Instructions Finlepsin tablets 200 mg No. 50
Composition
active ingredient: carbamazepine;
1 tablet contains 200 mg of carbamazepine;
excipients: microcrystalline cellulose, gelatin, croscarmellose sodium, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: round white tablets with a double-sided bevel and a deep dividing line on one side, convex on the other side, with a smooth surface, solid edges and uniform appearance.
Pharmacotherapeutic group
Antiepileptics. Carboxamide derivatives. Carbamazepine. ATX code N03A F01.
Pharmacological properties
Pharmacodynamics
As an anticonvulsant: the spectrum of activity of Finlepsin® covers partial seizures (simple and complex) with and without secondary generalization, generalized tonic-clonic seizures, as well as combinations of these types of seizures.
The mechanism of action of carbamazepine, the active ingredient of the drug, is only partially understood. Carbamazepine stabilizes the membranes of overexcited nerve cells, inhibits the occurrence of repeated neuronal discharges, and reduces synaptic conduction of excitatory impulses. It is 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 the 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 the inhibition of dopamine and noradrenaline metabolism.
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 partly 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, Finlepsin® 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 clinical manifestations of the syndrome, such as excitability, tremor, gait disturbance. In patients with diabetes insipidus of central genesis, carbamazepine reduces diuresis and thirst.
It has been confirmed that as a psychotropic agent, Finlepsin® 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
Absorption. After oral administration, carbamazepine is absorbed somewhat slowly and almost completely. The half-life is 8.5 hours and has a large range (approximately 1.72-12 hours). After a single dose, the maximum concentration of carbamazepine in the blood plasma in adults is reached after 4-16 hours (very rarely - after 35 hours), in children - after approximately 4-6 hours. The concentration of carbamazepine in the blood plasma is not linearly dependent on the dose and when using higher doses, the plasma concentration curve has the form of a plateau.
Steady-state concentrations are reached after 2-8 days. There is no close correlation between the dose of carbamazepine and the steady-state plasma concentration.
Regarding therapeutic and toxic concentrations of carbamazepine in blood plasma, it is indicated that seizures may disappear at a plasma level of 4-12 μg/ml. Plasma concentrations of the drug exceeding 20 μg/ml worsen the picture of the disease.
At a concentration of the active substance in blood plasma of 5-18 mcg/ml, it eliminates pain in trigeminal neuralgia.
70-80% of carbamazepine is bound to plasma proteins. The fraction of carbamazepine not bound to proteins remains constant at a concentration of 50 μg/ml.
48-53% of the pharmacologically active metabolite carbamazepine-10,11-epoxide binds to plasma proteins. The concentration of carbamazepine in the cerebrospinal fluid is 33% of the concentration in plasma.
Carbamazepine penetrates the placental barrier and into breast milk.
In healthy people, the total plasma clearance is approximately 19.8 ml/h/kg, in patients with monotherapy - approximately 54.6 ml/h/kg, in patients with combination therapy - approximately 113.3 ml/h/kg. After a single oral dose of carbamazepine, 72% of the dose is excreted from the body by the kidneys in the form of metabolites. The remaining 28% is excreted in the feces, partly unchanged. Only 2-3% of the substance excreted in the urine is unchanged carbamazepine.
Features of pharmacokinetics in certain groups of patients.
Children: Due to the more rapid elimination of carbamazepine, children may require higher doses of carbamazepine (per kilogram of body weight) 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 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.
Finlepsin® 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
Finlepsin® should not be prescribed:
with established hypersensitivity to carbamazepine or to chemically similar drugs (such as tricyclic antidepressants), or to other components 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) and within 14 days after stopping their administration; in combination with voriconazole, as treatment may be ineffective.
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 carbamazepine concentrations and therapeutic effect. Similarly, discontinuation of a CYP3A4 inducer may decrease the rate of carbamazepine metabolism, 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.
Human microsomal epoxide hydrolase is the enzyme responsible for the formation of 10,11-transdiol derivatives of carbamazepine. Concomitant use of inhibitors of human microsomal epoxide hydrolase may lead to an increase in the concentration of carbamazepine-10,11-epoxide in the blood plasma.
Drugs that may increase carbamazepine plasma levels
Since an increase in the level of carbamazepine in the blood plasma may lead to undesirable reactions (such as dizziness, drowsiness, ataxia, diplopia), the dosage of the drug should be adjusted accordingly and/or its level in the blood plasma should be monitored when used simultaneously 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, viloxazine, trazodone.
Antiepileptic drugs: stiripentol, vigabatrin.
