Trileptal®
Trileptal® can be used both as monotherapy and in combination with other antiepileptic drugs. In both cases, the course of treatment begins with a clinically effective dose, the frequency of administration is 2 times a day. The dose may be increased depending on the response to therapy. When replacing another antiepileptic drug with Trileptal, at the beginning of taking Trileptal, the dose of the drug being replaced should be gradually reduced. When using Trileptal as adjunctive therapy as part of polytherapy, a dose reduction of concomitant antiepileptic drugs and/or a slower increase in the dose of Trileptal may be required.
Trileptal can be taken regardless of meals (during, after meals or between meals).
The recommendations below apply to patients with normal renal function. For this category of patients, there is no need to monitor plasma concentrations of the active substance in order to optimize Trileptal therapy.
The tablets are marked and can be broken into two pieces to make them easier to swallow.
When used in children under 3 years of age
who cannot swallow tablets, as well as in cases where it is impossible to measure the required dose when using the drug in tablet form, Trileptal® is prescribed in the form of an oral suspension.
Adults and elderly patients
Monotherapy:
The initial dose is 600 mg/day (8-10 mg/kg body weight/day), divided into 2 doses. A good therapeutic response was observed in the dose range of 600-2400 mg/day. If necessary, a gradual increase in dose is possible. The dose is increased by no more than 600 mg/day at intervals of approximately 1 week until the desired therapeutic response is achieved. In hospital settings, there is experience with rapidly increasing the dose to 2400 mg/day over 48 hours.
Combination therapy:
The initial dose is 600 mg/day (8-10 mg/kg body weight/day), divided into 2 doses. A good therapeutic response was observed in the dose range of 600-2400 mg/day. If necessary, a gradual increase in dose is possible. The dose is increased by no more than 600 mg/day at intervals of approximately 1 week until the desired therapeutic response is achieved.
Use of the drug Trileptal® in a daily dose above 2400 mg. There is limited experience with the use of the drug in daily doses of up to 4200 mg.
No special adjustment of the dosage regimen is required for elderly patients, since the therapeutic dose of the drug is set individually.
Special dosage adjustments for elderly patients
is not required, since the therapeutic dose of the drug is determined individually.
Children
In monotherapy and when using the drug as part of combination therapy:
The recommended initial dose is 8-10 mg/kg body weight/day, divided into 2 doses.
If necessary, a gradual increase in dose is possible to achieve the desired therapeutic effect. At intervals of approximately 1 week, the dose is increased by a maximum of 10 mg/kg/day, to a maximum daily dose of 60 mg/kg.
When using the drug Trileptal® as monotherapy and as part of combination therapy, when adjusted for body weight, the apparent clearance in children decreases significantly with increasing age. Children aged 1 month to 4 years
a dose of the drug 2 times higher than the dose for adults may be required when adjusted for body weight;
Children aged 4 to 12 years
may require a dose 50% higher than the adult dose when adjusted for body weight.
In children aged 1 month to 4 years, the effect of antiepileptic drugs - inducers of liver enzymes on their apparent clearance is more pronounced than in children of older age groups (when adjusted for body weight). When using the drug Trileptal® in children aged 1 month to 4 years in combination with antiepileptic drugs - inducers of liver enzymes, a dose of oxcarbazepine may be required 60% higher (when adjusted for body weight) than with monotherapy with the drug Trileptal® or when using it in combination with antiepileptic drugs that do not induce enzymes. For children of older age groups, when conducting combination therapy with Trileptal® with liver enzyme inducers, a slight increase in the dose of the drug may be required compared to monotherapy.
In children under 3 years of age
the drug should be used in the form of an oral suspension due to the difficulties of using solid dosage forms in this age group.
No dosage adjustment is required in patients with mild to moderate liver dysfunction
.
For patients with impaired renal function (creatinine clearance less than 30 ml/min)
The recommended starting dose is 300 mg/day and should be increased slowly until the desired therapeutic response is achieved.
Instructions for use of oral suspension
Trileptal dose conversion table from mg to ml.
| Dose in milligrams (mg) | Dose in milliliters (ml) |
| 10 mg | 0.2 ml |
| 20 mg | 0.3 ml |
| 30 mg | 0.5 ml |
| 40 mg | 0.7 ml |
| 50 mg | 0.8 ml |
| 60 mg | 1.0 ml |
| 70 mg | 1.2 ml |
| 80 mg | 1.3 ml |
| 90 mg | 1.5 ml |
| 100 mg | 1.7 ml |
| 200 mg | 3.3 ml |
| 300 mg | 5.0 ml |
| 400 mg | 6.7 ml |
| 500 mg | 8.3 ml |
| 600 mg | 10.0 ml |
| 700 mg | 11.7 ml |
| 800 mg | 13.3 ml |
| 900 mg | 15.0 ml |
| 1000 mg | 16.7 ml |
Before taking the oral suspension, the bottle should be shaken thoroughly and the required amount of suspension should be immediately measured. The required dose (ml) is drawn from the bottle using the supplied syringe. When using a 10 ml syringe (supplied with a 250 ml bottle - for adults and older children), the amount of suspension should be rounded to 0.5 ml. When using a 1 ml syringe (supplied with a 100 ml bottle - for young children), the amount of suspension should be rounded to 0.1 ml. After each use, close the bottle tightly and wipe the syringe with a clean, dry cloth. The suspension can be taken directly from the syringe or diluted with a small amount of water before use. Store an open bottle for no more than 7 weeks.
Oral suspension and film-coated tablets are interchangeable in equivalent doses.
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.
Trileptal tablet film 600 mg pack contact cell/pack of cards x50
ATX code: N03AF02 (Oxcarbazepine) Active substance: oxcarbazepine (oxcarbazepine) Rec.INN registered by WHO Dosage form TRILEPTAL® tablets, coated. film-coated, 600 mg: 10, 20, 30 or 50 pcs. reg. No.: P N015199/01 dated 06/18/09 - Registration period. beat not limited Release form, composition and packaging Tablets, film-coated, gray-green, oval, slightly biconvex, scored on both sides, marked “T/D” on one side, “C/G” on the other.
1 tab. oxcarbazepine 150 mg
Excipients: anhydrous colloidal silicon dioxide - .0.8 mg, crospovidone - 10 mg, hypromellose (hydroxypropyl methylcellulose/cellulose HP-M 603) - 4.2 mg, magnesium stearate - 2.2 mg, microcrystalline cellulose (Avicel PH 102) - 32.8 mg.
