LAMICTAL PILLS 5MG

Antiepileptic drug. Lamotrigine is a blocker of potential-dependent sodium channels. In the culture of neurons, it causes a potential-dependent blockade of continuously repeated 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 the depolarization caused by glutamate.

The effectiveness of Lamictal in preventing mood disorders in patients with bipolar disorders has been demonstrated in two fundamental clinical studies. As a result of a combined analysis of the obtained results, it was found that the duration of remission, defined as the time until the first episode of depression occurred and before the first mania / hypomania / mixed episode after stabilization, was longer in the lamotrigine group compared to placebo. The duration of remission is more pronounced for depression.

Pharmacokinetics

Suction

After oral administration, lamotrigine is rapidly and completely absorbed from the gastrointestinal tract, practically without being subjected to the first-pass metabolism of the system. WITHmax in plasma is reached approximately 2.5 hours after taking the drug.Time to reachmax slightly increased after a meal, but the degree of absorption remains unchanged. The pharmacokinetics of lamotrigine is linear when taking a single dose of up to 450 mg (the highest dose studied). There are significant inter-individual fluctuations in the maximum concentration in the equilibrium state, however, with rare fluctuations in each individual person.

Distribution

Lamotrigine binds to plasma proteins by approximately 55%. It is unlikely that the release of the drug from the connection with the protein could lead to the development of a toxic effect. Vd is 0.92-1.22 l / kg.

Metabolism

The enzyme uridine diphosphate glucuronyltransferase (UDP-glucuronyltransferase) is involved in lamotrigine metabolism. Lamotrigine slightly increases its own metabolism, depending on the dose.

Removal

In healthy adults, lamotrigine clearance in a 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 intestines. Clearance and T1/2 do not depend on the dose. T1/2 in healthy adults, it averages from 24 hours to 35 hours. In patients with Gilbert's syndrome, there was a decrease in the clearance of the drug by 32% compared with the control group, which, however, did not go beyond the normal values ​​for the general population. On t1/2 Lamotrigine is greatly influenced by co-medications. Average t1/2 decreases to approximately 14 hours while taking it with drugs that stimulate glucuronization, such as Carbamazepine and phenytoin, and rises on average to 70 hours when taken together with valproate.

Pharmacokinetics in special clinical situations

In children, lamotrigine clearance in terms of body weight is higher than in adults; it is highest in children under 5 years old. In children T1/2 lamotrigine is usually less than in adults. Its average value is approximately 7 hours while taking it with drugs that stimulate glucuronization, such as carbamazepine and phenytoin, and rises on average to 45-50 hours when taken together with valproate.

Clinically significant differences in the clearance of lamotrigine in elderly patients compared with young patients were not found.

In case of kidney dysfunction, the initial dose of lamotrigine is calculated in accordance with the standard regimen of antiepileptic drug administration. Dose reduction may be required only with a significant decrease in renal function.

Initial, increasing and maintenance doses should be reduced by approximately 50% in patients with moderate hepatic insufficiency (class B on the Child-Pugh scale) and 75% in patients with severe hepatic insufficiency (class C on the Child-Pugh scale). Increasing the dose and maintenance dose should be adjusted depending on the clinical effect.

Indications

Epilepsy

for adults and children over 12 years old

- epilepsy (partial and generalized seizures, including tonic-clonic convulsions, as well as seizures in Lennox-Gastaut syndrome) as part of combination therapy or monotherapy.

for children from 2 to 12 years

- epilepsy (partial and generalized seizures, including tonic-clonic convulsions, as well as seizures with Lennox-Gasto syndrome) as part of combination therapy (after achieving control of epilepsy against the background of combination therapy, concomitant anti-epileptic drugs can be canceled and lamotrigine should be continued in monotherapy);

- monotherapy typical absensov.

Bipolar disorder

for adults (18 years and older)

- to prevent mood disorders (depression, mania, hypomania, mixed episodes).

Dosage and administration

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 increasing the dose to 50 mg 1 time / day for the next 2 weeks. Then the dose should be increased by 50-100 mg every 1-2 weeks, until it reaches the optimal therapeutic effect. The standard maintenance dose to maintain the optimal therapeutic effect is 100-200 mg / day in 1-2 doses. Some patients to achieve a therapeutic effect require the appointment of Lamictal at a dose of 500 mg / day.

