Lamotrigine

Pharmacological properties

lamotrigine is an anticonvulsant drug that blocks the voltage-dependent sodium channels of presynaptic membranes of neurons in the phase of slow inactivation. blocks the excessive release of neurotransmitters, mainly glutamic acid, an “exciting” amino acid that plays a key role in the development of epileptic seizures.

Pharmacokinetics After oral administration, it is rapidly and completely absorbed in the digestive tract. C_max in blood plasma is reached after about 2.5 hours, the time of its achievement can increase after eating without changing the degree of absorption. Has a linear pharmacokinetic profile when taken up to 450 mg. Plasma protein binding is about 55%. Distribution volume - 0.92–1.22 l / kg. It is metabolized in the liver with the participation of the enzyme glucuronyl transferase with the formation of N-glucuronide. Adult clearance is on average 39 ± 14 ml / min, T_½ - 29 hours, regardless of the dose of the drug. It penetrates into breast milk in a concentration reaching 40-60% of the concentration in blood plasma. It is excreted mainly in the form of metabolites (glucuronides) and partially (10%) unchanged with urine, about 2% - with feces.

With concomitant use with drugs inducing microsomal oxidative liver enzymes, T_½ decreases to about 14 hours, when combined with valproic acid preparations (inhibit microsomal oxidative enzymes of the liver) - increases to 70 hours. Lamotrigine does not affect the pharmacokinetics of other antiepileptic drugs.

In children under 12 years of age, lamotrigine clearance calculated by body weight is higher than in adults, T_½ - less. The highest clearance in children under the age of 5 years. In patients of young and old age, significant differences in clearance are not observed.

In patients with chronic renal failure, the average clearance is 0.42 ml / min / kg, in patients on hemodialysis, 0.33 ml / min / kg between hemodialysis sessions and 1.57 ml / min / kg during hemodialysis ; average values ​​of T_½ - 42.9; 57.4 and 13 hours, respectively. During a 4-hour hemodialysis session, about 20% of lamotrigine is excreted.

In patients with impaired liver function of mild, moderate and severe degrees (Child, Pugh classes A, B and C), the average clearance values ​​are 0.31; 0.24 and 0.1 ml / min / kg, respectively.

Indications

Epilepsy in adults and children over the age of 12 years (monotherapy or additional therapy for partial and generalized seizures, including tonic-clonic seizures, as well as seizures associated with Lennox-gasto syndrome).

Epilepsy in children aged 2-12 years (as an additional therapy for partial and generalized seizures, including tonic-clonic seizures, as well as seizures associated with Lennox-Gastaut syndrome).

After achieving seizure control, you can stop taking additional drugs and continue with Epileptal monotherapy.

Monotherapy of typical absences.

Bipolar Disorders (adults): to prevent phases of emotional disturbances, mainly by preventing depressive episodes.

Application

Epileptal tablets should be swallowed whole without chewing or breaking.

If the prescribed dose of Epileptal does not correspond to the amount of active substance in the tablet, it is necessary to prescribe the lowest dose that corresponds to the whole tablet.

Epilepsy

Monotherapy for adults and children from the age of 12 years (tab. 1). The initial dose of Epileptal is 25 mg once a day for 2 weeks, then take 50 mg / day for the next 2 weeks, then the dose is increased by 50-100 mg every 1-2 weeks until the optimal effect is achieved. The usual maintenance dose is 100-200 mg / day for 1-2 doses. For some patients, a dose of 500 mg / day may be required.

Children aged 2-12 years (table. 2). The initial dose of Epileptal for the treatment of typical absences is 0.3 mg / kg of body weight per day in 1-2 doses for 2 weeks, then 0.6 mg / kg of body weight per day in 1-2 doses is taken over the next 2 weeks . Subsequently, the dose is increased by 0.6 mg / kg body weight every 1-2 weeks until the optimal effect is achieved. The usual maintenance dose is 1–10 mg / kg body weight per day in 1–2 doses. For some patients, a higher dose may be required.

Due to the risk of rash, the initial dose and the rate of further dose increase should not be exceeded.

Combination therapy

Adults and children over the age of 12 years (see table. 1). For patients taking valproate (alone or with other antiepileptic drugs), the initial dose of Epileptal is 25 mg every other day for 2 weeks, then 25 mg daily for the next 2 weeks. After this, 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 usual maintenance dose is 100–200 mg / day in 1–2 doses.

For patients taking other antiepileptic drugs or other drugs, lamotrigine glucuronidation inducers, in combination with or without other antiepileptic drugs (with the exception of sodium valproate), the initial dose of Epileptal is 50 mg once a day for 2 weeks, then 100 mg / day in 2 doses for 2 weeks. Then the dose must be increased (by a 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. For some patients, a dose of 700 mg / day may be required.

For patients who take other drugs that do not significantly induce or inhibit lamotrigine glucuronidation (see INTERACTIONS), the initial dose of Epileptal is 25 mg once a day for 2 weeks, then 50 mg once a day for the next 2 weeks . After this, the dose must be increased (by a maximum of 50–100 mg / day) every 1-2 weeks until the optimal therapeutic effect is achieved. The usual maintenance dose is 100–200 mg / day in 1–2 doses.

Patients who take antiepileptic drugs whose interaction with lamotrigine is unknown, it is recommended to apply such a treatment regimen as for patients who take lamotrigine with valproate. Due to the risk of rash, the initial dose and the rate of further dose increase should not be exceeded.

Children aged 2-12 years (see table. 2). For children who receive sodium valproate in combination with or without other antiepileptic drugs, the initial dose of Epileptal is 0.15 mg / kg body weight per day in 1 dose for 2 weeks, then 0.3 mg / kg body weight per day in 1 dose over the next 2 weeks. Further, the dose must be increased (by a maximum of 0.3 mg / kg body weight) every 1-2 weeks until the optimal therapeutic effect is achieved.The maintenance dose is 1–5 mg / kg body weight in 1–2 doses (maximum - 200 mg / day).

For children who take other antiepileptic drugs or other drugs, lamotrigine glucuronidation inducers, in combination with or without other antiepileptic drugs (excluding sodium valproate), the initial dose of Epileptal is 0.6 mg / kg body weight per day in 2 divided doses 2 weeks, then 1.2 mg / kg of body weight per day for the next 2 weeks. In the future, the dose should be increased (by a maximum of 1.2 mg / kg body weight) every 1-2 weeks until the optimal therapeutic effect is achieved. The average maintenance dose is 5-15 mg / kg of body weight per day in 2 doses (maximum 400 mg / day).

For children who take other drugs that do not significantly induce or inhibit glucuronidation of lamotrigine (see INTERACTIONS), the initial dose of Epileptal is 0.3 mg / kg of body weight per day in 1-2 doses for 2 weeks, then 0. 6 mg / kg body weight per day in 1-2 doses over the next 2 weeks. After this, the dose must be increased (by a maximum of 0.6 mg / kg body weight) every 1-2 weeks until the optimal therapeutic effect is achieved. The usual maintenance dose is 1–10 mg / kg body weight per day in 1–2 doses. The maximum dose is 200 mg / day.

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