Zeptol - instructions for use, doses, side effects, contraindications

Excipients: microcrystalline cellulose - 33.0 mg, povidone K 30 - 3.0 mg, silicon dioxide colloid - 2.0 mg, hypromellose 2910 (methocel E5) - 1.50 mg, corn starch - 41.48 mg, bronopol - 0.02 mg, prdescribelparahydroxybenzoate sodium (sodium propyl paraben) - 0.11 mg, talc purified - 4.0 mg, magnesium stearate - 2.0 mg, sodium carboxymethyl starch (type A) -10.0 mg, sodium lauryl sulfate-3.0 mg.

Description:Round, flat, white tablets, chamfered and marked "ZEPTOL 200"on the one hand and the dividing risk on the other.

Pharmacotherapeutic group:Antiepileptic remedy

ATX: & nbsp

N.03.A.F.01 Carbamazepine

Pharmacodynamics:

Antiepileptic agent (dibenzazepine derivative), which also has a normotimic, antimanic, antidiuretic (in patients with diabetes insipidus) and analgesic (in patients with neuralgia).

The mechanism of action is associated with the blockade of potential-dependent Na + -channels, which leads to the stabilization of the membrane of overexcited neurons, inhibition of the occurrence of serial discharges of neurons, and a decrease in synaptic impulses. Prevents re-education 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 contribute to the anticonvulsant effect of the drug.

Effective with focal (partial) epileptic attacks (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 attacks (usually ineffective in small attacks - petit mal, 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 reduced irritability and aggressiveness. Influence at cognitive function and psychomotor performance depends on dose. The onset of an anticonvulsant effect varies from a few hours to several days (sometimes up to 1 months 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. 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).

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

Pharmacokinetics:

Absorption - slow, but fairly complete (eating does not affect the speed and degree of absorption). After a single dose, the maximum concentration (C_max) is achieved after 12 hours.

Equilibrium concentrations of the drug in the plasma are achieved after 1-2 weeks (the rate of achievement depends on the individual characteristics of metabolism: autoinduction of enzyme systems of the liver,heteroinduction of other concomitant medications), as well as the patient's condition, the dose of the drug and the duration of treatment. 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%. In the cerebrospinal fluid (further CSF) and saliva, concentrations are created in proportion to the amount of the active substance unbound with proteins (20-30%). Penetrates through the placental barrier. Concentration in breast milk is 25-60% from that in plasma.

Metabolised in the liver, mainly along the epoxy pathway with the formation of the main metabolites: active - carbamazepine-10,11epoxy and an inactive conjugate with glucuronic acid. The main isoenzyme providing the metabolism of carbamazepine in carbamazepine-10,11-epoxide is cytochrome CYP3A4. As a result of these metabolic reactions, a low-activity metabolite 9-hydroxy-methyl-10-carbamoylacridan is also formed. Can induce own metabolism. Is the inducer of isoenzymes CYP3A4, CYP3A5 and CYP3A7 in the liver.

The half-life (T1 / 2) of a single dose of 25-65 h (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 (monooxygenase system inducers - phenytoin, phenobarbital), T1 / 2 - an average of 9-10 hours.

After a single oral intake of 400 mg of carbamazepine 72% the accepted dose is excreted in urine and 28% with feces. About 2 % dose is excreted in the urine in the form of unchanged carbamazepine, about 1%-as 10,11-epoxy metabolite.

Children due to faster elimination of carbamazepine may require the use of higher doses of the drug at the 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 function or the liver is not yet available.

Indications:

- Epilepsy (excluding absence, 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);

- trigeminal neuralgia;

- idiopathic glossopharyngeal neuralgia;

- Pain in the defeat of peripheral nerves in diabetes mellitus, pain in diabetic neuropathy, polyuria and polydipsia of neurohormonal nature in diabetes insipidus of central genesis;

- epileptiform cramps in multiple sclerosis, spasms of facial muscles with trigeminal neuralgia, tonic convulsions, paroxysmal speech and movement disorders (paroxysmal dysarthria and ataxia), paroxysmal paresthesia and pain attacks;

- fromindra alcohol abstinence (anxiety, convulsions, hyperexcitability, sleep disturbances);

- psychotic disorders (affective and schizoaffective disorder, psychosis, disturbance of the limbic system).

