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

Excipients: Povidone (polyvinylpyrrolidone, low molecular weight medical 12600 + 2700) - 8.8 mg colloidal silicon dioxide (Aerosil) - 3.2 mg Sodium carboxymethyl starch (sodium starch glycolate) - 9.6 mg magnesium stearate (magnesium stearate) - 3, 2 mg, talc - 9.6 mg, potato starch - up to the mass of the tablet 320 mg.

Description:

Round tablets white or white with a yellowish hue of color, flat-cylindrical shape with a risk and a facet.

Pharmacotherapeutic group:Antiepileptic remedy

ATX: & nbsp

N.03.A.F.01 Carbamazepine

Pharmacodynamics:

Carbamazepine is a dibenzazepine derivative and has antiepileptic, neurotropic and psychotropic antidiuretic action.

As the antiepileptic agent stabilizes neuronal membranes perevozbuzhdonnyh suppresses serial bits of neurons and reduces excitatory synaptic transmission pulses.This action is achieved, presumably, due to blockade of sodium channels, as a result of which the repeated occurrence in the depolarized neurons of sodium-dependent action potentials is prevented. Reduces the release of the neurotransmitter glutamate. The psychotropic effect of carbamazepine, apparently, is due to the inhibition of the metabolism of dopamine and norepinephrine.

Reduces the frequency of seizures, anxiety, depression, irritability and aggressiveness in patients with epilepsy. The effect on cognitive function in epileptic patients is variable. Prevents the occurrence of paroxysmal pain in neuralgia. With alcohol withdrawal syndrome increases the threshold of convulsive readiness, reduces the increased nervous excitability, tremor, gait disturbance. Used to treat affective disorders as an antipsychotic and normotimic agent. When diabetes insipidus reduces diuresis and thirst.

Pharmacokinetics:

Absorption - slow, but fairly complete (eating does not significantly affect the speed and degree of absorption). After a single dose, the maximum concentration of carbamazepine in the blood plasma is reached after 12 hours.

Equilibrium concentrations of carbamazepine in plasma are achieved after 1-2 weeks of admission. Among the patients, there are significant individual differences in the values of equilibrium concentrations in the therapeutic range: in most patients these values range from 4 to 12 μg / ml (17-50 μmol / l). The connection with blood plasma proteins in children is 55-59%, in adults 70-80%. The apparent volume of distribution is 0.8-1.9 l / kg. The concentration of unchanged carbamazepine in the cerebrospinal fluid and saliva is proportional to the amount of the active substance unbound with proteins (20-30%). Penetrates through the placental barrier. Concentration in breast milk is 25-60% of that in plasma.

Carbamazepine is metabolized in the liver, mainly along the epoxide pathway to form metabolites: active - carbamazepine-10,11-epoxide and low-activity - 9-hydroxy-methyl-10-carbamoylacridan. The main isoenzyme providing the biotransformation of carbamazepine in carbamazepine-10,11-epoxide is the cytochrome P450 isoenzyme ZA4. The content of carbamazepine-10,11-epoxide is about 30% of the level of carbamazepine in plasma. Biotransfarmation of carbamazepine-10,11-epoxide into carbamazepine-10,11-trans-diol takes place with the help of microsomal enzyme epoxide hydrolase.Another way of carbamazepine metabolism is the formation of various monohydroxylated derivatives, as well as N-glucuronides. The half-life after a single reception averages about 36 hours (ranging from 25 to 65 hours), after repeated administration - 16-24 hours in patients receiving additional other antiepileptic drugs that induce liver enzymes, the half-life of carbamazepine -. average 9- 10 hours

It is excreted mainly in the form of inactive metabolites with urine (approximately 70%) and feces (about 30%). About 2 % is excreted in the urine in the form of unchanged carbamazepine and about 1% - in the form of carbamazepine-10,11-epoxide.

