Epileptal
Producer: JSC Pharmak Ukraine
Code of automatic telephone exchange: N03AX09
Release form: Firm dosage forms. Tablets.
General characteristics. Structure:
Active ingredient: Lamotrigine;
1 tablet contains a lamotridzhin of 25 mg, 50 mg or 100 mg in terms of 100% substance;
excipients: lactoses monohydrate, cellulose microcrystallic, sodium krakhmalglikolit (type A), povidone, ferrous oxide yellow (Е 172), magnesium stearate.
Pharmacological properties:
Pharmacodynamics. Lamotridzhin – anticonvulsant drug, blocks potentsialzavisimy natrium channels of presynaptic membranes of neurons in a phase of a slow inactivation. Inhibits excess release of neurotransmitters, mainly glutaminic acid – the "exciting" amino acid playing a key role in development of epileptic seizures.
Pharmacokinetics. After intake it is quickly and completely soaked up from digestive tract. The maximum concentration in a blood plasma is reached approximately in 2,5 hours, time of its achievement can increase after meal without change of extent of absorption. Has a linear pharmacokinetic profile at reception to 450 mg. Linkng with proteins of plasma – about 55%. Distribution volume – 0,92-1,22 l/kg. It is metabolized in a liver with the participation of glyukuroniltransferaza enzyme with formation of a N-glucuronide. The clearance at adults averages 39±14 ml/min., an elimination half-life – 29 hours irrespective of a drug dose. Gets into breast milk in the concentration reaching 40-60% of concentration in a blood plasma. About 2% – with excrements are removed mainly in the form of metabolites (glucuronides) and partially (less than 10%) in an invariable view with urine.
At a concomitant use with the drugs inducing microsomal oxidizing enzymes of a liver, the elimination half-life decreases approximately till 14 o'clock, at a combination to valproic acid drugs (inhibit microsomal oxidizing enzymes of a liver) – increases till 70 o'clock. Lamotridzhin does not exert impact on pharmacokinetics of other antiepileptic drugs.
Children up to 12 years have a clearance of a lamotridzhin calculated on body weight, above than at adults, the elimination half-life is less. The highest clearance at children up to 5 years. At young and elderly patients of significant differences of clearance it is not observed.
At patients with a chronic renal failure average values of clearance make 0,42 ml/min., at the patients who are on a hemodialysis – 0,33 ml/min. between sessions of a hemodialysis and 1,57 ml/min. during a hemodialysis; average values of an elimination half-life – 42,9 hours, 57,4 and 13 hours respectively. During the 4-hour session of a hemodialysis about 20% of a lamotridzhin are removed.
At patients with abnormal liver functions of easy, average and heavy degree (classes A, B and C on Chayldu-Pyyu) average values of clearance make 0,31, 0,24 and 0,1 ml/min. respectively.
Pharmaceutical characteristics
Main physical and chemical properties: tablets on 25 mg and 100 mg of a round form with a biconvex surface, pale yellow color; tablets on 50 mg of a round form, ploskotsilindrichesky with risky and a facet, pale yellow color. On a surface the insignificant mramornost and impregnations are allowed.
Indications to use:
Epilepsy at adults and children is more senior than 12 years (monotherapy or additional therapy at partial and generalized attacks, including toniko-clonic attacks, and also the attacks connected with Lennox-Gasto's syndrome).
Epilepsy at children from 2 to 12 years (as additional therapy at partial and generalizirovanny attacks, including toniko-clonic attacks, and also attacks connected with Lennox-Gasto's syndrome).
After achievement of control of attacks reception of additional drugs it is possible to stop and continue monotherapy by Epileptal.
Monotherapy of typical absentias epileptica.
Bipolar disorders (adult): for the prevention of phases of emotional disturbances, preferential warning depressive episodes.
Route of administration and doses:
Epileptal it is necessary to swallow of tablets whole, without chewing and without breaking.
If the appointed Epileptal's dose does not correspond to amount of active ingredient in a tablet, it is necessary to appoint the smallest dose which corresponds to the whole tablet.
Epilepsy
Monotherapy of adults and children is more senior than 12 years (see tab. 1).
The initial dose of Epileptal makes 25 mg of 1 times a day for 2 weeks, then accept 50 mg/days for the next 2 weeks, further the dose is increased by 50-100 mg by each 1-2 weeks before achievement of optimum effect. The usual maintenance dose makes 100-200 mg/days for 1-2 receptions. The dose of 500 mg/days can be necessary for some patients.
