Description
Release form
Tablets
Packing
15 pcs. – blister packs (2) – packs of cardboard.
10 pcs – blister packs (3) – packs of cardboard.
Pharmacological Action
Lamotrigine is a voltage-gated sodium channel blocker. Reduces the pathological activity of neurons without inhibiting their function. It stabilizes neuronal membranes by influencing the Na + channels, blocks the excess release of glutamate, without reducing its normal release.
Pharmacokinetics
Absorption. Lamotrigine is rapidly and completely absorbed from the intestine, practically without undergoing a presystemic metabolism of the first passage. The maximum plasma concentration is reached after approximately 2, 5 hours after oral administration of the drug. The time to reach maximum concentration slightly increases after a meal, but the degree of absorption remains unchanged. Pharmacokinetics is linear when taking a single dose of up to 450 mg (the largest dose studied). Significant interindividual fluctuations of the maximum concentration in the equilibrium state are observed, 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 binding to the protein could lead to the development of a toxic effect. The volume of distribution is 0.92-1.22 l / kg.
Metabolism. In the metabolism of lamotrigine, the enzyme uridine diphosphate glucuronyl transferase (UDP-glucuronyl transferase) is involved.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 P450 cytochrome system.
Withdrawal. In healthy adults, clearance of lamotrigine 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% – by the intestines. Ground clearance and elimination half-life are dose-independent. The half-life in healthy adults is on average from 24 hours to 35 hours. In patients with Gilbert’s syndrome, a decrease in clearance of the drug was observed by 32% compared with the control group, which however, it did not go beyond the limits of normal values for the general population.
Co-administration of drugs has a great influence on the half-life of lamotrigine.
The average elimination half-life decreases to about 14 hours when given concomitantly with glucuronidation-stimulating drugs, such as carbamazepine and phenytoin, and rises to an average of 70 hours when coadministered with valproic acid.
Special patient groups
Children
In children, the clearance of lamotrigine, based on body weight, is higher than in adults, it is highest in children under 5 years of age. In children, the half-life of lamotrigine is usually shorter than in adults. Its average value is approximately 7 hours when administered concurrently with drugs that stimulate glucuronidation, such as carbamazepine and phenytoin, and increases on average up to 45-50 hours when used together with valproic acid.
Elderly patients
No clinically significant differences in lamotrigine clearance in elderly patients compared with younger patients were found.
Patients with impaired renal function
In case of impaired renal function, the initial dose of lamotrigine is calculated in accordance with the standard antiepileptic drug regimen. Dose reduction may be required only with a significant decrease in renal function.
Patients with impaired liver function
Initial, increasing, and maintenance doses should be reduced by approximately 50% in patients with moderate hepatic insufficiency (Child-Pugh stage B) and 75% in patients with severe hepatic insufficiency (stage C by Child Pugh). The dose increase and maintenance dose should be adjusted depending on the clinical effect.
Clinical efficacy in patients with bipolar disorder
Effectiveness in preventing mood disorders in patients with bipolar disorder has been demonstrated in two basic clinical trials.
As a result of a combined analysis of the results, it was found that the duration of remission, defined as the time until the first episode of depression and before the first episode of mania / hypomania / mixed after stabilization, was longer in the lamotrigine group compared with placebo. The duration of remission is more pronounced for depression.
Indications
Epilepsy
Adults and children (over 12 years old)
epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures with Lennox-Gastaut syndrome) as part of combination therapy or monotherapy.
Children from 3 to 12 years old
epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures with Lennox-Gastaut syndrome) as part of combination therapy. After achieving control of epilepsy in combination therapy, concomitant antiepileptic drugs (PEP) can be canceled and lamotrigine continued in monotherapy.
Monotherapy of typical absences.
Bipolar Disorders
Adults (18 years of age and older)
to prevent mood disorders (depression, mania, hypomania, mixed episodes) in patients with bipolar disorder.
Contraindications
Hypersensitivity to lamotrigine or any component of the drug. Children’s age up to 3 years (for this dosage form).
