Lamictal - instructions for use, dose, side effects, contraindications

Name of components	Quantity, mg / tablet
Name of components	Dosage 25 mg	Dosage 50 mg	Dosage 100 mg
Active substance:
Lamotrigine	25,0	50,0	100,0
Excipients:
Lactose Monohydrate	24,7	49,4	98,8
Microcrystalline cellulose	24,7	49,4	98,8
Sodium carboxymethyl starch	2,5	5,0	10,0
Povidone	2,5	5,0	10,0
Magnesium stearate	0,4	0,8	1,6
Dye iron oxide yellow	0,2	0,4	0,8

Description:

Dosage of 25 mg:

Tablets from pale yellow to yellow-brown color, square with rounded corners. One side is flat with an embossed "GSEC7 ", the other side is multifaceted, with a convex square with a squashed figure of 25.

Dosage 50 mg:

Tablets from pale yellow to yellow-brown color, square with rounded corners. One side is flat, with an embossed "GSEE1 ", the other side is multifaceted, with a convex square with a squashed figure of 50.

Dosage of 100 mg:

Tablets from pale yellow to yellow-brown color, square with rounded corners. One side is flat, with an embossed "GSEE5 ", the other side is polyhedral, with a convex square with an extruded figure of 100.

Pharmacotherapeutic group:antiepileptic agent

ATX: & nbsp

N.03.A.X Other antiepileptic drugs

N.03.A.X.09 Lamotrigine

Pharmacodynamics:

Lamotrigine is a blocker of potential-dependent sodium channels. In neuronal culture, it induces a potential-dependent blockade of continuously recurring impulses and suppresses the pathological release of glutamic acid (an amino acid that plays a key role in the development of epileptic seizures), and also inhibits depolarization caused by glutamate.

Pharmacokinetics:

Suction

Lamotrigine is rapidly and completely absorbed from the intestine, practically without undergoing a first-pass systemic metabolism.The maximum concentration in the plasma is achieved approximately 2.5 hours after oral administration of the drug. The time to reach the maximum concentration increases slightly after ingestion, but the degree of absorption remains unchanged.

Pharmacokinetics is linear in the administration of a single dose up to 450 mg (the highest dose studied). There are significant individual fluctuations in the maximum concentration in the equilibrium state, but with occasional fluctuations in each individual patient.

Distribution

Lamotrigine binds to plasma proteins approximately 55%. It is unlikely that the release of the drug from binding to proteins can lead to the development of a toxic effect.

The volume of distribution is 0.92-1.22 l / kg.

Metabolism

In the metabolism of lamotrigine, the enzyme uridine-diphosphate-glucuronyltransferase (UDP-glucuronyltransferase) participates. Lamotrigine to a small extent increases its own metabolism in a dose-dependent manner. However, no NickSuch data confirming that lamotrigine affects the pharmacokinetics of other antiepileptic drugs and that between lamotrigine and otherdrugs metabolized by the cytochrome P450 system, interaction is possible.

Excretion

In healthy adults, the average equilibrium clearance of lamotrigine averages 39 ± 14 ml / min. Lamotrigine is metabolized to form glucuronides, which are excreted by the kidneys.

Less than 10% of the drug is excreted through the kidneys in an unchanged form, about 2% through the intestine.

Clearance and half-life do not depend on the dose. The half-life in healthy adults is on average between 24 and 35 hours. In patients with Gilbert's syndrome, the clearance of the drug was reduced by 32% compared with the control group, which, however, did not exceed the limits of normal values for the general population.

For the half-life of lamotrigine, the simultaneous use of medications is of great importance.

The average half-life is reduced to approximately 14 hours, while simultaneous use with induction drugs glucuronidation, such as carbamazepine and phenytoin, and increases, on average, up to 70 hours with simultaneous application with valproate.

Special patient groups

Children

In children the clearance of lamotrigine is higher for body weight than for adults; it is highest in children under 5 years old. In children, the half-life of lamotrigine is usually shorter than in adults. Its mean value is approximately 7 hours when used concomitantly with preparations that induce glucuronidation, such as carbamazepine and phenytoin, and rises on average to 45-50 hours with simultaneous application with valproate.

Elderly patients

Clinically significant differences in the clearance of lamotrigine in elderly patients in comparison with young patients were not detected.

Patients with impaired renal function

If the renal function is impaired, the initial dose of lamotrigine is calculated according to the standard regimen of the antiepileptic drug. Dose reduction may be required only with a significant decrease in kidney function.

Patients with impaired hepatic function

Initial, increasing and maintenance doses should be reduced by approximately 50% in patients with moderate hepatic impairment (class AT Child-Pugh classification) and 75% in patients with severe hepatic impairment (Child-Pugh class C).

The dose increase and the maintenance dose should be adjusted depending on the clinical effect.

Clinical efficacy in patients with bipolar affective disorder

Efficacy in preventing mood disorders in patients with bipolar disorders has been demonstrated in two fundamental clinical studies. AT A combined analysis of the results showed that the duration of remission, defined as the time to the onset of the first episode of depression and to the first episode of mania / hypomania / mixed episodes of mania and hypomania after stabilization, was longer in the lamotrigine group compared with placebo.

The duration of remission is more pronounced for depression.

Indications:

Epilepsy

Children from 3 to 12 years old

Epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures in the Lennox-Gastaut syndrome) as part of a combination therapy.

After achieving epilepsy control against a background of combined therapy, concomitant antiepileptic drugs (PEP) can be reversed, and lamotrigine is continued in monotherapy.

Monotherapy of typical absences.

Adults and children (over 12 years)

Epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures in the Lennox-Gastaut syndrome) in combination therapy or monotherapy.

Bipolar affective disorder

Adults (18 years and over)

Prevention of mood disorders (depression, mania, hypomania, mixed episodes) in patients with bipolar affective disorder.

Contraindications:

Hypersensitivity to lamotrigine or any other component of the drug.

Pregnancy and lactation:

Fertility

Studies on the reproductive function of animals with lamotrigine did not reveal any impairment of fertility.

Studies on the effect of lamotrigine on human fertility have not been conducted.

Pregnancy

The risk associated with a PEP as a whole

Women who are capable of procreation should consult with specialists.

If a woman is planning a pregnancy, the need for treatment of PEP should be reviewed. Women who are treated with epilepsy should avoid sudden discontinuation of antiepileptic therapy,as this can lead to the resumption of seizures, which can have serious consequences for the woman and the unborn child. In the offspring of mothers who received PEP, the risk of congenital malformations increases by 2-3 times in comparison with the expected incidence of the general population, which is about 3%. The most frequently detected defects are hare lip, heart and vascular defects, neural tube defects. Multiple PEP therapy is associated with a higher risk of congenital malformations than monotherapy, in this regard? If possible, monotherapy should be used.

