Carbamazepine

General characteristics. Structure:

Active agent: carbamazepine of 200 mg;

excipients: potato starch, lactoses monohydrate (sugar milk), magnesium stearate, sodium starch glycollate (sodium carboxymethylstarch, примогель), povidone (Kollidon 30), talc.

Description
Tablets of color, white or white with a yellowish shade, ploskotsilindrichesky, with a facet and risky.

Pharmacological properties:

Pharmacodynamics. Carbamazepine is derivative dibenzazepine and possesses antiepileptic, psychotropic, antidiuretic, weak m-holinoblokiruyushchim action. As antiepileptic means, stabilizes membranes of the overexcited neurons, suppresses serial categories of neurons and reduces synoptic transfer of exciting impulses. This action is reached, presumably due to blockade of natrium channels. therefore, repeated emergence in the depolarized neurons sodium - dependent action potentials is prevented. Reduces release of a neurotransmitter of a glutamate. Psychotropic effect of carbamazepine, apparently, is caused by oppression of exchange of a dopamine and Norepinephrinum. Reduces the frequency of attacks, alarm, a depression, irritability and aggression at patients with epilepsy. Influence on cognitive functions at patients with epilepsy is variable. Prevents emergence of paroxysmal pains at neuralgia. At a syndrome of alcoholic abstinence raises a threshold of convulsive readiness, reduces the increased nervous irritability, a tremor, gait disturbances. It is used for treatment of affective frustration as antipsychotic and normotimichesky means. At not diabetes mellitus reduces a diuresis and feeling of thirst.

Pharmacokinetics. Absorption — slow, but rather full (meal significantly does not influence the speed and extent of absorption). After a single dose, the maximum concentration in a blood plasma is reached in 12 hours; equilibrium concentration — is reached in 1–2 weeks. Essential interindividual distinctions of values of equilibrium concentration in the therapeutic range are observed. Communication with proteins of a blood plasma of 70 — 80%.

Concentration of not changed carbamazepine in cerebrospinal fluid and in saliva is proportional to amount of active agent, untied with proteins (20 — 30%). Concentration in breast milk makes 25 — 60% of that in plasma. Gets through a placental barrier.

It is metabolized in a liver, it is preferential on an epoxy way with formation of metabolites: active — carbamazepine-10,11-epoxide and low-active — 9-hydroxy-methyl-10 карбамоилакридан. The main isoenzyme providing carbamazepine biotransformation in carbamazepine-10,11-epoxide is CYP3A4. Content of carbamazepine-10,11-epoxide makes about 30% of carbamazepine level in plasma. Biotransformation of carbamazepine-10,11-epoxide in a carbamazepine-10,11-transdiol occurs by means of microsomal enzyme hydrolase epoxide. Other way of metabolism of carbamazepine — formation of various monohydroxylated derivatives, and also N-glucuronides. The elimination half-life after one-time reception averages about 36 hours (from 25 to 65 hours fluctuate), after repeated reception — 16–24 h. At the patients receiving in addition other antiepileptic drugs inducing liver enzymes, on average 9–10 h. It is removed in the form of inactive metabolites preferential by kidneys (about 70%) and intestines (about 30%). About 2% are removed by kidneys in the form of not changed carbamazepine and 1% in the form of carbamazepine-10,11-epoxide.

At children owing to more bystry removal of carbamazepine, use of higher doses of drug at the rate on 1 kg of body weight, in comparison with adults can be required.

There are no data that the pharmacokinetics of carbamazepine changes at patients of advanced age. Patients with renal failures or a liver have no data on carbamazepine pharmacokinetics.

Indications to use:

• Epilepsy, excepting absentias epileptica, myoclonic and sluggish attacks (monotherapy or as a part of complex therapy):
difficult and simple partial attacks (with loss or without loss of consciousness) with secondary generalization or without it;
generalized toniko-clonic attacks. The mixed forms of epileptic attacks.

