Carbamazepine - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 82.0 mg, polysorbate 80 (tween 80) 3.2 mg, potato starch -15.2 mg, silicon dioxide colloid 1.8 mg, povidone 14.6 mg, magnesium stearate 3.2 mg.

The average weight of the tablet is 320 mg.

Description:

Tablets white or white with a yellowish hue of color, flat-cylindrical shape with chamfer and risk.

Pharmacotherapeutic group:antiepileptic agent

ATX: & nbsp

N.03.A.F.01 Carbamazepine

Pharmacodynamics:

Antiepileptic agent (derivative of dibenzazepine), also has antidepressant, antipsychotic and antidiuretic effect. Possesses and analgesic effect in patients with neuralgia.

The mechanism of action is associated with the blockade of potential-dependent Na + channels, which leads to stabilization of the neuronal membrane, inhibition of the occurrence of serial discharges of neurons, and a decrease in synaptic impulses.Prevents the re-formation of Na + -dependent action potentials in depolarized neurons. Reduces the release of the excitatory neurotransmitter amino acid glutamate, increases the reduced convulsive threshold of the central nervous system and, thus, reduces the risk of developing an epileptic attack. Increases the conductance for K +, modulates the potential-dependent Ca2 + channels, which can also cause the anticonvulsant effect of the drug.

Corrects epileptic personality changes and, in the long run, improves the communicability of patients, contributes to their social rehabilitation. Can be prescribed as the main therapeutic drug and in combination with other anticonvulsants.

Effective in focal (partial) epileptic seizures (simple and complex), accompanied or not accompanied by secondary generalization, with generalized tonic-clonic epileptic seizures, and also with a combination of these types of seizures (usually ineffective in small seizures - petitmal, absences and myoclonic seizures) .

Patients with epilepsy (especially in children and adolescents) have a positive effect on the symptoms of anxiety and depression, as well as a decrease in irritability and aggressiveness. The effect on cognitive function and psychomotor parameters depends on the dose and is highly variable.

The onset of anticonvulsant effect varies from several hours to several days (sometimes up to 1 month due to autoinduction of metabolism).

In the case of essential and secondary neuralgia of the trigeminal nerve, in most cases it prevents the occurrence of painful attacks. Effective for alleviating neurogenic pain in the dry spinal cord, post-traumatic paresthesia and postherpetic neuralgia. Relaxation of pain in trigeminal neuralgia is noted after 8-72 hours.

With alcohol withdrawal syndrome, it increases the threshold of convulsive readiness (which is usually reduced in this condition) and reduces the severity of clinical manifestations of the syndrome (increased excitability, tremor, gait disturbance).

In patients with diabetes insipidus leads to rapid compensation of water balance, reduces diuresis and thirst.

Antipsychotic (antimanic) action develops after 7-10 days, may be due to oppression of the metabolism of dopamine and norepinephrine.

Pharmacokinetics:

Absorption is slow, but complete, eating does not significantly affect the speed and degree of absorption. After a single oral intake, the maximum concentration in the blood plasma of C max is reached after 12 hours. After a single oral intake of 400 mg of carbamazepine, the mean Сmах the unchanged active substance is about 4.5 μg / ml. Time to reach the maximum concentration in the blood plasma (TСmах) - 4-5 hours with oral administration.

Equilibrium concentrations of the drug in the plasma are achieved after 1-2 weeks (the rate of achievement depends on the individual characteristics of the metabolism: autoinduction of the liver enzyme systems, heteroinduction of other, simultaneously used drugs), as well as the patient's condition, dose of the drug and the duration of treatment. There are significant interindividual differences in the values of equilibrium concentrations in the therapeutic range: in diseased patients the values range from 4 to 12 μg / ml (17-50 μmol / l).

The concentrations of carbamazepine-10,11-epoxide (pharmacologically active metabolite) are about 30% of the concentration of carbamazepine.

