Lamolep pills 25mg №30

Composition

One pill contains the active ingredient 25 mg, 50 mg or 100 mg of lamotrigine.

Pharmacological properties

Pharmacodynamics

Stabilizes the voltage-dependent sodium tubules of the cell membrane and blocks the release of neurotransmitters, mainly glutamate. Being

glutamate plays a key role in the occurrence of epileptic seizures by an activating amino acid.

Pharmacokinetics

Suction:

quickly and completely absorbed in the intestine, not significantly undergoing the primary metabolism in the liver. 2.5 hours after ingestion, the maximum plasma concentration is reached. Food intake slows down the process of absorption, but does not affect its effectiveness. Single-dose pharmacokinetics, not

exceeding 450 mg is linear. The concentration in the saturation stage is a distinct individual character.

Distribution:

bioavailability - 98%. Communication with proteins is 55%. The volume of distribution is 0.92-1.22 l / kg body weight.

Metabolism is carried out in the liver. Among all metabolites, N-glucuronides are predominant. To a moderate degree, dose-dependent, lamotrigine induces its own metabolism.

Excretion:

the average clearance at the saturation stage in healthy adults is 39 ± 14 ml / min. Output together

with urine in the form of a conjugate of glucuronide, less than 10% - unchanged.About 2% of the active substance and degradation products are derived along with feces.

The clearance and half-life do not depend on the dosage, T1 / 2 in healthy volunteers - 24-35 hours. It is excreted in breast milk.

Childhood:

clearance, calculated per kg of body weight, in children is higher than in adults, is highest up to 5 years of age. The half-life is usually shorter than in adults, while taking an enzyme inducer is 7 hours, and when taking valproate sodium, it is 45-60 hours.

Elderly age:

Lamotrigine clearance of young and elderly patients with epilepsy is minimally different from each other.

Indications for use

Epilepsy

Adults and children over 12 years old:

as monotherapy or in combination with other antiepileptic drugs for the treatment of partial and generalized seizures, including tonic-clonic convulsions and convulsive seizures in Lennox-Gastaut syndrome.

Children over 2 years:

in combination with other antiepileptic drugs for the treatment of partial and generalized seizures, including tonic-clonic

seizures and convulsive seizures in Lennox-Gastaut syndrome.

Bipolar disorder

Patients older than 18 years:

prevention and treatment, mainly episodes of depression.

Contraindications

Hypersensitivity to any of the components of the drug; children's age (up to 2 years); pregnancy; lactation period.

Carefully

Renal failure (due to possible cumulation of the glucuronide metabolite).It is necessary to carefully prescribe lamotrigine to children as a drug of choice for monotherapy in the treatment of epilepsy.

Pregnancy and lactation period

Pregnancy.

Acceptance of lamotrigine during pregnancy is contraindicated unless

The expected benefit to the pregnant woman is greater than the potential risk to the fetus.

Lactation.

The number of observations during the breastfeeding period is limited. The concentration of lamotrigine in breast milk is 40-60% of the plasma concentration. You should carefully weigh the benefits of breastfeeding while taking the drug and the likelihood of side effects in an infant.

Dosage and administration

Epilepsy Monotherapy

Adults and children over 12 years old: initial dose for 2 weeks, 25 mg once a day; in the next 2 weeks, 50 mg once a day. Further

every 1-2 weeks, you can increase the daily dose by 50-100 mg until the optimal effect is achieved. Usually supportive daily

a dose distributed over one or two doses is 100–200 mg. In isolated cases, the desired effect is provided with doses of 500 mg / day.

Combination Therapy for Epilepsy

Adults and children over 12 years of age: for patients taking sodium valproate in combination with other antiepileptic drugs or without them, the initial dose of lamotrigine for two weeks is 25 mg every other day; over the next two weeks, 25 mg is taken daily, once a day.In the next every 1-2 weeks, the dose can be increased by 25-50 mg

until the optimum effect is achieved.

The usual supporting daily dose is 100-200 mg in 1-2 doses.

Patients taking antiepileptic drugs, which is an enzyme inducer (phenytoin, Carbamazepine, phenobarbital, primidone), in combination with other antiepileptic drugs or without them,

but not taking sodium valproate, the initial daily dose of lamotrigine for two weeks is 50 mg once a day; over the next two weeks, 100 mg per day, for 2 doses. In the future, every 1-2

weeks, you can increase the dose of no more than 100 mg to obtain the optimal effect. The usual supporting daily dose is 200-400 mg in 1-2 doses.

In rare cases, 700 mg / day is required.

In the case of treatment with antiepileptic drugs, the pharmacokinetic interaction of which with lamotrigine is unknown, the dose of lamotrigine should be increased in smaller doses according to the scheme described for receiving sodium valproate.

