Composition, form of production and packaging
Tablets from pale yellow to yellow-brown, square with rounded corners, one side flat with an embossed "GSEC7" inscription, the other side is polyhedral, with a convex square with a squashed "25".
1 tab.
lamotrigine 25 mg
Excipients: lactose monohydrate - 24.7 mg, microcrystalline cellulose - 24.7 mg, sodium carboxymethyl starch - 2.5 mg, povidone - 2.5 mg, magnesium stearate - 0.4 mg, iron oxide pigment yellow 0.2 mg.
10 pieces. - blisters (3) - packs of cardboard.
Tablets from pale yellow to yellow-brown, square with rounded corners, one side flat with an embossed "GSEE1" inscription, the other side is polyhedral, with a convex square with a squashed "50".
1 tab.
lamotrigine 50 mg
Excipients: lactose monohydrate - 49.4 mg, microcrystalline cellulose - 49.4 mg, sodium carboxymethyl starch - 5 mg, povidone - 5 mg, magnesium stearate - 0.8 mg, ferric oxide yellow oxide - 0.4 mg.
10 pieces. - blisters (3) - packs of cardboard.
Tablets from pale yellow to yellow-brown, square with rounded corners, one side flat with an embossed "GSE5" inscription, the other side is polyhedral, with a convex square with a squashed "100".
1 tab.
lamotrigine 100 mg
Excipients: lactose monohydrate 98.8 mg, microcrystalline cellulose 98.8 mg, sodium carboxymethyl starch 10 mg, povidone 10 mg, magnesium stearate 1.6 mg, iron oxide yellow oxide 0.8 mg.
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Antiepileptic drug. 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.
The efficacy of lamichtal in preventing mood disorders in patients with bipolar disorders has been demonstrated in two fundamental clinical studies. A combined analysis of the results showed that the duration of remission, defined as the time before the onset of the first episode of depression and before the first episode of mania / hypomania / mixed after stabilization, lasted longer in the lamotrigine group compared with placebo. The duration of remission is more pronounced for depression.
PHARMACOKINETICS
Suction
After ingestion lamotrigine is rapidly and completely absorbed from the digestive tract, practically without undergoing the first systemic pre-systemic metabolism. Cmax in plasma is achieved approximately 2.5 hours after taking the drug. The time to reach C max slightly increases after ingestion, but the degree of absorption remains unchanged. The pharmacokinetics of lamotrigine is linear in the administration of a single dose to 450 mg (the highest dose studied). Significant interindividual oscillations of C max in an equilibrium state are observed, but with rare fluctuations in each individual.
Distribution
Lamotrigine binds to plasma proteins by approximately 55%. It is unlikely that the release of the drug from the bond with the protein could lead to the development of a toxic effect. V d is 0.92-1.22 l / kg.
Metabolism
In the metabolism of lamotrigine, the enzyme uridine-diphosphate-glucuronyltransferase (UDP-glucuronyltransferase) participates. Lamotrigine in a small degree increases its own metabolism depending on the dose. However, there is no evidence that lamotrigine affects the pharmacokinetics of other antiepileptic drugs and that interaction is possible between lamotrigine and other drugs metabolized by the cytochrome P450 system.
Excretion
In healthy adults, lamotrigine clearance in the state of equilibrium concentrations averages 39 ± 14 ml / min. Lamotrigine is metabolized to glucuronides, which are excreted by the kidneys. Less than 10% of the drug is excreted by the kidneys unchanged, about 2% - through the intestine. Clearance and T 1/2 are dose independent. T1/2 in healthy adults is an average of 24 hours to 35 hours. In patients with Gilbert's syndrome, the clearance of the drug was reduced by 32% compared to the control group, which, however, did not exceed the limits of normal values ​​for the general population. T 1/2 of lamotrigine is greatly influenced by co-administered medications. The mean T 1/2 is reduced to approximately 14 hours with concomitant administration with glucuronizing stimulants such as carbamazepine and phenytoin, and rises to an average of 70 hours with co-administration with valproate.