The connection with plasma proteins in children is 55 - 59%, in adults 70 - 80%. The apparent volume of distribution is 0.8 - 1.9 l / kg. In cerebrospinal fluid and saliva, concentrations are created in proportion to the amount of active substance unbound with proteins (20-30%). Penetrates through the placental barrier.

Concentration in breast milk is 25 - 60% of that in plasma.

Metabolised in the liver, mainly along the epoxide route with the formation of the main metabolites: active - carbamazepine-10,11-epoxide and inactive conjugate with glucuronic acid. The main isoenzyme providing the biotransformation of carbamazepine in carbamazepine-10,11-epoxide is cytochrome P450 (CYP ZA4). As a result of these metabolic reactions, a low-activity metabolite of 9-hydroxy-methyl-10 carbamoylacridan is also formed. Can induce own metabolism. The concentration of carbamazepine-10,11-epoxide is 30 % of the concentration of carbamazepine.

The half-life (T1 / 2) after taking a single oral dose is 25-65 hours (an average of about 36 hours), after repeated administration depending on the duration of treatment 12-24 hours (due to autoinduction of the monooxygenase system of the liver).In patients receiving additionally other anticonvulsants - inducers of the monooxygenase system (phenytoin, phenobarbital), the half-life is an average of 9 to 10 hours.

After taking 400 mg of carbamazepine once inside, 72% of the dose is taken with urine and 28% with feces. About 2% of the dose is taken with urine in the form of unchanged carbamazepine, about 1% - in the form of 10,11-epoxide metabolite.

Children, due to faster elimination of carbamazepine, may require the use of higher doses of the drug at a rate of 1 kg of body weight compared with adults.

There is no evidence that the pharmacokinetics of carbamazepine change in elderly patients (compared with older adults).

Data on the pharmacokinetics of carbamazepine in patients with impaired renal or hepatic function have not been reported to date.

Indications:

Epilepsy (except absences, myoclonic or flaccid seizures) - partial seizures with complex and simple symptoms, primary and secondary generalized forms of seizures with tonic-clonic seizures, mixed forms of seizures (monotherapy or in combination with other anticonvulsant drugs);

Idiopathic neuralgia of the trigeminal nerve, trigeminal neuralgia with multiple sclerosis (typical and atypical), idiopathic neuralgia of the glossopharyngeal nerve.

Acute manic conditions (monotherapy and in combination with drugs Li⁺ and other antipsychotic drugs). Faznoprotekae affective "disorders (including bipolar), prevention of exacerbations, the weakening of clinical manifestations during exacerbation.

Alcohol abstinence syndrome (anxiety, convulsions, hyperexcitability, sleep disturbances).

Diabetic neuropathy with pain syndrome.

Polyuria and polydipsia of neurohormonal nature in diabetes insipidus of central genesis.

Contraindications:

Hypersensitivity to carbamazepine or chemically similar drugs (eg, tricyclic antidepressants) or to other components of the drug, bone marrow disorders - hematopoiesis, acute "intermittent" porphyria, including history, atrioventricular blockade, simultaneous administration with monoamine oxidase inhibitors (structural similarity with tricyclic antidepressants).

Carefully:

With caution should apply the drug in the following conditions and diseases: decompensated chronic heart failure, hyponatremia of dilution (syndrome of hypersecretion of antidiuretic hormone, hypopituitarism, hypothyroidism, insufficiency of the adrenal cortex), advanced age, active alcoholism (central nervous system depression, carbamazepine metabolism is increasing), oppression of bone marrow hematopoiesis; hepatic insufficiency, chronic renal failure, prostatic hyperplasia, increased intraocular pressure.

Monotherapy epilepsy begins with the appointment of small doses, individually increasing them to achieve the desired therapeutic effect.

It is advisable to determine the concentration in the plasma in order to select the optimal dose, especially with combination therapy.

When transferring a patient to carbamazepine should gradually reduce the dose of the previously prescribed antiepileptic agent until its complete cancellation.

