Carbamazepine

Pharmacological properties

finlepsin retard is an anticonvulsant derivative of tricyclic iminostilbene. exhibits antiepileptic, neurotropic and psychotropic activity. the therapeutic effect is primarily due to inhibition of the synaptic transmission of excitation and, as a consequence, a decrease in the spread of convulsive attacks. at higher concentrations, carbamazepine causes a decrease in post-tetanic potentiation. finlepsin retard reduces the severity of pain in trigeminal neuralgia. this effect is due to inhibition of the synaptic transmission of irritation in the spinal nucleus of the trigeminal nerve. with diabetes insipidus, finlepsin retard has an antidiuretic effect, possibly due to a hypothalamic effect on osmoreceptors.

Pharmacokinetics After oral administration, carbamazepine is absorbed slowly and almost completely.

The half-life period is 8.5 hours and has a wide range (about 1.72–12 hours). After a single dose of C_max plasma carbamazepine in adults is achieved after 4-16 hours (very rarely after 35 hours), in children after about 4-6 hours. The concentration of carbamazepine in blood plasma is not linearly dose-dependent, and when used at higher doses, the plasma concentration curve has the form of a plateau.

When prolonged-release tablets are used, a lower concentration of carbamazepine in the blood plasma is achieved than with conventional tablets.

Equilibrium concentration is reached after 2-8 days. There is no close correlation between the dose of carbamazepine and a stable concentration in equilibrium in blood plasma.

Regarding the therapeutic and toxic concentrations of carbamazepine in blood plasma, it is indicated that seizures may disappear with a plasma level of 4–12 μg / ml. The concentration of the drug in blood plasma in excess of 20 μg / ml, worsens the picture of the disease.

Finlepsin retard at a concentration of the active substance in blood plasma of 5-18 μg / ml eliminates pain in trigeminal neuralgia.

70–80% of carbamazepine binds to plasma proteins. Part of carbamazepine unbound with proteins at a concentration of 50 μg / ml remains constant. 48–53% of the pharmacologically active metabolite carbamazepine-10, 11-epoxide binds to plasma proteins. The concentration of carbamazepine in CSF is 33% of the plasma concentration.

Carbamazepine crosses the placental barrier and is excreted in breast milk.

After a single dose, carbamazepine is excreted from plasma with T_½ 36 h. With prolonged treatment T_½ decreases by 50% due to the induction of microsomal liver enzymes.

In healthy individuals, the total clearance from blood plasma is about 19.8 ml / h / kg body weight, in patients with monotherapy - about 54.6 ml / h / kg, in patients with combined treatment - about 113.3 ml / h / kg

After a single oral administration of carbamazepine, 72% of the dose in the form of metabolites is excreted from the body by the kidneys. The remaining 28% is excreted along with feces, partially - unchanged. Only 2-3% of a substance excreted in urine is carbamazepine unchanged.

Indications

Epilepsy: complex or simple partial seizures (with or without loss of consciousness) with or without secondary generalization; generalized tonic-clonic seizures; mixed forms of convulsive seizures.

Finlepsin retard can be used both as monotherapy and as part of combination therapy.

Acute manic conditions; maintenance therapy for bipolar affective disorders to prevent exacerbations or to reduce the severity of clinical manifestations of exacerbation.

Alcohol withdrawal syndrome.

Idiopathic trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis (typical and atypical).

Idiopathic neuralgia of the glossopharyngeal nerve.

Application

Finlepsin retard is prescribed orally, usually the daily dose should be divided into 2 doses. You can take the drug during, after a meal or in between meals, with a small amount of liquid.

Before starting treatment, patients belonging to the Chinese Han ethnic group or patients of Thai origin should, if possible, be screened for HLA-B * 1502, since this allele can provoke the development of severe carbamazepine-associated Stevens-Johnson syndrome.

Epilepsy. Treatment begins with the use of a low daily dose, which is then slowly increased (adjusted, taking into account the needs of each individual patient) until the optimal effect is achieved.

In cases where this is possible, Finlepsin retard should be prescribed as monotherapy, but when used with other drugs, a regimen of the same gradual increase in the dose of the drug is recommended. If Finlepsin retard is added to the existing antiepileptic therapy, the dose should be increased gradually, while the doses of the drugs used are not changed or adjusted if necessary.

To select the optimal dose of the drug, it may be useful to determine the level of active substance in the blood plasma. The therapeutic concentration of the drug in blood plasma should be 4-12 μg / ml.

