Konvulsan

General characteristics. Structure:

Active agent: ламотриджин - 25 mg, 50 mg 100 mg or 200 mg.
excipients: magnesium carbonate, cellulose microcrystallic, povidone, pigment light yellow: lactoses monohydrate, ferrous oxide yellow; кросповидон (полиплаздон XL 10), magnesium stearate.
Description: round, ploskotsilindrichesky tablets of light yellow color with an engraving on the one hand "25" (for tablets of 25 mg), "50" (for tablets of 50 mg), "100" (for tablets of 100 mg), "200" (for mg tablets 200).

Pharmacological properties:

Pharmacodynamics. Lamotridzhin is a blocker potential - dependent natrium channels, suppresses pathological release of glyutaminovy acid (the amino acid playing a key  role in development of epileptic seizures), and also inhibits the depolarization caused glyutamaty.

Pharmacokinetics. Absorption. Lamotridzhin is quickly and completely soaked up from intestines, practically without being exposed to presistemny metabolism of the first passing. The maximum concentration in plasma is reached approximately in 2,5 h after administration of drug inside. Time of achievement of the maximum concentration increases a little after meal, but extent of absorption remains invariable. At reception of a single dose to 450 mg the pharmacokinetics has linear character. Considerable interindividual fluctuations of the maximum concentration in an equilibrium state, however, with rare fluctuations at each certain patient are observed. Distribution
Lamotridzhin contacts proteins of plasma approximately for 55%. It is improbable that release of drug from communication with protein can lead to development of toxic effect. The volume of distribution makes 0,92-1,22 l/kg. Metabolism
UDF-glyukuroniltransferaz's enzyme takes part in metabolism of a lamotridzhin. Lamotridzhin in small degree increases own metabolism depending on a dose. There are no data, confirmatory that ламотриджин influences pharmacokinetics of other antiepileptic drugs (PEP) and that between lamotridzhiny and other drugs which are metabolized system of P 450 cytochrome interaction is possible. Elimination
At adults the clearance of a lamotridzhin in a condition of equilibrium concentration averages 39 j_14 of ml/min. Lamotri-dzhin is metabolized to glucuronides which are removed with urine, less than 10% of drug are allocated with urine in not changed look, about 2% - with excrements. The clearance and an elimination half-life do not depend on a dose. The elimination half-life at adults averages of 24 h to 35 h. At patients with Gilbert's syndrome decrease in clearance of drug by 32% was observed that, however, did not overstep the bounds of normal values for the general population.
On an elimination half-life of a lamotridzhin the great influence is exerted jointly by the accepted medicines (see. "Interaction with other medicines"). Children
At children the clearance of a lamotridzhin when calculating is one body weight higher, than at adults (it is highest at children up to 5 years). The elimination half-life of a lamotridzhin is usually shorter, than at adults. Its average value approximately equals 7 h at co-administration with the drugs stimulating a glyukuronization such as carbamazepine and Phenytoinum, and increases on average to 45-50 h at joint appointment with Valproatum (see the sections "Mode of Appointment and Dose", "Interaction with Other Medicines"). Patients of advanced age
Clinically significant distinctions in clearance of a lamotridzhin in comparison with young patients are not found in patients of advanced age. Patients with a renal failure
The dose decline can be required only at considerable depression of function of kidneys.
Patients with an abnormal liver function
The initial, increasing and supporting doses have to be reduced approximately by 50% at patients with moderate degree of a liver failure (a stage In on Chayld-Pyyu) and for 75% - at patients with heavy (a stage With on Chayld-Pyyu) a liver failure. Increase in a dose and a maintenance dose have to be adjusted depending on clinical effect.

Indications to use:

• as additional or monotherapies of epilepsy (partial and generalized attacks, including sink-to-clonic spasms, and also attacks at Lennox's syndrome - Gasto) at adults and children are more senior than 12 years;
• as additional therapy of epilepsy (partial and generalized attacks, including toniko-clonic spasms, and also attacks at Lennox's syndrome - Gasto) at children from 2 to 12 years. After achievement of control of epilepsy against the background of kombininirovanny therapy, the accompanying PEP can be cancelled and reception of a lamotridzhin is continued as monotherapy;
• monotherapy of typical absentias epileptica. Bipolar disorders
For prevention of disturbances of mood (a depression, a mania, a hypomania, the mixed episodes) at adults with bipolar disorders.

