Trileptal

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Trileptal: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Trileptal

ATX code: N03AF02

Active ingredient: oxcarbazepine (oxcarbazepine)

Producer: Novartis Pharma SpA (Italy), Delpharm Yuning S. A. S. (France)

Description and photo update: 2018-21-11

Prices in pharmacies: from 372 rubles.

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Trileptal is an anticonvulsant drug.

Release form and composition

Dosage forms of Trileptal:

film-coated tablets: slightly biconvex, oval, with a dividing line on both sides, in three doses: 150 mg - gray-green, marked "C / G" on one side, "T / D" on the other; 300 mg - yellow, marked "CG / CG" on one side, "TE / TE" on the other; 600 mg - light pink, marking “CG / CG” on one side, “TF / TF” on the other (10 pcs. In blisters, in a cardboard box of 1, 2, 3 or 5 blisters);
suspension for oral administration: liquid with a fruity odor from almost white to weak brown or weak red [100 or 250 ml in dark glass vials, in a cardboard box 1 bottle complete with a dosing syringe (1 ml or 10 ml) and adapter].

1 tablet contains:

active substance: oxcarbazepine - 150 mg, 300 mg or 600 mg;
auxiliary components: crospovidone, anhydrous colloidal silicon dioxide, magnesium stearate, hydroxypropyl methylcellulose (hypromellose / cellulose HP-M 603), microcrystalline cellulose (Avicel PH 102);
shell composition: titanium dioxide, talc, hydroxypropyl methylcellulose (hypromellose / cellulose HP-M 603).

In addition, the tablet contains:

dose of 150 mg: iron oxide black (E172), iron oxide red (E172), iron oxide yellow (E172), macrogol 4000;
dose of 300 mg: iron oxide yellow, macrogol 8000 (polyethylene glycol 8000);
dose 600 mg: iron oxide black, iron oxide red, macrogol 4000.

1 ml of suspension contains:

active substance: oxcarbazepine - 60 mg;
auxiliary components: ascorbic acid, sorbic acid, sodium saccharinate, propyl parahydroxybenzoate, methyl parahydroxybenzoate, macrogol 400 stearate, dispersible cellulose (sodium carmellose and microcrystalline cellulose), yellow plum-lemon aroma 39K020 [propylene glycol solution) (16%) and ethanol (16%], 70% liquid sorbitol, distilled propylene glycol, purified water.

Pharmacological properties

Pharmacodynamics

Trileptal is an antiepileptic drug, the active ingredient of which is oxcarbazepine. Its pharmacological action is primarily due to the activity of its metabolite, a monohydroxy derivative (MHD). The mechanism of action of the drug is associated to a greater extent with the blockade of voltage-gated sodium channels. This leads to a decrease in synaptic impulse conduction, helps to stabilize overexcited neuronal membranes and to inhibit the occurrence of serial neuronal discharges.

The anticonvulsant effect of Trileptal is realized due to an increase in the conductivity of potassium ions and modulation of calcium channels, which are activated by a high potential of the membrane. No receptor binding and significant interactions with brain neurotransmitters were noted. Experimental studies have confirmed the pronounced anticonvulsant effect of oxcarbazepine and IHP.

For epileptic seizures in children and adults, Trileptal is clinically effective in monotherapy and in combination therapy.

Trileptal can be used to replace other antiepileptic drugs, the use of which does not allow achieving a sufficient therapeutic response to therapy.

Pharmacokinetics

Film-coated tablets and oral suspension are biologically equivalent.

After oral administration of tablets, absorption from the gastrointestinal tract of oxcarbazepine occurs quickly and almost in full (more than 95%). It is metabolized to a large extent with the formation of a 10-monohydroxy derivative (MHD), a pharmacologically active metabolite. After a single dose of a 600 mg tablet on an empty stomach, the maximum concentration (C _max) in the blood plasma of MHP is reached after 5 hours and averages 31.5 μmol / L.

After a single dose of the suspension at a dose of 600 mg on an empty stomach, C _{max of} MHP in blood plasma is achieved after 6 hours and averages 24.9 μmol / L.

