TRILEPTAL 150MG PILLS

Coated tablets

Composition

1 coated pill contains: oxcarbazepine 150 mg.
Excipients: colloidal silicon dioxide, microcrystalline cellulose, hypromellose, crospovidone, Magnesium stearate, macrogol 8000, talc, titanium dioxide (E171), purified water, ferric oxide yellow (E172).

Packing

50 pcs.

Mechanism of action

Trileptal is an antiepileptic drug. The pharmacological activity of Trileptal is caused, first of all, by the action of its metabolite, the monohydroxy derivative (IHP). The mechanism of action of oxcarbazepine and its MHD is mainly associated with the blockade of potential-dependent sodium channels, which leads to stabilization of the over-excited neuronal membranes, inhibiting the occurrence of serial neuronal discharges and reducing synaptic impulses. In addition, the implementation of the anticonvulsant action of the drug contributes to an increase in the conductivity of potassium ions and modulation of Calcium channels activated by a high membrane potential. No significant interactions with brain neurotransmitters or receptor binding were noted. Experimental studies have shown that oxcarbazepine and IHD have a pronounced anticonvulsant effect.
The effectiveness of Trileptal with partial (focal) epileptic seizures (simple, complex; partial seizures with or without secondary generalization) and with generalized tonic-clonic seizures has been demonstrated both with monotherapy and with Trileptal as part of combination therapy. The efficacy of replacing various antiepileptic drugs (such as Carbamazepine, Gabapentin, lamotrigine, phenytoin, and valproate) with trileptal monotherapy has been confirmed. In children (aged 3-17 years), Trileptal was studied as part of combination therapy in comparison with placebo and as monotherapy in comparison with phenytoin. The effectiveness of Trileptal in the dose range from 600 mg to 2400 mg per day was confirmed in all parameters of primary efficacy, such as a change in the frequency of attacks from the baseline (when studying combination therapy) and the time to reach the end points or the proportion of patients who reached the end points (with monotherapy study).
The drug was studied in clinical studies in children aged 1 month and older. In partial seizures, trileptal monotherapy was shown to be effective in children aged 1 month to 16 years with poorly controlled or first-time seizures, as well as the effectiveness of Trileptal in combination therapy in children aged 1 month to 4 years with badly controlled seizures 1 -2 antiepileptic drugs.
It was shown that the effectiveness of Trileptal is similar to the efficacy of first-choice drugs (ie, valproic acid, phenytoin, carbamazepine), and tolerability is statistically significantly better than phenytoin, which was assessed by a smaller number of cases of discontinuation of therapy due to adverse events and long stay on therapy. For 12 months, trileptal monotherapy in patients with partial and generalized tonic-clonic seizures in both groups, the proportion of patients who had complete relief of seizures was similar.

Indications and usage

- Simple and complex partial epileptic seizures with secondary generalization or without it in adults and children aged 1 month and older.
- Generalized tonic-clonic epileptic seizures in adults and children aged 2 years and older.
- Trileptal is a first-line drug for monotherapy or as part of combination therapy.
- Trileptal can be used to replace other antiepileptic drugs in cases where the use of the latter does not achieve a satisfactory therapeutic response to treatment.

Contraindications

Hypersensitivity to oxcarbazepine or any other components of the drug.

The experience of using Trileptal during pregnancy is limited.Available reports suggest a possible connection with the use of the drug during pregnancy with the development of birth defects (for example, wolf mouth). It is necessary to carefully compare the expected benefits of therapy and its possible complications, especially in the first trimester of pregnancy in the event that a woman receiving Trileptal has a pregnancy, or if the question of prescribing Trileptal occurs during pregnancy.
Minimum effective doses should be used. The patient should be warned about possible violations of the development of the fetus and the need for antenatal diagnosis. It is known that during pregnancy, folic acid deficiency develops. Antiepileptic drugs can exacerbate this deficiency, which is one of the possible causes of impaired fetal development, so additional folic acid supplementation is recommended. There are reports that the use of antiepileptic drugs during pregnancy can lead to increased bleeding in the newborn. As a precautionary measure, the prescription of vitamin K1 is recommended in the last few weeks of pregnancy, as well as to newborns whose mothers received Trileptal. Oxcarbazepine and IHP penetrate the placental barrier and are excreted in breast milk. The ratio of concentrations in milk and plasma was 0.5 for both substances. The effect on oxcarbazepine and IHD on a newborn, which was administered with mother's milk, is unknown.Therefore it is not necessary to apply Trileptal when breastfeeding.