Shell composition: titanium dioxide - 1.253 mg, talc - 0.715 mg, hypromellose (hydroxypropyl methylcellulose / cellulose HP-M 603) - 7.14 mg, iron oxide black (E172) - 0.022 mg, iron oxide red (E172) - 0.003 mg, iron oxide yellow (E172) - 0.152 mg, macrogol 4000 - 0.715 mg.
10 pieces. - blisters (1) - cardboard packs. 10 pieces. - blisters (2) - cardboard packs. 10 pieces. - blisters (3) - cardboard packs. 10 pieces. - blisters (5) - cardboard packs.
Yellow film-coated tablets, oval, slightly biconvex, scored on both sides, marked “TE/TE” on one side and “CG/CG” on the other.
1 tab. oxcarbazepine 300 mg
Excipients: colloidal anhydrous silicon dioxide - 1.6 mg, crospovidone - 20 mg, hypromellose (hydroxypropyl methylcellulose/cellulose HP-M 603) - 8.4 mg, magnesium stearate - 4.4 mg, microcrystalline cellulose (Avicel PH 102) - 65.6 mg.
Shell composition: titanium dioxide - 1.497 mg, talc - 5.323 mg, hypromellose (hydroxypropyl methylcellulose / cellulose HP-M 603) - 7.351 mg, iron oxide yellow (E172) - 0.499 mg, macrogol 8000 (polyethylene glycol 8000) - 1.331 mg.
10 pieces. - blisters (1) - cardboard packs. 10 pieces. - blisters (2) - cardboard packs. 10 pieces. - blisters (3) - cardboard packs. 10 pieces. - blisters (5) - cardboard packs.
The film-coated tablets are light pink, oval, slightly biconvex, scored on both sides, marked “TF/TF” on one side and “CG/CG” on the other.
1 tab. oxcarbazepine 600 mg
Excipients: anhydrous colloidal silicon dioxide - 3.2 mg, crospovidone - 40 mg, hypromellose (hydroxypropyl methylcellulose/cellulose HP-M 603) - 16.8 mg, magnesium stearate - 8.8 mg, microcrystalline cellulose (Avicel PH102) - 131.2 mg.
Shell composition: titanium dioxide - 3.655 mg, talc - 1.859 mg, hypromellose (hydroxypropyl methylcellulose/cellulose HP-M 603) - 18.564 mg, iron oxide black (E172) - 0.011 mg, iron oxide red (E172) - 0.052 mg, macrogol 4000 - 1.859 mg.
10 pieces. - blisters (1) - cardboard packs. 10 pieces. - blisters (2) - cardboard packs. 10 pieces. - blisters (3) - cardboard packs. 10 pieces. - blisters (5) - cardboard packs.
Clinical and pharmacological group: Anticonvulsant drug Pharmacotherapeutic group: Anticonvulsant drug
Indications: simple and complex partial epileptic seizures with or without secondary generalization in adults and children aged 1 month and older,
- generalized tonic-clonic epileptic seizures in adults and children aged 2 years and older.
ICD-10 codes ICD-10 code Indication G40 Epilepsy
Dosage regimen The drug Trileptal® can be used both as monotherapy and in combination with other antiepileptic drugs. In both cases, the course of treatment begins with a clinically effective dose, the frequency of administration is 2 times a day. The dose may be increased depending on the response to therapy. If you replace another antiepileptic drug with Trileptal®, when you start taking Trileptal®, you should gradually reduce the dose of the drug being replaced. When using Trileptal® as part of combination therapy, a dose reduction of concomitant antiepileptic drugs and/or a slower increase in the dose of Trileptal® may be required due to an increase in the total dose of antiepileptic drugs.
Trileptal® can be taken regardless of meals (during, after meals or between meals).
The tablets are marked and can be broken into two pieces to make them easier to swallow.
When using the drug Trileptal® in children under 3 years of age and in other patients who cannot swallow tablets, as well as in cases where it is impossible to measure the required dose when using the drug in tablet form, the drug Trileptal® is used in the form of an oral suspension. Oral suspension and tablets are interchangeable in equivalent doses.
Table for converting the dose of Trileptal® from mg to ml.
Dose in milligrams (mg) Dose in milliliters (ml) 10 mg 0.2 ml 20 mg 0.3 ml 30 mg 0.5 ml 40 mg 0.7 ml 50 mg 0.8 ml 60 mg 1.0 ml 70 mg 1.2 ml 80 mg 1.3 ml 90 mg 1.5 ml 100 mg 1.7 ml 200 mg 3.3 ml 300 mg 5.0 ml 400 mg 6.7 ml 500 mg 8.3 ml 600 mg 10.0 ml 700 mg 11.7 ml 800 mg 13.3 ml 900 mg 15.0 ml 1000 mg 16.7 ml
The therapeutic effect of the drug Trileptal® (oxcarbazepine) is primarily due to the action of its metabolite, MGP.
Routine determination of plasma concentrations of oxcarbazepine or MHD is not warranted. However, monitoring the concentration of MHD in the blood plasma can be used to clarify the patient’s compliance with the drug regimen (compliance) or in situations where a change in the clearance of MHD is possible, for example, changes in renal function, pregnancy, simultaneous use with drugs that increase the activity of “liver” enzymes. In the above situations, the dose of Trileptal® should be adjusted taking into account the concentration of MHD in the blood plasma (measured 2-4 hours after administration), which should be maintained at the level Adults
Monotherapy: and combination therapy
The initial dose is 600 mg/day (8-10 mg/kg body weight/day), divided into 2 doses. If necessary, a gradual increase in dose is possible. The dose is increased by no more than 600 mg/day at intervals of approximately 1 week until the desired therapeutic response is achieved. A good therapeutic response is observed in the dose range of 600-2400 mg/day, with most patients having a good clinical response at a dose of 900 mg/day.
In patients who have not previously received therapy with antiepileptic drugs, the effective dose is 1200 mg/day, in patients who have previously received but responded poorly to therapy with other antiepileptic drugs - 2400 mg/day.
The use of the drug Trileptal® in a daily dose of 2400 mg as part of combination therapy without reducing the dose of another antiepileptic drug was accompanied by poor tolerability in most patients, mainly due to the development of adverse events from the nervous system. The use of Trileptal® in daily doses above 2400 mg has not been studied.
Children and teenagers
Trileptal® is intended for use in children aged 1 month and older. The use of the drug in children under 1 month of age has not been studied in controlled clinical studies.
When monotherapy with Trileptal® and when using the drug as part of combination therapy, the recommended initial dose of 8-10 mg/kg body weight per day is divided into 2 doses.