The degree and rate of absorption of oxcarbazepine do not change with simultaneous intake of food.

The apparent volume of distribution of IHP is 49 liters.

The binding of IHP to blood plasma proteins, to a greater extent to albumin, is approximately 40%. The degree of binding does not depend on the concentration of the drug in the blood serum. With alpha _1- acid glycoprotein binding of oxcarbazepine and MHD does not occur.

Oxcarbazepine and its active metabolite cross the placental barrier.

In the blood plasma, the content of oxcarbazepine is 2%, MHP - 70%, the rest are secondary metabolites that are rapidly eliminated from the plasma.

The equilibrium concentration of MHP in the blood plasma is reached after 2-3 days while taking Trileptal 2 times a day. In the equilibrium state, the linear and dose-dependent character of the pharmacokinetic parameters of MHP remains in the range of 300–2400 mg per day.

Cytosolic liver enzymes rapidly metabolize oxcarbazepine to IHP. Then it is conjugated with glucuronic acid. The amount of MHP, corresponding to 4% of the dose taken, is oxidized to form 10,11-dihydroxy derivative (DHP), which is an inactive metabolite.

Oxcarbazepine is excreted mainly through the kidneys in the form of metabolites (more than 95% of the dose, of which 80% are MHP, about 13% are oxcarbazepine conjugates, about 3% are inactive DHP) and unchanged (less than 1%).

About 4% of the dose is excreted through the intestines.

Apparent T _1/2 (half-life) of oxcarbazepine is 1.3–2.3 hours, IHP is on average 9.3 hours.

Patients over the age of 60 years do not need a special dose adjustment, since the selection of the therapeutic dose of Trileptal is made individually.

The IHD clearance, adjusted for body weight, decreases in children with increasing age and body weight, approaching the clearance of adults. So at the age from 1 month to 4 years it is about 93%, and in children 4-12 years old - 43%, higher than the clearance of adults. Based on this, it is assumed that when taking the same doses, adjusted for body weight, the AUC (total concentration) of MHP in blood plasma in children compared with adults is 2 times lower at the age from 1 month to 4 years, and is 2/3 from AUC of adults - at 4-12 years. In children 13 years of age and older, the weight-adjusted IHP clearance is presumably the same as in adults.

Pharmacokinetic parameters of the drug are the same in patients of both sexes in childhood, adulthood and old age.

Mild and moderate liver dysfunction does not affect the pharmacokinetic parameters of oxcarbazepine and MHP. Pharmacokinetics in patients with severe liver dysfunction has not been studied.

Renal clearance of IHP is linearly dependent on creatinine clearance (CC).

With CC less than 30 ml / min, a single dose of Trileptal at a dose of 300 mg causes an increase in T _{1/2 of} MHP up to 16-19 hours (by 60-90%), AUC - 2 times.

Physiological changes in the body that occur during pregnancy can contribute to a gradual decrease in the level of MHP in the blood plasma.

Indications for use

According to the instructions, Trileptal is used as monotherapy and in combination with other antiepileptic drugs in the treatment of the following diseases:

simple and complex partial epileptic seizures without secondary generalization or with it in children aged 1 month of life and adults;
generalized tonic-clonic epileptic seizures in patients aged 2 years and older.

Contraindications

breast-feeding;
age: up to 3 years - for tablets, up to 1 month of life - for suspension;
individual intolerance to the components of the drug.

Special care should be taken when prescribing Trileptal to patients with established hypersensitivity to carbamazepine, since hypersensitivity reactions to oxcarbazepine may develop in 25-30% of patients in this group. It should be borne in mind that the risk of developing hypersensitivity reactions to the drug, including multiple organ disorders, is also present in patients with no history of hypersensitivity to carbamazepine.

It is necessary to use Trileptal with caution in patients with severely impaired liver function.

Prescribing the drug during pregnancy is possible in special cases, especially in the first trimester, only if the expected effect of therapy for the mother justifies the possible threat to the fetus.