The risk associated with taking lamotrigine

Lamotrigine has a slight inhibitory effect on the reductase of dihydrofolic acid and therefore, theoretically, can lead to an increased risk of embryonic and fetal developmental disorders due to decreased levels of folic acid. You should consider the possibility of taking folic acid during pregnancy planning and in the early stages of pregnancy.

Post-registration data from several prospective pregnancy registers made it possible to document the outcomes of pregnancies for about 8,700 women who received monotherapy with Lamictal® in the first trimester of pregnancy.In general, the findings do not confirm a general increase in the risk of congenital malformations. Although there are reports of an increased risk of developing oral malformations from a limited number of pregnancy registries, a completed case-control study did not reveal an increased risk of developing oral malformations compared to other serious developmental malformations following lamotrigine application.

Data on the use of Lamictal® in combined therapy is not sufficient to assess whether the risk of developmental defects is associated with other drugs used in combination with lamotrigine.

As with other drugs, Lamictal® should be given during pregnancy only if the expected therapeutic benefit exceeds the potential risk.

Physiological changes in pregnancy can affect the concentration of lamotrigine and / or its therapeutic effect. There are reports of a decrease in the concentration of lamotrigine in the blood during pregnancy. The appointment of the drug Lamictal to pregnant women should be provided with the appropriate state of patient management tactics.

Breastfeeding period

Lamotrigine penetrates into breast milk to a varying degree, the total concentration of lamotrigine in breastfed infants may reach about 50% of the lamotrigine concentration registered with the mother. Thus, in some infants who are breast-fed, the serum concentrations of lamotrigine may reach levels at which pharmacological effects are manifested. It is necessary to correlate the potential benefits of breastfeeding and the potential risk of developing unwanted reactions in the child.

If the woman taking the drug Lamicital^®, decides to breast-feed, the child should monitor the appearance of any unwanted reactions.

Dosing and Administration:

Inside.

Tablets should be swallowed whole, not chewed, not broken.

If the calculated dose of Lamectal^® (for example, when used in children (only with epilepsy) or in patients with impaired liver function) can not be divided into a whole number of tablets of a lower dosage, the patient should be given a dose that corresponds to the nearest value of the whole tablet of a lower dosage.

Renewal of the drug

In the event of a resumption of the drug Lamiktal® doctors should assess the need to improve the maintenance dose in patients who had stopped taking the drug for any reason, since high initial doses and exceeding the recommended dose is associated with the risk of developing severe rash. The more time passed after the last dose, the more care should be taken to increase the dose to the maintenance dose. If the time after discontinuation is greater than 5 half-lives, the lamotrigine dose should be increased to a maintenance dose according to the appropriate schedule.

Lamectal® therapy should not be resumed in patients whose discontinuation of treatment was associated with the appearance of a rash, unless the potential benefit of such therapy clearly exceeds possible risks.

Epilepsy

Monotherapy for epilepsy

Adults and children over 12 years of age (Table 1)

The initial dose of Lamictal® in monotherapy is 25 mg once a day for 2 weeks, followed by a dose increase of 50 mg once a day for 2 weeks.Then the dose should be increased as much as 50-100 mg every 1-2 weeks, until the optimal therapeutic effect is achieved.

The usual maintenance dose for achieving the optimal therapeutic effect is 100-200 mg / day in 1 or 2 doses. Some patients need a dose of Lamictal® 500 mg / day to achieve the desired therapeutic effect.

Children aged 3 to 12 years (Table 2)

The initial dose of Lamictal® in monotherapy of patients with typical absences is 0.3 mg / kg / day in 1 or 2 doses for 2 weeks, followed by a dose increase of 0.6 mg / kg / day in 1 or 2 doses during the following 2 weeks. The dose should then be increased to a maximum of 0.6 mg / kg every 1-2 weeks until the optimal therapeutic effect is achieved. This circumstance allows relatively accurately dose the drug in children with a body weight of 40 kg or more.

Usual the maintenance dose for achieving the optimal therapeutic effect is 1 to 10 mg / kg / day in 1 or 2 doses, although some patients with typical absences have higher doses to achieve the desired therapeutic effect.

Because of the risk of developing the rash, the initial dose of the drug and the recommended regime for increasing the dose should not be exceeded.

In the combination therapy of epilepsy

Adults and children over 12 years of age (Table 1)

In patients who already receive valproate in combination with or without other PET, the initial dose of Lamictal® is 25 mg every other day for 2 weeks, then 25 mg once a day for 2 weeks. Then the dose should be increased by a maximum of 25-50 mg every 1-2 weeks, until the optimal therapeutic effect is achieved.

Usual the maintenance dose for achieving the optimal therapeutic effect is 100-200 mg / day in 1 or 2 doses.

In patients who receive concomitant therapy with PEP or other drugs that induce glucuronization of lamotrigine in combination or without other PEP (with the exception of valproate), the initial dose of Lamictal® is 50 mg once a day for 2 weeks, then 100 mg / day in 2 divided doses for 2 weeks.

Then the dose should be increased to the maximum of 100 mg every 1-2 weeks, until the optimal therapeutic effect is achieved.The usual maintenance dose is 200-400 mg / day in 2 divided doses.

Some patients may need a dose of 700 mg / day to achieve the desired therapeutic effect.

In patients taking other drugs that do not significantly inhibit or induce glucuronization of lamotrigine, the initial dose of Lamictal® is 25 mg once a day for 2 weeks, then 50 mg once a day for 1 week. Then the dose should be increased as much as 50-100 mg every 1-2 weeks, until the optimal therapeutic effect is achieved.

The usual maintenance dose is 100-200 mg / day in 1 or 2 doses.

Table 1. Recommended dosage regimen of the drug Lamicital^® in the treatment of epilepsy in adults and children over 12 years of age

Dosing regimen		A week 1-2	A week 3-4	Supportive dose
Monotherapy		25 mg (1 time per day)	50 mg (1 time per day)	100-200 mg (in 1 or 2 reception). To achieve a therapeutic effect,gut be increased by 50-100 mg every 1-2 of the week.
Combination therapy with valproate, regardless of other concomitant therapy		12,5 mg (appointed by 25 mg every other day)	25 mg (1 time per day)	100-200 mg (in 1 or 2 divided doses). To achieve a therapeutic effect of the dose may be increased by 25-50 mg every 1-2 of the week.
Combination therapy without valproate	This regimen should be used with phenytoin, carbamazepine, phenobarbital, primidone or other inducers of lamotrigine glucuronization	50 mg (1 time per day)	100 mg (in 2 admission)	200 400 mg (in 2 reception). To achieve a therapeutic effect, doses can be increased by 100 mg every 1-2 weeks.
	This mode must used with other drugs that do not substantially inhibit and induce glucuronization of lamotrigine	25 mg (1 time per day)	50 mg (1 time per day)	100- 200 mg (in 1 or 2 reception). To achieve a therapeutic effect, the dose can be increased by 50-100 mg every 1-2 of the week.
In patients, receiving PET, the pharmacokinetic interaction of which with lamotrigine at Currently unknown, should be used dosing, recommended for applications lamotrigine in combination with valproate.