Contraindications:

- Hypersensitivity to carbamazepine and to other components of the drug;

- disorders of bone marrow hematopoiesis (anemia, leukopenia);

- acute intermittent porphyria (including in the anamnesis);

- atrioventricular block;

- Simultaneouslyth prescribing lithium and inhibitora MAO.

Carefully:

Decompensated chronic heart failure, hyponatremia of dilution (ADH hypersecretion syndrome, hypopituitarism, hypothyroidism, adrenal cortex insufficiency), liver and kidney function deficiency, elderly age, active alcoholism (CNS depression is increased, carbamazepine metabolism is increased), oppression of bone marrow hematopoiesis against medications in history), prostatic hyperplasia, increased intraocular pressure, in combination with sedative-hypnotics.

Pregnancy and lactation:

For women of childbearing age, Zaptol is administered as a monotherapy if possible in a minimally effective dose, since the incidence of congenital anomalies in newborns from mothers taking combined antiepileptic treatment is higher than in monotherapy.

When pregnancy occurs, it is necessary to compare the expected benefit of therapy and possible complications, especially in the first trimester of pregnancy. It is known that children of mothers with epilepsy are predisposed to violations of intrauterine development, including developmental defects.Zeptol is able to increase the risk of these disorders. There are isolated reports of cases of congenital diseases and malformations, including non-vertebral arches (spina bifida).

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. Therefore, before the planned pregnancy is recommended folic acid.

In order to prevent hemorrhagic complications in newborns, in the last weeks of pregnancy, as well as newborns, it is recommended to prescribe vitamin K.

Carbamazepine penetrates into breast milk, so the benefits and possible undesirable effects of breastfeeding should be compared in the context of ongoing therapy. With the continuation of breastfeeding on the background of taking the drug should be established observation of the child due to the possibility of developing adverse reactions (eg, pronounced drowsiness, allergic skin reactions).

Dosing and Administration:

Inside. The drug can be taken at a time,after eating or in between meals with a small amount of liquid.

The drug can be used as a monotherapy or as part of a combination therapy.

Given the drug interaction and the different pharmacokinetics of antiepileptic drugs, elderly patients of Zepthol dose should be selected with caution.

With 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. To determine the optimal dose of the drug, it is recommended to determine the concentration of the active substance in the blood plasma. 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, carry out appropriate correction of the doses of the drugs 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 this omission became noticed, while you can not take a double dose of the drug.

For adults the initial dose of 100-200 mg 1-2 times a day. Then the dose is slowly increased to 400-600 mg 2 times a day. The maximum daily dose is 1600-2000 mg.

For children at the age of 4 years and younger it is recommended to start treatment with the application of 20-60 mg / day and increase the dose by 20-60 mg every other day.

For children at the age of over 4 years treatment can be started with the use of the drug at a dose of 100 mg / day; The dose is increased gradually - every week by 100 mg.

Supportive doses for children are 10-20 mg / kg / day (in several steps):

Age of child	Daily dose
up to 1 year	100-200 mg (in 1 administration)
1-5 years	200-400 mg (in 1-2 administration)
6-10 years	400-600 mg (in 2-3 divided doses)
11-15 years old	600-1000 mg (in 2-3 administrations)

With neuralgia of the trigeminal nerve and neurogenic pain syndromee: 100-200 mg twice a day, then gradually increase the dose by no more than 200 mg per day until the pain ceases (on average 600-800 mg), then reduced to the lowest effective dose. The effect usually occurs 1 to 3 days after the start of treatment. Assign the drug for a long time; with the premature cancellation of the drug pain can resume. In the treatment of elderly patients, the initial dose is 100 mg 2 times a day.

