Lamotrigine (Lamictal, Lamitor, Lamolep, Sezar)

Lamictal®

For oral administration.

Lamictal® Chewable/Dissoluble Tablets may be chewed, dissolved in a small volume of water (at least enough to cover the entire tablet), or swallowed whole with a small amount of water.

If the calculated dose of lamotrigine (for example, when used in children for the treatment of epilepsy or in patients with impaired liver function) is not equal to whole tablets, then the patient should be prescribed a dose that corresponds to fewer whole tablets.

Resumption of drug use

If Lamictal is restarted, the physician should evaluate the need to increase the maintenance dose in patients who have stopped taking lamotrigine for any reason, as high initial doses and exceeding the recommended dose are associated with a risk of severe rash. The more time has passed since the last dose of the drug, the more caution you should increase the dose to maintenance. If the time after discontinuation exceeds 5 half-lives, the dose of lamotrigine should be increased to a maintenance dose according to an appropriate dosage regimen.

It is recommended not to restart Lamictal therapy in patients in whom lamotrigine treatment was discontinued due to rash, unless the potential benefit clearly outweighs the risk.

Epilepsy

Dose escalation and maintenance doses recommended for adults and adolescents over 12 years of age (Table 2) and children and adolescents 2 to 12 years of age (Table 3) are listed below. Due to the risk of developing a rash, the initial dose of the drug and the subsequent dose escalation regimen should not be exceeded.

When discontinuing concomitant AEDs or adding AEDs or other drugs while taking lamotrigine, be aware that this may affect the pharmacokinetics of lamotrigine.

Table 2. Recommended dosage regimen for the treatment of epilepsy in adults and adolescents (over 12 years of age)

Table 3. Recommended dosage regimen for the treatment of epilepsy in children (from 2 to 12 years inclusive)

To ensure that the therapeutic dose is maintained, it is necessary to monitor the child’s body weight and adjust the dose of the drug if it changes. Patients aged 2 to 6 years are likely to require a maintenance dose at the upper end of the recommended range. After achieving control of epilepsy during combination therapy, concomitant antiepileptic drugs (AEDs) can be discontinued and Lamictal® continued as monotherapy.

Children under 2 years old

Data on the safety and effectiveness of lamotrigine as a combination therapy for partial-onset seizures in children aged 1 month to 2 years are limited. There are no data on use in children under 1 month of age. Therefore, Lamictal® is not recommended for use in children under 2 years of age. However, in case of clinical need, a decision may be made to prescribe the drug.

Bipolar affective disorder

Dose escalation and maintenance doses recommended for adults over 18 years of age are listed in the tables below. The bridge dosing regimen involves increasing the lamotrigine dose over 6 weeks to a maintenance stabilization dose (Table 4), after which other psychotropic medications and/or AEDs may be discontinued as clinically indicated (Table 5). Dose adjustments following the addition of other psychotropic medications and/or AEDs are also listed below (Table 6). Due to the risk of rash, the initial dose of the drug and the subsequent dose escalation regimen should not be exceeded.

Table 4. Recommended dose escalation regimen to achieve a maintenance daily stabilization dose for the treatment of bipolar affective disorder in adults aged 18 years or older

*Target stabilization dose varies depending on clinical response.

Once the target daily maintenance stabilization dose has been achieved, other psychotropic medications may be discontinued as indicated in the dosing schedule below.

Table 5. Maintenance stabilizing total daily dose in adults 18 years of age or older for the treatment of bipolar disorder after discontinuation of concomitant medications

* if necessary, the dose can be increased to 400 mg/day.

There is no clinical experience with adjusting daily doses of Lamictal® after adding other drugs. however, based on drug interaction studies, the following recommendations can be made (Table 6).

Table 6. Daily dosage adjustments for the treatment of bipolar affective disorder in adults aged 18 years and older after the addition of other drugs

discontinuation of the drug Lamictal® in patients with bipolar affective disorder

During clinical trials, abrupt discontinuation of lamotrigine did not cause an increase in the frequency, severity, or nature of adverse reactions compared to placebo. Thus, patients can be discontinued from the drug Lamictal without gradually reducing its dose.

children and adolescents under 18 years of age

Lamictal® is not recommended for the treatment of bipolar disorder in children and adolescents under 18 years of age because randomized drug withdrawal trials failed to demonstrate significant efficacy and an increase in reports of suicidal behavior was observed.

general recommendations for dosing of Lamictal® in special groups of patients

women taking hormonal contraceptives

When using a combination of ethinyl estradiol/levonorgestrel (30 mcg/150 mcg), the clearance of lamotrigine approximately doubles, which leads to a decrease in lamotrigine levels. After dose titration, higher maintenance doses of lamotrigine (up to a twofold increase) may be required to achieve maximum therapeutic response. During the week without contraceptive use, a twofold increase in lamotrigine levels was observed. Dose-related adverse reactions cannot be ruled out. therefore, contraception that does not include a contraceptive-free week (eg, continuous hormonal contraceptives or non-hormonal methods) should be considered as first-line therapy.

Initiation of hormonal contraceptives in patients already receiving maintenance doses of lamotrigine and not receiving inducers of lamotrigine glucuronidation

in most cases, an increase in the maintenance dose of lamotrigine is required, but not more than 2 times. From the moment the use of hormonal contraceptives is started, it is recommended to increase the dose of lamotrigine by 50-100 mg every week, depending on the individual clinical response. It is not recommended to exceed these doses unless the patient's clinical condition requires a further increase in the dose of Lamictal®.

