Lamolep, pills 100mg, 30pcs

Composition

of 1 tab. :

lamotrigine 100 mg

Auxiliary substances:

colloidal anhydrous silicon dioxide,

magnesium stearate,

povidone,

sodium carboxymethyl starch,

lactose monohydrate,

microcrystalline cellulose.

Pharmacological action

Anticonvulsant (antiepileptic) drug. Stabilizes potential-dependent sodium channels of cell membranes. It also blocks the release of neurotransmitters, mainly glutamic acid (which plays a key role in the development of epileptic seizures).

Pharmacokinetics

Suction

After ingestion, it is rapidly and completely absorbed from the intestine, and is not significantly affected by the “first pass”effect. Cmax is reached 2.5 hours after oral use. Food intake slows down the absorption process, but does not affect its effectiveness. Bioavailability – 98%. The pharmacokinetics of the drug after a single dose not exceeding 450 mg is linear. Concentration in the equilibrium state has a pronounced individual character.

Distribution

Protein binding is 55%. It is unlikely that the displacement of lamotrigine from binding to proteins can cause a toxic effect. Vd is 0.92-1.22 l / kg of body weight. It is excreted in breast milk. The concentration in breast milk is 40-60% of the plasma concentration. In some cases, the concentration of the drug in the blood serum of children whose mothers took the drug during lactation reaches a therapeutic level.

Metabolism

Biotransformed in the liver under the action of uridine diphosphate glucuronyl transferase. N-glucuronides predominate among the metabolites. Lamotrigine modestly and dose-dependently induces its own metabolism.

Deduction

The average steady-state clearance in healthy adults is 39±14 ml/min. It is excreted together with urine in the form of glucuronide conjugate, less than 10% – unchanged, about 2% (unchanged and in the form of metabolites) “with feces. ” Clearance and T1 / 2 do not depend on the dose. T1 / 2 of healthy volunteers is 24-35 h

. Pharmacokinetics in special clinical cases

Clearance, calculated per kg of body weight, is higher in children than in adults, and is highest up to 5 years of age. T1 / 2 in children is usually shorter than in adults.

T1 / 2 in children with simultaneous use with enzyme inducers is 7 hours, with sodium valproate – 45-60 hours.

The clearance of lamotrigine in the elderly and younger patients is minimally different from each other.

Indications

Epilepsy

for adults and children over 12 years

• 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 the Lennox-gastaux syndrome);

for children 2 to 12 years

• in a combination therapy for the treatment of partial and generalized seizures (including tonic-clonic convulsions and convulsive seizures in the Lennox-gastaux syndrome).

Bipolar Disorder

for adults (18 years and older)

• for the prevention and treatment of mainly episodes of depression.

Use during pregnancy and lactation

Lamolep is contraindicated during pregnancy, except in cases where the expected therapeutic benefit to the mother exceeds the potential risk to the fetus.

Due to the inhibitory effect of lamotrigine on dihydrofolate reductase, fetal malformations are likely to develop when the drug is used during pregnancy, but the current data are insufficient to determine the degree of safety.

Data on the use of the drug during breastfeeding is limited. In some cases, the concentration of the drug in the blood serum of children whose mothers took the drug during lactation reaches a therapeutic level. When using the drug during lactation, the benefits of breast-feeding and the likelihood of side effects in the child should be carefully weighed.

Use in children

Caution should be exercised when prescribing the drug to children as the drug of choice for monotherapy of epilepsy. Contraindication: children under 2 years of age.

Contraindications

• children under 2 years of age;
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to lamotrigine or any component of the drug.

Caution should be exercised when prescribing the drug to patients with renal insufficiency (due to possible accumulation of the glucuronide metabolite).

Caution should be exercised when prescribing the drug to children as the drug of choice for monotherapy of epilepsy.

Use in patients with liver function disorders

For moderate hepatic impairment (Child-Pugh class B), the initial, increasing and maintenance dose should be reduced by approximately 50%, and for severe hepatic impairment (Child-Pugh class C), by 75%. Increasing and maintaining doses should be adjusted depending on the clinical effect.