• Acute maniacal states and a maintenance therapy of bipolar affective disorders for the purpose of prevention of aggravations or decrease in expressiveness of clinical manifestations.

• In complex therapy of a syndrome of alcoholic abstinence.

• An epileptiform neuralgia (idiopathic, at multiple sclerosis), idiopathic neuralgia of a glossopharyngeal nerve.

• A pain syndrome at a diabetic neuropathy.

• A polyuria and a polydipsia at not diabetes mellitus of the central genesis.

Route of administration and doses:

Inside, regardless of meal with a small amount of liquid. 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 2000 mg.

For children under 5 years an initial dose of 20-60 mg a day with increase on 20–60 mg each two days. At children from 5 years the initial dose makes 100 mg/day, with the subsequent increase on 100 mg a week. The maintenance dose for children makes 10–20 mg/kg of body weight a day for 2–3 receptions.

Neuralgia of trigeminal or yazykoglotochiy nerves: an initial dose of 200-400 mg/day, then the dose is gradually raised no more than on 200 mg a day up to the termination of pains (on average, to 600 — 800 mg), then reduced to a minimal effective dose. 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, sedative and somnolent drugs.

Polyuria and polydipsia at not diabetes mellitus: an average dose for adults — 200 mg 2 — 3 times a day. At children the dose is selected taking into account the body weight and age.

Pain syndrome at a diabetic neuropathy: 200 mg 2 — 4 times a day.

Acute maniacal states and maintenance therapy of bipolar affective disorders: a daily dose of 400-1600 mg (an average daily dose of 200-600 mg) in 2–3 receptions a day. In acute cases the dose is raised quickly enough. At a maintenance therapy increase in a dose has to be gradual and small.

Features of use:

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 number of thrombocytes, reticulocytes, and also concentration of iron in blood serum), the general analyses of urine and determination of level of urea to blood. Drug has weak anticholinergic activity. Therefore in case of use of drug for patients with the increased intraocular pressure constant control of this indicator is necessary.

Periodic definition of concentration of carbamazepine in a blood plasma in cases of increase in frequency of emergence of epileptic attacks is recommended, at treatment of children, at pregnant women, in case of its use as a part of complex therapy, development of the expressed side effects.

There are separate messages on disturbances of male fertility and/or disturbances of a spermatogenesis. However the causal interrelation of these disturbances with administration of drug is so far not proved.

Cross-reactions of hypersensitivity can arise between carbamazepine and Phenytoinum or okskarbazepiny.

Monotherapy of epilepsy is begun with purpose of small doses, individually raising them to achievement of desirable therapeutic effect. At transfer of the patient into carbamazepine it is necessary to reduce gradually a dose of earlier appointed antiepileptic medicine up to its full cancellation. The sudden termination of reception of carbamazepine can provoke epileptic attacks. If it is necessary to interrupt sharply treatment, it is necessary to transfer the patient to other antiepileptic medicine under cover of the drug shown in such cases (for example, the diazepam entered intravenously or rektalno or Phenytoinum entered intravenously). Several cases of vomiting, diarrhea and/or subnutrition, spasms and/or respiratory depressions at newborns whose mothers accepted carbamazepine along with other anticonvulsant medicines are described (perhaps, these reactions represent manifestations at newborns of a syndrome of "cancellation"). Before purpose of carbamazepine 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 for patients of advanced age 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.

Before an initiation of treatment it is also necessary to conduct a blood picture research (including calculation of thrombocytes, reticulocytes), concentration of iron to blood serum, the general analysis of urine, concentration of urea in blood, an electroencephalography, definition of concentration of electrolytes in blood serum (and periodically during treatment as development of a hyponatremia is possible). Afterwards these indicators should be controlled within the first month of treatment weekly, and then monthly.