Table 1. The recommended scheme of a lecheniyaepilepsiya for a vzroslykha of children is more senior than 12 years
2-yanedelya 3-ya 4-yanedet the mode of treatment of a 1-yaa the Maintenance dose
Monotherapy of 25 mg/days 50 mg/days 100-200 mg/days (for 1-2 receptions)
(1 reception) (1 reception) it is reached gradual
increase in a dose up to 50-100 mg
each 1-2 weeks
Combination therapy about reception on 25 mg/days 100-200 mg/days
sodium Valproatum, without watching 25 mg every other day (1 reception) (for 1-2 receptions) it is reached
on other accompanying drugs gradual increase in a dose
on 25-50 mg each 1-2 weeks
Combined This scheme of treatment of 50 mg/days 100 mg/days 200-400 mg/days
therapy without it is necessary to apply: (1 reception) (2 receptions) (for 2 receptions)
Valproatum – with Phenytoinum, it is reached gradual
sodium increase in a dose on
– з carbamazepine, 100 mg everyone
1-2 weeks
– з phenobarbital,
– з Primidonum
or with others
inductors
glyukuronization
lamotridzhina
This scheme of treatment of 25 mg/day 50 mg/day 100-200 mg/day
it is necessary to apply (1 reception) (1 reception) (for 1-2 receptions) it is reached
with other drugs, gradual increase
which significantly not doses to 50-100 mg
induce or each 1-2 weeks
do not oppress
glyukuronization
lamotridzhina
Children aged from 2 up to 12 years (see tab. 2).
The initial dose of Epileptal for treatment of typical absentias epileptica makes 0,3 mg/kg of weight bodies/days in 1-2 receptions within 2 weeks, bodies/days in 1-2 receptions for the next 2 weeks then accept 0,6 mg/kg of weight. Further the dose is raised on 0,6 mg/kg of body weight by each 1-2 weeks to achievement of optimum effect. The usual maintenance dose makes 1-15 mg/kg of weight bodies/days in 1-2 receptions. Higher dose can be necessary for some patients.
Because of risk of developing of rash the initial dose and rate of further increase in a dose should not be exceeded.
Combination therapy
Adults and children are more senior than 12 years (see tab. 1).
For the patients accepting Valproatum (separately or with other antiepileptic drugs), the initial dose of Epileptal makes 25 mg every other day for 2 weeks, then – on 25 mg daily within the next 2 weeks. After that the dose should be increased (as much as possible by 25-50 mg/days) each 1-2 weeks before achievement of optimum therapeutic effect. The usual maintenance dose makes 100-200 mg/days in 1-2 receptions.
For the patients accepting other antiepileptic drugs or other drugs, inductors of a glyukuronization of a lamotridzhin in a combination with other antiepileptic drugs or without them (except for sodium Valproatum), the initial dose of Epileptal makes 50 mg of 1 times a day for 2 weeks, further – 100 mg/days in 2 receptions for 2 weeks. Then the dose needs to be increased (as much as possible by 100 mg) each 1-2 weeks before achievement of optimum therapeutic effect. The usual maintenance dose makes 200-400 mg/days in 2 receptions. The dose of 700 mg/days can be necessary for some patients.
For patients who accept other drugs which significantly are not inducing or not oppressing a glyukuronization of a lamotridzhin (see. "Interaction with other medicines and other types of interactions"), the initial dose of Epileptal makes 25 mg of 1 times a day for 2 weeks, further – 50 mg of 1 times a day within the next 2 weeks. After that the dose needs to be increased (as much as possible by 50-100 mg/days) each 1-2 weeks before achievement of optimum therapeutic effect. The usual maintenance dose makes 100-200 mg/days in 1-2 receptions.
Patients who accept antiepileptic drugs which interaction with lamotridzhiny is unknown are recommended to apply such scheme of treatment, as well as to patients who accept ламотриджин with Valproatum.
Due to the risk of developing of rash the initial dose and rate of further increase in a dose cannot be exceeded.
Children from 2 to 12 years (see tab. 2). To children who receive sodium Valproatum in a combination with other antiepileptic drugs or without them the initial dose of Epileptal makes 0,15 mg/kg of body weight a day in 1 reception for 2 weeks (in need of reception of the calculated dose in 2,5-5 mg reception of 5 mg of Epileptal every other day for the first two weeks is allowed. If the calculated dose is less than 2,5 mg, it is not recommended to take Epileptal), then – 0,3 mg/kg of body weight a day for 1 reception for the next 2 weeks. Further the dose needs to be increased (as much as possible by 0,3 mg/kg of body weight) each 1-2 weeks before achievement of optimum therapeutic effect. The maintenance dose makes 1-5 mg/kg of body weight in 1-2 receptions (maximum – 200 mg/days).
For children who accept other antiepileptic drugs or other drugs, inductors of a glyukuronization of a lamotridzhin in combination with other antiepileptic drugs or without them (excepting sodium Valproatum), the initial dose of Epileptal makes 0,6 mg/kg of body weight a day in 2 receptions for 2 weeks, then – 1,2 mg/kg of body weight a day for the next 2 weeks. Further the dose should be increased (as much as possible by 1,2 mg/kg of body weight) each 1-2 weeks before achievement of optimum therapeutic effect. The average maintenance dose makes 5-15 mg/kg of body weight a day in 2 receptions (at most 400 mg/days).