Route of administration and doses:

Inside. If the calculated dose of a lamotridzhin (for example, at appointment to children or patients with an abnormal liver function) cannot be divided into the whole quantity of tablets, then to the patient such dose which corresponds to the closest value of the whole tablet in lower dosage has to be appointed.
Because of risk of development of rash it is not necessary to exceed an initial dose of drug and the recommended mode of increase in doses.

Epilepsy

Monotherapy at adults and children is more senior than 12 years.
The initial dose of a lamotridzhin at monotherapy makes 25 mg within 2 weeks with the subsequent increase in a dose to 50 mg within 2 weeks once a day once a day. Then it is necessary to increase a dose by 50-100 mg each 1-2 weeks, before achievement of optimum therapeutic effect. Usually maintenance dose makes 100-200 mg a day in one or two receptions. It is required to some patients to 500 mg/days.

Additional therapy at adults and children is more senior than 12 years.
At the patients receiving Valproatum in combination with other PEP or without them the initial dose of a lamotridzhin makes 25 mg every other day within 2 weeks, further - on 25 mg within 2 weeks once a day. Then the dose should be increased as much as possible by 25-50 mg/days each 1-2 weeks, the optimum therapeutic effect will not be reached yet. Usually, the maintenance dose makes 100-200 mg/days in one or two receptions. At the patients receiving the accompanying therapy of PEP or other drugs which stimulate a glyukuronization of a lamotridzhin in combination with other PEP or without them (except for Valproatum), the initial dose of a lamotridzhin makes 50 mg within 2 weeks, further once a day - 100 mg/days in two steps within 2 weeks. Then the dose increases as much as possible by 100 mg each 1-2 weeks, before achievement of optimum therapeutic effect. Usually maintenance dose makes 200-400 mg a day in two steps. About 700 mg/days can be required by some patients. At patients who accept окскарбазепин in combination with any other inductors or inhibitors of a glyukuronization of a lamotridzhin or without them the initial dose of a lamotridzhin makes 25 mg within 2 weeks, further once a day - 50 mg/days in one step within 2 weeks. Then the dose increases as much as possible by 50-100 mg each 1-2 weeks, before achievement of optimum therapeutic effect. Usually maintenance dose makes 100-200 mg a day in one or two receptions. Because of risk of development of rash it is not necessary to exceed an initial dose of drug and the recommended mode of increase in doses.

Monotherapy at children from 2nd to 12 years.
The initial dose of a lamotridzhin at monotherapy of patients with typical absentias epileptica makes 0,3 mg/kg/days in one or in two steps within 2 weeks with the subsequent increase in a dose to 0,6 mg/kg/days in one or two receptions within 2 weeks. Then the dose is raised as much as possible on 0,6 mg/kg by each 1-2 weeks to achievement of optimum therapeutic effect. Usually maintenance dose makes from 1 to 15 mg/kg/days in one or two receptions though higher doses are required for some patients.

Additional therapy at children aged from the 2nd up to 12 years.
At the children accepting Valproatum in combination with other PEP or without them the initial dose of a lamotridzhin makes 0,15 mg/kg within 2 weeks, further once a day - 0,3 mg/kg a day in one step within 2 weeks. Then the dose can be increased by 0,3 mg/kg each 1-2 weeks, before achievement of optimum therapeutic effect. The usual maintenance dose makes 1 - 5 mg/kg a day in one or in two steps. The maximum daily dose - 200 mg.
At the patients accepting as the accompanying therapy of PEP or other drugs stimulating a glyukuronization of a lamotridzhin (in combination with other PEP or without them (except for Valproatum)), the initial dose of a lamotridzhin makes 0,6 mg/kg a day in 2 receptions within 2 weeks, further - 1,2 mg/kg/days in two steps within 2 weeks. Then the dose increases as much as possible by 1,2 mg/kg/days each 1-2 weeks, before achievement of optimum therapeutic effect. The usual maintenance dose makes 5-15 mg/kg a day in two steps with the maximum dose of 400 mg/days.
At the patients accepting окскарбазепин without any other inductors or inhibitors of a glyukuronization of a lamotridzhin, the initial dose of a lamotridzhin makes 0,3 mg/kg/days for one or two receptions within 2 weeks, further - 0,6 mg/kg/days in one or two receptions within 2 weeks. Then the dose increases as much as possible by 0,6 mg/kg each 1-2 weeks, the optimum therapeutic effect will not be reached yet. Usually maintenance dose makes 1-10 mg/kg/days in one or two receptions. The maximum dose makes 200 mg/days.
To be sure that the therapeutic dose is supported it is necessary to control the weight of the child and to adjust a drug dose at its change. Exact dosing when performing initial therapy lamotridzhiny in tablets on 5 mg is impossible if the weight of the child is less than 17 kg.
Most likely, that children aged from 2 up to 6 years will need the greatest maintenance doses.