Precautions
Chronic renal failure, allergic reactions, or skin rashes with a history of other antiepileptic drugs.
Use during pregnancy and lactation
Clinical data on the safety of lamotrigine during pregnancy and lactation are insufficient.
When deciding whether to use during pregnancy, the expected benefit of the therapy for the mother and the potential risk to the fetus should be compared.
Preliminary data show that lamotrigine passes into breast milk at a concentration of 40-45% of the plasma concentration. In a small number of infants whose mothers received lamotrigine, no side effects were noted.
Special instructions
Use with caution in patients with renal failure.
Lamotrigine should not be used in elderly patients.
When severe allergic skin reactions occur, lamotrigine should be discontinued.
With the sudden cancellation of lamotrigine, an increase in the manifestations of epilepsy is possible, so it is necessary to gradually stop treatment, reducing the dose for 2 weeks.
With simultaneous use with carbamazepine, dizziness, diplopia, ataxia, visual impairment, and nausea are possible. These phenomena, as a rule, pass with a decrease in the dose of carbamazepine.
Lamotrigine should not be used in children under 2 years of age.
Effect on the ability to drive vehicles and control mechanisms
During the treatment period, a slowdown in the rate of psychomotor reactions is observed. This must be taken into account by persons involved in potentially hazardous activities that require increased attention and rapid psychomotor reactions.
Composition
Active substance: one tablet contains lamotrigine 200 mg.
Excipients: low-substituted hyprolose, calcium carbonate, sodium carboxymethyl starch, colloidal silicon dioxide, magnesium aluminum silicate, magnesium stearate, sodium saccharinate, povidone, microcrystalline cellulose, blackcurrant flavor.
Dosage and administration of
When administered orally for adults and children over 12 years of age, the initial single dose is 25-50 mg, maintenance doses are 100-200 mg / day. In rare cases, doses of 500-700 mg / day may be required.
For children aged 2 to 12 years, the initial dose is 0.2-2 mg / kg / day, the maintenance dose is 1-15 mg / kg / day.
The maximum daily dose for children aged 2 to 12 years, depending on the treatment regimen used, is 200-400 mg.
The frequency of administration, the intervals between doses with increasing doses depend on the treatment regimen used, the patient’s response to the treatment.
Side effects
From the side of the central nervous system: headache, dizziness, drowsiness, sleep disturbances, feeling tired, aggressive, confused.
From the digestive system: nausea, impaired liver function.
From the hemopoietic system: leukopenia, thrombocytopenia.
Allergic reactions: skin rash (usually maculopapular), angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, lymphadenopathy.
Drug Interactions
When used simultaneously with anticonvulsants, metabolism inducers in the liver (including phenytoin, carbamazepine, phenobarbital, primidone), lamotrigine metabolism is accelerated.
With the simultaneous use of lamotrigine and carbamazepine or phenytoin, a decrease in T1 / 2 of lamotrigine occurs. There are reports of dizziness, ataxia, diplopia, blurred vision and nausea in patients taking carbamazepine after starting treatment with lamotrigine.
Due to the inhibition of microsomal liver enzymes under the influence of sodium valproate, while the use of lamotrigine is slowed down, T1 / 2 lamotrigine increases.
Overdose
Single dose administration exceeding maximum therapeutic doses of 10-20 times has been reported. Overdose was manifested by symptoms including nystagmus, ataxia, and coma impairment.
Treatment: hospitalization and appropriate symptomatic therapy. In case of recent (less than 2 hours) administration of the drug, it is necessary to wash the stomach.
Storage Conditions
In a dark place, at 15-25 ° C.
Keep out of the reach and sight of children.
Shelf life
3 years.
Do not use after the expiration date printed on the package.
Deystvuyushtee substance
lamotrigine
Conditions of release from drugstores
Prescription
Formulation
tablets
Possible product names
SEISAR 0.2 N30 TABL
Seizar tab 200mg x 30
SEISAR TAB. 200MG No. 30
SEISAR TABL. 200 mg N30
seisar tablets 200 mg, 30 pcs.
Alkaloid AD Skopye, Macedonia