Because of the risk of developing the rash, do not exceed the initial dose of the drug Lamictal® and the recommended dose-increasing regimen.

Children aged 3 to 12 years (Table 2)

Children taking valproate in combination with other PEPs or without them, the initial dose of Lamictal® is 0.15 mg / kg / day once a day for 2 weeks, then 0.3 mg / kg / day once a day for 2 weeks. Then the dose can be increased maximally at 0.3 mg / kg every 1-2 weeks, until the optimal therapeutic effect is achieved.

The usual maintenance dose for achieving the optimal therapeutic effect is 1-5 mg / kg / day in 1 or 2 doses.

The maximum dose is 200 mg / day.

In children who receive PEP or other drugs that induce glucuronization of lamotrigine, in combination with or without other PEP (with the exception of valproate), the initial dose of Lamycal^®is 0.6 mg / kg / day in 2 divided doses for 2 weeks, then 1.2 mg / kg / day in 2 divided doses for 2 weeks. Then the dose should be increased to the maximum at 1.2 mg / kg every 1-2 weeks until the optimal therapeutic effect is achieved.

The usual maintenance dose at which the optimal therapeutic effect is achieved is 5-15 mg / kg / day in 2 divided doses.

The maximum dose is 400 mg / day.

In patients taking other drugs that do not substantially inhibit or induce glucuronization of lamotrigine, the initial dose of Lamycal^® is 0.3 mg / kg / day in 1 or 2 doses for 2 weeks, then 0.6 mg / kg / day in 1 or 2 doses for 2 weeks. The dose should then be increased to a maximum of 0.6 mg / kg every 1-2 weeks until the optimal therapeutic effect is achieved.

The usual maintenance dose at which the optimal therapeutic effect is achieved is 1 to 10 mg / kg / day in 1 or 2 doses.

The maximum dose is 200 mg / day.

It is likely that patients aged 3 to 6 years will require a maintenance dose at the upper border recommended range.

To be confident that a therapeutic dose is maintained, it is necessary to monitor the weight of the child's body and adjust the dose of the drug when it changes. Because of the risk of developing the rash, the initial dose of the drug and the subsequent dose-increasing regimen should not be exceeded.

Table 2. Recommended dosage regimen of Lamictal® in the treatment of epilepsy in children aged 3 to 12 years

Mode dosing		A week 1-2	A week 3-4	Maintenance dose
Monotherapy typical absences		0.3 mg / kg (in 1 or 2 admission)	0.6 mg / kg (in 1 or 2 admission)	Increase the dose by 0.6 mg / kg every 1-2 weeks until a maintenance dose of 1-10 mg / kg (prescribed in 1 or 2 doses) is reached to a maximum dose of 200 mg / day.
Combination Therapy from valproate, regardless of other concomitant therapy		0,15 mg / kg (1 time per day)	0.3 mg / kg (1 time per day)	Increase the dose by 0.3 mg / kg every 1-2 weeks until a maintenance dose of 1-5 mg / kg / day (prescribed in 1 or 2 doses) to a maximum dose of 200 mg / day.
Combined therapy without valproate	This regimen should be used with phenytoin, carbamazepine, phenobarbital, primidone or other inducers of lamotrigine glucuronization	0.6 mg / kg (in 2 admission)	1.2 mg / kg (in 2 admission)	Increase the dose by 1.2 mg / kg every 1-2 weeks until a maintenance dose of 5-15 mg / kg / day (prescribed in 1 or 2 doses) to a maximum dose of 400 mg / day.
	This mode should be used with drugs that do not inhibit and induce glucuronization of lamotrigine.	0.3 mg / kg (in 1 or 2 admission)	0.6 mg / kg (in 1 or 2 admission)	Increasing the dose by 0.6 mg / kg every 1-2 weeks until a maintenance dose of 1-10 mg / kg / day (in 1 or 2 admission) to a maximum dose of 200 mg / day.
Have patients, receiving PET, the pharmacokinetic interaction of which with lamotrigine is currently unknown, should be used dosing, recommended for applications lamotrigine in combination with valproate. If the calculated daily dose in patients taking valproate is 1-2 mg, then you can assign lamotrigine in a dose of 2 mg every other day for the first two weeks. If the calculated daily dose in patients taking valproate is less than 1 mg, lamotrigine should not be appointed.

Children under 3 years

The use of Lamectal® has not been studied as monotherapy in children under 2 years of age or as an adjunctive therapy in children under 1 month of age. The safety and efficacy of Lamictal® as an additional Therapy of partial seizures in children aged 1 month to 2 years is not established.

In children under 3 years of age, the use of solid dosage forms (which can not be dissolved beforehand, etc.) is not allowed.

General recommendations on the dosage regimen in the treatment of epilepsy

If the associated PEP is canceled, or the PEP is added, or on the background of taking lamotrigine other medications or PEP it is necessary to take into account the fact that this can have an effect on the pharmacokinetics of lamotrigine.

Bipolar affective disorder

Adults aged 18 years and over

Because of the risk of rash, do not exceed the initial dose of the drug and the subsequent regime of increasing doses. It is necessary to follow a transitional dosing regimen that includes a 6-week increase in the dose of Lamictal® up to the maintenance stabilizing dose (Table 3), after which, in the presence of indications, it is possible to cancel other psychotropic drugs and / or PEP (Table 4).

Table 3. Recommended mode of increasing the dose of Lamictal® to achieve a maintenance daily stabilizing dose for adults (over 18 years of age) with bipolar affective disorder

Mode dosing	Weeks 1-2	Weeks 3-4	Week 5	Target stabilizing dose (week 6) **
a) Combination therapy with glucuroniac inhibitorsand lamotrigine, for example, valproate	12.5 mg (25 mg every other day)	25 mg (1 time per day)	50 mg (at 1 or 2 admission per day)	100 mg (at 1 or 2 admission at day), the maximum daily dose of 200 mg
b) Combination therapy with lamotrigine glucuronide inhibitors in patients not taking inhibitors, such as valproate. This regimen should be used with phenytoin, carbamazepine, phenobarbital,primidone or other inducers of lamotrigine glucuronization.	50 mg (1 time per day)	100 mg (at 2 admission to day)	200 mg (at 2 admission to day)	300 mg at week 6 of therapy, if necessary, increase the dose to 400 mg / day at week 7 of therapy (at 2 admission per day)
at) Monotherapy with lamotrigine or combined therapy in patients taking other drugs that do not have a significant inducing or inhibitory effect on the glucotoninization of lamotrigine.	25 mg (1 time per day)	50 mg (at 1 or 2 admission per day)	100 mg (at 1 or 2 admission per day)	200 mg (100 mg to 400 mg) (at 1 or 2 admission per day)
Note: in patients taking pap, the pharmacokinetic interaction of which with lamotrigine is currently unknown, a dose-boost regimen recommended for lamotrigine in combination with valproate should be used.