To confirm maintenance of baseline lamotrigine levels, consider measuring serum lamotrigine levels before and after initiation of hormonal contraceptives. If necessary, dose adjustment should be made. For women taking hormonal contraceptives that include one week without the use of the active drug (a “contraceptive-free week”), serum lamotrigine levels should be monitored during week 3 of the active drug, that is, days 15 to 21 of the pill cycle. . therefore, contraception that does not include a contraceptive-free week (eg, continuous hormonal contraceptives or non-hormonal methods) should be considered as first-line therapy.

discontinuation of hormonal contraceptives in patients already receiving maintenance doses of lamotrigine and not receiving inducers of lamotrigine glucuronidation

in most cases, a reduction in the maintenance dose of lamotrigine is required, but not more than 50%. It is recommended to gradually reduce the daily dose of lamotrigine by 50-100 mg/day every week (the rate of reduction should not exceed 25% of the daily dose per week) over 3 weeks, unless the patient's clinical condition requires a different approach.

To ensure that baseline lamotrigine levels are maintained, consider measuring serum lamotrigine levels before and after discontinuation of hormonal contraceptives. For women wishing to stop taking hormonal contraceptives that include one week without the use of the active drug (a “contraceptive-free week”), serum lamotrigine levels should be monitored during week 3 of the active drug, that is, days 15 to 21 of the cycle. taking pills. Blood samples to assess lamotrigine levels after permanently stopping a contraceptive should not be collected during the first week after stopping the pills.

Initiation of lamotrigine in patients already using hormonal contraceptives

Dose increases should be carried out according to the usual recommendations for use presented in the tables.

Initiation and discontinuation of hormonal contraceptives in patients already taking maintenance doses of lamotrigine and taking inducers of lamotrigine glucuronidation

No adjustment of the recommended lamotrigine maintenance dose may be necessary.

use with atazanavir/ritonavir combination

If lamotrigine is added to existing atazanavir/ritonavir therapy, there is no need to adjust the recommended lamotrigine dose increase regimen. In patients already taking maintenance doses of lamotrigine and not using glucuronidation inducers, it may be necessary to increase the dose of lamotrigine when adding the atazanavir/ritonavir combination or to reduce the dose of lamotrigine if the atazanavir/ritonavir combination is discontinued. To determine the need for lamotrigine dose adjustment, lamotrigine plasma levels should be monitored before and for 2 weeks after starting or stopping the use of the atazanavir/ritonavir combination.

use together with lopinavir/ritonavir

If lamotrigine is added to existing lopinavir/ritonavir therapy, there is no need to adjust the recommended lamotrigine dose increase regimen. In patients already taking maintenance doses of lamotrigine and not using glucuronidation inducers, it may be necessary to increase the dose of lamotrigine when adding lopinavir/ritonavir or to reduce the dose of lamotrigine if discontinuing lopinavir/ritonavir. To determine the need for dose adjustment of lamotrigine, lamotrigine plasma levels should be monitored before and for 2 weeks after starting or stopping the use of lopinavir/ritonavir.

elderly patients (over 65 years old)

no adjustment of the dosage regimen is required compared to the recommended regimen. The pharmacokinetics of lamotrigine in this age group are not significantly different from those in older adults.

patients with impaired renal function

Lamictal® should be administered with caution to patients with renal failure. In patients with end-stage renal failure, initial doses of Lamictal* should be calculated depending on the concomitant medications the patient is taking. in patients with significant renal impairment, reduced maintenance doses may be effective.

patients with liver dysfunction

Initial, escalating and maintenance doses should generally be reduced by approximately 50% in patients with moderate (Child Pugh B) and 75% severe (Child Pugh C) liver dysfunction. escalation and maintenance doses should be adjusted based on clinical response.

Lamictal, 30 pcs., 100 mg, tablets

Inside.

Epilepsy:
adults and children over 12 years of age who have not received sodium valproate,
an initial dose of 25 mg once a day for 2 weeks, then 50 mg once a day for 2 weeks, then the dose is increased by 50-100 mg every 1 week. –2 weeks until the optimal therapeutic effect is achieved. Maintenance dose: 100–200 mg/day in 1 or 2 divided doses (some patients require a dose of 500 mg/day).

Dose escalation schedule for lamotrigine monotherapy in adults and children over 12 years of age

For patients receiving sodium valproate,

initial dose: 25 mg every other day for 2 weeks, then 25 mg daily for the next 2 weeks, after which the dose is increased by a maximum of 25–50 mg/day every 1–2 weeks until the optimal therapeutic effect is achieved. Maintenance dose: 100–200 mg/day in 1 or 2 doses.

Patients taking antiepileptic drugs that induce liver enzymes in combination with or without other antiepileptic drugs (except sodium valproate),

initial dose: 50 mg once a day for 2 weeks, then 100 mg/day in 2 doses for 2 weeks. Then the dose is increased by a maximum of 100 mg every 1–2 weeks until the optimal therapeutic effect is achieved. The maintenance dose to achieve the optimal therapeutic effect is 200–400 mg/day in 2 divided doses. Some patients may require a dose of 700 mg/day to achieve the desired effect.

Dose escalation scheme for combination therapy in adults and children over 12 years of age

Children 2 to 12 years of age receiving sodium valproate with or without other antiepileptic drugs

initial dose - 0.15 mg/kg 1 time per day for 2 weeks; then - 0.3 mg/kg 1 time per day for 2 weeks. Then the dose is increased by 0.3 mg/kg every 1–2 weeks until the optimal therapeutic effect is achieved. Maintenance dose: 1–5 mg/kg/day in 1 or 2 doses. The maximum daily dose is 200 mg.

