Finlepsin, tablets 200 mg 50 pcs

Indications

The drug Finlepsin® is generally ineffective in absences and myoclonus-epilepsy.

Active ingredient

Composition

How to take, the dosage

Ingestion. The drug may be taken with meals, after meals or between meals. Tablets should be taken with a small amount of liquid. The drug can be used both in monotherapy and in combination therapy.

With regard to drug interactions and pharmacokinetics of antiepileptic drugs, the dose of Finlepsin® should be adjusted with caution in elderly patients.

Epilepsy

The drug should be used in monotherapy whenever possible.

The drug is not used for minor seizures (petit mal, absans) and myoclonic seizures.

The treatment starts with a small daily dose, which is then slowly increased until optimal effect is achieved.

The dose of carbamazepine is adjusted individually to achieve adequate seizure control. To determine the optimal dose of the drug, plasma concentrations of the active ingredient are recommended, which are usually 4-12 µg/mL (17-50 µmol/L).

When Finlepsin® is added to other antiepileptic drugs being taken, the dose of Finlepsin® is increased gradually.

If necessary, the doses of the drugs taken are adjusted accordingly. The initial dose of carbamazepine for adults is 100-200 mg once or twice a day.

The dose is then slowly increased until optimal therapeutic effect is achieved; this is usually achieved at a dose of 400 mg 2-3 times daily. Some patients may need to increase the daily dose to 1600 mg or 2000 mg.

Ternal neuralgia

The starting dose for adults is 200-400 mg daily. It is slowly increased until the pain has disappeared (usually to a dose of 200 mg 3-4 times a day). Then the dose is gradually reduced to a minimum maintenance dose.

The maximum recommended dose for adults is 1200 mg/day. When pain resolves, therapy with the drug should be gradually discontinued until the next pain attack occurs.

The recommended starting dose for elderly patients is 100 mg 2 times daily, then the dose is slowly increased until pain resolves, which is usually achieved at a dose of 200 mg 3-4 times daily. Thereafter, the dose should be gradually reduced to the minimum maintenance dose.

In trigeminal neuralgia in this category of patients, the maximum recommended dose is 1200 mg/day. When pain resolves, therapy with the drug should be gradually discontinued until the next pain attack occurs.

Alcohol withdrawal syndrome

The average dose is 200 mg 3 times daily. In severe cases during the first few days the dose may be increased (for example, to a dose of 400 mg 3 times a day). In severe manifestations of alcohol withdrawal, treatment is started with the use of the drug in combination with drugs providing sedative and hypnotic effects (e.g., clomethiazole, chlordiazepoxide). After resolution of the acute phase, treatment with the drug may be continued in monotherapy.

Acute manic states and maintenance treatment of affective (bipolar) disorders

The daily dose is 400-1600 mg. The average daily dose is 400-600 mg (in 2-3 doses). In acute manic states, the dose should be increased rather quickly. In maintenance therapy of bipolar disorders, in order to ensure optimal tolerability, each subsequent dose increase should be small, the daily dose increasing gradually.

Application in children

The main indication for the use of Finlepsin® in children is epilepsy. This dosage form of the drug should be used to treat the same forms of epilepsy in children over 4 years of age as in adults. Treatment can be started with a dose of 100 mg/day; the dose is increased gradually, by no more than 100 mg per week.

Children 4 years of age and younger are recommended to take carbamazepine in other dosage forms (syrup).

Maintaining doses: for children set at 10-20 mg/kg body weight per day (in several doses).

Age of child

Daily dose

4-5 years

200-400 mg per day

4-5 years

200-400 mg per day/p>

6-10 years

400-600 mg per day

11-15 years

600-1000 mg per day

>15 years

800-1200 mg (as for adults)

Maximal doses: For children aged <6 years is 35 mg/kg/day, 6-15 years is 1000 mg/day, >15 years is 1200 mg/day.

Since there is insufficient reliable information about its use for other indications in children, it is recommended to choose the dosing regimen according to the age and body weight of the child and not to exceed the doses stated in the table.

Cessation of the drug

The sudden discontinuation of the drug may provoke an epileptic seizure, so carbamazepine should be withdrawn gradually over 6 months or more. If it is necessary to discontinue the drug in a patient with epilepsy, switching to another antiepileptic drug should be done under the cover of the drug indicated in such cases.