Pharmacokinetics in special clinical cases
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, T 1/2 lamotrigine is usually less than in adults. Its mean value is approximately equal to 7 hours with simultaneous administration with drugs stimulating glucuronization, such as carbamazepine and phenytoin, and rises to an average of 45-50 hours with co-administration with valproate.
Clinically significant differences in the clearance of lamotrigine in elderly patients in comparison with young patients were not detected.
If the renal function is impaired, the initial dose of lamotrigine is calculated according to the standard antiepileptic drug prescription schedule. Dose reduction may be required only with a significant decrease in kidney function.
The initial, increasing and maintenance doses should be reduced by approximately 50% in patients with moderate degree of hepatic insufficiency (class B on the Child-Pugh scale) 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.
INDICATIONS
Epilepsy
for adults and children over 12 years
- epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures in the Lennox-Gastaut syndrome) as part of combination therapy or monotherapy.
for children from 3 to 12 years
- epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures in the Lennox-Gastaut syndrome) as part of combination therapy. After achieving epilepsy control against the background of combined therapy, concomitant antiepileptic drugs can be withdrawn and lamotrigine continued in monotherapy;
- monotherapy of typical absences.
Bipolar disorders
for adults (18 years and over)
- Prevention of mood disorders (depression, mania, hypomania, mixed episodes) in patients with bipolar affective disorders.
DOSING MODE
Inside.
Tablets should be swallowed whole, not chewed, not broken.
If the calculated dose of lamotrigine (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 lower dosage.
Renewal of the drug: if Lamictal В® is resumed, physicians should evaluate the need to increase the maintenance dose in patients who stop taking the drug for any reason, since high initial doses and excess of the recommended dose 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.
Therapy with Lamictal В® should not be resumed in patients whose lamotrigine withdrawal was associated with the onset of 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 В® in monotherapy is 25 mg 1 time / day for 2 weeks, followed by an increase in the dose to 50 mg 1 time / 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 maintaining the optimal therapeutic effect is 100-200 mg / day in 1-2 doses. Some patients require a dose of Lamicital В® 500 mg / day to achieve a therapeutic effect.
Children aged 3 to 12 years (Table 2)
The initial dose of Lamictal В® 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 for 2 weeks. Then the dose should be increased by 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. The usual maintenance dose for achieving the optimal therapeutic effect is 1 to 10 g / 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, do not exceed the initial dose of the drug and the recommended dose titration regime.
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 lamotrigine is 25 mg every other day for 2 weeks, then 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. The usual 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 В® is 50 mg 1 time / day for 2 weeks, 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 a therapeutic effect.
In patients taking other drugs that do not significantly inhibit or induce glucuronization of lamotrigine, the initial dose of Lamictal В® is 25 mg 1 time / day for 2 weeks, then 50 mg / day 1 time / 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 is 100-200 mg / day in 1 or 2 doses.
Table 1. Recommended dosage regimen of Lamictal В® in the treatment of epilepsy in adults and children over 12 years of age
Destination mode Week 1-2 Week 3-4 Maintenance dose
Monotherapy 25 mg 1 time / day 50 mg 1 time / day 100-200 mg 1 or 2 times / day; to achieve a therapeutic effect, doses can be increased by 50-100 mg every 1-2 weeks.
Combination therapy with Lamycal and preparations of valproic acid, regardless of other concomitant therapy, 12.5 mg (given at 25 mg every other day) 25 mg once a day 100-200 mg (in 1 or 2 admission); to achieve a therapeutic effect, doses can be increased by 25-50 mg every 1-2 weeks.
Combination therapy without valproic acid:
with phenytoin, carbamazepine, phenobarbital, primidon, or other inducers, lamotrigine glucuronin 50 mg 1 time / day 100 mg (in 2 divided doses) 200-400 mg (in 2 divided doses); to achieve a therapeutic effect, doses can be increased by 100 mg every 1-2 weeks.
with other drugs that do not substantially inhibit and induce glucuronidation of lamotrigine 25 mg once / day 50 mg once / day 100-200 mg (in 1 or 2 administrations); to achieve a therapeutic effect, the dose can be increased by 50-100 mg every 1-2 weeks.