Instructions for the use of Trileptal: method and dosage

Trileptal tablets and suspension are taken orally 2 times a day, regardless of food intake. The tablets should not be chewed; to facilitate swallowing, they can be broken into 2 parts at risk.

Treatment begins with a clinically effective dose, which can then be increased based on response to therapy.

When switching from another antiepileptic drug, its cancellation is carried out, gradually reducing the dose from the moment you start taking Trileptal.

Due to an increase in the total antiepileptic dose when Trileptal is prescribed as part of a combination therapy with other antiepileptic drugs, it is necessary to start its use with the lowest dose and to slowly increase it and / or reduce the doses of simultaneously taken antiepileptic drugs.

Due to the bioequivalence of the suspension and tablets, it is possible to interchange dosage forms if necessary. To switch from a dose in mg to a dose in ml, use a dosing syringe and the following dose correspondence:

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 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 ml;
400 mg: 6.7 ml;
500 mg: 8.3 ml;
600 mg: 10 ml;
700 mg: 11.7 ml;
800 mg: 13.3 ml;
900 mg: 15 ml;
1000 mg: 16.7 ml.

Treatment should be accompanied by periodic monitoring of the level of MHP in the blood plasma in order to confirm strict adherence to the patient's therapy regimen or to adjust the dose. Particular attention should be paid to patients with impaired renal function, during pregnancy and while taking drugs that increase the activity of liver enzymes. In this category of patients, dose adjustment is performed if the level of MHP in the blood plasma is 2–4 hours after taking a single dose of Trileptal above 35 mg / l.

Recommended dosage for monotherapy and combination therapy:

adults: initial daily dose - Trileptal 600 mg, divided into 2 doses (at the rate of 8-10 mg per 1 kg of body weight per day). To achieve the desired therapeutic response, the dose can be increased by no more than 600 mg once every 7 days. Typically, the clinical effect is provided by a daily dose in the range of 600-2400 mg. When taking the drug at a dose of 2400 mg per day as part of a combination therapy, it is necessary to consider lowering the dose of a concomitant antiepileptic agent;
children: initial dose - at the rate of 8-10 mg per 1 kg of body weight per day, divided into 2 doses. As part of combination therapy, the target daily dose of 30–46 mg per 1 kg must be reached no earlier than 14 days after the start of therapy. To achieve the desired therapeutic response, the dose can be increased by 10 mg per kg with an interval of 7 days. The maximum daily dose is 60 mg per 1 kg of body weight. In children aged 1 month to 4 years, when using Trileptal in combination with antiepileptic drugs that are inducers of liver enzymes, it may be necessary to increase the dose of oxcarbazepine by 60% (when adjusted for body weight) of the dose for monotherapy. Older children in a similar situation may require only a slight increase in the dose of Trileptal compared to monotherapy.

In case of impaired renal function with CC less than 30 ml / min, the initial daily dose should not exceed 300 mg. Under the close supervision of a physician, the dose can be increased at intervals of at least 7 days, until a dose is reached that provides the desired therapeutic response.

Correction of the dosage regimen in patients over the age of 65 is required in case of impaired renal function with CC less than 30 ml / min. If there is a risk of hyponatremia in elderly patients, plasma sodium levels should be carefully monitored.

With mild to moderate liver dysfunction, dosage adjustment is not required. Care should be taken in severe liver dysfunction.

Side effects

Undesirable effects established during clinical trials and the use of Trileptal in clinical practice:

on the part of the psyche: often - apathy, emotional lability, confusion, agitation, nervousness, depression;
from the nervous system: very often - headache, dizziness, drowsiness; often - impaired attention, ataxia, nystagmus, tremor, amnesia;
on the part of the blood and lymphatic system: infrequently - leukopenia; very rarely - agranulocytosis, suppression of bone marrow hematopoiesis, aplastic anemia, pancytopenia, thrombocytopenia;
from the digestive system: very often - nausea, vomiting; often - abdominal pain, constipation, diarrhea; very rarely - pancreatitis;
from the endocrine system: very rarely - hypothyroidism;
on the part of the immune system: very rarely - multiple organ disorders and hypersensitivity reactions in the form of skin rash and fever, anaphylactic reactions; possibly - shortness of breath, bronchospasm, interstitial inflammation, pulmonary edema, bronchial asthma, leukopenia, eosinophilia, thrombocytopenia, splenomegaly, lymphadenopathy, liver damage (changes in liver function parameters, hepatitis), edema in the joints, myalgia, arthralgia, hepatic encephalic, proteinuria, interstitial nephritis, angioedema;
on the part of nutrition and metabolism: often - hyponatremia (more often over the age of 65); very rarely - hyponatremia with sodium levels less than 125 mmol / L (usually during the first three months of taking Trileptal), manifests itself as convulsive attacks, vomiting, nausea, decreased level of consciousness, encephalopathy, confusion, hypothyroidism, visual impairment (including blurred vision), folic acid deficiency;
on the part of the organ of hearing and labyrinth disorders: often - systemic dizziness;
on the part of the organ of vision: very often - diplopia; often - disturbances and / or blurred vision;
on the part of the cardiovascular system: very rarely - arterial hypertension, arrhythmias, atrioventricular block;
from the hepatobiliary system: very rarely - hepatitis;
dermatological reactions: often - rash, acne, alopecia; infrequently - urticaria; very rarely - angioedema, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), systemic lupus erythematosus, erythema multiforme;
general disorders: very often - feeling tired; often - asthenia;
laboratory indicators: infrequently - increased activity of alkaline phosphatase, liver enzymes; very rarely - an increase in the activity of lipase, amylase.

In children aged 1 month to 4 years, taking Trileptal very often causes drowsiness, often vomiting, ataxia, irritability, decreased appetite, fatigue, lethargy, nystagmus, tremors, increased levels of uric acid concentration in the blood.

Side effects of Trileptal, recorded in the post-marketing period:

dermatological reactions: rash with systemic manifestations and eosinophilia, acute generalized exanthematous pustulosis;
from the musculoskeletal and connective tissue: a decrease in bone mineral density, osteopenia, osteoporosis, bone fractures;
on the part of nutrition and metabolism: syndrome of inadequate secretion of antidiuretic hormone - lethargy, nausea, dizziness, decreased osmolality of blood plasma, vomiting, headache, confusion and other symptoms from the nervous system;
from the nervous system: speech disorders, including dysarthria (more often during the dose selection period);
others: fall.

Overdose

Symptoms include drowsiness, nausea, vomiting, confusion, fatigue, headache, hyponatremia, hyperkinesia, diplopia, blurred vision, miosis, aggression, agitation, shortness of breath, decreased respiratory rate, lengthening the interval QT _c, lowering blood pressure (BP), dizziness, ataxia, nystagmus, tremor, lack of coordination, convulsions, loss of consciousness, coma, dyskinesia.

Treatment: there is no specific antidote. Immediate gastric lavage, intake of activated charcoal. Ensuring control of vital body functions, including cardiac conduction, water and electrolyte balance, respiratory system functions. Appointment of symptomatic and supportive therapy.

special instructions

If the course of epileptic seizures worsens, Trileptal should be discontinued.

There is a risk of developing immediate hypersensitivity reactions (type I), manifested by the appearance of rash, pruritus, urticaria, angioedema and anaphylactic reactions. External manifestations can be accompanied by the development of disorders from the liver, lymphatic system, blood and other organs.

Angioedema and anaphylaxis reactions can occur not only with the first, but also with repeated administration of the drug. If symptoms of hypersensitivity reactions, including immediate type, appear, the use of Trileptal should be discontinued immediately and alternative therapy should be used.