In some patients, with the use of retard tablets, it may be necessary to increase the dose of the drug.

Adults The recommended initial dose is 100-200 mg 1-2 times a day, then gradually increase the dose to achieve the optimal effect; usually the daily dose is 800–1200 mg, which is divided into 2 doses. Some patients may require a dose of Finlepsin retard reaching 1600 mg or even 2000 mg / day.

Elderly patients. Given the drug interactions and the different pharmacokinetics of antiepileptic drugs, elderly patients should be selected with caution in finlepsin retard doses.

Children from the age of 5 years. Usually, treatment should be carried out at a dose of 10–20 mg / kg body weight per day (in several doses).

Children aged 5-10 years - 400-600 mg / day.

Children aged 10-15 years - 600-1000 mg / day.

Acute manic conditions and supportive treatment of affective (bipolar) disorders. The dose range is 400-1600 mg / day in 2 divided doses.

Typically, therapy is carried out at a dose of 400-600 mg / day in 2 divided doses. In the treatment of acute manic conditions, the dose of Finlepsin retard should be increased quite quickly to 800 mg / day. With maintenance therapy for bipolar disorder, a gradual increase in low doses is recommended to ensure optimal tolerance.

Alcohol withdrawal syndrome. The average dose is 600 mg / day in 2 divided doses. In severe cases, the dose can be increased during the first few days (for example, up to 1200 mg / day, divided into 2 doses). In severe manifestations of alcohol withdrawal, treatment begins with a combination of Finlepsin retard with sedative-hypnotic drugs (for example, clomethiazole, chlordiazepoxide), adhering to the above dosage instructions. After the acute phase is completed, treatment with Finlepsin retard can be continued as monotherapy.

Idiopathic trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis (typical and atypical). Idiopathic neuralgia of the glossopharyngeal nerve. The initial dose of Finlepsin retard is 200-400 mg / day (100 mg 2 times a day for elderly patients).It should be slowly increased until the pain disappears (usually up to a dose of 400-800 mg, divided into 1-2 doses). In some cases, a daily dose of 1600 mg may be required. After the cessation of pain, the dose should be gradually reduced to the minimum maintenance.

Contraindications

Finlepsin Retard should not be prescribed:

• with established hypersensitivity to carbamazepine or chemically similar drugs (tricyclic antidepressants), or other components of the drug;
• with AV block;
• history of inhibition of bone marrow function;
• patients with a history of hepatic porphyria (e.g., acute intermittent porphyria, mixed porphyria, late skin porphyria);
• in combination with MAO inhibitors;
• in combination with voriconazole, as treatment may be ineffective.

Side effects

Marked side effects more often occurred with combined treatment than with monotherapy. depending on the dose and mainly at the beginning of treatment, certain side effects may occur. in general, they disappear on their own after 8-14 days or after a temporary dose reduction.

On the part of the blood and lymphatic system: leukocytosis, eosinophilia, leukopenia, thrombocytopenia, folic acid deficiency, agranulocytosis, aplastic anemia, pancytopenia, erythrocytic aplasia, anemia, megaloblastic anemia, acute intermittent porphyria hemorrhagic porphyria, variega bone marrow failure.

On the part of the immune system: drug rashes with eosinophilia and systemic symptoms (DRESS), delayed multi-organ hypersensitivity with fever, skin rashes, vasculitis, lymphadenopathy; signs resembling lymphoma; arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and abnormal results of liver tests that occur in various combinations, the syndrome of the disappearance of bile ducts (destruction and disappearance of the intrahepatic bile ducts); aseptic meningitis with myoclonus and peripheral eosinophilia, anaphylactic reaction, angioedema, hypogammaglobulinemia. Other organs may be involved (e.g., liver, lungs, kidneys, pancreas, myocardium, large intestine).

From the endocrine system: edema, fluid retention, weight gain, hyponatremia, and a decrease in blood plasma osmolarity through the effect of carbamazepine, similar to the action of antidiuretic hormone, which sometimes leads to hyperhydration, which is accompanied by lethargy, vomiting, headache, confusion and neurological disorders, increased prolactin levels with or without clinical symptoms, such as galactorrhea and gynecomastia; abnormal thyroid function test results: decreased L-thyroxine (FT₄, T₄, T₃) and an increase in TSH, which usually takes place without clinical manifestations, impaired bone metabolism (a decrease in plasma calcium and 25-hydroxycolcalcaliferol in the blood plasma, which leads to osteomalacia / osteoporosis, an increase in cholesterol, including HDL cholesterol and triglycerides. Carbamazepine can reduce plasma folate levels and a decrease in vitamin B levels due to carbamazepine has also been reported₁₂ in blood plasma and an increase in homocysteine ​​levels.