^** The target stabilizing dose varies depending on the clinical effect.

a) Combination therapy with glucuronine inhibitors lamotrigine, for example, valproate

The initial dose of Lamictal® in patients, additionally taking drugs that inhibit glucuronization, such as valproate, is 25 mg every other day for 2 weeks, then 25 mg once a day for 2 weeks. The dose should be increased to 50 mg once a day (or in 2 divided doses) at week 5. The usual target dose for obtaining the optimal therapeutic effect is 100 mg / day (in 1 or 2 doses). However, the dose may be increased to a maximum daily dose of 200 mg, depending on the clinical effect.

b) Combined therapy with inducers of glucuronization lamotrigine in patients who do not take inhibitors, such as valproate. This regimen should be used with phenytoin, carbamazepine, phenobarbital, primidone and other inducers of lamotrigine glucuronization

Initial dose of Lamectal^® among such patients, simultaneously taking drugs that induce glucuronization lamotrigine, and not taking valproate, is 50 mg once a day for 2 weeks, then 100 mg / day in 2 divided doses for 2 weeks. At 5 weeks, the dose should be increased to 200 mg / day in 2 divided doses. At 6 weeks, the dose can be increased to 300 mg / day, but the usual target dose for achieving the optimal therapeutic effect is 400 mg / day (in 2 divided doses), and is prescribed starting from week 7 of treatment.

at) Monotherapy with lamotrigine or combined therapy in patients taking drugs that do not have a significant inducing or inhibitory effect on glucuronization lamotrigine

The initial dose of Lamictal® is 25 mg once daily for 2 weeks, then 50 mg / day (in 1 or 2 admission) for 2 weeks. On week 5 The dose should be increased to 100 mg / day. The usual target dose for achieving the optimal therapeutic effect is 200 mg / day (in 1 or 2 doses). However, in clinical trials, doses ranging from 100 to 400 mg were used.

After reaching the target daily maintenance stabilizing dose, other psychotropic drugs may be withdrawn (Table 4).

Table 4. Supportive stabilizing total daily dose of Lamictal® for the treatment of bipolar affective disorder after withdrawal of concomitant psychotropic drugs or PEP

Dosing regimen	Week 1	Week 2	Week 3 and beyond *
a) After the abolition of glucuronide inhibitorsthelamotrigine, for example, valproate	Double the stabilizing dose, not exceeding 100 mg / week. That is, the target stabilizing dose of 100 mg / day is increased by 1 week to 200 mg / day.	Save the dose of 200 mg / day in 2 divided doses.
b) After the elimination of glucuronis inducersthe lamotrigine, depending on the initial dose. This regimen should be used when using phenytoin, carbamazepine, phenobarbital, primidon or other inducers glucuronization of lamotrigine	400 mg	300 mg	200 mg
	300 mg	225 mg	150 mg
	200 mg	150 mg	100 mg
at) After the abolition of other psychotropic drugs the patients, Do not take inducers or inhibitors glucuronization of lamotrigine	Maintain the target dose achieved during the regimen (200 mg / day in 2 divided doses from 100 mg to 400 mg).
Note: in patients taking PET, the pharmacokinetic interaction of which with lamotrigine is currently unknown, it is recommended that the current dose of lamotrigine be maintained and that the lamotrigine dose should be selected based on the clinical response.

* If necessary, the dose may be increased to 400 mg / day.

a) lamotrigine therapy after withdrawal of combination therapy with lamotrigine glucuronide inhibitors, for example, valproate

Immediately after the abolition of valproates, the target The stabilizing dose of Lamictal® should be double and maintain at this level.

b) lamotrigine therapy after withdrawal of combined therapy with inducers of glucuronization of lamotrigine, depending on the initial maintenance dose. This regimen should be used when using phenytoin, carbamazepine, phenobarbital, primidon, or other inducers of lamotrigine glucuronization

Dose Lamectal® should be gradually reduced within 3 weeks after the elimination of glucuronine inducers.

c) Lamotrigine therapy after withdrawal of concomitant psychotropic drugs, not having an inhibitory or inducing effect on the glucuronization of lamotrigine

During the withdrawal of concomitant medications, the target dose of Lamictal®, achieved during the enhancement regimen, should be maintained.

Correction of a daily dose of Lamycal® in patients with bipolar affective disorder after the addition of other drugs

There is no clinical experience in correcting daily doses of Lamycatal^® after the addition of other drugs. However, based on studies on drug interactions, the following recommendations can be made (Table 5).

Table 5.Correction of daily doses of Lamictal® in patients with bipolar affective disorder after addition of other drugs

Dosing regimen	The current stabilizing dose of lamotrigine (mg / day)	Week 1	Week 2	Week 3 and onwards
a) Addition of lamotrigine glucuronin inhibitors (eg, valproate), depending on the initial dose of lamotrigine	200 mg	100 mg	Save the dose of 100 mg / day.
	300 mg	150 mg	Save the dose of 150 mg / day.
	400 mg	200 mg	Save the dose of 200 mg / day.
b) The addition of inducers of glucuronization of lamotrigine in patients not receiving valproate, depending on the initial dose of lamotrigine. This regimen should be used when using phenytoin, carbamazepine, phenobarbital, primidon, or other inducers of lamotrigine glucuronization.	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) Adding other drugs have a significant inducing or inhibitory effect on the glucuronization of lamotrigine	Maintain the target dose achieved during the regimen (200 mg / day, dose range from 100 mg to 400 mg).
Note: in patients taking PEP, the pharmacokinetic interaction of which with lamotrigine is currently unknown,The dosing regimen recommended for lamotrigine in combination with valproate should be used.

The withdrawal of Lamectal® therapy in patients with bipolar affective disorder

During clinical trials, abrupt withdrawal of Lamictal® did not increase the frequency, severity, or change in the nature of adverse reactions compared with placebo.

Thus, patients can cancel the drug Lamiktal® without gradually reducing its dose.

Children and teenagers under 18 years of age

Lamectal® is not indicated for the treatment of bipolar affective disorder in children and adolescents under the age of 18 years. The safety and efficacy of lamotrigine in bipolar affective disorder in patients in this age group were not evaluated. Therefore, recommendations for dosing can not be given.