In combination therapy, the target dose of Trileptal®, 30-46 mg/kg per day, should be achieved no less than 2 weeks from the start of therapy. If necessary, a gradual increase in dose is possible to achieve the desired therapeutic effect. The dose is increased at intervals of approximately 1 week in increments of no more than 10 mg/kg/day to a maximum of 60 mg/kg/day. When using the drug Trileptal® in monotherapy and as part of combination therapy, when adjusted for body weight, the apparent clearance of MHD in children decreases significantly with increasing age. Children aged 1 month to 4 years may require a dosage that is 2 times the adult dose when adjusted for body weight; children aged 4 to 12 years may require a dose 50% higher than the adult dose when adjusted by body weight.
In children aged 1 month to 4 years, the effect of antiepileptic drugs - liver enzyme inducers on their apparent clearance is more pronounced than in children of older age groups (when adjusted for body weight). When using the drug Trileptal® in children aged 1 month to 4 years in combination with antiepileptic drugs - inducers of liver enzymes, a dose of oxcarbazepine may be required 60% higher (when adjusted for body weight) than with monotherapy with the drug Trileptal® or when using it in combination with antiepileptic drugs that do not induce enzymes. For children of older age groups, when conducting combination therapy with Trileptal® with liver enzyme inducers, a slight increase in the dose of the drug may be required compared to monotherapy.
In children under 3 years of age, the drug should be used in syrup form due to the difficulties of using solid dosage forms in this age group.
Patients aged >65 years
Special adjustment of the dosage regimen in this category of patients is necessary if renal function is impaired (creatinine clearance less than 30 ml/min). If there is a risk of developing hyponaremia, careful monitoring of sodium levels in the blood plasma is necessary.
Patients with liver dysfunction
No dosage adjustment is required in patients with mild to moderate liver dysfunction. There are no data on the use of Trileptal® in patients with severe liver dysfunction, and therefore caution must be exercised when using the drug in patients in this category.
Patients with impaired renal function
For patients with impaired renal function (creatinine clearance less than 30 ml/min), the recommended initial dose is 300 mg/day; the dose should be increased slowly, at intervals of at least 1 week, until the desired therapeutic response is achieved. Careful monitoring of patients is necessary during dose selection.
Side effects The most frequently reported adverse reactions were: drowsiness, headache, dizziness, diplopia, nausea, vomiting, fatigue (more than 10% of patients).
Clinical studies have shown that undesirable effects are usually mild or moderate, transient in nature and observed mainly at the beginning of therapy.
The data below summarizes the information on adverse reactions (ARs) recorded during clinical trials, as well as data on the safety profile of the drug obtained during its use in clinical practice. HPs are grouped according to the MedDRA classification of organs and organ systems, and are listed in descending order of importance.
Criteria for assessing the frequency of adverse events: very often (≥1/10), often (≥1/100, From the blood and lymphatic system: infrequently - leukopenia, very rarely - suppression of bone marrow hematopoiesis, agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia.
On the part of the immune system: very rarely - anaphylactic reactions, hypersensitivity reactions (including multiple organ disorders), which are characterized by phenomena such as rash and increased body temperature. Possible damage to the circulatory and lymphatic systems (eosinophilia, thrombocytopenia, leukopenia, lymphadenopathy, splenomegaly), liver (hepatitis, changes in liver function tests), damage to muscles and joints (myalgia, swelling in the joints, arthralgia), nervous system (hepatic encephalopathy), kidneys (renal failure, interstitial nephritis, proteinuria), lungs (pulmonary edema, bronchospasm, bronchial asthma, interstitial inflammation, shortness of breath), angioedema.
From the endocrine system: very rarely - hypothyroidism.
From the side of metabolism and nutrition: often - hyponatremia (more often observed in patients aged >65 years), very rarely - clinically significant hyponatremia (sodium concentration). From the psyche: often - agitation (including nervousness), emotional lability, confusion consciousness, depression, apathy.
From the nervous system: very often - drowsiness (22.5%), headache (14.6%), dizziness (22.6%), often - ataxia, tremor, nystagmus, impaired attention, amnesia.
From the organ of vision: very often - diplopia (13.9%), often - blurred vision, visual impairment.
From the organ of hearing and labyrinthine disorders: often - systemic dizziness.
From the heart: very rarely - AV block, arrhythmias.
Vascular disorders: very rarely - arterial hypertension.
From the digestive system: very often - vomiting (11.1%), nausea (14.1%), often - diarrhea, abdominal pain, constipation, very rarely - pancreatitis.
From the liver and biliary tract: very rarely - hepatitis.
From the skin and subcutaneous tissues: often - rash, alopecia, acne, infrequently - urticaria, very rarely Stevens-Johnson syndrome, toxic epidermal necrolysis (drug-induced Lyell's syndrome), angioedema, erythema multiforme, systemic lupus erythematosus.
General disorders and disorders at the injection site: very often - feeling of fatigue (12%), often - asthenia.
Laboratory and instrumental data: infrequently - increased activity of liver enzymes, alkaline phosphatase, very rarely - increased activity of amylase, lipase.
In clinical studies conducted in children aged 1 month to 4 years, somnolence was most commonly observed (in 11% of patients). With a frequency of >1% - Adverse reactions identified in the post-marketing period based on individual reports and cases described in the literature.
Since data on adverse reactions in the post-marketing period were obtained from voluntary reports from a population of unknown size, it is impossible to estimate the frequency of their occurrence (frequency unknown). Adverse reactions are classified by organ system; within each organ system, adverse reactions are arranged in decreasing order of severity.
From the side of the track and subcutaneous tissues
Drug rash with eosinophilia and systemic manifestations, acute generalized exanthematous pustulosis.
From the musculoskeletal and connective tissue side
There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients receiving long-term treatment with Trileptal®. The mechanism of the effect of oxcarbazepine on bone metabolism is not clear.
Metabolism and nutrition
Syndrome of inappropriate secretion of antidiuretic hormone, manifested by lethargy, nausea, dizziness, decreased plasma osmolality, vomiting, headache, confusion and other symptoms of the nervous system.
Injuries, intoxications and complications of manipulations
A fall.
From the nervous system
Speech disorders (including dysarthria), especially during dose selection.
Contraindications for use: children under 3 years of age,
- hypersensitivity to oxcarbazepine or any other components of the drug.
The drug should be prescribed with caution to patients with known hypersensitivity to carbamazepine, because in this group of patients, hypersensitivity reactions to oxcarbazepine may develop in approximately 25-30% of cases. 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.
The use of Trileptal® in patients with severe liver dysfunction has not been studied, so the drug should be used with caution in this category of patients.
