TRILEPTAL film-coated tablets 600 mg No. 50
There are reports of a risk of worsening the course of epileptic seizures when using the drug Trileptal®. An increased risk of worsening seizures has been observed, mainly in children, but can also occur in adults. If, while using the drug Trileptal®, there is a worsening of the course of epileptic seizures, the use of the drug should be discontinued. Hypersensitivity reactions When using the drug Trileptal® in clinical practice, in isolated cases (post-marketing reports), the development of immediate type hypersensitivity reactions (type I), including rash, itching, urticaria, angioedema and anaphylactic reactions, was observed. Hypersensitivity reactions can cause the development of disorders of the skin, liver, blood and lymphatic system and other organs, both individually and as part of a systemic reaction. Angioedema and anaphylactic reactions affecting the larynx, vocal folds (glottis area), tongue, lips, and eyelids developed both during the first and repeated doses of the drug Trileptal®. If immediate hypersensitivity develops, Trileptal® should be discontinued immediately and alternative therapy should be prescribed. The drug should be used with caution in patients with known hypersensitivity to carbamazepine, because in this group of patients, in approximately 25-30% of cases, hypersensitivity reactions to oxcarbazepine may develop. In patients who do not have a history of hypersensitivity to carbamazepine, it is also possible to develop hypersensitivity reactions to the drug, including multiple organ disorders. If signs and symptoms of hypersensitivity reactions occur, Trileptal® should be discontinued immediately. Hyponatremia Hyponatremia (serum sodium less than 125 mmol/l) was observed in 2.7% of patients receiving Trileptal®, which was usually not accompanied by clinical manifestations and did not require adjustment of therapy. The sodium content is normalized upon discontinuation (dose reduction) of the drug Trileptal® or conservative treatment (restriction of fluid intake). In patients with a history of impaired renal function and low serum sodium levels (for example, in patients with syndrome of inappropriate antidiuretic hormone secretion), or in patients receiving concomitant treatment with drugs that promote sodium excretion from the body (diuretics, drugs that affect secretion of antidiuretic hormone), before starting therapy with Trileptal®, the sodium content in the blood serum should be determined. In the future, serum sodium levels should be monitored 2 weeks after the start of therapy and then monthly for 3 months or as needed. Particular attention should be paid to these risk factors in elderly patients. If it is necessary to use diuretics and other drugs that reduce serum sodium levels in patients receiving therapy with Trileptal®, the same recommendations should be followed. If clinical symptoms of hyponatremia appear, the sodium content in the blood serum should be determined. For other patients, serum sodium levels can be determined during routine blood tests. It is necessary to monitor body weight in all patients with heart failure to promptly diagnose fluid retention. If fluid retention occurs or as symptoms of heart failure progress, serum sodium levels should be determined. If hyponatremia occurs, the amount of fluid consumed should be limited. Because When using oxcarbazepine, cardiac conduction disturbances may occur in very rare cases; careful monitoring of patients with previous conduction disturbances (atrioventricular block, arrhythmia) receiving Trileptal® is necessary. Hematological changes According to post-marketing reports, when treated with Trileptal®, patients in very rare cases experienced the development of agranulocytosis, aplastic anemia and pancytopenia. Given the low incidence of agranulocytosis, aplastic anemia and pancytopenia, as well as associated factors (for example, concomitant use of other medications, the presence of concomitant diseases), a cause-and-effect relationship between the development of these adverse events and the use of the drug cannot be established. If symptoms of severe suppression of bone marrow hematopoiesis develop, it is necessary to consider discontinuing the drug. Suicidal thoughts and behavior Episodes of suicidal behavior and suicidal ideation have been reported in patients receiving anticonvulsants. The results of a meta-analysis of randomized placebo-controlled trials showed a small increase in the risk of developing suicidal behavior in patients receiving anticonvulsants. The mechanism for increasing the risk of suicide in this category of patients has not been established. Therefore, at all stages of treatment, careful monitoring of patients receiving treatment with the drug is necessary. Patients and medical personnel should be warned about the risk of suicidal thoughts and episodes in patients receiving therapy with Trileptal®. Dermatological reactions When using the drug Trileptal®, the development of serious dermatological reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exudative erythema multiforme, has been very rarely reported. Patients with the above dermatological reactions may require hospitalization due to the development of life-threatening conditions; very rarely lethal outcomes are possible. When using the drug Trileptal®, dermatological reactions were observed in both children and adults, and developed on average 19 days after starting the drug. There are isolated reports of cases of recurrence of serious skin reactions when taking Trileptal® is resumed. If skin reactions develop while using the drug Trileptal®, you should consider discontinuing the drug and using another antiepileptic drug. Correlation with HLA-B*1502 There is considerable evidence to support the role of human leukocyte antigen (HLA) alleles in the development of serious skin reactions in patients with a predisposition to such conditions. Due to the similarity in the chemical structure of oxcarbamazepine and carbamazepine, there is a possibility of developing Stevens-Johnson syndrome and Lyell's syndrome in patients with the HLA-B*1502 allele in the genome taking oxcarbazepine. In patients of Chinese and Thai nationality, there was a clear connection between the development of Stevens-Johnson syndrome and Lyell's syndrome when using carbamazepine and the presence of the human leukocyte antigen HLA-B*1502 allele in