For patients taking hepatic enzyme-inducing antiepileptic drugs, with or without other antiepileptic drugs (except sodium valproate),

initial dose - 0.6 mg/kg/day in 2 divided doses for 2 weeks, subsequently - 1.2 mg/kg/day in 2 divided doses for 2 weeks. Then the dose is increased by a maximum of 1.2 mg/kg every 1–2 weeks until the optimal therapeutic effect is achieved. The average maintenance dose to achieve the optimal therapeutic effect is 5–15 mg/kg/day in 2 divided doses. The maximum daily dose is 400 mg. To achieve optimal effect in children, it is necessary to systematically monitor body weight in order to adjust doses in accordance with changes in the child's body weight.

Scheme of increasing doses for combination therapy in children from 2 to 12 years

Bipolar disorders (to prevent the development of a depressive episode). Orally, chewing, dissolving in a small amount of water or swallowing whole with water.

Dose escalation regimen to achieve a maintenance daily stabilizing dose in adults (over 18 years of age) with bipolar disorder

*Stabilization dose varies depending on clinical response

Adults over 18 years of age taking Lamictal in combination with antiepileptic drugs, liver enzyme inhibitors (including sodium valproate),

25 mg every other day for 2 weeks, then 25 mg daily for 2 weeks, then 50 mg/day in 1 or 2 doses for 1 week; stabilizing dose - 100 mg/day in 1 or 2 doses (varies depending on the clinical effect). The maximum dose is 200 mg/day.

Therapy with Lamictal in combination with antiepileptic drugs that induce liver enzymes (carbamazepine, phenobarbital), without sodium valproate,

initial dose: 50 mg once a day for 2 weeks, then 100 mg/day in 2 divided doses for 2 weeks. The dose is increased by 5 weeks to 200 mg/day in 2 doses and to 300 mg/day by 6 weeks. To achieve the optimal therapeutic effect - 400 mg/day in 2 doses, starting from 7 weeks.

Therapy with Lamictal and drugs with an unknown nature of interaction (lithium drugs, bupropion). Monotherapy with Lamictal:

initial dose: 25 mg/day for 2 weeks, then 50 mg/day in 1 or 2 doses for 2 weeks. The dose should be increased to 100 mg/day for 5 weeks. To achieve an optimal therapeutic effect, a dose of 200 mg/day is required in 1 or 2 doses.

Once the daily maintenance stabilizing dose is reached, other psychotropic drugs can be discontinued.

Daily dose of Lamictal required to stabilize mood in bipolar disorders after discontinuation of concomitant psychotropic or antiepileptic drugs

Therapy with Lamictal after discontinuation of antiepileptic drugs, liver enzyme inhibitors (including sodium valproate):

after discontinuation of sodium valproate, the stabilizing dose is doubled, not exceeding 100 mg/week. For example, a stabilizing dose of 100 mg/day is increased in the first week to 200 mg/day, in the second, third week and then the dose of 200 mg/day is maintained in 2 doses. If necessary, the dose can be increased to 400 mg/day.

Therapy with Lamictal after discontinuation of antiepileptic drugs that induce liver enzymes (carbamazepine), depending on the initial maintenance dose:

The dose of Lamictal is gradually reduced over 3 weeks.

Therapy with Lamictal after withdrawal of psychotropic drugs or other antiepileptic drugs, the nature of the interaction of which with lamotrigine is unknown (lithium drugs, bupropion):

the same maintenance dose is maintained.

Lamotrigine dosage regimen for bipolar disorders after adding other drugs to therapy

Addition of antiepileptic drugs, liver enzyme inhibitors (sodium valproate), depending on the initial dose of lamotrigine:

with a stabilizing dose of 200 mg/day, in the first week - reduce it to 100 mg/day, in the second, third week and beyond - maintain 100 mg/day. At a dose of 300 mg/day, in the first week, reduce to 150 mg/day and then keep unchanged; at a dose of 400 mg/day, in the first week, reduce to 200 mg/day and then keep unchanged.

Addition of antiepileptic drugs that induce liver enzymes (carbamazepine) in patients not receiving sodium valproate, depending on the initial dose of lamotrigine:

at a dose of 200 mg/day, in the first week keep it unchanged, in the second - increase to 300 mg/day, in the third and further - increase to 400 mg/day.

At a dose of 150 mg/day in the first week, keep it unchanged, in the second - increase to 225 mg/day, in the third and further - increase to 300 mg/day. At a dose of 100 mg/day, keep it unchanged in the first week, increase to 150 mg/day in the second, increase to 200 mg/day in the third and further.

Addition of other psychotropic or antiepileptic drugs, the nature of the interaction of which with lamotrigine is unknown:

maintain a maintenance dose of 200 mg/day in 2 divided doses (from 100 to 400 mg).

In patients with hepatic impairment, initial, escalating, and maintenance doses should be reduced by ~50% and 75% in patients with moderate (stage B) and severe (stage C) hepatic impairment, respectively. In the future, they should be adjusted depending on the clinical effect. If renal function is impaired, a reduction in the maintenance dose is recommended. Patients over 65 years of age do not require changes to the dosage regimen. There are no dosage recommendations for children under 18 years of age.