From the side of metabolism and eating disorders: folate deficiency, decreased appetite, acute porphyria, chronic porphyria.

From the side of the psyche: hallucinations (visual or auditory), depression, lack of appetite, anxiety, aggressive behavior, agitation, nervous excitement, confusion, activation of latent psychosis, mood changes, such as depressive or manic mood swings, phobias, lack of motivation, involuntary movements such as asterixis.

From the nervous system: general weakness, dizziness, ataxia, drowsiness, sedation, fatigue, headache, abnormal reflex movements (e.g. tremor, large-scale tremor, dystonia, tic), nystagmus, orofacial dyskinesia, slow thinking, speech disorders (e.g. dysarthria or slurred speech), choreoathetosis, peripheral neuropathy, paresthesias, muscle weakness and paresis, taste disturbance, malignant antipsychotic syndrome, memory impairment, ataxic and cerebellar disorders, which hen accompanied by headache.

From the side of the organ of vision: conjunctivitis, impaired accommodation (diplopia, blurred vision), increased intraocular pressure, clouding of the lens, retinotoxicity, oculomotor disturbances.

On the part of the organ of hearing and the vestibular apparatus: hearing impairment, tinnitus, tinnitus, hyperacusis, hypoacusia, impaired perception of pitch.

From the cardiovascular system: intracardiac conduction disturbances, bradycardia, arrhythmia, worsening coronary heart disease, congestive heart failure, circulatory collapse, AV blockade with syncope, hypertension or hypotension, vasculitis, thrombophlebitis, thromboembolism (e.g. pulmonary embolism).

From the respiratory system: hypersensitivity from the lungs, which is characterized by an increase in body temperature, shortness of breath, pulmonitis or pneumonia. In the event of such hypersensitivity reactions, the drug should be discontinued.

From the digestive system: loss of appetite, dry mouth, nausea, vomiting, diarrhea, constipation, abdominal pain, stomatitis, gingivitis, glossitis, pancreatitis, colitis.

Hepatobiliary disorders: changes in liver function test indices (increase in gamma-glutamyl transferase level, increase in alkaline phosphatase, transaminases), jaundice, various forms of hepatitis (cholestatic, hepatocellular, granulomatous, mixed), life-threatening acute hepatitis, liver failure.

On the part of the skin and subcutaneous fat: allergic dermatitis, urticaria, pruritus, exfoliative dermatitis, erythroderma, necrosis of the surface of the skin with the formation of blisters (Lyells syndrome), photosensitivity, redness of the skin with polymorphic rashes in the form of spots and the formation of nodes, with hemorrhages ( exudative erythema multiforme, erythema multiforme, Stevens-Johnson syndrome), petechial hemorrhages in the skin and lupus erythematosus (disseminated lupus erythematosus, alopecia), diaphoresis, changes in skin igmentation, acne, hirsutism, vasculitis, purpura, increased sweating, acute generalized exanthematous pustulosis (AGEP), lichenoid keratosis, onychomydesis.

From the musculoskeletal system: arthralgia, myalgia, muscle cramps, muscle pain, fractures, decreased bone mineral density.

From the kidneys and urinary tract: proteinuria, hematuria, oliguria, dysuria, pollakiuria, urinary retention, tubulointerstitial nephritis, renal failure, increased blood urea / azotemia, frequent urination.

On the part of the reproductive system and mammary glands: impaired spermatogenesis (with a decrease in the number and / or motility of spermatozoa), erectile dysfunction, impotence, decreased sexual desire.

Infections and infestations: reactivation of human herpes virus type VI.

Deviation of laboratory test results: hypogammaglobulinemia.

special instructions

Carbamazepine should be prescribed only under medical supervision, only after assessing the benefit / risk ratio and subject to careful monitoring of patients with cardiac, hepatic or renal impairment, history of hematological adverse reactions to other drugs,or patients with interrupted carbamazepine therapy.

A general urinalysis and determination of the level of urea nitrogen in the blood at the beginning and with a certain frequency during therapy is recommended.

