Inside. If the calculated dose of lamotrigine (for example, when administered to children or patients with impaired liver function) can not be divided into a whole number of tablets, the patient should be given a dose that corresponds to the nearest value of the whole tablet at a lower dosage.
Because of the risk of developing the rash, the initial dose of the drug and the recommended regime for increasing doses should not be exceeded.
Epilepsy
Monotherapy in adults and children over 12 years of age
The initial dose of lamotrigine with monotherapy is 25 mg once a day for 2 weeks, followed by an increase in the dose to 50 mg once a day for 2 weeks. Then the dose should be increased by 50-100 mg every 1-2 weeks, until the optimal therapeutic effect is achieved. Usually the maintenance dose is 100-200 mg per day in one or two doses. Some patients require up to 500 mg / day.
Additional therapy in adults and children over 12 years of age
In patients receiving valproate in combination with other PETs or without them, the initial dose of lamotrigine is 25 mg every other day for 2 weeks,in the future - 25 mg once a day for 2 weeks. Then the dose should be increased as much as 25-50 mg / day every 1-2 weeks, until the optimal therapeutic effect is achieved. Usually, the maintenance dose is 100-200 mg / day in one or two doses.
In patients receiving concomitant therapy with PEP or other drugs that stimulate the glucuronization of lamotrigine, in combination with or without other PEP (with the exception of valproate), the initial dose of lamotrigine is 50 mg once daily for 2 weeks, then 100 mg / day in two divided doses for 2 weeks. Then the dose increases by a maximum of 100 mg every 1-2 weeks, until the optimal therapeutic effect is achieved. Usually the maintenance dose is 200-400 mg per day in two divided doses. Some patients may require up to 700 mg / day.
Patients who take oxcarbazepine in combination with any other inducers or inhibitors of glucuronization of lamotrigine or without them, the initial dose of lamotrigine is 25 mg once a day for 2 weeks, then 50 mg / day at one time for 2 weeks. Then the dose increases by max. 50-100 mg every 1-2 weeks, until the optimal therapeutic effect is achieved.Usually the maintenance dose is 100-200 mg per day in one or two doses.
Because of the risk of developing the rash, the initial dose of the drug and the recommended regime for increasing doses should not be exceeded.
Monotherapy in children from 2 to 12 years
The initial dose of lamotrigine in monotherapy of patients with typical absences is 0, 3 mg / kg / day in one or two doses for 2 weeks, followed by a dose increase of 0.6 mg / kg / day in one or two doses during 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. Typically, the maintenance dose is 1 to 15 mg / kg / day in one or two doses, although some patients require higher doses.
Additional therapy in children aged 2 to 12 years
In children taking valproate in combination with other PEPs or without them, the initial dose of damogrigine is 0.15 mg kg once daily for 2 weeks, then 0.3 mg / kg per day for one week for 2 weeks . The dose can then be increased by 0.3 mg / kg every 1-2 weeks, until the optimal therapeutic effect is achieved. The usual maintenance dose is 1 to 5 mg / kg per day in one or two doses. The maximum daily dose is 200 mg.
In patients taking PEP or other drugs stimulating the glucuronization of lamotrigine (in combination with or without others (except for valproate)), the initial dose of lamotrigine is 0.6 mg / kg per day in 2 divided doses for 2 weeks, further - 1,2 mg / kg / day. in two divided doses for 2 weeks. Then the dose is increased to a maximum of 1.2 mg / kg / day. every 1-2 weeks, until the optimal therapeutic effect is achieved. The usual maintenance dose is 5-15 mg / kg per day in two divided doses with a maximum dose of 400 mg / day.
In patients receiving oxcarbazepine without any other inducers or inhibitors of lamotrigine glucuronin, the initial dose of lamotrigine is 0.3 mg / kg / day. for one or two doses for 2 weeks, then 0.6 mg / kg / day in one or two doses for 2 weeks. Then the dose rises as much as 0.6 mg / kg every 1-2 weeks until the optimal therapeutic effect is achieved. Usually the maintenance dose is 1-10 mg / kg / day. in one or two admission. The maximum dose is 200 mg / day.
To be sure that a therapeutic dose is maintained, it is necessary to control the weight of the child and adjust the dose of the drug as it changes.Precise dosing during initial lamotrigine therapy in tablets of 5 mg is not possible if the child's weight is less than 17 kg.
Most likely, children between the ages of 2 and 6 years will need the largest maintenance doses.
