Tegretol cr retard pills 400mg №30

Mechanism of action

Antiepileptic drug. Tegretol is a dibenzoazepine 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 using Tegretol as monotherapy in patients with epilepsy (especially in children and adolescents), the psychotropic effect of the drug was noted, which, in particular, was manifested in a positive effect on the symptoms of anxiety and depression, as well as in reducing irritability and aggressiveness. According to a number of studies, the effect of Tegretol on cognitive function and psychomotor parameters 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 memorize 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 mania, for maintenance treatment of bipolar affective (manic-depressive) disorders (both as monotherapy and in combination with antipsychotics, antidepressants or lithium drugs), in schizoaffective psychosis, 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, sinceglutamate 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.

Suction
After oral administration, Carbamazepine is absorbed almost completely, although relatively slowly. After taking one regular pill of C_max achieved after 12 hours. There are no clinically significant differences in the degree of absorption of the active substance after the application of various dosage forms of the drug for oral administration. After a single dose of 400 mg of carbamazepine, the average value of C_max unchanged active substance is about 4.5 μg / ml.
After ingestion (single or repeated) pills retard C_maxachieved within 24 hours, its value is 25% less than in the case of taking a regular tablet. When taking retard pills daily variations in plasma concentrations of carbamazepine are less pronounced, with any significant reduction in the minimum value of C_ss not marked.When taking the drug in the form of retard pills 2 times / day, fluctuations in the concentration of the active substance in the plasma are very small. The bioavailability of the active substance from retard pills is approximately 15% lower than that of other dosage forms of the drug.
Food intake does not significantly affect the rate and extent of absorption of carbamazepine, no matter what dosage form of Tegretol is used.
C_ss plasma carbamazepine is reached within 1-2 weeks, which depends on the individual metabolism (autoinduction of the liver enzyme systems with carbamazepine, heteroinduction by other, simultaneously used drugs), as well as the patient's condition, the dose of the drug and the duration of treatment. Significant inter-individual differences in C values ​​are observed._ss in the therapeutic range: in most patients, these values ​​range from 4 to 12 mcg / ml (17-50 mcmol / l). The concentration of carbamazepine-10,11-epoxide (pharmacologically active metabolite) is about 30% of the concentration of carbamazepine.
Distribution
The binding of carbamazepine to plasma proteins is 70-80%. The concentration of unchanged carbamazepine in the cerebrospinal fluid and saliva is proportional to the proportion of active substance not bound to proteins (20–30%). The concentration of carbamazepine in breast milk is 25-60% of its level in the blood plasma.
Carbamazepine crosses the placental barrier. If we take the absorption of carbamazepine as complete, the apparent V_dmakes 0.8-1.9 l / kg.
Metabolism
Carbamazepine is metabolized in the liver, predominantly along the epoxy pathway, resulting in the formation of the main metabolites - 10,11-transdiol derivative and its conjugate with glucuronic acid. The main isoenzyme providing biotransformation of carbamazepine to carbamazepine-10,11-epoxide is cytochrome P₄₅₀ 3A4. As a result of these metabolic reactions, the little active metabolite 9-hydroxymethyl-10-carbamoyl acridane is also formed.
Removal
After a single dose of the drug inside T_1/2 unchanged carbamazepine averages about 36 hours, and after repeated administration of the drug - an average of 16-24 hours (due to autoinduction of the monooxygenase system of the liver), depending on the duration of treatment. In patients taking other drugs at the same time, inducing the same enzyme system of the liver (for example, phenytoin, phenobarbital), T_1/2carbamazepine averages 9-10 hours.
After a single dose of 400 mg of carbamazepine, 72% of the dose taken is excreted in the urine and 28% in the feces. About 2% of the dose taken are excreted in the urine as unchanged carbamazepine, about 1% as a pharmacologically active 10,11-epoxy metabolite, and about 30% as final metabolites resulting from the epoxy metabolic pathway.
Pharmacokinetics in special clinical situations
In children, due to the faster elimination of carbamazepine, it may be necessary to use higher doses of the drug per kg of body weight, compared with adults.
There are no data that would indicate that the pharmacokinetics of carbamazepine is changed in elderly patients (compared with adults of young age).
There are no data on the pharmacokinetics of carbamazepine in patients with impaired renal or liver function.