Carbamazepine has to be immediately cancelled at emergence of the allergic reactions or symptoms presumably testimonial of development of a syndrome of Stephens-Johnson or a Lyell's disease. Slight skin reactions (the isolated macular or makulopapulezny dieback) usually take place within several days or weeks even at continuation of treatment or after a drug dose decline (the patient has to be under fixed observation of the doctor at this time).

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. Messages on emergence at women of bleedings during the period between periods in cases when oral contraceptives were at the same time applied are known. Carbamazepine can negatively affect reliability of peroral contraceptive medicines therefore women of reproductive age during treatment should apply alternative methods of protection from pregnancy. Carbamazepine has to be applied only under medical observation. It is necessary to inform patients information on the precursory symptoms of toxicity inherent to probable hematologic disturbances, and also on symptoms from integuments and a liver. The patient is informed on need to see immediately a doctor in case of such undesirable reactions as fever, pharyngalgias, rash, an ulceration of a mucous membrane of an oral cavity, causeless developing of "bruises", hemorrhages in the form of petechias or a purpura. In most cases passing or permanent decrease in number of thrombocytes and/or leukocytes is not a harbinger of the beginning of aplastic 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 number of thrombocytes and, perhaps, reticulocytes, and also to define concentration of iron in blood serum.

The progressing symptomless leukopenia demands 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. Before an initiation of treatment also measurement in need of intraocular pressure is recommended to conduct ophthalmologic examination, including an eyeground research a slit lamp. In case of purpose of drug patients with the increased intraocular pressure need constant control of this indicator. It is recommended to refuse the ethanol use.

Though the interrelation between a carbamazepine dose, its concentration and clinical performance or portability is very insignificant, nevertheless regular definition of concentration of carbamazepine can be useful in the following situations: at sharp increase in frequency of attacks; to check whether the patient accepts drug properly; during pregnancy; at treatment of children or teenagers; at suspicion on drug absorption disturbance; at suspicion on development of toxic reactions if the patient accepts several medicines. At women of reproductive age carbamazepine has to be applied whenever possible in the form of monotherapy (using minimum effective dose) - the frequency of congenital anomalies of the newborns born by women to whom the combined antiepileptic treatment, above, than at those who received each of these medicines in the form of monotherapy was carried out. At pregnancy approach (at the solution of a question of purpose of carbamazepine during pregnancy) it is necessary to compare carefully expected advantages of therapy and its possible complications, especially in the first 3 months of pregnancy. It is known that the children born at mothers having epilepsy are predisposed to disturbances of pre-natal development, including malformations. Carbamazepine, as well as all other antiepileptic medicines, is capable to increase risk of emergence of these disturbances. There are single messages on cases of inborn diseases and malformations, including not fusion of handles of vertebrae (spina bifida), a hypospadias. Information on a possibility of increase in risk of malformations and an opportunity to undergo antenatal diagnosis has to be provided to patients. Antiepileptic medicines increase the deficit of folic acid which is often observed during pregnancy that can promote increase in frequency of inborn defects at children (to and during pregnancy additional reception 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 K1 vitamin. Carbamazepine gets into breast milk, it is necessary to compare advantages and possible undesirable effects of breastfeeding in the conditions of the continuing therapy. Mothers accepting carbamazepine can nurse the children provided that for the child observation concerning development of possible side reactions will be established (for example, the expressed drowsiness, allergic skin reactions).

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:

Mental disturbances: hallucinations (visual or acoustical), depression, anorexia, concern, agressive behavior, agitation, disorientation, strengthening of psychosis. Disturbances from a nervous system: dizziness, ataxy, drowsiness, feeling of fatigue, headache, diplopia, accommodation disturbances, tremor, muscular dystonia, tics, nystagmus, orofatsialny dyskinesia, oculomotor disturbances, dysarthtia, choreoathetoid frustration, peripheral neuropathy, paresthesias, paresis, taste disturbances, malignant antipsychotic syndrome.