General recommendations for dosing of Lamictal® in specific patient groups

Women taking hormonal contraceptives

a) Use of Lamectal® by patients already receiving hormonal contraceptives: despite,that oral hormonal contraceptives increase the clearance of lamotrigine, there is no need for special recommendations on the regimen of increasing the dose of Lamictal ® only on the basis of hormonal contraceptives. The dose increase regimen should follow recommended guidelines, depending on whether Lamectal® is added to valproate (lamotrigine glucuronide inhibitors) or lamotrigine glucuronide inducers; or Lamictal® is used in the absence of valproate or inducer of lamotrigine glucuronization (see Table 1 for epilepsy and Table 3 for bipolar affective disorder).

b) The use of hormonal contraceptives by patients who are already receiving maintenance doses of Lamictal® and NOT receiving inducers of lamotrigine glucuronization: in most cases, an increase in the maintenance dose of lamotrigine is required, but not more than 2-fold. When appointing hormonal contraceptives it is recommended to increase the dose of lamotrigine by 50-100 mg / day every week, depending on the clinical picture. Do not exceed these figures if the clinical condition of the patient does not require a further increase in the dose of Lamictal®.

c) Discontinuation of hormonal contraceptive use by patients already receiving maintenance doses of Lamictal® and NOT receiving lamotrigine glucuronide inducers: in most cases, a dose reduction of Lamicthal® is required, but no more than 50%. It is recommended to gradually reduce the daily dose of Lamictal® preparation by 50-100 mg every week (the rate of reduction should not exceed 25% of the daily dose per week) for more than 3 weeks if the clinical state of the patient does not require otherwise.

The use of atazanavir in combination with ritonavir

Despite the fact that, when combined with atazanavir in combination with ritonavir, the concentration of lamotrigine in the plasma decreased, correction of the dosing regimen of Lamictal® with simultaneous use with atazanavir in combination with ritonavir is not required. Increasing the dose of Lamictal® should be based on recommendations based on whether lamotrigine to therapy with valproate (inhibitors of glucuronization lamotrigine) or to therapy with lamotrigine glucuronine inducers, or lamotrigine It is used in the absence of valproate or inductor glucuronization lamotrigine.

In patients already taking maintenance doses of the drug Lamiktal® and not taking inducers of lamotrigine glucuronidation, the application of atazanavir in combination with ritonavir dose of lamotrigine may need to be increased and cases of atazanavir in combination with ritonavir - lower.

Patients of advanced age (over 65 years)

There is no need to correct the dosage regimen in comparison with the recommended regimen. The pharmacokinetics of lamotrigine in this age group does not differ from that of adults under the age of 65 years.

Impaired liver function

The initial, maintenance and increasing doses generally be reduced by approximately 50% and 75% in patients with moderate (stage B of Child-Pugh) and heavy (step C by Child-Pugh) degree human liver, respectively. Increasing and maintenance doses should be adjusted depending on the clinical effect.

Impaired renal function

Patients with renal insufficiency should be cautioned with Lamicthal®.In patients with end-stage renal failure, initial doses of Lamictal® should be calculated according to the dosing regimen for patients taking PEP. In patients with a significant decrease in renal function, a reduction in maintenance doses may be recommended.

Side effects:

Undesirable reactions identified in clinical trials in patients with epilepsy or bipolar affective disorder were divided into separate sections, specific to indications for use. Additional unwanted reactions revealed during post-registration observation but both indications for use are included in the section "Post-registration surveillance". When reviewing the general safety profile of Lamictal®, the information contained in all three sections should be consulted.

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥ 1/10), often (≥ 1/100 and <1/10), infrequently (≥ 1/1 000 and <1/100), rarely (≥ 1/10 000 and <1/1000), rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.

Frequency of occurrence of undesirable reactions

Epilepsy

The following adverse reactions have been identified in clinical trials in patients with epilepsy and in determining the overall safety profile of Lamictal® should be considered in conjunction with adverse reactions identified in clinical trials in patients with bipolar affective disorder and post-marketing use of the drug.

Disturbances from the skin and subcutaneous tissues

Very often: skin rash.

Rarely: Stevens-Johnson syndrome.

Very rarely: toxic epidermal necrolysis.

AT double-blind additional clinical studies in adults skin rash occurred in 10% of patients and less, taking the drug Lamictal®, and in 5% of patients taking placebo. In 2% of patients, skin rash caused the withdrawal of Lamictal®. Rash, usually maculopapular in nature, mainly appears during 8 weeks after initiation of therapy and is carried out after the withdrawal of Lamictal®.

There are reports of rare cases of severe, potentially life-threatening skin rash, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome). Although in most cases, when the drug was withdrawn, the symptoms developed in reverse, some patients had irreversible scarring, and in rare cases, deaths associated with taking the drug were recorded.

The overall risk of developing the rash is closely related to:

- high initial doses of Lamiktal® and exceeding the recommended dose when applied;

- concomitant use of valproate.

There have also been reports of rash development in a syndrome of hypersensitivity associated with various systemic manifestations (see disorders of the immune system **).

Violations of the blood and lymphatic system

Very rarely: hematologic disorders (including neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis), lymphadenopathy.

Hematologic disorders and lymphadenopathy may or may not be associated with hypersensitivity syndrome (see violations by immune systems **).

Immune system disorders

Very rarely: hypersensitivity syndrome ** (including symptoms such as fever, lymphadenopathy, facial edema, blood disorders and liver function, disseminated intravascular coagulation (DVS), multiple organ failure).

** There have also been reports of rash development in a syndrome of hypersensitivity associated with various systemic manifestations, including fever, lymphadenopathy, facial edema and blood disorders and liver function. The syndrome occurs with varying degrees of clinical severity and may in rare cases lead to the development of DIC syndrome and multiple organ failure. It is important to note that early manifestations of hypersensitivity (eg, fever, lymphadenopathy) may be present even in the absence of obvious signs of a rash. If such signs and symptoms develop, the patient should be immediately examined by a doctor, and if no other cause of symptoms is established, Lamictal® should be discontinued.

Disorders of the psyche

Often: aggressiveness, irritability.

Very rarely: tics, hallucinations, confusion.

Disturbances from the nervous system

Very often: headache,

Often: drowsiness, insomnia, dizziness, tremor.

Infrequently: ataxia.

Rarely: nystagmus.

Disturbances on the part of the organ of sight

Infrequently: diplopia, blurred vision.

Disorders from the gastrointestinal tract

Often: nausea, vomiting, diarrhea.

Disturbances from the liver and bile ducts

Very rarely: increased activity "hepatic" enzymes, impaired liver function, hepatic insufficiency. Dysfunction of the liver usually develops in combination with hypersensitivity reactions, but in isolated cases it was noted in the absence of obvious signs of hypersensitivity.

Disturbances from musculoskeletal and connective tissue

Very rarely: a lupus-like syndrome.

General disorders and disorders at the site of administration

Often: fatigue.