Carbamazepine should be immediately withdrawn if there are allergic reactions or symptoms presumably indicative of the development of Stevens-Johnson syndrome or Lyell's syndrome.Slightly expressed skin reactions (isolated macular or maculopapular exanthema) usually pass for several days or weeks, even with the continuation of treatment or after a decrease in the dose of the drug (the patient at this time should be under close supervision of the doctor). It should take into account the possibility of activation of latent psychoses, and in elderly patients - the possibility of developing disorientation or excitation.

There are reports of women developing bleeding during menstruation in cases when oral contraceptives were used concomitantly with carbamazepine. It is necessary to inform patients about the early signs of toxicity inherent in probable hematologic disorders, as well as symptoms from the skin and liver. The patient is informed of the need to consult a doctor immediately if there are undesirable reactions such as fever, sore throat, rash, ulceration of the oral mucosa, an unreasonable appearance of bruises, hemorrhages in the form of petechiae or purpura.Neprogressiruyuschayaa symptomatic leukopenia does not require discontinuation of the drug, but the treatment should be discontinued when a progressive leukopenia or leucopenia, accompanied by clinical symptoms of the infectious disease.

In women of reproductive age carbamazepine should where possible be used as a monotherapy using the minimum effective dose - frequency of congenital anomalies in infants born to women who underwent a combined anti-epileptic medication, higher than in those who received each of these antiepileptic drugs in monotherapy.

Pregnancy and lactation:

At the onset of pregnancy (when deciding whether to prescribe carbamazepine during pregnancy), it is necessary to carefully compare the expected benefits of therapy and its possible complications, especially in the first 3 months. pregnancy.

It is known that children born to mothers with epilepsy are predisposed to violations of intrauterine development, including malformations. Carbamazepine, like all other antiepileptic drugs, is capable of increasing the risk of these disorders.There are isolated reports of cases of congenital diseases and malformations, including non-vertebral arches (spina bifida). Patients should be provided with information on the possibility of increasing the risk of malformations and the ability to undergo antenatal diagnostics.

Antiepileptic drugs increase the deficiency of folic acid, which is often observed during pregnancy, which can contribute to an increase in the frequency of birth defects in children (additional folic acid intake is recommended before and during pregnancy). In order to prevent increased bleeding in newborns, in the last weeks of pregnancy, as well as newborns, vitamin K1 is recommended.

Carbamazepine penetrates into breast milk, it is necessary to compare the benefits and possible undesirable consequences of breastfeeding in conditions of continuing therapy. Mothers accepting Carbamazepine, can breast-feed their children, provided that the child will be monitored for the development of possible adverse reactions (eg, severe drowsiness, allergic skin reactions).

Several cases of epileptic seizures, vomiting, diarrhea, and / or reduced diets, seizures and / or respiratory depression in newborns whose mothers were taken carbamazepine simultaneously with other anticonvulsants (perhaps these reactions are manifestations of the newborn "withdrawal" syndrome).

Dosing and Administration:

Inside, regardless of food intake, along with a small amount of liquid.

With epilepsy, in cases where it is possible, carbamazepine should be administered as a monotherapy. Treatment begins with the application of a small daily dose, which is then slowly increased until an optimal effect is achieved.

The addition of carbamazepine to already conducted antiepileptic therapy should be carried out gradually, while the doses of the drugs used do not change or, if necessary, correct.

For adults, the initial dose is 100-200 mg 1-2 times a day. Then the dose is slowly increased to achieve the optimal therapeutic effect (usually 400 mg 2-3 times a day, maximum -1.6-2 g / day).

With neuralgia of the trigeminal nerve on the first day, 200-400 mg / day is prescribed,gradually increase by no more than 200 mg / day until the pain ceases (an average of 400-800 mg / day), and then reduced to the lowest effective dose. In pain syndrome of neurogenic origin, the initial dose is 100 mg twice a day on the first day, then the dose is increased by no more than 200 mg / day, if necessary, increasing it by 100 mg every 12 hours until the pain is weakened. The maintenance dose is 200-1200 mg / day in several doses.