For children who accept other drugs which significantly are not inducing or not oppressing a glyukuronization of a lamotridzhin (see the section "Interaction with Other Medicines and Other Types of Interactions") the initial dose of Epileptal makes 0,3 mg/kg of body weight a day in 1-2 receptions for 2 weeks, further – 0,6 mg/kg of body weight a day in 1-2 receptions within the next 2 weeks. After that the dose needs to be increased (as much as possible by 0,6 mg/kg of body weight) each 1-2 weeks before achievement of optimum therapeutic effect. The usual maintenance dose makes 1-10 mg/kg of body weight a day in 1-2 receptions. The maximum dose – 200 mg/days.
For the correct calculation of a maintenance dose it is necessary to control the body weight of the child.
Children who accept antiepileptic drugs which interaction with lamotridzhiny is unknown are recommended to apply the same scheme of treatment, as to patients who accept ламотриджин with Valproatum.
2-yanedelya 3-ya 4-yanedet the mode of treatment of a 1-yaa the Maintenance dose
Monotherapy of typical absentias epileptica of 0,3 mg/kg 0,6 mg/kg 1-10 mg/kg
(1-2 receptions) (1-2 receptions) (for 1-2 receptions)
it is reached gradual
increase in a dose on
To 0,6 mg/kg there are each 1-2 weeks,
at most-200 mg/days
Combination therapy from 0,15 mg/kg 0,3 mg/kg 1-5 mg/kg
sodium Valproatum, without looking (1 reception) (1 reception) (for 1-2 receptions)
on other accompanying it is reached gradual
drugs increase in a dose on
To 0,3 mg/kg there are each 1-2 weeks,
at most – 200 mg/days
Kombinirovannya This scheme of treatment of 0,6 mg/kg 1,2 mg/kg 5-15 mg/kg
therapy without it is necessary to apply: (2 receptions) (2 receptions) (for 2 receptions)
Valproatum – with Phenytoinum, it is reached gradual
sodium – with carbamazepine, increase in a dose on
To 1,2 mg/kg there are each 1-2 weeks,
– with phenobarbital, at most – 400 mg/days
– with Primidonum
or with others
inductors
glyukuronization
lamotridzhina
This scheme of treatment 0,3 mg/kg 0,6 mg/kg 1-10 mg/kg follow (in 1-2 receptions)
to apply with others (1-2 receptions) (1-2 receptions) it is reached gradual
drugs, which increase in a dose on
significantly each 1-2 weeks do not induce 0,6 mg/kg,
or do not oppress at most – 200 mg/days
glyukuronization of a lamotridzhin
Because of risk of developing of rash the initial dose and rate of further increase in a dose should not be exceeded. It must be kept in mind that in case of lack of tablets Epileptal in a dose of 2 mg it is correct to begin treatment to children with body weight less than 17 kg it is impossible.
Bipolar disorders
Adults. Because of risk of developing of rash the initial dose and rate of further increase in a dose should not be exceeded.
Epileptal is recommended to accept to patients with bipolar disorders with the increased risk of depressive episodes in the future.
It is necessary to adhere to the transitional mode of use given below. This mode includes increase in a dose of a lamotridzhin to achievement of the supporting stabilization dose for 6 weeks (see tab. 3) then reception of other psychotropic and/or antiepileptic drugs can be stopped in case of clinical expediency (see tab. 4).
It is necessary to consider need of additional therapy for the purpose of the prevention of maniacal episodes as efficiency of use of Epileptal at a maniacal syndrome is authentically not established.
Tablitsa3. The recommended scheme of increase in a dose of a lamotridzhin for achievement of the supporting stabilizatsionnoysutochny dose at лечениивзрослыхс bipolar disorders
Mode of treatment 1-2-yanedelya 3-4-yanedelya 5-yanedelya Stabilization dose
(6-yanedelya)
a) Additional 12,5 mg (25 mg 25 mg 50 mg 100 mg (1 time a day or for 2
therapy with inhibitors every other day) (1 time a day) (1 time in days of reception)
glyukuronization or for 2
lamotridzhina, for example, reception) (the maximum daily
with Valproatum dose of 200 mg)
b) Additional 50 mg 100 mg 200 mg 300 mg for the 6th week, increasing to
therapy with inductors (1 time a day) (for 2 receptions) (for 2 receptions) 400 mg/day if necessary
glyukuronization for the 7th week (for 2 receptions)
lamotridzhina at patients,
which do not accept
inhibitors, such, as
Valproatum.
