Lamotrin

General characteristics. Structure:

Active agent: lamotridzhina of 50 mg or 100 mg;

Excipients: cellulose microcrystallic, silicon dioxide colloid anhydrous, polyvinylpirrolidone, sodium carboxymethylstarch, magnesium stearate, lactoses monohydrate.

Pharmacological properties:

Pharmacodynamics. Lamotridzhin - derivative a feniltriazina - antiepileptic means which mechanism of action is caused by blockade of potentsialzavisimy natrium channels of presynaptic membranes of neurons and suppression of excess emission of exciting neurotransmitters, first of all a glutamate (the amino acid playing an important role in development of an epileptic attack).

Pharmacokinetics. After intake drug is quickly and completely absorbed in a digestive tract. The maximum concentration in plasma is reached in 2,5 hours after intake. Meal extends this time, but does not influence extent of absorption. Linkng with proteins of plasma makes 55%. Lamotridzhin is exposed to intensive metabolism, the main metabolite is the N-glucuronide. The elimination half-life at adults averages 29 hours. Children have an elimination half-life less, than at adults. Metabolites are removed generally by kidneys (less than 10% - in not changed look), about 2% - with excrements.

Indications to use:

- Epilepsy 
- As monotherapy or additional therapy of partial and generalized attacks of epilepsy, including toniko-clonic attacks, and also the attacks connected with Lennox-Gasto's syndrome.
- Bipolar disturbances at adults are more senior than 18 years 
- For prevention of development of a depressive episode.

Route of administration and doses:

Epilepsy at adults and children is more senior than 12 years which do not receive sodium Valproatum.
The initial dose at monotherapy by Lamotrin makes 25 mg within 2 weeks once a day; in the next 2 weeks – on 50 mg once a day. Further each one-two weeks it is possible to raise a daily dose on 50–100 mg until the optimum therapeutic effect is reached. Usually supporting daily dose distributed on one or two receptions, makes 100–200 mg. In certain cases achievement of therapeutic effect requires a dose of 500 mg a day.
The recommended scheme of increase in doses for adults and children is more senior
12 years at monotherapy by Lamotrin
I-II week III-IV nedelyapodderzhivayushchy dose

25 mg of 1 times a day
50 mg of 1 times in sutki100-200 mg a day (for one or two receptions). For achievement of a therapeutic dosage effect each 1–2 weeks can be increased by 50–100 mg.
Additional therapy.
For the patients accepting sodium Valproatum in a combination with other antiepileptic drugs or without them the initial daily dose of Lamotrin within two weeks makes 25 mg every other day; within the next two weeks daily accept 25 mg of Lamotrin. In the subsequent each 1-2 weeks raise a dose on 25-50 mg a day until the optimum therapeutic effect is reached. Further the supporting daily dose makes 100-200 mg distributed on one or two receptions.
For the patients accepting the anti-epileptics inducing microsomal enzymes of a liver (Phenytoinum, carbamazepine, phenobarbital, Primidonum) in a combination with other antiepileptic drugs or without them (except for sodium Valproatum), the initial daily dose of Lamotrin within two weeks makes 50 mg once a day; within the next two weeks – on 100 mg the day distributed on two receptions. Further each 1–2 weeks raise a dose no more, than on 100 mg, to obtaining optimum therapeutic effect. A maintenance dose for achievement of optimum therapeutic effect – 200–400 mg a day in 2 receptions. The dose of 700 mg a day can be necessary for some patients for achievement of desirable effect.
The same scheme of increase in doses, as is recommended to the patients accepting antiepileptic drugs which nature of interaction is not known at reception of a lamotridzhin with sodium Valproatum. Children from 2 to 12 years.
For the children accepting sodium Valproatum (in a combination with other antiepileptic drugs or without them), the initial daily dose of Lamotrin within two weeks makes 0,15 mg/kg of body weight once a day; within the next two weeks –
on 0,3 mg/kg of body weight once a day. Further each 1–2 weeks it is possible to increase a dose by 0,3 mg/kg until the optimum effect is reached. The usual supporting daily dose makes 1–5 mg/kg, distributed on 1–2 receptions. The maximum daily dose should not exceed 200 mg. For the children who are accepting the anti-epileptics inducing microsomal enzymes of a liver (Phenytoinum, carbamazepine, phenobarbital, Primidonum), in a combination with other antiepileptic drugs or without them but which are not accepting sodium Valproatum, the initial daily dose of Lamotrin within two weeks is equal to 0,6 mg/kg and is distributed on two receptions a day; within the next two weeks – 1,2 mg/kg a day for two receptions. Further each 1–2 weeks it is possible to increase a dose no more, than by 1,2 mg/kg until the optimum effect is reached. The usual supporting daily dose makes 5–15 mg/kg for 2 receptions. The maximum daily dose should not exceed 400 mg. For achievement of optimum effect at children it is necessary to watch systematically body weight to adjust doses according to changes of body weight of the child.
The same scheme of increase in doses, as is recommended to the patients accepting antiepileptic drugs which nature of interaction is not established at reception of a lamotridzhin with sodium Valproatum.
If the calculated daily dose makes 1–2 mg, it is allowed to apply 2 mg of Lamotrin every other day within the first two weeks. If the calculated dose is less than 1 mg, it is not recommended to accept Lamotrin.
The maintenance dose which corresponds to the top level of the recommended doses can be necessary for children from 2 to 6 years.
Children up to 2 years.
Information concerning use of drug for treatment of children up to 2 years is absent.
Bipolar disturbances (for the purpose of prevention of development of a depressive episode).
The adult 18 years, accepting Lamotrin in combination with antiepileptic drugs, inhibitors of liver enzymes are more senior (including from sodium Valproatum): on 25 mg every other day within 2 weeks, then – 25 mg daily within 2 weeks, further – 50 mg a day in 1 or 2 receptions within 1 week; the stabilizing dose – 100 mg a day in 1 or 2 receptions (changes depending on clinical effect). The maximum dose – 200 mg a day.
Therapy by Lamotrin in combination with the antiepileptic drugs inducing liver enzymes (carbamazepine, phenobarbital) without Valproatum sodium: an initial dose – 50 mg of 1 times a day within 2 weeks, then 100 mg a day in 2 receptions within 2 weeks. The dose is increased by 5th week to 200 mg a day in 2 receptions and to 300 mg a day by 6th week. For achievement of optimum therapeutic effect – 400 mg a day in 2 receptions, since 7th week.