General recommendations for the dosage of Convulsan in the treatment of epilepsy
With the withdrawal of concomitant PEP, the transfer to lamotrigine monotherapy or the appointment of other medications or PET on the background of lamotrigine, it must be taken into account that this may affect the pharmacokinetics of lamotrigine.
Bipolar disorders in adults
It is necessary to follow the transitional dosing regimen, which includes increasing the dose of lamotrigine for 6 weeks to a maintenance stabilizing dose (Table 1), after which, if there are indications, it is possible to cancel other psychotropic and / or PEP (Table 2).
Table 1. Recommended scheme of increasing doses to achieve maintenance daily stabilizing dose for bipolar disorders in adults.
| Dosing regimen | 1-2 a week | 3-4 a week | 5 a week | Target stabilizing dose (from 6 weeks) |
| a) Combination therapy with lamotrigine glucuronide inhibitors, for example, valproate. | 12.5 mg (25 mg every other day) | 25 mg (1 time per day) | 50 mg (for 1-2 administration per day) | 100 mg (for 1 -2 admission per day), the maximum daily dose of 200 mg |
| b) Combined therapy with inductors of lamotrigine glucuronization 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 (for 2 doses per day) | 200 mg (for 2 doses per day) | 300 mg at week 6 of therapy, if necessary, increase doses> up to 400 mg at week 7 of therapy (for 2 doses) |
| c) Convulsant Monotherapy or additional therapy in patients taking lithium preparations, bupropion, olanzapine, oxcarbazepine or 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 (for 1-2 administration per day) | 100 mg (for 1-2 administration per day) | 200 mg (from 100 mg to 400 mg for 1 -2 administration per day) |
| Note: v patients receiving PEP, the pharmacokinetic interaction of which with lamotrigine has not been studied, it is necessary to use the regimen for increasing doses, as recommended for lamotrigine in combination with valproate. |
The target stabilizing dose varies depending on the clinical effect
a) Additional therapy in patients taking lamotrigine glucuronide inhibitors (eg, valproate)
The initial dose of lamotrigine in patients taking glucuronidation inhibitory drugs (such as valproate) is 25 mg every other day for 2 weeks, then 25 mg once daily for 2 weeks. The dose should be increased to 50 mg (for 1-2 doses) at week 5. Usually the target dose is 100 mg / day (for 1-2 doses). The maximum daily dose is 200 mg
b) Additional therapy in patients taking drugs simultaneously, stimulating glucuronization of lamotrigine and not taking lamotrigine glucuronine inhibitors (eg valproate).
This regimen should be used with phenytoin, carbamazepine, phenobarbital, primidone and other inducers of lamotrigine glucuronization.
The initial dose of lamotrigine is 50 mg once a day for 2 weeks, then 100 mg per day in two divided doses for 2 weeks. On the 5th week, the dose should be increased to 200 mg per day in two divided doses. At the 6th week, the dose can be increased to 300 mg per day, but usually, the target dose is 400 mg per day (in two divided doses), and is prescribed starting at week 7 of treatment.
c) Monotherapy with Convulsant or additional therapy in patients taking lithium drugs, bupropion, olanzapine, oxcarbazepine or other drugs that do not have a significant inducing or inhibitory effect on the glucotoninization of lamotrigine.
The initial dose of lamotrigine is 25 mg once a day for 2 weeks, then 50 mg per day (in 1 or 2 admission) for 2 weeks. The dose should be increased to 100 mg per day at week 5. Usually the target dose is 200 mg per day (in 1 or 2 admission). After reaching the target maintenance stabilizing dose, other psychotropic drugs may be withdrawn (Table 2).
Table 2. Supporting a stabilizing daily dose for the treatment of bipolar disorders after withdrawal of concomitant psychotropic or PET.
| Dosing regimen | 1 Week | 2 weeks | 3 weeks and more |
| a) After the withdrawal of inhibitors of glucuronization of lamotrigine (eg, valproate). | Double the stabilizing dose, not exceeding 100 mg / week. Those. the target stabilizing dose of 100 mg / day increases in 1 week to 200 mg / day. | Save the dose of 200 mg / day in 2 divided doses. |
| b) After abolition of inducers of gluturidin glucuronization, depending on the initial dose.This regimen should be used when using phenytoin, carbamazepine, phenobarbital, primidon, or other inducers of lamotrigine glucuronization | 400 mg | 300 mg | 200 mg |
| 300 mg | 225 mg | 150 mg |
| 200 mg | 150 mg | 100 mg |
| c) After the abolition of other psychotropic or PEP in patients not taking inducers or inhibitors of glucuronin glucuronin (including lithium preparations, bupropion, olanzapine, oxcarbazepine). | Maintain the target dose achieved during the enhancement regimen (200 mg /cducks in 2 doses; a range of doses from 100 mg to 400 mg). |
Note: Patients receiving PEP, whose pharmacokinetic interaction with lamotrigine is not currently known, is recommended dosing regimen, as with lamotrigine with valproate.