This scheme of treatment
it is necessary to apply:
– with Phenytoinum,
– with carbamazepine,
– with phenobarbital,
– with Primidonum
or with others
inductors
glyukuronization
lamotridzhina
c) Monotherapy of 25 mg 50 mg 100 mg 200 mg
(1 time a day) (1 time a day (1 time a day (from 100 to 400 mg)
lamotridzhiny or or for 2 receptions) or for 2 receptions) (1 time a day or
for 2 receptions)
additional therapy
at patients, which
apply others
drugs, which
significantly not
oppress or not
induce a glyukuronization
lamotridzhina
The scheme of achievement of the supporting stabilization dose (the stabilization dose can change depending on the clinical answer).
a) Additional therapy with inhibitors of a glyukuronization of a lamotridzhin, for example, with Valproatum. An initial dose – 25 mg every other day for 2 weeks, then 25 mg of 1 times a day the next 2 weeks. It is necessary to increase a dose to 50 mg a day (in 1-2 receptions) on the 5th week. A usual dose for achievement of the optimum answer are 100 mg a day (in 1-2 receptions). However the dose can be increased to the maximum 200 mg/days depending on the clinical answer.
b) Additional therapy with inductors of a glyukuronization of a lamotridzhin at patients who do not accept inhibitors, such as Valproatum. This scheme should be applied with Phenytoinum, carbamazepine, phenobarbital, Primidonum or other inductors of a glyukuronization of a lamotridzhin.
Initial dose – 50 mg of 1 times a day for 2 weeks, then 100 mg/days (divided into 2 receptions) the next 2 weeks. It is necessary to increase a dose to 200 mg/days (in 2 receptions) for the 5th week. It is possible to increase a dose to 300 mg/days for the 6th week, however a usual dose for achievement of the optimum answer are 400 mg/days (in 2 receptions) which can be appointed from 7th week.
c) Monotherapy lamotridzhiny or additional therapy at patients who use other drugs which significantly are not inducing and not oppressing a glyukuronization of a lamotridzhin (see the section "Interaction with Other Medicines and Other Types of Interactions").
Initial dose for these patients of 25 mg of 1 times a day for 2 weeks, then 50 mg/days (in 1-2 receptions) the next 2 weeks. It is necessary to increase a dose to 100 mg/days on the 5th week.
Usual dose for achievement of the optimum answer are 200 mg/days (in 1-2 receptions). After achievement of the necessary supporting stabilization dose reception of other psychotropic drugs can be stopped according to below the provided scheme (see tab. 4).
Table 4. The supporting stabilization dose at bipolar the rasstroystvakhsdalneyshy termination of reception accompanying psychotropic or protivoepilepticheskikhsredstvo
The treatment mode 1-yanedelya 2-yanedelya from a 3-ynedela
a) With further to Double stabilization to Support this dose 200
dose, without exceeding 100 mg/mg/days (divided on
reception termination week, for example, 2 receptions)
inhibitors stabilization
glyukuronization a dose of 100 mg a day
for example, to increase a lamotridzhin within 1 week
Valproatum to 200 mg/days
b) With further cancellation of 400 mg 300 mg 200 mg
glyukuronization inductors
lamotridzhina in
dependences on initial
doses.
This scheme of treatment 300 mg 225 mg 150 mg follow
to apply:
– with Phenytoinum,
– with carbamazepine,
– with phenobarbital,
– with Primidonum of 200 mg 150 mg 100 mg
or with others
glyukuronization inductors
lamotridzhina
c) With the further termination to Support the dose received at increase in a dose
reception of other drugs,
significantly not oppressing (200 mg/days), divided into 2 receptions (100-400 mg)
or not inducing
glyukuronization of a lamotridzhin
Note. Patients who accept antiepileptic drugs with unknown influence on pharmacokinetics of a lamotridzhin should apply the scheme of increase in a dose which is recommended for the accompanying use of Valproatum.
The patients accepting antiepileptic drugs with unknown influence on pharmacokinetics of a lamotridzhin should apply the mode of treatment at which the existing Epileptal's dose remains and her correction is carried out on the basis of a clinical state.
The scheme of change of daily dosing of Epileptal for patients with bipolar disorders at additional purpose of other drugs (see tab. 5).
Table 5. The scheme of izmeneniyasutochny dosing of a lamotridzhin for patients with bipolar disorders at dopolnitelnomnaznacheniidrugy drugs
The treatment mode Stabilizatsion 1-yanedelya 2-yanedelya from a 3-ynedela
Nye dose
lamotridzhina
(mg/days)
Additional purpose of 200 mg 100 mg to Support this dose
glyukuronization inhibitors
lamotridzhina, for example, (100 mg/days)
Valproatum, in dependence
from an initial dose
lamotridzhina of 300 mg 150 mg to Support this dose
(150 mg/days)
400 mg 200 mg to Support this dose
(200 mg/days)
Additional purpose of 200 mg 200 mg 300 mg 400 mg
glyukuronization inductors
lamotridzhina patient,
not accepting Valproatum,
and depending on initial
doses of a lamotridzhin.