In the treatment of elderly patients and patients with hypersensitivity, the initial dose is 100 mg 2 times a day.

Alcohol abstinence syndrome: the average dose is 200 mg 3 times a day; in severe cases during the first few days the dose can be increased to 400 mg 3 times a day. At the beginning of treatment for severe manifestations of abstinence it is recommended to appoint in combination with sedative-hypnotic drugs (clomethiazole, chlordiazepoxide).

Non-diabetes mellitus: the average dose for adults is 200 mg 2-3 times a day.

Diabetic neuropathy, accompanied by pain: the average dose is 200 mg 2-4 times a day.

In the prevention of relapses affective and schizoaffective psychoses - 600 mg / day in 3-4 divided doses.

In acute manic states and affective (bipolar) disorders, daily doses of 400-1600 mg.The average daily dose is 400-600 mg (in 2-3 doses). In acute manic state, the dose is increased rapidly, with maintenance therapy of affective disorders. Gradually (to improve tolerability).

Side effects:

When assessing the frequency of occurrence of various adverse reactions, the following grades are used: very often - 10% and more often; often - 1-10%; sometimes 0.1-1%; rarely - 0,01-0,1%; very rarely - less than 0.01%.

Dose-dependent adverse reactions usually occur within a few days, both spontaneously and after a temporary dose reduction. The development of adverse reactions from the CNS may be due to a relative overdose of the drug or significant fluctuations in the concentration of the active substance in the blood plasma. In such cases it is recommended to monitor the concentration of the drug in the plasma.

From the nervous system: very often - dizziness, ataxia, drowsiness, general weakness; often - headache, paresis of accommodation; sometimes - abnormal involuntary movements (eg, tremor, "fluttering" tremor - asterixis, dystonia, tics); nystagmus; rarely - orofacial dyskinesia, oculomotor disorders, speech disorders (eg, dysarthria), choreoathetoid disorders, peripheral neuropathy, paresthesia, myasthenia gravis,paresis; very rarely - malignant neuroleptic syndrome.

Disorders of the psyche: rarely - hallucinations (visual or auditory), depression, decreased appetite, anorexia, anxiety, aggressive - behavior, agitation, disorientation; very rarely - activation of psychosis, suicidal behavior (including thoughts of suicide).

From the skin and subcutaneous tissues: often - allergic reactions, allergic dermatitis, urticaria; sometimes - exfoliative dermatitis, erythroderma; rarely - systemic lupus erythematosus, itching; very rarely - multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), photosensitivity, multiform and nodal erythema, skin pigmentation disorders, purpura, acne, sweating, hair loss.

Hypersensitivity reactions: rarely - multiorgan hypersensitivity reactions of delayed type with fever, skin rashes, vasculitis (including erythema nodosum as a manifestation of cutaneous vasculitis), lymphadenopathy, signs resembling lymphoma, arthralgia, leukopenia, eosinophilia,hepatosplenomegaly and altered indicators of liver function (these manifestations occur in various combinations), and other organs (for example, lungs, kidneys, pancreas, myocardium, large intestine) may also be involved. Very rarely - aseptic meningitis with myoclonus and peripheral eosinophilia, anaphylactoid reaction, angioedema, allergic pneumonitis or eosinophilic pneumonia. If the above-mentioned allergic reactions occur, the drug should be discontinued.

On the part of the blood and lymphatic system: very often - leukopenia; often - thrombocytopenia, eosinophilia; rarely - leukocytosis, lymphadenopathy, deficiency of folic acid; very rarely - agranulocytosis, aplastic anemia, pancytopenia, anemia, true erythrocyte aplasia, megaloblastic anemia, acute "intermittent" porphyria, reticulocytosis, hemolytic anemia.

From the gastrointestinal tract: very often - nausea, vomiting; often - dry mouth; sometimes diarrhea, constipation; rarely - abdominal pain; very rarely - glossitis, stomatitis, pancreatitis.