Bipolar affective disorder

The following adverse reactions were identified in clinical trials in patients with bipolar affective disorder and in determining the overall safety profile of Lamictal® should be considered in conjunction with adverse reactions,Identified during clinical trials in patients with epilepsy and post-registration follow-up.

Disturbances from the skin and subcutaneous tissue

Very often: skin rash.

Rarely: Stevens-Johnson syndrome.

In evaluating all studies (controlled and uncontrolled) of Lamycal^® In patients with bipolar affective disorder, a skin rash occurred in 12% of all patients receiving Lamictal®, whereas skin rash in controlled clinical trials in patients with bipolar affective disorder occurred in 8% of patients who received the drug Lamycal^®, and y 6% of patients receiving placebo.

Disturbances from the nervous system

Very often: headache.

Often: agitation, drowsiness, dizziness.

Disturbances from musculoskeletal and connective tissue

Often: arthralgia.

General disorders and disorders at the site of administration

Often: pain, back pain.

Post-Business Monitoring

This section includes unwanted reactions, identified during post-registration observation for both indications for use. When determining the general safety profile of Lamictal®, these adverse reactions should be considered in conjunction with undesirable reactions, revealed during clinical trials in patients with epilepsy and bipolar affective disorder.

Disturbances from the skin and subcutaneous tissues

Rarely: alopecia.

Disorders of the psyche

Rarely: nightmares.

Disturbances from the nervous system

Very often: drowsiness, ataxia, headache, dizziness.

Often: nystagmus, tremor, insomnia.

Rarely: aseptic meningitis.

Very rarely: agitation, instability of gait, motor disorders, worsening of symptoms of Parkinson's disease, extrapyramidal disorders, choreoathetosis.

There are reports that the Lamictal® preparation may worsen the symptoms of Parkinson's disease in patients with Parkinson's disease and, in isolated cases, cause extrapyramidal symptoms and choreoathetosis in patients without previous disorders.

Disturbances on the part of the organ of sight

Very often: diplopia, blurred vision,

Rarely: conjunctivitis.

Disorders from the gastrointestinal tract

Very often: nausea, vomiting,

Often: diarrhea.

Only with epilepsy

Disturbances from the nervous system

Very rarely: increased frequency of convulsive seizures.

Overdose:

Symptoms

When receiving doses exceeding 10-20 times the maximum therapeutic, cases with a lethal outcome were recorded. The overdose was manifested by symptoms including nystagmus, ataxia, impaired consciousness, epileptic seizure and to whom. In patients with overdose, the interval is also widened QRS (lengthening the time of intraventricular conduction).

Treatment

Recommended hospitalization and maintenance therapy in accordance with the clinical picture or recommendations of the National Toxicology Center.

Interaction:

UDF-glucuronyltransferase is the main enzyme that metabolizes lamotrigine. There is no evidence of the ability of lamotrigine to cause clinically significant induction or inhibition of microsomal liver enzymes. In this regard, the interaction between lamotrigine and drugs metabolized by cytochrome P450 isoenzymes is unlikely.

Lamotrigine can induce its own metabolism, but this effect is moderately expressed and has no clinically significant effects.

Table 6. Effect of other drugs on the glucuronidation of lamotrigine

Powerful inhibitors of glucuronin glucuronin	Powerful inducers of lamotrigine glucuronin	Drugs that have little effect on glucuronin glucuronin
Valproic acid	Carbamazepine, phenytoin, primidon, phenobarbital, rifampicin, lopinavir / ritonavir, atazanavir / ritonavir, combined ethinyl estradiol / levonorgestrel	Preparations lithium, bupropion, olanzapine, oxcarbazepine, felbamate, gabapentin, levetiracetam, pregabalinum, topiramate, zonisamide, aripiprazole

The effect of other oral contraceptives and hormone replacement therapy has not been studied, although they may have a similar effect on the pharmacokinetic parameters of lamotrigine.

Interactions with a PEP

Valproic acid, which inhibits lamotrigine glucuronin, reduces the rate of its metabolism and lengthens its average half-life in almost 2 times.

Some PEPs (such as phenytoin, carbamazepine, phenobarbital and primidon), which induce microsomal liver enzymes, Accelerate lamotrigine glucuronin and its metabolism. The development of unwanted reactions from the central nervous system, including dizziness, ataxia,diplopia, blurred vision and nausea in patients who started taking carbamazepine on the background of lamotrigine therapy. These symptoms usually occurred after a reduction in the dose of carbamazepine. A similar effect was observed with the use of healthy lamotrigine and oxcarbazepine in healthy volunteers, the result of lower doses was not studied.

With the simultaneous use of lamotrigine in a dose 200 mg and oxcarbazepine in a dose 1200 mg oxcarbazepine, nor lamotrigine do not interfere with each other's metabolism. Combined application of felbamate in a dose 1200 mg 2 once a day and lamotrigine 100 mg 2 once a day did not lead to clinically significant changes in the pharmacokinetics of lamotrigine.

With the simultaneous use of lamotrigine and gabapentin, the apparent clearance of lamotrigine did not change.

Possible drug interactions between levetiracetam and lamotrigine were investigated in assessing the serum concentrations of both drugs during placebo-controlled clinical trials. These data show that lamotrigine and levetiracetam do not affect the pharmacokinetics of each other.

There was no effect of pregabalin in the dose 200 mg 3 times a day at equilibrium concentrations of lamotrigine, thus pregabalinum and lamotrigine do not interact pharmacokinetically with each other.

The use of topiramate did not lead to a change in the lamotrigine concentration in the plasma. However, the use of lamotrigine led to an increase in the concentration of topiramate by 15%.

The administration of zonisamide (in a dose of 200-400 mg per day) during the clinical program concomitantly with lamotrigine (at a dose of 150-500 mg per day) did not lead to a change in the pharmacokinetic parameters of lamotrigine.

Studies have shown that lamotrigine does not affect the concentration of other PEP in the blood plasma. Research results in vitro showed that lamotrigine does not displace other PEPs from the connection with plasma proteins.

Interactions when combined with other psychotropic drugs

Lamotrigine at a dose of 100 mg / day does not cause a violation of the pharmacokinetics of anhydrous lithium gluconate 2 g 2 once a day for 6 days) with their simultaneous application.

Multiple admission of bupropion inside does not have a statistically significant effect on the pharmacokinetics of a single dose of lamotrigine and causes a slight increase AUC (area under the pharmacokinetic curve "concentration-time") lamotrigine glucuronide.

Olanzapine in a dose of 15 mg reduces AUC and C_m_Ohlamotrigine an average of 24% and 20%, respectively, which is clinically insignificant. Lamotrigine in a dose of 200 mg does not change the kinetics of olanzapine.

Multiple administration of lamotrigine at a dose of 400 mg per day did not have a clinically significant effect on the pharmacokinetics of risperidone after taking a single dose 2 mg by healthy volunteers.