Dosage and administration

Trileptal can be used both as monotherapy and in combination with other anti-epileptic drugs. In both cases, the treatment begins with a clinically effective dose divided into two doses. 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 replacement drug should be gradually reduced. When using Trileptal as an additional therapy as part of a polytherapy, a reduction in the dose of concomitant antiepileptic drugs and / or a slower increase in the dose of Trileptal may be required. Trileptal can be taken regardless of the meal (during, after a meal or in between meals). The recommendations below apply to patients with normal renal function. For this category of patients, there is no need to monitor the concentration of the active substance in the plasma in order to optimize the treatment with Trileptal. There are risks on the tablets, they can be broken into 2 parts to facilitate swallowing. In controlled clinical trials, the use of Trileptal in a daily dose above 2400 mg has not been studied. There is limited experience with the use of Trileptal in a daily dose of up to 4200 mg.
Adults and elderly patients as monotherapy: The initial dose is 600 mg / day (8-10 mg / kg of body weight per day), divided into two doses. A good therapeutic response was observed in the dose range of 600-2400 mg / day. If necessary, a gradual increase in dose. The dose is increased by no more than 600 mg / day with an interval of about 1 week, until a desired therapeutic response is achieved. In stationary conditions, there is experience of rapidly increasing the dose to 2400 mg / day for 48 hours.
When administered as part of a combination therapy: The initial dose is 600 mg / day (8-10 mg / kg / 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. The dose is increased by no more than 600 mg / day with an interval of about 1 week, until a desired therapeutic response is achieved.
Use in elderly patients: A special correction of the dosage regimen for elderly patients is not required, since the therapeutic dose of the drug is determined individually.
For children The recommended initial dose is 8–10 mg / kg body weight / day, divided into two doses, both with monotherapy and with Trileptal as part of combination therapy. In clinical studies of the use of Trileptal as part of combination therapy in pediatric practice in children aged 3 to 17 years, the average dose of the drug was 31 mg / kg / day (from 6 to 51 mg / kg / day) with a target dose of 46 mg / kg / days In clinical studies of the use of Trileptal as part of combination therapy in children aged 1 month to 4 years, 56% of patients received a dose of at least 55 mg / kg / day with a target dose of 60 mg / kg / day.If necessary, to achieve the desired therapeutic effect, a gradual increase in the dose is possible: with an interval of about 1 week, the dose is increased to a maximum of 10 mg / kg / day, up to a maximum daily dose of 60 mg / kg body weight. When using Trileptal as monotherapy and as part of a combination therapy, when adjusting for body weight, the apparent clearance in children decreases significantly with increasing age. Children aged 1 month to 4 years may require a dose of the drug, 2 times the dose for adults, when adjusting for body weight; Children aged 4 to 12 years may require a dose exceeding 50% of the dose for adults, when adjusting for 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 Trileptal in children aged 1 month to 4 years in combination with antiepileptic drugs - liver enzyme inducers, a dose of oxcarbazepine may be 60% higher (when adjusted for body weight) than with trileptal monotherapy or when used in combination with antiepileptic agents that do not induce enzymes. For children of older age groups, when conducting tripleptal combination therapy with liver enzyme inducers, a slight increase in the dose of the drug may be required compared with monotherapy.
When using Trileptal in younger children (up to 3 years) who cannot swallow tablets, and also in cases where it is impossible to measure the required dose when using the drug in the form of tablets, the drug is preferably used in the form of a suspension due to the difficulties of using solid medicinal forms in this age group. Suspension for oral administration and coated tablets are interchangeable in equivalent doses.
No dosing regimen requiredin patients with mild to moderate hepatic impairment. 
For patients with impaired renal function (creatinine clearance less than 30 ml / min), the recommended initial dose is 300 mg / day and should be increased slowly until the desired therapeutic response is achieved.