Interaction

Carbamazepine is not recommended to be used concomitantly with MAO inhibitors. MAO inhibitors should be discontinued at least 2 weeks before using the drug, or earlier if the clinical situation allows.

Cytochrome P4503A4 (CYP3A4) is the major isoenzyme responsible for the formation of carbamazepine-10,11-epoxide (active metabolite). Concomitant use of CYP3A4 isoenzyme inhibitors with the drug may increase the concentration of carbamazepine in blood plasma, which, in turn, may cause adverse reactions. Concomitant use of CYP3A4 isoenzyme inducers may lead to accelerated metabolism of carbamazepine and thus to a possible decrease in its plasma concentration and, consequently, to a possible reduction in therapeutic effect of the drug. Cancellation of simultaneously taken inducers of CYP3A4 isoenzyme may decrease the rate of biotransformation of carbamazepine, and as a consequence, lead to increased plasma concentrations of carbamazepine.

Carbamazepine is a potent inducer of CYP3A4 isoenzyme and other enzymatic hepatic systems of the first and second phase of drug metabolism, and when used simultaneously with drugs metabolized by CYP3A4 isoenzyme, may cause induction of metabolism and decrease their plasma concentrations.

Because the conversion of carbamazepine-10,11-epoxide to carbamazepine-10,11-transdiol occurs via microsomal epoxide hydrolase, use of carbamazepine concomitantly with microsomal epoxide hydrolase inhibitors may lead to increased plasma concentration of carbamazepine-10,11-epoxide.

Drugs that may increase plasma concentrations of carbamazepine:

Because increased plasma concentrations of carbamazepine may lead to BP (e.g., dizziness, somnolence, ataxia, diplopia), in these situations the drug dose should be adjusted and/or plasma concentrations of carbamazepine should be determined regularly.

The drugs that may increase plasma concentrations of carbamazepine-10,11-epoxide are: loxapine, quetiapine, primidone, progabide, valproic acid, valnoktamide, and valpromide.

Because increased plasma concentrations of carbamazepine-10,11-epoxide may lead to adverse reactions (e.g., dizziness, somnolence, ataxia, diplopia), in these situations the drug dose should be adjusted and/or plasma concentrations of carbamazepine-10,11-epoxide should be determined regularly.

Drugs that may decrease plasma concentrations of carbamazepine:

The dose of carbamazepine may need to be adjusted if used concomitantly with the above drugs.

Influence of carbamazepine on plasma concentrations of drugs used as concomitant therapy

Concomitant use with carbamazepine may decrease plasma concentrations, decrease or even completely discontinue the effect of some drugs, and therefore the need to adjust the dose of the following drugs according to clinical guidelines should be considered:

Combinations to consider

In concomitant use of carbamazepine with levetiracetam, an increase in the toxic effects of carbamazepine has been noted in individual cases.

Increased hepatotoxicity caused by isoniazid has been reported in cases where it was used concomitantly with carbamazepine.

The combined use of carbamazepine and lithium or metoclopramide, as well as carbamazepine and neuroleptic agents (haloperidol, thioridazine) may increase the frequency of adverse neurological reactions (in the latter combination – even at therapeutic plasma concentrations of the active substances).

The concomitant use of carbamazepine with some diuretics (hydrochlorothiazide, furosemide) may lead to hyponatremia accompanied by clinical manifestations.

Carbamazepine may antagonize the action of nondepolarizing myorelaxants (e.g., pancuronium bromide). If this combination of drugs is used, it may be necessary to increase the dose of these myorelaxants; patients should be closely monitored, as the effects of myorelaxants may be reversed more rapidly than expected.

There have been reports of bleeding from the vagina between menstruation when concomitant use of the drug with hormonal contraceptives (breakthrough bleeding). The drug may reduce the effect of hormonal contraceptives due to induction of microsomal enzymes.

Carbamazepine, as well as other psychotropic drugs, may decrease the tolerance to alcohol. In this regard, it is recommended that the patient refrain from drinking alcohol.

The concomitant use of carbamazepine and oral direct anticoagulants (e.g., rivaroxaban, dabigatran, apixaban, edoxaban) may lead to decreased plasma concentrations of the oral direct anticoagulant, which leads to a risk of thrombosis. Thus, caution should be exercised for signs and symptoms of thrombosis when concomitant use of these drugs is necessary.