The development of hyponatremia during the use of oxcarbazepine, as a rule, is not accompanied by clinical manifestations and does not require therapy correction. The sodium content is normalized by restricting fluid intake or reducing the dose of Trileptal. The risk of developing hyponatremia is in patients with a history of functional impairment of the kidneys and an initially low sodium content in the blood serum, which arose against the background of the syndrome of inadequate secretion of antidiuretic hormone, simultaneous treatment with agents that promote sodium excretion from the body. Before starting the use of Trileptal, the sodium content in the blood serum should be determined. Treatment should be accompanied by monitoring this indicator regularly - 14 days after the start of therapy, then 1 time in 30 days for 3 months or as needed. Patients with heart failure should be advised to carry out body weight control in order to diagnose fluid retention in the body in a timely manner.

With a pronounced suppression of bone marrow hematopoiesis, the cancellation of Trileptal is required.

While taking anticonvulsants, patients have an increased risk of developing suicidal behavior, therefore, during the entire period of treatment, the patient must be carefully monitored.

The development of skin reactions is the basis for considering replacing Trileptal with another antiepileptic drug. The incidence of dermatological reactions, in addition to the dose of anticonvulsant drugs, patient compliance, the simultaneous use of other drugs or the presence of concomitant diseases, can be significantly influenced by the presence of the human leukocyte antigen alleles HLA-B * 1502 and HLA-A * 3101 in a patient. Alleles of the HLA-B * 1502 antigen are more common in residents of China, Korea, India, Malaysia, Thailand. Among the peoples of the Caucasian, Negroid races, Indians, Hispanics and Japanese, the probability of having this allele is insignificant. Prescribing a drug to a patient who may be a carrier of the HLA-B * 1502 allele,should be done on the basis of the results of preliminary genotyping for this allele. Techniques with high resolution should be used, the test is considered positive when at least one of the alleles is found, negative - the complete absence of alleles.

If symptoms of hepatitis appear, Trileptal must be canceled.

In children, especially under the age of two years, before starting drug therapy, it is recommended to conduct a study to determine the level of concentration of thyroid hormones and monitor this indicator throughout the period of taking Trileptal.

Abrupt withdrawal of the antiepileptic drug should not be allowed, this can increase the frequency of seizures.

Alcohol consumption during therapy can increase the sedative effect.

Influence on the ability to drive vehicles and complex mechanisms

During the period of application of Trileptal, care should be taken when driving vehicles or complex mechanisms.

If dizziness, drowsiness, ataxia, diplopia, blurred and impaired vision, depression of consciousness or other undesirable phenomena appear on the background of therapy, one should refrain from performing potentially dangerous activities.

Application during pregnancy and lactation

Women with epilepsy are prone to having children with developmental disabilities.

The limited experience of using Trileptal during pregnancy suggests the effect of the drug on the development of the following congenital defects in children whose mothers took oxcarbazepine during gestation: cleft hard palate and upper lip, atrial or atrioventricular septal defect, tuberous sclerosis, Down syndrome, and bilateral hip dysplasia, ear malformations.

During the period of taking Trileptal, patients of childbearing age should use intrauterine contraceptives, since hormonal oral contraceptives do not provide reliable contraception.

The appointment of Trileptal during pregnancy is indicated only in special cases, especially in the first trimester, if the expected effect of therapy for the mother justifies the possible threat to the fetus, the minimum effective dose should be used.

The patient should be informed about the risk of fetal disorders and the mandatory antenatal diagnosis.

If conception occurs during the period of an effective antiepileptic course of therapy, treatment cannot be interrupted, as this can cause the progression of the disease and negatively affect the condition of the mother and fetus.

Due to the risk of increased folic acid deficiency against the background of antiepileptic therapy during gestation, the simultaneous use of folic acid preparations is recommended. In addition, vitamin K _{1 is} indicated to prevent increased bleeding in a newborn in the last few weeks of pregnancy.

To ensure maximum control of symptoms of the disease during pregnancy and after delivery, it is necessary to conduct a study to determine the concentration of MHP in blood plasma.

The drug passes into breast milk, therefore, if you need to take Trileptal during lactation, breastfeeding should be stopped.

Pediatric use

Age contraindications:

tablets: children under three years old;
suspension: infants up to 1 month of age.

With impaired renal function

The initial daily dose for patients with CC below 30 ml / min should be 300 mg. An increase in the dose of Trileptal until the desired therapeutic response is achieved should be performed at intervals of at least 7 days, carefully monitoring the patient's condition during this period.

