Instructions for Carbamazepine-Zdorovye tablets 200 mg blister No. 20
Composition
active ingredient: carbamazepine;
1 tablet contains carbamazepine 200 mg;
Excipients: lactose monohydrate, microcrystalline cellulose, copovidone, povidone, croscarmellose sodium, calcium stearate, sodium lauryl sulfate.
Dosage form
Pills.
Main physicochemical properties: white or almost white tablets, flat-cylindrical, with a score and a bevel.
Pharmacotherapeutic group
Antiepileptics. Carboxamide derivatives. ATX code N03A F01.
Pharmacological properties
Pharmacodynamics
As an anticonvulsant: the spectrum of activity of the drug as an antiepileptic drug covers: partial seizures (simple and complex) with and without secondary generalization; generalized tonic-clonic seizures, as well as combinations of the above types of seizures.
The mechanism of action of carbamazepine, the active substance of the drug, is only partially understood. Carbamazepine stabilizes the membranes of overexcited nerve fibers, inhibits the occurrence of repeated neuronal discharges and reduces synaptic conduction of excitatory impulses. It is quite possible that the main mechanism of action of the drug may be the prevention of the re-formation of sodium-dependent action potentials in depolarized neurons by blocking sodium channels, which depends on the duration of use and voltage.
While a reduction in glutamate release and stabilization of neuronal membranes may explain the drug's anticonvulsant effects, the antimanic effect of carbamazepine may be due to inhibition of dopamine and noradrenaline metabolism.
When used as monotherapy in patients with epilepsy (especially in children and adolescents), the psychotropic effect of the drug was noted, which was partially manifested by a positive effect on symptoms of anxiety and depression, as well as a decrease in irritability and aggressiveness. According to a number of studies, the effect of the drug on cognitive function and psychomotor performance was dose-dependent and was either questionable or negative. In other studies, a positive effect of the drug on indicators characterizing attention, learning ability and memory was noted.
As a neurotropic agent, the drug is effective in some neurological diseases: for example, it prevents pain attacks in idiopathic and secondary trigeminal neuralgia. In addition, the drug can be used to relieve neurogenic pain in various conditions, including spinal cord tuberculosis, post-traumatic paresthesias and post-herpetic neuralgia. In alcohol withdrawal syndrome, the drug increases the threshold of convulsive readiness (which is reduced in this condition) and reduces the severity of clinical manifestations of the syndrome, such as excitability, tremor, gait disturbance. In patients with diabetes insipidus of central genesis, the drug reduces diuresis and thirst.
It has been confirmed that as a psychotropic agent, the drug is effective in affective disorders, namely: for the treatment of acute manic states, for the maintenance treatment of bipolar affective (manic-depressive) disorders (both monotherapy and in combination with neuroleptics, antidepressants or lithium preparations).
Pharmacokinetics
After taking the tablets, carbamazepine is absorbed almost completely, although somewhat slowly. After a single dose of a regular tablet, Cmax in the blood plasma is reached after 12 hours. There are no clinically significant differences in the degree of absorption of the active substance after using different dosage forms of carbamazepine for oral administration. After a single oral dose of a tablet containing 400 mg of carbamazepine, the average Cmax of the unchanged active substance reaches about 4.5 μg/ml.
The bioavailability of various oral dosage forms of carbamazepine has been shown to be in the range of 85-100%.
Food intake does not significantly affect the rate and extent of absorption of carbamazepine.
Steady-state plasma concentrations of the drug are reached within 1-2 weeks, which depends on the individual characteristics of metabolism (autoinduction of liver enzyme systems by carbamazepine, heteroinduction by other drugs used simultaneously), as well as on the patient's condition, dose of the drug and duration of treatment. There are significant interindividual differences in the values of equilibrium concentrations in the therapeutic range: in most patients, these values range from 4 to 12 μg/ml (17-50 μmol/l). The concentrations of carbamazepine-10,11-epoxide (a pharmacologically active metabolite) reach almost 30% compared to the concentrations of carbamazepine.
