Instructions for Carbamazepine-Darnitsa tablets 200 mg No. 50
Composition
active ingredient: carbamazepine;
1 tablet contains carbamazepine 200 mg;
Excipients: microcrystalline cellulose, potato starch, povidone, colloidal anhydrous silicon dioxide, croscarmellose sodium, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: tablets of white or white with a creamy pink tint, flat-cylindrical shape, with a bevel and a score.
Pharmacotherapeutic group
Antiepileptic drugs. Carbamazepine. ATX code N03A F01.
Pharmacological properties
Pharmacodynamics
As an anticonvulsant, carbamazepine is effective in focal (partial) seizures (simple and complex), which are accompanied or not accompanied by secondary generalization, in generalized tonic-clonic seizures, as well as a combination of the above types of seizures.
The mechanism of action of carbamazepine is only partially understood. Carbamazepine stabilizes the membranes of overexcited nerve fibers, prevents 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 is to prevent the re-formation of sodium-dependent action potentials in depolarized neurons by blocking sodium channels, which depends on the duration of use and voltage.
Reduction of glutamate release and stabilization of neuronal membranes may explain the anticonvulsant effect of the drug; the antimanic effect of carbamazepine may be due to inhibition of dopamine and norepinephrine metabolism.
In clinical studies, when carbamazepine was 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 carbamazepine 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, carbamazepine is effective in some neurological diseases: for example, it prevents pain attacks in idiopathic and secondary trigeminal neuralgia. In addition, carbamazepine is used to relieve neurogenic pain in various conditions, including spinal cord tuberculosis, post-traumatic paresthesias and post-herpetic neuralgia. In alcohol withdrawal syndrome, carbamazepine increases the threshold for seizure readiness (which is reduced in this condition) and reduces the severity of such clinical manifestations of the syndrome as excitability, tremor, gait disturbance. In patients with diabetes insipidus of central genesis, the drug reduces diuresis and thirst.
It has been confirmed that carbamazepine as a psychotropic agent is effective in affective disorders: 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
Absorption. After ingestion, carbamazepine is absorbed almost completely, although somewhat slowly. After a single dose of the tablet, the maximum concentration in the blood plasma (Cmax) is reached after 12 hours. Clinically significant differences in the degree of absorption of the active substance after the use of different dosage forms of carbamazepine for oral administration are not noted. After a single dose of 400 mg of carbamazepine, the average Cmax value of the unchanged active substance reaches about 4.5 μg/ml.
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, depending 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, drug dose and duration of treatment. There are significant individual differences in the values of steady-state 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.
The bioavailability of different carbamazepine preparations may vary, which may lead to a reduced effect when using the drug or the risk of epileptic seizures while taking the drug or the occurrence of excessive side effects.
Metabolism. 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).
Elimination. After a single oral dose, the elimination half-life 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 elimination half-life of carbamazepine is on average 9-10 hours. The average elimination half-life of the 10,11-epoxide metabolite from blood plasma is approximately 6 hours after a single oral dose of the drug.
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 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 people).
Patients with renal or hepatic impairment: There are currently no data on the pharmacokinetics of carbamazepine in patients with renal or hepatic impairment.
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. Carbamazepine 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 exacerbations. Alcohol withdrawal syndrome. Idiopathic trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis (typical and atypical). Idiopathic glossopharyngeal neuralgia.
Contraindication
The medicine 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 catalyzing 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 adverse reactions. Concomitant use of CYP3A4 inducers may increase the metabolism of carbamazepine, resulting in a potential decrease in serum concentrations of carbamazepine and 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 the plasma concentrations of other drugs that are predominantly metabolized by CYP3A4 by inducing their metabolism.
Human microsomal epoxide hydrolase is the enzyme responsible for the formation of 10,11-transdiol derivatives of carbamazepine-10,11-epoxide. Concomitant use of inhibitors of human microsomal epoxide hydrolase may lead to an increase in the plasma concentration of carbamazepine-10,11-epoxide.
Drugs that may increase carbamazepine plasma levels.
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 the treatment of HIV (e.g. ritonavir).
Carbonic anhydrase inhibitors: acetazolamide.
Cardiovascular drugs: diltiazem, verapamil.