Children due to more rapid withdrawal 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 are changing in elderly patients. Data on the pharmacokinetics of carbamazepine in patients with impaired renal or hepatic function are not yet available.

Indications:

Epilepsy (monotherapy or as part of complex therapy):

-complex and simple partial seizures (with or without loss of consciousness) with or without secondary generalization;

- generalized tonic-clonic seizures; mixed forms of epileptic seizures.

Acute manic conditions and maintenance therapy of bipolar affective disorders in order to prevent exacerbations or reduce the severity of clinical manifestations.

In complex therapy of alcohol withdrawal syndrome.

Neuralgia of the trigeminal nerve (idiopathic, with multiple sclerosis), idiopathic neuralgia of the glossopharyngeal nerve.

Contraindications:

- Hypersensitivity to any of the components of the drug or chemically similar medicinal products (tricyclic antidepressants);

- oppression of bone marrow hematopoiesis in the anamnesis;

- hepatic porphyria;

- atrioventricular block;

- simultaneous administration of monoamine oxidase inhibitors (MAO) and within two weeks after their withdrawal;

- children under 4 years;

- the period of breastfeeding.

Carefully:With caution should be used at low levels of white blood cells or platelets; mixed forms of epileptic seizures, including absences; in old age; with cardiac, hepatic or renal insufficiency; increased intraocular pressure; hyponatremia of breeding, hypothyroidism; hyperplasia of the prostate.

Pregnancy and lactation:

When pregnancy occurs (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 of pregnancy. Treatment of pregnant women with epilepsy should be carried out with extreme caution. 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) and other congenital anomalies: defects in the development of craniofacial structures, cardiovascular and other organ systems, hypospadias. Patients should be provided with information on the possibility of increasing the risk of malformations and the ability to undergo antenatal diagnostics.

With sufficient clinical efficacy for women of childbearing age, the drug should be prescribed as a monotherapy, as the incidence of congenital fetal anomalies with combined antiepileptic therapy is higher than when the drugs are prescribed as monotherapy.

The drug should be given in the lowest effective dose. It is recommended to regularly monitor the concentration of active substance in the blood plasma.

During pregnancy, effective antiepileptic treatment should not be interrupted, as the progression of the disease can have a negative effect on the mother and on the fetus.

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

Described several cases of seizures and / or respiratory depression, vomiting, diarrhea and / or reduced power in neonates whose mothers had taken the drug at the same time with other anticonvulsants (perhaps these reactions are manifestations of neonatal withdrawal syndrome).

Carbamazepine penetrates into breast milk, so you should compare the benefits and possible undesirable effects of breastfeeding in conditions of ongoing therapy. With continued breastfeeding patients receiving carbamazepine should be set for child surveillance in connection with the possibility of side reactions (e.g., severe sleepiness, allergic skin reactions).

Dosing and Administration:

The drug should be taken orally, regardless of food intake, along with a small amount of liquid.

Epilepsy: if possible, carbamazepine should be administered as a monotherapy. Treatment begins with 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 outgradually, if necessary, appropriate correction of the doses taken.

If the patient forgot to take the next dose of the drug in a timely manner, you should take the missed dose as soon as the omission became noticed, and you can not take a double dose of the drug.

For adults the initial dose is 100-200 mg once or twice a day. Then the dose is slowly increased until the optimal therapeutic effect is achieved; it is usually achieved at a dose of 400 mg 2-3 times a day. Some patients may require an increase in the daily dose to 1600 mg or 2000 mg.

Children older than 4 years, the initial dose is 100 mg / day, the dose is increased gradually, every week by 100 mg to achieve the optimal effect.

The maintenance dose for children is 10-20 mg / kg per day (in several ways): for 4-5 years, 200-400 mg (in 1-2 doses), 6-10 years for 400-600 mg (in 2- 3 receptions), for 11-15 years - 600-1000 mg (in 2-3 receptions). The maximum daily dose of carbamazepine for children is 1 g.