Use in patients with impaired renal function

Caution should be exercised when prescribing the drug to patients with renal insufficiency.

Use in elderly patients

Correction of the dosage regimen in elderly patients (older than 65 years) is not required (since the pharmacokinetics in this age group does not differ from those in adults).

Side effects

Adverse reactions are presented separately for each indication, using the following conditional classification of the frequency of adverse reactions: very common (>1/10), often (>>1/100,1/1000, >>< 1/100), rare (>1/10 000, < 1/100), rare (>

In patients with epilepsy

From the hematopoietic system:  very rarely – neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis.

Allergic reactions:  very often-in the first 8 weeks of therapy, a skin rash (maculopapular) that disappears after lamotrigine withdrawal; rarely-Stevens-Johnson syndrome, very rarely-hypersensitivity syndrome (including symptoms such as fever, lymphadenopathy, facial swelling, blood and liver disorders, DIC syndrome, multi-organ disorders), toxic epidermal necrolysis (Lyell’s syndrome, in some cases recovery with scarring).

From the central nervous system:  very often-headache; often-irritability, drowsiness, insomnia, dizziness, tremor, nystagmus, ataxia, anxiety; sometimes – aggressiveness; very rarely-increased excitability, hallucinations, confusion, balance disorders, worsening of Parkinson’s disease, extrapyramidal disorders, choreoathetosis, increased frequency of seizures.

From the side of the visual organ:  very often – diplopia, blurred vision; rarely-conjunctivitis.

From the digestive system:  often – nausea, vomiting; very rarely-increased levels of liver enzymes, impaired liver function, liver failure.

Other services:  often – increased fatigue; very rarely-lupus-like syndrome.

In patients with bipolar disorder

In addition to the above symptoms, the following phenomena are also possible.

Musculoskeletal disorders:  often-arthralgia, myalgia, back pain.

Interaction

When used concomitantly, valproic acid preparations competitively block liver enzymes and interfere with lamotrigine metabolism, almost doubling its average T1 / 2, extending it to 70 hours.

Antiepileptic drugs-inducers of liver enzymes (such as phenytoin, carbamazepine, phenabarbital and primidone), as well as paracetamol, stimulate lamotrigine metabolism and reduce its T1 / 2 by 2 times, up to 14 hours (phenytoin, carbamazepine). In patients taking carbamazepine, lamotrigine use may cause undesirable effects from the central nervous system, including dizziness, ataxia, diplopia, decreased visual acuity and nausea. Reducing the dose of carbamazepine usually leads to the disappearance of these phenomena.

When used concomitantly, lamotrigine does not affect the concentration of other antiepileptic drugs in plasma, as well as the concentration of ethinyl estradiol and levonorgestrel (which are part of simultaneously used oral contraceptives).

When used concomitantly, lamotrigine does not reduce the clearance of drugs that are metabolized by CYP2D6.

Concomitant use of clozapine, phenelzine, risperidone, sertaline, and trazodone does not appear to affect lamotrigine clearance.

There are no data on the effect of lamotrigine on the pharmacokinetics of other antiepileptic drugs and on the drug interaction between it and drugs metabolized with the participation of cytochrome P450 isoenzymes.

It can be combined with sedatives, antiepileptic drugs and anxiolytics.

How to take it, course of use and dosage

Epilepsy

In adults and children over 12 years of age for monotherapy, the initial dose of Lamolep is 25 mg 1 time/day for the first 2 weeks; in the next 2 weeks – 50 mg 1 time/day. In the future, every 1-2 weeks, it is possible to increase the dose by 50-100 mg, until the optimal therapeutic effect is achieved. The maintenance dose to maintain the optimal therapeutic effect is usually 100-200 mg / day in 1-2 doses. In some cases, to achieve a therapeutic effect, it is necessary to prescribe the drug at a dose of 500 mg / day.

As part of combination therapy, when combined with valproic acid preparations in combination with other antiepileptic drugs or without them, the initial dose of Lamolep for the first 2 weeks is 25 mg every other day; in the future – daily 25 mg 1 time/day for the next 2 weeks. In the future, every 1-2 weeks, it is possible to increase the dose by 25-50 mg, until the optimal therapeutic effect is achieved. The maintenance dose is usually 100-200 mg / day in 1-2 divided doses.