From skin and its appendages: allergic dermatitis, small tortoiseshell, exfoliative dermatitis, erythrosis, system lupus erythematosus, itch, Stephens-Johnson's syndrome, toxic epidermal necrolysis, reactions of a photosensitization, multiformny and knotty erythema, disturbances of a xanthopathy, purple, acne, perspiration, hair loss. It was reported about exceptional cases of a hirsutism, however the causal interrelation of this complication with administration of drug remains not clear.

From system of a hemopoiesis: leukopenia, thrombocytopenia, eosinophilia, leukocytosis, lymphadenopathy, deficit of folic acid, agranulocytosis, aplastic anemia, pancytopenia. anemia, a true erythrocyte aplasia, megaloblastny anemia, a variyegatny porphyria, a late skin porphyria, the acute "alternating" porphyria, a reticulocytosis, hemolitic anemia.

From gepatobiliarpy system: increase in level gamma глутамилтранспептидазы, increase in level of an alkaline phosphatase, increase in activity of "hepatic" transaminases, hepatitis (cholestatic, the parenchymatous (hepatocellular) or mixed type), jaundice, granulematozny hepatitis, a liver failure. From digestive tract: nausea, vomiting, dryness in a mouth, diarrhea, a lock, abdominal pains, a glossitis, stomatitis, pancreatitis.

Hypersensitivity reactions: multiorgan hypersensitivity of the slowed-down type with the fever, skin rashes, a vasculitis, lymphadenopathy, signs reminding a lymphoma, an arthralgia, a leukopenia, an eosinophilia, a gepatosplenomegaliya and the changed indicators of function of a liver (the specified manifestations meet in various combinations). Also other bodies (lungs, kidneys, a pancreas, a myocardium, a large intestine) can be involved. Aseptic meningitis with a myoclonus and a peripheral eosinophilia; anaphylactic reactions, Quincke's disease.

From cardiovascular system: disturbances of endocardiac conductivity; increase or a lowering of arterial pressure, bradycardia, arrhythmia, an atrioventricular block with faints, a collapse, congestive heart failure, an exacerbation of coronary heart disease, thrombophlebitis, a thrombembolia.

From endocrine system and a metabolism: hypostases, a liquid delay, increase in body weight, a hyponatremia and decrease in osmolarity of plasma owing to the effect similar to effect of antidiuretic hormone that in rare instances leads to water intoxication (a cultivation hyponatremia) which is followed by a lethargy, vomiting, a headache, a disorientation and neurologic disturbances; the increase in level of prolactin which is followed or not followed by a galactorrhoea, a gynecomastia; changes of indicators of function of a thyroid gland — decrease in level of hormones of a thyroid gland (TZ, free and connected T4) and increase in level of thyritropic hormone that usually is not followed by clinical manifestations; disturbances of metabolism of a bone tissue (decrease in level of calcium and a 25-gidroksikolekaltsiferol in a blood plasma) that leads to osteomalacy; increase in concentration of cholesterol, including cholesterol of lipoproteins of high density and triglycerides.

From urinogenital system: intersticial nephrite, a renal failure, an albuminuria, a hamaturia, an oliguria, an azotemia, the speeded-up urination, an ischuria, disorders of sexual function, disturbance of a spermatogenesis.

From sense bodys: disturbances of flavoring feelings, phacoscotasmus, increase in intraocular pressure, conjunctivitis; disorders of hearing.

From skeletal and muscular system: arthralgias, muscular pains, muscular weakness, muscular spasms.

From respiratory system: the hypersensitivity reactions which are characterized by fever, short wind, a pneumonitis or pneumonia.

Change of results of laboratory researches: hypogammaglobulinemia.

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, a hyperreflexia (in the beginning), a hyporeflexia (later); spasms, psychomotor frustration, myoclonus, hypothermia, mydriasis).

From cardiovascular system: tachycardia, a lowering of arterial pressure (ABP), sometimes increase in the ABP, disturbance of intra ventricular conductivity with expansion of the QRS complex; cardiac standstill.