Lamictal®

Epilepsy

Adults and children over 12 years old

For monotherapy

The initial dose of Lamictal is 25 mg 1 time / day for the first 2 weeks, followed by an increase in dose to 50 mg 1 time / day over the next 2 weeks. The dose should then be increased by 50-100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose to maintain the optimal therapeutic effect is 100-200 mg/day in 1-2 doses. Some patients require Lamictal at a dose of 500 mg/day to achieve a therapeutic effect.

As part of combination therapy when using Lamictal together with valproic acid drugs in combination with other antiepileptic drugs (AEDs) or without them

The initial dose of Lamictal is 25 mg every other day for the first 2 weeks; subsequently – 25 mg 1 time/day for the next 2 weeks. Then the dose should be increased by a maximum of 25-50 mg/day every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose to maintain the optimal therapeutic effect is 100-200 mg/day in 1-2 doses.

As part of combination therapy with concomitant therapy with AEDs or other drugs that induce glucuronidation of lamotrigine (phenytoin, carbamazepine, phenobarbital and primidone), in combination or without other AEDs (except for valproic acid drugs)

The initial dose of Lamictal is 50 mg 1 time / day for the first 2 weeks, then for the next 2 weeks - 100 mg / day in 2 doses. Then the dose is increased by 100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 200-400 mg/day in 2 divided doses. Some patients may require a dose of 700 mg/day to achieve a therapeutic effect.

As part of combination therapy with oxcarbazepine, with or without any other inducers or inhibitors of lamotrigine glucuronidation

The initial dose of Lamictal is 25 mg 1 time / day for the first 2 weeks, then 50 mg / day in 1 dose for the next 2 weeks. Then the dose is increased by a maximum of 50-100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 100-200 mg per day in 1 or 2 doses.

Due to the risk of developing a rash, the initial dose of the drug and the recommended dose escalation regimen should not be exceeded.

Table 1. Recommended dosage regimen for the treatment of epilepsy in adults and children over 12 years of age.

Children aged 2 to 12 years

It should be noted that accurate initial therapy with Lamictal in 5 mg tablets according to the proposed dosage regimen is impossible if the child’s body weight is less than 17 kg. Children ages 2 to 6 years are likely to require the highest maintenance doses.

Initial dose of Lamictal for monotherapy of typical absence seizures

is 0.3 mg/kg body weight/day in 1 or 2 doses during the first 2 weeks, followed by increasing the dose to 0.6 mg/kg/day in 1 or 2 doses over the next 2 weeks. The dose should then be increased by a maximum of 0.6 mg/kg every 1-2 weeks until the optimal therapeutic effect is achieved. The usual maintenance dose for optimal therapeutic effect is 1 to 10 mg/kg/day in 1 or 2 divided doses, although some patients with typical absence seizures require higher doses to achieve therapeutic effect.

As part of combination therapy when using Lamictal with valproic acid drugs in combination with or without other AEDs

The initial dose of Lamictal is 0.15 mg/kg body weight 1 time/day for the first 2 weeks, then 0.3 mg/kg 1 time/day for the next 2 weeks. The dose should then be increased by 0.3 mg/kg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 1-5 mg/kg/day in 1-2 doses. The maximum daily dose is 200 mg.

As part of combination therapy with concomitant therapy with AEDs or other drugs that induce glucuronidation of lamotrigine (phenytoin, carbamazepine, phenobarbital and primidone), in combination with or without other AEDs (except for valproic acid drugs)

The initial dose of Lamictal is 0.6 mg/kg/day in 2 divided doses during the first 2 weeks, then 1.2 mg/kg/day in 2 divided doses over the next 2 weeks. Then the dose should be increased by a maximum of 1.2 mg/kg/day every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose at which the maximum therapeutic effect is achieved is 5-15 mg/kg/day in 2 divided doses. The maximum daily dose is 400 mg.

As part of combination therapy with oxcarbazepine without any other inducers or inhibitors of lamotrigine glucuronidation

The initial dose of Lamictal is 0.3 mg/kg body weight 1 or 2 times/day for the first 2 weeks, then 0.6 mg/kg/day in 1 or 2 doses over the next 2 weeks. Then the dose is increased by a maximum of 0.6 mg/kg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 1-10 mg/kg/day in 1 or 2 divided doses. The maximum dose is 200 mg/day.

To ensure that the therapeutic dose is maintained, it is necessary to monitor the child's body weight and adjust the drug dose as it changes.

Due to the risk of developing a rash, the initial dose of the drug and the recommended dose escalation regimen should not be exceeded.

Table 2. Recommended dosage regimen for the treatment of children with epilepsy aged 2 to 12 years (total daily dose in mg/kg body weight).

There is insufficient information on the use of Lamictal in children under 2 years of age

.

When discontinuing concomitant antiepileptic drugs to switch to Lamictal monotherapy or when prescribing other drugs or AEDs while taking Lamictal, it is necessary to take into account that this may affect the pharmacokinetics of lamotrigine.

Bipolar disorders

Adult patients over 18 years of age

Due to the risk of developing a rash, the initial dose of the drug and the subsequent dose escalation regimen should not be exceeded.

It is necessary to follow a transitional dosing regimen, which includes increasing the dose of lamotrigine over 6 weeks to a maintenance stabilizing dose (Table 3), after which, if indicated, other psychotropic and/or antiepileptic drugs can be discontinued (Table 4).

Table 3. Recommended dosage escalation schedule to achieve a maintenance daily stabilization dose for adults (over 18 years of age) with bipolar disorders.

The maintenance stabilizing dose varies depending on the clinical effect.