Carbamazepine exhibits mild anticholinergic activity, therefore, patients with increased intraocular pressure should be warned and consulted about possible risk factors.

It should be remembered about the possible activation of latent psychoses, and in relation to elderly patients - about the possible activation of confusion and the development of anxiety arousal.

The drug is usually ineffective for absences (small seizures) and myoclonic seizures. Some cases indicate that increased seizures may occur in patients with atypical absences.

Hematologic effects. With the use of the drug, the development of agranulocytosis and aplastic anemia is associated; however, due to the extremely low incidence of these conditions, it is difficult to assess the significant risk with carbamazepine.

Patients should be informed of early signs of toxicity and symptoms of possible hematologic disorders, as well as symptoms of dermatological and liver reactions. The patient should be warned that in the event of reactions such as fever, sore throat, skin rashes, oral ulcers, bruising that easily occur, pinpoint hemorrhages or hemorrhagic purpura, you should immediately consult a doctor.

If the number of leukocytes or platelets decreases significantly during therapy, the patients condition should be carefully monitored, and a constant general blood test of the patient should also be performed. Treatment with carbamazepine must be discontinued if the patient develops leukopenia, which is severe, progressive, or is accompanied by clinical manifestations, such as fever or sore throat. The use of carbamazepine should be discontinued when signs of inhibition of bone marrow function appear.

Periodically or often there is a temporary or steady decrease in the number of platelets or leukocytes in connection with taking carbamazepine. However, for most of these cases, their temporality was confirmed and they do not indicate the development of aplastic anemia or agranulocytosis. Before starting therapy and periodically during its conduct, a blood test should be performed, including determination of the platelet count (as well as, possibly, the number of reticulocytes and the level of hemoglobin).

Serious dermatological reactions. Serious dermatological reactions, including toxic epidermal necrolysis (TEN) or Lyells syndrome, Stevens-Johnson syndrome (SJS), are very rare with carbamazepine. Patients with serious dermatological reactions may require hospitalization, as these conditions can be life threatening and have a fatal outcome. Most cases of SJS / TEN develop during the first few months of treatment with carbamazepine. With the development of signs and symptoms indicative of serious dermatological reactions (SJS, Lyells syndrome / TEN), carbamazepine should be discontinued immediately and alternative therapy should be prescribed.

Pharmacogenomics. There is increasing evidence of the effect of various HLA alleles on the patient’s propensity for adverse reactions associated with the immune system.

Communication with (HLA) -B * 1502. Retrospective studies in Chinese patients of the Khan ethnic group showed a pronounced correlation between skin reactions of SJS / TEN associated with carbamazepine and the presence of human leukocyte antigen (HLA), allele (HLA) -B * 1502 in these patients. A high frequency of reports on the development of SJS (rather rarely than very rarely) is characteristic of some countries in Asia (for example, Fr.Taiwan, Malaysia and the Philippines), where the allele (HLA) -B * 1502 prevails among the population. The number of carriers of this allele among the population of Asia is 15% in the Philippines, in Thailand, Hong Kong and Malaysia, ≈10% - on Fr. Taiwan, almost 4% in Northern China, ≈2-4% in South Asia (including India), and 1% in Japan and Korea. The distribution of the allele (HLA) -B * 1502 is insignificant among European, African peoples, among the native population of America and Latin American countries.

In patients who are considered to be genetically related to risk groups, testing for the presence of an allele (HLA) -B * 1502 should be performed before starting carbamazepine treatment. If the analysis for the presence of an allele (HLA) -B * 1502 gives a positive result, then treatment with carbamazepine should not be started, except in cases where there are no other therapeutic options. Patients who have been tested and tested negative for (HLA) -B * 1502 have a low risk of developing SJS, although very rarely such reactions can still develop.

Currently, due to the lack of data, it is not known for certain whether there are risks for all people of Southeast Asian descent.

Allele (HLA) -B * 1502 may be a risk factor for the development of SJS / TEN in Chinese patients who receive other antiepileptic drugs that may be associated with the occurrence of SJS / TEN. Thus, the use of other drugs that may be associated with the occurrence of SJS / TEN should be avoided in patients with the allele (HLA) -B * 1502, if other alternative therapy can be used. Genetic screening of patients whose nationalities are characterized by a low allele coefficient (HLA) -B * 1502 is usually not recommended. Screening is usually not recommended in individuals already receiving carbamazepine, since the risk of an SJS / TEN is significantly limited to the first few months, regardless of whether the patient has an allele (HLA) -B * 1502 in the genes.