The following adverse reactions were reported most frequently: drowsiness, headache, dizziness, diplopia, nausea, vomiting, feeling tired (more than in 10% of patients). In clinical studies, it was shown that undesirable effects are usually mild or moderately pronounced, are transient in nature and are observed mainly at the beginning of therapy. The data below summarizes the information on adverse events registered during clinical trials, as well as data on the safety profile of the drug, obtained during its use in clinical practice.
From the hemopoietic system: sometimes - leukopenia, very rarely - thrombocytopenia.
On the part of the immune system: very rarely, hypersensitivity reactions (including abnormal liver function indicators, rash, fever, lymphadenopathy, eosinophilia, arthralgia).
Metabolism: often - hyponatremia; very rarely, clinically significant hyponatremia (sodium concentration <125 mmol / l), leading to the development of such manifestations and symptoms as convulsive seizures, confusion, decreased consciousness, encephalopathy, visual disturbances (including blurred vision), nausea vomiting. Such hyponatremia occurs, as a rule, during the first 3 months of drug therapy; in some patients, more than 1 year after the start of treatment with Trileptal.
From the side of the central nervous system: very often - drowsiness, headache, dizziness; often - ataxia, tremor, nystagmus, impaired attention, amnesia; confusion, depression, apathy, agitation, emotional lability.
From the senses: very often - diplopia; often - visual impairment, blurred vision, vertigo.
Since the cardiovascular system: very rarely - arrhythmias, AV blockade.
From the digestive tract: very often - nausea, vomiting; often - diarrhea, constipation, abdominal pain; sometimes - increased activity of liver enzymes; very rarely - pancreatitis and / or increased levels of lipase and / or amylase, hepatitis.
Dermatological reactions: often - rash, alopecia, acne.
Allergic reactions: sometimes - urticaria; very rarely - angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme.
Other: very often - feeling tired; often - asthenia; very rarely - systemic lupus erythematosus.
In children: in clinical studies conducted in children aged 1 month to 4 years, drowsiness was most often observed (in 11% of patients). With a frequency of> 1% - <10% (often) there was ataxia, irritability, vomiting, lethargy, fatigue, nystagmus, tremor, loss of appetite, and an increase in the concentration of uric acid in the blood.

With caution, prescribe the drug to patients with a known hypersensitivity to carbamazepine, because approximately 25-30% of these patients may develop hypersensitivity reactions to oxcarbazepine. Hypersensitivity reactions may also develop in patients without a history of hypersensitivity to carbamazepine. In the event of the development of hypersensitivity reactions, Trileptal should be immediately canceled.
Very rarely was reported the development of serious dermatological reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exudative erythema multiforme with the use of Trileptal. Patients with serious dermatological reactions may require hospitalization due to the development of life-threatening conditions; fatal outcomes are very rare.Hypersensitivity reactions to trileptal were observed in both children and adults, developing on average after 19 days. There are separate reports of cases of recurrence of skin reactions with the resumption of taking Trileptal. With the development of skin reactions on the background of the use of Trileptal should consider the question of discontinuation of the drug and the appointment of another antiepileptic agent.
In 2.7% of patients receiving Trileptal, hyponatremia (serum sodium concentration less than 125 mmol / l) was observed, which usually was not accompanied by clinical manifestations and did not require correction of therapy. Sodium concentration is normalized with the cancellation (dose reduction) of Trileptal or conservative treatment (limiting fluid intake). In patients who already have impaired renal function and low serum sodium concentration, or in patients receiving concomitant treatment with drugs that promote the excretion of sodium from the body (diuretics, drugs that affect the secretion of antidiuretic hormone), before starting treatment with Trifleptal, concentration should be determined sodium in serum. In the future, the concentration of sodium in the serum should be monitored 2 weeks after the start of therapy and then monthly for 3 months or as needed. Special attention should be given to these risk factors in elderly patients. If necessary, the appointment of diuretics and other drugs that reduce the concentration of sodium in the serum, patients receiving therapy with Trileptal should follow the same recommendations.With the appearance of clinical symptoms that allow to suspect hyponatremia, the concentration of sodium in the blood serum should be measured. For the remaining patients, the measurement of serum sodium concentration can be carried out during routine blood tests.
It is necessary to control body weight in all patients with heart failure for the timely determination of fluid retention. In the case of fluid retention or with the progression of symptoms of heart failure, the concentration of sodium in the serum should be determined. In the event of hyponatremia, limit the amount of fluid consumed. Despite the fact that in clinical studies there were no cases of cardiac conduction disturbances during the administration of oxcarbazepine, careful monitoring of patients with previous conduction disorders (AV block, arrhythmia) receiving Trileptal is necessary.
There are reports of very rare cases of hepatitis, which in most cases were safely resolved. If you suspect that you have hepatitis, you should consider withdrawing the drug.
Women of childbearing age who take oral contraceptives should be warned that the simultaneous use of Trileptal can lead to a decrease in the effectiveness of hormonal contraceptives. In this category of patients receiving Trileptal, the additional use of non-hormonal methods of contraception is recommended.In women of childbearing age, trileptal is recommended to be used, if possible, as a monotherapy. Like any other antiepileptic drugs, Trileptal should be discontinued gradually, due to the risk of an increase in the incidence of seizures.