This scheme of treatment follows
to apply: 150 mg 150 mg 225 mg 300 mg
– with Phenytoinum,
– with carbamazepine,
– with phenobarbital,
– with Primidonum of 100 mg 100 mg 150 mg 200 mg
or with others
glyukuronization inductors
lamotridzhina
Additional appointment to Support the dose reached after the mode of increase in a dose
other drugs,
significantly not oppressing (200 mg / to Dob)
or not inducing (100-400 mg)
glyukuronization of a lamotridzhin
Note. Patients who accept antiepileptic drugs with unknown influence on pharmacokinetics of a lamotridzhin should apply the scheme of increase in a dose which is recommended for the accompanying use of Valproatum.
The termination of reception of a lamotridzhin by patients with bipolar disorders
It is possible without gradual dose decline at once.
Repeated initiation of treatment.
When to the patient who stopped treatment appoint repeatedly treatment Epileptaly, it is necessary to establish accurately need of increase in a maintenance dose because there is a risk of developing of rashes because of a high initial dose and exceeding of the recommended scheme of increase in a dose of a lamotridzhin. The more it is necessary to pay an interval between time of reception of the previous dose, the more attention to the mode of increase in a dose up to the level of a maintenance dose. If the interval in reception of a lamotridzhin exceeded an elimination half-life by 5 times, the dose of a lamotridzhin is increased to the existing scheme supporting according to. It is not recommended to begin repeatedly treatment lamotridzhiny if treatment was stopped in connection with emergence of rash. In that case at the solution of a question of rather repeated purpose of drug it is necessary to weigh the expected advantage of treatment and possible risk.
General recommendations about dosing for special groups of patients
The women accepting hormonal contraceptives
a) An initiation of treatment lamotridzhiny at patients who already accept hormonal contraceptives.
The dose is increased according to the recommended scheme in cases when ламотриджин it is added to Valproatum (inhibitor of a glyukuronization of a lamotridzhin) or to the inductor of a glyukuronization of a lamotridzhin, or ламотриджин it is added without Valproatum or the inductor of a glyukuronization of a lamotridzhin (see tab. 1 and tab. 3).
b) The beginning of a course of treatment hormonal contraceptives at patients who already accept maintenance doses of a lamotridzhin and is not accepted by inductors of a glyukuronization of a lamotridzhin.
The maintenance dose of a lamotridzhin will need to be increased twice.
It is recommended that from an initiation of treatment hormonal contraceptives a dose of a lamotridzhin to increase from 50 to 100 mg/days every week according to the individual clinical response to treatment. Increase in a dose should not exceed the specified level if only according to the clinical answer such increase in a dose is not necessary.
c) The termination of a course of treatment hormonal contraceptives at patients who already accept maintenance doses of a lamotridzhin and is not accepted by inductors of a glyukuronization of a lamotridzhin.
It will be in most cases necessary to reduce a maintenance dose of a lamotridzhin to 50%. It is recommended to reduce a daily dose of a lamotridzhin gradually from 50 to 100 mg every week (no more than 25% of the general dose a week) for 3 weeks if according to the individual clinical answer treatment is not appointed in a different way.
Use together with atazanavirom/ritonaviry. Though use of an atazanavira/ritonavir reduces concentration of a lamotridzhin in a blood plasma, to change the recommended schemes of increase in dosing of Epileptal, being based on use of an atazanavira/ritonavir, it is not necessary. Increase in a dose of drug has to be based on recommendations depending on schemes of use of Epileptal.
At patients who already apply maintenance doses of Epileptal and do not use glyukuronization inductors, Epileptal's dose can be increased if treatment atazanavirom/ritonaviry is added, or to reduce if treatment atazanavirom/ritonaviry stops.
Patients of advanced age (65 years are more senior). It is not necessary to change a dose.
Liver failure. The initial dose, increase in a dose and a maintenance dose need to be reduced generally by 50% at patients with moderated (a scale of Chaylda-Pyyu, degree In) and for 75% with heavy (a scale of Chaylda-Pyyu, degree C) a liver failure. Increase in a dose and a maintenance dose are adjusted according to clinical effect.
Renal failure. At appointment as the patient it is necessary to be careful with a renal failure. At treatment of patients with an end-stage of a renal failure the initial dose of a lamotridzhin is based on the individual scheme of antiepileptic treatment, at treatment of patients with a considerable renal failure it is necessary to reduce a maintenance dose of a lamotridzhin.
Features of use:
Skin reactions. For the first 8 weeks from an initiation of treatment lamotridzhiny there can be side effect from skin in the form of rash. In most cases rashes moderate also pass without treatment, however was reported about emergence of heavy skin reactions, such as Stephens-Johnson's syndrome and a toxic epidermal necrolysis that demanded hospitalization and the termination of treatment by Epileptal.
At children the risk of developing of serious skin rashes is higher, than at adults.
