Tegretol pills 200mg №50

Packaging

In the blister of 10 tablets. In packing 5 blisters.

Mechanism of action

Tegretol is an antiepileptic drug. Tegretol is a dibenzodiazepine derivative. Along with antiepileptic, the drug also has neurotropic and psychotropic effects. As an antiepileptic agent, Tegretol is effective in focal (partial) epileptic seizures (simple and complex), accompanied or not accompanied by secondary generalization, in generalized tonic-clonic epileptic seizures, and also in a combination of the indicated types of seizures.

In clinical studies with the use of Tegretol as monotherapy in patients with epilepsy (especially in children and adolescents), the psychotropic effect of the drug was noted, which, in particular, manifested itself in a positive effect on anxiety and depression symptoms, as well as in reducing irritability and aggressiveness.According to a number of studies, the effect of Tegretol on cognitive function and psychomotor performance depended on the dose and was either questionable or negative. In other studies, a positive effect of the drug on the indicators characterizing attention, ability to learn and remember was noted.

As a neurotropic agent, Tegretol is effective in a number of neurological diseases, for example, it prevents painful attacks in idiopathic and secondary trigeminal neuralgia. In addition, Tegretol is used to relieve neurogenic pain in various conditions, including spinal cord sinuses, post-traumatic paresthesias and postherpetic neuralgia. In alcohol withdrawal syndrome, Tegretol raises the threshold of convulsive readiness (which is reduced in this state) and reduces the severity of the clinical manifestations of the syndrome, such as excitability, tremor, and gait disturbances. In patients with central diabetes insipidus, Tegretol reduces diuresis and thirst.

As a psychotropic agent, Tegretol is effective in affective disorders, namely for the treatment of acute manic states, for maintenance treatment of bipolar affective (manic-depressive) disorders (both as monotherapy and in combination with antipsychotics, antidepressants or lithium drugs), schizoaffective psychoses, manic psychosis where it is used in combination with neuroleptics, as well as in acute polymorphic schizophrenia (rapid cycling episodes).

The mechanism of action is associated with the blockade of potential-dependent sodium channels, which leads to stabilization of the membranes of overexcited neurons, inhibiting the occurrence of serial discharges of neurons and reducing synaptic conduction of impulses. Anticonvulsant action is mainly due to the stabilization of the membranes of neurons and a decrease in the release of glutamate, a decrease in the activity of the excitatory neurotransmitter amino acid glutamate, since glutamate is the main mediator; there is not a single publication about the role of aspartate. Increases the reduced convulsive threshold of the central nervous system and, thus, reduces the risk of an epileptic seizure. Increased potassium conductivity and modulation of Calcium channels activated by a high membrane potential can also contribute to the anticonvulsant action of the drug. Eliminates epileptic personality changes and ultimately increases the communicability of patients and contributes to their social rehabilitation. May be prescribed as a primary therapeutic agent and in combination with other anticonvulsants.

Indications and usage

Epilepsy:
- Complicated or simple partial epileptic seizures (with loss or without loss of consciousness) with or without secondary generalization.
- Generalized tonic-clonic epileptic seizures.
- Mixed forms of epileptic seizures (Tegretol can be used both as monotherapy and as part of combination therapy; Tegretol is usually ineffective for small attacks / petit mal, absans / and myoclonic attacks).

Contraindications

AV blockade.
- A history of episodes of suppression of bone marrow hematopoiesis or information about acute intermittent porphyria.
- Combination with MAO inhibitors (structural similarity with tricyclic antidepressants). Before the appointment of Tegretol, MAO inhibitors should be canceled at least 2 weeks later or, if the clinical situation allows, even for a longer period.
- Hypersensitivity to Carbamazepine or chemically similar drugs (for example, tricyclic antidepressants) or to other components of the drug.

Pregnancy and Breastfeeding

Treatment with Tehretol epilepsy during pregnancy should be carried out with extreme caution.

In women of childbearing age, Tegretol should, if possible, be used as monotherapy, since the incidence of congenital fetal abnormalities born by women who have been treated with a combination of antiepileptic drugs is higher than those who received each of these funds as monotherapy. The minimum effective dose of Tegretol should be prescribed. Regular monitoring of plasma levels of carbamazepine is recommended.