The general recommendations about Konvulsan's dosing at treatment of epilepsy
At cancellation of the accompanying PEP, transfer into monotherapy lamotridzhiny or appointment against the background of reception of a lamotridzhin of other medicines or PEP it is necessary to take into account that it can exert impact on pharmacokinetics of a lamotridzhin.

Bipolar disturbances at adults

It is necessary to follow the transitional mode of dosing which includes increase within 6 weeks of a dose of a lamotridzhin to the supporting stabilizing dose (table 1) then, in the presence of indications, it is possible to cancel others psychotropic and/or PEP (table 2).

Table 1. The recommended scheme of increase in doses for achievement of the stabilizing dose supporting daily at bipolar disturbances at adults.

Dosing mode	1-2 week	3-4 week	5 week	The target stabilizing dose (since the 6th week)
a) Combination therapy inhibitors of a glyukuronization of a lamotridzhin, for example, Valproatum.	12,5 mg (25 mg every other day)	25 mg (1 time a day)	50 mg (for 1-2 receptions a day)	100 mg (for 1-2 receptions a day), maximum daily dose of 200 mg
b) A combination therapy with inductors of a glyukuronization of a lamotridzhin at the sick not accepting inhibitors, such as Valproatum. This mode has to be used with Phenytoinum, carbamazepine, phenobarbital, Primidonum or other inductors of a glyukuronization of a lamotridzhin.	50 mg (1 time a day)	100 mg (for 2 receptions a day)	200 mg (for 2 receptions a day)	300 mg on the 6th week of therapy, if necessary to increase a dose to 400 mg on the 7th week of therapy (for 2 receptions)
c) Monotherapy by Konvulsan or additional therapy at the patients accepting lithium drugs, бупропион, olanzapine, окскарбазепин or other drugs which have no the considerable inducing or inhibiting effect on a glyukuronization of a lamotridzhin.	25 mg (1 time a day)	50 mg (for 1-2 receptions a day)	100 mg (for 1-2 receptions a day)	200 mg (from 100 mg to 400 mg for 1-2 receptions a day)
Note: at the patients accepting PEP which pharmacokinetic interaction with lamotridzhiny is not studied it is necessary to use the mode of increase in doses as it is recommended for a lamotridzhin in combination with Valproatum.

The target stabilizing dose changes depending on clinical effect.
a) Additional therapy at the patients accepting inhibitors of a glyukuronization of a lamotridzhin (for example, Valproatum).
The initial dose of a lamotridzhin at the patients accepting the drugs inhibiting a glyukuronization (such as Valproatum), makes 25 mg every other day within 2 weeks, then 25 mg within 2 weeks once a day. It is necessary to increase a dose to 50 mg (for 1-2 receptions) on the 5th week. Usually target dose makes 100 mg/day (for 1-2 receptions). The maximum daily dose - 200 mg
b) Additional therapy at the patients who are at the same time accepting the drugs stimulating a glyukuronization of a lamotridzhin and not accepting inhibitors of a glyukuronization of a lamotridzhin (for example Valproatum).
This mode has to be used with Phenytoinum, carbamazepine, phenobarbital, Primidonum and other inductors of a glyukuronization of a lamotridzhin. The initial dose of a lamotridzhin makes 50 mg within 2 weeks once a day, then 100 mg a day in two steps within 2 weeks. On the 5th week it is necessary to increase a dose to 200 mg a day in two steps, On the 6th week the dose can be increased to 300 mg a day, however usually, the target dose makes 400 mg a day (in two steps), and is appointed, since 7th week of treatment.
c) Monotherapy by Konvulsan or additional therapy at the patients accepting lithium drugs, бупропион, olanzapine, окскарбазепин or other drugs which has no the considerable inducing or inhibiting effect on a glyukuronization of a lamotridzhin.
The initial dose of a lamotridzhin makes 25 mg within 2 weeks once a day, then 50 mg a day (in 1 or in 2 receptions) within 2 weeks, the Dose it is necessary to increase to 100 mg a day on the 5th week. Usually target dose makes 200 mg a day (in 1 or 2 receptions). After achievement of the target supporting stabilizing dose other psychotropic drugs can be cancelled (table 2).