At the same time, drowsiness was noted:

- in 12 out of 14 patients with simultaneous application of lamotrigine and risperidone;

- the 1 of 20 patients taking risperidone only;

- no patient with a single lamotrigine.

In a study in 18 adult patients with bipolar affective disorder, who received the prescribed scheme lamotrigine in a dose of 100 mg / day or more, doses of aripiprazole increased from 10 mg / day to a final value of 30 mg / day during the 7-day period and then continued treatment with taking the drug 1 time per day for another 7 days. There was an average decrease of about 10% C_max and lamotrigine AUC. Probably, such influence will not have clinical consequences.

The inhibition of lamotrigine by amitriptyline, bupropion, clonazepam, fluoxetine, haloperidol or lorazepam has a minimal effect on the formation of the primary metabolite lamotrigine 2-N-glucuronide.

The study of the metabolism of bupuralol with microsomal liver enzymes isolated in humans allows us to conclude that lamotrigine does not reduce the clearance of drugs metabolized predominantly by the isoenzymes CYP2D6. Research results in vitro also suggest that clozapine, phenelzine, risperidone, sertraline or trazodone hardly can influence the clearance of lamotrigine.

Interactions with hormonal contraceptives

Effect of hormonal contraceptives on the pharmacokinetics of lamotrigine

The intake of combined oral contraceptives containing 30 μg of ethinylestradiol and 150 μg of levonorgestrel causes approximately a twofold increase in lamotrigine clearance (after oral administration), which leads to a decrease AUC and C_m_Ohlamotrigine on average by 52% and 39%, respectively. Within a week, free from taking the active drug, an increase in the plasma concentration of lamotrigine is observed. the concentration of lamotrigine. measured at the end of this week before the next dose, on average in 2 times higher than during the period of active therapy.

The influence of lamotrigine on the pharmacokinetics of hormonal contraceptives

In the period of equilibrium concentrations lamotrigine in a dose of 300 mg does not affect the pharmacokinetics of ethinyl estradiol, a component of the combined oral contraceptive. There was a slight increase in the clearance of the second component of the oral contraceptive - levonorgestrel, which led to a decrease in AUC and C_m_Oh levonorgestrel by 19% and 12%, respectively. The measurement of serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol during this study revealed a slight decrease in suppression of ovarian hormonal activity in some women, although measurement of plasma progesterone concentration in none of the 16 women showed hormonal evidence of ovulation. The effect of a moderate increase in the clearance of levonorgestrel and changes in plasma concentrations of FSH and LH on ovarian ovarian activity has not been established. The effect of other doses of lamotrigine (except for 300 mg / day) has not been studied, and studies involving other hormonal drugs have not been conducted.

Interactions with other drugs

Rifampicin increases clearance lamotrigine and reduces its half-life by induction microsomal liver enzymes responsible for glucuronidation. Patients receiving rifampicin as a concomitant therapy, the lamotrigine prescribing regimen should be consistent with the regimen recommended for the simultaneous use of lamotrigine and drugs. inducing glucuronation.

When using lopinavir and / or ritonavir, a decrease of about 50% of lamotrigine plasma concentration was observed, possibly due to the induction of glucuronidation. In patients who simultaneously take lopinavir and / or ritonavir, the dosing regimen should be recommended lamotrigine with concomitant glucuronation inducers.

In a study in healthy volunteers, the administration of atazanavir and / or ritonavir (300 mg / 100 mg) reduced the values AUC and C_m_Oh lamotrigine (in a single dose of 100 mg) by about 32% and 6%, respectively.

Research results in vitro showed that lamotrigine is an inhibitor of cationic carriers of organic substrates in potentially clinically significant concentrations.These data show that lamotrigine is a more potent inhibitor (half inhibitory concentration (IC₅₀) varies from 53.8 nmol / l to 186 nmol / l, respectively) than cimetidine.

Influence at laboratory indicators

Lamotrigine is said to affect the conduct of some rapid urine analysis methods in order to detect prohibited drugs that can lead to false positive results, especially when phencyclidine (dissociative anesthetic) is detected. To confirm a positive result, a more specific alternative chemical method should be used.

Special instructions:

Skin rash

There are reports of side effects from the skin that may occur within the first 8 weeks after lamotrigine therapy begins. Most rashes are mild and pass alone, but there are reports of rashes that require hospitalization of the patient and stopping lamotrigine. They included potentially life-threatening skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome).

Severe skin reactions in adult patients using lamotrigine in accordance with generally accepted recommendations, develop with a frequency of approximately 1 in 500 patients with epilepsy. Approximately half of these cases registered Stevens-Johnson syndrome (1 per 1000 patients).

In patients with bipolar disorders, the incidence of severe skin rashes according tolInitial studies are approximately 1 per 1000 patients.

Children have a higher risk of developing severe skin rashes than adults. According to available data, the frequency of skin rashes that required hospitalization in children was from 1 to 300 to 1 per 100 sick children.

In children, the initial manifestations of the rash can be mistaken for infection, so doctors should take into account the possibility of children reacting to a drug that manifests itself in the development of rash and fever in the first 8 weeks of therapy.

In addition, the overall risk of rash is largely related to:

- a high initial dose of lamotrigine and an excess of the recommended rate of increase in lamotrigine doses;

- simultaneous application with valproate.

Caution is necessary when appointing patients,who had a history of allergic reactions or a rash in response to taking other antiepileptic drugs, since the incidence of rash (not classified as severe) in patients with such anamnesis was three times more common with lamotrigine than in patients with a history of non-history. If a rash is found, all patients (adults and children) should be examined by a doctor immediately. The admission of lamotrigine should be stopped immediately, except when it is clear that the development of the rash is not associated with taking the drug. It is not recommended to resume lamotrigine in cases where its previous appointment was canceled due to the development of a skin reaction, unless the expected therapeutic effect of the drug does not exceed the risk of side effects. It has been reported that the rash may be part of a hypersensitivity syndrome associated with various systemic manifestations, including fever, lymphadenopathy, facial puffiness, and blood and liver abnormalities. The severity of the manifestation of the syndrome varies widely and in rare cases can lead to the development of the syndrome of DVS and multi-organ failure.It should be noted that early manifestations of the hypersensitivity syndrome (ie fever, lymphadenopathy) can be observed even if there are no obvious manifestations of the rash. When developing such symptoms, the patient should immediately consult a doctor and, if no other cause of symptoms is established, lamotrigine should be canceled.

Aseptic meningitis

The development of aseptic meningitis is reversible when the drug is withdrawn in most cases and is resumed in a number of cases with a re-appointment. Repeated administration leads to a rapid return of symptoms, which are often more severe. Lamotrigine Do not re-appoint to patients whose discontinuation of treatment has been associated with aseptic meningitis.