In patients taking PEP, the pharmacokinetic interaction of which with lamotrigine is currently unknown, a dosing regimen recommended for lamotrigine in combination with valproate should be used.
Because of the risk of developing the rash, the initial dose of Lamictal В® and the recommended dose-increasing regimen should not be exceeded.
Children aged 3 to 12 years (Table 2)
In children taking valproate in combination with other PET or without them, the initial dose of lamotrigine is 0.15 mg / kg / day 1 time / day for 2 weeks, then 0.3 mg / kg / day 1 time / day for 2 weeks. Then the dose can be increased by as much as 0.3 mg / kg every 1-2 weeks until the optimal therapeutic effect is achieved. The usual maintenance dose is 1-5 mg / kg / day in 1 or 2 doses. The maximum daily dose is 200 mg / day.
In children who receive PET or other drugs that induce glucuronization of lamotrigine, in combination with or without other PEP (with the exception of valproate), the initial dose of Lamictal В® is 0.6 mg / kg / day in 2 divided doses for 2 weeks, - 1.2 mg / kg / day in 2 divided doses for 2 weeks. The dose should then be increased by no more than 1.2 mg / kg / day 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 2 times / day. The maximum dose is 400 mg / day.
In patients taking other drugs that do not significantly inhibit or induce lamotrigine glucuronin, the initial dose of lamotrigine is 0.3 mg / kg / day in 1 or 2 doses for 2 weeks, then 0.6 mg / kg / day for 1 or 2 doses within 2 weeks. Then the dose should 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 at which the optimal therapeutic effect is achieved is 1-10 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 sure 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 as 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 В® in the treatment of epilepsy in children aged 3 to 12 years
Destination mode Week 1-2 Week 3-4 Maintenance dose
Monotherapy at typical absences 0.3 mg / kg (in 1 or 2 doses) 0.6 mg / kg (in 1 or 2 doses) Increasing the dose by 0.6 mg / kg every 1-2 weeks until a maintenance dose of 1-10 mg / kg / day (appointed in 1 or 2 admission) to a maximum dose of 200 mg / day
Combination therapy with lamitcal and valproic acid preparations, regardless of other concomitant therapy 0.15 mg / kg 1 time / day 0.3 mg / kg 1 time / day Increase in the dose by 0.3 mg / kg every 1-2 weeks until a maintenance dose of 1-5 mg / kg / day (appointed in 1 or 2 admission) to a maximum dose of 200 mg / day
Combination therapy without valproate:
with phenytoin, carbamazepine, phenobarbital, primidon, or other inducers of lamotrigine glucuronin 0.6 mg / kg (in 2 divided doses) 1.2 mg / kg (in 2 doses) Increase in the dose of 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
with drugs that do not inhibit or induce glucuronization of lamotrigine 0.3 mg / kg (in 1 or 2 doses) 0.6 mg / kg (in 1 or 2 doses) Increase the dose by 0.6 mg / kg every 1-2 weeks until a maintenance dose of 1 -10 mg / kg / day (prescribed in 1 or 2 doses) to a maximum dose of 200 mg / day
In patients taking PEP, the pharmacokinetic interaction of which with lamotrigine is currently unknown, a dosing regimen recommended for lamotrigine in combination with valproate should be used.
If the calculated daily dose in patients taking valproate is 1-2 mg, then lamotrigine can be given at 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 prescribed.
Children under 3 years
The use of Lamictal В® is not studied as a monotherapy in children under 2 years of age or as an adjunctive therapy in children younger than 1 month . The safety and efficacy of Lamictal В® as an adjunctive therapy for partial seizures in children aged 1 month to 2 years have not been established.
In children under 3 years of application of solid dosage forms (that can not be pre-dissolved, etc.) are not allowed.
General dosing recommendations for lamotrigine in the treatment of epilepsy
If you cancel or concomitant AEDs adding probes, or the use of lamotrigine in patients receiving other drugs or AEDs should take into account the fact that it may have an effect on the pharmacokinetics of lamotrigine.
Bipolar affective disorder
adult patients older than 18 years
because of the risk of rash should not exceed the initial dose and subsequent dose increase regimen.