Alcohol abstinence syndrome: the average dose is 200 mg twice a day.In severe cases, in the first days the dose can be increased to 600 mg 2 times a day. At the beginning of treatment for severe phenomena, withdrawal is prescribed in combination with detoxification therapy and sedative-hypnotic drugs.

Non-diabetes mellitus: the average dose for adults is 200 mg 2-3 times a day. Diabetic neuropathy, accompanied by pain: 200 mg 2-4 times a day.

For the treatment and prevention of affective disorders: in the first week the daily dose of 200 - 400 mg. Subsequently, the dose is increased by 200 mg per week, bringing it to 1 g / day. The daily dose is evenly divided into 2 doses.

The transition to carbamazepine treatment should be gradual, with a decrease in the dose of the previous drug. Stop treatment should be gradual. The duration of treatment is determined by the doctor.

Side effects:

When assessing the frequency of occurrence of various adverse reactions, the following grades are used: very often 10% or more; often - 1-10%; infrequently - 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 central nervous system may be due to a relative overdose of the drug or significant fluctuations in the concentrations of the active substance in the plasma.In such cases it is recommended to monitor the concentration of drugs in the plasma.

From the side of the central nervous system (hereinafter referred to as the CNS): very often - dizziness, ataxia, drowsiness, a sense of fatigue; often - headache, diplopia, impaired vision accommodation (eg, blurred vision); infrequently - abnormal involuntary movements (eg, tremor, "fluttering" tremor - asterixis, dystonia, tics); nystagmus; rarely - orofacial dyskinesia, oculomotor disorders, speech disorders (eg, dysarthria), choreoathetosis, peripheral neuropathy, paresthesia, paresis; very rarely - taste disorders, malignant neuroleptic syndrome. The role of the carbamazepine as the drug causing or contributing to the development of neuroleptic malignant syndrome, especially when it is administered in conjunction with antipsychotics, remains unclear.

From the psychic sphere: rarely - hallucinations (visual or auditory), depression, anorexia, anxiety, aggression, agitation, disorientation; very rarely - activation of psychosis.

Allergic reactions: very often - allergic dermatitis, urticaria,which can be significantly pronounced; infrequently - exfoliative dermatitis, erythroderma; rarely - systemic lupus erythematosus, itching; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitivity reactions, erythema multiforme and nodosum, skin pigmentation disorders, purpura, acne, sweating, hair loss. There have been reports of rare cases of hirsutism, but the cause-and-effect relationship of this complication with taking the drug remains unclear.

Hypersensitivity reactionsSeldom - multiorgan delayed type hypersensitivity with fever, skin rashes, vasculitis, lymphadenopathy, symptoms resembling lymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function, and destruction of the intrahepatic bile ducts with a reduction in their number (as shown manifestations occur in different combinations ). Other organs may also be involved (eg, lungs, kidneys, pancreas, myocardium, large intestine). Very rarely - aseptic meningitis with myoclonus and peripheral eosinophilia, anaphylactic reaction, angioedema.If the above-mentioned allergic reactions occur, the drug should be discontinued.

On the part of the organs of hematopoiesis: 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, variegate porphyria, late cutaneous porphyria, acute "intermittent" porphyria, reticulocytosis, hemolytic anemia.

From the digestive system (further GIT): very often - nausea, vomiting; often - dry mouth; infrequently - diarrhea, constipation; rarely - abdominal pain; very rarely - glossitis, stomatitis, pancreatitis.

From the side of the liver: 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; infrequently - increased activity of transaminases; rarely - hepatitis of cholestatic, parenchymal (hepatocellular) or mixed type, destruction of intrahepatic bile ducts with a decrease in their number, jaundice; very rarely - granulomatous hepatitis, hepatic insufficiency.

From the side of the cardiovascular system (further SSS): rarely - violations intracardiac conduction; decrease or increase in blood pressure (BP); very rarely - bradycardia, arrhythmias, atrio-ventricular blockade with syncope, collapse, chronic heart failure, exacerbation of coronary heart disease, thrombophlebitis, thromboembolism (eg, pulmonary embolism).