Therapy by Lamotrin and drugs with the unknown nature of interaction (lithium drugs, bupropiony). Monotherapy by Lamotrin: an initial dose – 25 mg a day within 2 weeks, then 50 mg a day in 1 or 2 receptions within 2 weeks. It is necessary to increase a dose to 100 mg a day on the 5th week. The dose of 200 mg a day in 1 or 2 receptions is necessary for achievement of optimum therapeutic effect.
As soon as the daily supporting stabilizing dose is reached, other psychotropic drugs can be cancelled.

Features of use:

At children to whom the diagnosis" epilepsy" is made for the first time, are not recommended to begin treatment with monotherapy by Lamotrin.
If Lamotrin provides good control of attacks, other antiepileptic drugs can be cancelled.
Upon transition to monotherapy by Lamotrin or at additional purpose of other antiepileptic drugs at treatment by Lamotrin it is necessary to consider a possibility of change of pharmacokinetics of a lamotridzhin.
At emergence of rash on skin it is necessary to examine immediately the patient (both the adult, and the child) and to cancel Lamotrin's reception if there are no proofs that skin rash is not connected with administration of drug.
Sharp cancellation of Lamotrin, as well as other antiepileptic means, can provoke increase in frequency of attacks. Unless the condition of the patient demands sharp drug withdrawal (for example, at emergence of rash), Lamotrin's dose needs to be reduced gradually, for at least 2 weeks.
Patients of advanced age (65 years are more senior).
To change a dose there is no need. The pharmacokinetics of a lamotridzhin in this age group does not differ from that at patients of middle age.
Renal failure.
It is necessary to use drug for treatment of patients with a renal failure with care.
Liver failure.
The initial dose, increase in doses and maintenance dose have to be reduced in general by 50% at patients with moderate and for 75% – with a heavy liver failure. Increase in doses and a maintenance dose korrigirutsya according to clinical effect.
Pregnancy.
Information concerning safety of use of Lamotrin during pregnancy is insufficient; at the solution of a question concerning purpose of drug during pregnancy it is necessary to estimate the expected advantage for mother and possible risk for a fruit.
Lactation.
Information concerning Lamotrin's use in the period of a lactation is limited.
Preliminary data show what ламотриджин gets into breast milk in concentration which reach 40–60% of its concentration in plasma. At some babies whose mothers accepted ламотриджин the level of a lamotridzhin in blood serum reached levels at which the pharmacological effect was possible. Therefore the advantage of feeding has to be compared by a breast with possible risk of emergence of side effects at the child.
Influence on ability to manage motor transport and mechanisms.
During treatment by Lamotrin emergence of dizziness and a diplopia is possible. Patients are recommended to consult with the doctor concerning a possibility of driving and work with moving mechanisms against the background of Lamotrin's use since reaction to treatment by anticonvulsant drugs is characterized by individual differences.