When using Lamolep as part of a combination therapy with drugs that induce lamotrigine glucuronidation (phenytoin, carbamazepine, phenobarbital, primidone), in combination with or without other antiepileptic drugs (but not taking valproic acid preparations) during the first 2 weeks, the initial dose is 50 mg 1 time/day, then for the next 2 weeks – 100 mg/day in 2 doses. In the future, it is possible to increase the dose by 100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The maintenance dose is usually 200-400 mg / day in 1-2 divided doses. In some cases, a dose of 700 mg/day may be required.

When used in combination with an antiepileptic drug whose pharmacokinetic interaction with lamotrigine has not been established, the dose of Lamolep should be increased gradually (and to a lesser extent) according to the scheme described for combination therapy with sodium valproate.

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

Treatment option Weeks 1-2 Weeks 3-4 Maintenance dose monotherapy 25 mg 1 time/day 50 mg 1 time/day 100-200 mg 1 or 2 times/day; to achieve a therapeutic effect, the dose can be increased by 50-100 mg every 1-2 weeks Combined therapy with Lamolep and valproic acid preparations, regardless of other concomitant therapy 12.5 mg (or 25 mg every other day)25 mg 1 time/day 100-200 mg (in 1 or 2 doses); to achieve a therapeutic effect, the dose can be increased by 25-50 mg every 1-2 weeks Combined therapy without valproic acid preparations (with phenytoin, carbamazepine, phenobarbital, primidone or other inducers of lamotrigine glucuronidation)50 mg 1 time / day 100 mg (in 2 divided doses)200-400 mg (in 2 divided doses); to achieve a therapeutic effect, the dose is increased by 100 mg every 1-2 weeks. When combined therapy with antiepileptic drugs, the pharmacokinetic interaction of which with lamotrigine is currently unknown, the regimen recommended for the appointment of lamotrigine in combination with valproic acid preparations should be used

In children aged 2 to 12 years of age in combination therapy with valproic acid preparations in combination with other antiepileptic drugs or without them, the initial daily dose of Lamolep for the first 2 weeks is 0.15 mg/kg of body weight 1 time/day, for the next 2 weeks – 0.3 mg/kg 1 time/day. Then, every 1-2 weeks, the dose should be increased by 0.3 mg / kg until the optimal therapeutic effect is achieved. The average maintenance dose is 1-5 mg / kg / day in 1-2 divided doses. The maximum daily dose is 200 mg.

As part of combination therapy with other antiepileptic drugs or other drugs that induce lamotrigine glucuronidation (phenytoin, carbamazepine, phenobarbital and primidone), in combination with other AEDs or without them (with the exception of valproic acid preparations)the initial dose of Lamolep for the first 2 weeks is 0.6 mg / kg / day in 2 doses, then for the next 2 weeks – 1.2 mg / kg/day in 2 doses. Then, every 1-2 weeks, the dose should be increased by a maximum of 1.2 mg / kg / day until the optimal therapeutic effect is achieved. The maintenance dose is on average 5-15 mg / kg / day in 2 divided doses. The maximum daily dose is 400 mg.

When used in combination with an antiepileptic drug whose pharmacokinetic interaction with lamotrigine has not been established, the dose of Lamolep should be increased gradually (and to a lesser extent) according to the scheme described for combination therapy with sodium valproate.

Table 2. Recommended dosage regimen in the treatment of children with epilepsy aged 2 to 12 years (total daily dose in mg/kg of body weight).

Prescribing regimen Weeks 1-2 Weeks 3-4 Maintenance dose-combined therapy with valproic acid preparations regardless of other concomitant therapy 0.15 mg / kg 1 time/day 0.3 mg / kg 1 time/day*Increasing the dose by 0.3 mg / kg every 1-2 weeks until a maintenance dose of 1-5 mg/kg/day is reached (in 1-2 doses) to a maximum dose of 200 mg / day Combined therapy without valproic acid preparations with phenytoin, carbamazepine, phenobarbital, primidone or other inducers of lamotrigine glucuronidation 0.6 mg/kg (in 2 doses)1.2 mg / kg (in 2 divided doses)Higher doses of 1.2 mg/kg every 1-2 weeks to achieve a maintenance dose of 5-15 mg/kg/day (1-2 doses) to a maximum dose of 400 mg/sutu patients receiving antiepileptic funds, which pharmacokinetic interaction with lamotrigine is currently not known, should be used to use the mode recommended for appointment of lamotrigine in combination with valproic acid drugs

in doses are intact tablets.