Use during pregnancy and breastfeeding Children of patients with epilepsy are more often than others predisposed to developmental disorders, incl. birth defects. Experience with the use of Trileptal® during pregnancy is limited. Available reports indicate a possible connection between taking the drug during pregnancy and the development of congenital malformations (CMD). The most common malformations in children whose mothers received Trileptal® therapy during pregnancy were: atrial septal defect, atrioventricular septal defect, cleft of the hard palate and upper lip, Down syndrome, hip dysplasia (both uni- and bilateral), tuberous sclerosis and ear malformations. According to the North American Pregnancy Registry, the incidence of gross malformations, defined as structural abnormalities requiring surgical, medical or cosmetic correction, diagnosed within 12 weeks after birth was 2.0% (95% confidence interval 0.6 to 5.1%) among pregnant women taking in the first trimester, oxcarbazepine in monotherapy. Compared with pregnant women who were not treated with any antiepileptic drugs during pregnancy, the relative risk of developing malformations in children is 1.6 with a 95% confidence interval of 0.46 to 5.7.
Patients of childbearing age should use reliable methods of contraception during therapy with Trileptal® (optimally, intrauterine contraceptives), since when used simultaneously with oral contraceptives containing ethinyl estradiol or levonorgestrel, the effectiveness of these drugs may be reduced.
If the patient is planning a pregnancy or pregnancy is diagnosed while using the drug, as well as if the question arises about using the drug Trileptal® during pregnancy, it is necessary to carefully compare the expected benefits of therapy and the possible risk to the fetus, especially in the first trimester of pregnancy.
During pregnancy, the minimum effective dose of the drug should be used. If possible and with sufficient clinical efficacy in women of childbearing age and at least in the first trimester of pregnancy, Trileptal® should be used in monotherapy.
The patient should be warned about possible developmental disorders of the fetus and the need for antenatal diagnosis.
During pregnancy, effective antiepileptic treatment should not be interrupted, since progression of the disease may have a negative effect on the mother and fetus. It is known that folic acid deficiency develops during pregnancy. Antiepileptic drugs may exacerbate this deficiency, which is one of the possible causes of fetal developmental disorders, therefore additional intake of folic acid supplements before and during pregnancy is recommended.
When using the drug during pregnancy, it is necessary to take into account that the physiological changes that occur in the body during pregnancy can lead to a gradual decrease in the level of 10-monohydroxy derivatives in the blood plasma. To achieve maximum control over the symptoms of the disease in pregnant patients, it is necessary to regularly evaluate the clinical effect of the drug and determine the concentration of MHD in the blood plasma.
Determination of the level of MHD in blood plasma is also recommended in the postpartum period, especially if the dose of the drug was increased during pregnancy.
There are reports that the use of antiepileptic drugs during pregnancy may lead to increased bleeding in newborns. As a precautionary measure, the use of vitamin K1 is recommended in the last few weeks of pregnancy, as well as in newborns whose mothers received Trileptal®.
Rare cases of hypocalcemia have been reported in newborns whose mothers were treated with antiepileptic drugs. These cases were caused by disorders of calcium-phosphorus metabolism and bone mineralization.
Oxcarbazepine and MGP penetrate the placental barrier. Oxcarbazepine and MGP are excreted in breast milk. The concentration ratio in milk and plasma was 0.5 for both substances. Since the effect on newborns of oxcarbazepine and MHD supplied through breast milk is unknown, Trileptal® should not be used during breastfeeding.
Use in children under 1 month of age
There is no data on the safety and effectiveness of Trileptal® in children under 1 month of age.
Effect on fertility
There is no data on the effect of the drug on fertility in humans. Animal studies have shown no effects of oxcarbazepine and MGP on fertility in either sex at daily doses of 150 and 450 mg/kg, respectively. When using maximum doses of MHD in females, however, there was a disruption of the astral cycle, a decrease in the number of luteal bodies, a decrease in the number of implantations and the number of living embryos.
Use for liver dysfunction No dosage adjustment is required in patients with mild to moderate liver dysfunction. There are no data on the use of Trileptal® in patients with severe liver dysfunction, and therefore caution must be exercised when using the drug in patients in this category.
Use for impaired renal function For patients with impaired renal function (creatinine clearance less than 30 ml/min), the recommended initial dose is 300 mg/day, the dose should be increased slowly, at intervals of at least 1 week, until the desired therapeutic response is achieved. Careful monitoring of patients is necessary during dose selection.
Use in children Trileptal® is intended for use in children aged 1 month and older. The use of the drug in children under 1 month of age has not been studied in controlled clinical studies.
Use in elderly patients Special adjustment of the dosage regimen in this category of patients is necessary if renal function is impaired (creatinine clearance less than 30 ml/min). If there is a risk of developing hyponaremia, careful monitoring of sodium levels in the blood plasma is necessary. Special instructions 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, in very rare cases, cardiac conduction disturbances may occur; 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 thoughts 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, death is 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 predisposed 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 for 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-B*1502 allele, it is necessary to avoid the use of drugs that lead 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) when using 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*
Trileptal suspension 60mg/ml 100ml (Novartis)
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, 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. 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, the drug Trileptal® should be immediately discontinued. Hyponatremia Hyponatremia (serum sodium content less than 125 mmol/l) was observed in 2.7% of patients receiving the drug 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 can be determined during routine blood tests. Body weight monitoring is necessary 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, in very rare cases, cardiac conduction disturbances may occur; careful monitoring of patients with previous conduction disturbances (atrioventricular block, arrhythmia) receiving Trileptal® is required. Hematological changes According to post-marketing reports, patients with Trileptal® have been observed in very rare cases 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, discontinuation of the drug should be considered. Suicidal thoughts and behavior Episodes of suicidal behavior and suicidal thoughts were observed 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 Trileptal®, the development of serious dermatological reactions, such as: Stevens-Johnson syndrome, toxic epidermal necrolysis ( Lyell's syndrome), exudative erythema multiforme. 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 Trileptal®, discontinuation of the drug and the use of another antiepileptic drug should be considered. Correlation with HLA-B*1502 There is a significant amount of data confirming the role of human leukocyte antigen (HLA) alleles in the development of serious skin reactions in patients with 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 presence of 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 Johnson and Lyell's syndrome when using carbamazepine and the presence in their genome of the allele of the human leukocyte antigen HLA-B*1502. The frequency of occurrence of this allele in patients of Chinese nationality is 2-12%, in Thai - about 8%, among some groups of the Malaysian population - more 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) when using 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 given regions. Data 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 frequency of the alleles. 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 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, patients positive for the HLA-B*1502 or HLA-A*3101 alleles did not develop severe skin syndromes when using Trilertal®. When genotyping for the HLA-B*1502 allele, preference should be given to a method with a 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 have been reports of very rare cases of hepatitis, which in most cases were successfully resolved. If hepatitis is suspected, discontinuation of the drug should be considered. Hypothyroidism Hypothyroidism is an extremely rare adverse event when using oxcabazepine. Considering the influence of thyroid hormones on the development of children, in this category of patients, especially under the age of two years, it is recommended to determine the concentration of thyroid hormones before starting drug therapy, and also to monitor this indicator while using the drug Trileptal®. Simultaneous use of oral contraceptives Women of childbearing age Ages taking oral contraceptives simultaneously 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 the use of other antiepileptic drugs, abrupt cessation of therapy with Trileptal® should be avoided due to the risk of an increase in the frequency of convulsive seizures. Persons taking alcohol during drug therapy Trileptal® should be warned about the 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 the form of a suspension should not be used in patients with hereditary fructose intolerance. Impact on the performance of potentially hazardous activities , requiring special attention and quick reactions Due to the possibility of developing, during the use of the drug Trileptal®, such undesirable effects as dizziness, drowsiness, ataxia, diplopia, blurred vision, visual disturbances, 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 vehicles or operating machinery while using the drug. If the described adverse events occur, you should refrain from performing these activities.
