Карбамазепин-Акри®

General characteristics. Structure:

Active ingredient: 200 mg of carbamazepine.

Excipients — potato starch, hydroxypropyl cellulose, magnesium stearate.

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 (Smakh) is reached in 12 hours. Equilibrium concentration of drug in plasma are reached in 1-2 weeks. Concentration of Karbamazepin-10,11-epoksida (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 — Karbamazepin-10,11-epoksida and an inactive conjugate with glucuronic acid. A low-active metabolite 9-hydroxymethyl-10 карбамоилакридан is formed as well. Can induce own metabolism.

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:
- difficult or simple partial epileptic attacks (with loss or without loss of consciousness) with secondary generalization or without it;
- generalized toniko-clonic epileptic attacks, the mixed forms of epileptic attacks.
• In complex therapy of acute maniacal states, a maintenance therapy of bipolar affective disorders for the purpose of prevention of aggravations or weakening of clinical manifestations of an aggravation.
• Complex therapy of a syndrome of alcoholic abstinence.
• An idiopathic epileptiform neuralgia and an epileptiform neuralgia at multiple sclerosis (typical and atypical). Idiopathic neuralgia of a glossopharyngeal nerve.
• A pain syndrome at diabetic neuropathy.
• A polyuria and a polydipsia of the neurohormonal nature at not diabetes mellitus of the central genesis.

Route of administration and doses:

Inside, regardless of meal with a small amount of liquid. This dosage form is not applied at children up to 3 years.

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 from 3 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 neuralgia of trigeminal or glossopalatine nerves: 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 days 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.
Acute maniacal states and maintenance therapy of affective frustration: the daily dose varies from 400 to 1600 mg. An average daily dose — 400-600 mg (in 2-3 receptions). At an acute maniacal state the dose should be raised quickly enough. At a maintenance therapy of bipolar disorders for ensuring optimum portability each following increase in a dose has to be small, the daily dose increases gradually.

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.

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 digestive tract: 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: 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, TZ) 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 calcium ions 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 increases concentration of Karbamazepin-10,11-epoksida, at the same time perhaps simultaneous decrease in concentration in serum of a felbamat. 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 Primidonum of Carbamazepine from communication with proteins of plasma and increase in concentration pharmacological of an active metabolite (Karbamazepina-10,11-epoksida). Izotretinoin changes bioavailability and/or clearance of Carbamazepine and Karbamazepina-10,11-epoksida (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 alprazolam, 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 the level of Mephenytoinum 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 gepatotoksichny effects; strengthens formation of nefrotoksichny metabolites of a metoksifluran. Strengthens a hepatotoxic action of an isoniazid.

Contraindications:

Hypersensitivity to Karbamazepin 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; atrioventricular block; pregnancy and 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: respiratory depression, the hyperreflexia which is replaced with a hyporeflexia, a hypothermia, oppression of motility of a GIT, strengthening of expressiveness of side effects.

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 the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Not to use after the period of validity specified on packaging. A period of validity - 4 years.

Issue conditions:

According to the recipe

Packaging:

Tablets of 200 mg. On 10 tablets in a blister strip packaging. 2, 5 or 10 blister strip packagings together with the application instruction in a pack from a cardboard. On 500, 1000, 1500 or 2000 tablets in bank of orange glass. Each can together with the application instruction is wrapped brown paper or paper bag (for a hospital).