Table 2. The supporting stabilizing daily dose for treatment of bipolar disorders after cancellation accompanying psychotropic or PEP.

Dosing mode	1 week	2 week	3 week and further
a) After cancellation of inhibitors of a glyukuronization of a lamotridzhin (for example, Valproatum).	To double the stabilizing dose, without exceeding 100 mg/week. I.e. the target stabilizing dose of 100 mg/days increases in 1 week prior to 200 mg/days.	To keep a dose of 200 mg/days in 2 receptions.
b) After cancellation of inductors of a glyukuronization of a lamotridzhin depending on an initial dose. This mode has to be used at use of Phenytoinum, carbamazepine, phenobarbital, Primidonum or other inductors of a glyukuronization of a lamotridzhin	400 mg	300 mg	200 mg
	300 mg	225 mg	150 mg
	200 mg	150 mg	100 mg
c) After cancellation of others psychotropic or PEP at the patients who are not accepting inductors or inhibitors of a glyukuronization of a lamotridzhin (including lithium drugs, бупропион, olanzapine, окскарбазепин).	Support the target dose reached in the course of the increase mode (200 mg/days in 2 receptions; range of doses is from 100 mg to 400 mg).
Note: The dosing mode, as is recommended to the patients accepting PEP which nature of pharmacokinetic interaction with lamotridzhiny is not known now at reception of a lamotridzhin with Valproatum.

If necessary the dose can be increased to 400 mg/days.

a) Therapy Konvulsany ambassador of cancellation of additional therapy by inhibitors of a glyukuronization of a lamotridzhin (for example, Valproatum): right after cancellation of Valproatum, the stabilizing initial dose of a lamotridzhin doubles and supported at this level.
b) Therapy the Konvulsany ambassador of cancellation of additional therapy by inductors of a glyukuronization of a lamotridzhin depending on an initial maintenance dose.
This mode has to be used at use of Phenytoinum, carbamazepine, phenobarbital, Primidonum or other inductors of a glyukuronization of a lamotridzhin. The dose of a lamotridzhin gradually decreases within 3 weeks after cancellation of inductors of a glyukuronization.
c) Therapy the lamotridzhiny ambassador of cancellation accompanying psychotropic or PEP which do not have significant pharmacokinetic interactions with lamotridzhiny (for example, lithium drugs, бупропион, olanzapine, окскарбазепин).
During cancellation of the drugs accompanying a lamotridzhin the target dose of a lamotridzhin reached in the course of the increase mode has to be kept.
There is no clinical experience in correction of daily doses of a lamotridzhin after addition of other drugs. However on the basis of researches on interaction of drugs it is possible to make the following recommendations (table 3).

Table 3. Correction of daily doses of a lamotridzhin at patients with bipolar disturbance after accession to therapy of other drugs.

Dosing mode	The current stabilizing dose of a lamotridzhin (mg/days)	1 week	2 week	3 week and further
a) accession of inhibitors of a glyukuronization of a lamotridzhin (for example, Valproatum), depending on an initial dose of a lamotridzhin.	200 mg	100 mg	To keep a dose 100 mg/days
	300 mg	150 mg	To keep a dose 150 mg/days
	400 mg	200 mg	To keep a dose 200 mg/days
b) Connection of inductors of a glyukuronization of a lamotridzhin at the patients who are not receiving Valproatum depending on an initial dose of a lamotridzhin. This mode has to be used at use of Phenytoinum, carbamazepine, phenobarbital, Primidonum or other inductors of a glyukuronization of a lamotridzhin	200 mg	200 mg	300 mg	400 mg
	150 mg	150 mg	225 mg	300 mg
	100 mg	100 mg	150 mg	200 mg
c) Accession of other psychotropic or antiepileptic drugs with insignificant pharmacokinetic interaction with lamotridzhiny (for example, lithium drugs, бупропион, olanzapine, окскарбазепин).	Support the target dose reached in the course of the increase mode (200 mg/days; range of doses is from 100 mg to 400 mg).
Note: The dosing mode, as is recommended to the patients accepting PEP which nature of pharmacokinetic interaction with lamotridzhiny is not known now at reception of a lamotridzhin with Valproatum.