Should follow transition dosage regimen, which includes an increase in the dose for 6 weeks preparation Lamictal В®to a maintenance dose of stabilizer (Table 3), and then, if indicated, it is possible to cancel other psychotropic drugs and / or probe (Table 4).
Table 3. The recommended dose regimen increase Lamictal В® to achieve the stabilizing supports daily dose for adults (18 years or older) with bipolar disorder
Week 1-2 Week 3-4 Week 5 Target stabilizing dose (week 6) **
a) Combination Therapy inhibitors glucuronidation lamotrigine (e.g., valproate)
12.5 mg (25 mg every other day) 25 mg 1 time / day to 50 mg (in 1 or 2 divided doses) / d (100 mg, in 1 or 2 divided doses) / day with a maximum daily dose 200 mg
b) Combination therapy with inducers of lamotrigine glyukuronirovaniya in patients not taking inhibitors such as Valproate. This mode should be used with phenytoin, carbamazepine, phenobarbital, primidone or other inducers glucuronidation Lamotrigine
50 mg 1 time / day 100 mg (2 doses) / day to 200 mg (in 2 hours) / day to 300 mg for 6 weeks of therapy, if desired increase the dose up to 400 mg of a 7 week therapy (2 doses)
c) Monotherapy lamotrigine or a combination therapy in patients taking other medications which do not significantly inducing or inhibitory effect on glucuronidation lamotrigine
25 mg 1 time / day to 50 mg (1 or 2 divided doses) / day 100 mg (in 1 or 2 divided doses) / day to 200 mg (from 100 mg to 400 mg) in 1 or 2 doses / day
Patients taking AEDs pharmacokinetic interaction with lamotrigine is currently unknown, must izpolzovatsya mode increasing the dose recommended for the use of lamotrigine in combination with valproate.
Target ** anti dose varies depending on the clinical effect.
a) Combination therapy lamotrigine glucuronidation inhibitors, e.g., valproate
initial dose drug Lamictal В®in patients receiving additional drugs inhibiting glucuronidation, such as valproate, is 25 mg every other day for 2 weeks, then - 25 mg 1 time / day for 2 weeks. The dose should be increased to 50 mg 1 time / day (or in 2 divided doses) at 5 weeks. Normal target dose to obtain the optimal therapeutic effect is 100 mg / day (in 1 or 2 divided doses). However, the dose may be increased to a maximum daily dose of 200 mg depending on the clinical effect.
b) Combination therapy with inducers of lamotrigine glucuronidation in patients not taking inhibitors such as valproate. This mode should be used with phenytoin, carbamazepine, phenobarbital, primidone or other inducers of lamotrigine glucuronidation.
The initial dose of drug Lamictal В®patients receiving both drugs that induce glucuronidation of lamotrigine and valproate 50 mg 1 time / day for 2 weeks, then - 100 mg / day in 2 divided doses for 2 weeks. At 5th week, the dose should be increased to 200 mg / day in 2 divided doses. At week 6, the dose may be increased to 300 mg / day, though the usual target dose to achieve the optimal therapeutic effect is 400 mg / day (two doses) and assigned starting from the 7th week of treatment.
c) lamotrigine monotherapy or combination therapy in patients taking drugs that do not substantially inducing or inhibiting effect on the glucuronidation of lamotrigine
initial dose drug Lamictal В®1 is 25 mg once / day for 2 weeks, then - 50 mg / day (in 1 or 2 divided doses) for 2 weeks. The dose should be increased to 100 mg / day in the 5th week. Normal target dose to achieve the optimal therapeutic effect is 200 mg / day (in 1 or 2 divided doses). However, in clinical studies used a dose ranging from 100 mg to 400 mg.
After reaching the target daily maintenance dose stabilizing other psychotropic drugs may be canceled (Table 4).
Table 4. The supporting roll total daily dose of the drug Lamictal В® for the treatment of bipolar affective disorder after withdrawal concomitant psychotropic or probe.