Bipolar disorders

In the treatment of bipolar disorders, Lamolep is prescribed to prevent episodes of depression. At the same time, during short-term therapy, the maintenance dose of lamotrigine should be increased gradually, over 6 weeks, until the patient’s condition stabilizes. Then, if the clinical picture of the disease is appropriate, you can stop taking a psychotropic or other antiepileptic drug.

Adjuvant therapy may be necessary to prevent episodes of mania, as the effectiveness of lamotrigine in mania and manic states is ambiguous.

Table 3. Recommended daily maintenance dose selection scheme for adults (over 18 years of age) with bipolar disorders.

Dosage Regimenweeks 1-2 Weeks 3-4 Weeks 5 Maintenance Stabilizing dose (Week 6)Combination therapy with valproic acid preparations)12.5 mg (25 mg every other day)25 mg 1 time/day 50 mg / day (in 1-2 doses)100 mg/day( in 1-2 doses), maximum daily dose 200 mg Combined therapy with inducers of lamotrigine glucuronidation (without valproic acid preparations)50 mg 1 time/day 100 mg/day (in 2 divided doses)200 mg / day (in 2 divided doses)300 mg at week 6 of therapy, if necessary, increase the dose to 400 mg at week 7 of therapy (in 2 divided doses)Combination therapy with drugs that do not interact with lamotrigine 25 mg 1 time/day 50 mg / day (in 1-2 doses)100 mg/day (in 1-2 doses)200 mg (from 100 mg to 400 mg) in 1 or 2 doses of patients taking antiepileptic drugs, the pharmacokinetic interaction of which with lamotrigine has not been studied, it is necessary to apply the regimen recommended for the appointment of lamotrigine in combination with valproic acid preparations

As part of combination therapy with other antiepileptic drugs that inhibit liver enzymes (for example, with valproic acid preparations), for the first 2 weeks the initial dose of Lamolep is 25 mg every other day, then for the next 2 weeks – 25 mg 1 time/day. At week 5, the dose should be increased to 50 mg/day in 1-2 divided doses. To achieve an optimal therapeutic effect, a dose of 100 mg/day in 1-2 doses is required; the maintenance daily dose is 1-5 mg/kg of body weight in 1-2 doses. The maximum daily dose is 200 mg.

As part of combination therapy with antiepileptic drugs that induce liver enzymes (for example, carbamazepine, phenobarbital), in patients who do not receive valproic acid preparations, during the first 2 weeks the initial dose is 50 mg 1 time/day, then for the next 2 weeks – 100 mg/day in 2 doses, at week 5 the dose is increased to 200 mg/day in 2 doses. At week 6, the dose can be increased to 300 mg / day. At week 7, the daily dose can reach 400 mg in 2 divided doses.

In monotherapy or in combination therapy with drugs whose pharmacokinetic interaction with lamotrigine is unknown or possible, for the first 2 weeks the initial dose of Lamolep is 25 mg 1 time/day, then for the next 2 weeks – 50 mg/day in 1-2 doses, at week 5 the dose is increased to 100 mg / day in 1-2 doses. To achieve an optimal therapeutic effect, a dose of 200 mg/day in 1-2 doses is required. The maximum daily dose is 400 mg / day in 2 divided doses.

After reaching the daily maintenance stabilizing dose, other psychotropic drugs may be discontinued.

Table 4. Maintenance stabilizing total daily dose for the treatment of bipolar disorders after withdrawal of concomitant psychotropic or antiepileptic drugs.