If necessary, the dose may be increased to 400 mg / day.
a) Convulsan therapy after withdrawal of adjunctive therapy with lamotrigine glucuronide inhibitors (eg valproate): immediately after the abolition of valproate, stabilizing the initial dose of lamotrigine is doubled and maintained at this level.
b) Convulsan therapy after the abolition of additional therapy with lamotrigine glucuronin inductors, depending on the initial maintenance dose. This regimen should be used when using phenytoin, carbamazepine, phenobarbital, primidon, or other inducers of lamotrigine glucuronization. The dose of lamotrigine gradually decreases within 3 weeks after the elimination of glucuronization inducers.
c) Lamotrigine therapy after withdrawal of concomitant psychotropic or PEP that do not have significant pharmacokinetic interactions with lamotrigine (eg, lithium preparations, bupropion, olanzapine, oxcarbazepine).
During the withdrawal of lamotrigine-related drugs, the target lamotrigine dose achieved during the enhancement regimen should be maintained.
There is no clinical experience in correcting daily doses of lamotrigine after the addition of other drugs. However, based on studies on drug interactions, the following recommendations can be made (Table 3).
Table 3. Correction of daily doses of lamotrigine in patients with bipolar disorder after adherence to therapy with other drugs
| Dosing regimen | Current stabilizing dose of lamotrigine (mg / day) | 1 Week | 2 weeks | 3 weeks and more |
| a) addition of lamotrigine glucuronine 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 | Preserve the dose of 150 mg / day |
| 400 mg | 200 mg | Save the dose of 200 mg / day |
| b) Attachment 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) Accession other psychotropic or antiepileptic drugs with insignificant lamotrigine pharmacokinetic interaction with (e.g., lithium preparations bupropion, olanzapine, oxcarbazepine). | Maintain the target dose achieved in the course of the regimen (200 mg / day, range of doses from 100 mg to 400 mg). |
| Note: Patients, receiving probe, the nature of the pharmacokinetic interaction with lamotrigine which is not currently known, it recommended dosing regimen as when taking lamotrigine with valproate. |
Termination of lamotrigine therapy in patients with bipolar disorder: cancel lamotrigine you can immediately, without gradually reducing its dose.
Re-appointment
In case of resumption of lamotrigine, the doctor should evaluate the need to increase the maintenance dose in patients who stopped taking the drug for any reason, since high initial doses and excess of recommended doses are associated with a risk of developing a 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.
It is not recommended to resume the appointment of lamotrigine to patients who stopped taking the drug because of the rash, unless the potential benefit of the drug is significantly greater than the risk.
General recommendations for dosing lamotrigine in specific patient categories
Women taking hormonal contraceptives
a) The appointment of lamotrigine to patients already receiving hormonal contraceptives: There is no need to correct recommended regimens for increasing lamotrigine doses.
b) The administration of hormonal contraceptives to patients already receiving maintenance doses of lamotrigine and NOT receiving lamotrigine glucuronide inducers: may require an increase in the maintenance dose of lamotrigine, but no more than 2 times, depending on the individual clinical effect.
c) Discontinuation of hormonal contraceptive use by patients already receiving maintenance doses of lamotrigine and NOT receiving lamotrigine glucuronide inducers: it may be necessary to reduce the lamotrigine dose by a factor of 2, depending on the individual clinical effect.
Patients of advanced age (over 65 years)
Changes in the drug dosage adjustment schedule are not required.
Impaired liver function
The initial, increasing and maintenance doses should be reduced by approximately 50% and 75% in patients with moderate (stage B) and severe (stage C) hepatic insufficiency, respectively. Increasing and maintenance doses should be adjusted depending on the clinical effect.
Impaired renal function
Patients with a significant decrease in renal function may be recommended to reduce the maintenance dose.