their genome. The frequency of occurrence of this allele in patients of Chinese nationality is 2-12%, in Thai patients - about 8%, among some groups of the Malaysian population - 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 Caucasians, Blacks, Hispanics, Indians and Japanese is negligible ( Allele frequencies 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 the of their two chromosomes is almost twice the allele frequency. Thus, the percentage of patients who may be at risk is almost twice the allele frequency. When using the drug Trileptal® in possible carriers of the HLA-B*1502 allele, it is recommended to carry out genotyping according to this allele. The drug should be used in carriers of this allele only if the expected benefit from therapy outweighs the possible risk. The presence of this allele in people of Chinese nationality taking other antiepileptic drugs increases the risk of developing severe dermatological reactions. In patients with the HLA- allele B*1502 It is necessary to avoid the use of drugs leading to the development of Stevens-Johnson syndrome or Lyell's syndrome, with possible replacement with alternative drugs. Genotyping for the HLA-B*1502 allele before using Trileptal® is not necessary in patients belonging to populations with a low frequency of occurrence of this allele, as well as in patients already receiving therapy with this drug, since severe skin reactions were observed in most cases in the first months of treatment (regardless of the presence of HLA-B*1502). Correlation with HLA-B*3101 The presence of the HLA-A*3101 allele may be a risk factor for the development of severe skin lesions (Stevens-Johnson syndrome, Lyell's syndrome, drug rash with eosinophilia and systemic manifestations, acute generalized exanthematous pustulosis and macular nodular rash) in use of carbamazepine. The frequency of occurrence of the HLA-A*3101 allele of the human leukocyte antigen (HLA) gene may differ among different ethnic groups: about 2-5% in the European population, about 10% in the Japanese, about 6.7% in the Western European population, depending on geographical region. The allele frequency is less than 5% in the populations of Australia, Asia, Africa and North America, with exceptions ranging from 5% to 12%. A frequency of more than 15% has been found in some ethnic groups of South America (Argentina and Brazil), indigenous people of North America (Navajo and Sioux tribes, in Mexico - Sanora Seri), South India (Tamil Nadu), and 10-15% among other indigenous people these regions. These allele frequencies represent the percentage of chromosomes in specific populations that carry the allele. This means that the percentage of patients carrying a copy of the allele on at least one of their two chromosomes is almost twice the frequency of the allele. Thus, the percentage of patients who may be at risk is almost twice the allele frequency. There is no sufficient basis to recommend genotyping for this allele in patients before starting oxcarbazepine therapy. For patients already receiving therapy with Trileptal®, genotyping for this allele is not recommended, since skin reactions in most cases were observed in the first months of drug use (regardless of the presence of HLA-A*3101). However, the results of genotyping should not affect the degree of control of the patient's condition and the doctor's alertness regarding severe skin reactions. The development of severe skin lesions is possible in patients negative for these alleles. Also, in many cases, in patients positive for the HLA-B*1502 or HLA-A*3101 alleles, the development of severe skin syndromes was not observed when using the drug Trilertal®. When genotyping for the HLA-B*1502 allele, preference should be given to methods with high resolution. The test is considered positive if at least one of the alleles is detected, negative if no allele is detected. The same recommendations should be followed when genotyping for the HLA-A*3101 allele. The influence of other factors, such as the dose of anticonvulsants, patient compliance, concomitant therapy with other drugs, concomitant diseases, or the level of control of dermatological reactions, on the incidence and prevalence of severe skin reactions has not been established. Impaired liver function There are reports of very rare cases of hepatitis, which in most cases resolved safely. If hepatitis is suspected, discontinuation of the drug should be considered. Hypothyroidism Hypothyroidism is an extremely rare adverse event with oxcabazepine. Considering the influence of thyroid hormones on the development of children, in this category of patients, especially under the age of two, it is recommended to determine the concentration of thyroid hormones before starting drug therapy, and also to monitor this indicator during the use of the drug Trileptal®. Concomitant use of oral contraceptives Women of childbearing age taking oral contraceptives concomitantly with Trileptal should be warned about the possible decrease in the effectiveness of oral contraceptives. For this category of patients receiving Trileptal®, additional use of non-hormonal methods of contraception is recommended. Withdrawal syndrome As with other antiepileptic drugs, abrupt cessation of therapy with Trilertal should be avoided due to the risk of an increase in the frequency of convulsive seizures. Persons taking alcohol during therapy with Trileptal® should be warned of a possible increase in sedative effect. The drug Trileptal® in the form of an oral suspension contains ethanol in an amount of less than 100 mg per dose. The suspension also contains parabens, which may cause allergic reactions (possibly delayed). The oral suspension contains sorbitol, therefore Trileptal® in suspension form should not be used in patients with hereditary impaired fructose tolerance. Impact on the performance of potentially hazardous activities that require special attention and quick reactions Due to the possibility of development of such adverse effects as dizziness, drowsiness, ataxia, diplopia, blurred vision, visual impairment, hyponatremia, and depression of consciousness or other disorders of the central nervous system, especially at the beginning of treatment or during dose selection, patients should be careful when driving or operating machinery while using the drug. If the described adverse events occur, you should refrain from performing these activities.