Influence on serologic studies

Carbamazepine may cause false positive results in determining the concentration of perphenazine by high-performance liquid chromatography.

Carbamazepine and 10,11-epoxide carbamazepine may cause false-positive tricyclic antidepressant concentrations by polarization fluorescence immunoassay.

Special Instructions

The drug should only be taken under medical supervision.

Patients with mixed forms of epileptic seizures including absans and myoclonic seizures.

The drug is generally ineffective in absences (petit mal) and myoclonic seizures. In patients with mixed forms of epileptic seizures the drug should be used with caution and only under condition of regular medical supervision (because of possible seizure aggravation). In case of seizures worsening Finlepsin® should be discontinued.

Decrease in platelet and leukocyte counts

A transient or persistent decrease in platelet or leukocyte counts with varying frequency is noted during carbamazepine use. However, in most cases these phenomena are transient and are not usually precursors to the onset of aplastic anemia or agranulocytosis. Clinical blood counts, including platelet counts and possibly reticulocyte counts, as well as determination of serum iron concentration should be performed before initiating treatment, and periodically during treatment.

The patient should be advised of early signs of toxicity inherent in likely hematologic abnormalities, as well as skin and liver symptoms. Patients should be advised to contact a physician immediately if they experience adverse reactions such as fever, sore throat, rash, oral ulcers, hemorrhages without cause, hemorrhages as petechiae or purpura.

If leukocyte or platelet counts decrease (or tend to decrease) during therapy, the patient should be closely monitored and parameters of a complete clinical blood count should be controlled. If the signs of significant bone marrow depression are found, Finlepsin® should be discontinued.

Dermatological reactions

Severe dermatological reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome), have been very rarely reported with the use of the drug.

The drug Finlepsin® should be immediately discontinued and an alternative therapy should be chosen if signs and symptoms are observed suggestive of severe dermatological reactions such as Stevens-Johnson syndrome or Lyell’s syndrome. If severe (in some cases life-threatening) skin reactions develop, the patient must be hospitalized. In most cases, Stevens-Johnson syndrome and Lyell’s syndrome developed in the first months of therapy with the drug. These reactions developed in approximately 1-6 cases per 10,000 first-time users of the drug in countries with predominantly Caucasian populations.

The retrospective analysis in Japanese and Northern European patients demonstrated an association between severe skin lesions (Stevens-Johnson syndrome, Lyell syndrome, DRESS syndrome, acute generalized exanthematous pustulosis, and blotchy-knot rash) in carriers of the HLA-A*3101 human leukocyte antigen (HLA) allele and carbamazepine use.

The frequency of the HLA-A*3101 allele may differ in different ethnic groups: about 2-5% in the European population, about 10% in the Japanese population. The frequency of this allele in the majority of populations in Australia, Asia, Africa and North America is less than 5%, with some exceptions ranging from 5-12%. The frequency of more than 15% is established in some ethnic groups of South America (Argentina and Brazil), in indigenous peoples of North America (Navajo and Sioux tribes, in Mexico – Sanora Ceri), in South India (Tamil Nadu), and 10-15% – among other indigenous peoples of these regions.

When using carbamazepine in possible carriers of the HLA-A*3101 allele (e.g., Japanese, Caucasian, Native American, Hispanic, South Indian, and Arab patients), genotyping for this allele is recommended. Use in carriers of this allele only if the benefit of therapy outweighs the possible risk.

Patients already receiving carbamazepine should not be genotyped for this allele because severe skin reactions were seen in most cases in the first months of use (regardless of the presence of HLA-A*3101).

A retrospective analysis of carbamazepine use in Chinese and Thai patients showed a correlation between the incidence of Stevens-Johnson syndrome and Lyell syndrome and the presence of the HLA-B*1502 allele in the patient’s genome. The frequency of this allele in patients of Chinese ethnicity is 2-12% and in patients of Thai ethnicity about 8%.

The use of carbamazepine in patients in countries in the Asian region (Taiwan, Malaysia, Philippines), where there is a high prevalence of the HLA-B*1502 allele, has been found to increase the frequency of development (grading from “very rare” to “rare”) of Stevens-Johnson syndrome. The frequency of HLA-B*1502 allele prevalence is: in the Philippines and among some populations in Malaysia – more than 15%. The prevalence of the HLA-B*1502 allele in Korea and India is 2% and 6%, respectively. The prevalence of this allele in persons of Caucasoid, Negroid, Hispanic, Native American and Japanese races is insignificant (< 1%).