In patients of the Caucasian race, there is no relationship between the gene (HLA) -B * 1502 and the onset of SJS.

Communication with (HLA) -A * 3101. Human leukocyte antigen can be a risk factor for the development of skin adverse reactions, such as SJS, TEN, drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), maculopapular rash. If the analysis reveals the presence of the HLA-A * 3101 allele, then carbamazepine should be abstained.

Limit genetic screening. Genetic screening results should not replace appropriate clinical observation and treatment of patients. Other possible factors play a role in the occurrence of these severe skin adverse reactions, such as the dosage of an antiepileptic agent, adherence to the treatment regimen, and concomitant therapy. The effect of other diseases and the level of monitoring of skin disorders have not been studied.

Other dermatological reactions. Perhaps the development of transient and non-threatening lung dermatological reactions, for example, an isolated macular or maculopapular exanthema. Usually they pass after a few days or weeks, both with constant dosing and after a dose reduction. Since the early signs of more serious dermatological reactions can be very difficult to distinguish from mild rapid reactions, the patient should be monitored to immediately stop using the drug if the reaction worsens with its continuation.

The presence of an allele (HLA) -B * 1502 in a patient is not a risk factor for the occurrence of less serious adverse reactions to carbamazepine from the skin, such as hypersensitivity syndrome to anticonvulsants or minor rashes (maculopapular rash). However, it was found that the presence of (HLA) -B * 1502 may indicate a risk of the aforementioned reactions.

Hypersensitivity.Carbamazepine can provoke the development of hypersensitivity reactions, including a drug rash with eosinophilia and systemic symptoms (DRESS), multiple delayed-type hypersensitivity reactions with fever, rash, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, hepatic syndrome, leukenopenia, liver function syndrome, leukopenia, liver function syndrome, leukopenia, and hepatic syndrome, bile ducts (including destruction and disappearance of intrahepatic bile ducts).

Also a possible effect on other organs (lungs, kidneys, pancreas, myocardium, colon).

The presence of the HLA-A * 3101 allele in the patient is associated with the occurrence of less serious adverse reactions to carbamazepine from the skin, such as hypersensitivity syndrome to anticonvulsants or minor rashes (maculopapular rash).

Patients with hypersensitivity reactions to carbamazepine should be informed that about 25-30% of these patients may also have hypersensitivity reactions to oxcarbazepine.

With the use of carbamazepine and phenytoin, the development of cross hypersensitivity is possible.

In general, with the appearance of signs and symptoms indicating hypersensitivity, the use of carbamazepine should be stopped immediately.

Bouts. Carbamazepine should be used with caution in patients with mixed seizures that include absences (typical or atypical). In such circumstances, the drug can provoke seizures. In case of provoking seizures, carbamazepine should be discontinued immediately.

An increase in the frequency of seizures can be noted when switching from oral forms of the drug to suppositories.

Liver function. During the period of drug therapy, it is necessary to assess liver function at an initial level and periodically evaluate this function during therapy, especially in patients with a history of liver diseases and in the elderly. With an exacerbation of impaired liver function or in patients with an active phase of liver disease, you must immediately stop taking the drug.

Some indicators of laboratory tests that evaluate the functional state of the liver in patients taking carbamazepine may go beyond the norm, in particular gamma-glutamyl transferase. This is probably due to the induction of liver enzymes. Enzyme induction can also lead to a moderate increase in alkaline phosphatase levels. Such an increase in the functional activity of hepatic metabolism is not an indication for the abolition of carbamazepine.

Severe reactions from the liver with carbamazepine are very rare. In case of signs and symptoms of hepatic dysfunction or active liver disease, it is necessary to urgently examine the patient, and treatment with carbamazepine should be suspended until the results of the examination are obtained.

Kidney function. It is recommended to evaluate renal function and determine the level of blood urea nitrogen at the beginning and periodically during the course of therapy.

Hyponatremia. Cases of the development of hyponatremia with the use of carbamazepine are known. In patients with pre-existing renal impairment that is associated with decreased sodium levels, or in patients with concomitant treatment with drugs that lower sodium levels (such as diuretics, drugs that are associated with inadequate secretion of antidiuretic hormone), treatment should be determined blood sodium level. Then it should be measured every 2 weeks, then - with an interval of 1 month during the first 3 months of treatment or according to clinical necessity. This applies primarily to elderly patients. In this case, the amount of water consumed should be limited.