Compound
1 tablet of oxcarbazepine 150 mg, 300 mg or 600 mg.
Silicon dioxide, crospovidone, hypromellose, magnesium stearate, MCC - as excipients.
1 ml of oxcarbazepine 60 mg. Sodium saccharinate, sorbic acid, propyl parahydroxybenzoate, macrogol stearate, sorbitol , methyl parahydroxybenzoate, ascorbic acid, propylene glycol, cellulose, plum-lemon flavor, purified water - as excipients.
Interaction
It should be borne in mind that the active substance is an inhibitor of cytochrome CYP2C19, therefore the administration of large doses of this drug and Phenobarbital , Phenytoin leads to interaction.
The concentration of Phenytoin increases by 40% when Trileptal is co-administered above 1200 mg/day, and therefore the dose of Phenytoin can be reduced. The drug increases the concentration of Phenobarbital, at the same time Phenobarbital reduces its concentration by 30-31%.
Felbamate and Clobazam do not affect the concentration of this drug.
Valproic acid reduces concentration by 18%.
Prescription along with hormonal contraceptives leads to a decrease in the effectiveness of contraceptives.
Strengthens the sedative effect of ethanol .
Cimetidine , Erythromycin , Warfarin , Dextropropoxyphene do not affect MGP parameters.
Verapamil reduces the concentration of active metabolites by 20%.
Pharmacodynamics and pharmacokinetics
Pharmacodynamics
The mechanism of antiepileptic action is associated with the blockade of sodium channels, which respond to changes in membrane potential. This entails the stabilization of overexcited neurons, a decrease in the conduction of impulses in synapses and the suppression of serial discharges. In the antiepileptic effect of the drug, an increase in K+ conductivity and modulation of calcium channels, which are activated by high neuronal membrane potential, are also important. There are no interactions of the active substance with brain neurotransmitters.
Effective against epileptic seizures in monotherapy and combination therapy in adults and children. In addition, Trileptal has a normothimic effect - it eliminates circular mental disorders (mood fluctuations) and prevents the development of depression.
Pharmacokinetics
When taken orally it is well absorbed. Food intake does not affect the degree of absorption. Metabolized to form the active metabolite MHP (monohydroxy derivative). 40% of MGP is bound to blood proteins. After taking a suspension at a dose of 600 mg, Cmax MGP is achieved after 6 hours, and when taking the same dose in tablet form - after 4.5 hours. In the form of metabolites, 95% is excreted by the kidneys, 4% with feces.
Reviews about Trileptal
Reviews of Trileptal on forums indicate the effectiveness of this drug both in focal epileptic seizures and in generalized tonic-clonic ones . Many patients have successfully replaced Carbamazepine , Gabapentin , Phenytoin or Valproate with Trileptal alone on the recommendation of a physician.
Its effectiveness was no lower, and tolerability was much better, which made it possible to take this drug for a long time without complications. Thus, it is noted that within 12 months. treatment with this drug alone, a complete disappearance of seizures was observed in patients with a generalized form of epilepsy . All those who have taken the drug note that it, compared to Finlepsin and Carbamazepine , has fewer side effects.
“I finally switched from Finlepsin to Trileptal, after taking it the headache does not hurt, and the night attacks have passed. Among the side effects, I can complain about drowsiness.”
“Very good drug. I switched to Trileptal 300 and everything changed - minimal drowsiness, appetite as usual. Only positive reviews."
“I take 1800 mg (3 times 600), transferred a year ago. Compared to Finlepsin, I feel very cheerful, I walked around like a somnambulist on Finlepsin.”
“My daughter has been taking Trileptal for six years, she has no seizures, before that she took Finlepsin and had seizures at night.”
The most common adverse reactions are drowsiness, increased appetite, tearfulness, dizziness and double vision 40 minutes after taking the tablet.