From a respiratory organs: respiratory depression, fluid lungs. From the alimentary system: nausea and vomiting, a delay of evacuation of food from a stomach, decrease in motility of a large intestine.

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 muscular fraction of a kreatinfosofokinaza.

Interaction with other medicines:

Simultaneous use with CYP3A4 inhibitors can lead to increase in concentration of carbamazepine in plasma. Combined use of the inductors CYP3A4 can lead to acceleration of metabolism of carbamazepine and to possible decrease in its concentration in plasma. Cancellation of at the same time accepted inductors CYP3A4 can reduce the speed of biotransformation of carbamazepine and lead to increase in level of carbamazepine in a blood plasma. At simultaneous use with the drugs which are metabolized CYP3A4 induction of metabolism and decrease in their concentration in plasma is possible.

Drugs which can increase concentration of carbamazepine or carbamazepine-10,11-epoxide in plasma: dextropropoxyphene, ibuprofen, даназол, makrolidny antibiotics (for example, erythromycin, тролеандомицин, джозамицин, кларитромицин), fluoxetine, флувоксамин, нефазодон, пароксетин, Trazodonum, вилоксазин, стирипентол, вигабатрин, azoles (for example, итраконазол, кетоконазол, флуконазол, вориконазол), лоратадин, терфенадин, локсапин, olanzapine, кветиапин, isoniazid, HIV protease inhibitors (for example, ритонавир), acetazoleamide. verapamil, diltiazem, омепразол, оксибутинин, дантролен, тиклопидин, niacinamide (at adults, only in high doses), Cimetidinum, desipramine, придомин, valproic acid.

Drugs which can reduce concentration of carbamazepine in plasma: фелбамат, окскарбазепин, phenobarbital, фенсуксимид, Phenytoinum, фосфенитоин, Primidonum, прогабид, theophylline, Aminophyllinum, изотретиноин, rifampicin, Cisplatinum, doxorubicine; the vegetable drugs containing the St. John's Wort which is made a hole and, perhaps, also clonazepam, valproic acid or вальпромид.

Influence of carbamazepine on concentration in plasma of the drugs used as the accompanying therapy:

Carbamazepine can reduce concentration in plasma or reduce or even completely to level effects of the following drugs: methadone, paracetamol, phenazone (antipyrine), трамадол, doxycycline, peroral anticoagulants (warfarin, фенпрокумон, дикумарол, аценокумарол), бупропион, to tsitalopra, Trazodonum, tricyclic antidepressants (Imipraminum, amitriptyline, нортриптилин, кломипрамин), to klobaza, clonazepam, Ethosuximidum, фелбамат, ламотриджин, окскарбазепин, Primidonum, тиагабин, топирамат, valproic acid, зонисамид, итраконазол, praziquantel, иматиниб, clozapine, haloperidol, бромперидол, olanzapine, кветиапин, рисперидон, зипрасидон,

at therapy of HIV infection (индинавир, ритонавир, саквинавир), to alprazola; midazolam, theophylline, blockers of calcium channels of group of dihydropyridines (for example, фелодипин), digoxin, peroral contraceptive means (selection of alternative methods of contraception), glucocorticosteroids (for example, Prednisolonum, dexamethasone is necessary); cyclosporine, эверолимус, sodium left thyroxine, estrogen and/or progesterone. 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).

Combinations which should be taken into account:

Perhaps strengthening of the hepatotoxic caused by an isoniazid in case of simultaneous use with carbamazepine.

In case of joint appointment with levetiratsetamy, strengthening of toxic effect of carbamazepine is possible.

The combined use of carbamazepine and 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 show antagonism to action of not depolarizing muscle relaxants (for example, a pankuroniya bromide). In case of use of such combination of medicines there can be a need for 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 carefully.

Carbamazepine can reduce portability of alcohol. In this regard, the patient is recommended to refuse alcohol intake.

Joint reception with grapefruit juice can increase carbamazepine level in plasma.