As part of combination therapy with the combined use of Lamictal and other AEDs that inhibit liver enzymes (for example, with valproic acid preparations),

During the first 2 weeks, Lamictal is prescribed at a dose of 25 mg every other day, then 25 mg 1 time / day for the next 2 weeks, at week 5 the dose should be increased to 50 mg / day in 1-2 doses. The stabilizing dose at week 6 is 100 mg/day in 1-2 doses; however, it may be increased to a maximum daily dose of 200 mg depending on clinical response.

As part of combination therapy with the combined use of Lamictal and other AEDs that induce liver enzymes (for example, carbamazepine, phenobarbital), in patients not receiving valproic acid drugs,

during the first 2 weeks, Lamictal is prescribed at a dose of 50 mg 1 time / day, at 3-4 weeks - 100 mg / day in 2 doses, at week 5 - 200 mg / day in 2 doses. At week 6, the dose can be increased to 300 mg/day, however, the stabilizing dose to achieve the optimal therapeutic effect is 400 mg/day in 2 doses, and is prescribed starting from week 7.

With monotherapy

Lamictal or as
part of combination therapy when using Lamictal together with lithium drugs, bupropion, olanzapine, oxcarbazepine, without the use of inducers or inhibitors of lamotrigine glucuronidation
during the first 2 weeks Lamictal is prescribed in a dose of 25 mg 1 time / day, at 3-4 weeks - 50 mg/day in 1-2 doses, at week 5 - 100 mg/day in 1-2 doses. The stabilizing dose at week 6 is 200 mg/day in 1-2 doses. However, clinical trials used doses ranging from 100 to 400 mg.

After reaching the daily maintenance stabilizing dose, other psychotropic drugs may be discontinued.

Table 4. Maintenance stabilizing total daily dose for the treatment of bipolar disorders after discontinuation of concomitant psychotropic or antiepileptic drugs.

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

After discontinuation of additional therapy with inhibitors of lamotrigine glucuronidation (for example, valproic acid preparations)

, the stabilizing initial dose of lamotrigine is doubled and maintained at this level.

After discontinuation of additional therapy with inducers of lamotrigine glucuronidation (including phenytoin, carbamazepine, phenobarbital, primidone)

The dose of lamotrigine is gradually reduced over 3 weeks depending on the initial maintenance dose.

After discontinuation of concomitant psychotropic or antiepileptic drugs that do not have significant pharmacokinetic interactions with lamotrigine (for example, lithium, bupropion, olanzapine, oxcarbazepine)

The stabilizing dose of Lamictal achieved during the escalation regimen should be maintained.

There is no clinical experience with adjustment of daily doses of lamotrigine in patients with bipolar disorders after the addition of other drugs. However, based on drug interaction studies, the following recommendations can be made (Table 5).

Table 5. Adjustment of daily doses of lamotrigine in patients with bipolar disorder after adding other drugs to therapy.

During clinical trials of Lamictal for bipolar disorders, abrupt discontinuation of lamotrigine did not cause an increase in the frequency, severity, or nature of adverse reactions compared to placebo. Thus, Lamictal can be discontinued immediately, without gradually reducing the dose.

Lamotrigine is not indicated for bipolar disorder in children and adolescents under 18 years of age.

. The safety and effectiveness of lamotrigine for bipolar disorder have not been evaluated in patients in this age group.

When prescribing Lamictal to women already taking hormonal contraceptives,

Specific lamotrigine dose escalation regimens have not been developed (despite the fact that hormonal contraceptives increase the clearance of lamotrigine). Dosage escalation regimens should follow recommended guidelines depending on whether lamotrigine is administered with valproic acid (an inhibitor of lamotrigine glucuronidation) or an inducer of lamotrigine glucuronidation; or lamotrigine is prescribed in the absence of valproic acid or inducers of lamotrigine glucuronidation (Table 1 for epilepsy and Table 3 for bipolar disorder).

When prescribing hormonal contraceptives to patients already taking maintenance doses of Lamictal and not taking inducers of lamotrigine glucuronidation, in most cases an increase in the dose of lamotrigine is required, but not more than 2 times. When prescribing hormonal contraceptives, it is recommended to increase the dose of lamotrigine by 50 - 100 mg/day every week, depending on the clinical picture. It is not recommended to exceed these figures unless the patient's clinical condition requires a further increase in the dose of lamotrigine.

When stopping hormonal contraceptives in patients already taking maintenance doses of Lamictal and not taking inducers of lamotrigine glucuronidation, in most cases a lamotrigine dose reduction is required by half. It is recommended to gradually reduce the daily dose of lamotrigia by 50-100 mg every week (reduction of no more than 25% of the daily dose per week) for more than 3 weeks, depending on the clinical picture.

Despite the fact that when atazanavir/ritonavir is co-administered

Plasma concentrations of lamotrigine decreased; the recommended dose increase of lamotrigine is not required when co-administering atazanavir/ritonavir. Lamotrigine dose increases should be based on recommendations based on whether lamotrigine is added to therapy with valproic acid (an inhibitor of lamotrigine glucuronidation) or therapy with a glucuronidation inducer of lamotrigine, or whether lamotrigine is used in the absence of valproic acid or the glucuronidation inducer lamotrigine.

In patients already taking maintenance doses of lamotrigine and not taking inducers of lamotrigine glucuronidation, the lamotrigine dose may need to be increased when atazanavir/ritonavir is prescribed, and the lamotrigine dose may need to be reduced when atazanavir/ritonavir is discontinued.

Dosage regimen adjustments in elderly patients (over 65 years of age)

not required (since the pharmacokinetics in this age group do not differ from those in adults).