Under the condition of complete absorption of carbamazepine, the apparent volume of distribution is from 0.8 to 1.9 l/kg. Carbamazepine penetrates the placental barrier. 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 part of the active substance not bound to proteins (20-30%). The concentration of carbamazepine in breast milk is 25-60% of its level in plasma.
Carbamazepine is metabolized in the liver mainly by the epoxy pathway, resulting in the formation of the main metabolites - 10,11-transdiol derivative and its conjugate with glucuronic acid. The main isoenzyme that provides the biotransformation of carbamazepine to carbamazepine-10,11-epoxide is cytochrome P450 3A4. As a result of these metabolic reactions, a "minor" metabolite is also formed - 9-hydroxy-methyl-10-carbamoyl acridane. After a single oral administration of carbamazepine, approximately 30% of the active substance is determined in the urine as end products of epoxy metabolism. Other important biotransformation pathways of carbamazepine lead to the formation of various monohydroxylate derivatives, as well as carbamazepine N-glucuronide, which is formed with the participation of uridylyl diphosphate glucuronosyltransferase (UGT2B7).
After a single oral dose, the T½ of unchanged carbamazepine is on average 36 hours, and after repeated doses, it is on average 16-24 hours (due to autoinduction of the liver monooxygenase system), depending on the duration of treatment. In patients who are simultaneously taking other drugs that induce the same liver enzyme system (e.g. phenytoin, phenobarbital), the T½ of carbamazepine is on average 9-10 hours.
The mean T½ of the 10,11-epoxide metabolite from plasma is approximately 6 hours after a single oral dose of the epoxide.
After a single oral dose of 400 mg carbamazepine, 72% of the dose is excreted in the urine and 28% in the feces. Almost 2% of the dose is excreted in the urine as unchanged drug and approximately 1% as the pharmacologically active metabolite 10,11-epoxide.
Features of pharmacokinetics in certain groups of patients.
Children: Due to the more rapid elimination of carbamazepine, children may require higher doses of carbamazepine on a mg/kg body weight basis compared to adults to maintain therapeutic drug concentrations.
Elderly patients: There is no evidence to suggest that the pharmacokinetics of carbamazepine are altered in elderly patients (compared to young adults).
Patients with impaired renal or hepatic function. There are no data on the pharmacokinetics of carbamazepine in patients with impaired renal or hepatic function.
Indication
Epilepsy: complex or simple partial seizures (with or without loss of consciousness) with or without secondary generalization; generalized tonic-clonic seizures; mixed forms of seizures.
The drug can be used as monotherapy or as part of combination therapy.
Acute manic states; maintenance therapy in bipolar affective disorders to prevent exacerbations or to reduce the clinical manifestations of an exacerbation. Alcohol withdrawal syndrome. Idiopathic trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis (typical and atypical). Idiopathic glossopharyngeal neuralgia.
Contraindication
The drug should not be prescribed:
with established hypersensitivity to carbamazepine or to chemically similar drugs (such as tricyclic antidepressants), or to any other component of the drug; with atrioventricular block; in patients with a history of bone marrow depression; in patients with a history of hepatic porphyria (e.g. acute intermittent porphyria, mixed porphyria, porphyria cutanea tarda); in combination with monoamine oxidase inhibitors (MAO).
Interaction with other medicinal products and other types of interactions
Cytochrome P450 3A4 (CYP3A4) is the main enzyme that catalyzes the formation of the active metabolite carbamazepine-10,11-epoxide. Concomitant use of CYP3A4 inhibitors may lead to increased plasma concentrations of carbamazepine, which in turn may lead to the development of adverse reactions. Concomitant use of CYP3A4 inducers may increase the metabolism of carbamazepine, resulting in a potential decrease in serum concentrations of carbamazepine and the therapeutic effect. Similarly, discontinuation of a CYP3A4 inducer may reduce the rate of metabolism of carbamazepine, resulting in increased plasma levels of carbamazepine.