From the side of the cardiovascular system: rarely - violations of intracardiac conduction, a decrease or increase in blood pressure; very rarely - bradycardia, arrhythmias, atrioventricular blockade with syncope, collapse, aggravation or development of chronic heart failure, exacerbation of coronary heart disease (including the appearance or increase in angina attacks), thrombophlebitis, thromboembolic syndrome.

From the liver and biliary tract: very often - increased activity of gamma-glutamyltransferase (due to the induction of this enzyme in the liver), which usually has no clinical significance; often - increased activity of alkaline phosphatase of the blood; sometimes - increased activity of "liver" transaminases; rarely - hepatitis of cholestatic, parenchymal (hepatocellular) or mixed type, jaundice; very rarely - granulomatous hepatitis, hepatic insufficiency.

From the endocrine system and metabolism: often - edema, fluid retention, weight gain, hyponatremia and decreased plasma osmolarity due to an effect similar to that of antidiuretic hormone,which in rare cases leads to water intoxication (hyponatremia of breeding), accompanied by lethargy, vomiting, headache, disorientation and neurologic disorders; very rarely - hyperprolactinaemia (may be accompanied by galactorrhea and gynecomastia); decrease in concentration L-tiroksina (free thyroxine, thyroxine, triiodothyronine) and an increase in thyroid-stimulating hormone (usually not accompanied by clinical manifestations); disorders of calcium-phosphorus metabolism in bone tissue (decrease in calcium concentration and 25-hydroxy-cholecalciferol in plasma), leading to osteomalacia / osteoporosis; hypercholesterolemia (including high-density lipoprotein cholesterol) and hypertriglyceridemia.

From the side of the kidneys and urinary tract: very rarely - interstitial nephritis, renal failure, impaired renal function (eg, albuminuria, hematuria, oliguria, urea / azotemia increase), frequent urination, retention of urine, disorders of sexual function.

From the musculoskeletal and connective tissue: rarely - muscle weakness; very rarely - arthralgia, myalgia or cramps.

From the sense organs: very rarely - a violation of taste, clouding of the lens, conjunctivitis; Hearing impairment, incl. noise in the ears, hyperacusia, hypoacusia, changes in perception of the height of sound.

From the respiratory system: very rarely - hypersensitivity reactions characterized by fever, dyspnea, pneumonitis, or pneumonia.

Influence on the results of laboratory studies: very rarely - hypogammaglobulinemia.

Other: reported rare cases of hirsutism, but the causal relationship of this complication with the use of carbamazepine remains unclear.

Overdose:

Overdose is usually manifested by symptoms from the central nervous system, cardiovascular and respiratory systems.

Symptoms

From the central nervous system: oppression of central nervous system functions, disorientation, drowsiness, excitation, hallucinations, fainting, coma, visual disturbances (fog before the eyes), slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (at the beginning), hyporeflexia (later) , convulsions, psychomotor disorders, myoclonus, hypothermia, mydriasis.

From the side of the cardiovascular system: tachycardia, lowering blood pressure, sometimes raising blood pressure, violation of intraventricular conduction with expansion of the complex QRS, cardiac arrest.

From the respiratory system: respiratory depression, pulmonary edema.

From the gastrointestinal tract: nausea and vomiting, delayed evacuation of food from the stomach, decreased motility of the colon.

From the urinary system: urinary retention, oliguria or anuria; fluid retention; hyponatremia of breeding.

Laboratory indicators: hyponatremia, metabolic acidosis, hyperglycemia and glucosuria, increased muscle fraction of creatinine phosphokinase.

Treatment

There is no specific antidote. Treatment is based on the clinical condition of the patient. Hospitalization, determination of carbamazepine concentration in blood plasma (for confirmation of poisoning with this drug and assessment of the degree of overdose), gastric lavage, the appointment of activated charcoal (late evacuation of gastric contents can lead to delayed absorption and repeated appearance of intoxication symptoms during recovery period).Symptomatic supportive treatment in the intensive care unit, monitoring of heart function, body temperature, kidney and bladder function, correction of water-electrolyte balance disorders.

