactions: urticaria, exfoliative dermatitis, erythrosis, volchanochnopodobny syndrome, Stephens-Johnson's syndrome, toxic epidermal necrolysis, photosensitivity, multiformny and knotty erythema. Multiorgan reactions of hypersensitivity of the slowed-down type with the fever, skin rashes, a vasculitis, lymphadenopathy, signs reminding a lymphoma, arthralgias, a leukopenia, an eosinophilia, a gepatosplenomegaliya and the changed indicators of function of a liver are possible (the specified manifestations meet in various combinations). Also other bodies can be involved (for example, lungs, kidneys, a pancreas, a myocardium, a large intestine). Very seldom – aseptic meningitis with a myoclonus, the anaphylactic reaction, a Quincke's disease, reactions of hypersensitivity from lungs which are characterized by fever, short wind, a pneumonitis or pneumonia.            
From bodies of a hemopoiesis: leukopenia, thrombocytopenia, eosinophilia, leukocytosis, limfoadenopatiya; an agranulocytosis, aplastic anemia, a true erythrocyte aplasia, megaloblastichesky anemia, the acute alternating porphyria, a reticulocytosis, hemolitic anemia.            
From the alimentary system (further GIT): nausea, vomiting, dryness in a mouth, diarrhea or a lock, an abdominal pain, a glossitis, stomatitis, pancreatitis.            
From a liver: increase in activity gamma глутамилтрансферазы (usually has no clinical value), increase in activity of an alkaline phosphatase and "hepatic" transaminases, hepatitis (granulematozny, cholestatic, the parenchymatous (hepatocellular) or mixed type); liver failure.            
From cardiovascular system (further CCC): disturbances of endocardiac conductivity; decrease or increase in arterial pressure; bradycardia, arrhythmias, an atrioventricular block with faints, a collapse, aggravation or development of congestive heart failure, an exacerbation of coronary heart disease (including emergence or increase of attacks of stenocardia), thrombophlebitis, a thromboembolic syndrome.            
From endocrine system and a metabolism: hypostases, increase in body weight, a hyponatremia, increase in level of prolactin (can be followed by a galactorrhoea and a gynecomastia); decrease in level of L-thyroxine (free T4, T3) and increase in level of thyritropic hormone (TTG) (usually is not followed by clinical manifestations), disturbances of calcium-phosphorus exchange in a bone tissue (decrease in concentration of Sa2 + and 25-IT-cholecalciferol in a blood plasma); osteomalacy; hypercholesterolemia and gipertriglitseridemiya.            
From urinogenital system: intersticial nephrite, a renal failure, a renal failure (an albuminuria, a hamaturia, an oliguria, increase an urea/azotemia), the speeded-up urination, an ischuria, disorders of sexual function / impotence.            
From a musculoskeletal system: arthralgia, mialgiya or spasms.           
From sense bodys: disturbances of flavoring feelings, cataract, conjunctivitis; hyper - or a gipoakuziya, changes of perception of height of a sound.            
Others: disturbances of a xanthopathy, purple, acne, perspiration, alopecia.

Interaction with other medicines:

Carbamazepine increases activity of microsomal enzymes of a liver and can reduce efficiency of the drugs which are metabolized in a liver. Co-administration of carbamazepine with CYP ZA4 inhibitors can lead to increase in its concentration in a blood plasma. Combined use with the inductors CYP ZA4 can lead to acceleration of metabolism of carbamazepine and decrease in its concentration in a blood plasma, on the contrary, their cancellation can reduce the speed of biotransformation of carbamazepine and lead to increase in its concentration.            