Carbamazepine is a potent inducer of CYP3A4 and other phase I and phase II enzyme systems in the liver, and therefore may reduce plasma concentrations of other drugs that are predominantly metabolized by CYP3A4 by inducing their metabolism.
Drugs that may increase carbamazepine plasma levels. Since an increase in carbamazepine plasma levels may lead to adverse reactions (such as dizziness, drowsiness, ataxia, diplopia), the dosage of the drug should be adjusted accordingly and/or its plasma levels monitored when used concomitantly with the following drugs.
Analgesics, anti-inflammatory drugs: dextropropoxyphene, ibuprofen.
Androgens: danazol.
Antibiotics: macrolide antibiotics (e.g. erythromycin, troleandomycin, josamycin, clarithromycin), ciprofloxacin.
Antidepressants: desipramine, fluoxetine, fluvoxamine, nefazodone, paroxetine, trazodone, viloxazine.
Antiepileptics: stiripentol, vigabatrin.
Antifungals: azoles (e.g. itraconazole, ketoconazole, fluconazole, voriconazole). Alternative antiepileptic agents may be recommended for patients receiving voriconazole or itraconazole treatment.
Antihistamines: loratadine, terfenadine.
Antipsychotic drugs: olanzapine, loxapine, quetiapine.
Anti-tuberculosis drugs: isoniazid.
Antiviral drugs: protease inhibitors for HIV (e.g. ritonavir).
Carbonic anhydrase inhibitors: acetazolamide.
Cardiovascular drugs: diltiazem, verapamil.
Drugs for the treatment of digestive system diseases: cimetidine, omeprazole.
Muscle relaxants: oxybutynin, dantrolene.
Antiplatelet drugs: ticlopidine.
Other substances: grapefruit juice, nicotinamide (in adults, only in high doses).
Drugs that may increase the plasma levels of the active metabolite of carbamazepine-10,11-epoxide. Since increased plasma levels of the active metabolite of carbamazepine-10,11-epoxide may lead to the development of adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of the drug should be adjusted accordingly and/or the plasma levels of the drug should be monitored if the drug is taken concomitantly with the following drugs: loxapine, quetiapine, primidone, progabide, valproic acid, valnoctamide and valpromide.
Drugs that may reduce the plasma levels of carbamazepine. Dose adjustment of the drug may be necessary when used concomitantly with the following drugs.
Antiepileptic drugs: felbamate, methsuximide, oxcarbazepine, phenobarbitone, phensuximide, phenytoin (to avoid phenytoin intoxication and subtherapeutic carbamazepine concentrations, it is recommended to adjust the phenytoin plasma concentration to 13 μg/mL before starting carbamazepine treatment) and fosphenytoin, primidone, and clonazepam (although data on this are conflicting).
Anticancer drugs: cisplatin or doxorubicin.
Anti-tuberculosis drugs: rifampicin.
Bronchodilators or anti-asthma drugs: theophylline, aminophylline.
Dermatological drugs: isotretinoin.
Interaction with other substances: herbal preparations containing St. John's wort.
Mefloquine may antagonize the antiepileptic effect of the drug. Accordingly, the dose of the drug should be adjusted.
Isotretinoin has been reported to alter the bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide; plasma concentrations of carbamazepine should be monitored.
Effect of the drug on the plasma levels of concomitantly administered drugs. Carbamazepine may reduce the plasma levels of some drugs and reduce or eliminate their effects. Dosage adjustments of the following drugs may be necessary according to clinical requirements.
Analgesics, anti-inflammatory drugs: buprenorphine, methadone, paracetamol (long-term use of carbamazepine with paracetamol (acetaminophen) may be associated with the development of hepatotoxicity), phenazone (antipyrine), tramadol.
Antibiotics: doxycycline, rifabutin.