For violations of liver function

Caution should be exercised when using Trileptal in patients with severely impaired liver function.

With mild to moderate liver dysfunction, dosage adjustment is not required.

Use in the elderly

Elderly patients do not need a special correction of the dosage regimen.

The need to reduce the dose of Trileptal arises in case of impaired renal function with a CC below 30 ml / min. If there is a risk of hyponatremia, regular monitoring of the level of sodium concentration in blood plasma is required.

Drug interactions

With the simultaneous use of Trileptal:

phenobarbital, phenytoin and other drugs that are metabolized with the participation of the CYP2C19 isoenzyme can interact with Trileptal;
oral contraceptives, dihydropyridine calcium antagonists and other antiepileptic drugs, metabolized by cytochrome CYP3A4 and CYP3A5 enzymes, reduce their plasma concentrations (including carbamazepine - up to 22%);
cyclosporine and other immunosuppressants (substrates of isoenzymes CYP3A4 and CYP3A5) can lower their plasma levels;
drugs metabolized by uridine diphosphate-glucuronyltransferase or with the participation of the CYP3A4 isoenzyme may require an increase in their dose;
phenytoin increases the level of its concentration in blood plasma up to 40% while taking oxcarbazepine in a daily dose of 1200 mg or more;
phenobarbital increases its concentration in blood plasma by 15%;
carbamazepine, phenytoin and phenobarbital (strong inducers of cytochrome P ₄₅₀) reduce the concentration of MHP in the blood plasma by 29–40%, requiring appropriate dose adjustment of oxcarbazepine;
hormonal oral contraceptives reduce their total plasma concentration (including those containing ethinylestradiol - by 48–52%, levonorgestrel - by 32–52%), which causes a significant decrease in their effectiveness; the use of additional non-hormonal methods of contraception is recommended;
felodipine can reduce its total concentration by 28%, while maintaining therapeutic efficacy;
verapamil causes a decrease in the level of MHP in the blood plasma by only 20%, without disrupting the clinical action of Trileptal;
cimetidine, dextropropoxyphene, erythromycin do not violate the pharmacokinetic parameters of IHP;
viloxazine promotes a slight increase in plasma MHP concentration (by 10% with repeated joint use);
warfarin, tricyclic antidepressants do not cause clinically significant interactions with Trileptal;
ethanol can enhance its sedative effect;
lithium preparations increase the risk of neurotoxicity.

Analogs

Analogs of Trileptal are: Carbamazepine, Valproate, Gabapentin, Phenytoin, Finlepsin.

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 30 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Trileptal

Reviews of Trileptal prove its effectiveness in focal and generalized tonic-clonic epileptic seizures. When switching from combination therapy with other antiepileptic drugs to monotherapy with the drug, patients indicate a sufficient therapeutic response and significantly better tolerance. This allows them to avoid various complications with prolonged therapy.

It is noted that with the generalized form of epilepsy, monotherapy with Trileptal for a year made it possible to achieve complete disappearance of seizures. Compared to other drugs, Trileptal has fewer side effects, after taking it, there is no headache, there are no night attacks, many patients feel vigorous.

Often in the reviews there are also reports of side effects in the form of increased appetite, drowsiness, tearfulness, transient double vision, dizziness.

Price for Trileptal in pharmacies

The price of Trileptal for a package containing 50 tablets at a dose of 150 mg can range from 456 rubles, 50 Trileptal 600 mg tablets - from 1,514 rubles, for 1 bottle (100 ml) of suspension - from 450 to 542 rubles.

Trileptal: prices in online pharmacies

Drug name

Price

Pharmacy

Trileptal 150 mg film-coated tablets 50 pcs.

372 r

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Trileptal tablets p.p. 150mg 50 pcs.

382 r

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Trileptal 60 mg / ml oral suspension 100 ml 1 pc.

419 RUB

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Trileptal 600 mg film-coated tablets 50 pcs.

1272 RUB

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Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!