Additional therapy for Weeks 1 Week 2 Week 3 and beyond (max. dose 400 mg / day)After discontinuation of lamotrigine glucuronidation inhibitors (e. g. valproic acid preparations)The dose is increased by 2 times, no more than 100 mg / week, i. e. in 1 week the dose should be 200 mg / day, Save the dose of 200 mg/day in 2 receptions after discontinuation of lamotrigine glucuronidation inducers (for example, carbamazepine), depending on the initial dose.400 mg 300 mg 200 mg 300 mg 225 mg 150 mg 200 mg 150 mg 100 mg After withdrawal of other psychotropic or antiepileptic drugs in patients not taking inducers or inhibitors of lamotrigine glucuronidation (for example, lithium preparations, bupropion)An adjusted dose of 200 mg/day should be prescribed (the recommended dose is in the range of 100 mg to 400 mg). After discontinuation of an antiepileptic drug that does not interact with lamotrigine, it is recommended to increase the dose of Lamolep according to the scheme recommended when taking lamotrigine with valproic acid preparations

After discontinuation of additional therapy with lamotrigine glucuronidation inhibitors (for example, valproic acid preparations) The initial stabilizing dose of lamotrigine is doubled and remains at this level after discontinuation of valproic acid preparations.

After discontinuation of additional therapy with inducers of lamotrigine glucuronidation (for example, carbamazepine) the dose of lamotrigine is gradually reduced over 3 weeks.

After discontinuation of concomitant psychotropic or antiepileptic drugs that do not have a significant pharmacokinetic interaction with lamotrigine (for example, lithium preparations, bupropion), lamotrigine continues to be used at the dose selected during the increase mode.

There is no clinical experience in correcting daily doses of lamotrigine in patients with bipolar disorders after the addition of other drugs. However, based on drug interaction studies, the following recommendations can be made.

Table 5. Correction of daily lamotrigine doses in patients with bipolar disorder after joining therapy with other drugs.

Additional therapy: Initial dose of Lamolep (mg / day)Week 1 Week 2 Week 3 and further after discontinuation of lamotrigine glucuronidation inhibitors (for example, valproic acid preparations) depending on the initial dose of Lamolep 200 mg 100 mg Save the dose of 100 mg/day 300 mg 150 mg Save the dose of 150 mg/day 400 mg 200 mg Save the dose of 200 mg/daythe combination of lamotrigine glucuronidation inducers (for example, carbamazepine) in patients not receiving valproic acid preparations, depending on the initial dose Lamolep 200 mg 200 mg 300 mg 400 mg 150 mg 150 mg 225 mg 300 mg 100 mg 100 mg 150 mg 200 mgthe combination of other psychotropic or antiepileptic drugs with unknown pharmacokinetic interaction with lamotrigine (for example, lithium preparations, bupropion)The dose achieved during the increase regimen (200 mg / day); dose range from 100 mg to 400 mgpatients taking antiepileptic drugs, the nature of the pharmacokinetic interaction of which with lamotrigine is currently unknown, the dosage regimen used when taking lamotrigine with valproic acid preparations is recommended

Discontinuation of Lamolep for bipolar disorders does not require a gradual dose reduction.

The safety and efficacy of lamotrigine in bipolar disorder in children and adolescents under 18 years of age have not been evaluated, so there are no recommendations on the dosage regimen.

Tablets should be taken orally, without chewing and washed down with a small amount of water.

If the calculated dose of lamotrigine cannot be divided into a whole number of tablets of a lower dosage, then the patient should be assigned a dose that corresponds to the nearest value of the whole tablet in a lower dosage.

Correction of the dosage regimen in elderly patients (older than 65 years) is not required (since the pharmacokinetics in this age group does not differ from those in adults).

Moderate hepatic impairment (Child-Pugh class B) Initial, incremental, and maintenance doses should be reduced by approximately 50%, and in severe cases (Child-Pugh class C) by 75%. Increasing and maintaining doses should be adjusted depending on the clinical effect.

Caution should be exercised when prescribing the drug to patients with renal insufficiency. In end-stage renal failure, the initial dose of lamotrigine depends on the dosage regimen of another antiepileptic drug. For patients with significantly reduced renal function, a reduction in the maintenance dose may be recommended.