The frequencies of these alleles represent the percentage of chromosomes in certain populations that carry the allele. This means that the percentage of patients carrying a copy of the allele in at least one of their two chromosomes is almost twice the frequency of the allele. Thus, the percentage of patients who might be at risk is almost twice the frequency of the allele.

When using carbamazepine in possible carriers of the HLA-B*1502 allele, genotyping for this allele is recommended. The drug should be used in carriers of this allele only if the benefit of therapy outweighs the possible risk. Genotyping is not recommended in ethnic groups with a low incidence of this allele in their populations.

Patients already receiving carbamazepine should not be genotyped for this allele because severe skin reactions were observed in most cases in the first months of use (regardless of the presence of HLA-B*1502).

The identification of patients with the HLA-B*1502 allele and not using carbamazepine in these patients has been shown to reduce the incidence of carbamazepine-induced Stevens-Johnson syndrome or Lyell syndrome.

However, the results of genotyping should not affect the degree to which the patient is monitored and the physician’s alertness to severe skin reactions. The development of severe skin lesions is possible in patients negative for these alleles. Also, in many cases, patients who are positive for HLA-B*1502 or HLA-A*3101 alleles have not developed severe skin syndromes when using carbamazepine.

The effect of other factors, such as anticonvulsant medication dose, patient compliance, concurrent therapy with other drugs, comorbidities, or level of dermatologic reaction control, on the incidence and prevalence of severe skin reactions has not been established.

Mild skin reactions, such as isolated maculopapular or maculopapular exanthema, are in most cases transient and not severe, usually resolving within a few days or weeks with continued treatment or after reduction of the drug dose. However, since differential diagnosis between early manifestations of severe skin reactions and mild transient skin rashes may be difficult, the patient should be kept under medical supervision if any skin reactions develop (with the goal of discontinuing therapy in a timely fashion if the patient’s condition worsens).

There is an association between the HLA-A*3101 allele in the genome and the development of less severe skin reactions (such as hypersensitivity to anticonvulsants or non-serious maculopapular exanthema); this relationship has not been established for the HLA-B*1502 allele.

Hypersensitivity reactions

. When patients develop hypersensitivity to carbamazepine, various reactions may occur, including DRESS syndrome, delayed multi-organ manifestations of hypersensitivity with the development of fever, skin rash, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly, changes in liver function parameters and bile duct destruction syndrome with decreased number, which may occur in any combination. Other internal organs (including lungs, kidneys, pancreas, myocardium, colon) may also be affected.

In case of signs and symptoms of hypersensitivity, the drug should be stopped immediately.

Patients with known hypersensitivity to carbamazepine should be informed of the possibility of 25-30% of cases of hypersensitivity reactions to oxcarbazepine.

The development of cross-sensitivity reactions between carbamazepine and aromatic antiepileptic drugs (e.g., phenytoin, pyrimidone and phenobarbital) is possible.

Hyponatremia

The development of hyponatremia is associated with the use of carbamazepine. In patients with pre-existing renal impairment connected with low sodium content in serum or in patients receiving concomitant medicines, which reduce sodium content (e.g. diuretics, medicines which influence on antidiuretic hormone secretion), serum sodium content should be determined before starting carbamazepine therapy. Thereafter, sodium content should be determined after about two weeks and then monthly for the first three months of therapy, or as clinically necessary. These risk factors are particularly common in elderly patients. If hyponatremia is present, fluid restriction is important to determine the condition if clinically indicated.

Hypothyroidism

Carbamazepine may decrease serum thyroid hormone concentrations by enzyme induction, which requires increasing the dose of replacement therapy drugs in patients with hypothyroidism. In this category of patients, monitoring of thyroid function is necessary to select the dose of drugs of substitution therapy.

Hepatic disorders

Hepatic function tests should be performed before and during the use of Finlepsin®, especially in patients with a history of liver disease and in elderly patients. Finlepsin® should be discontinued immediately if pre-existing liver function abnormalities worsen or if active liver disease develops.

Renal dysfunction

Before starting treatment with the drug and periodically during therapy, urinalysis and determination of blood urea concentration are recommended.

M-cholinoblocking activity

The drug has weak m-cholinoblocking activity. Therefore, patients with elevated intraocular pressure, prostatic hyperplasia, and urinary retention should be closely monitored when the above drugs are used concomitantly.