For moderate (class B on the Child-Pugh scale) and severe liver dysfunction (class C on the Child-Pugh scale)

initial, escalating and maintenance doses should be reduced by approximately 50% and 75%, respectively. Incremental and maintenance doses should be adjusted based on clinical response.

For end-stage renal failure

The initial dose of lamotrigine is calculated in accordance with the standard antiepileptic drug regimen. For patients with a significant decrease in renal function, a reduction in the maintenance dose may be recommended.

Lamictal chewable/dissolvable tablets can be chewed, dissolved in a small volume of water (enough to cover the entire tablet), or swallowed whole with a small amount of water.

If the calculated dose of lamotrigine (for example, when prescribed to children or patients with impaired liver function) cannot be divided into a whole number of lower-strength tablets, then the patient should be prescribed a dose that corresponds to the nearest whole tablet at a lower dosage.

When restarting lamotrigine, the physician should evaluate the need to increase the maintenance dose in patients who have discontinued the drug for any reason, as high initial doses and higher than recommended doses are associated with a risk of severe rash. The more time has passed since the last dose of the drug, the more caution you should increase the dose to maintenance. If the time after discontinuation exceeds 5 half-lives, the dose of lamotrigine should be increased to a maintenance dose according to an appropriate dosage regimen.

Lamotrigine therapy should not be restarted in patients whose lamotrigine treatment was discontinued because of rash, unless the potential benefit of such therapy clearly outweighs the potential risk.

Lamotrigine (Lamictal, Lamitor, Lamolep, Sezar)

Epilepsy

Adults and children over 12 years old

For monotherapy, the initial dose of Lamictal is 25 mg 1 time / day for the first 2 weeks, followed by an increase in dose to 50 mg 1 time / day over the next 2 weeks. The dose should then be increased by 50-100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose to maintain the optimal therapeutic effect is 100-200 mg/day in 1-2 doses. Some patients require Lamictal at a dose of 500 mg/day to achieve a therapeutic effect.

As part of combination therapy when using Lamictal together with valproic acid drugs in combination with other antiepileptic drugs (AEDs) or without them, the initial dose of Lamictal is 25 mg every other day for the first 2 weeks; subsequently – 25 mg 1 time/day for the next 2 weeks. Then the dose should be increased by a maximum of 25-50 mg/day every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose to maintain the optimal therapeutic effect is 100-200 mg/day in 1-2 doses.

As part of combination therapy with concomitant therapy with AEDs or other drugs that induce glucuronidation of lamotrigine (phenytoin, carbamazepine, phenobarbital and primidone), in combination or without other AEDs (except for valproic acid drugs), the initial dose of Lamictal is 50 mg 1 time / day for the first 2 weeks, then over the next 2 weeks - 100 mg / day in 2 doses. Then the dose is increased by 100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 200-400 mg/day in 2 divided doses. Some patients may require a dose of 700 mg/day to achieve a therapeutic effect.

As part of combination therapy with oxcarbazepine in combination with or without any other inducers or inhibitors of lamotrigine glucuronidation, the initial dose of Lamictal is 25 mg 1 time / day for the first 2 weeks, then 50 mg / day in 1 dose for the next 2 weeks. Then the dose is increased by a maximum of 50-100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 100-200 mg per day in 1 or 2 doses.

Due to the risk of developing a rash, the initial dose of the drug and the recommended dose escalation regimen should not be exceeded.

Table 1. Recommended dosage regimen for the treatment of epilepsy in adults and children over 12 years of age.

Children aged 2 to 12 years

It should be noted that accurate initial therapy with Lamictal in 5 mg tablets according to the proposed dosage regimen is impossible if the child’s body weight is less than 17 kg. Children ages 2 to 6 years are likely to require the highest maintenance doses.

The initial dose of Lamictal for monotherapy of typical absence seizures is 0.3 mg/kg body weight/day in 1 or 2 divided doses during the first 2 weeks, followed by a dose increase to 0.6 mg/kg/day in 1 or 2 divided doses over the next 2 weeks. The dose should then be increased by a maximum of 0.6 mg/kg every 1-2 weeks until the optimal therapeutic effect is achieved. The usual maintenance dose for optimal therapeutic effect is 1 to 10 mg/kg/day in 1 or 2 divided doses, although some patients with typical absence seizures require higher doses to achieve therapeutic effect.

As part of combination therapy when using Lamictal with valproic acid drugs in combination with other AEDs or without them, the initial dose of Lamictal is 0.15 mg/kg body weight 1 time/day for the first 2 weeks, then 0.3 mg/kg 1 time/day over the next 2 weeks. The dose should then be increased by 0.3 mg/kg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 1-5 mg/kg/day in 1-2 doses. The maximum daily dose is 200 mg.

As part of combination therapy with concomitant therapy with AEDs or other drugs that induce glucuronidation of lamotrigine (phenytoin, carbamazepine, phenobarbital and primidone), in combination with or without other AEDs (except for valproic acid drugs), the initial dose of Lamictal is 0.6 mg/kg/day in 2 divided doses during the first 2 weeks, then - 1.2 mg/kg/day in 2 divided doses over the next 2 weeks. Then the dose should be increased by a maximum of 1.2 mg/kg/day every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose at which the maximum therapeutic effect is achieved is 5-15 mg/kg/day in 2 divided doses. The maximum daily dose is 400 mg.