The therapy termination lamotridzhiny at patients with bipolar disorder: it is possible to cancel ламотриджин at once, without gradual decrease in its dose.

Repeated appointment
In case of resuming of reception of a lamotridzhin the doctor has to estimate need of increase in a maintenance dose at patients who stopped administration of drug for any reasons as high initial doses and exceeding of the recommended doses are associated with risk of development of heavy rash. Than more passed time after the last administration of drug, those with bigger care should raise a dose to supporting. If time after the termination of reception exceeds 5 elimination half-lives, then the dose of a lamotridzhin has to raise to supporting according to the corresponding scheme.
It is not recommended to resume purpose of a lamotridzhin to patients who stopped administration of drug in connection with developing of rash if only the potential advantage of purpose of drug, significantly, does not exceed risk.

The general recommendations about dosing of a lamotridzhin at special categories of patients

The women accepting hormonal contraceptives
a) Purpose of a lamotridzhin the patient who is already receiving hormonal contraceptives: there is no need for correction of the recommended modes of increase in doses of a lamotridzhin.
b) Purpose of hormonal contraceptives the patient who is already receiving maintenance doses of a lamotridzhin and not receiving inductors глюкуронизацш a lamotridzhina: increase in a maintenance dose of a lamotridzhin, but no more, than twice depending on individual clinical effect can be required.
c) The termination of reception of hormonal contraceptives by patients, already receiving maintenance doses of a lamotridzhin and not receiving inductors of a glyukuronization of a lamotridzhin: the dose decline of a lamotridzhin twice depending on individual clinical effect can be required.
Patients of advanced age (65 years are more senior)
Change of the scheme of selection of doses of drug is not required.
Abnormal liver function
The initial, increasing and supporting doses should be reduced approximately by 50% and 75% at patients with moderated (a stage In) and heavy (a stage C) degree of a liver failure respectively. The increasing and supporting doses have to be adjusted depending on clinical effect.
Renal failure
Decrease in a maintenance dose can be recommended to patients with considerable depression of function of kidneys.

Features of use:

Skin rash
At children the risk of development of heavy skin rashes is higher, than at adults. According to the available data the frequency of the skin rashes which demanded hospitalization at the children sick with epilepsy, made from 1 on 300 to 1 on 100 children.
At children initial displays of rash can be mistakenly taken for an infection therefore doctors have to take a possibility of the reaction of children to drug which is shown development of rash and fever in the first 8 weeks of therapy into account. Besides, the total risk of development of rash is considerably connected with:
- A high initial dose of a lamotridzhin and exceeding of the recommended speed of increase in doses of a lamotridzhin.
- The combined use with Valproatum.
At detection of rash all patients (adults and children) have to be quickly examined by the doctor. Reception of a lamotridzhin has to be immediately stopped unless it is obvious that development of rash is not connected with administration of drug. It is not recommended to resume reception of a lamotridzhin in cases when its previous appointment was cancelled in connection with development of skin reaction if only the expected therapeutic effect of use of drug does not exceed risk of side effects.
Degidrofolatreduktaza
Lamotridzhin is weak inhibitor of a degidrofolatreduktaza therefore there is a probability of intervention of drug in metabolism of folates at its long appointment. However it was shown that ламотриджин did not cause essential changes of concentration of hemoglobin, the average volume of erythrocytes, at concentration of folates of erythrocytes of serum of duration of purpose of drug till 1 year and did not reduce concentration of folates in erythrocytes at purpose of a lamotridzhin duration up to 5 years.
The patients accepting other drugs containing ламотриджин
It is impossible to appoint Konvulsan sick, already receiving any other drugs,
containing ламотриджин without consultation of the doctor.
Epilepsy
Sharp cancellation of reception of a lamotridzhin, as well as other PEP, can provoke development of spasms. If the sharp termination of therapy is not safety requirement (for example, at emergence of rash), the dose of a lamotridzhin should be reduced gradually within 2 weeks.
In literature there are messages that heavy convulsive attacks, including the epileptic status, can lead to development of a rabdomioliz, multiorgan disturbances and the IDCS, sometimes with a fatal outcome. Similar cases were observed also at treatment of patients lamotridzhiny. Bipolar disorders
The possibility of commission of suicide attempts is characteristic of bipolar disorders therefore treatment of such patients has to be carried out under careful observation.