Antifungals: azoles (e.g., itraconazole, ketoconazole, fluconazole, voriconazole). Alternative antiepileptic agents may be recommended for patients receiving voriconazole or itraconazole treatment.
Antihistamines: terfenadine, loratadine.
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: verapamil, diltiazem.
Drugs for the treatment of gastrointestinal diseases: cimetidine, omeprazole.
Muscle relaxants: oxybutynin, dantrolene.
Antiplatelet drugs: ticlopidine.
Drugs that may increase the level of the active metabolite carbamazepine-10,11-epoxide in blood plasma
Since increased levels of the active metabolite carbamazepine-10,11-epoxide in the blood plasma may lead to the development of adverse reactions (e.g. dizziness, drowsiness, ataxia, diplopia), the dosage of carbamazepine should be adjusted accordingly and/or the plasma levels of the drug monitored if Finlepsin® is taken concomitantly with the following drugs: loxapine, quetiapine, primidone, progabide, valproic acid, valnoctamide and valpromide.
Drugs that may reduce carbamazepine plasma levels
Dose adjustment of Finlepsin® may be necessary when used simultaneously 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) and fosphenytoin, primidone, and clonazepam (although data on this are conflicting).
Anticancer drugs: doxorubicin, cisplatin.
Anti-tuberculosis drugs: rifampicin.
Bronchodilators or anti-asthma drugs: theophylline, aminophylline.
Dermatological drugs: isotretinoin.
Others: preparations containing St. John's wort (Hypericum perforatum).
Mefloquine may antagonize the antiepileptic effect of carbamazepine. The dose of carbamazepine should be adjusted accordingly.
Isotretinoin alters the bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide; plasma concentrations of carbamazepine should be monitored.
Effect of carbamazepine on 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 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), tramadol, phenazone (antipyrine).
Antibiotics: doxycycline, rifabutin.
Anticoagulants: oral anticoagulants (e.g., warfarin, phenprocoumon, dicumarol, acenocoumarol).
Antidepressants: bupropion, citalopram, mianserin, nefazodone, sertraline, trazodone, tricyclic antidepressants (e.g. imipramine, amitriptyline, nortriptyline, clomipramine).
Antiemetics: aperpitant.
Antiepileptic drugs: clobazam, clonazepam, eslicarbazepine, ethosuximide, felbamate, primidone, lamotrigine, oxcarbazepine, tiagabine, topiramate, valproic acid, zonisamide. Under the influence of carbamazepine, plasma concentrations of phenytoin may increase or decrease. In exceptional cases, this may cause a state of confusion and even coma. There are few reports of increased plasma concentrations of mephenytoin.
Antifungals: voriconazole, itraconazole, 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, risperidone, quetiapine, ziprasidone, aripiprazole, paliperidone.
Antiviral drugs: protease inhibitors for the treatment of HIV (e.g. ritonavir, indinavir, saquinavir).
Anxiolytics: midazolam, alprazolam.
Bronchodilators or anti-asthma drugs: theophylline.
Contraceptives: Hormonal contraceptives. In patients using hormonal contraceptives, contraceptive efficacy may be reduced and breakthrough bleeding may occur. Therefore, alternative methods of contraception should be considered.
Cardiovascular drugs: calcium channel blockers (dihydropyridine group), e.g. felodipine, digoxin, isradipine, 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.
Others: 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).
Carbamazepine may antagonize the effects of non-depolarizing muscle relaxants (e.g. pancuronium). The dose 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.
Concomitant use of carbamazepine with direct-acting oral anticoagulants (rivaroxaban, dabigatran, apixaban, edoxaban) may lead to a decrease in the plasma concentration of direct-acting oral anticoagulants, thereby increasing the risk of thrombosis. Therefore, if concomitant use is necessary, the patient should be carefully monitored for signs and symptoms of thrombosis.
Other interactions
Neurotoxic effects may be enhanced by concomitant use of carbamazepine and lithium salts. Careful monitoring of the concentration of both drugs is necessary. Patients should not take neuroleptics for 8 weeks before starting treatment with carbamazepine, as well as during treatment with carbamazepine.
Particular attention should be paid to the following symptoms of neurotoxicity: unsteady gait, ataxia, horizontal nystagmus, excessive reflexes, muscle spasm.
There are reports in the literature that when taking carbamazepine in patients using neuroleptics, the risk of developing neuroleptic malignant syndrome or Stevens-Johnson syndrome increases.
