The drug should be taken only with medical supervision.
Patients with mixed forms of epileptic seizures, including absence and myoclonic seizures
The drug is ineffective in absences (petit mal) and myoclonic seizures. In patients with mixed forms of epileptic seizures, the drug should be used with caution and only on condition that regular medical supervision is provided (due to possible increased seizures). In case of increased seizures, the drug should be discarded.
Leukopenia and thrombocytopenia
During the application of the drug at different frequencies, there is a transient or persistent decrease in the number of platelets or leukocytes.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 consult a doctor immediately if there are undesirable reactions such as fever, sore throat, rash, oral ulcers, an unreasonable occurrence of hemorrhages, haemorrhages in the form of petechiae or purpura.
In those cases when the low content of leukocytes or platelets (or the tendency to decrease them) during the treatment, it is necessary to closely monitor the patient's condition and the parameters of the developed clinical blood test. If signs of significant bone marrow suppression are revealed, the drug should be canceled.
Dermatological reactions
With the use of carbamazepine, very severe dermatological reactions were very rare, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome). The drug should be immediately withdrawn and alternative therapy should be selected if there are signs and symptoms presumably indicative of the development of severe dermatological reactions - for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 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 frequency of dermatological reactions in patients who first take the drug in countries with predominantly european population is from 1 to 6 per 10 000 cases of the drug.
Retrospective analysis data from patients of Japanese nationality and inhabitants of Northern Europe demonstrated a link between severe skin lesions (Stevens-Johnson syndrome, Lyell syndrome,drug rash with eosinophilia and systemic manifestations, acute generalized exanthematous pustulosis and patchy-nodular rash) in carriers of the HLA-A * 3101 allele of the human leukocyte antigen (HLA) gene and the use of carbamazepine.
The frequency of the HLA-A * 3101 allele may differ for different ethnic groups. The allele frequency is less than 5% in the population of Europe, Australia, Asia, Africa and North America, exceptions range from 5% to 12%. The frequency of more than 15% is found in some ethnic groups of South America (Argentina and Brazil), the indigenous peoples of North America (the Navajo and Siocs, Sanora Seri in Mexico), South India (Tamil Nadu), and 10-15% among other indigenous people these regions.
When prescribing carbamazepine, it is recommended that the HLA-A * 3101 allele carriers (for example, Japanese patients, Caucasians, Native Americans, Hispanics, people of southern India and Arabs) be genotyped with this allele. Prescribe the drug carriers of this allele should be only if the benefit of therapy exceeds the possible risk.
Patients already receiving therapy with the drug,it is not recommended to carry out genotyping on this allele, since severe skin reactions in most cases were noted in the first months of application (regardless of the presence of HLA-A * 3101).
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.
When carbamazepine is used in countries of the Asian region (Thailand, Malaysia, Philippines), where the prevalence of the HLA-B * 1502 allele is noted, an increase in the incidence of severe dermatological reactions (from the gradation "very rare" to "rarely"), including Stevens syndrome -Johnson and Lyell's syndrome.
The frequency of 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, 2-4% in South Asia (including India) in Japan and Korea - less than 1%. The prevalence of this allele among Caucasians, Negroid, Latino and Native Americans is negligible.
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 humans of Caucasoid, Negroid races, Hispanics and Native Americans, genotyping of the HLA-B * 1502 allele prior to prescribing is not necessary.
Patients who are already receiving therapy with the drug are not recommended to carry out genotyping for this allele, since severe skin reactions in most cases were noted in the first months of application (regardless of the presence of HLA-B * 1502.
It has been shown that the identification of patients with the presence of the HLA-B * 1502 allele and the lack of prescription of carbamazepine in such patients reduces the incidence of carbamazepine-induced Stevens-Johnson syndrome or Lyell syndrome.
However, the results of genotyping should not affect the degree of control over the patient's condition and the doctor's vigilance regarding severe skin reactions. The development of severe skin lesions is possible in patients who are negative for these alleles.Also in many cases, patients with positive HLA-B * 1502 or HLA-A * 3101 alleles did not develop severe skin syndrome with carbamazepine.
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 and prevalence of severe skin reactions has not been established.
Slightly expressed skin reactions, for example, isolated macular or maculopapular exanthema, in most cases are transient and non-severe, usually occur for several days or weeks with continued treatment or after a reduction in the dose of the drug.
Nevertheless, since differential diagnosis between early manifestations of severe skin reactions and mild skin transient skin rashes can be difficult, with the development of any skin reactions the patient should be under the supervision of a physician in order to timely stop therapy with the drug in case of deterioration of the patient's condition.