Intense diuresis, hemodialysis and peritoneal dialysis are ineffective (dialysis is indicated by a combination of severe poisoning and kidney failure). In young children, there may be a need for blood transfusion.

With a decrease in blood pressure: shown in / introduction of dopamine or dobutamine; with heart rhythm disturbances, treatment is selected individually; with convulsions - the introduction of benzodiazepines (eg, diazepam) or other anticonvulsants (eg, phenobarbital) with caution because of the possible increase in respiratory depression; with the development of hyponatremia of dilution (water intoxication) - restriction of the introduction of fluids and slow administration of 0.9% solution NaCl (can help prevent the development of damage to the "brain").

It is recommended to carry out hemosorption on carbon sorbents.

Interaction:

Cytochrome CYP3A4 is the main enzyme that provides the metabolism of carbamazepine.Simultaneous administration of carbamazepine with inhibitors CYP3A4 can lead to an increase in its concentration in the blood plasma and cause side reactions. Joint application of inducers CYP3A4 can lead to an acceleration of the metabolism of carbamazepine, a decrease in the concentration of carbamazepine in the blood plasma and a decrease in the therapeutic effect; on the contrary, their withdrawal can reduce the rate of carbamazepine metabolism and lead to an increase in the concentration of carbamazepine in the plasma.

Increase the concentration of carbamazepine in plasma: verapamil, diltiazem, felodipine,

dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazol, desipramine, nicotinamide (in adults, only in high doses); macrolides (erythromycin, josamycin, clarithromycin, troleandomycin); azoles (itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, isoniazid, propoxyphene, grapefruit juice, viral protease inhibitors used in the treatment of HIV infection (for example, ritonavir) - correction of the dosing regimen or monitoring of carbamazepine concentration in plasma is required.

Reduce the concentration of carbamazepine phenobarbital, phenytoin, primidon, metsuksimide, fensuksimid, theophylline, rifampicin, cisplatin, doxirubicin, possibly: clonazepam, valpromid, valproic acid, oxcarbazepine and herbal preparations containing St. John's wort perfumed (Hypericum perforatum). Felbamate reduces the concentration of carbamazepine in plasma and increases the concentration of carbamazepine-10,11-epoxide, while a simultaneous decrease in serum felbamate concentration is possible.

There are reports of the possibility of displacing carbamazepine with valproic acid and primidone from the association with plasma proteins and increasing the concentration of pharmacologically active metabolite (carbamazepine-10,11-epoxide).

Isotretinoin changes the availability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide (control of carbamazepine concentration in plasma is necessary).

Carbamazepine can reduce the plasma concentration (reduce or even completely neutralize the effects) and require correction of the doses of the following drugs: clobazam, clonazepam, ethosuximide, primidon, valproic acid, alprazolam, GCS (prednisolone, dexamethasone), cyclosporine, doxycycline, haloperidol, methadone, oral preparations containing estrogens and / or progesterone (the choice of alternative methods of contraception), theophylline, oral anticoagulants (warfarin, fenprocumone, dicumarol), lamotrigine, topiramate, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, felbamate, tiagabine, oxcarbazepine, protease inhibitors HIV infection (indinavir, ritonavir, saquinovir), calcium channel blockers (a group of dihydropyridones, for example, felodipine), itraconazole, levothyroxine, midazolam, olazapine, praziquantel, risperidone, tramadol, and ziprasidone.

It has been reported that in patients receiving carbamazepine phenytoin plasma levels may either rise or fall, and mephenytoin level - increase (in rare cases). Carbamazepine when combined with paracetamol increases the risk of its toxic effect on the liver and reduces therapeutic effectiveness (acceleration of the metabolism of paracetamol). The simultaneous appointment of carbamazepine with phenothiazines, pimozide, thioxanthenes, molindone, haloperidol, maprotiline, clozapine and tricyclic antidepressants leads to increased inhibitory action on the central nervous system and weaken the anticonvulsant effect of carbamazepine.Monoamine oxidase inhibitors increase the risk of developing hyperpyretic crises, hypertensive crises, seizures, and death (prior to the administration of carbamazepine, monoamine oxidase inhibitors should be discontinued at least 2 weeks or, if the clinical situation permits, even over a longer period). Simultaneous use of carbamazepine with diuretics (hydrochlorothiazide, furosemide) can lead to hyponatremia, accompanied by clinical manifestations.