Co-administration of carbamazepine with fenotiaziny, phenobarbital, felbamaty, fensuksimidy, fosfenitoiny, progabidy, Aminophyllinum, izotretinoiny, Pimozidum, molindony, the haloperidol, Maprotilinum, clozapine, tricyclic antidepressants, rifampicin, tetracycline, Cisplatinum, doxorubicine, Primidonum, theophylline, valproic acid, vegetable drugs containing the St. John's Wort which is made a hole can lead to reduction of concentration of carbamazepine in a blood plasma and to decrease in its anticonvulsant action.

MAO inhibitors increase risk of development of giperpireticheky crises, hypertensive crises, spasms, death (before purpose of carbamazepine MAO inhibitors have to be cancelled at least for 2 weeks or if the clinical situation, even for bigger term allows). Accelerates metabolism of indirect anticoagulants, hormonal contraceptive medicines, folic acid; prazikvantet, can strengthen elimination of hormones of a thyroid gland. Accelerates metabolism of medicines for the general anesthesia (an enfluran, a halothane, Ftorotanum) with increase in risk of hepatotoxic effects; strengthens formation of nefrotoksichny metabolites of a metoksifluran. Strengthens a hepatotoxic action of an isoniazid. Myelotoxic medicines strengthen manifestations of a gematotoksichnost of drug.

Contraindications:

• hypersensitivity to any of components of drug or medicines (tricyclic antidepressants), similar on a chemical structure; - an atrioventricular block,

• oppression of a marrowy hemopoiesis in the anamnesis — the acute "alternating" porphyria,

• a concomitant use of monoamine oxidase inhibitors (MAO) and within 2 weeks after their cancellation,

• children's age up to 5 years - the breastfeeding period.

With care: low level of leukocytes or thrombocytes; the mixed forms of epileptic attacks including an absentia epileptica; advanced age; heart, liver or renal failure; the increased intraocular pressure; cultivation hyponatremia; hypothyroidism; prostate hyperplasia; active alcoholism (oppression of the central nervous system (CNS) amplifies, carbamazepine metabolism), oppression of a marrowy hemopoiesis against the background of reception of medicines (in the anamnesis amplifies); pregnancy (the increased risk of development of disturbances of pre-natal development, including malformations).

Overdose:

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

Treatment: the specific antidote is absent. Treatment is based on a clinical condition of the patient. Hospitalization, definition of concentration of carbamazepine in plasma (for confirmation of poisoning with this medicine and assessment of extent of overdose), a gastric lavage, purpose of absorbent carbon are shown (late evacuation of gastric contents can lead to the delayed absorption on 2 both 3 days and to repeated emergence of symptoms of intoxication during recovery). The artificial diuresis, a hemodialysis and peritoneal dialysis are inefficient (dialysis is shown at a combination of a serious poisoning and renal failure). Small children can have a need for exchange hemotransfusion.

The symptomatic supporting treatment in intensive care unit, monitoring of functions of heart, body temperature, corneal reflexes, functions of kidneys and a bladder, correction of electrolytic frustration. At decrease in the ABP: situation with the lowered head end, plasma substitutes, at inefficiency — are intravenously entered a dopamine or Dobutaminum; at disturbances of a heart rhythm — treatment is selected individually; at spasms — benzodiazepines (for example diazepam), with care are entered (because of possible increase in respiratory depression) other anticonvulsant medicines are entered (for example phenobarbital). At development of a hyponatremia of cultivation (water intoxication) — restriction of administration of liquids and slow intravenous infusion of 0,9% of NaCl solution (can promote prevention of edematization of a brain). Carrying out hemosorption on coal sorbents is recommended.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets on 200 mg.

On 10, 15, 25 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 3, 5 blister strip packagings on 10 tablets or on 2, 4 blister strip packagings on 15 tablets, or on the 2nd blister strip packagings on 25 tablets, or on 1, 2 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.