When pregnancy occurs in a woman receiving Tegretol, or if the question arises about the appointment of Tegretol during pregnancy, it is necessary to carefully compare the expected benefits of therapy and its possible complications, especially in the first trimester of pregnancy.

It is known that children born to mothers with epilepsy are more likely to be predisposed to intrauterine growth disorders, including developmental defects. It has been reported that carbamazepine, like all major antiepileptic drugs, can increase the risk of these disorders, although there is no definitive confirmation of this, which would have been obtained from controlled studies using Tegretol as monotherapy, until now. There are, however, sporadic reports of cases of congenital diseases and malformations, including spinal bifida and other congenital anomalies (including craniofacial and cardiovascular systems) that were observed in patients taking Tegretol. Patients should be provided with information about the possibility of increasing the risk of malformations and the opportunity to undergo antenatal diagnosis.

It is known that during pregnancy, folic acid deficiency develops. It has been reported that antiepileptic drugs increase this deficiency. This may contribute to an increased incidence of birth defects in children born to women taking anti-epileptic drugs. Therefore, an additional intake of folic acid is recommended before and during pregnancy.

In order to prevent increased bleeding in newborns, women in the last weeks of pregnancy, as well as newborns, are recommended to prescribe vitamin K 1.Carbamazepine is excreted in breast milk, the concentration in it is 25-60% of the level in the blood plasma. Therefore, it is necessary to compare the advantages and possible undesirable effects of breastfeeding in the context of ongoing therapy with Tegretol. Mothers taking Tegretol may continue breastfeeding, but with the proviso that the child will be monitored for the development of possible side effects (for example, severe drowsiness, allergic skin reactions).

Dosage and administration

The drug can be taken during, after a meal or in between meals with a small amount of liquid.

In epilepsy, when possible, Tegretol should be administered as monotherapy. Treatment begins with the use of a small daily dose, which is subsequently slowly increased to achieve the optimal effect. To select the optimal dose of the drug, it is recommended to determine the level of the active substance in the blood plasma. In the case when Tegretol is added to the already existing antiepileptic therapy, this should be done gradually, while the doses of the drugs used are not changed or, if necessary, corrected.
For adults, the initial dose of Tegretol is 100-200 mg 1 or 2 times / day. Then the dose is slowly increased to achieve the optimal therapeutic effect; it is usually achieved at a dose of 400 mg / day, prescribed in 2-3 doses.Some patients may require a dose of Tegretol, which is 1.6 g / day or 2 g / day.
In children aged 4 years and under, it is recommended to begin treatment with the use of 20-60 mg / day and increase the dose by 20-60 mg every other day.
In children over the age of 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. Maintenance doses for children are 10-20 mg / kg / day (in several doses):

With trigeminal neuralgia, the initial dose of Tegretol is 200-400 mg / day. It is slowly increased to the disappearance of pain (usually up to a dose of 200 mg 3-4 times / day), and then gradually reduced to the minimum support. The recommended initial dose for elderly patients is 100 mg 2 times / day.

With alcohol withdrawal syndrome, the average dose is 200 mg 3 times / day. In severe cases, during the first few days, the dose may be increased (for example, up to a dose of 400 mg 3 times / day). In severe manifestations of alcohol withdrawal, treatment is started with a combination of Tegretol with sedative-hypnotic drugs (for example, with clomethiazole, chlordiazepoxide). After the resolution of the acute phase, treatment with Tehretol can be continued as monotherapy.

With central diabetic diabetes mellitus, the average dose for adults is 200 mg 2-3 times / day. In children, the dose of the drug should be reduced in accordance with the age and weight of the child.

In diabetic neuropathy with pain, the average dose of Tegretol is 200 mg 2-4 times / day.

In acute manic states and supportive treatment of affective (bipolar) disorders, daily doses are 400-1600 mg. The average daily dose is 400-600 mg (in 2-3 doses). In the acute manic state, the dose of Tegretol should be increased rather quickly. In the case of maintenance therapy of bipolar disorders, in order to ensure optimal tolerability, it is recommended to gradually increase the dose by a small amount.