Mental disorders

As latent mental disorders may worsen with the use of the drug, elderly patients should be monitored for symptoms such as confusion and psychomotor agitation.

Suicidal behavior or intentions

Suicidal behavior or intentions have been reported in patients treated with anticonvulsants for several indications. Results of a meta-analysis of randomized placebo-controlled trials showed a small increase in the risk of suicidal behavior in patients receiving anticonvulsants. The mechanism of increased suicidal behavior in this patient population has not been established. Therefore, careful monitoring of suicidal behavior and intentional symptoms and decision making about appropriate treatment is necessary. Patients (and their caregivers) should be strongly encouraged to seek medical attention if symptoms of suicidal behavior or intentions occur.

Endocrinological disorders

Because of enzyme induction, carbamazepine may impair the therapeutic effect of oral contraceptives containing estrogens and/or progesterone. Patients with preserved reproductive potential should be advised to use alternative methods of contraception during therapy with the drug. Bleeding from the vagina between menstruations has been reported with concomitant use of the drug with hormonal contraceptives (breakthrough bleeding).

Pregnancy and patients with preserved reproductive potential

The use of the drug during pregnancy may be associated with a risk to the fetus (see section “Pregnancy and breastfeeding”). The use of the drug in pregnancy is possible only if the expected benefits justify the potential risks.

Pregnant patients and patients with preserved reproductive potential should be fully informed about the risks to the fetus associated with the potential teratogenic effects of carbamazepine (see section “Pregnancy and Breastfeeding”).

Patients with preserved reproductive potential should use reliable contraception during therapy and for 2 weeks after the last dose of the drug (see Endocrinologic Disorders, as well as the sections on Interaction with Other Drugs and Pregnancy and Breastfeeding.)

Determination of plasma carbamazepine concentration

While there is little relationship between drug dose, plasma carbamazepine concentration, clinical efficacy or tolerability, regular determination of carbamazepine concentration may nevertheless be appropriate in the following situations if there is a sudden increase in seizure frequency, to see if the patient is taking the drug properly; during pregnancy; when treating children or adolescents; if carbamazepine absorption disorders are suspected; if toxic reactions are suspected if the patient is taking multiple medications.

Falls

The drug therapy was accompanied by ataxia, dizziness, somnolence, hypotension, confusion, sedation (see Side effects), which may lead to falls and, consequently, to fractures or other injuries. In patients with concomitant diseases, conditions, or receiving concomitant drug therapy with drugs that may exacerbate the above effects, the risk of falls during long-term therapy with the drug should be regularly evaluated.

Influence on driving, operating machinery

The ability of a patient taking Finlepsin®

The ability to respond quickly, especially at the beginning of therapy or during dose adjustment, may be impaired by the disease itself (e.g., seizures) as well as by adverse events such as dizziness, drowsiness, ataxia, diplopia, accommodation disorder, and visual impairment. Patients should be advised of the possible dangers of driving and operating machinery.

Synopsis

Contraindications

With caution

In patients with a history of heart disease (including decompensated chronic heart failure), liver disease (including hepatic failure), renal disease (including renal failure), adverse hematologic reactions to other medications, or when previously treated with carbamazepine is discontinued, therapy should be given only after careful analysis of the relationship between the expected treatment effect and possible risk of therapy with careful regular monitoring of the patient.

The drug should be used with caution in patients:

Side effects

Certain types of adverse reactions (ARs), such as CNS (dizziness, headache, ataxia, drowsiness, fatigue, diplopia), digestive system (nausea, vomiting), and allergic skin reactions are very common or frequent, especially at the start of treatment with the drug or when using an excessively high initial dose of the drug or when treating older patients.

Dose-dependent HF usually resolves within a few days, either spontaneously or after a temporary reduction in the drug dose. The development of adverse CNS reactions may be a consequence of a relative overdose of the drug or significant fluctuations in plasma concentrations of the active substance. In such cases it is recommended to monitor the plasma concentration of the active substance.

The adverse drug reactions (ADRs) are grouped according to the MedDRA classification of organs and organ systems, within each group listed in decreasing order of frequency of occurrence. Within each group, the frequency of IUDs is listed in decreasing order of importance.