Carbamazepine may increase the elimination of thyroid hormones, thereby increasing the need for these hormones in patients with thyroid insufficiency. Thyroid hormone concentrations should be determined at the beginning and end of treatment in patients receiving thyroid hormone replacement therapy. Adjustment of the hormone dose may be necessary. Thyroid function may be altered, especially during concomitant administration of carbamazepine and other antiepileptic drugs (such as phenobarbital).
In the case of simultaneous use of carbamazepine with serotonin reuptake inhibitors (for example, fluoxetine), serotonin syndrome may develop.
Finlepsin® should not be used in combination with nefazodone (an antidepressant), as it may cause a significant decrease in the concentration of nefazodone in the blood plasma and a complete loss of its effectiveness. When nefazodone and Finlepsin® are taken simultaneously, the concentration of carbamazepine in the blood plasma increases and the concentration of its active metabolite, carbamazepine-10,11-epoxide, decreases.
Concomitant use of carbamazepine with antiarrhythmic drugs, cyclic antidepressants, or erythromycin increases the risk of cardiac conduction disorders.
Contraindicated interaction
Since carbamazepine is structurally similar to tricyclic antidepressants, Finlepsin® is not recommended for use simultaneously with MAO inhibitors. At least two weeks should elapse between the start of carbamazepine and the end of MAO inhibitors, or more if the patient's clinical condition allows.
Impact on serological studies
Carbamazepine may give a false-positive result in HPLC (high-performance liquid chromatography) assays for perphenazine concentration.
Carbamazepine and carbamazepine-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 subject to careful monitoring in patients with cardiac, hepatic or renal disorders, with impaired sodium metabolism, myotonic dystrophy, adverse hematological reactions to other drugs in history, or 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 psychoses, and in elderly patients, the possible activation of confusion and the development of anxiety.
The drug is usually ineffective in absence (petit mal) and myoclonic seizures. Individual cases indicate that patients with atypical absence seizures may experience an increase in seizures. Finlepsin® should not be used in patients with absence seizures.
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 haemorrhage or haemorrhagic purpura, they should seek immediate medical attention.
The morphological composition of the blood should be checked before starting treatment, then checked for a month at weekly intervals and then once a month. After 6 months of treatment, 2-4 tests per year are sufficient. 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 also be performed regularly. Carbamazepine treatment should be discontinued if the patient develops leukopenia that is severe, progressive, or accompanied by clinical manifestations, such as fever or sore throat. Carbamazepine should be discontinued if signs of bone marrow suppression appear.
Periodically or frequently, a temporary or persistent decrease in the number of platelets or leukocytes is noted in connection with the use of carbamazepine. However, for most of these cases, their transience is confirmed and they do not indicate the development of aplastic anemia or agranulocytosis. Before starting therapy and periodically during it, a blood test should be performed, including determining the number of platelets (and, possibly, the number of reticulocytes and hemoglobin levels). Treatment should be discontinued if leukopenia (mainly neutropenia), thrombocytopenia, including that accompanied by symptoms of allergy, fever, sore throat, skin bruising or hemorrhages.
Due to the occurrence of the undesirable reactions mentioned above and hypersensitivity reactions, it is necessary to monitor the morphological composition of the blood, kidney and liver function, the concentration of carbamazepine in the blood and the concentration of other anticonvulsants during combination therapy, especially during long-term treatment.
Blood tests at short intervals (weekly) are required in the event of: fever, infection, skin rash, fatigue, sore throat, mouth ulcers, bruising, increased aminotransferase activity, decreased leukocyte count <3000/mm3 or granulocyte count <1500/mm3, decreased platelet count <125000/mm3, decreased reticulocyte count <0.3% = 20000/mm3, increased plasma iron concentration >150 mcg%.
Carbamazepine discontinuation is required in the event of: bruising or purpuric bleeding, liver failure, decreased red blood cell count <4,000,000/mm3, decreased hematocrit <32%, decreased hemoglobin concentration below 11 g/dL, decreased leukocyte count <2,000/mm3 and, accordingly, granulocytes <1,000/mm3 or platelets <80,000/mm3, symptomatic hematopoietic disorders.
Serious dermatological reactions. Serious dermatological reactions, including toxic epidermal necrolysis (TEN) or Lyell's syndrome and
Stevens-Johnson syndrome (SJS) is a rare event with carbamazepine. Patients with serious dermatological reactions may 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, such as SJS, Lyell's syndrome/TEN (such as progressive skin rash with blistering or mucosal lesions), carbamazepine should be discontinued immediately and alternative therapy should be instituted. Patients should be advised of the signs and symptoms suggestive of a hypersensitivity reaction and monitored closely for skin reactions.