Efficacy and tolerability of Trileptal (oxcarbazepine) in epilepsy
The main requirements for modern AEDs are maximum therapeutic effectiveness and a wide spectrum of action with a minimum of side effects (AE) [2]. Currently, old AEDs are used less and less: phenobarbital due to severe adverse events, and domestic diphenin due to low effectiveness. Valproates, while remaining the basic drugs in pediatric epileptology, often lead to a number of serious adverse events [8,14] and have a pronounced teratogenic effect [10]. Carbamazepine drugs have proven themselves well in the treatment of epilepsy in children and adults. Prolonged forms are especially convenient. At the same time, the carbamazepine metabolite (epoxide) is a fairly active and toxic chemical compound that predetermines some side effects in case of drug overdose [3]. A new drug synthesized on the basis of carbamazepine, oxcarbazepine (Trileptal, Novartis), largely lacks the adverse effects of its predecessor. The mechanism of action of oxcarbazepine is associated with the blockade of voltage-dependent sodium and calcium channels, which leads to the stabilization of neuronal membranes, inhibition of neuronal discharges and has a powerful anticonvulsant effect [1,11,20]. Peak drug concentrations are achieved on average 4.5 hours after a single oral dose. The half-life is 8–10 hours, binding to blood plasma proteins is about 40%. The therapeutic level of the drug in blood plasma is 10–35 mcg/ml. The drug is excreted primarily by the kidneys. Recommended doses for adults are 1200–2400 mg/day, for children 20–40 mg/kg/day. twice, less often in 3 doses [4]. Slow titration of the dose is recommended, reaching the minimum maintenance dose in at least 14 days. The purpose of our study was to study the effectiveness of oxcarbazepine (Trileptal, Novartis) in the treatment of epilepsy, as well as to analyze the frequency and nature of side effects. We observed 30 patients with epilepsy (16 men and 14 women) who received Trileptal for 6 months. and more. The age of the patients was from 5 months. up to 25 years (average – 12.5 years). The study was dominated by children under 18 years of age – 87%. Symptomatic and presumably symptomatic forms of epilepsy made up the main group - 29 patients, and 1 patient was diagnosed with idiopathic epilepsy with isolated generalized convulsive seizures. Trileptal was prescribed in combination therapy when previous AEDs were insufficiently effective (28 patients) or as monotherapy (2 patients). Clinical effectiveness was assessed by the effect of the drug on the frequency of attacks: complete remission; reduction in attacks by more than 50%; insufficient effectiveness (less than 50%) or lack of effect; increased frequency of attacks (aggravation). The frequency and nature of PE were analyzed. At the end of the study, the “retention on therapy” parameter was determined: the number of patients who continued to take Trileptal after 6 months. therapy and the number of patients who stopped taking it for various reasons. Study results Symptomatic (17 patients) and presumably symptomatic (12 patients) forms of epilepsy dominated the study. Only 1 patient was diagnosed with idiopathic epilepsy with generalized seizures. Patients with frequent polymorphic seizures resistant to basic AEDs also predominated. The main types of attacks in the examined patients were asymmetrical tonic axial, dialeptic and secondary generalized paroxysms. Trileptal doses ranged from 225 to 2100 mg/day, which was 15–44 mg/kg/day. In 28 cases, the drug was prescribed in combination therapy when added mainly to valproate or topiramate. All patients underwent slow dose titration with gradual increases over 4–7 weeks. The effectiveness and tolerability of Trileptal therapy were assessed after 6 months. or more from the start of taking the drug. The maximum follow-up period was 1.5 years. The following results were obtained during the study: clinical remission - 4 patients (13.3%); significant reduction in the frequency of attacks – 21 (70%); no effect or insignificant effectiveness – 3 (10%); aggravation of attacks – 2 (6.7%). The greatest effectiveness of Trileptal was found in dialeptic and automotor seizures as part of temporal lobe epilepsy, as well as in focal motor and secondary generalized convulsive seizures. To a lesser extent, Trileptal was effective in hypermotor and tonic axial seizures. In 1 patient with idiopathic generalized epilepsy, the drug completely stopped generalized seizures (follow-up 1.5 years). In this case, Trileptal was prescribed as monotherapy at a dose of 1200 mg/day. (15 mg/kg/day) instead of sodium valproate, which caused severe obesity and opsomenorrhea. Of particular note is the effectiveness of Trileptal in 7 patients aged 5 to 14 months. with attacks in the form of asymmetric infantile spasms (West syndrome, mimicking symptomatic focal epilepsy). In all patients of this group, the addition of Trileptal led to a significant reduction in spasms, converting them from serial to single and abortive. In 1 case, complete clinical (but not electrical) remission was observed for 8 months. Drug dosages varied from 18 to 44 mg/kg/day. The smallest effect of Trileptal was obtained in patients with pseudogeneralized seizures: focal epileptic myoclonus, negative myoclonus, atypical absence seizures. This type of seizures was observed mainly in frontal lobe epilepsy with the presence of the phenomenon of secondary bilateral synchronization on the EEG. It was in this group of patients that 2 cases of seizure aggravation were identified: negative myoclonus and atypical absence seizures, which required discontinuation of the drug. The study showed good tolerability of Trileptal in most patients. Side effects highly likely associated with the drug were observed in 6 patients (20%). The following AEs were noted: drowsiness (2), double vision (2), irritability (1), insomnia (1). It should be noted that in 5 of 6 cases, AEs occurred during the dose titration period and disappeared within 3–8 weeks. Diplopia in two patients occurred during the gradual replacement of carbamazepine with Trileptal, when the patients took these drugs simultaneously for some time. Only in 1 case (3.3% of the total group) severe irritability in combination with the low effectiveness of the drug served as a reason to discontinue Trileptal. As a result of the analysis of the “retention on therapy” parameter, the following results were obtained: after 6 months. 