Considering the drug interaction and the different pharmacokinetics of antiepileptic drugs, elderly patients should take the dose of Tegretol with caution.

Certain types of side effects, such as those of the central nervous system (dizziness, headache, ataxia, drowsiness, general weakness, diplopia), gastrointestinal tract (nausea, vomiting) or allergic skin reactions, occur more or less frequently, especially in the beginning of treatment with Tehretol, when using too large initial dose of the drug or in the treatment of elderly patients.

Dose-dependent side effects usually disappear within a few days, both spontaneously and after a temporary reduction in the dose of the drug. The development of side effects from the central nervous system can be a consequence of the 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 level of the active substance in the blood plasma.

From the side of the central nervous system and peripheral nervous system: very often - dizziness, ataxia, drowsiness, general weakness; often - headache, diplopia, accommodation accommodation disturbances (for example, blurring of vision); sometimes abnormal involuntary movements (for example, tremor, fluttering tremor / asterixis /, dystonia, tics); nystagmus; rarely, orofacial dyskinesia, oculomotor disorders, speech disorders (for example, dysarthria or slurred speech), choreoathetoid disorders, peripheral neuritis, paresthesias, muscle weakness, and symptoms of paresis. The role of carbamazepine as a drug that causes or promotes the development of a malignant neuroleptic syndrome, especially when carbamazepine is prescribed in conjunction with neuroleptics, remains unclear.

From the mental sphere: rarely - hallucinations (visual or auditory), depression, loss of appetite, anxiety, aggressive behavior, agitation, disorientation; very rarely - activation of psychosis.

Allergic reactions: very often - allergic skin reactions, urticaria, which can be significantly pronounced; sometimes exfoliative dermatitis, erythroderma; rarely, lupus-like syndrome, pruritus; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Dermatological reactions: very rarely - photosensitivity, erythema multiforme and nodular, disorders of skin pigmentation, purpura, acne, increased sweating, hair loss. Rare cases of hirsutism have been reported, but the causal relationship of this complication with Tegretol is unclear.

From the hemopoietic system: very often - leukopenia; often - thrombocytopenia, eosinophilia; rarely - leukocytosis, lymphadenopathy, folic acid deficiency; very rarely - agranulocytosis, aplastic anemia, true erythrocyte aplasia, megaloblastic anemia, acute intermittent porphyria, reticulocytosis, hemolytic anemia.

Liver: very often - an increase in the level of gamma-glutamyltransferase (due to the induction of this enzyme in the liver), which usually has no clinical significance; often - increased levels of alkaline phosphatase; sometimes - increased transaminase levels; rarely - cholestatic, parenchymal (hepatocellular) or mixed hepatitis, jaundice; very rarely - granulomatous hepatitis, liver failure.

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

Hypersensitivity Reactions: rarely, multiorgan delayed-type hypersensitivity with fever, skin rashes, vasculitis, lymphadenopathy, signs resembling lymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly, and altered liver function indicators (these manifestations occur in various combinations). Other organs can also be involved (for example, lungs, kidneys, pancreas, heart, colon); very rarely, aseptic meningitis with myoclonus and peripheral eosinophilia; anaphylactic reaction, angioedema.At occurrence of the above reactions of hypersensitivity use of the drug should be discontinued.

Since the cardiovascular system: rarely, intracardiac conduction disorders; hypertension or hypotension; very rarely - bradycardia, arrhythmias, AV blockade with fainting, collapse, congestive heart failure , exacerbation of coronary artery disease, thrombophlebitis, thromboembolic syndrome.