The following gradations were used to estimate the frequency of occurrence of various NLDs: “very often” – ≥1/10, “often” – ≥1/100 – < 1/10, “infrequently” – ≥1/1000 – < 1/100 “rarely” – ≥1/10000 – < 1/1000, “very rarely” – < 1/10000, including individual reports.

Psychiatric disorders: rarely – hallucinations (visual or auditory), depression, aggression, anxiety, agitation, confusion; very rarely – activation of psychosis.

Nervous system disorders: very common – ataxia, dizziness, somnolence; common – diplopia, headache; infrequent – abnormal involuntary movements (e.g., tremor, “fluttering” tremor (asterixis), muscle dystonia, tic), nystagmus; rarely – dyskinesia, oculomotor disorders, speech disorders (e.g., dysarthria, slurred speech), choreoathetosis, peripheral neuropathy, paresthesias, paresis; very rarely – malignant neuroleptic syndrome, aseptic meningitis with myoclonus and peripheral eosinophilia, dysgeusia.

Skin and subcutaneous tissue disorders: very often – urticaria, which can be significantly pronounced, allergic dermatitis; infrequently – exfoliative dermatitis; rarely – systemic lupus erythematosus, skin itching; very rare – Stevens-Johnson syndrome (classified as “rare” in some countries in Asia), toxic epidermal necrolysis (Lyell syndrome), photosensitization reactions, erythema multiforme, erythema nodosa, skin pigmentation disorders, purpura, acne, hyperhidrosis, alopecia, hirsutism.

Disorders of the blood and lymphatic system: very common – leukopenia; common – thrombocytopenia, eosinophilia; rare – leukocytosis, lymphadenopathy; very rare – agranulocytosis, aplastic anemia, pancytopenia, true erythrocytic aplasia, anemia, megaloblastic anemia, reticulocytosis, hemolytic anemia.

Agranulocytosis and aplastic anemia may develop while taking the drug. However, due to the fact that these conditions occur very rarely, it is difficult to quantify the risk of their occurrence. It is known that the cumulative risk of developing agranulocytosis in the general untreated population is 4.7 cases per 1 million population per year and aplastic anemia is 2.0 cases per 1 million population per year.

Disorders of the digestive system: very often – nausea, vomiting; often – dry mouth; infrequently – diarrhea, constipation; rarely – abdominal pain; very rarely – glossitis, stomatitis, pancreatitis.

Hepatic and biliary tract disorders: rarely – hepatitis of cholestatic, parenchymatous (hepatocellular) or mixed type, destruction of intrahepatic bile ducts with decreased number, jaundice; very rarely – liver failure, granulomatous liver damage.

Disorders of the immune system: rare – delayed-type multiple organ hypersensitivity with fever, skin rashes, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function indices and destruction of intrahepatic bile ducts with decreased number (the above manifestations occur in various combinations). Other organs may also be involved (e.g., lungs, kidneys, pancreas, myocardium, colon); very rarely – anaphylactic reaction, angioedema, hypogammaglobulinemia. In case of the above reactions of hypersensitivity the drug should be discontinued.

Cardiac disorders: rare – intracardiac conduction disorders; very rare – arrhythmia, atrioventricular block with syncope, bradycardia, chronic heart failure, exacerbation of coronary heart disease.

Vascular disorders: rare – arterial hypertension or hypotension; very rare – circulatory collapse, thrombophlebitis, thromboembolism (e.g., pulmonary embolism).

Endocrine system disorders: frequent – edema, fluid retention, increased body weight, hyponatremia and decreased blood osmolarity due to an effect similar to that of antidiuretic hormone, which in rare cases leads to water intoxication (dilution hyponatremia), accompanied by lethargy, vomiting, headache, disorientation and neurological disorders; very rare – galactorrhea, gynecomastia.

Disorders of metabolism and nutrition: rarely – folic acid deficiency, decreased appetite; very rarely – acute porphyria (acute intermittent porphyria and mixed porphyria), non-acute porphyria (late cutaneous porphyria).

Renal and urinary tract disorders: very rare – tubulointerstitial nephritis, renal failure, renal dysfunction (e.g., albuminuria, hematuria, oliguria, increased blood urea concentration/azotemia), urinary retention, frequent urination.

Gender and mammary gland disorders: very rarely – disorders of sexual function/erectile dysfunction, disorder of spermatogenesis (decreased sperm count and motility).