Increase concentration of carbamazepine in plasma: verapamil, diltiazem, фелодипин, dextropropoxyphene, вилоксазин, fluoxetine, флувоксамин, Cimetidinum, acetazoleamide, даназол, desipramine, niacinamide (at adults, only in high doses); macroleads (erythromycin, джозамицин, кларитромицин, тролеандомицин); azoles (итраконазол, кетоконазол, флуконазол), терфенадин, лоратадин, the isoniazid, the propoxyhair dryer, grapefruit juice, inhibitors of virus protease used at therapy of HIV. Felbamat reduces concentration of carbamazepine in plasma and carbamazepine – 10,11 – epoxide, at the same time perhaps simultaneous decrease in concentration in serum of a felbamat increases concentration. Concentration of carbamazepine is reduced by phenobarbital, Phenytoinum, Primidonum, метсуксимид, фенсуксимид, theophylline, rifampicin, cisplates, доксирубицин, it is possible: clonazepam, вальпромид, valproic acid, окскарбазепин and the vegetable drugs containing a St. John's Wort made a hole (Hypericum perforatum). There are messages on a possibility of replacement by valproic acid and carbamazepine Primidonum from communication with proteins of plasma and increase in concentration pharmacological of an active metabolite (carbamazepine-10,11-epoxide). Izotretinoin changes bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide (monitoring of concentration of carbamazepine in plasma is necessary). Carbamazepine can reduce concentration in plasma (to reduce or even completely to level effects) and to demand correction of doses of the following drugs: klobazama, clonazepam, an Ethosuximidum, Primidonum, valproic acid, an alprazolama, glucocorticosteroids (Prednisolonum, dexamethasone), cyclosporine, doxycycline, a haloperidol, methadone, peroral drugs containing estrogen and/or progesterone (selection of alternative methods of contraception), theophylline, peroral anticoagulants (warfarin, a fenprokumon, a dikumarol), a lamotridzhina, a topiramata, tricyclic antidepressants (Imipraminum, amitriptyline, a nortriptilin, a klomipramin), clozapine, a felbamat, a tiagabin, an okskarbazepin, inhibitors of the proteases applied at therapy of HIV infection (an indinavir, a ritonavir, a sakvinovir), blockers of calcium channels (group of digidropiridon, for example, фелодипин is necessary), an itrakonazola, left thyroxine, midazolam, an olazapin, a prazikvantel, a risperidon, a tramadol, a tsiprazidon. There are messages that against the background of carbamazepine reception Phenytoinum level in a blood plasma can both increase, and to decrease, and Mephenytoinum level – to increase (in rare instances). Carbamazepine at combined use with paracetamol increases risk of its toxic influence on a liver and reduces a therapeutic effectiveness (paracetamol metabolism acceleration). Co-administration of carbamazepine with fenotiaziny, Pimozidum, thioxanthenes, molindony, a haloperidol, Maprotilinum, clozapine and tricyclic antidepressants leads to strengthening of the oppressing action on TsNS and to easing of anticonvulsant effect of carbamazepine. Co-administration with diuretics (a hydrochlorothiazide, furosemide) can lead to the hyponatremia which is followed by clinical manifestations. Reduces effects of not depolarizing muscle relaxants (pankuroniya). Reduces portability of ethanol. Accelerates metabolism of indirect anticoagulants, hormonal contraceptive drugs, folic acid; prazikvantet, can strengthen elimination of hormones of a thyroid gland. Accelerates metabolism of means for the general anesthesia (an enfluran, a halothane, Ftorotanum) with increase in risk of gepatoksichny effects; strengthens formation of nefrotoksichny metabolites of a metoksifluran. Strengthens a hepatotoxic action of an isoniazid.

Contraindications:

Hypersensitivity to carbamazepine and similar medicines (tricyclic antidepressants) in the chemical relation or to any other component of drug, the acute alternating porphyria (including in the anamnesis), a concomitant use of monoamine oxidase inhibitors (further MAO inhibitors) and within 2 weeks after their cancellation, disturbance of a marrowy hemopoiesis, an atrioventricular block, pregnancy and the period of a lactation.            

With care – a cultivation hyponatremia, advanced age, alcohol intake, oppression of a marrowy hemopoiesis against the background of reception of medicines (in the anamnesis); a prostate hyperplasia, increase in intraocular pressure, the expressed heart failure, a liver failure, a chronic renal failure.

Overdose:

Symptoms: usually reflect disturbances from TsNS, CCC and respiratory system.

From TsNS and sense bodys: oppression of the TsNS functions, disorientation, drowsiness, excitement, hallucinations, unconscious states, coma; visual disturbances ("fog" before eyes), a dysarthtia, a nystagmus, an ataxy, dyskinesia; spasms, psychomotor frustration, myoclonus, mydriasis.           

From CCC: tachycardia, decrease in the ABP, sometimes increase in the ABP, disturbance of intra ventricular conductivity with expansion of the QRS complex; cardiac standstill.            

From a respiratory organs: fluid lungs.            

From the alimentary system: nausea and vomiting, a delay of evacuation of food from a stomach.            

From an urinary system: ischuria, oliguria or anury; liquid delay; cultivation hyponatremia.             

Laboratory indicators: leukocytosis or leukopenia, hyponatremia, metabolic acidosis, hyperglycemia and glucosuria, increase in the KFK muscular fraction. Treatment: the specific antidote is absent. A gastric lavage, purpose of absorbent carbon (late evacuation of gastric contents can lead to the delayed absorption for 2-3 days and to repeated emergence of symptoms of intoxication), symptomatic therapy. The artificial diuresis, a hemodialysis and peritoneal dialysis are inefficient (dialysis is shown at a combination of a serious poisoning and renal failure). Children can have a need for exchange hemotransfusion. Carrying out hemosorption on coal sorbents is recommended.

Storage conditions:

List B. In dry, protected from light and the place, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets of 200 mg. On 10 tablets in a blister strip packaging or on 40 tablets in bank from glass melt or on 50 tablets in bank from polymeric material. 5 blister strip packagings or one bank from glass melt or from polymeric material together with the application instruction in a pack from a cardboard.