On the part of the endocrine system and metabolism: often - edema, fluid retention, weight gain, hyponatremia and decrease in plasma osmolarity due to an effect similar to the action of antidiuretic hormone, which in rare cases leads to dilution hyponatremia, accompanied by lethargy, vomiting, headache, disorientation and neurological disorders; very rarely - an increase in prolactin level, accompanied or not accompanied by such manifestations as galactorrhea, gynecomastia; changes in thyroid function parameters - a decrease in the level of L-thyroxin (FT4, T 4, T 3) and an increase in the level of thyroid-stimulating hormone, which is usually not accompanied by clinical manifestations; disorders of bone tissue metabolism (reduction of calcium and 25-OH-colecalciferol in the blood plasma), which leads to osteomalacia; in some cases - an increase in the concentration of cholesterol (Xc), including Xc-HDL, and triglycerides.

From the genitourinary system: very rarely - interstitial nephritis, renal failure,renal dysfunction (eg, albuminuria, hematuria, oliguria, urea increase / azotemia), frequent urination, urinary retention, sexual dysfunction / impotence.

From the senses: very rarely - taste disturbances, clouding of the lens, conjunctivitis; hearing disorders, incl. tinnitus, hyperacusia, hypoacusia, changes in perception of pitch.

From the musculoskeletal system: very rarely - arthralgia, muscle aches or cramps.

On the part of the respiratory system: very rarely - hypersensitivity reactions of the lungs, characterized by fever, shortness of breath, pneumonitis or pneumonia.

Agranulocytosis and aplastic anemia may develop during the administration of Tegretol. However, due to the fact that these conditions occur very rarely, it is difficult to calculate the specific values ​​of their risk. It is known that the total risk of agranulocytosis in the general population that did not receive treatment is 4.7 cases per 1 million population per year, and aplastic anemia - 2.0 cases per 1 million population per year.

During the use of Tegretol with a different frequency, a transient or persistent decrease in the number of platelets or leukocytes is observed. However, in most cases, these side effects are transient and usually are not precursors to the onset of aplastic anemia or agranulocytosis. However, before starting treatment, as well as periodically in the course of treatment, clinical blood tests should be carried out, including counting the number of platelets and, possibly, reticulocytes, as well as determine the level of serum iron.

In cases where a low level of the number of leukocytes or platelets (or a tendency to decrease them) is noted during treatment, one should carefully monitor the patient's condition and the indicators of a comprehensive clinical blood test. If signs of significant bone marrow depression are detected, Tegretol should be canceled.

Tegretol should be immediately discontinued if signs and symptoms are noted that presumably indicate the development of severe dermatological reactions, such as Stevens-Johnson syndrome or Lyell's syndrome.

Tegretol should be used only if medical supervision is provided. Caution must be exercised when using Tegretol in patients with mixed forms of epileptic seizures, including absences (typical and atypical). In all these cases, Tegretol may cause an increase in seizures. If this happens, Tegretol should be canceled.

It is necessary to bring to the attention of patients information about the early signs of toxicity inherent in probable hematological disorders, as well as symptoms of the skin and liver. The patient is informed of the need to immediately consult a doctor in the event of such adverse reactions as fever, sore throat, rash, oral ulcers, causeless hematomas, hemorrhages in the form of petechiae or purpura.

Patients who have a history of heart disease, liver, kidney,hematological adverse reactions to other drugs or the cancellation of previously treated treatment with Tehretol, the drug should be prescribed only after a careful analysis of the ratio of the expected effect of treatment and the possible risk of therapy and with careful and regular monitoring.

Before starting treatment with Tegretol and periodically in the course of therapy, it is recommended to study a general urinalysis and blood urea level. Mild skin reactions, for example, isolated macular or maculo-papular exanthema, in most cases are transient and mild, usually disappearing within a few days or weeks even with continued treatment or after lowering the dose of the drug. Nevertheless, the patient at this time should be under close medical supervision. Tegretol has a weak anticholinergic activity. Therefore, in the case of the use of the drug in patients with elevated intraocular pressure, constant monitoring of this indicator is necessary.

It is necessary to take into account the possibility of activation of latent proceeding psychosis, and in elderly patients the possibility of developing disorientation or arousal. To date, individual reports of violations of male fertility and / or impaired spermatogenesis have been registered. However, the causal relationship of these disorders with the reception Tegretola has not yet been established.There are reports of the occurrence of bleeding in women during the period between menstruation in cases when oral contraceptives were used simultaneously. Tegretol can significantly reduce the therapeutic effect of oral contraceptive drugs due to the induction of microsomal enzymes, therefore, women of childbearing age during treatment with Tegretol should use alternative methods of birth control.