Dosage regimen Week 1 Week 2 Week 3 onwards *
a) After canceling lamotrigine glucuronidation inhibitors such as valproic acid preparations Double the stabilizing dose not exceeding 100 mg / week, i.e. target roll dose of 100 mg / day for 1 week, increased to 200 mg / day. Save dose of 200 mg / day in 2 doses
b) After canceling inductors glucuronidation of lamotrigine according to the initial dose. This mode should be used when applying phenytoin, carbamazepine, phenobarbital, primidone or other inducers glucuronidation Lamotrigine 400 mg 300 mg 200 mg
300 mg 225 mg 150 mg
200 mg 150 mg 100 mg
After the cancellation of other psychotropic drugs in patients not taking inducers or inhibitors of glucuronidation of lamotrigine Maintain stabilizing dose achieved during mode increasing (200 mg / day in 2 divided doses, the dosage range from 100 mg to 400 mg)
Note: patients taking AEDs pharmacokinetic interaction with lamotrigine is currently unknown, it is recommended to maintain the current dose of lamotrigine and lamotrigine dose selection should be carried out based on clinical response.
* Dose may be increased to 400 mg / day, if necessary.
a) Therapy of lamotrigine after cancellation the combined therapy lamotrigine glucuronidation inhibitors (e.g., valproate)
Immediately after withdrawal valproate target stabilizing drug dose LamictalВ® should be doubled and maintained at that level.
b) Therapy of lamotrigine after discontinuation of combination therapy with inducers of lamotrigine glucuronidation depending on original maintenance dose. This mode should be used when applying phenytoin, carbamazepine, phenobarbital, primidone or other inducers glucuronidation lamotrigine
Dose Lamictal В® should gradually decrease 3 weeks after cancellation inductors glucuronidation.
c) Therapy of lamotrigine after cancellation concomitant psychotropic medications or no inhibitory effect on the induction of lamotrigine glucuronidation
during cancel of concomitant medications should be stored target dose drug Lamictal В®Achieved in the process of raising mode.
Correction of the daily dose of the drug Lamictal В® in patients with bipolar affective disorder after addition of other drugs
No clinical experience by correcting the daily doses of the drug Lamictal В® in patients with bipolar affective disorder after addition of other drugs. However, the following guidelines (Table 5) may be given on the basis of studies on the interaction of drugs.
Table 5. Correction of daily doses of the drug Lamictal В® in patients with bipolar affective disorder after addition of other drugs
Dosage Current anti lamotrigine dose (mg / day) Week 1 Week 2 Week 3 and further
a) Adding inhibitors glucuronidation lamotrigine (e.g., valproic acid formulations) depending on the initial dose of lamotrigine 200mg 100mg Save dose of 100 mg / day
300 mg 150 mg Save dose of 150 mg / day
400 mg 200 mg Save dose 200 mg / d
b) Adding lamotrigine glucuronidation inhibitors in patients not receiving valproic acid formulations, depending on the initial dose of lamotrigine. This mode should be used when applying phenytoin, carbamazepine, phenobarbital, primidone or other inducers glyukuronirovaniya Lamotrigine 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) Addition of other drugs that have no significant inducing or inhibitory effect on glucuronidation of lamotrigine Maintain target dose achieved during mode increasing (200 mg / day range of doses from 100 mg to 400 mg)
Note: patients taking AEDs pharmacokinetic interaction with lamotrigine is currently unknown, is to be used the dosage regimen recommended for the use of lamotrigine in combination with valproate.
Cancel therapy with Lamictal В® in patients with bipolar disorder
during clinical trials abrupt withdrawal of the drug Lamictal В®It did not cause any increase in frequency, severity or change the nature of adverse events compared with placebo. Thus, patients may cancel drug Lamictal В® without a gradual reduction of its dose.
Children and teenagers under 18 years of
drug Lamictal В® is not indicated for the treatment of bipolar disorder in children and adolescents younger than 18 years . Safety and efficacy of lamotrigine in bipolar disorder in patients in this age group have not been assessed. Thus, dosage recommendations can not be given.