VIight organ disorders: often – accommodation disorders (including blurred vision); very rare – blurred lens, conjunctivitis.

Hearing and labyrinth disorders: very rare – hearing disorders, including tinnitus, hyperacusis, hypoacusis, changes in pitch perception.

Muscular and connective tissue disorders: rare – muscle weakness; very rare – disorders of bone metabolism (decreased plasma calcium and 25-hydroxycholecalciferol, leading to osteomalacia/osteoporosis), arthralgia, myalgia and muscle spasm.

Disorders of the respiratory system, chest and mediastinum organs: very rare – hypersensitivity reactions characterized by fever, shortness of breath, pneumonitis or pneumonia.

General disorders and disorders at the site of administration: very often – increased fatigue.

Laboratory and instrumental findings: very common – increase in gamma-glutamyltransferase activity (due to induction of hepatic enzymes), which usually has no clinical significance; common – increase in blood alkaline phosphatase activity; infrequent – increase in transaminase activity; very rarely – increase of intraocular pressure, increased concentration of cholesterol, including high density lipoprotein cholesterol and triglycerides, changes of thyroid function parameters – decrease of L-thyroxine concentration (free and bound fraction) and triiodothyronine, increased concentration of thyroid hormone, which is usually not accompanied with clinical manifestations, increased concentration of prolactin in blood.

Desirable phenomena detected in the post-registration period (reports were obtained from a population of uncertain size, so the frequency of occurrence cannot be determined, “frequency unknown”):

Infectious and parasitic diseases: reactivation of herpes simplex virus type 6. Disorders of the blood and lymphatic system: bone marrow failure.

Injuries, intoxications and complications of manipulation: falls (associated with ataxia, dizziness, somnolence, arterial hypotension, confusion, sedation caused by taking the drug).

Nervous system disorders: sedation, memory impairment.

Gastrointestinal tract disorders: colitis.

Immune system disorders: drug rash with eosinophilia and systemic manifestations (DRESS syndrome).

Skin and subcutaneous tissue disorders: acute generalized exanthematous pustulosis, lichenoid keratosis, onychomadesis.

Muscular and connective tissue disorders: bone fracture.

Laboratory and instrumental findings: decreased bone density.

If any of the side effects listed in the instructions are worsened, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

Overdose is usually manifested by CNS, cardiovascular and respiratory system symptoms, as well as the phenomena described under Side effects.

The following symptoms and complaints may occur in case of overdose.

Central nervous system: Depression of CNS functions; impaired consciousness, disorientation, somnolence, agitation, hallucinations, coma; blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (initially), hyporeflexia (later); convulsions, psychomotor disorders, myoclonus, hypothermia, mydriasis.

Respiratory system: respiratory depression, pulmonary edema.

Cardiovascular system: tachycardia, arterial hypotension or in some cases arterial hypertension, conduction disorders with enlarged QRS complex; cardiac arrest and fainting caused by cardiac arrest.

Gastrointestinal system: vomiting, delayed passage of food from the stomach, decreased motility of the colon.

Mineral system: urinary retention, oliguria or anuria; fluid retention; water intoxication (dilutional hyponatremia) due to the effect of carbamazepine similar to that of antidiuretic hormone.

Skeletal and muscular system: there are reports of rhabdomyolysis associated with carbamazepine use.

Changes in laboratory parameters: hyponatremia, possible metabolic acidosis, possible hyperglycemia, increased activity of muscle fraction of creatine phosphokinase.

Treatment

There is no specific antidote. Initial treatment should be based on the clinical condition of the patient; hospitalization is indicated. Plasma concentrations of carbamazepine are determined to confirm poisoning from this agent and assess the degree of overdose.

Gastric evacuation, gastric lavage, and activated charcoal are performed. Late evacuation of gastric contents may lead to delayed absorption and reappearance of intoxication symptoms during recovery. Symptomatic supportive treatment in the intensive care unit, monitoring of cardiac function, careful correction of water-electrolyte balance disorders are used.

Hemosorption with carbon sorbents is recommended. Hemodialysis is an effective method of treatment in carbamazepine overdose. There may be a recurrence of symptoms of overdose on the 2nd and 3rd day after its onset, which is due to delayed absorption of carbamazepine.

Pregnancy use

Pregnancy

Risk summary

. Carbamazepine rapidly crosses the blood-placental barrier and is found in high concentrations in fetal tissues, especially in the liver and kidneys.