From the endocrine system and metabolismFrequently - edema, fluid retention, weight gain, hyponatremia and reduced blood osmolarity due to an effect similar to the action of antidiuretic hormone, which rarely leads to water intoxication (hyponatremia dilution), accompanied by lethargy, vomiting, headache, disorientation and neurologic violations; very rarely - an increase in the concentration of blood prolactin, accompanied or not accompanied by such manifestations as galactorrhea, gynecomastia; changes in the function of the thyroid gland - reduced concentration L-tiroksina (free thyroxine, thyroxine, triiodothyronine) and an increase in thyroid-stimulating hormone (TSH) concentration,which is usually not accompanied by clinical manifestations; metabolic disorders of bone tissue (decrease in calcium and 25-hydroxycholecalciferol in the blood), which leads to osteomalacia / osteoporosis; increased cholesterol concentrations, including high-density lipoprotein cholesterol, and triglycerides.

From the genitourinary system: very rarely - interstitial nephritis, renal insufficiency, renal dysfunction (eg, albuminuria, hematuria, oliguria, urea / azotemia increase), frequent urination, urinary retention, sexual function / impotence disorders, spermatogenesis disorders (decrease in the number of spermatozoa and their mobility) .

From the musculoskeletal system: rarely - muscle weakness; very rarely - arthralgia, muscle pain or cramps.

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

Overdose:

Symptoms: usually reflect abnormalities from the CNS, SSS and respiratory system.

From the side of the central nervous system and sensory organs: oppression of CNS functions, disorientation, drowsiness, agitation, hallucinations, coma; blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (at the beginning), hyporeflexia (later); convulsions, psychomotor disorders, myoclonus, hypothermia, mydriasis).

On the part of the CAS: tachycardia, decreased blood pressure, sometimes increased blood pressure, intraventricular conduction disorders with expansion of the complex QRS; fainting, cardiac arrest.

On the part of the respiratory system: respiratory depression, pulmonary edema.

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

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

Laboratory indicators: leukocytosis or leukopenia, hyponatremia, metabolic acidosis is possible, hyperglycemia and glucosuria are possible, and the activity of the muscle fraction of creatine phosphokinase is increased. .

Treatment: there is no specific antidote. Treatment is based on the clinical condition of the patient; hospitalization is shown,determination of carbamazepine concentration in plasma (for confirmation of poisoning with this medicine and assessment of the degree of overdose), 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). 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 exchange blood transfusion. Symptomatic maintenance treatment in the intensive care unit, monitoring of functions heart, body temperature, corneal reflexes, kidney and bladder function, correction of electrolyte disorders. With a decrease in blood pressure: the position with the lowered head end, plasma substitutes, with ineffectiveness - in / in dopamine or dobutamine; at heart rhythm disturbances - treatment is selected individually; when convulsions - the introduction of benzodiazepines (eg, diazepam), with caution (because of the possible increase in respiratory depression), the introduction of other anticonvulsant drugs (eg, phenobarbital).With the development of hyponatremia of dilution (water intoxication) - restriction of the introduction of fluids and slow intravenous infusion of 0.9% solution NaCl (can help prevent the development of brain edema). It is recommended to carry out hemosorption on carbon sorbents.

Interaction:

Cytochrome P4503A4 (CYP3A4) is the main enzyme providing formation of carbamazepine-10,11-epoxide (active metabolite). Simultaneous application of Zeptol with inhibitors of isoenzyme CYP3A4 can lead to an increase in the concentration of carbamazepine in the plasma and 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 of the drug. The cancellation of simultaneously taken isoenzyme inducers CYP3A4 can reduce the rate of biotransformation of carbamazepine and lead to an increase in its concentration in the blood plasma.

Carbamazepine is a strong inducer of isoenzyme CYP3A4 and other enzyme hepatic systems of the first and second phases of the metabolism of drugs and with simultaneous use 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-transdiol occurs with the aid of microsomal epoxide hydrolase, the use of Zeptol together with the inhibitors of microsomal epoxide hydrolase can lead to an increase in the plasma concentration of carbamazepine-10,11-epoxide.