Hormonal contraceptives

Effect of hormonal contraceptives on the pharmacokinetics of lamotrigine

It was shown that the combination drug ethinylestradiol / levonorgestrel (30 μg / 150 μg) approximately 2 times increases the clearance of lamotrigine, which leads to a decrease in lamotrigine in the plasma. With his appointment to achieve the maximum therapeutic effect, it is necessary to increase maintenance doses of lamotrigine, but not more than 2 times.Women who no longer take inductors of lamotrigine glucuronin and who take hormonal contraceptives whose treatment regimen includes a week of taking an inactive drug (or a weekly break in taking a contraceptive), a gradual transient increase in lamotrigine concentration will be observed during this period of time. The increase in concentration will be greater if the next increase in the lamotrigine dose is carried out immediately before or during the inactive drug intake. Medical workers should master the clinical skills of conducting women who, when lamotrigine is being treated, begin or stop taking hormonal contraceptives, as this may require a correction for the lamotrigine dose.

Other oral contraceptives and hormone replacement therapy have not been studied, though they may similarly affect the pharmacokinetic parameters of lamotrigine.

The influence of lamotrigine on the pharmacokinetics of hormonal contraceptives

Joint appointment of lamotrigine and combined hormonal contraceptive (containing ethinyl estradiol and levonorgestrel) leads to a moderate increase in the clearance of levonorgestrel and changes in the concentration of FSH and LH. The effect of these changes on ovulatory activity of the ovaries is unknown. However, it can not be ruled out that in some patients receiving lamotrigine and hormonal contraceptives, these changes can cause a decrease in the effectiveness of contraceptives. Such patients should be instructed about the need to immediately inform the doctor about changes in the nature of the menstrual cycle, i.e. about sudden bleeding.

Dihydrofolate reductase

Lamotrigine is a weak inhibitor of dihydrofolate reductase, so there is a possibility that the drug will interfere with the metabolism of folate with its long-term use. However, it was shown that lamotrigine did not cause significant changes in the concentration of hemoglobin, the average volume of erythrocytes, the concentration of folate, serum erythrocytes with a duration of administration of the drug to 1 year and did not reduce the concentration of folate in erythrocytes when lamotrigine is prescribed for up to 5 years.

Effect of lamotrigine on the cationic carrier of organic substrates

Lamotrigine is an inhibitor of tubular secretion by affecting the cationic protein carrier. This can lead to an increase in the plasma concentrations of certain drugs that are excreted mainly through the kidneys. The joint administration of lamotrigine and substrates with a narrow therapeutic range, such as dofetilide, is not recommended.

Renal insufficiency

A single appointment of lamotrigine to patients with severe renal insufficiency did not reveal significant changes in lamotrigine concentration. However, the accumulation of a glucuronide metabolite is very likely, so caution should be exercised in the treatment of patients with renal insufficiency.

Patients taking other drugs containing lamotrigine

You can not assign lamotrigine (in usual tablets or in soluble / chewable tablets) to patients already receiving any other formulations containing lamotrigine, without consulting a doctor.

Epilepsy

The abrupt withdrawal of lamotrigine, as well as other PEPs, can provoke the development of seizures. If abrupt discontinuation of therapy is not a safety requirement (for example, with the appearance of a rash), the dose of lamotrigine should be reduced gradually over 2 weeks.There are reports in the literature that severe convulsive seizures, including epileptic status, can lead to the development of rhabdomyolysis, polyorganism disorders and disseminated intravascular coagulation, sometimes with a fatal outcome. Similar cases were observed in the treatment of patients with lamotrigine.

Suicidal risk

Symptoms of depression and / or bipolar disorder may be noted in patients with epilepsy. Patients with epilepsy and concomitant bipolar disorder are at high risk of suicide.

At 25-50% of patients with bipolar disorder there was at least one suicidal attempt; in such patients, there may be a worsening of suicidal thoughts and suicidal behavior (suicidality) when taking medications for the treatment of bipolar disorder, including lamotrigine, as well as without treatment. Suicidal thoughts and suicidal behavior were noted in patients taking PEP for several indications, including epilepsy and bipolar disorder. Meta-analysis of randomized placebo-controlled studies of PEP (including lamotrigine) showed a slight increase in suicidal risk.The mechanism of this action is unknown, and the available data do not exclude the possibility of increasing the risk of suicide with lamotrigine. Therefore, patients should be carefully monitored for suicidal thoughts and behavior. Patients (and caregivers) should be informed of the need for medical advice in the event of such symptoms.

Bipolar affective disorder

Children and teenagers under 18 years of age

Treatment with antidepressants is associated with an increased risk of suicidal thoughts and behavior in children and adolescents with major depression and other mental disorders.

Clinical deterioration in patients with bipolar affective disorder

In patients with bipolar disorder receiving lamotrigine, you should carefully monitor the symptoms of clinical deterioration (including the emergence of new symptoms) and suicidal, especially at the beginning of the course of treatment and at the time of dose change. Patients who have a history of suicidal thoughts or suicidal behavior, young patients and patients,who have been found to have a largely suicidal ideation before starting therapy, are in a high-risk group for suicidal thoughts or suicidal behavior, such patients should be closely monitored during treatment.

Patients (and caregivers) should be warned about the need to monitor any worsening of the patient's condition (including the appearance of new symptoms) and / or the appearance of suicidal thoughts / behaviors or thoughts of harm to themselves and should seek medical help immediately if these symptoms are present.

In doing so, the situation should be evaluated and appropriate changes made to the treatment regimen, including the possibility of discontinuing the drug in patients who have a clinical impairment (including the appearance of new symptoms) and / or suicidal thoughts / behavior, especially if these symptoms are severe, with sudden onset and previously not noted.

Effect on the ability to drive transp. cf. and fur:

Two studies conducted with the participation of healthy volunteers showed that the effect of lamotrigine on accurate visual-motor coordination, eye movements and subjective sedation did not differ from the effectnorI'm a placebo.There are reports of side effects of lamotrigine of a neurological nature, such as dizziness and diplopia. Therefore, before getting behind the wheel of the car or controlling the mechanisms, patients should assess the effect of lamotrigine on their condition.

Since the effect of all antiepileptic drugs has individual variability, patients should consult their physician about the possibility of driving a car.

Form release / dosage:

Tablets, 25 mg, 50 mg and 100 mg.

Packaging:

For 10 tablets in a blister of PVC / aluminum foil.

For 3 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014213 / 01

Date of registration:25.06.2010 / 29.03.2012

Expiration Date:Unlimited

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GLAXO OPERATIONS UK, Limited United Kingdom

GlaxoSmithKline Pharmaceuticals, S.A. Poland

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp29.11.2016

Illustrated instructions

Instructions

Lamictal® (Lamictal®)