Anticoagulants: oral anticoagulants (e.g. warfarin, phenprocoumon, dicumarol and acenocoumarol).
Antidepressants: bupropion, citalopram, mianserin, nefazodone, sertraline, trazodone, tricyclic antidepressants (e.g. imipramine, amitriptyline, nortriptyline, clomipramine).
Antiemetics: aperpitant.
Antiepileptic drugs: clobazam, clonazepam, ethosuximide, felbamate, lamotrigine, oxcarbazepine, primidone, tiagabine, topiramate, valproic acid, zonisamide. Both increased and decreased phenytoin plasma levels due to carbamazepine have been reported, as well as isolated cases of increased mephenytoin plasma levels.
Antifungals: itraconazole, voriconazole, ketoconazole. Alternative antiepileptic agents may be recommended for patients receiving treatment with voriconazole or itraconazole.
Anthelmintic drugs: praziquantel, albendazole.
Anticancer drugs: imatinib, cyclophosphamide, lapatinib, temsirolimus.
Neuroleptic drugs: clozapine, haloperidol and bromperidol, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, paliperidone.
Antiviral drugs: protease inhibitors for the treatment of HIV (e.g. indinavir, ritonavir, saquinavir).
Anxiolytics: alprazolam, midazolam.
Bronchodilators or anti-asthma drugs: theophylline.
Cardiovascular drugs: calcium channel blockers (dihydropyridine group), e.g. felodipine, isradipine, digoxin, quinidine, propranolol, simvastatin, atorvastatin, lovastatin, cerivastatin, ivabradine.
Corticosteroids: in particular prednisolone, dexamethasone.
Drugs used to treat erectile dysfunction: tadalafil.
Immunosuppressants: cyclosporine, everolimus, tacrolimus, sirolimus.
Thyroid medications: levothyroxine.
Interaction with other drugs: drugs containing estrogens and/or progesterones (alternative methods of contraception should be considered); buprenorphine, gestrinone, tibolone, toremifene, mianserin, sertraline.
Drug combinations that require separate consideration: Concomitant use of carbamazepine and levetiracetam may lead to increased toxicity of carbamazepine.
Concomitant use of carbamazepine and isoniazid may lead to increased hepatotoxicity of isoniazid.
The simultaneous use of carbamazepine and lithium or metoclopramide, as well as carbamazepine and neuroleptics (haloperidol, thioridazine) may lead to increased neurological side effects (in the case of the latter combination, even at therapeutic levels in the blood plasma).
Combination therapy with the drug and some diuretics (hydrochlorothiazide, furosemide) may lead to symptomatic hyponatremia.
Carbamazepine may antagonize the effects of non-depolarizing muscle relaxants (e.g. pancuronium). Doses of these drugs may need to be increased and patients should be monitored closely because of the possibility of a more rapid than expected recovery from neuromuscular blockade.
Carbamazepine, like other psychotropic drugs, may reduce alcohol tolerance, so patients are advised to abstain from alcohol.
Contraindicated interaction. Since carbamazepine is structurally similar to tricyclic antidepressants, the drug is not recommended for use simultaneously with MAO inhibitors; before starting the drug, it is necessary to stop taking the MAO inhibitor (at least two weeks or earlier if clinical circumstances allow).
Effect on serological tests: Carbamazepine may give a false-positive result in HPLC (high-performance liquid chromatography) assays for perphenazine concentration.
Carbamazepine and 10,11-epoxide may give a false-positive result in the polarized fluorescence immunoassay for tricyclic antidepressant concentrations.
Application features
The drug 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 disorders, a history of hematological adverse reactions to other drugs, and patients with interrupted courses of carbamazepine therapy.
It is recommended to perform a complete urinalysis and determine the level of urea nitrogen in the blood at the beginning and at certain intervals during therapy.
The drug exhibits mild anticholinergic activity, therefore patients with increased intraocular pressure should be warned and advised about possible risk factors.