Side effects:

Information is divided into adverse reactions at patients with epilepsy and adverse reactions at patients with bipolar disorder. However for consideration of a profile of safety of a lamotridzhin in general, it is necessary to take data of both sections into account.
The following conditional classification of frequency of undesirable effects is used: very often (> 1/10), it is frequent (> 1/100, <1/10), infrequently (> 1/1000, <1/100), is rare (> 1/10.000, <1/1000), is very rare (<1/10.000).

Epilepsy
Disturbances from skin and hypodermic cellulose
At monotherapy:
Very often: skin rashes.
At other types of a clinical use.
Very often: skin rashes; seldom: malignant exudative erythema (Stephens Johnson's syndrome); very seldom: toxic epidermal necrolysis.
Rash, generally makulopapulezny, usually develops within the first 8 weeks of the moment of the beginning of therapy and passes after drug withdrawal.
There are messages on exceptional cases of development of the heavy, potentially life-threatening damages of skin including Stephens-Johnson's syndrome and a toxic epidermal necrolysis (Lyell's disease). Though in most cases at drug withdrawal there was involution of symptoms, some patients had irreversible hems on skin, and the deaths connected with administration of drug were in rare instances registered.
The general risk of development of rash was substantially connected with:

high initial dose of a lamotridzhin and exceeding of the recommended rates of building of doses of a lamotridzhin.
the accompanying purpose of Valproatum.
development of rash was also considered as manifestation of the syndrome of hypersensitivity connected with various system manifestations.
Hemopoietic and lymphatic systems
Very seldom: the hematologic disturbances including a neutropenia, a leukopenia, anemia, thrombocytopenia, a pancytopenia, aplastic anemia, an agranulocytosis. Hematologic disturbances can be, and can be not connected with a hypersensitivity syndrome.
Disturbances from immune system
Very seldom: a hypersensitivity syndrome (including such symptoms as fever, a lymphadenopathy, puffiness of the person, disturbance from blood and function of a liver, a syndrome disseminated intravascular coagulation (IDCS), multiorgan disturbances).
Rash is also considered as a part of the syndrome of hypersensitivity connected with various system manifestations including fever, a limfoadenopatiya, puffiness of the person, disturbance from blood and function of a liver. The syndrome proceeds with varying severity and can lead, in rare instances, to development of the IDCS and weed to organ disturbances. It is important to note that early manifestations of hypersensitivity (i.e. fever, a limfoadenopatiya) can take place even in the absence of strong indications of rash. At development of similar symptoms of the patient it has to be immediately examined by the doctor and if other reason of symptoms is not established, ламотриджин it has to be cancelled.
infrequently: aggression; very seldom: tics, hallucinations, confusion of consciousness.
Frustration of a nervous system
At monotherapy
Very often: irritability, headache; often: drowsiness, sleeplessness, dizziness, tremor; infrequently: ataxy.
At other types of clinical use
Very often: headache, dizziness; often; irritability, nystagmus, tremor, ataxy, drowsiness, sleeplessness; infrequently: aggression; very seldom: tics, hallucinations, confusion of consciousness; very seldom: agitation, instability, motive frustration, deterioration in symptoms of a disease of Parkinson, extrapyramidal frustration, choreoathetosis, increase in frequency of convulsive attacks.
Vision disorders
Very often: diplopia, sight illegibility; seldom: conjunctivitis. Gastrointestinal frustration
At monotherapy:
Often: nausea
At other types of clinical use:
Often: nausea, diarrhea.
Gepato-biliarnye disturbances
Very seldom: increase in levels of liver enzymes, abnormal liver function, liver failure.
Abnormal liver functions usually develop in combination with hyperreactivity symptoms, but in isolated cases were noted also in lack of strong indications of hypersensitivity.
Disturbances from muscular and connecting fabrics
Very seldom: volchanochnopodobny syndrome
Disturbances of the general character
Often: fatigue.
Bipolar disturbance
Disturbances from skin and hypodermic cellulose
Very often: skin rash; seldom: Stephens's syndrome - Johnson;
Frustration of a nervous system
Very frequent: headache; frequent: agitation, drowsiness, dizziness.
Disturbances from muscular and connecting fabrics
Often: arthralgia
Disturbances of the general character
Often: pain, dorsodynia.