Drugs that can enhance carbamazepine concentration in plasma blood: verapamil, diltiazem, omeprazole, oxybutynin, dantrolene, ticlopidine, felodipine, dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, nefazodone, paroxetine, trazodone, viloxazine, styipentol, vigabatrin, acetazolamide, ibuprofen, danazol, nicotinamide (in adults, only in high doses); macrolide antibiotics (erythromycin, josamycin, clarithromycin, troleandomycin); azoles (itraconazole, ketoconazole, fluconazole, voriconazole), terfenadine, loratadine, olanzapine, isoniazid, inhibitors of the viral protease of HIV infection (for example, ritonavir), perhaps - cimetidine, desipramine.

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

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

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 dose of Zepthol should be corrected and / or the concentration of carbamazepine-10,11-epoxide in the blood plasma.

Drugs that can reduce the concentration of carbamazepine in blood plasma: felbamate, oxcarbazepine, phenobarbital, phenytoin, phosphenytoin, primidon, mezuximide, fensuximide, theophylline, aminophylline, isotretinoin, rifampicin, cisplatin or - doxorubicin, herbal preparations containing Hypericum perforatum (Hypericum perforatum), and although the data are partially contradictory, possibly also clonazepam.

With simultaneous use with the above drugs may require dose adjustment of Zepthol.

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

When combined 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 and 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, used in the therapy of HIV infection (indinavir, ritonavir, saquinavir), alprazolam, midazolam, theophylline, calcium channel blockers of the dihydropyridine group (eg, felodipine), digoxin, oral contraceptive means (alternative methods of contraception are necessary), glucocorticosteroids (for example, prednisolone, dexamethosone), ciclosporin, everolimus; levothyroxine, preparations containing estrogens and / orprogesterone.

It has been reported that in patients receiving carbamazepine phenytoin plasma levels may either rise or fall, and mephenytoin level - increase (in rare cases).

Combinations that should be taken into account

In the appointment of carbamazepine together with levetiracetam in some cases, increased toxic effects of carbamazepine.

There are reports of increased hepatotoxicity caused by isoniazid, when it was used concomitantly with carbamazepine.

The combined use of carbamazepine and lithium or metoclopramide, as well as carbamazepine and neuroleptics (haloperidol, thioridazine) may lead to an increase in the frequency of unwanted neurologic reactions (in the case of the latter combination - even with therapeutic concentrations of active substances in the blood plasma. The simultaneous use of carbamazepine with certain diuretic drugs (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 combinations of drugs are used, it may be necessary to increase the dose of these muscle relaxants; careful monitoring of patients should be carried out, as possible a faster, than expected, cessation of muscle relaxants.

Reported the occurrence of bleeding in women 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 enzymes.

Carbamazepine, as well as other psychotropic drugs, can reduce the tolerance of alcohol. In this regard, the patient is recommended to abandon the use of alcohol.

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

Special instructions:

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 starting treatment, and also periodically during the treatment, clinical blood tests should be performed, including counting the number of platelets and, possibly, reticulocytes, as well as determining 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 immediately consult a doctor if there are undesirable reactions such as fever, sore throat, rash, ulceration of the oral mucosa, unreasonable occurrence of hemorrhages, haemorrhages in the form of petechiae or purpura.

When Zeptol was used, very severe dermatological reactions were very rare, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome). Zepthol should be immediately withdrawn if signs and symptoms are suspected to be indicative of the development of severe dermatological reactions - for example, Stevens-Johnson syndrome or Lyell syndrome.With the development of severe (in some cases life-threatening patient) skin reactions, the patient must 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.

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

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

With the use of carbamazepine in patients in the countries of the Asian region (Thailand, Malaysia, Philippines), where the prevalence of the HLA-BM502 allele is noted, an increase in the incidence of severe dermatological reactions (from the gradation "very rarely" to "rarely"), including Stevens syndrome -Johnson and Lyell's syndrome.The frequency of the distribution of the HLA-B * 1502 allele is more than 15% in the Philippines, Thailand, Hong Kong and Malaysia, 10% in Taiwan, 4% in Northern China, and 2-4% in South Asia, including India, , 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, it is recommended that carriers of the HLA-B * 1502 allele (for example, Chinese nationals) be genotyped according to 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 HLA-B * 1502 allele before prescribing Zepthol is not necessary.