Carbamazepine weakens the effects of nondepolarizing muscle relaxants (pancuronium). If such a combination is used, it may be necessary to increase the dose of muscle relaxants, and careful monitoring of patients should be carried out, since a faster cessation of their effect is possible.

Carbamazepine reduces the tolerance of alcohol, in this regard, patients are recommended to abandon the use of alcohol.

Accelerates the metabolism of indirect anticoagulants, hormonal contraceptives, folic acid, praziquantel, can enhance the elimination of thyroid hormones.Accelerates the metabolism of drugs for general anesthesia (enflurane, halothane, ftorotan) with an increased risk of hepatotoxic effects; enhances the formation of nephrotoxic metabolites of methoxyflurane.

Enhances the hepatotoxic effect of isoniazid.

Myelotoxic agents increase the manifestation of hematotoxicity of carbamazepine. With the joint administration of carbamazepine and levetiracetam in some cases, the toxic effect of carbamazepine was noted.

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

Special instructions:

The drug is usually not effective in absences and myoclonic seizures.

The drug should be used only under the condition of regular medical supervision.

During the administration of the drug at different frequencies there is a transient or persistent decrease in the number of platelets and leukocytes, which in most cases is not a harbinger of the onset of aplastic anemia or agranulocytosis. Before the start of treatment, and periodically during the treatment should be carried out clinical blood tests, including counting the number of platelets and, possibly, reticulocytes, as well as determine the concentration of iron in the blood plasma.

Before starting treatment with the drug and periodically during the therapy, it is recommended to study the general urine and urea level in the blood, to determine the concentration of electrolytes in the blood serum (because it is possible to develop hyponatremia). Before the beginning of treatment and in the process, it is necessary to study the liver functions, especially in patients whose history includes information on liver diseases, as well as in elderly patients. In case of exacerbations of already existing violations of the liver function or when there is an active liver disease, the drug should be canceled.

The drug has a weak cholinergic activity, so when using the drug in patients with increased intraocular pressure, a constant monitoring of this indicator is necessary.

Carbamazepine may decrease the effectiveness of medications containing estrogens and / or progesterone, therefore, women of reproductive age should be treated with alternative methods of protection from pregnancy during drug treatment.

Regular determination of the concentration of carbamazepine in blood plasma is necessary in the following situations: with a sharp increase in the frequency of seizures; for,To check whether the patient is taking the drug properly; during pregnancy; when treating children or adolescents; if there is a suspicion of impaired absorption of the drug; if there is a suspected development of toxic reactions in the event that the patient takes several medications.

To date, individual reports of male fertility impairment and / or spermatogenesis disorders have been reported (the relationship of these disorders to carbamazepine has not yet been established).

A sudden discontinuation of carbamazepine may provoke epileptic seizures. If it is necessary to abruptly discontinue treatment, the patient should be transferred to another antiepileptic agent under the cover of the drug shown in such cases (for example, diazepam administered intravenously or rectally, or phenytoin administered intravenously).

In patients receiving antiepileptic drugs, there is an increased risk of suicidal behavior, including thoughts of suicide. In this regard, the patient's condition should be carefully monitored in order to timely detect the progression of depression, suicidal behavior,other changes in mood or unusual behavior of the patient.

Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving a vehicle and other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 200 mg.

Packaging:By 10, 15 20 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1, 2, 3, 4, 5 contour squares with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number: P N002612 / 01-2003

Date of registration:15.08.2011

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia

Information update date: & nbsp15.08.2011

Illustrated instructions

Instructions

Carbamazepine (Carbamazepine)