Side effects:

Skin and hypodermic fabrics: very often – skin rash; seldom – Stephens-Johnson's syndrome; very seldom – a toxic epidermal necrolysis. The probability of emergence of rash is, seemingly, closely connected with high doses, excessively in high gear increases in doses and with a concomitant use of Valproatum.
At children the risk of developing of heavy skin rash is higher, than at adults. At children the first symptoms of skin rash can be mistakenly regarded as symptoms of an infection therefore doctors have to pay special attention to a possibility of development of side effect on drug at children who within the first 8 weeks of administration of drug have a skin rash and fever.
Blood and lymph: very seldom – a neutropenia, a leukopenia, anemia, thrombocytopenia, a pancytopenia, aplastic anemia, an agranulocytosis.
Immune system: very seldom - a hypersensitivity syndrome (high temperature, a lymphadenopathy, a face edema, disturbances from a liver and blood, the disseminated intravascular coagulation (DIC) and multiple insufficiency of bodies).
Skin rash is a component of the syndrome of hypersensitivity proceeding with various degrees of severity, sometimes with development of DVK and multiple insufficiency of bodies.
It is necessary to remember that early manifestations of raised
sensitivity (for example high temperature, a lymphadenopathy) can arise also without rash. At these symptoms it is necessary to inspect repeatedly the patient and to stop treatment by Lamotrin if development of symptoms cannot be explained with other reason.
Mental disturbances: often – irritability, infrequently – aggression, it is very rare - a tic, hallucinations and confusion of consciousness.
Nervous system: very often – a headache, dizziness; often – a nystagmus, a tremor, drowsiness, sleeplessness; infrequently – an ataxy; very seldom – alarming excitement, balance loss, motive frustration, an exacerbation of a disease of Parkinson, extrapyramidal frustration, a choreoathetosis, increase of convulsive attacks.
Organs of sight: very often – a diplopia, decrease in visual acuity; seldom – conjunctivitis.
Digestive tract: often – nausea, vomiting, diarrhea.
Gepatobiliarny system: very seldom – increase in indicators of functional hepatic trials, an abnormal liver function, a liver failure.
Abnormal liver functions are usually connected with hypersensitivity reactions, however cases without visible signs of hypersensitivity take place.
Musculoskeletal system and connecting fabrics: very seldom – symptoms of a system lupus erythematosus.
General disturbances: often – fatigue.

Interaction with other medicines:

There are no authentic proofs that ламотриджин can cause clinically significant stimulation or oppression of the oxidizing enzymes of a liver participating in metabolism of medicines. Lamotridzhin can induce own metabolism, however this effect moderate and has no considerable clinical effects.
Lamotridzhin does not change concentration of ethinylestradiol and levonorgestrel in plasma after reception of oral contraceptives. However, as well as at other types of long therapy, at the patients accepting oral contraceptives changes of a menstrual cycle are possible.
Valproatum oppressing microsomal enzymes of a liver slows down metabolism of a lamotridzhin and increases the period of its semi-removal approximately twice.
There are messages on by-effects from the central nervous system (dizziness, an ataxy, a diplopia, reduction of visual acuity and nausea) at patients who accepted carbamazepine along with lamotridzhiny. These phenomena usually disappear at reduction of a dose of carbamazepine.
Though cases of change of concentration of other antiepileptic drugs in plasma are described, control researches showed what ламотриджин does not influence concentration in plasma of other antiepileptic means. Results of the researches in vitro showed what ламотриджин does not influence linkng of other antiepileptic drugs with serum proteins.
Antiepileptic drugs (Phenytoinum, carbamazepine, phenobarbital and Primidonum) inducing microsomal enzymes of a liver strengthen metabolism of a lamotridzhin.

Contraindications:

Hypersensitivity to drug components.

Overdose:

Overdose symptoms: dizziness, headache, drowsiness, vomiting, nystagmus, ataxy, disturbance of consciousness, lump.
Treatment: for the purpose of reduction of absorption of drug it is necessary to wash out a stomach and to give to the patient enterosorbents. The patient needs to be hospitalized in intensive care unit for carrying out the corresponding symptomatic and maintenance therapy.

Storage conditions:

To store in unavailable to children, the dry place at a temperature from 15 to 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging, on 3 planimetric strip packagings in a pack cardboard.