Interaction with other medicines:

The average elimination half-life decreases approximately to 14 h at co-administration with the drugs stimulating a glyukuronization such as carbamazepine and Phenytoinum, and raises on average to 70 h at joint appointment with Valproatum.
Uridinediphosphate (UDF) of a glyukuroniltransferaz is the main enzyme metabolizing ламотриджин. There are no data on ability of a lamotridzhin to cause clinically significant induction or inhibition of oxidizing enzymes of a liver. In this regard interactions between lamotridzhiny and the drugs which are metabolized system of enzymes of P450 cytochrome it is improbable. Lamotridzhin can stimulate own metabolism, but this effect is expressed moderately and has no clinically significant effects.

Table 4. Influence of other drugs on a glyukuronization of a lamotridzhin.

The drugs having expressed suppressing effect on a glyukuronization of a lamotridzhin	The drugs having expressed stimulating effect on a glyukuronization of a lamotridzhin	The drugs which do not have a considerable overwhelming or promoting effect on a glyukuronization of a lamotridzhin
Valproatum	carbamazepine Phenytoinum Primidonum phenobarbital rifampicin the combined drug etiniloestradiol/ levonorgestrel	lithium drugs бупропион olanzapine окскарбазепин

Influence of other oral contraceptives and hormonal replacement therapy was not studied though they can exert similar impact on pharmacokinetic indicators of a lamotridzhin.

Interactions with PEP
Valytroat who suppresses a glyukuronization of a lamotridzhin reduces the speed of his metabolism and extends its average elimination half-life almost twice.
Certain antiepileptic drugs (such as Phenytoinum, carbamazepine, phenobarbital and Primidonum) which stimulate system of metabolizing enzymes of a liver, accelerate a glyukuronization of a lamotridzhin and his metabolism. It was reported about development of undesirable effects from TsNS including dizziness, an ataxy, a diplopia, an illegibility of sight and nausea at the patients who began to accept carbamazepine against the background of therapy lamotridzhiny. These symptoms usually passed after a carbamazepine dose decline. The similar effect was observed at purpose of a lamotridzhin and okskarbazepin to healthy volunteers, the result of decrease in doses was not studied.
Lamotridzhin does not force out other PEP from their communication with proteins of plasma.
At co-administration of a lamotridzhin in a dose of 200 mg and an okskarbazepina in a dose of 1200 mg, neither окскарбазепин and nor ламотриджин do not break metabolism of each other.

The interactions including other psychotropic drugs
Lamotridzhin in a dose of 100 mg/day does not cause disturbance of pharmacokinetics of an anhydrous gluconate of lithium (on 2 g 2 times a day within 6 days) at their joint appointment.
Repeated purpose of a bupropion inside does not exert statistically considerable impact on pharmacokinetics of a single dose of a lamotridzhin and causes insignificant increase in AUC (the area under a curve "Concentration time") a lamotridzhina of a glucuronide.
Olanzapine in a dose of 15 mg AUC and Smakh lowers a lamotridzhin on average by 24% and 20% respectively. Changes of such level usually do not assume the clinical importance. Lamotridzhin in a dose of 200 mg does not change olanzapine kinetics.
The inhibition of a lamotridzhin amitriptyline, bupropiony, clonazepam, fluoxetine, a haloperidol or lorazepam exerts the minimum impact on formation of primary metabolite of a lamotridzhin of a 2-N-glucuronide. Studying of metabolism of a bufuralol the microsomal enzymes of a liver emitted at the person allows to draw a conclusion that ламотриджин does not reduce clearance of drugs, элиминирующихся preferential CYP2D6 isoenzymes. Results of the researches in vitro also allow to assume that clozapine, фенелзин, рисперидон, sertraline or Trazodonum can hardly exert impact on clearance of a lamotridzhin.