Indications and usage

- epilepsy: complex 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);
- acute manic states and supportive therapy of bipolar affective disorders in order to prevent exacerbations or alleviate the clinical manifestations of exacerbations;
- alcohol withdrawal syndrome;
- idiopathic trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis (typical and atypical); idiopathic neuralgia of the glossopharyngeal nerve;
- diabetic neuropathy with pain;
- non-sugar diabetes of central genesis; polyuria and polydipsia neurohormonal nature.

The drug can be taken during, after a meal or in between meals with a small amount of liquid.
Retard pills (whole pill or half, if so prescribed by the doctor) should be swallowed whole, not chewed, with a small amount of liquid. Since the active substance is released from retard pills slowly and gradually, they are prescribed 2 times / day.
Transferring a patient from taking conventional pills to receiving retard tablets: clinical experience shows that in some patients with retard tablets, it may be necessary to increase the dose of the drug.
Considering the drug interaction and the different pharmacokinetics of antiepileptic drugs, elderly patients should take the dose of Tegretol with caution.
Atepilepsy when it is possible, Tegretol should be prescribed as monotherapy.
Treatment begins with the use of a small daily dose, which is subsequently slowly increased to achieve the optimal effect.
For the selection of the optimal dose of the drug may be useful 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.
Foradults 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, a component of 1.6 g or even 2 g per day.
Havechildren ages 4 and underIt is recommended to begin treatment with the use of 20-60 mg / day and increase the dose by 20-60 mg every other day.
Havechildren over 4 years old 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: 10-20 mg / kg / day (in several doses).

Attrigeminal 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. Recommended starting dose forelderly patientsmakes 100 mg 2 times / day.
Atalcohol withdrawal syndromethe 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.
Atcentral diabetes mellitusaverage dose foradults is 200 mg 2-3 times / day. Havechildren The dose of the drug should be reduced in accordance with the age and weight of the child.
Atdiabetic neuropathy with pain The average dose of Tegretol is 200 mg 2-4 times / day.
Atacute manic states and maintenance 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.

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.
In assessing the frequency of occurrence of various adverse reactions, the following gradations were used: “very often” -> = 10%; "often" - from> = 1% to <10%; "sometimes" - from> = 0.1% to <1%; "rarely" - from> = 0.01% to <0.1%; "very rarely" - <0.01%.
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.
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, and possibly 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 symptoms 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 ischemic 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, T4, T3) and an increase in the level of thyroid-stimulating hormone, which is usually not accompanied by clinical manifestations; impaired bone tissue metabolism (reduced levels of calcium and 25-OH-cholecalciferol in the blood plasma), which leads to osteomalacia; in some cases - increasing the concentration of cholesterol,including high-density lipoprotein cholesterol, and triglycerides.
From the genitourinary system: very rarely, interstitial nephritis, renal failure, impaired renal function (for example, albuminuria, hematuria, oliguria, increased urea / 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.

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

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 in the event that 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 the cleft of the vertebrae (spina bifida) and other congenital anomalies (includingcraniofacial and cardiovascular systems), which 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 K₁.
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 benefits 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).

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 - for example, Stevens-Johnson syndrome or Lyell's syndrome.
Tegretol should be used only if medical supervision is provided.
Caution should 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.
Before the appointment of Tegretol and in the process of treatment, it is necessary to study the function of the liver, especially in patients with a history of liver disease, as well as in elderly patients. In the case of an increase in the already existing liver dysfunction or when an active liver disease appears, Tegretol should be immediately 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, liver, kidney diseases, adverse hematological reactions to other drugs, or to discontinue previously treated treatment with Tegretol should be prescribed only after careful analysis of the ratio of the expected effect of treatment and possible risk of therapy, and attentive 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. However, 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.
The possibility of activation of latently proceeding psychosis should be taken into account, and in elderly patients the possibility of disorientation or arousal development.
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, however, regular determination of the level of carbamazepine may 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.
Influence on ability to drive motor transport and control mechanisms
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.

arising from overdose, usually reflect damage to the central nervous system, cardiovascular and respiratory systems.
Central nervous system: depression of central nervous system functions; 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.
The cardiovascular system: tachycardia, arterial hypotension, sometimes - hypertension, conduction disorders with the expansion of the QRS complex; cardiac arrest, syncope.
Gastrointestinal tract: vomiting, delayed passage of food from the stomach, decreased motility of the colon.
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 from laboratory indicators: hyponatremia, possible metabolic acidosis, possible hyperglycemia, increased muscle fraction creatininephosphokinase.
Treatment. Initially, 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 shown in / in the introduction of dopamine or dobutamine; 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) - limiting the introduction of fluids,