The best results in the treatment of SCD and TEN are achieved through early detection and immediate discontinuation of all medications that may be causing them. Early discontinuation is associated with better prognosis.
If a patient develops carbamazepine-related SCD or TEN, carbamazepine treatment should not be restarted.
Pharmacogenomics
There is increasing evidence that different HLA alleles influence a patient's susceptibility to immune-related adverse reactions.
Linkage with (HLA)-B*1502
Patients considered to be genetically at risk should be tested for the presence of carbamazepine before starting treatment.
(HLA)-B*1502 allele. If a patient tests positive for the (HLA)-B*1502 allele, carbamazepine treatment 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 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 in patients with the (HLA)-B*1502 allele should be avoided if other, alternative therapies are available. Genetic screening is generally not recommended for patients with ethnicities with a low incidence of the (HLA)-B*1502 allele. Screening is generally not recommended for individuals already receiving carbamazepine, as the risk of SCD/TEN is largely limited to the first few months, regardless of whether the patient has the (HLA)-B*1502 allele.
In Caucasian patients, there is no association between the (HLA)-B*1502 allele and the occurrence of SSc.
Relationship with (HLA)-A*3101
Human leukocyte antigen may be a risk factor for the development of cutaneous adverse reactions such as SJS, TEN, drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and maculopapular rashes in individuals of European descent and Japanese people.
The frequency of the HLA-A*3101 allele varies significantly among ethnic groups. Among Europeans, it is 2-5%, and among Japanese, it is ≈10%.
The presence of the HLA-A*3101 allele may increase the risk of skin reactions (mostly mild) from 5% overall among all patient groups to 26% in individuals of European descent, while the absence of this allele may reduce the risk mentioned above from 5% to 3.8%.
If the analysis reveals the presence of the HLA-A*3101 allele, then the use of carbamazepine should be avoided.
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. 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 adverse skin reactions to carbamazepine, such as anticonvulsant hypersensitivity syndrome or minor rashes (maculopapular rash). However, the presence of (HLA)-B*1502 has not been shown to be associated with the risk of the aforementioned skin reactions.
During treatment with carbamazepine, patients should avoid exposure to the sun due to photosensitivity.
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 intrahepatic bile ducts), which may occur in various combinations.
Other organs (lungs, kidneys, pancreas, myocardium, colon) may also be affected.
Patients with hypersensitivity reactions to carbamazepine should be informed that approximately 25-30% of such patients may also have hypersensitivity reactions to oxcarbazepine.
In general, if signs and symptoms suggestive of hypersensitivity appear, carbamazepine should be discontinued immediately.
Cross-hypersensitivity may occur when carbamazepine is used with aromatic antiepileptic drugs (e.g. phenytoin, primidone and phenobarbital).
Seizures: Carbamazepine should be used with caution in patients with mixed seizures that include absences (typical or atypical). In such circumstances, the drug may precipitate seizures. If seizures are precipitated, carbamazepine should be discontinued immediately.
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. In case of exacerbation of liver function disorders or in patients with active 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 (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 are very rare. If signs and symptoms of hepatic dysfunction or active liver disease occur, the patient should be evaluated urgently and carbamazepine treatment should be discontinued until the results of the evaluation are available.
Renal function: It is recommended to assess renal function, urinalysis, and 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. Fluid intake should be restricted in this case.
Hypothyroidism: Carbamazepine may reduce thyroid hormone levels, therefore, an increase in the dose of thyroid hormone replacement therapy is necessary for patients with hypothyroidism.
Anticholinergic effects. Carbamazepine exhibits moderate anticholinergic activity. Therefore, patients with elevated intraocular pressure and urinary retention should be closely monitored during therapy. Intraocular pressure should be measured regularly in patients with glaucoma.
Psychiatric effects: The possibility of activation of latent psychosis and, in elderly patients, confusion or agitation should be borne in mind.
Caution: If carbamazepine is used to prevent seizures in alcohol withdrawal syndrome, the drug should always be used in a hospital setting.
It should be noted that the side effects of carbamazepine may be similar to symptoms of alcohol withdrawal. This should be borne in mind when treating patients with alcohol withdrawal syndrome with Finlepsin®.
Suicidal ideation and behavior. There have been several reports of suicidal ideation and behavior in patients receiving antiepileptic drugs. A meta-analysis of placebo-controlled trials of antiepileptic drugs 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 persons