Although the relationship between the dose of the drug and the level of carbamazepine in the blood plasma, as well as between the level of carbamazepine in the blood plasma and its clinical efficacy or tolerability is very small, regular determination of the level of carbamazepine may nevertheless be useful in the following situations: with a sharp increase in the frequency of attacks; in order to check whether the patient is taking the drug properly; during pregnancy; in the treatment of children or adolescents; in case of suspicion of drug absorption; if you suspect the development of toxic reactions in case the patient takes several drugs.

A sudden discontinuation of Tegretol can trigger epileptic seizures. If you have to abruptly interrupt treatment with Tehretol of a patient with epilepsy, in this case it is necessary to switch to another antiepileptic drug under the guise of the drug shown in such cases (for example, diazepam, administered iv or rectal, or phenytoin administered iv).Perhaps the development of cross-reactions of hypersensitivity to carbamazepine and oxcarbazepine. Hypersensitivity cross-reactions can also occur between carbamazepine and phenytoin. Tegretol, 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.

Several cases of epileptic seizures and / or respiratory depression in newborns whose mothers took Tegretol along with other anticonvulsants have been described. In addition, several cases of vomiting, diarrhea and / or diminished nutrition in newborns have also been reported in connection with the use of Tegretol by mothers. Perhaps these reactions are manifestations of withdrawal syndrome in newborns.

The ability of the patient receiving Tegretol to react quickly, especially at the beginning of therapy or during the dose selection period, may be impaired due to the occurrence of dizziness and drowsiness. Therefore, when driving a car or controlling mechanisms, the patient should be careful.

CYP3A4 isoenzyme is the main enzyme that provides the formation of carbamazepine-10,11-epoxide. The simultaneous use of inhibitors of CYP3A4 with Tegretol may lead to an increase in plasma carbamazepine concentration, which, in turn, may cause side effects. The combined use of CYP3A4 inducers can lead to an acceleration of Tegretol metabolism and, thus, to a possible decrease in plasma concentration of carbamazepine, and, consequently, to a possible decrease in the severity of the therapeutic effect. Canceling simultaneously administered inducers of CYP3A4 can reduce the rate of carbamazepine biotransformation and, as a result, lead to an increase in plasma levels of carbamazepine.

Plasma carbamazepine levels can increase Verapamil , diltiazem, dextropropoxyphene, viloxazine, Fluoxetine , fluvoxamine; possibly cimetidine, acetazolamide, danazol, desipramine, nicotinamide (in adults, only in high doses); nefazodone, macrolide antibiotics (for example, Erythromycin , troleandomycin, josamycin, clarithromycin); azoles (for example, itraconazole, Ketoconazole , fluconazole), terfenadine, loratadine , grapefruit juice, viral protease inhibitors (in the treatment of HIV infection, for example, ritonavir). Since elevated plasma levels of carbamazepine can lead to side effects (for example, dizziness, drowsiness, ataxia, diplopia), in these situations you should correct the dose of Tegretol and / or regularly examine plasma plasma levels of carbamazepine.

Plasma carbamazepine levels can decrease phenobarbital, phenytoin, primidone, probid or theophyllus, as well as metsaximid, pensouximide, rifampicin, Cisplatin , or doxorubicin , and although the data are partially contradictory, it is also possible that clonazepam, valproic acid, or valpromidine may also be used in a combination of voloproic acid or valxopromin or doxorubicin, and, although it is partially contradictory, it is also possible Hypericum perforatum).On the other hand, there are reports that valproic acid, valpromid and primidone increase the plasma concentration of the pharmacologically active metabolite, carbamazepine-10,11-epoxide. Therefore, a dose adjustment of Tegretol may be required.

In case of simultaneous administration with felbamate it is possible to decrease the concentration of carbamazepine in the serum, associated with an increase in the concentration of carbamazepine-epoxide, while it is possible to decrease the serum concentration of felbamate.