Neuralgia of the trigeminal or glossopharyngeal nerves: the initial dose is 200-400 mg / day, the dose is gradually increased by no more than 200 mg / day until the pain ceases (on average, up to 400-800 mg / day), and then reduced to the minimum effective dose.In the treatment of elderly patients and patients with hypersensitivity, the initial dose is 100 mg twice a day.

Alcohol withdrawal: 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 with severe manifestations of alcohol withdrawal, treatment is recommended in combination with drugs that have sedative and hypnotic effects (for example, clomethiazole, chlordiazepoxide). After resolving the acute phase, treatment with the drug can be continued as a monotherapy.

Acute manic conditions and maintenance therapy of bipolar affective disorders: daily dose of 400-1600 mg. The average daily dose is 400-600 mg (in 2-3 doses). In acute manic state, the dose should be increased rather quickly. With maintenance therapy of bipolar disorders, in order to ensure optimal tolerability, each next dose increase should be small, the daily dose increases gradually.

The length of the course of treatment depends on the indications, the effectiveness of the treatment, the patient's response to therapy.

Side effects:

From the central nervous system: dizziness, ataxia, drowsiness, fatigue, headache, diplopia, accommodation disorders, tremor, muscular dystonia, tics, nystagmus, orofacial dyskinesia, oculomotor disorders, speech disorders (eg, dysarthria), choreoathetoid disorders, peripheral neuropathy, paresthesia, paresis, malignant neuroleptic syndrome.

From the psychic sphere: hallucinations (visual or auditory), depression, decreased appetite, anxiety, aggressive behavior, agitation, disorientation, increased psychosis.

Hypersensitivity reactions: multi-organ hypersensitivity delayed type with fever, skin rashes, vasculitis, lymphadenopathy, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function (these manifestations occur in various combinations). Other organs may also be involved (eg, lungs, kidneys, pancreas, myocardium, large intestine). Aseptic meningitis with myoclonus and peripheral eosinophilia, anaphylactic reaction, angioedema.

From the skin: Allergic dermatitis, urticaria, exfoliative dermatitis, erythroderma, systemic lupus erythematosus, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitivity reaction, erythema multiforme and nodosum, a violation of skin pigmentation, purpura, acne, sweating, hair loss. There have been reports of cases of hirsutism, but the causal relationship of this complication to the use of carbamazepine remains unclear.

From the genitourinary system: disorders of sexual function, impaired spermatogenesis (decrease in the number of spermatozoa and their motility).

From the urinary system: interstitial nephritis, renal insufficiency, albuminuria, hematuria, oliguria, azotemia, frequent urination, urinary retention.

From the endocrine system and metabolism: edema, fluid retention, weight gain, hyponatremia and decreased plasma osmolarity due to an effect similar to that of antidiuretic hormone, leading to water intoxication (hyponatremia of the dilution), accompanied by lethargy, vomiting, headache,disorientation and neurological disorders; hyperprolactinemia (may be accompanied by galactorrhea and gynecomastia); a decrease in the concentration of triiodothyronine and thyroxin and an increase in the thyroid-stimulating hormone concentration, which is usually not accompanied by clinical manifestations; disturbance of calcium-phosphorus metabolism in bone tissue (decrease in the concentration of calcium ions and 25-hydroxycolecalciferol in plasma), which leads to osteomalacia; increased cholesterol concentrations, including high-density lipoprotein cholesterol and triglycerides.

From the side of the musculoskeletal system: arthralgia, myalgia, muscle weakness, convulsions.

From the digestive system: nausea, vomiting, dry mouth, diarrhea or constipation, abdominal pain, glossitis, stomatitis, pancreatitis.

From the hepatobiliary system: increase in indicators gammaglutamyltransferase, alkaline phosphatase, transaminase, cholestatic hepatitis, parenchymatous (hepatocellular) or mixed type, jaundice, granulomatous hepatitis, liver failure.