At children the first symptoms of skin rashes can be mistakenly taken for an infection therefore doctors should pay attention to a possibility of development of side reaction on drug at children who have rashes and fever for the first 8 weeks of therapy.
The general risk of developing of skin rashes of skin rashes, obviously, is closely connected with high initial doses of a lamotridzhin and exceeding of the recommended scheme of increase in doses at therapy lamotridzhiny, and also with the accompanying use of Valproatum.
With care it is necessary to apply ламотриджин to treatment of patients who had an allergy or rashes at use of other antiepileptic drugs in the anamnesis as the frequency of emergence of moderate rashes after treatment lamotridzhiny at this group of patients was 3 times higher, than in group without such anamnesis.
At emergence of an enanthesis it is necessary to examine immediately the patient (both the adult, and the child) and to stop Epileptal's reception. It is not recommended to begin repeatedly treatment lamotridzhiny if it was stopped because of emergence of rashes owing to the previous treatment lamotridzhiny. In that case at the solution of a question of rather repeated purpose of drug it is necessary to weigh the expected advantage of treatment and possible risk. Also it was reported that skin rashes are a part of a syndrome of hypersensitivity which is followed by various system symptoms (see the section "Side reactions"). Precursory symptoms of a syndrome of hypersensitivity (for example, fever and a lymphadenopathy) can arise even in the absence of skin rashes. In the presence of such symptoms of the patient it is necessary to examine immediately and, in the absence of other reasons, to stop Epileptal's reception.
Aseptic meningitis which is one of hypersensitivity symptoms in most cases has involution, however in certain cases can be returned at repeated purpose of a lamotridzhin. Repeated purpose of a lamotridzhin causes bystry return of symptoms which often have more difficult character. Patients to whom ламотриджин it was cancelled in connection with emergence of aseptic meningitis cannot appoint ламотриджин repeatedly.
Suicide risk. At treatment of patients with various indications (including epilepsy) antiepileptic drugs it was reported about suicide intentions and behavior. According to the metaanalysis of randomized placebos of controlled clinical trials using antiepileptic drugs, including ламотриджин, insignificant increase in risk of suicide intentions and behavior was shown. The mechanism of this risk is unknown, however the available data do not exclude a possibility of increase in this risk in connection with use of a lamotridzhin. Therefore patients need to be controlled carefully on existence of signs of suicide intentions at them and behavior. In case of such signs sick and those who look after them have to ask for medical care.
According to literature, heavy epileptic attacks can cause рабдомиолиз, multiorgan insufficiency and a syndrome of the disseminated intravascular blood coagulation, sometimes with a lethal outcome. Similar cases are possible also against the background of treatment lamotridzhiny.
Bipolar disorders. It is necessary to watch patients who are treated by Epileptal concerning bipolar disorder attentively in case of clinical deterioration (that includes emergence of new symptoms) and at a suitsidalnost, especially at the beginning of a course of treatment or during dosing change. At some patients, at those at whom the suicide behavior or thoughts were noted in the anamnesis at youth and at patients who showed substantially suicide intentions prior to treatment, the risk of emergence of suicide thoughts or suicide attempts can increase that demands attentive observation during treatment.
Patients and persons who look after them should be warned about need of observation at any deterioration in their state (including emergence of new symptoms) and/or emergence of suicide intentions / behavior or tendency to self-damage immediately to ask for medical care at emergence of these symptoms. In such cases it is necessary to introduce amendments in the therapeutic mode or even to stop treatment.
Children and teenagers. Treatment by antidepressants is connected with the increased risk of suicide intentions and behavior at children and teenagers with big depressive frustration and other psychiatric frustration.
Reception of hormonal contraceptives. The patients accepting hormonal contraceptives "ethinylestradiol of 30 mkg / левоноргестрель 150 mkg" have to reside under observation of the doctor and in most cases dose adjustment of a lamotridzhin is necessary for them, they have to report timely about changes in a menstrual cycle, for example about emergence of sudden bleeding (detailed information see in the sections "Route of Administration and Doses" and "Interaction with Other Medicines and Other Types of Interactions").
Digidrofolatreduktaza. Epileptal is weak inhibitor of a digidrofolatreduktaza therefore at prolonged use its influence on metabolism of folates is possible. However at prolonged use of a lamotridzhin there were no essential changes of amount of hemoglobin, average volume of erythrocytes, concentration of folates in blood serum and erythrocytes for 1 year and concentration of folates in erythrocytes for 5 years.
Renal failure. In researches of a single dose at patients with end-stages of a renal failure of concentration of a lamotridzhin in a blood plasma significantly did not change. However accumulation of a glyukuronidny metabolite is possible. Therefore at treatment of patients with damages of kidneys it is necessary to adhere to care.
Patients who accept other drugs containing ламотриджин. Epileptal do not appoint to patients who are already treated by any other drug containing ламотриджин.