AT combination therapy with the combined use of Lamictal with valproic acid preparations in combination with other antiepileptic drugs (PEP) or without them The initial dose of Lamictal is 25 mg every other day for the first 2 weeks; in the future - 25 mg 1 time per day for the next 2 weeks. Then the dose should be increased to 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.

AT the composition of combination therapy with concomitant therapy with AED or other drugs that induce glucuronization of lamotrigine (phenytoin, carbamazepine, phenobarbital and primidone), with or without other AEDs (with the exception of valproic acid) The initial dose of Lamictal is 50 mg 1 time / day for the first 2 weeks, then 100 mg / day for 2 doses in the next 2 weeks. Then the dose is increased by 100 mg every 1-2 weeks, until the optimum therapeutic effect is reached. The standard 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.

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

Because of the risk of rash, the initial dose of the drug and the recommended mode of increasing doses should not be exceeded.

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

Children aged 2 to 12 years

It should be noted that the exact conduct of initial therapy with Lamictal pills of 5 mg according to the proposed dosing regimen is not possible if the child’s body weight is less than 17 kg Most likely, children between the ages of 2 and 6 will need the highest maintenance doses.

Initial dose of lamictal when monotherapy of typical absences is 0.3 mg / kg body weight / day in 1 or 2 doses in the first 2 weeks, followed by increasing the dose to 0.6 mg / kg / day in 1 or 2 doses in the next 2 weeks. Then the dose should be increased to a maximum of 0.6 mg / kg every 1-2 weeks until the optimum therapeutic effect is achieved. The usual maintenance dose to achieve the optimal therapeutic effect ranges from 1 to 10 mg / kg / day in 1 or 2 doses, although some patients with typical absences need higher doses to achieve a therapeutic effect.

AT the composition of combination therapy with the use of Lamictal with valproic acid preparations in combination with other AEDs or without them The initial dose of Lamictal is 0.15 mg / kg of body weight 1 time / day for the first 2 weeks, and later - 0.3 mg / kg 1 time / day for the next 2 weeks. Then the dose should be increased by 0.3 mg / kg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose in this case is 1-5 mg / kg / day in 1-2 doses. The maximum daily dose is 200 mg.

AT composition of combination therapy with concomitant therapy with AED or other drugs,induce lucotrigine glucuronidation (phenytoin, carbamazepine, phenobarbital and primidone), in combination with other AEDs or without them (except for valproic acid preparations) The initial dose of Lamictal is 0.6 mg / kg / day in 2 divided doses for the first 2 weeks, and further, 1.2 mg / kg / day in 2 divided doses in the next 2 weeks. Then, the dose should be increased to a maximum of 1.2 mg / kg / day every 1-2 weeks until the optimum therapeutic effect is achieved. The standard maintenance dose at which the maximum therapeutic effect is achieved is 5-15 mg / kg / day in 2 doses. The maximum daily dose is 400 mg.

AT combination therapy with oxcarbazepine without any other inducers or inhibitors of lamotrigine glucuronization The initial dose of Lamictal is 0.3 mg / kg of body weight 1 or 2 times / day during the first 2 weeks, further 0.6 mg / kg / day in 1 or 2 doses over the next 2 weeks. The dose is then increased to a maximum of 0.6 mg / kg every 1-2 weeks, until the optimum therapeutic effect is reached. The standard maintenance dose is 1-10 mg / kg / day in 1 or 2 doses. The maximum dose is 200 mg / day.

To be sure that the therapeutic dose is maintained, it is necessary to control the body weight of the child and adjust the dose of the drug when it changes.

Because of the risk of rash, the initial dose of the drug and the recommended mode of increasing doses should not be exceeded.

Table 2.The recommended dosing regimen for treating 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 children under 2 years old.

When canceling concomitant antiepileptic drugs for switching to Lamictal monotherapy or when prescribing other medicines or AED while taking Lamictal, it must be taken into account that this may affect the pharmacokinetics of lamotrigine.

Bipolar disorder

Adult patients over 18 years old

Due to the risk of a rash, the initial dose of the drug and the subsequent mode of increasing doses should not be exceeded.

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 3), after which, if indicated, you can cancel other psychotropic and / or antiepileptic drugs (Table 4).

Table 3. Recommended dosage regimen to achieve a supporting daily stabilizing dose for adults (over 18) for bipolar disorders.