From the hematopoiesis: leukopenia, thrombocytopenia, eosinophilia, leukocytosis, lymphadenopathy,deficiency of folic acid, agranulocytosis, aplastic anemia, pancytopenia, anemia, true erythrocyte aplasia, megaloblastic anemia, variegate porphyria, acute intermittent porphyria, late cutaneous porphyria, reticulocytosis, hemolytic anemia.

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

From the sense organs: dysfunctions, clouding of the lens, conjunctivitis, increased intraocular pressure, hearing disorders.

From the side of the cardiovascular system: violations of intracardiac conduction, decrease or increased blood pressure, bradycardia, arrhythmias, atrioventricular blockade with syncope, collapse, chronic heart failure, exacerbation of ischemic heart disease, thrombophlebitis, thromboembolism.

Laboratory indicators: hypogammaglobulinemia.

Overdose:

Symptoms

- central nervous system: oppression of central nervous system functions up to coma, disorientation, drowsiness, agitation, hallucinations, visual disturbances (fog before the eyes), dysarthria, nystagmus, ataxia,dyskinesia, hyperreflexia alternating to hyporeflexia, convulsions, psychomotor disorders, myoclonus, hypothermia, mydriasis;

- the cardiovascular system: tachycardia, decrease or increase of arterial pressure, violations of intraventricular conduction with expansion of the complex QRS; heart failure;

- respiratory system: respiratory depression, pulmonary edema;

- digestive system: nausea and vomiting, delayed evacuation of food from the stomach, decreased motility of the colon;

- urinary system: retention of urine, oliguria or anuria; fluid retention; hyponatremia of breeding;

- laboratory indicators: leukocytosis or leukopenia, hyponatremia, metabolic acidosis, hyperglycemia and glucosuria, increase of the muscle fraction of creatine phosphokinase.

Treatment: there is no specific antidote. Gastric lavage, the appointment of activated charcoal (late evacuation of gastric contents can lead to delayed absorption on days 2 and 3 and the re-emergence of symptoms of intoxication during recovery), hospitalization, symptomatic therapy.

Intense diuresis, hemodialysis and peritoneal dialysis are ineffective (dialysis is indicated by a combination of severe poisoning and kidney failure).

It is recommended to carry out hemosorption on carbon sorbents.

Interaction:

Isozyme of cytochrome P4503A4 (CYP3A4) is the main enzyme providing formation of carbamazepine-10,11-epoxide (active metabolite). Simultaneous use of carbamazepine with isozyme inhibitors CYP3A4 can lead to an increase in its concentration in the plasma, which, in turn, can cause side reactions. Joint application of isoenzyme inducers CYP3A4 can lead to an acceleration of the metabolism of carbamazepine and, thus, to a possible decrease in its concentration in the plasma and, consequently, to a possible decrease in the severity of the therapeutic effect. The cancellation of simultaneously taken isoenzyme inducers CYP3A4 can reduce the rate of biotransformation of carbamazepine and, as a result, lead to an increase in its concentration in the blood plasma.

Carbamazepine is a strong inducer of isoenzyme CYP3A4 and enzyme hepatic systems of the first and second phases and with simultaneous application with drugs metabolized by isoenzyme CYP3A4, can induce induction of metabolism and a decrease in their concentration in plasma.

Since the conversion of carbamazepine-10,11-epoxide to carbamazepine-10,11-trans-diol takes place with the microsomal enzyme of epoxide hydrolase, the use of the drug together with epoxyhydrolase inhibitors can lead to an increase in the plasma concentration of carbamazepine-10,11-epoxide.