There is a correlation between the presence of the HLA-A * 3101 allele in the genome and the development of less severe skin reactions (such as hypersensitivity syndrome to anticonvulsant or mildly dense muculopapular exanthema), for the HLA-B * 1502 allele such a relationship is not established.
Hypersensitivity reactions
With the development of hypersensitivity to carbamazepine, patients can be observed as separate lesions of the skin, liver (including damage to the intrahepatic ducts), blood and lymphatic systems or other organs, and their combination, which should be considered as a systemic reaction. In case of development of symptoms and symptoms of hypersensitivity to the drug, it should be immediately canceled.
Patients with known hypersensitivity to carbamazepine should be informed about the possibility of 25-30% of cases of development of hypersensitivity reactions to oxcarbazepine. Cross-reactivity hypersensitivity is also found between carbamazepine and phenytoin.
Dysfunction of the liver
Before the appointment of the drug and during the treatment it is necessary to conduct a study of 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 with the appearance of active liver disease carbamazepine should be immediately canceled.
Renal impairment
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.
M-holinoblocking activity
The drug has a weak m-cholinoblocking activity. In the case of using the drug in patients with increased intraocular pressure, continuous monitoring of this indicator is necessary. It is necessary to control the retention of urine in patients.
Mental disorders
Since the use of the drug may exacerbate latent mental disorders, care should be taken to monitor elderly patients for the purpose of identifying such symptoms as confusion and psychomotor agitation.
Suicidal behavior or intentions
In patients who received anticonvulsants for a number of indications, there were cases of suicidal behavior or intentions. The results of a meta-analysis of randomized placebo-controlled trials showed a slight increase in riskthe development of suicidal behavior in patients receiving anticonvulsant drugs. The mechanism of strengthening suicidal behavior in this category of patients is not established. Therefore, it is necessary to carefully monitor the symptoms of suicidal behavior and intentions and to decide on the appropriate treatment. Patients or caregivers should be strongly advised to seek help from a doctor in case of symptoms of suicidal behavior or intent.
Endocrinological disorders
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.
To date, very rare reports of male fertility impairment and / or spermatogenesis disorders have been recorded.
Hypothyroidism
Carbamazepine can cause a decrease in thyroid hormone levels (triiodothyronine and thyroxine) and an increase in the concentration of thyroid-stimulating hormone, which increases the risk of hypothyroidism, and therefore the determination of thyroid hormone levels during treatment with carbamazepine is appropriate.In patients receiving substitution therapy with thyroid hormone drugs, carbamazepine may increase the risk of developing subclinical or overt hypothyroidism, so these patients should be monitored for thyroid function in the early stages of carbamazepine treatment.
Hyponatremia
When carbamazepine was used, cases of hyponatremia were noted. In most cases, hyponatremia proceeds asymptomatically. However, in some patients it can manifest clinically in the form of weakness, dizziness, lethargy, confusion, absent-mindedness, irritability. TO Symptoms of hyponatremia may also include drowsiness, fainting and coma. The severity of the hyponatremic effect correlates with the dose being taken, the high therapeutic or toxic concentration of carbamazepine in the blood plasma, and the low baseline sodium level. It is advisable to measure the level of sodium in the plasma before starting therapy with carbamazepine. The main method for the treatment of hyponatremia is to reduce the dose or abolish carbamazepine. which is usually enough to normalize the sodium level.Depending on the concentration of sodium, it may be necessary to limit the intake of fluid or in severe cases - the introduction of hypertonic solution. In this case, it is necessary to take into account the risk of developing central myelinolysis (necrosis) of the variolium bridge. In case of suspicion of newly diagnosed epilepsy, an alternative anticonvulsant (sodium valproate, phenytoin) should be prescribed.
Determination of the concentration of carbamazepine in the blood plasma
Although the relationship between the dose of the drug, the concentration of carbamazepine in plasma and its clinical efficacy or tolerability is very small, however, the regular definition of carbamazepine concentrations may be appropriate in the following situations: a sharp increase in the frequency of attacks, in order to check whether the patient takes a drug due way; during pregnancy; when treating children or adolescents; with suspected carbamazepine absorption abnormalities; if there is a suspected development of toxic reactions in the event that the patient takes several medications. The therapeutic concentration of carbamazepine in blood plasma is 4-12 μg / ml (17-50 μmol / g).
Alcohol consumption
For the duration of therapy, you must refrain from drinking alcohol. carbamazepine strengthens its depressing effect on the nervous system.