Epilepsy. The sharp termination of reception of Epileptal, as well as other antiepileptic means, can provoke increase in frequency of attacks. Except for cases when the condition of the patient demands the sharp termination of administration of drug (as, for example, at emergence of rashes), it is necessary to reduce Epileptal's dose gradually, not less than 2 weeks.
Drug contains lactose therefore to patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption it is impossible to use drug.
Ability to influence speed of response at control of motor transport or work with other mechanisms
At use of drug it is necessary to take into account possibility of side reactions from a nervous system and an organ of sight therefore at emergence of such side effects it is necessary to refuse driving or work with other mechanisms.
Side effects:
For assessment of frequency of emergence of side effect such classification was used: very often (> 1/10), it is frequent (> 1/100 <1/10), infrequently (> 1/1 000 <1/100), is rare (> 1/10 000 <1/1 000), is very rare (<1/10 000).
From skin and hypodermic fabric: very often – skin rashes. Skin rashes had makulo-papular character, arose within 8 weeks from an initiation of treatment more often and disappeared after the termination of reception of a lamotridzhin. It was sometimes reported about emergence of heavy life-threatening skin reactions, including Stephens-Johnson's syndrome and a toxic epidermal necrolysis (Lyell's disease). Though most of patients recovered посля the terminations of administration of drug, some of them had irreversible hems; in isolated cases these symptoms led to a lethal outcome. The general risk of developing of skin rashes, obviously, is closely connected with high initial doses of a lamotridzhin and exceeding of the recommended scheme of increase in doses during therapy lamotridzhiny, and also with the accompanying use of Valproatum. Also it was reported that skin rashes are a part of a syndrome of hypersensitivity which is followed by various system symptoms (see. "From immune system").
From blood and lymphatic system: very seldom – hematologic deviations (that include a neutropenia, a leukopenia, anemia, thrombocytopenia, a pancytopenia, aplastic anemia and an agranulocytosis), a lymphadenopathy. Hematologic deviations can be both are connected, and not connected with a hypersensitivity syndrome.
From immune system: very seldom – the hypersensitivity syndrome, including such symptoms as fever, a lymphadenopathy, swelled persons, changes of blood and an abnormal liver function. Also it was reported about rashes as parts of a syndrome of hypersensitivity which was followed by various system symptoms. The syndrome can have various degrees of severity and occasionally can lead to the disseminated intravascular blood coagulation and multiorgan insufficiency. In the presence of such symptoms of the patient it is necessary to examine immediately and, in the absence of other reasons, to stop Epileptal's reception.
Mental disturbances: often – aggression, irritability; very seldom – a tic, hallucinations and confusion of consciousness.
From a nervous system: very often – a headache, drowsiness; often – sleeplessness, dizziness, a tremor; infrequently – an ataxy; seldom – a nystagmus; very seldom – aseptic meningitis (see. "Features of use"), alarming excitement, balance loss, motive frustration, increase in frequency of attacks; an exacerbation of a disease of Parkinson, extrapyramidal frustration and a choreoathetosis at patients with this pathology.
From an organ of sight: infrequently – a diplopia, a veil before eyes; seldom – conjunctivitis.
From digestive tract: often – nausea, vomiting, diarrhea.
From gepatobiliarny system: very seldom – increase in indicators of functional hepatic tests, an abnormal liver function, a liver failure.
From a musculoskeletal system and connecting fabrics: often – an arthralgia, it is very rare – volchanochnopodobny reactions.
General frustration: often – increased fatigue, a dorsodynia.
Interaction with other medicines:
It was established that the uridindifosfoglyukuroniltransferraza is an enzyme which is responsible for metabolism of a lamotridzhin. There are no proofs that ламотриджин can cause clinically significant stimulation or oppression of oxidizing enzymes of a liver which take part in metabolism of drugs, and it is improbable that there can be an interaction between lamotridzhiny and drugs which are metabolized tsitokhromny P450 by enzymes. Lamotridzhin can induce own metabolism, but this effect moderate and has no considerable clinical effects.
Drugs which do not oppress and do not induce a glyukuronization of a lamotridzhin: Lithium, Bupropion, Olanzapin, Okskarbazepin, Felbamat, Gabapentin, Levetiratsetam, Pregabalin, Topiramat, Zonizamid, Aripiprazol do not influence metabolism of a lamotridzhin.
Drugs which considerably oppress a glyukuronization of a lamotridzhin. Valproatum which brakes a glyukuronization of a lamotridzhin reduces metabolism of a lamotridzhin and increases an average elimination half-life approximately twice.
Results of the researches invitro demonstrate what ламотриджин ° does not force out other antiepileptic drugs from their communication with proteins.