Drugs that can increase the concentration of carbamazepine in plasma: ibuprofen, verapamil, diltiazem, felodipine, dextropropoxyphene, viloxazine, nefazodone, paroxetine, trazodone, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazol, desipramine, omeprazole, oxybutynin, dantrolene, ticlopidine, nicotinamide (in adults, only in high doses); macrolide antibiotics (erythromycin, josamycin, clarithromycin, troleandomycin); azoles (itraconazole, ketoconazole, fluconazole, voriconazole), terfenadine, loratadine, isoniazid, propoxyphene, HIV protease inhibitors (eg, ritonavir) - correction of the dosing regimen or monitoring of carbamazepine concentration in plasma is required.

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

Since an increase in the level of carbamazepine in the blood plasma can lead to side effects (for example, dizziness, drowsiness, ataxia, diplopia), in these situations, the dose of the drug should be corrected and / or the carbamazepine concentration in the blood plasma determined regularly.

Drugs that can increase the concentration of carbamazepine-10,11-epoxide in blood plasma: loxapine, quetiapine, primidon, progabide, valproic acid, valnoctamide and valpromid.

Since an increase in the level of carbamazepine-10,11-epoxide in blood plasma can lead to side reactions (for example, dizziness, drowsiness, ataxia, diplopia), in these situations, the dosage of the drug should be corrected and / or the carbamazepine concentration 10,11 -epoxide in the blood plasma.

Drugs that can reduce the concentration of carbamazepine in blood plasma: felbamate, oxcarbazepine, phenobarbital, phenytoin, phosphenytoin, primidon, progabide, aminophylline, isotretinoin, mezuximide, fensuximide, theophylline, rifampicin, cisplatin or doxorubicin, herbal preparations containing St. John's wort (Hypericum perforatum), perhaps: clonazepam. With simultaneous use with the above drugs, you may need to adjust the dose of carbamazepine.

Isotretinoin modifies the bioavailability and / or clearance of carbamazepine and karbamazepina- 10,11-epoxide (requires monitoring carbamazepine plasma concentration).

The effect of carbamazepine on the plasma concentration of drugs used as concomitant therapy

With simultaneous use with carbamazepine, a decrease in plasma concentration, a decrease or even a complete cessation of action of certain drugs is possible.

When used simultaneously with carbamazepine, you may need to adjust the doses of the following drugs: methadone, paracetamol, phenazone (antipyrine), tramadol, doxycycline, oral anticoagulants (warfarin, fenprokumone, dicoumarol, acenocoumarol), bupropion, citalopram, trazodone, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clobazam, clonazepam, ethosuximide, felbamate, lamotrigine, oxcarbazepine, primidon, tiagabine, topiramate, valproic acid, zonisamide, itraconazole, praziquantel, imatinib, clozapine, haloperidol, bromperidol, olanzapine, quetiapine, risperidone, ziprasidone, HIV protease inhibitors (indinavir, ritonavir, saquinavir), alprazolam, midazolam, theophylline, blockers of calcium channels of the muscle relaxants, glucocorticosteroids (prednisolone, dexamethasone), cyclosporine, levothyroxine.

Women may experience bleeding in the period between menstruation in cases when oral contraceptives were used simultaneously. The drug may reduce the therapeutic effect of oral contraceptive preparations due to the induction of microsomal effects.

There are reports that, when taking carbamazepine, the concentration of phenytoin in the plasma can both increase and decrease, and the concentration of mephenitoin increases (in rare cases).

Combinations that should be taken into account

It is possible to increase the hepatotoxicity caused by isoniazid, in case of simultaneous application with carbamazepine.

In case of simultaneous application with levetiracetam, the toxic effect of carbamazepine may be increased.

The combined use of carbamazepine and lithium or metoclopramide,as well as carbamazepine and neuroleptic drugs (haloperidol, thioridazine) may lead to an increase in the incidence of unwanted neurologic reactions (in the case of the latter combination, even with therapeutic concentrations of active substances in the blood plasma).

Carbamazepine, when used concomitantly with paracetamol, increases the risk of its toxic effect on the liver and reduces therapeutic effectiveness (acceleration of the metabolism of paracetamol).