General recommendations for dispensing the drug Lamictal В® in special patient populations
Women taking hormonal contraceptives
a) Use of the drug Lamictal В® patients already receiving hormonal contraceptives: despite the fact that oral hormonal contraceptives increase the clearance of lamotrigine, no need for special recommendations for dose escalation regimen of the drug Lamictal В® only on the basis of hormonal contraceptives. Increasing doses mode must conform to the recommended instructions depending on whether the drug is added Lamictal В® to valproate (lamotrigine glucuronidation inhibitors) or inducers of lamotrigine glucuronidation; or drug Lamictal В®It is used in the absence of valproate or inducers glucuronidation lamotrigine (See. Table 1 for epilepsy and Table 3 for bipolar affective disorder).
b) The use of hormonal contraceptives patients already receiving maintenance doses of drug Lamictal В® and receiving inductors glucuronidation of lamotrigine in most cases requires increasing maintenance dose of lamotrigine, but not more than 2 times. In the appointment of hormonal contraceptives is recommended to increase the dose of lamotrigine by 50-100 mg / day each week, depending on the clinical picture. It is not recommended to exceed these figures, if the clinical condition of the patient does not require further increase the drug dose Lamictal В® .
c) Termination of hormonal contraceptives patients already receiving maintenance doses of drug Lamictal В® and receiving inductors glyukuronirovaniya lamotrigine: in most cases requires a reduced dose of the drug Lamictal В® , but not more than 50%. Recommended gradual decrease in the daily dose Lamictal В® 50-100 mg every week (reduction rate must not exceed 25% of the daily dose per week) for 3 weeks, unless the patient's clinical condition requires otherwise.
Use of atazanavir in combination with ritonavir
Despite the fact, that when combined with atazanavir in combination with ritonavir plasma concentrations of lamotrigine decreased, the correction of the dosing of the drug Lamictal В® while the use of atazanavir in combination with ritonavir are required. Increasing doses Lamictal В® should be performed on the basis of the recommendations based on whether lamotrigine is added to valproate therapy (lamotrigine glucuronidation inhibitors) or to therapy inductors glucuronidation of lamotrigine or lamotrigine applied in the absence of valproate or inducers of lamotrigine glucuronidation.
In patients already taking maintenance doses of the drug Lamictal В®and receiving inductors glucuronidation of lamotrigine in the application of atazanavir in combination with ritonavir dose of lamotrigine may need to be increased and the abolition of atazanavir in combination with ritonavir - lower.
Elderly patients (over 65 years)
is not required correction dosing regimen compared to the recommended scheme. The pharmacokinetics of lamotrigine in this age group does not differ from that of adults under the age of 65 years.
Abnormal liver function
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) liver disorders degreerespectively. Increasing and maintenance doses should be adjusted depending on clinical response.
Renal dysfunction
in patients with renal insufficiency drug Lamictal В® should be used with caution. Patients with end-stage renal failure the initial dose of the drug Lamictal В® should be calculated according to the dosing schedule for patients taking AEDs. Patients with a significant decrease in renal function may be recommended to decrease maintenance doses.
SIDE EFFECT
Adverse reactions identified during clinical trials in patients with epilepsy or bipolar disorder were divided into separate sections for specific indications. Additional adverse reactions identified during post-marketing surveillance of both indications for use of included in subsection "post-marketing surveillance." When considering the safety of the drug Lamictal general В® should be familiar with the information contained in all three sections.
Adverse reactions shown below are listed in accordance with a lesion of organs and organ systems, and frequency of occurrence. The frequency of occurrence is defined as follows: very common (1/10?), Common (1/100, <1/10?), Infrequently, rarely (1/10 000, <(1/1000, <1/100?)? 1/1000), very rare (<1/10 000, including isolated cases). Frequency categories were formed on the basis of clinical trials of the drug and post-marketing surveillance .
The frequency of adverse reactions
Epilepsy
following adverse reactions were discovered during clinical trials in patients with epilepsy and in determining the overall safety profile of the drug Lamictal В®They should be considered together with undesirable reactions identified in clinical trials in patients with bipolar disorder and post-marketing the drug.
Skin and subcutaneous tissue: very often - skin rash; rarely - Stevens-Jones