Drugs which considerably induce a glyukuronization of a lamotridzhin. Some antiepileptic drugs (such as Phenytoinum, carbamazepine, phenobarbital and Primidonum) which induce liver enzymes, induce metabolism of a glyukuronization of a lamotridzhin and accelerate metabolism of a lamotridzhin. There are messages on by-effects from the central nervous system which included dizziness, an ataxy, a diplopia, opacification of sight and nausea at patients who received carbamazepine along with lamotridzhiny. These phenomena usually disappear at reduction of a dose of carbamazepine.
At reception of rifampicin the level of removal increased and the elimination half-life of a lamotridzhin owing to induction of the liver enzymes responsible for a glyukuronization decreased. At patients who received the accompanying therapy by rifampicin it is necessary to apply the treatment mode recommended for treatment lamotridzhiny and the corresponding inductors of a glyukuronization.
According to the researches conducted on healthy volunteers lopinavir/ritonavir approximately twice reduce concentration of a lamotridzhin in plasma by induction of a glyukuronization. For treatment of patients who already apply lopinavir/ritonavir it is necessary to adhere to the mode of therapy recommended at use of a lamotridzhin and inductors of a glyukuronization. According to researches on healthy volunteers, use of an atazanavira/ritonavir (300 mg / 100 mg) reduced AUC and Cmax of a lamotridzhin in a blood plasma (in a dose of 100 mg) on average by 32% and 6% respectively.
Interaction with other psychotropic substances. Amitriptyline, бупропион, to hlonazepa, флюоксетин, a haloperidol or lorazepam can influence formation of primary metabolism of a lamotridzhin, N-glucuronide only in the minimum degree. According to studying of metabolism of a bufuralol in microsomes of a liver of the person it is possible to define what ламотриджин does not reduce clearance of drugs which are metabolized mainly by means of CYP2D6. Results of invitro of experiments also give the chance to claim that they can hardly influence clearance of a lamotridzhin clozapine, фенелзин, рисперидон, sertraline or Trazodonum.
In clinical trial with involvement of 18 adult patients with bipolar disorder who received ламотриджин (>/=100 mg/day) doses of an aripiprazol were increased from 10 mg/day to 30 mg/day within 7 days and were appointed within 7 days. About 10% of reduction of Cmax and AUC of a lamotridzhin were generally noted. It is not expected that the effect of such changes will have clinical effects.
Interaction with hormonal contraceptives. At reception of hormonal contraceptives in a combination "ethinylestradiol of 30 mkg / левоноргестрель 150 mkg", increase in removal of a lamotridzhin was noted approximately twice. Concentration of a lamotridzhin gradually increased in blood serum throughout a week break, reaching concentration closer to the end of a week break on average is approximately twice higher, than at combined use of drugs.
The constant dose of a lamotridzhin of 300 mg did not influence pharmacokinetics of ethinylestradiol which is a part of the combined tablet of an oral contraceptive. Continuous small increase in removal левоноргестреля was observed. Influence of change of level of the serumal follicle-stimulating and luteinizing hormones and insignificant increase in removal левоноргестреля on activity of an ovarian ovulation is unknown. Influence of a lamotridzhin in a daily dose over 300 mg was not investigated. Researches of other hormonal contraceptives were also not conducted.
Lamotridzhin is inhibitor of renal tubular secretion through proteins of organic cationic conveyors. It can cause increase in plasma level of some drugs which are excreted mainly in the above-stated way. Therefore Epileptal's use with the OCT substrates 2 having a narrow therapeutic index, for example with dofetilidy is not recommended.
Contraindications:
Hypersensitivity to drug components.
Overdose:
Symptoms: dizziness, headache, drowsiness, vomiting, nystagmus, ataxy, disturbance of consciousness, lump.
Treatment: gastric lavage, hospitalization of the patient and carrying out a maintenance therapy.
Use during pregnancy or feeding by a breast
Epileptal is appointed during pregnancy only if the expected advantage for mother exceeds possible risk for a fruit. It was reported about the increased risk of emergence of such inborn defect as the isolated crevice in a mouth.
There were cases of reduction of level of a lamitridzhin during pregnancy therefore pregnant women who accept ламотриджин should reside under observation of the doctor.
Lamotridzhin gets into breast milk therefore the advantage of feeding by a breast needs to be compared to possible risk of emergence of side effect at the child.
Children
There is no enough information concerning Epileptal's use for treatment of children under 2 years of patients with epilepsy therefore it is not recommended to use drug of this age category.
Epileptal is not intended for treatment of bipolar disorders at children and teenagers (see. "Features of use"). Studying of safety and efficiency of use of Epileptal for treatment of bipolar disorders in this age group was not carried out. Respectively, it is impossible to make recommendations concerning a drug dosing.
Storage conditions:
Period of validity. 3 years. Not to use drug after the termination of the period of validity specified on packaging. To store in the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.
Issue conditions:
According to the recipe
Packaging:
On 10 tablets in the blister. On 3 blisters in a pack.