The simultaneous use of carbamazepine with phenothiazine derivatives, pimozide, thioxanthene derivatives, molindone, haloperidol, maprotiline, clozapine and tricyclic antidepressants leads to an intensifying inhibitory effect on the central nervous system and a weakening of the anticonvulsant effect of carbamazepine.

MAO 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 with diuretics (hydrochlorothiazide, furosemide) can lead to hyponatremia, accompanied by clinical manifestations. Carbamazepine may exhibit antagonism to the action of nondepolarizing muscle relaxants (for example, pancuronium bromide). If such a combination is used, it may be necessary to increase the dose of muscle relaxants, and careful monitoring of the patients is necessary, since a faster cessation of their effect is possible).

Reduces the tolerance of ethanol.

Accelerates the metabolism of indirect anticoagulants, hormonal contraceptive drugs, folic acid, praziquantel, can enhance the elimination of thyroid hormones.

Accelerates the metabolism of the drug for general anesthesia (enflurane, halothane, ftorotan) with an increased risk of hepatotoxic effects; strengthens education nephrotoxic metabolites of methoxyflurane.

Special instructions:

The drug is usually ineffective at absences (petit mal) and myoclonic seizures. The drug should be used only on condition that regular medical supervision is provided.

During the application of the drug at different frequencies, there is a transient or persistent decrease in the number of platelets or leukocytes.However, in most cases, these phenomena are transient and usually do not precede 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 the concentration of iron in the blood serum.

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. the occurrence of such undesirable reactions as fever, sore throat, rash, ulcers in the mouth, the causeless occurrence of bruising, hemorrhages in the form of petechiae or purpura.

With the use of carbamazepine, very rare (<1/10000) severe dermatological reactions have been reported, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome). With the development of severe (in some cases life-threatening patient) skin reactions, the patient should be hospitalized in a hospital.In most cases, Stevens-Johnson syndrome and Lyell's syndrome developed during the first months of therapy with the drug.

According to a retrospective analysis of the use of the drug in patients of Chinese nationality, there is a correlation between the frequency of severe dermatological reactions and the presence in the patient's genome of an allele HLA-B* 1502 gene of human leukocyte antigen (HLA).

When carbamazepine is used in patients in countries of the Asian region (Thailand, Malaysia, Philippines), where the prevalence of the allele is noted HLA-At * 1502, there was an increase in the incidence of development (from the gradation of "very rare" (<1/10000) to "rarely" (> 1/10000 - <1/1000)) severe dermatological reactions, including Stevens-Johnson syndrome and Lyell's syndrome . Allele spreading frequency HLA-B*1502 in the Philippines, Thailand, Hong Kong and Malaysia - more than 15%, in Taiwan - 10%, in North China - 4%, in South Asia (including India) - 2-4%, in Japan and Korea - less than 1%. The prevalence of this allele in Caucasians, Negroid and Americanoid (Latino and Indian) races is insignificant.

When prescribing carbamazepine, possible carriers of the allele HLA-B* 1502 (for example, people of Chinese nationality) it is recommended to carry out genotyping on this allele. Prescribe the drug carriers of this allele should be only if the benefit of therapy exceeds the possible risk. In the face of the Caucasoid, Negroid and Americanic races, genotyping along the allele HLA-B* 1502 before prescribing carbamazepine is optional.

Patients already receiving carbamazepine therapy are not recommended to carry out genotyping for this allele, since severe skin reactions in most cases were noted in the first months of application (regardless of the presence HLA-B* 1502 alleles).

However, the results of genotyping by allele HLA-B* 1502 should not influence the degree of control over the patient's condition and the doctor's caution regarding severe skin reactions. The development of Stevens-Johnson and Lyell syndromes is possible in patients negative for the allele HLA-B1502. Also in many cases, people of Chinese nationality, positive for the allele HLA-B* 1502, when carbamazepine was used, there was no development of Stevens-Johnson and Lyell syndromes.