As part of combination therapy with oxcarbazepine without any other inducers or inhibitors of lamotrigine glucuronidation, the initial dose of Lamictal is 0.3 mg/kg body weight 1 or 2 times a day for the first 2 weeks, then 0.6 mg/kg/day 1 or 2 times a day. 2 doses over the next 2 weeks. Then the dose is increased by a maximum of 0.6 mg/kg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 1-10 mg/kg/day in 1 or 2 divided doses. The maximum dose is 200 mg/day.

To ensure that the therapeutic dose is maintained, it is necessary to monitor the child's body weight and adjust the drug dose as it changes.

Due to the risk of developing a rash, the initial dose of the drug and the recommended dose escalation regimen should not be exceeded.

Table 2. Recommended dosage regimen for the treatment of children with epilepsy aged 2 to 12 years (total daily dose in mg/kg body weight).

There is insufficient information on the use of Lamictal in children under 2 years of age .

When discontinuing concomitant antiepileptic drugs to switch to Lamictal monotherapy or when prescribing other drugs or AEDs while taking Lamictal, it is necessary to take into account that this may affect the pharmacokinetics of lamotrigine.

Bipolar disorders

Adult patients over 18 years of age

Due to the risk of developing a rash, the initial dose of the drug and the subsequent dose escalation regimen should not be exceeded.

It is necessary to follow a transitional dosing regimen, which includes increasing the dose of lamotrigine over 6 weeks to a maintenance stabilizing dose (Table 3), after which, if indicated, other psychotropic and/or antiepileptic drugs can be discontinued (Table 4).

Table 3. Recommended dosage escalation schedule to achieve a maintenance daily stabilization dose for adults (over 18 years of age) with bipolar disorders.

The maintenance stabilizing dose varies depending on the clinical effect.

As part of combination therapy with the combined use of Lamictal and other AEDs that inhibit liver enzymes (for example, with valproic acid preparations), Lamictal is prescribed at a dose of 25 mg every other day for the first 2 weeks, then 25 mg 1 time / day for the next 2 weeks, at week 5 the dose should be increased to 50 mg/day in 1-2 doses. The stabilizing dose at week 6 is 100 mg/day in 1-2 doses; however, it may be increased to a maximum daily dose of 200 mg depending on clinical response.

As part of combination therapy with the combined use of Lamictal and other AEDs that induce liver enzymes (for example, carbamazepine, phenobarbital), in patients not receiving valproic acid drugs, during the first 2 weeks Lamictal is prescribed at a dose of 50 mg 1 time / day, for 3 Week 4 - 100 mg/day in 2 divided doses, week 5 - 200 mg/day in 2 divided doses. At week 6, the dose can be increased to 300 mg/day, however, the stabilizing dose to achieve the optimal therapeutic effect is 400 mg/day in 2 doses, and is prescribed starting from week 7.

When using Lamictal monotherapy or as part of combination therapy when using Lamictal together with lithium drugs, bupropion, olanzapine, oxcarbazepine, without the use of inducers or inhibitors of lamotrigine glucuronidation during the first 2 weeks, Lamictal is prescribed at a dose of 25 mg 1 time / day, for 3-4 weeks - 50 mg/day in 1-2 doses, at week 5 - 100 mg/day in 1-2 doses. The stabilizing dose at week 6 is 200 mg/day in 1-2 doses. However, clinical trials used doses ranging from 100 to 400 mg.

After reaching the daily maintenance stabilizing dose, other psychotropic drugs may be discontinued.

Table 4. Maintenance stabilizing total daily dose for the treatment of bipolar disorders after discontinuation of concomitant psychotropic or antiepileptic drugs.

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

After discontinuation of additional therapy with inhibitors of lamotrigine glucuronidation (for example, valproic acid), the stabilizing initial dose of lamotrigine is doubled and maintained at this level.

After discontinuation of additional therapy with inducers of lamotrigine glucuronidation (including phenytoin, carbamazepine, phenobarbital, primidone), the dose of lamotrigine is gradually reduced over 3 weeks depending on the initial maintenance dose.

After discontinuation of concomitant psychotropic or antiepileptic drugs that do not have significant pharmacokinetic interactions with lamotrigine (for example, lithium, bupropion, olanzapine, oxcarbazepine), the stabilizing dose of Lamictal achieved during the escalation regimen should be maintained.

There is no clinical experience with adjustment of daily doses of lamotrigine in patients with bipolar disorders after the addition of other drugs. However, based on drug interaction studies, the following recommendations can be made (Table 5).

Table 5. Adjustment of daily doses of lamotrigine in patients with bipolar disorder after adding other drugs to therapy.

During clinical trials of Lamictal for bipolar disorders, abrupt discontinuation of lamotrigine did not cause an increase in the frequency, severity, or nature of adverse reactions compared to placebo. Thus, Lamictal can be discontinued immediately, without gradually reducing the dose.

Lamotrigine is not indicated for bipolar disorder in children and adolescents under 18 years of age . The safety and effectiveness of lamotrigine for bipolar disorder have not been evaluated in patients in this age group.

When prescribing Lamictal to women already taking hormonal contraceptives, special lamotrigine dose escalation regimens have not been developed (despite the fact that hormonal contraceptives increase the clearance of lamotrigine). Dosage escalation regimens should follow recommended guidelines depending on whether lamotrigine is administered with valproic acid (an inhibitor of lamotrigine glucuronidation) or an inducer of lamotrigine glucuronidation; or lamotrigine is prescribed in the absence of valproic acid or inducers of lamotrigine glucuronidation (Table 1 for epilepsy and Table 3 for bipolar disorder).