For children from 2 to 12 years old who take sodium valproate in combination with other antiepileptic drugs or without them, the initial daily dose of lamotrigine for two weeks is 0.15 mg / kg body weight, one

once a day; over the next two weeks, 0.3 mg / kg of body weight once a day. Then every 1-2 weeks you can increase the dose by 0.3 mg / kg until the optimal effect is achieved.Normal supportive

the daily dose is 1-5 mg / kg for 1-2 doses. The maximum daily dose should not exceed 200 mg.

Children taking an antiepileptic agent an enzyme-inducer (phenytoin, carbamazepine, phenobarbital, primidone) in combination with other antiepileptic drugs or without them, but not taking

sodium valproate, the initial daily dose of lamotrigine for two weeks should be 0.6 mg / kg for 2 doses per day; over the next two weeks, 1.2 mg / kg / day in 2 divided doses. Then every 1-2 weeks

You can increase the dose by no more than 1.2 mg / kg until the optimum effect is achieved.

The usual supporting daily dose is 5-15 mg / kg in two doses. The maximum daily dose should not exceed 400 mg.

In the case of treatment with antiepileptic drugs, the pharmacokinetic interaction of which with lamotrigine is unknown, the dose of lamotrigine should be increased in smaller doses according to the scheme described for receiving sodium valproate.

Bipolar disorder

In the case of bipolar disorders, lamotrigine is prescribed to prevent episodes of depression. In the case of short-term treatment, the maintenance dose of lamotrigine should be increased gradually,

for 6 weeks, until the patient's condition stabilizes. Following this, with the appropriate clinical picture of the disease, you can stop taking a psychotropic and / or other antiepileptic drug.

For the prevention of episodes of mania may require adjuvant therapy, because the effectiveness of lamotrigine in the case of mania and manic states is ambiguous.

Dosage when administered in combination with enzyme inhibitors, for example. sodium valproate

For patients taking an enzyme inhibitor, for example. sodium valproate, the initial dose of lamotrigine for two weeks is 25 mg / kg every other day; over the next two weeks, 25 mg / kg once a day. In the fifth week, the daily dose should be increased to 50 mg, distributed to 1-2 doses. Usually a dose is required to achieve the optimal therapeutic effect.

100 mg / day (for 1-2 doses), supporting a daily dose of 1-5 mg / kg for 1-2 doses. The maximum daily dose should not exceed 200 mg.

Dosage when administered in combination with enzyme inducers, for example. carbamazepine and phenobarbital, but without sodium valproate.

For patients taking antiepileptic agent-enziminuktor (carbamazepine, phenobarbital), but not taking sodium valproate, the initial daily dose of lamotrigine for two weeks is

50 mg once daily; then, over the next two weeks, 100 mg / day for 2 doses per day. On the 5th week, the daily dose should be increased to 200 mg (in two doses). On the 6th week, the daily dose can reach 300 mg, on the 7th week, the daily dose, divided into two doses, can reach 400 mg.

In the case of treatment with an antiepileptic agent, the pharmacokinetic interaction of which with lamotrigine is unknown or that is possible, and

also in the case of lamotrigine monotherapy, the initial daily dose for the first 2 weeks is 25 mg once a day; over the next two weeks - 50 mg in 2 divided doses. On the 5th week, the dose is increased to 100 mg.

Usually the optimal daily dose is 200 mg in 1-2 doses. The maximum dose may be 400 mg / day. After discontinuation of the enzyme inhibitor (eg, valproate), prescribed in combination, the initial stabilizing dose of lamotrigine should be doubled and continue to be prescribed after discontinuation of valproate. After cancellation of the enzyme inducer (eg, carbamazepine), administered in combination, the dose of lamotrigine should be

gradually, over 3 weeks, reduce.

Children's age (<18 years): the efficacy and safety of the drug in this age group has not been studied, therefore, there are no recommendations on dosage.

General dosage recommendations:

To accept inside, without chewing and washing down with a small amount of water.

In the case when the calculated dose includes an incomplete tablet, a dose equal to the whole number of tablets should be prescribed.

Advanced age (> 65 years old):

age adjustment dose is not required, because the pharmacokinetics of the drug is not significantly different from that observed in the young population.

Liver failure:

with moderate severity of liver failure (stage B on Child-Pag), the initial and maintenance doses, as well as dose titration, should be 50% lower than usual; in stage C (according to Child-Pag), i.e.in severe severity - 75% lower. Increasing and maintenance doses depend on

clinical response of the patient.

Renal impairment:

caution should be exercised in the appointment of the drug for renal failure. In the final stage of renal failure

the initial dose of lamotrigine depends on the dosage regimen of another anti-epileptic drug; with a significant reduction in renal function, a reduced maintenance dose may be sufficient.

Side effect

From the side of blood-forming organs:

neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis.