24 patients (80%) continued taking Trileptal, and 6 (20%) stopped taking the drug. The reasons for refusal to take the drug (by the patient, his family or the attending physician) were: increased frequency of attacks (2), low efficiency (2), side effects (1), financial difficulties (1). Discussion As a result of the study, the positive effect of Trileptal in the treatment of epilepsy was noted in 83% of cases. Side effects were observed in 20% of patients, but drug discontinuation was required in only 1 case. The “retention in therapy” parameter was 80%. Currently, a large number of serious studies around the world have proven the high clinical effectiveness and relative safety of Trileptal in the treatment of epilepsy [1,3–7,11–13]. In a review article, Schmidt & Elger [16] reported 21 publications on the use of Trileptal in 2191 patients with epilepsy. Trileptal has been shown to be highly effective and well tolerated in doses of 600–2400 mg/day. (30–46 mg/kg/day), as a basic drug for epilepsy in children, adolescents and adults. The drug is recommended as a basic drug (including as initial monotherapy) for symptomatic focal forms of epilepsy with simple partial, complex partial and secondary generalized seizures. Our study showed high effectiveness (reduction of seizures in all cases) for infantile spasms as part of symptomatic focal epilepsy in children of the first year of life. Northam et al. [13] also demonstrated the promise of using Trileptal for focal epileptic seizures in young children (average - 20.4 months) and noted good tolerability of the drug in this age category. Glauser et al. [9] conducted a double-blind, placebo-controlled study on the effectiveness of oxcarbazepine as an adjunctive therapy for epilepsy in children. This multicenter study included 267 children aged 3 to 17 years with refractory partial epileptic seizures (138 received oxcarbazepine and 129 placebo). The dose of the drug varied from 6 to 51 mg/kg/day. (average – 31.4 mg/kg/day). Oxcarbazepine was shown to be significantly more effective in the treatment of focal epilepsy compared to placebo. The addition of oxcarbazepine led to complete remission in 4% of patients (placebo in 1%) and a reduction in the frequency of attacks by more than 50% in 41% (placebo in 22%). The effectiveness of the drug was noted both in simple and complex partial seizures, and in secondary generalized convulsive seizures and did not depend on the gender and age of the patients. After 28 days from the start of oxcarbazepine therapy, the overall frequency of attacks in patients decreased by 35% (placebo - by 9%). Even more encouraging results are presented in the publication of Serdaroglu et al. [17]. The authors analyzed the effectiveness of oxcarbazepine as monotherapy in 42 children (mean age 11.9 years) with symptomatic focal epilepsy and epilepsy with isolated generalized seizures. The drug was prescribed in a dose of 10 to 45 mg/kg/day. (with slow titration). After 6 months from the start of therapy, complete remission of seizures was found in 87.5% of patients: 91.7% with generalized epilepsy and 81.2% with focal epilepsy. In our study, Trileptal was prescribed to only 1 patient with idiopathic generalized epilepsy; At the same time, complete remission of attacks was achieved. It is obvious that the use of Trileptal may be promising for epilepsy with isolated generalized convulsive seizures in cases where valproate or topiramate are not effective enough or lead to the development of PE. One of the first studies on the results of Trileptal use in various forms of epilepsy in adolescents and adults was performed by Van Parys & Meinardi [19] on a Dutch cohort of patients. The vast majority of patients received carbamazepine with unsatisfactory results before oxcarbazepine was prescribed. Among 253 patients treated with Trileptal, clinical remission was observed in 8% of cases and a significant reduction in seizures in 33%. Aggravation of attacks was observed in 6 patients (2%); in the remaining 57% of patients, no significant changes were noted during therapy. According to the authors, oxcarbazepine can be successfully used in cases where carbamazepine drugs are not effective enough. In this regard, the study of Albani et al. is of interest. [3], who showed the possibility of simultaneously switching patients from carbamazepine to oxcarbazepine without gradual replacement and without dose titration. Moreover, according to the authors, the replacement of carbamazepine with oxcarbazepine should be carried out at a dose rate of 1:1.5 (for example, 800 mg of carbamazepine is simultaneously replaced by 1200 mg of oxcarbazepine). In a study by Beydoun et al. [5] compared the effectiveness of oxcarbazepine in monotherapy and as part of combination therapy for refractory focal epilepsy in adults at a dose of 600–2400 mg/day. Among 42 patients receiving monotherapy with oxcarbazepine and 34 patients receiving combination treatment, the results were distributed as follows: with monotherapy, remission of attacks was achieved in 9.5% of cases, and a reduction in the frequency of attacks by 50% or more - in 57.1%, general reduction in the frequency of attacks - 59.7%; with combination therapy, remission was achieved in 2.9% of cases, a reduction in the frequency of attacks by 50% or more - in 32.4%, a general reduction in the frequency of attacks - in 28%. Thus, the greater effectiveness of oxcarbazepine when used as monotherapy was convincingly demonstrated. Christe et al. [7] studied the comparative effectiveness of oxcarbazepine and sodium valproate in 249 adolescents and adults with newly diagnosed focal epilepsy (focal and secondary generalized seizures). Equal effectiveness was found for oxcarbazepine (remission 56.6%) and valproate (remission 53.8%) in the treatment of newly diagnosed focal epilepsy. There was also no significant difference in the incidence of PE. This study allows us to position oxcarbazepine as a basic drug in the treatment of focal epilepsy. Along with effectiveness, of course, the most important characteristic of the drug is its tolerability - one of the main components of the concept of “quality of life” for patients. The tolerability of oxcarbazepine, the frequency and nature of AEs have been analyzed in a large number of publications. Our study demonstrated good tolerability of the drug, the absence of serious AEs, and the discontinuation of Trileptal due to AEs in only 1 patient (3.3%). Beydoun et al. [5] analyzed the frequency and nature of PE when oxcarbazepine was prescribed to 76 adolescents and adults at a dose of 600–2400 mg/day. The drug was discontinued due to PE in 13% of cases. Most PEs were mild and moderate in nature. The following AEs were noted: fatigue, drowsiness, irritability, headache, diplopia, nausea, skin rash. In several cases, a transient increase in the level of liver enzymes in the blood occurred without any clinical manifestations. All AEs were observed significantly more often during polytherapy. Only in 2 cases (2.6%) were serious adverse events observed: acute psychosis (1) and hyponatremia (1). According to our observations, diplopia occurs only in cases where carbamazepine is gradually withdrawn with a slow titration of the dose of oxcarbazepine and patients receive both drugs simultaneously for some time. To prevent this adverse event, it is recommended to immediately switch patients from carbamazepine to Trileptal [3]. Hyponatremia (a decrease in plasma sodium levels below 125 mmol/ml) is a serious potential adverse event when taking oxcarbazepine. However, the incidence of this PE is low, and in pediatric practice it occurs rarely [6]. However, you should monitor your blood sodium levels while taking oxcarbazepine. Also, unlike carbamazepine, there are rare cases of skin rash when prescribing Trileptal - 2.7% in the study by Bourgeois & D'Souza [6]. Of note is the original study by Van Parys & Meinardi [19] on the analysis of AEs experienced by patients taking carbamazepine after switching to oxcarbazepine. It turned out that out of 164 patients who had PE on carbamazepine, in 129 (79%) they gradually disappeared when switching to Trileptal. Skin manifestations were leveled out in 72.5% of patients when carbamazepine was replaced with Trileptal. Thus, the significantly better tolerability of oxcarbazepine compared with carbamazepine was convincingly demonstrated. To date, there is the only serious publication by Montouris [12] devoted to studying the safety of oxcarbazepine during pregnancy. Using available databases and global registries, the author analyzed pregnancy outcomes in women taking Trileptal. Data were obtained on 248 women who received Trileptal as monotherapy, and on 61 women who received Trileptal in combination with other AEDs. Congenital malformations were detected in 6 cases out of 248 (2.4%) and in 4 out of 61 (6.6%). The risk of congenital malformations in the general population, according to the author, is 2–4%. Thus, the safety of using Trileptal during pregnancy in monotherapy and a slight increase in the risk of malformations in combination with other AEDs has been shown. However, most authors recommend refraining from prescribing oxcarbazepine to pregnant women, since the number of observations in the world is still limited. The most important characteristic of the drug is the “retention on therapy” indicator, which reflects the number of patients who continued to take the drug after a certain period of time after the start of treatment and the number of patients who stopped taking it for various reasons. Our study found a high retention rate on therapy: 80% of patients continued to take Trileptal continuously after 6 months. from the start of treatment. The reasons for refusing to take the drug were: increased frequency of attacks (2), low effectiveness (2), side effects (1), financial difficulties (1). Retention on Trileptal monotherapy after 1 year was analyzed in the study by Rainesalo et al. [15] in 175 adult patients with epilepsy. Patients were divided into 2 groups: 1 – starting monotherapy with Trileptal (97 people) and 2 – monotherapy with Trileptal in case of ineffectiveness of other previously prescribed AEDs (78). The percentage of deduction in therapy in the 1st group was 91%, and in 2 - 77%. The abolition of therapy due to side effects was stated in 1 group only in 3%of cases, in 2 - in 14%, and due to loss of efficiency - in the 1st group - in 2%, in 2 - in 8%. Thus, a high indicator of deduction on therapy with trileptal and a low percentage of treatment for treatment due to PE or loss of efficiency over time was demonstrated. The best effect was observed when prescribing a trileptal as starting monotherapy. Thus, we conducted the study and analysis of existing publications indicate the high efficiency and good tolerance of Okskarbazepine (trileptala) in the treatment of epilepsy in children and young adults. The high efficiency of the drug has been proved with symptomatic and presumably symptomatic focal forms of epilepsy with focal motor, automotor and secondary generated attacks. In this category of patients, trileptal can be prescribed as starting monotherapy. In focal forms of epilepsy with pseudo -generated attacks and the phenomenon of secondary bilateral synchronization on EEG, trileptal can lead to an aggravation of seizures and epileptiform changes to the EEG. At the same time, in these cases, the addition of average doses of trileptal to valproates can be quite safe and effective. The question of the use of trileptal in the treatment of idiopathic epilepsy with isolated generalized convulsive attacks is the subject of discussion. Trilepal, of course, is highly effective with isolated generalized convulsive attacks, but it can, like carbamazepine, lead to the connection of absans and myoclonus. In this regard, in our opinion, the drug may be prescribed for this syndrome in case of insufficient effectiveness or poor tolerance of topiramate and valPaters. All studies show the best tolerance of Okskarbazepine, including when compared with carbamazepine. Heavy PEs arose extremely rarely. In the first months of therapy, it is recommended to control the level of sodium in the blood, especially in adult patients. To reduce the risk of developing PE, slow title of the dose of trileptal within 4-6 weeks is recommended. However, when replacing carbamazepine with trileptal, it is advisable to do it at once. Preliminary studies showed the safety of monotherapy with trileptal during pregnancy.
Literature 1. Zenkov L.R. The role of oxcarbazepine in the treatment of epilepsy.// Consilium medicum, 2005, volume 7 No. 8, pp. 710–714 2. Mukhin K.Yu., Petrukhin A.S. Epileptic syndromes. Diagnostics and standards of therapy, // Moscow, 2005, 143 C 3. Albani F., Grassi B., Ferrara R., Turrini R., Baruzi A. Immediate (overnight) switching from carbamazepine monotherapy is equivalent to a progressive switch./ /Seizure, 2004; 13:254–263 4. Beydoun A, Kutluay E. Oxcarbazepine. Expert Opin Pharmacother, 2002; 3:59–71 5. Beydoun A., Sachdeo RC, Kutluay E., McCague K., DSouza J. Sustained efficacy and long-term safety of oxcarbazepine: one-year open-label extension of a study in refractory partial epilepsy. // Epilepsia, 2003, 44(9): 1160–1165 6. Bourgeois B., DSouza J. Long-term safety and tolerance of oxcarbazepine in children: a review of clinical experience.// Epilepsy& Behavior, 7 ((2005) , pp 375–382 7. Christe W., Kramer G., Vigonius U., Pohlmann H., Steinhoff B., Brodie M., Moore A. A double–blind controlled clinical trial: oxcarbazepine versus sodium valproate in newlywed adults diagnosed epilepsy. // Epilepsy research 26 (1997), pp 451–460 8. Demir E.; Aysun S. Weight gain associated with valproate in childhood // Pediatr Neurol. – 2000. – 22(5) – P. 361– 4. 9. Glauser TA, Nigro M., Sachdeo R., Pasteris LA, Weinstein S., Abou–Khalil B., Frank LM, Grinspan A., Guarino T., Bettis D. Adjunctive therapy with oxcarbazepine in children with partial seizures // Neurology 2000; 54:2237–2244 10. Morrow JJ Craig Antiepileptic drugs in pregnancy: current safety and other issues // Expert Opin Pharmacother. – 2003. – V. 4(4). – P. 445–446 11 McLean MJ Oxcarbazepine: mechanisms of action In: Levy RH, Mattson RH, Meldrum BS, et al., eds. Antiepileptic drugs. 5th ed. Philadelphia: Lipincott Williams & Wilkins, 2001:451–8 12. Montouris G. Safety of the new antiepileptic drug oxcarbazepine during pregnancy.// Current medical research and opinion, vol.21, 5 2005, pp. 693–701 13. Northam RS, Hernandez AW, Litzinger MJ, Minecan DN, Glauser TA, Mangat S., Zheng C., Souppart C., Sturm Y. Oxcarbazepine in infants and young children with partial seizures. // Pediatr Neurol 2005 ; 33:337–344 14. Novak GP; Maytal J; Alshansky A; Eviatar L; Sy Kho R; Siddique Q. Risk of excessive weight gain in epileptic children treated with valproate // J Child Neurol. – 1999. – V. 14(8). – P. 490–5. 15. Rainesalo S., Peltola J., Auvinen A., Keranen T. Retention rate of oxcarbazepine monotherapy in an unselected population of adult epileptics.// Seizure, 2005 (14), pp. 72–74 16. Schmidt D., Elger CE What is the evidence that oxcarbazepine and carbamazepine are distinctly different antiepileptic drugs? Epilepsy & Behavior, 5 2004, pp. 627–635 17. Serdaroglu G., Kurul S., Tutuncuoglu S., Dirik E., Sarioglu B. Oxcarbazepine in the treatment of childhood epilepsy. // Pediatr Neurol 2003; 28:37–41 18. Vainionpaa LK; Rattya J.; Knip M.; Tapanainen JS; Pakarinen AJ; Lanning P.; Tekay A.; Myllyla VV; Isojarvi JI Valproate induced hyperandrogenism during pubertal maturation in girls with epilepsy // Ann Neurol. – 1999 – V 45(4) – P. 444–50. 19. Van Parys JA, Meinardi H. Survey of 260 epileptic patients treated with oxcarbazepine (Trileptal) on a named–patient basis. // Epilepsy Research 19 (1994) 79–85 20. White HS Pediatric epilepsy: diagnosis and therapy. – 2001. – P.301–316. 21. Wolf P. Determinants of outcome in childhood epilepsy.// Acta neurol scand, 2005: 112 (Suppl. 182): 5–8
Trileptal
Children of patients with epilepsy are more often than others predisposed to developmental disorders, incl. birth defects. Experience with the drug during pregnancy is limited. Available reports indicate a possible connection between taking the drug during pregnancy and the development of congenital malformations (CMD). The most common malformations in children whose mothers received drug therapy during pregnancy were: atrial septal defect, atrioventricular septal defect, cleft of the hard palate and upper lip, Down syndrome, hip dysplasia (both unilateral and bilateral) , tuberous sclerosis and ear malformations. According to the North American Pregnancy Registry, the incidence of gross malformations, defined as structural abnormalities requiring surgical, medical, or cosmetic correction, diagnosed within 12 weeks after birth was 2.0% (95% confidence interval 0.6 to 5.1%) among pregnant women taking in the first trimester, oxcarbazepine in monotherapy. Compared with pregnant women who were not treated with any antiepileptic drugs during pregnancy, the relative risk of developing malformations in children is 1.6 with a 95% confidence interval of 0.46 to 5.7.
Patients of childbearing age should use reliable methods of contraception during drug therapy (optimally, intrauterine contraceptives), since when used simultaneously with oral contraceptives containing ethinyl estradiol or levonorgestrel, the effectiveness of these drugs may be reduced.
If the patient is planning a pregnancy or pregnancy is diagnosed while using the drug, as well as if the question arises about using the drug during pregnancy, it is necessary to carefully compare the expected benefits of therapy and the possible risk to the fetus, especially in the first trimester of pregnancy.
During pregnancy, the minimum effective dose of the drug should be used. If possible and with sufficient clinical efficacy in women of childbearing age and at least in the first trimester of pregnancy, the drug should be used in monotherapy.
The patient should be warned about possible developmental disorders of the fetus and the need for antenatal diagnosis.
During pregnancy, effective antiepileptic treatment should not be interrupted, since progression of the disease may have a negative effect on the mother and fetus. It is known that folic acid deficiency develops during pregnancy. Antiepileptic drugs may exacerbate this deficiency, which is one of the possible causes of fetal developmental disorders, therefore additional intake of folic acid supplements before and during pregnancy is recommended.
When using the drug during pregnancy, it is necessary to take into account that the physiological changes that occur in the body during pregnancy can lead to a gradual decrease in the level of 10-monohydroxy derivatives in the blood plasma. To achieve maximum control over the symptoms of the disease in pregnant patients, it is necessary to regularly evaluate the clinical effect of the drug and determine the concentration of MHD in the blood plasma.
Determination of the level of MHD in blood plasma is also recommended in the postpartum period, especially if the dose of the drug was increased during pregnancy.
There are reports that the use of antiepileptic drugs during pregnancy may lead to increased bleeding in newborns. As a precautionary measure, the use of vitamin K1 is recommended in the last few weeks of pregnancy, as well as in newborns whose mothers received the drug.
Rare cases of hypocalcemia have been reported in newborns whose mothers were treated with antiepileptic drugs. These cases were caused by disorders of calcium-phosphorus metabolism and bone mineralization.
Oxcarbazepine and MGP penetrate the placental barrier. Oxcarbazepine and MGP are excreted in breast milk. The concentration ratio in milk and plasma was 0.5 for both substances. Since the effect on newborns of oxcarbazepine and MHD supplied through breast milk is unknown, the drug should not be used during breastfeeding.
Use in children under 1 month of age
There is no data on the safety and effectiveness of the drug in children under 1 month of age.
Effect on fertility
There is no data on the effect of the drug on fertility in humans. Animal studies have shown no effects of oxcarbazepine and MGP on fertility in either sex at daily doses of 150 and 450 mg/kg, respectively. When using maximum doses of MHD in females, however, there was a disruption of the astral cycle, a decrease in the number of luteal bodies, a decrease in the number of implantations and the number of living embryos.