Interactions with hormonal contraceptives
Influence of hormonal contraceptives but pharmacokinetics of a lamotridzhin.
Reception of the combined oral contraceptives containing 30 mkg of an etiniloestradiol and 150 mkg of levonorgestrel causes approximately double increase in clearance of a lamotridzhin (after its intake) that also Smakh leads to decrease in AUC a lamotridzhin on average for 52% and 39% respectively. Within a week, free from reception of active drug, increase in plasma concentration of a lamotridzhin, at the same time the concentration of a lamotridzhin measured at the end of this week before introduction of the following dose on average is observed is twice higher, than during active therapy.
Influence of a lamotridzhin on pharmacokinetics of hormonal contraceptives
The period of equilibrium concentration ламотриджин in a dose of 300 mg does not influence pharmacokinetics of an etiniloestradiol - a component of the combined oral contraceptive. Small increase in clearance of the second component of an oral contraceptive - levonorgestrel is noted that led to decrease in AUC and Smakh of levonorgestrel for 19% and 12% respectively. Measurement of serumal FSG, LG and oestradiol during this research revealed small reduction of suppression of hormonal activity of ovaries at some women though measurement of plasma progesterone at one of 16 women did not reveal hormonal confirmations of an ovulation. Influence of moderate increase in clearance of levonorgestrel and change of the FSG and LG plasma levels on ovulyatsionny activity of ovaries is not established. Influence of other doses of a lamotridzhin (except 300 mg/day) was not studied and researches with inclusion of other hormonal drugs were not conducted.

Interactions with other drugs
Rifampicin increases clearance of a lamotridzhin and reduces its elimination half-life thanks to stimulation of the liver enzymes responsible for a glyukuronization. The patient receiving rifampicin as the accompanying therapy, the mode of purpose of a lamotridzhin has to correspond to the scheme recommended at the joint purpose of a lamotridzhin and means stimulating a glyukuronization.

Influence on ability to drive the car and others to others mechanisms

It is not recommended to be engaged during treatment in the types of activity (including to drive the car) demanding speed of psychomotor reactions.

Contraindications:

Hypersensitivity to any of drug components, children's age up to 2 years (there is no experience of use).

With care:
pregnancy, lactation period, chronic renal failure.

Use at pregnancy and a lactation
Pregnancy
As well as other drugs, ламотриджин it has to be appointed at pregnancy only if the expected therapeutic advantage for mother exceeds potential risk for a fruit. The physiological changes developing at pregnancy can exert impact on concentration of a lamotridzhin and/or its therapeutic effect. There are messages on decrease in concentration of a lamotridzhin during pregnancy. Purpose of a lamotridzhin has to be provided to pregnant women with tactics of maintaining patients corresponding to a state.
Lactation
According to preliminary data ламотриджин gets into breast milk in concentration, the corresponding about 40% - 60% of concentration in a blood plasma of mother. Concentration of a lamotridzhin in a blood plasma of the children who are on breastfeeding can reach values at which the pharmacological effect develops.
It is necessary to correlate potential advantage of feeding by breast milk and potential risk of development of side effects in the child.

Overdose:

It was reported about a single dose of the doses exceeding maximum therapeutic at 10-20 times. The overdose was shown by the symptoms including a nystagmus, an ataxy, disturbances of consciousness and a coma.
Treatment: gastric lavage, hospitalization and performing symptomatic therapy.

Storage conditions:

Period of validity 3 years. Not to use after expiry date. In protected from light, the place, unavailable to children, at a temperature not above 30 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets of 25 mg, 50 mg 100 mg, 200 mg. On 7, 10 or 14 tablets in the blister from PVC / aluminum foil; on 2, 4 blisters (on 7 tablets) or on 1, 3 blisters (on 10 tablets), or on 1, 2 blisters (on 14 tablets) together with the application instruction in a cardboard pack.