On the part of the immune system, allergic reactions:

in the first 8 weeks of treatment, a skin rash appears (usually maculopapular), disappears after the abolition of lamotrigine; Stevens-Johnson syndrome; syndrome

hypersensitivity (high temperature,

lymphadenopathy, swelling of the face, changes in blood parameters and hepatic function, disseminated intravascular coagulation and multiple organ

failure); toxic epidermal necrolysis (Layel syndrome, in some cases recovery with scar formation).

From the nervous system:

headache, irritability, drowsiness, insomnia, dizziness,

tremor, nystagmus, ataxia, anxiety; aggressiveness; agitation, hallucinations, blackout and confusion, imbalance, worsening of the course of Parkinson's disease,extrapyramidal symptoms, choreoathetosis, increased convulsive seizures.

On the part of the organ of vision:

diplopia, blurred vision, conjunctivitis.

From the digestive tract:

nausea, vomiting; increased levels of liver function, liver failure.

From the musculoskeletal system:

individual lupus-like reactions.

General, dose-dependent:

increased fatigue.

In bipolar disorders in addition to the above symptoms are possible: from the musculoskeletal system: arthralgia.

Other dose-dependent:

myalgia, back pain.

Symptoms:

nystagmus, ataxia, headache, drowsiness, vomiting, impairment of consciousness, even coma.

Inpatient treatment with maintenance and symptomatic therapy; gastric lavage and the introduction of Activated carbon may be required.

Interaction with other drugs Valproate sodium competitively blocks liver enzymes and interferes with the metabolism of lamotrigine, almost doubling its average T1 / 2, extending it to 70 hours.

Antiepileptic drugs-inducers of hepatic enzymes (phenytoin, carbamazepine, phenobarbital, primidone), Paracetamol stimulate lamotrigine metabolism and shorten its T1 / 2 by 2 times, i.e. up to 14 hours (phenytoin, carbamazepine). In patients taking carbamazepine, administration of lamotrigine may cause an increase in adverse reactions from the central nervous system: dizziness, ataxia, diplopia, decreased visual acuity and nausea. Reducing the dose of carbamazepine usually leads to the disappearance of complaints.

Does not affect plasma concentrations of other antiepileptic drugs, concentrations of ethinyl estradiol and levonorgestrel after taking oral contraceptives. Lamotrigine does not reduce the clearance of drugs, primarily those that are eliminated from the body thanks to CYP2D6. Clozapine, phenelzine, Risperidone, sertaline and trazodone, apparently, do not affect the clearance of lamotrigine. There are no data on the effect of lamotrigine on the pharmacokinetics of other antiepileptic drugs and on drug interactions between it and drugs that depend on CYP450.

Compatible with sedative, antiepileptic and anxiolytic agents.

special instructions

If Lamolep provides good control of epilepsy attacks, other antiepileptic drugs can be stopped.

An objective measure of the effectiveness of treatment is the ability to reduce the frequency of spikes on the EEG by 78-98%. In the first 8 weeks of treatment, skin reactions may develop. Skin rashes usually are of mild severity, spontaneously disappear, but severe forms are possible, requiring hospitalization and cessation of lamotrigine therapy (eg,

Stevens-Johnson and toxic epidermal necrolysis). High initial doses and acceleration of the prescribed rate of increase in the dose of lamotrigine, as well as

simultaneous reception of valproate contribute to the appearance of skin rashes. In order to avoid the appearance of a skin rash, the indicated doses and rates of their increase should be strictly observed.

Children are more susceptible to the development of severe forms of skin reactions (the frequency of cases requiring hospitalization of children is 1: 300 x 1: 100).

Long-term treatment with lamotrigine can change the metabolism of folic acid, because Lamotrigine is a weak inhibitor of dihydrofolate reductase.

In case of lactose intolerance, it should be taken into account that the 25 mg pill of Lamolep contains 16.35 mg of lactose monohydrate, 50 mg of the pill - 32.5 mg and 100 mg of the pill - 65 mg. Despite the fact that when taking oral contraceptives, lamotrigine does not affect the concentrations of ethinyl estradiol and levonorgestrel, changing the menstrual cycle during lamotrigine therapy in those taking oral contraceptives requires close attention of the attending physician.

When treating patients with renal failure on hemodialysis, it should be borne in mind that on average during 4-hour hemodialysis, 20% of lamotrigine is eliminated from the body.

Epilepsy

Abrupt cessation of lamotrigine treatment provokes epileptic seizures, up to epileptic status. Therefore, with the exception of

Special cases (eg, with the appearance of a skin rash) requiring immediate cessation of treatment, drug withdrawal should be carried out gradually, with a smooth, over 2 weeks, dose reduction.

Bipolar disorder

Patients with a tendency to suicide are characteristic of bipolar disorders, therefore treatment of people with an increased suicidal tendency must be accompanied by careful observation of patients. The effect of the drug on the ability to drive and mechanisms whose work is associated with an increased risk of injury

During treatment, it is prohibited to drive a car and engage in activities that require increased concentration and speed

psychomotor reactions.

Storage conditions

In the dark place at room temperature.