Hypothyroidism. Carbamazepine can reduce the concentration of thyroid hormones, therefore, it is necessary to increase the dose of thyroid hormone replacement therapy for patients with hypothyroidism.

Anticholinergic effects. Carbamazepine exhibits moderate anticholinergic activity. Therefore, patients with increased intraocular pressure should be monitored during therapy.

Psychotic effects. It should be remembered that the probability of activation of latent psychosis in elderly patients - confusion or arousal.

Suicidal thoughts and behavior. Several reports of suicidal thoughts and behavior have been reported in patients receiving antiepileptic drugs. A meta-analysis of data from placebo-controlled studies of antiepileptic drugs also indicates a slight increase in the risk of suicidal thoughts and behavior. The mechanism for the occurrence of such a risk is unknown, and the available data do not exclude an increased risk of suicidal thoughts and behavior for carbamazepine.

Therefore, patients should be examined for suicidal thoughts and behavior, and if necessary, appropriate treatment should be prescribed. Patients (and caregivers) should be advised to see a doctor if signs of suicidal thoughts and behavior appear.

Endocrine effects. Due to the induction of liver enzymes, carbamazepine can cause a decrease in the therapeutic effect of estrogen and / or progesterone preparations. This can lead to decreased contraceptive effectiveness, relapse of symptoms, or breakthrough bleeding or spotting. Patients taking carbamazepine and for whom hormonal contraception is necessary should receive a drug containing at least 50 micrograms of estrogen, or alternative non-hormonal methods of contraception should be considered for such patients.

Monitoring the level of the drug in blood plasma. Despite the fact that the correlation between the dose and the level of carbamazepine in the blood plasma, as well as between the level of the carbamazepine in the blood plasma and the clinical efficacy and tolerability is not reliable, monitoring the level of the drug in the blood plasma may be appropriate in the following cases: with a sudden increase in the frequency of attacks, checking compliance the patient, during pregnancy, in the treatment of children and adolescents; with suspected violation of absorption, with suspected toxicity and the use of more than one drug.

Dose reduction and drug withdrawal syndrome. A sudden withdrawal of the drug can trigger seizures, so carbamazepine should be withdrawn gradually over a period of 6 months. If it is necessary to immediately discontinue the drug in patients with epilepsy, the transition to a new antiepileptic drug should be carried out against the background of therapy with appropriate drugs.

Use during pregnancy and lactation. Treatment with carbamazepine in pregnant women with epilepsy should be carried out with extreme caution.

In animals, oral administration of carbamazepine caused the development of defects.

In children whose mothers have epilepsy, a tendency to intrauterine developmental disorders, including congenital malformations, is revealed. It has been reported that carbamazepine, like most antiepileptic drugs, increases the frequency of these disorders, but there is no convincing evidence in controlled trials of carbamazepine monotherapy. At the same time, intrauterine developmental disorders and congenital malformations associated with carbamazepine were reported, including spina bifida and other congenital malformations, such as maxillofacial defects, cardiovascular malformations, hypospadias and malformations of various body systems.

Keep in mind the following data:

• the use of carbamazepine in pregnant women with epilepsy requires special attention;
• if a woman taking carbamazepine has become pregnant, is planning a pregnancy, or it is necessary to use carbamazepine during pregnancy, the potential benefits of using the drug should be carefully weighed against the possible risk (especially in the first trimester of pregnancy);
• women of reproductive age, if possible, carbamazepine should be prescribed as monotherapy;
• It is recommended to prescribe the minimum effective dose and monitor the level of carbamazepine in blood plasma;
• patients should be informed about the possibility of increasing the risk of congenital malformations and should be given the opportunity of prenatal screening;
• during pregnancy, effective antiepileptic therapy should not be interrupted, since an exacerbation of the disease threatens the health of both the mother and the baby.

Observation and prevention. It is known that during pregnancy, folic acid deficiency may develop. Antiepileptic drugs can increase the level of folic acid deficiency, therefore, they recommend the additional appointment of folic acid before and during pregnancy.

Newborns. In order to prevent coagulation disorders in newborns, it is recommended to prescribe vitamin K₁ mothers during the last weeks of pregnancy and newborns. Several cases of seizures and / or