Drugs for the treatment of gastrointestinal 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 level of the active metabolite of carbamazepine-10,11-epoxide in blood plasma.
Since increased plasma levels of the active metabolite carbamazepine-10,11-epoxide may lead to adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), plasma levels of carbamazepine should be monitored and/or the dosage adjusted accordingly when co-administered with the following drugs: loxapine, quetiapine, primidone, progabide, valproic acid, valnoctamide and valpromide.
Drugs that may reduce the level of carbamazepine in the blood plasma.
Dose adjustment of the drug may be necessary when used concomitantly with the following drugs.
Antiepileptic drugs: felbamate, methsuximide, oxcarbazepine, phenobarbital, 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), 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 (changes the bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide; it is necessary to monitor the concentration of carbamazepine in the blood plasma).
Interaction with other substances: herbal preparations containing St. John's wort (Hypericum perforatum).
Mefloquine may antagonize the antiepileptic effect of carbamazepine and the dose of the drug may need to be adjusted accordingly.
The effect of carbamazepine on the plasma levels of concomitantly prescribed 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 as clinically indicated.
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). Concomitant use may result in decreased concentrations of oral anticoagulants, leading to a risk of thrombosis. Therefore, if concomitant use is necessary, closer monitoring for signs and symptoms of thrombosis is recommended.
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 have been reported with carbamazepine, and in isolated cases increased mephenytoin plasma levels have been reported. In exceptional cases, this may lead to confusion and even coma.
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.
Contraceptives: Hormonal contraceptives. In patients using hormonal contraceptives, contraceptive efficacy may be reduced and breakthrough bleeding may occur (alternative methods of contraception should be considered).
Cardiovascular drugs: calcium channel blockers (dihydropyridine group), e.g. felodipine, isradipine, digoxin, quinidine, propranolol, simvastatin, atorvastatin, lovastatin, cerivastatin, ivabradine.
Corticosteroids: 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 carbamazepine 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 will require close monitoring due to the possibility of a more rapid than expected recovery of 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, it is not recommended to use it 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).
Treatment in combination with voriconazole may be ineffective.
Impact on serological studies.
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
Carbamazepine should be prescribed only under medical supervision, only after assessing the benefit/risk ratio and with careful monitoring of patients with cardiac, hepatic or renal disorders, a history of haematological adverse reactions to other medicinal products 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.
Carbamazepine exhibits mild anticholinergic activity, therefore patients with elevated intraocular pressure should be warned and counseled about possible risk factors.
One should be aware of the possible activation of latent psychosis, and in elderly patients, the possibility of anxiety and activation of confusion.
The drug is usually ineffective in absence (petit mal) and myoclonic seizures. Individual cases indicate that increased seizures are possible in patients with atypical absences.
Hematological effects. The use of the drug is associated with the development of agranulocytosis and aplastic anemia. However, due to the fact that such conditions occur very rarely, it is difficult to assess the significance of the risk. It is known that the total risk of developing agranulocytosis in the general population not treated with carbamazepine reached 4.7 cases per 1 million population per year, and aplastic anemia - 2 cases per 1 million population per year.
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. Patients should be warned that in case of reactions such as fever, sore throat, skin rash, mouth ulcers, easy bruising, petechial haemorrhage or haemorrhagic purpura, they should seek medical advice immediately.
Periodically or frequently, a temporary or persistent decrease in platelet or leukocyte counts has been reported in association with carbamazepine. However, most of these cases have been confirmed to be transient and do not indicate the development of aplastic anemia or agranulocytosis. Before starting therapy and periodically during it, a blood test should be performed, including determination of the platelet count (and possibly the reticulocyte count and hemoglobin level).
Serious dermatological reactions. Serious dermatological reactions, including toxic epidermal necrolysis (TEN) or Lyell's syndrome and Stevens-Johnson syndrome (SJS), have occurred very rarely with carbamazepine. Patients with serious dermatological reactions require hospitalization, as these conditions can be life-threatening and fatal. Most cases of SJS/TEN occur within the first few months of carbamazepine treatment. If signs and symptoms suggestive of serious dermatological reactions (e.g., TSN, Lyell's syndrome/TEN) develop, carbamazepine 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.