Overdose

Symptoms: nystagmus, ataxia, headache, vomiting, drowsiness, impaired consciousness up to coma.

Treatment: admission to a hospital and appropriate maintenance and symptomatic therapy; if necessary, gastric lavage and use of activated charcoal.

Special instructions

There are no data confirming clinically significant inducing and inhibitory effects of lamotrigine on oxidative enzymes in the liver. The ability of the drug to induce its own metabolism is small and probably has no clinical significance.

Lamolep should not be administered concomitantly with other lamotrigine-containing medications.

If Lamolep provides good control of seizures, other antiepileptic drugs may be discontinued.

An objective criterion for the effectiveness of treatment is the ability to reduce the frequency of peaks on the EEG by 78-98%.

Skin reactions may occur during the first 8 weeks of treatment. Skin rashes are usually mild and disappear spontaneously. Severe forms may develop that require hospitalization and discontinuation of lamotrigine therapy (for example, Stevens-Johnson syndrome and toxic epidermal necrolysis). The use of the drug in high initial doses and the acceleration of the recommended rate of increase in the dose of lamotrigine, as well as the simultaneous use of valproic acid preparations, contribute to the appearance of skin rashes. To reduce the likelihood of developing such dermatological reactions, the indicated doses and the rate of their increase should be strictly observed.

Children are more likely to develop severe skin reactions (the frequency of cases requiring hospitalization of children is 1/300-1/100).

Early symptoms of an allergic rash can easily be confused with an infectious rash, so if a high fever and rash occur during the first 8 weeks of treatment, a drug reaction should be assumed.

It is important to remember that early manifestations of hypersensitivity reactions (for example, high fever, lymphadenopathy) can occur without a rash. If a rash appears (regardless of the patient’s age), a thorough examination of the patient should be performed immediately and lamotrigine therapy should be discontinued if the development of dermatological symptoms cannot be explained by another reason.

The appearance of the rash can be accompanied by various systemic manifestations of hypersensitivity (high body temperature, lymphadenopathy, facial edema, reactions from the liver and hematopoietic system). The severity of hypersensitivity reactions may vary, sometimes it is possible to develop disseminated intravascular coagulopathy and multiple organ functional insufficiency. It should be borne in mind that early signs of hypersensitivity (for example, high body temperature, lymphadenopathy) are not always accompanied by a skin rash.

Liver function disorders are usually part of hypersensitivity syndrome, but are not always accompanied by other symptoms.

Long-term treatment with lamotrigine may alter folic acid metabolism, as lamotrigine is a weak inhibitor of dihydrofolate reductase. At the same time, long-term,12-month treatment with lamotrigine does not significantly affect the level of hemoglobin, the average volume of red blood cells, the concentration of folic acid in plasma and red blood cells, and after 5 years of treatment – on the concentration of folic acid.

In case of lactose intolerance, it should be taken into account that tablets containing 25 mg of lamotrigine contain 16.35 mg of lactose monohydrate, containing 50 mg – 32.5 mg,100 mg – 65 mg.

Despite the fact that when taking oral contraceptives, lamotrigine does not affect the concentration of ethinyl estradiol and levonorgestrel, menstrual disorders during lamotrigine therapy in patients taking oral contraceptives require close attention of the attending physician.

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

Abrupt discontinuation of lamotrigine treatment provokes epileptic seizures, up to status epilepticus. Therefore, with the exception of special cases (for example, the appearance of a skin rash) that require immediate discontinuation of therapy, discontinuation of the drug should be carried out gradually with a gradual dose reduction over 2 weeks.

Severe seizures and status epilepticus can lead to the development of rhabdomyolysis, multiple organ failure, and disseminated intravascular coagulopathy, sometimes with a fatal outcome. Similar cases have occurred in connection with the use of lamotrigine.

Bipolar disorders are characterized by a tendency to suicide, so when prescribing the drug to patients with a tendency to suicide, careful monitoring of patients is required.

Influence on the ability to drive motor vehicles and manage mechanisms

During treatment, it is forbidden to drive a car or engage in activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets are white or almost white in color, biconvex, with the inscription “L100” on one side.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

5 years

Active ingredient

Lamotrigine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets