Composition, form of production and packaging
Tablets are white, oblong, with engraved "ESL 800" on one side and risk on the other.
1 tab.
eslikarbazepine acetate 800 mg
Excipients: povidone K59 / 32 - 62.2 mg, croscarmellose sodium - 53.3 mg, magnesium stearate - 17.8 mg.
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (6) - packs of cardboard.
10 pieces. - blisters (9) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Mechanism of action
The exact mechanisms of action of eslikarbazepine acetate are unknown. However, according to the results of electrophysiological studies of inv itro , eslikarbazepine acetate and its metabolites stabilize the inactivated state of potential-dependent sodium channels, preventing their activation and, thus, supporting the periodic excitation of neurons.
Pharmacodynamic effects
Eslikarbazepine acetate and its active metabolites prevent the development of epileptic seizures in pre-clinical models, which allows predicting its anticonvulsant effect in humans. In humans, the pharmacological activity of eslikarbazepine acetate is mainly due to its active metabolite, eslikarbazepine.
Clinical efficacy and safety
Efficacy and safety of eslacarbazepine acetate was established in four double-blind, placebo-controlled, Phase 3 studies in 1703 adult patients with partial epileptic seizures refractory to treatment with other (one to three) antiepileptic drugs (PEP). The concomitant use of oxcarbazepine and felbamate in these studies was excluded.
The use of eslikarbazepine acetate in single daily doses of 400 mg, 800 mg and 1200 mg was studied. It was found that the use of eslikarbazepine acetate in doses of 800 mg and 1200 mg once a day is significantly more effective in reducing the frequency of seizures compared with placebo during the 12-week maintenance period.
According to the combined results of all Phase 3 studies, the proportion of patients with at least 50% response was (among 1581 analyzed) 19.3% for the placebo group, 20.8% for the group taking 400 mg eslikarbazepine acetate, 30.5% for the group taking 800 mg eslikarbazepine acetate and 35.3% for 1200 mg of eslikarbazepine acetate per day.
Patients of advanced age (over 65 years)
The safety and efficacy of eslacarbazepine acetate as adjunctive therapy for partial epileptic seizures in elderly patients was evaluated in an uncontrolled 26-week study in 72 patients over the age of 65 years. The results of the study showed that the incidence of adverse events associated with taking the drug in this population (65.3%) was similar to that obtained in patients participating in double-blind phase 3 studies (66.8%). The most common adverse events associated with taking the drug were dizziness (12.5%), drowsiness (9.7%), fatigue, seizures and hyponatremia (8.3% each), nasopharyngitis (6.9%) and upper respiratory tract infections (5.6%) . 50 of the 72 patients who started the study completed the 26-week treatment period, which corresponds to a 69.4% retention rate on the drug.
PHARMACOKINETICS
Suction
Eslikarbazepine acetate is largely metabolized in eslikarbazepine. After oral administration, the concentration of eslikarbazepine acetate in blood plasma, as a rule, remains below the level of quantitative determination. The time to reach the maximum concentration (T max ) of eslikarbazepine in plasma is 2-3 hours after administration. Bioavailability of the drug can be considered high, since the amount of metabolites found in the urine is more than 90% of the dose of eslikarbazepine acetate.
Distribution
The binding of eslikarbazepine to plasma proteins is relatively low (<40%), and does not depend on its concentration. According to the results of in vitro studies, thepresence of warfarin, diazepam, digoxin, phenytoin and tolbutamide does not significantly affect the degree of binding of eslikarbazepine to plasma proteins.Eslikarbazepine, in turn, has virtually no effect on binding to plasma proteins of warfarin, diazepam, digoxin, phenytoin and tolbutamide.
Metabolism
Eslikarbazepine acetate at the first passage through the liver is rapidly and intensively metabolized into its main active metabolite - eslikarbazepine by hydrolysis. The maximum concentration (C max ) of eslikarbazepine in plasma is achieved 2-3 h after the administration, and the equilibrium concentration after 4-5 days of application of the drug once a day, which corresponds to an effective half-life of about 20-24 h. healthy volunteers and adult patients with epilepsy, the apparent half-life was 10-20 and 13-20 hours, respectively.
A small number of the following metabolites are found in the plasma: R-lycarbazepine and oxcarbazepine, which have pharmacological activity, as well as conjugates of eslikarbazepine acetate, eslikarbazepine, R-lycarbazepine and oxcarbazepine with glucuronic acid.
Eslikarbazepine acetate does not affect its own metabolism and clearance.
Eslikarbazepine is a weak inducer of the isoenzyme CYP3A4 and has an inhibitory effect on the isoenzyme CYP2C19 (see the section "Drug Interactions").
In the course of experimental studies on fresh human hepatocytes, the ability of eslikarbazepine to insignificantly induce the activity of the isoenzyme UGT1A1 involved in glucuronation reactions has been revealed.
Excretion
Metabolites of eslikarbazepine acetate are excreted from the systemic blood stream, mainly by the kidneys, in unchanged form and as conjugates with glucuronic acid. Eslikarbazepine and its glucuronide account for more than 90% of all metabolites excreted in the urine (about 2/3 are excreted as eslycarbazepine and 1/3 - in the form of glucuronide).
Linearity / Nonlinearity
In the dose range of 400-1200 mg, both in healthy volunteers and in patients with epilepsy, eslikarbazepine acetate has a linear and dose-dependent pharmacokinetics.
Use in special patient groups
Patients of advanced age (over 65 years). The pharmacokinetic profile of eslikarbazepine acetate does not change in elderly patients with creatinine clearance (CC)> 60 ml / min (see section "Dosage regimen").
Patients with renal insufficiency. Metabolites of eslikarbazepine acetate are excreted from the systemic blood stream, mainly by the kidneys. According to the results of the study with the participation of patients with mild to severe renal insufficiency, the clearance of the drug depends on the function of the kidneys. During treatment with the drug Exalieff В®, it is recommended that its dose be adjusted at a CC <60 ml / min (see section "Dosage regimen").
Metabolites of eslikarbazepine acetate are excreted from the blood plasma during hemodialysis.
Patients with hepatic insufficiency. The pharmacokinetics and metabolism of eslikarbazepine acetate have been studied in healthy volunteers and patients with moderate hepatic insufficiency after repeated administration of the drug. Moderate hepatic insufficiency did not affect the pharmacokinetics of eslikarbazepine acetate.In the case of mild and moderate hepatic insufficiency, dose adjustment is not required (see section "Dosage regimen.")
In patients with severe hepatic insufficiency, the pharmacokinetics of eslikarbazepine have not been studied.
Influence of sex. Studies involving patients and healthy volunteers did not reveal the dependence of the pharmacokinetics of eslikarbazepine acetate on sex.
INDICATIONS
Exalieff В® is prescribed to adults as an adjunctive therapy for partial epileptic seizures with or without secondary generalization.
DOSING MODE
Exalieff В® is prescribed in addition to ongoing anticonvulsant therapy. Exalieph В® is taken orally regardless of food intake. The tablet can be divided into two equal parts.
The recommended initial dose is 400 mg once a day, after 1-2 weeks the dose is increased to 800 mg once a day. Taking into account the individual response to treatment, the dose can be increased to 1200 mg once a day.
The use in elderly patients (over 65 years)
Correction of the dose of the drug is not required, provided that the kidney function is not impaired.
Patients with renal insufficiency
In the treatment of patients with renal insufficiency, care should be taken and dosage adjustment should be performed depending on the value of the CC:
- CK> 60 ml / min: dose adjustment is not required.
- KK 30-60 ml / min: initial dose of 400 mg every other day for 2 weeks, then 400 mg once a day. However, taking into account the individual response, the dose can be increased.
- QC <30 ml / min: use in patients with severe renal insufficiency is not recommended due to insufficient data.
Patients with hepatic insufficiency
In the case of mild and moderate hepatic insufficiency, dose adjustment is not required.
The pharmacokinetics of eslikarbazepine acetate in patients with severe hepatic insufficiency has not been studied (see the sections "Pharmacokinetics", "Special instructions"), therefore its use in this category of patients is not recommended.
Use in children under 18 years of age
The safety and efficacy of eslacarbazepine acetate in children and adolescents under the age of 18 years have not been established. No data available.
SIDE EFFECT
In placebo-controlled trials involving 1,842 adult patients with partial epileptic seizures (1282 of whom received eslacarbazepine acetate and 560 placebo), 50.7% of patients in the eslcarbazepine acetate group and 27.7% of the placebo group took undesirable reactions.
Unwanted reactions were generally mild or moderate in severity and occurred mainly in the first weeks of therapy.
The undesirable reactions that occurred during the therapy with the drug Exalieff В® are mainly dose-dependent reactions associated with the membership of the carboxamide class. The most frequent adverse reactions that occurred during clinical trials in adult patients with epilepsy, both in the eslikarbazepine acetate group and in the control group were dizziness, drowsiness, headache, and nausea. Most adverse reactions were observed in less than 3% of patients in both groups.
The table below lists all the undesirable reactions recorded in the safety database of eslikarbazepine acetate, presented according to the system-organ classification and frequency of their occurrence. In this case, all the adverse events associated with taking the drug were taken into account in double-blind clinical studies in the eslikarbazepine acetate group. The following criteria were also taken into account: frequency of occurrence exceeding that in the placebo group, severity, severity and cause-effect relationship in each case, compliance with the pharmacological properties of eslikarbazepine acetate, as well as data from open-label research and post-marketing data.
Undesirable reactions are divided according to the frequency of their occurrence on: very frequent? 1/10, frequent from? 1/100 to <1/10, infrequent from? 1/1000 to <1/100, rare from? 1/10 000 to <1/1000. In each category, adverse reactions are presented in descending order of severity.
Very Frequent Frequent Infrequent Rare
Disorders from the blood and lymphatic system Anemia Thrombocytopenia Leukopenia
Immune system disorders Hypersensitivity
Endocrine Disorders Hypothyroidism
Disorders from the Metabolism and Nutrition Hyponatremia Reduced Appetite Disbalance of Electrolytes Dehydration Hypochloremia
Mental disturbances Insomnia Apathy Depression Nervous Agitation Irritant Attention Deficit / Hyperactivity Confusion Mood Lability of mood Tearfulness Slowing speed of psychomotor reactions Psychotic disorders
Disturbances of the nervous system Dizziness Drowsiness Headache Attention Disorder Tremor Ataxia Imbalance Impaired coordination of movement Memory loss Amnesia Increased drowsiness Sedative effect Aphasia Dysaestia Dystonia Sluggishness Parosmia Cerebrospinal syndrome Seizures Peripheral neuropathy Nystagm Disorders of speech Dysarthria Burning sensation Paresthesia Migraine
Dysplasia of the eye Disturbed vision Vision disorder Oscilloscopy Disturbance of friendly eyeball movements Conjunctival hyperemia
Hearing disorders and labyrinthine disturbances Vertigo Hearing loss Noise in the ears
Heart disorders Heart palpitations Bradycardia
Vascular disorders Hypertension (including hypertensive crisis) Arterial hypotension Orthostatic hypotension Tides Feeling of cold in the hands and feet
Respiratory, thoracic and mediastinal disorders Nasal bleeding Pain in chest
Disturbances from the gastrointestinal tract Nausea Vomiting Diarrhea Constipation Dyspepsia Gastritis Abdominal pain Dry mouth Discomfort in the abdomen Dish bloating Gingivitis Melena Toothache Pancreatitis
Disturbances from the liver and bile ducts
Disturbances from the skin and subcutaneous tissues Rash Alopecia Dryness of the skin Increased sweating Erythema Skin lesion Itching
Disturbances from musculoskeletal and connective tissue Myalgia Metabolic disorders of bone tissue Muscle weakness Pain in limbs
Disorders from the kidneys and urinary tract Urinary tract infections
General disorders and disorders at the site of administration Fatigability Disturbance of gait Asthenia Malady Chills Peripheral edema
Laboratory and instrumental data Reduced blood pressure (BP) Decreased body weight Increased blood pressure Reduced blood sodium concentration Reduced blood chloride levels Increased osteocalcin content Decreased hematocrit Reduced hemoglobin concentration in blood Increased activity of "liver" transaminases
Injury, intoxication and complications of manipulation Toxicity of the drug Falling Thermal burn
Description of some unwanted reactions
Impaired vision and nervous system
With the simultaneous administration of eslikarbazepine acetate and carbamazepine in placebo-controlled studies, the following adverse reactions were noted: diplopia (in 11.4% of patients with simultaneous carbamazepine and 2.4% of patients not taking carbamazepine), impaired coordination of movements (in 6.7% of patients with simultaneous admission carbamazepine and 27% of patients who did not take carbamazepine) and dizziness (in 30.0% of patients with simultaneous carbamazepine and 11.5% of patients not taking carbamazepine) (see section " idents interaction ").
PR interval
The prolongation of the PR interval is associated with the use of eslikarbazepine. In this case, the occurrence of unwanted reactions, (for example, atrioventricular blockade, syncope, bradycardia). In patients taking eslikarbazepine acetate, atrioventricular blockade of the second and higher degree was not observed.
Undesirable reactions associated with belonging to the class of carboxamides
During the placebo-controlled studies of eslikarbazepine acetate, there were no rare adverse reactions such as bone marrow suppression, anaphylactic reactions, severe skin reactions (eg, Stevens-Johnson syndrome), systemic lupus erythematosus, or severe arrhythmia. However, these reactions have been identified with the use of oxcarbazepine, and therefore, their occurrence can not be completely ruled out against the background of eslacarbazepine acetate therapy.
In long-term use in combination with structurally related PEP-carbamazepine and oxcarbazepine, bone mineral density, osteopenia, osteoporosis and fractures were reported to decrease. The mechanism of the effect of drugs on the metabolism of bone tissue is not known.
Announcement of unwanted reactions
It is extremely important to notify about undesirable reactions that occurred during the post-marketing use of the drug. This will allow you to control the benefit / risk ratio when using it. Please inform medical workers of any undesired reactions to the address given in this manual.
CONTRAINDICATIONS
- hypersensitivity to the active ingredient, other carboxamide derivatives (eg carbamazepine, oxcarbazepine) or to any of the excipients.
- Atrioventricular block of the second or third degree.
- Patients with severe renal failure (CK <30 ml / min) (data on the use of the drug in this category of patients is not enough);
- Patients with severe hepatic impairment (pharmacokinetics of eslikarbazepine acetate in this category of patients have not been studied);
- Children under 18 years of age (there are no safety and efficacy data for this category of patients).
Carefully
Low concentration of thyroxine in the blood.
Violations of cardiac conduction or concomitant administration of drugs that promote the prolongation of the PR interval (see section "Special instructions").
Renal failure mild and moderate severity (dose correction should be carried out in accordance with creatinine clearance (see. "Metering mode")).
Liver failure mild and moderate severity (due to the limited clinical data).
Hyponatremia (see. "Special Instructions" section).
PREGNANCY AND LACTATION
Common risks associated with epilepsy and receiving PEP
There is evidence that the prevalence of birth defects in children born to women with epilepsy is 2-3 times higher than in the general population. The following defects are detected more often: the splitting of the upper lip, malformations of the cardiovascular system and neural tube defects. Combination therapy with anticonvulsants is accompanied by an increased risk of birth defects compared to a monotherapy, in connection with what is necessary, if possible, to appoint monotherapy.
Women with childbearing potential stored, especially planning a pregnancy should be seen by a specialist. The need for antiepileptic therapy was evaluated in women planning a pregnancy. Unacceptable abrupt withdrawal of anticonvulsant therapy due to the risk of an epileptic seizure, which can lead to serious consequences for both mother and fetus.
Women with childbearing potential stored and contraception
noted undesirable interaction eslikarbazepina acetate with oral contraceptives. During treatment, and until the end of the current menstrual cycle after its completion, it is necessary to use an alternative, effective and safe method of contraception.
Pregnancy
Data on the use eslikarbazepina acetate in pregnant women are missing. Studies on animals have found reproductive toxicity of the drug. Feasibility of drug destination Eksalief В® should be evaluated again, if during reception it occurs or planned pregnancy. It is recommended to prescribe the minimum effective dose of the drug and, if possible, give preference to monotherapy even in the first trimester of pregnancy. Female patients should be warned about an increased risk of congenital malformations in the fetus and provide an opportunity for prenatal screening.
Monitoring and precautions
Antiepileptic drugs may contribute to the development of folic acid deficiency, which further cause abnormalities in the fetus. When planning a pregnancy, and after the occurrence of medication is recommended to take extra folic acid. Specific prenatal diagnosis of congenital malformations should be offered even for women who take folic acid.
Neonates
In neonates whose mothers received anticonvulsant therapy, there have been cases of bleeding. As a preventive measure for women in the last weeks of pregnancy and newborn children should be given vitamin K1.
Breast-feeding
No data on the penetration eslikarbazepina acetate in human breast milk. The studies revealed the penetration eslikarbazepina acetate in breast milk of animals. Breast-feeding should be discontinued at the time of appointment eslikarbazepina acetate, because you can not eliminate the risk for the child.
fertility
Effect eslikarbazepina acetate fertility and the first generation progeny was evaluated in a study in rats and mice. In a study in male and female rats were detected violation of female fertility. In a study on mice, effects on embryo development, but this effect can also be caused by a decrease in the number of corpora lutea. The mice showed an increased risk of common disorders and major skeletal abnormalities. No impact on the performance of the first generation offspring fertility in rats and mice were observed
APPLICATION FOR FUNCTIONS OF THE LIVER
In the treatment of patients with renal failure caution and to conduct correction of the dose depending on the value QC:
- QA> 60 ml / min the dose correction is not required.
- CC 30-60 ml / min: initial dose of 400 mg every other day for 2 weeks followed by 400 mg once a day. However, taking into account the individual response the dose can be increased.
- QC <30 mL / minute: the use in patients with severe renal failure is not recommended due to insufficient data.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In case of mild or moderate hepatic insufficiency dose adjustment is required.
So its application in these patients is not recommended Pharmacokinetics eslikarbazepina acetate in patients with severe hepatic impairment has not been studied (see. Forums "Pharmacokinetics", "Special Instructions").
APPLICATION IN ELDERLY PATIENTS
Correction dose is not required, provided that renal function is not compromised.
SPECIAL INSTRUCTIONS
Suicidal Behavior
In appointing anticonvulsant drugs for several indications have been cases of suicidal behavior. Meta-analysis of randomized placebo controlled trials of antiepileptic drugs also showed a slight increase in risk of suicidal behavior. The mechanism of this phenomenon is not known, the available data do not exclude the possibility of similar reactions in patients receiving eslikarbazepina acetate. Thus, patients should be monitored for signs of suicidal behavior, and also considered appropriate treatment options. If you experience any signs of suicidal behavior in patients (and caregivers of patients) should seek medical advice.
Disturbances from the nervous system
Admission eslikarbazepina acetate may be accompanied by undesirable reactions in the central nervous system such as dizziness and somnolence, which increases the risk of accidental injury.
Oral contraception
Eslikarbazepina acetate may reduce the effectiveness of hormonal contraception. In applying the drug Eksalief В® it is recommended to use additional non-hormonal contraceptive methods (see. The sections "Patient interaction" and "Pregnancy and lactation").
Other precautions
If necessary, cancel drug Eksalief В® , it should be done gradually in order to minimize the risk of increasing the frequency of epileptic seizures.
Do not appoint eslikarbazepina acetate together with oxcarbazepine as possible overexposure to the active metabolites.
Information about the cancellation of related antiepileptic drugs during treatment with Eksalief В® (transition to monotherapy) are absent.
Skin reactions
during the additional placebo-controlled studies in patients with epilepsy at 1.1% of the total population of patients receiving Eksalief В® , marked by an adverse reaction in the form of skin rashes. When symptoms of hypersensitivity to the drug, Eksalief В® should be canceled.
The presence of the allele HLA-B * 1502
There is evidence that the allele HLA-B * 1502 is present in the Chinese Han nationality, natives of Thailand and other Asian countries, is associated with risk of developing Stevens-Johnson syndrome, during treatment with carbamazepine. The chemical structure of eslikarbazepina acetate is close to that of carbamazepine, and there is a possibility of increased risk of Stevens-Johnson syndrome in patients with the presence of the allele HLA-B * 1502 in the treatment of eslikarbazepina acetate. The prevalence of the allele HLA-B * 1502 among the Chinese Han nationality and the natives of Thailand is about 10%. Before assigning carbamazepine or chemically related compounds, if possible, should be screened for a given population of patients for the presence of said allele. Application eslikarbazepina acetate in patients with proven presence of the allele HLA-B * 1502 can be justified,if the benefits from the use outweigh the risks.
Because of the prevalence of this allele among the natives of other Asian countries (about 15% of the inhabitants of the Philippines and Malaysia), screening for the presence of the allele HLA-B * 1502 can also be appropriate.
Patients another ethnicity (Caucasian, African, Spanish, Japanese and Koreans) allele, HLA-B * 1502 is extremely rare (less than 1%).
The presence of the allele HLA-A * 3101
There is evidence to suggest that the allele HLA-A * 3101 present in Caucasians and Japanese, the treatment with carbamazepine increased the risk of allergic skin reactions such as Stevens-Johnson syndrome, toxic epidermalnyynekroliz, drug rash, accompanied by eosinophilia or less severe acute generalizovannyyekzentematoznyypustulez. Prevalence allele HLA-A * 3101 varies widely and ethnic populations ranges from 2 to 5% of the European population and about 10% of the Japanese. The presence of the allele HLA-A * 3101 may increase the risk of carbamazepine-induced cutaneous reactions (in most cases, less severe) from 5% in the general population and 26% among Caucasians, while lack of it, in turn, may reduce the risk of a 5 to 3.8%.
Data to recommend screening patients for the presence of the allele HLA-A * 3101 before prescribing carbamazepine or chemically-related compounds, is not enough.
Use of carbamazepine or chemically related compounds in patients with proven by the presence of allele HLA-A * 3101 can be justified if the benefits of using outweigh the risks.
Hyponatremia
Hyponatremia marked as unwanted reactions to the drug application Eksalief В®in 1.2% of patients. In most cases, hyponatremia is asymptomatic, but it can be accompanied by clinical symptoms, as the strengthening of epileptic seizures, confusion or the appearance of human consciousness. The incidence of hyponatremia increases with increasing dose eslikarbazepina acetate. When hyponatremia due to renal insufficiency history or the result of simultaneous reception of drugs that can cause hyponatremia (e.g., diuretics, desmopressin, carbamazepine), before and during treatment eslikarbazepina acetate, as well as in the development of clinical symptoms hyponatremia necessary to control the concentration of sodium in the serum. With the development of clinically significant hyponatremia eslikarbazepina acetate should be discontinued.
PR interval
In clinical studies eslikarbazepina acetate observed lengthening the interval PR. Care must be taken under certain conditions (e.g., at low concentrations of thyroxine, cardiac conduction disorders), or simultaneous administration of medicaments which, according to available data, accompanied by an elongation PR interval.
Renal insufficiency
In the treatment of patients with renal failure caution and to conduct correction of the dose according to the creatinine clearance (see. "Metering mode"). When CC <30 ml / min using the product Eksalief В® is not recommended due to insufficient data.
Liver failure
owing to the limited clinical data for patients with mild to moderate hepatic impairment, in this category of patients Eksalief В® used with caution. Due to the absence of clinical data not recommended Eksalief В® patients with severe liver failure.
Effects on ability to drive and use machines
Special study of the effect of the drug on the performance of potentially hazardous activities that require high concentration and psychomotor speed reactions were not carried out. Some patients may occur (especially at the beginning of treatment): dizziness, drowsiness or blurred vision. Patients should be warned that the likely violation of the physical and / or mental ability to operate a vehicle or machinery, and to recommend to refrain from such activities to establish the effect on it of the drug.
OVERDOSE
Accidental overdosing eslikarbazepina acetate following reactions observed in the central nervous system: vertigo, staggering gait and hemiparesis.
Treatment: a specific antidote is unknown. In case of overdose shows the corresponding symptomatic and supportive treatment. effectively removed if necessary metabolites eslikarbazepina acetate hemodialysis (see., "Pharmacological properties" section
DRUG INTERACTION
Drug interactions studies were conducted only in adults.
Eslikarbazepina acetate actively metabolized in eslikarbazepin which is outputted mainly by glyukuronirovaniya. In vitro eslikarbazepin is a weak inducer of CYP3A4 isoenzyme and UDP-glucuronyltransferases. In vivo it increases the metabolism of drugs which are advantageously oxidized isoenzyme CYP3A4 (eg simvastatin), which may require increasing doses of such drugs when used together with eslikarbazepina acetate. Eslikarbazepin in vivo may enhance the metabolism of drugs which come into conjugation reaction with UDP-glucuronyltransferases. The appointment or termination of the drug Eksalief В®And changing its mode of dosing, the enzyme activity is stabilized during 2-3 weeks, which should be considered when necessary dose adjustments drugs taken in conjunction with the preparation Eksalief В® .
Eslikarbazepin inhibits isozyme CYP2C19, which causes the potential dose-dependent interaction with it drugs that are metabolized mainly involving isoenzyme CYP2C19 (e.g., phenytoin).
Interaction with other AEDs
Carbamazepine
In a study involving healthy volunteers simultaneous application eslikarbazepina acetate at a dose of 800 mg once a day and carbamazepine 400 mg twice daily resulted in a reduction of the active metabolite - eslikarbazepina (average 32%), which most likely caused indutsirovaniemglyukuronirovaniya. At the same time enhance the action of carbamazepine or its metabolite - carbamazepine epoxide was observed. Thus, taking into account the individual response to therapy, the combined administration with carbamazepine, may require increased doses eslikarbazepina acetate. Studies involving patients show that while the appointment with carbamazepine increased the risk of the following adverse reactions: diplopia, incoordination of movement and dizziness.We can not exclude the risk of amplification of other specific adverse reactions caused by the simultaneous intake of carbamazepine and eslikarbazepina acetate.
Phenytoin
In a study involving healthy volunteers simultaneous application eslikarbazepina acetate at a dose of 1200 mg once daily and phenytoin resulted in a reduction of the active metabolite, eslikarbazepina (on average 31-33%), which most likely caused indutsirovaniemglyukuronirovaniya. In this case there was an increase phenytoin action (on average 31-35%), which presumably is caused by inhibition of isozyme CYP2C19. Thus, taking into account the individual response to the combined treatment assignment may need to increase the dose eslikarbazepina acetate and phenytoin dose reduction.
Lamotrigine
glucuronidation is a major route of metabolism and eslikarbazepina Lamothe