When prescribing hormonal contraceptives to patients already taking maintenance doses of Lamictal and not taking inducers of lamotrigine glucuronidation, in most cases an increase in the dose of lamotrigine is required, but not more than 2 times. When prescribing hormonal contraceptives, it is recommended to increase the dose of lamotrigine by 50 - 100 mg/day every week, depending on the clinical picture. It is not recommended to exceed these figures unless the patient's clinical condition requires a further increase in the dose of lamotrigine.

When stopping hormonal contraceptives in patients already taking maintenance doses of Lamictal and not taking inducers of lamotrigine glucuronidation, in most cases a lamotrigine dose reduction is required by half. It is recommended to gradually reduce the daily dose of lamotrigia by 50-100 mg every week (reduction of no more than 25% of the daily dose per week) for more than 3 weeks, depending on the clinical picture.

Although lamotrigine plasma concentrations were decreased atazanavir/ritonavir was co-administered Lamotrigine dose increases should be based on recommendations based on whether lamotrigine is added to therapy with valproic acid (an inhibitor of lamotrigine glucuronidation) or therapy with a glucuronidation inducer of lamotrigine, or whether lamotrigine is used in the absence of valproic acid or the glucuronidation inducer lamotrigine.

In patients already taking maintenance doses of lamotrigine and not taking inducers of lamotrigine glucuronidation, the lamotrigine dose may need to be increased when atazanavir/ritonavir is prescribed, and the lamotrigine dose may need to be reduced when atazanavir/ritonavir is discontinued.

dosage adjustment is required in elderly patients (over 65 years of age) (since the pharmacokinetics in this age group do not differ from those in adults).

For moderate (Child-Pugh class B) and severe (Child-Pugh class C) liver dysfunction, the initial, escalating and maintenance doses should be reduced by approximately 50% and 75%, respectively. Incremental and maintenance doses should be adjusted based on clinical response.

For end-stage renal failure, the initial dose of lamotrigine is calculated in accordance with the standard antiepileptic drug regimen. For patients with a significant decrease in renal function, a reduction in the maintenance dose may be recommended.

Lamictal chewable/dissolvable tablets can be chewed, dissolved in a small volume of water (enough to cover the entire tablet), or swallowed whole with a small amount of water.

If the calculated dose of lamotrigine (for example, when prescribed to children or patients with impaired liver function) cannot be divided into a whole number of lower-strength tablets, then the patient should be prescribed a dose that corresponds to the nearest whole tablet at a lower dosage.

When restarting lamotrigine, the physician should evaluate the need to increase the maintenance dose in patients who have discontinued the drug for any reason, as high initial doses and higher than recommended doses are associated with a risk of severe rash. The more time has passed since the last dose of the drug, the more caution you should increase the dose to maintenance. If the time after discontinuation exceeds 5 half-lives, the dose of lamotrigine should be increased to a maintenance dose according to an appropriate dosage regimen.

Lamotrigine therapy should not be restarted in patients whose lamotrigine treatment was discontinued because of rash, unless the potential benefit of such therapy clearly outweighs the potential risk.

Publications in the media

(Lamoiriginum) INN

Synonyms. Lamictal.

Composition and release form. Tablets of 0.025, 0.05 and 0.1 g of lamotrigine.

Indications. Epilepsy (mono- and auxiliary therapy for partial and generalized seizures).

Pharmachologic effect. Lamotrigine is an anticonvulsant that can block the action of excitatory non-irotransmitter amino acids (glutamate and aspartate). Blockade of voltage-dependent sodium channels, prevention of the release of excitatory amino acids and stabilization of presynaptic neuronal membranes provide its anticonvulsant effect. Lamotrigine exerts its action through NMDA receptors of excitatory amino acids. Pharmacokinetics. When taken orally, the drug is absorbed quickly and completely from the gastrointestinal tract into the blood; the bioavailability of lamotrigine is 98%; food intake does not affect bioavailability. The volume of distribution is 1.2 l/kg. Peak plasma concentrations are observed on average 2.5 hours after administration. Binds to plasma proteins by 55%. The drug is almost completely metabolized in the liver with the formation of the main metabolite - N-glucuronide. T1/2 is 29 hours. It is excreted mainly in the urine in the form of the main metabolite and, partially, unchanged. Side effects . Nausea, vomiting; feeling tired, headache, dizziness, irritability, drowsiness, tremor; blurred vision, diplopia; allergic reactions; lymphadenopathy. Contraindications. Severe diseases of the liver, kidneys; hypersensitivity to the drug.

Adverse reactions when interacting with other drugs. The drug is not recommended to be taken simultaneously with drugs that depress the central nervous system and with alcohol due to the dangerous potentiation of effects. Valproic acid, chloramphenicol, cimetidine inhibit the metabolism of lamotrigine and may increase its side effects. Carbamazepine, when taken simultaneously with lamotrigine, causes dizziness, diplopia, and blurred vision. The clearance of lamotrigine increases when it is taken simultaneously with carbamazepine or phenobarbital, or phenytoin, or primidone, which leads to a decrease in its T1/2. Information for the patient. Lamotrigine is prescribed to adults and children 0.05 g 2 times a day 30-40 minutes before meals or, to avoid irritation of the gastric mucosa, after meals. If necessary, the daily dose can be increased. Alcohol and other CNS depressants should not be used during treatment with lamotrigine. Use caution when driving. Lamotrigine should be avoided during pregnancy. The drug is discontinued gradually to avoid a sharp exacerbation of the disease. Missed dose: Take the missed dose as soon as possible; if there is no time left to take the missed dose, do not take it; do not take double doses.