The influence of other factors, such as the dose of anticonvulsant drugs, the compliance of patients, simultaneous therapy with other drugs, concomitant diseases or the level of control over dermatological reactions, the incidence of severe skin reactions (and mortality in patients with Stevens-Johnson syndrome and Lyell's syndrome) is not established .

Slightly expressed skin reactions, for example, isolated macular or maculopapular exanthema, in most cases are transient and mild, usually pass for several days or weeks while continuing treatment or after reducing the dose of the drug. Nevertheless, since the differential diagnosis between early manifestations of severe skin reactions and mild transient skin rashes can be difficult, with the development of any skin reactions the patient should be under the supervision of a doctor (in order to timely stop therapy with the drug in case of deterioration of the patient's condition).

The relationship between the presence of an allele in the genome HLA-B* 1502 and the development of non-severe skin reactions (such as hypersensitivity reactions, isolated macular or maculopapular exanthema) has not been established.

With the development of hypersensitivity to the drug in patients can be observed as individual lesions of the skin, liver, blood and lymphatic systems or other organs, and their combination, which should be regarded as a systemic reaction. Patients with known hypersensitivity to carbamazepine should be informed about the possibility of 25-30% cases of development of reactions of hypersensitivity to oxcarbazepine.

Cross-reactivity of hypersensitivity is also found between carbamazepine and phenytoin.

Before starting treatment with the drug and periodically during therapy, a general urine and urea test in the blood is recommended.

Before the appointment of the drug and during the treatment it is necessary to study the liver function, especially in patients whose history includes information on liver disease, as well as in elderly patients. In case of strengthening of already existing violations of the liver function or when there is an active liver disease, the drug should be immediately canceled.

The drug has a weak anticholinergic activity.Therefore, in the case of using the drug in patients with increased intraocular pressure, constant monitoring of this indicator is necessary.

It should take into account the possibility of activation of latent psychoses, and in elderly patients - the possibility of development of disorientation or psychomotor agitation.

Treatment with antiepileptic drugs, including carbamazepine, may be accompanied by the appearance of suicidal attempts / suicidal intentions. Patients (and attendants) should be warned about the need to monitor the occurrence of suicidal attempts / suicidal intentions and in the event of symptoms immediately seek medical help.

There are some reports of violations of male fertility and / or violations of spermatogenesis. However, the causal relationship between these disorders and carbamazepine has not been proven to date.

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

Although the relationship between the dose of the drug, the concentration of carbamazepine in the blood plasma, its clinical efficacy or tolerability is very low, nevertheless, a regular determination of the carbamazepine concentration may be appropriate in the following cases: with a sharp increase in the frequency of seizures, in order to check whether the patient the drug is properly administered; during pregnancy; when treating children or adolescents; with suspected drug absorption abnormalities; if there is a suspicion of the development of toxic reactions in the event that the patient takes several medicines.

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

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

For the duration of therapy, it is necessary to refrain from drinking alcohol, since carbamazepine enhances the depressant effect of alcohol on the central nervous system.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions (the reaction rate may be disturbed due to dizziness and drowsiness, especially at the beginning of treatment or during the dose selection period).

Form release / dosage:

Tablets 200 mg.

Packaging:

10 tablets per contour cell pack.

For 50, 100 tablets are placed in polymer cans.

Each bank, 5, 10 contour mesh packages together with the instruction for use is placed 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:

5 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N003681 / 01

Date of registration:05.06.2009 / 21.04.2016

Expiration Date:Unlimited

The owner of the registration certificate:SYNTHESIS, JSC Joint-stock Kurgan Society of Medical Preparations and Products SYNTHESIS, JSC Joint-stock Kurgan Society of Medical Preparations and Products Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp07.12.2017

Illustrated instructions

Instructions

Carbamazepine (Carbamazepine)