One should be aware of the possible activation of latent psychoses, and in elderly patients, the possible activation of confusion and anxiety.
The drug is usually ineffective in absence (petit mal) and myoclonic seizures. Anecdotal evidence suggests that increased seizures may occur in patients with atypical absences.
Hematological effects. Agranulocytosis and aplastic anemia have been associated with the use of the drug; however, the extremely low incidence of these conditions makes it difficult to estimate a significant risk with the drug. The overall risk for untreated patients is 4.7 persons/1,000,000 per year for agranulocytosis and 2 persons/1,000,000 per year for aplastic anemia.
Patients should be informed about the early signs of toxicity and symptoms of possible haematological disorders, as well as symptoms of dermatological and hepatic reactions. The patient should be warned that in the event of reactions such as fever, sore throat, skin rash, mouth ulcers, easy bruising, petechial haemorrhages or haemorrhagic purpura, they should seek medical advice immediately.
If the number of leukocytes or platelets decreases significantly during therapy, the patient's condition should be closely monitored and a complete blood count should be performed regularly. Treatment with the drug should be discontinued if the patient develops leukopenia that is severe, progressive, or accompanied by clinical manifestations, such as fever or sore throat. The drug should be discontinued if signs of bone marrow suppression appear.
Serious dermatological reactions. Serious dermatological reactions, including Lyell's syndrome (LS) and Stevens-Johnson syndrome (SJS), have been reported very rarely with the use of the drug. Patients with serious dermatological reactions may require hospitalization, as these conditions can be life-threatening and fatal. Most cases of SJS/LS occur within the first few months of treatment with the drug. If signs and symptoms suggestive of serious dermatological reactions (e.g. SJS, SL) develop, the drug should be discontinued immediately and alternative therapy should be instituted.
Pharmacogenomics: There is increasing evidence that different HLA alleles influence a patient's susceptibility to immune-related adverse reactions.
Association with (HLA)-B*1502. There are retrospective studies in Han Chinese patients that have shown a strong correlation between carbamazepine-associated cutaneous reactions of SS/SL and the presence of the human leukocyte antigen (HLA) allele (HLA)-B*1502 in these patients. A higher frequency of reports of SS (rare rather than very rare) is characteristic of some Asian countries (e.g. Taiwan, Malaysia and the Philippines), where the (HLA)-B*1502 allele is prevalent in the population. The number of carriers of this allele in the Asian population is more than 15% in the Philippines, Thailand, Hong Kong and Malaysia, approximately 10% in Taiwan, almost 4% in northern China, approximately 2% to 4% in South Asia (including India), and less than 1% in Japan and Korea. The prevalence of the (HLA)-B*1502 allele is insignificant among European, African, Native American, and Latin American populations.
Patients considered to be genetically at risk should be tested for the presence of the (HLA)-B*1502 allele before starting treatment with the drug. If a patient tests positive for the (HLA)-B*1502 allele, treatment with the drug should not be started unless there are no other therapeutic options. Patients who are tested and test negative for (HLA)-B*1502 are at low risk of developing SSc, although very rarely such reactions may still occur.
At this time, due to a lack of data, it is not known for sure whether all people of Southeast Asian descent are at risk.
The (HLA)-B*1502 allele may be a risk factor for the development of SS/SL in Chinese patients receiving other antiepileptic drugs that may be associated with the development of SS/SL. Therefore, the use of other drugs that may be associated with the development of SS/SL in patients with the (HLA)-B*1502 allele should be avoided if other, alternative therapies are available. Genetic screening of patients from ethnic groups with a low rate of the (HLA)-B*1502 allele is generally not recommended. Screening of patients already receiving the drug is generally not recommended because the risk of SS/SL is largely limited to the first few months, regardless of the presence of the (HLA)-B*1502 allele in the patient's genes.
In Caucasian patients, there is no association between the (HLA)-B*1502 allele and the occurrence of SSc.