Inhibitors of microsomal enzymes: Oxcarbazepine and its pharmacologically active metabolite MHP are inhibitors of cytochrome CYP2C19. Thus, the simultaneous administration of high doses of Trileptal and drugs metabolized by CYP2C19 (phenobarbital, phenytoin) can lead to an interaction. For some patients, it may be necessary to reduce the dose of drugs - substrates of CYP2C19. Oxcarbazepine and MHP have been shown to interact poorly or not at all with the following microsomal isoenzymes: CYP1A2, CYP2A6, CYP2C9, CYP2D9, CYP2E1, CYP4A4 and CYP4C11.
Inductors of microsomal enzymes: Oxcarbazepine and MHP are inducers of CYP3A4 and CYP3A5 cytochromes involved in the metabolism of dihydropyridine calcium antagonists, oral contraceptives and antiepileptic drugs (for example, carbamazepine). The simultaneous appointment of Trileptal and substrates of CYP3A4 and CYP3A5 can reduce the concentration of the latter in the blood plasma.
In vitro, IHP is a weak inducer of UDP-glucuronyl transferase and, therefore, it is unlikely that it can in vivo affect the metabolism of drugs excreted as conjugates (for example, valproic acid and lamotrigine).But, taking into account even the weak inductor ability of oxcarbazepine and IHP, it may be necessary to increase the doses of related drugs metabolized by the CYP3A4 system or UDP glucouronyl transferase. If it is necessary to cancel Trileptal, the doses of these drugs should be adequately reduced.
In vitro studies have confirmed the weak inductor ability of oxcarbazepine and IHP in relation to the isoenzymes of the subsystems of the enzymes CYP2B and CYP3A4. The induction effect of oxcarbazepine and IHP on other CYP isoenzymes is unknown.
Antiepileptic drugs (PEP): possible interactions of trileptal and other antiepileptic drugs have been evaluated during clinical trials. The concentration of phenytoin in the blood plasma is increased to 40% with the simultaneous appointment of Trileptal in a dose of 1200 mg / day and above. Therefore, when using doses of Trileptal above 1200 mg / day, it may be necessary to reduce the dose of phenytoin. The increase in serum concentration of phenobarbital is approximately 15% with simultaneous administration with Trileptal. The simultaneous administration of strong inducers of cytochrome P 450 isoenzymes (i.e., carbamazepine, phenytoin, and phenobarbital) reduces plasma MHD concentrations (by 29–40%). Trileptal had no signs of autoinduction.
Hormonal contraceptives: Trileptal's interaction with ethinyl estradiol and levonorgestrel was noted. The mean AUC values ​​for them decreased by 48–52% and 35–52%, respectively.No data available for other oral or implantable contraceptives. Nevertheless, the simultaneous appointment of Trileptal and hormonal contraceptives can lead to a decrease in the effectiveness of the latter.
Calcium channel blockers: the simultaneous use of trileptal and felodipine can lead to a decrease in the AUC value of felodipine by 28%, although plasma concentrations remain within the therapeutic range. Co-administration with Verapamil may reduce serum concentrations of IHD by 20%. A decrease in serum concentrations of IHD is clinically insignificant.
Interaction with other drugs: cimetidine, Erythromycin, dextropropoxyphene do not affect the pharmacokinetic parameters of IHP; Viloxazin has little effect on plasma IHP concentration (IHP concentration increases by 10% after repeated co-administration). No interaction with Warfarin was noted when taking both single and multiple doses of Trileptal. Trileptal may enhance the sedative effect of ethanol.

There are isolated reports of overdose of the drug. The maximum dose described in the reports was 24 g.
Symptoms: drowsiness, dizziness, nausea, vomiting, hypokinesia, hyponatremia, ataxia, nystagmus.
Treatment: there is no specific antidote. Conduct symptomatic and supportive treatment.In the case of a recent intake of the drug, gastric lavage and the use of Activated carbon to reduce absorption are recommended.