It has been reported that isotretinoin alters the bioavailability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide; in this case, plasma carbamazepine concentration monitoring is required.

Carbamazepine can reduce plasma concentrations or reduce or even completely neutralize the effects of certain drugs. You may need a dose adjustment for the following drugs: clobazam, clonazepam, ethosuximide, primidone, valproic acid, alprazolam; corticosteroids (for example, prednisone, dexamethasone); Cyclosporine, Digoxin , Doxycycline , cephalus imipramine, Amitriptyline , nortriptyline, clomipramine), clozapine, oxcarbazepine, protease inhibitors,used in the treatment of HIV infection (indinavir, ritonavir, saquinavir), calcium channel blockers (a group of dihydropyridines, for example, felodipine), itraconazole, levothyroxine, midazolam, olanzapine , drugs containing estrogen and / or Progesterone , praziquantell, withdrawn, and heart rate; .

There are reports that in patients receiving carbamazepine, the level of phenytoin in the blood plasma can both increase and decrease, and the level of mephenytoin increases (in rare cases).

With the joint use of carbamazepine and Paracetamol (acetaminophen) may decrease the bioavailability of the latter.

There are reports of increased hepatotoxicity caused by isoniazid, in cases where it was used simultaneously with carbamazepine.

Combined use of carbamazepine and lithium or Metoclopramide , as well as carbamazepine and neuroleptic drugs (haloperidol, thioridazine) can lead to an increase in the frequency of unwanted neurological reactions (in the case of the latter combination - even with therapeutic concentrations of active substances in the blood plasma).

The simultaneous use of Tegretol with some diuretic agents (hydrochlorothiazide, furosemide) can lead to hyponatremia, accompanied by clinical manifestations.

Carbamazepine may counteract the effects of non-depolarizing muscle relaxants (for example, pancuronium). In the case of the use of such a combination of drugs, it may be necessary to increase the dose of these muscle relaxants; Careful monitoring of patients should be carried out.perhaps a faster than expected cessation of muscle relaxants.

Symptoms:
Central nervous system - depression of the functions of the central nervous system; disorientation, drowsiness, agitation, hallucinations, coma; blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (first), hyporeflexia (later); convulsions, psychomotor disorders, myoclonus, hypothermia, mydriasis.

Respiratory system - respiratory depression, pulmonary edema. Cardiovascular system Tachycardia, arterial hypotension; sometimes - hypertension, disturbances of conductivity with expansion of the QRS complex; cardiac arrest, syncope. GIT Vomiting, delayed passage of food from the stomach, decreased colon motility. Urinary system Urinary retention, oliguria or anuria; fluid retention; dilution hyponatremia due to the effect of carbamazepine, similar to the effect of antidiuretic hormone.

Changes in laboratory parameters - hyponatremia, possible metabolic acidosis, possible hyperglycemia, increased muscle fraction creatininephosphokinase.

Treatment: At first, treatment should be based on the clinical condition of the patient; hospitalization is indicated. Concentration of carbamazepine in plasma is carried out to confirm the poisoning by this agent and to assess the degree of overdose. Carried out the evacuation of the contents of the stomach, gastric lavage, the use of activated charcoal.Late evacuation of gastric contents can lead to delayed absorption and the reappearance of symptoms of intoxication during the recovery period. Symptomatic supportive therapy is used in the intensive care unit, monitoring of heart function, careful correction of electrolyte disorders. There is no specific antidote.

Special recommendations: with the development of arterial hypotension, iv administration of dopamine or dobutamine is indicated; with the development of cardiac arrhythmias, treatment is selected individually; with the development of seizures - the introduction of anticonvulsants, with the development of hyponatremia (water intoxication) - restriction of fluid intake, which may help prevent the development of cerebral edema. It is recommended to conduct hemosorption on coal sorbents. The ineffectiveness of forced diuresis, hemodialysis, and peritoneal dialysis has been reported. It is necessary to anticipate the possibility of re-amplification of symptoms of overdose on the second and third day after its onset, due to the slow absorption of the drug.

The drug should be stored at a temperature not higher than 25 ° C; protect from moisture.