Linkage with (HLA)-B*1502
Retrospective studies in Han Chinese patients have shown a strong correlation between carbamazepine-associated cutaneous reactions of SS/TEN and the presence of the human leukocyte antigen (HLA)-B*1502 allele 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 predominant 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 medicinal product. If a patient tests positive for the (HLA)-B*1502 allele, treatment with the medicinal product should not be initiated 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.
Until now, 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 SCD/TEN in Chinese patients receiving other antiepileptic drugs that may be associated with the development of SCD/TEN. Therefore, the use of other drugs that may be associated with the development of SCD/TEN should be avoided in patients with the (HLA)-B*1502 allele if other, alternative therapies are available. Genetic screening is not usually performed in patients of ethnicities with a low rate of the (HLA)-B*1502 allele or in cases where patients are already receiving carbamazepine, since the risk of SCD/TEN 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 serious dermatological reactions such as SJS, TEN, drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), maculopapular rash. If the test 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 treatment regimen, 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. These 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.
Hypersensitivity: Carbamazepine may cause hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms (DRESS), delayed-type multiple hypersensitivity reactions with fever, rash, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly, abnormal liver function tests, and vanishing bile duct syndrome (including destruction and disappearance of the intrabiliary ducts), which may occur in various combinations. Other organs (lungs, kidneys, pancreas, myocardium, large intestine) may also be affected.
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.
If signs and symptoms suggestive of hypersensitivity appear, the use of the medicinal product should be discontinued immediately.
Seizures: Carbamazepine should be used with caution in patients with mixed seizures that include absences (typical or atypical). In such circumstances, carbamazepine may precipitate seizures. If seizures are precipitated, 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 during therapy, especially in patients with a history of liver disease and in elderly patients. Patients with exacerbation of liver function disorders or patients with active liver disease should immediately discontinue the drug.
Some laboratory tests used to assess liver function may be abnormal in patients taking carbamazepine, including gamma-glutamyltransferase (GGT). 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 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. Measurements should then be made every 2 weeks, then at monthly intervals for the first 3 months of treatment or as clinically indicated. This is particularly true in elderly patients. In this case, water intake should be restricted.
Hypothyroidism: Carbamazepine may reduce thyroid hormone levels, and therefore, an increase in the dose of thyroid hormone replacement therapy may be 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 considered.
Endocrine effects. Due to the induction of liver enzymes, carbamazepine may cause a decrease in the therapeutic effect of estrogen and/or progesterone preparations. This may lead to reduced contraceptive efficacy, recurrence of symptoms, or breakthrough bleeding or spotting. Patients taking carbamazepine and for whom hormonal contraception is necessary should receive a preparation containing at least 50 mcg of estrogen, or alternative non-hormonal methods of contraception should be considered for such patients.
Monitoring of drug plasma levels. Although the correlation between dosage and carbamazepine plasma levels, and between carbamazepine plasma levels and clinical efficacy and tolerability of the drug, is uncertain, monitoring of its plasma levels may be appropriate in the following cases: 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 using more than one drug.
Dose reduction and drug withdrawal. Abrupt drug withdrawal may precipitate seizures, so carbamazepine should be withdrawn gradually over 6 months. If abrupt withdrawal of carbamazepine is necessary, patients with epilepsy should be switched to a new antiepileptic drug while receiving appropriate therapy (e.g., intravenous or rectal diazepam or intravenous phenytoin).
Important information about excipients.
This medicinal product contains sodium compounds, therefore caution should be exercised when administering it to patients on a controlled sodium diet.
Ability to influence reaction speed when driving vehicles or other mechanisms
The ability of a patient taking carbamazepine to react quickly (especially at the beginning of therapy or during the dose adjustment period) may be impaired due to dizziness and drowsiness, so the patient should be careful when driving a car or working with 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 studies of carbamazepine alone. Intrauterine growth retardation and congenital malformations have also 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 carbamazepine in pregnant women with epilepsy requires special attention. If a woman receiving carbamazepine becomes pregnant, plans to become pregnant, or needs to use the drug during pregnancy, the potential benefits of using the drug should be carefully weighed against the possible risks (especially in the first trimester of pregnancy). Women of reproductive age should be prescribed carbamazepine if possible.