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

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

The influence of other factors, such as the dose of anticonvulsant drugs, patient compliance, simultaneous therapy with other drugs, concomitant diseases or the level of control of 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 (isolated macular or maculopapular exanthema) in most cases are transient and non-severe and usually take place for several days or weeks, even with continued treatment or after a reduction in the dose of the drug.

However, since differential diagnosis between early manifestations of severe skin reactions and mild to moderate transient skin eruptions can be difficult,in the development of any skin reactions, the patient should be under medical supervision (with a view to the timely termination of drug therapy in case of deterioration of the patient's condition).

The relationship between the presence in the genome allele HLA-B * 1502 and the development of mild skin reactions (such as hypersensitivity reaction, or isolated makuleznaya maculopapular rash) is not installed.

With the development of hypersensitivity to Zeptolu patients may be observed as separate skin lesions, liver (including intrahepatic bile duct disease), blood and lymphatic system, or other organs, and a combination thereof that should be considered as a systemic reaction. In the case of development of symptoms and symptoms of hypersensitivity to Zeptol, the drug should be immediately discontinued.

Patients with known hypersensitivity to carbamazepine should be informed about the possibility of developing hypersensitivity reactions to oxcarbazepine approximately in 25-30% of cases.

Cross-reactive hypersensitivity reactions can also occur between carbamazepine and phenytoin.

Before starting treatment with the drug and periodically during the therapy, it is recommended to study the general urine test and determine the concentration of urea in the blood. Before the appointment of carbamazepine and in the process of treatment, it is necessary to study the liver function, especially in patients whose history includes information on liver diseases, 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.

Before the beginning of treatment it is recommended to conduct an ophthalmological examination, including examination of the fundus and measurement of intraocular pressure. In the case of prescribing, patients with increased intraocular pressure require constant monitoring of this indicator.

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

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 carbamazepine, its concentration and clinical efficacy or tolerability is very low, nevertheless, a regular determination of the carbamazepine concentration may be useful in the following situations: with a sharp increase in the frequency of seizures; 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 suspicion of the development of toxic reactions in the event that the patient takes several medicines.

In some cases, treatment with antiepileptic drugs was accompanied by the appearance of suicidal attempts / suicidal intentions. This was also confirmed by a meta-analysis of randomized, placebo-controlled trials using antiepileptic drugs. Since the mechanism of occurrence of suicidal attempts with the use of antiepileptic drugs is not known, we can not exclude their occurrence and treatment of patients with Zeptol.Patients and attendants should be warned about the need to monitor the occurrence of suicidal thoughts / suicidal behavior and, in the event of symptoms, seek medical help immediately.

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 agent under the cover of the drug shown in such cases (for example, diazepam administered intravenously or rectally, orphenytoin administered intravenously).

Prior to the appointment of the drug, MAO inhibitors should be withdrawn at least 2 weeks or, if the clinical situation permits, even for a longer period.

During the treatment period, do not drink alcohol.

Effect on the ability to drive transp. cf. and fur:The ability of a patient taking Zeptol to respond quickly, especially at the beginning of therapy or during the dose selection period, can be disrupted by the occurrence of dizziness and drowsiness. Therefore, when driving a car or controlling mechanisms, the patient should be cautious.

Form release / dosage:

Tablets of 200 mg.

Packaging:10 tablets per strip, made of aluminum foil.

10 strips, together with instructions for use, are placed in a cardboard box.

Storage conditions:In a dry, the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date indicated on the packaging.

Terms of leave from pharmacies:On prescription

Registration number:П N011348 / 01

Date of registration:05.09.2011

Expiration Date:Unlimited

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp11.10.2017

Illustrated instructions

Instructions

Zeptol (Zeptol)