Children of patients with epilepsy are more likely than others to have developmental abnormalities, including birth defects. Despite the lack of conclusive data from controlled studies about a causal relationship between these disorders and maternal carbamazepine monotherapy, cases of congenital diseases and malformations, including failure of vertebral arches (spina bifida and other congenital anomalies have been reported with the use of the drug: developmental defects of craniofacial structures, cardiovascular and other organ systems, and hypospadias.

According to the North American Pregnancy Registry, the incidence of gross malformations related to structural anomalies requiring surgical, medical, or cosmetic correction diagnosed within 12 weeks of birth was 3.0% in mothers who took carbamazepine as monotherapy in the first trimester and 1.1% in mothers who were not taking any anti-epileptic drugs.

Clinical significance

The treatment with Finlepsin® in pregnant women with epilepsy should be used with extreme caution.

If it is necessary to use the drug in pregnant women, and if pregnancy is diagnosed during the use of the drug, or if the patient plans to become pregnant, the balance of expected benefits and possible risks should be carefully evaluated, especially in the first trimester of pregnancy.

With sufficient clinical efficacy in patients with preserved reproductive potential, Finlepsin® should be used in monotherapy because the incidence of congenital fetal abnormalities is higher with combined antiepileptic therapy than with monotherapy with these drugs. Depending on the drugs in combination therapy, the risk of birth defects may increase, especially when valproate is added to therapy.

Finlepsin® should be used at the lowest effective dose. Regular monitoring of plasma concentrations of the active substance is recommended. With effective anticonvulsant control in pregnant women, minimal plasma concentrations of carbamazepine (therapeutic range 4-12 mcg/ml) should be maintained, since there are reports of possible dose-dependent risk of birth defects (for example, the incidence of birth defects was lower when using a dose less than 400 mg per day than when using higher doses).

Patients should be advised of the possibility of increased risk of malformations and the need for antenatal diagnostics for this reason.

The effective antiepileptic treatment should not be interrupted during pregnancy, because the progression of the disease can have adverse effects on the mother and the fetus.

Control and prevention

Folio acid deficiency is known to develop during pregnancy. Antiepileptic drugs have been reported to exacerbate this deficiency. This may contribute to an increased incidence of birth defects in children born to women taking antiepileptic drugs. Because of the above, additional folic acid supplementation is recommended before and during pregnancy.

In order to prevent increased bleeding in newborns, vitamin K1 is recommended for women in the last weeks of pregnancy as well as for newborns.

Newborns

A few cases of epileptic seizures and/or respiratory depression have been described in newborns whose mothers took the drug concomitantly with other anticonvulsants. In addition, several cases of vomiting, diarrhea, and/or hypotrophy have also been reported in newborns whose mothers received the drug. It is possible that these reactions are manifestations of neonatal withdrawal syndrome.

Doclinical data

The various preclinical studies in animals (mice, rats, rabbits) have summarized that carbamazepine has little or no teratogenic potential when used at doses consistent with those used in humans. However, data from preclinical studies were insufficient to rule out a teratogenic effect of carbamazepine. In a study of reproductive toxicity, a delayed weight gain in the offspring was observed when the drug was used in lactating rats at a dose of 192 mg/kg per day.

Breastfeeding

Carbamazepine penetrates into breast milk, where its concentration is 25-60% of that in blood plasma. In connection with the above, if it is necessary to use the drug during breastfeeding, the ratio of the expected benefits of breastfeeding to the possible risk of side effects of the drug should be carefully evaluated. Newborns who receive breast milk should be monitored for the earliest possible diagnosis of side effects (e.g., pronounced somnolence, allergic skin reactions). Cases of cholestatic hepatitis have been described in neonates who received carbamazepine antenatally or with breast milk, and therefore these neonates should be monitored for the earliest possible diagnosis of hepato-biliary system side effects.

Contraception

Patients of preserved reproductive potential should use reliable contraception during therapy and for 2 weeks after the last dose of the drug. Due to the induction of enzymes, carbamazepine may weaken the therapeutic effect of oral contraceptives containing estrogens and/or progesterone. Patients with preserved reproductive potential should be recommended to use alternative methods of contraception during therapy with the drug.

Effects on reproductive potential

There have been very rare reports of decreased male fertility and/or impaired spermatogenesis.

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