Association with HLA-A*3101. Human leukocyte antigen may be a risk factor for the development of cutaneous adverse reactions such as SSRI, SL, DRESS, AGEP, maculopapular rashes. If the analysis reveals the presence of the HLA-A*3101 allele, the drug should be discontinued.
Limitations of genetic screening. Genetic screening results should not replace appropriate clinical monitoring and treatment of patients. Other possible factors such as antiepileptic drug dosage, adherence to therapy, and concomitant medications play a role in the occurrence of these severe skin adverse reactions. The impact of other diseases and the level of monitoring of skin disorders have not been studied.
Other dermatological reactions. Transient and non-life-threatening mild dermatological reactions, such as isolated macular or maculopapular exanthema, may also occur. They usually resolve within a few days or weeks, both with continued dosing and after dose reduction. Since early signs of more serious dermatological reactions may be difficult to distinguish from mild transient reactions, the patient should be closely monitored to ensure that the drug is discontinued promptly if the reaction worsens with continued use.
The presence of the HLA-A*3101 allele in a patient has been associated with the occurrence of less serious skin adverse reactions to carbamazepine, such as anticonvulsant hypersensitivity syndrome or minor rashes (maculopapular rashes). However, the presence of (HLA)-B*1502 has not been shown to be associated with the risk of these skin reactions.
The presence of the HLA-A*3101 allele in a patient is associated with the occurrence of less serious adverse skin reactions to carbamazepine, such as anticonvulsant hypersensitivity syndrome or minor rashes (maculopapular rashes).
Patients with hypersensitivity reactions to carbamazepine should be informed that approximately 25-30% of such patients may also have hypersensitivity reactions to oxcarbazepine.
When using carbamazepine and phenytoin, cross-hypersensitivity may develop.
In general, if signs and symptoms suggestive of hypersensitivity appear, the drug should be discontinued immediately.
Seizures. The drug should be used with caution in patients with mixed seizures that include absences (typical or atypical). In such circumstances, the drug may provoke seizures. If seizures are provoked, the drug should be discontinued immediately.
An increase in the frequency of attacks is possible when switching from oral forms of the drug to suppositories.
Liver function. During therapy with the drug, it is necessary to assess liver function at baseline and periodically assess this function during therapy, especially in patients with a history of liver disease and in elderly patients. In case of exacerbation of liver function disorders or in patients with an active phase of liver disease, the drug should be discontinued immediately.
Some laboratory tests used to assess liver function may be abnormal in patients taking carbamazepine, including gamma-glutamyltransferase. This is likely due to induction of liver enzymes. Enzyme induction may also result in a modest increase in alkaline phosphatase. This increase in liver function is not an indication for discontinuation of carbamazepine.
Severe hepatic reactions due to carbamazepine use are very rare. If signs and symptoms of hepatic dysfunction or active liver disease occur, the patient should be evaluated urgently and treatment with the drug should be discontinued until the results of the examination are available.
Renal function: It is recommended to assess renal function and determine blood urea nitrogen levels at the beginning and periodically during therapy.
Hyponatremia. Hyponatremia has been reported with carbamazepine. In patients with pre-existing renal impairment associated with low sodium levels or in patients receiving concomitant sodium-lowering medicinal products (such as diuretics, medicinal products associated with inappropriate antidiuretic hormone secretion), serum sodium levels should be measured before treatment. Thereafter, measurements should be performed every 2 weeks, then at monthly intervals for the first 3 months of treatment or as clinically indicated. This is particularly important in elderly patients. Fluid intake should be restricted in this case.
Hypothyroidism. Carbamazepine may reduce thyroid hormone concentrations, therefore, an increase in the dose of thyroid hormone replacement therapy is necessary for patients with hypothyroidism.
Anticholinergic effects. The drug exhibits moderate anticholinergic activity. Therefore, patients with increased intraocular pressure and urinary retention should be closely monitored during therapy.
Psychiatric effects: The possibility of activation of latent psychosis and, in elderly patients, confusion or agitation should be borne in mind.
Suicidal ideation and behavior. There have been several reports of suicidal ideation and behavior in patients receiving antiepileptic drugs. There is information about a meta-analysis of data obtained during placebo-controlled trials of antiepileptic drugs, which also showed a small increased risk of suicidal ideation and behavior. The mechanism of this risk is unknown, and the available data do not exclude an increased risk of suicidal ideation and behavior for carbamazepine.
Therefore, patients should be monitored for suicidal thoughts and behavior and, if necessary, treated appropriately. Patients (and caregivers of patients) should be advised to seek medical advice if signs of suicidal thoughts and behavior appear.
Monitoring of plasma drug levels. Although the correlation between dosage and carbamazepine plasma levels, and between carbamazepine plasma levels and clinical efficacy and tolerability, is uncertain, monitoring of plasma drug levels may be appropriate in the following situations: in case of a sudden increase in seizure frequency, to check patient compliance, during pregnancy, in the treatment of children and adolescents, in case of suspected malabsorption, in case of suspected toxicity, and when more than one drug is used.
Dose reduction and drug withdrawal. Abrupt withdrawal of the drug may precipitate seizures, so carbamazepine should be withdrawn gradually over 6 months. If abrupt withdrawal of the drug is necessary in patients with epilepsy, the switch to a new antiepileptic drug should be made against the background of therapy with appropriate drugs (e.g., diazepam intravenously, rectally, or phenytoin intravenously).
If the patient has been diagnosed with an intolerance to some sugars, contact your doctor before taking this medicinal product.
Ability to influence reaction speed when driving vehicles or other mechanisms
The ability of a patient taking the drug to react quickly (especially at the beginning of therapy or during the dose adjustment period) may be impaired due to dizziness and drowsiness, therefore the patient should be careful when driving a car or using other mechanisms.
Use during pregnancy or breastfeeding
In animals, oral administration of carbamazepine caused the development of defects.
Infants born to mothers with epilepsy are at increased risk of intrauterine growth retardation, including congenital malformations. Carbamazepine, like most antiepileptic drugs, has been reported to increase the incidence of these disorders, but there is no conclusive evidence from controlled trials of carbamazepine monotherapy. However, intrauterine growth retardation and congenital malformations have been reported in association with carbamazepine, including spina bifida and other congenital anomalies such as maxillofacial defects, cardiovascular malformations, hypospadias, and malformations of various body systems.
The following data should be kept in mind.
The use of the drug in pregnant women with epilepsy requires special attention. If a woman receiving the drug becomes pregnant, plans to become pregnant, or needs to use the drug during pregnancy, the potential benefit of using the drug should be carefully weighed against the possible risk (especially in the first trimester of pregnancy). Women of reproductive age should be prescribed the drug as monotherapy whenever possible. It is recommended to prescribe the minimum effective dose and monitor the level of carbamazepine in the blood plasma. Patients should be informed of the possible increased risk of developing congenital malformations and should be given the opportunity for antenatal screening. Effective antiepileptic therapy should not be interrupted during pregnancy, since exacerbation of the disease will threaten the health of both the mother and the child.
Monitoring and prevention. It is known that folic acid deficiency may develop during pregnancy. Antiepileptic drugs may increase the level of folic acid deficiency, therefore, additional folic acid administration is recommended before and during pregnancy.
Newborns. In order to prevent blood clotting disorders in newborns, it is recommended to prescribe vitamin K1 to mothers during the last weeks of pregnancy and to newborns.
There are several known cases of convulsions and/or respiratory depression in newborns, several cases of vomiting, diarrhea and/or poor appetite in newborns, which are associated with the use of the drug and other anticonvulsants.
Breastfeeding. Carbamazepine passes into breast milk (25-60% of plasma concentration). Benefits of breastfeeding with
