Lamal tablets 50 mg blister No. 30

Instructions Lamal tablets 50 mg blister No. 30

Composition

active ingredient: lamotrigine;

1 tablet contains lamotrigine 25 mg or 50 mg, or 100 mg, or 200 mg;

excipients: low-substituted hydroxypropylcellulose, calcium carbonate, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, aluminum-magnesium silicate, magnesium stearate, sodium saccharin, povidone, microcrystalline cellulose, blackcurrant flavor 501017 AP0551 (maltodextrin, flavorings, glycerol triacetate (E 1518), triethyl citrate (E 1505), ammonium sulfate caramel (E 150D).

Dosage form

Pills.

Main physicochemical properties:

25 mg tablets: white, round biconvex tablets;

50 mg or 100 mg or 200 mg tablets: white, round, biconvex tablets with a score on one side.

Pharmacotherapeutic group

Antiepileptics. Other antiepileptics. ATX code N03A X09.

Pharmacological properties

Pharmacodynamics.

Lamotrigine is an anticonvulsant that works by blocking voltage-gated sodium channels in the presynaptic membrane, which reduces the release of neurotransmitters into the synaptic cleft, primarily glutamate, an amino acid that plays an important role in the onset of an epileptic seizure.

Pharmacokinetics.

After oral administration, the drug is rapidly and completely absorbed from the gastrointestinal tract. The maximum plasma concentration Cmax is reached after 2–3 hours. The time to reach Cmax is slightly prolonged after food intake, but the extent of absorption does not change.

Lamotrigine is metabolized in the liver by glucuronidation. The half-life is significantly dependent on concomitant medications. Less than 10% of lamotrigine is excreted in the urine without being absorbed by the body. Almost 2% is excreted in the feces. The half-life of lamotrigine averages 24–35 hours.

Penetrates into breast milk in concentrations that are 40–60% of those in blood plasma.

Indication

Epilepsy:

adults and adolescents from 13 years of age: monotherapy and adjunctive therapy of epilepsy, in particular partial and generalized seizures, including tonic-clonic seizures, as well as seizures associated with Lennox-Gastaut syndrome. Lamal® is prescribed as adjunctive therapy, but in Lennox-Gastaut syndrome it can be prescribed as an initial antiepileptic drug (AED);

Children aged 2 to 12 years: adjunctive therapy in epilepsy, particularly partial and generalized seizures, including tonic-clonic seizures, as well as seizures associated with Lennox-Gastaut syndrome.

Monotherapy of typical minor epileptic seizures.

Bipolar disorders in adults.

To prevent cases of emotional disorders, mainly to prevent depressive episodes in patients with bipolar I disorder.

Lamal® is not indicated for the emergency treatment of manic or depressive episodes.

Contraindication

Hypersensitivity to lamotrigine or to any of the excipients of the drug.

Interaction with other medicinal products and other types of interactions

Uridine diphosphoglucuronyltransferase has been identified as the enzyme responsible for the metabolism of lamotrigine. There is no evidence that lamotrigine causes clinically significant induction or inhibition of hepatic microsomal enzymes involved in drug metabolism, and interactions between lamotrigine and drugs metabolized by cytochrome P450 enzymes are unlikely. Lamotrigine may induce its own metabolism, but this effect is modest and of no clinical consequence (see Table 1).

Effect of other drugs on lamotrigine glucuronidation

Table 1.

*See section “Method of administration and dosage”.

** Other oral contraceptives and hormone replacement drugs have not been studied, but they

may similarly affect the pharmacokinetic properties of lamotrigine.

Interaction with antiepileptic drugs.

Certain antiepileptic drugs (such as phenytoin, carbamazepine, phenobarbital and primidone) that induce hepatic enzymes inhibit the glucuronidation metabolism of lamotrigine and accelerate the metabolism of lamotrigine. Therefore, patients taking these drugs with lamotrigine should follow the correct dosage recommendations (see section 4.2).

There have been reports of central nervous system (CNS) adverse events including dizziness, ataxia, diplopia, blurred vision, and nausea in patients receiving carbamazepine concomitantly with lamotrigine. These events usually resolve when the carbamazepine dose is reduced. A similar effect has been observed in studies of lamotrigine and oxcarbazepine in healthy adult volunteers, but dose reduction has not been studied. There have been reports in the literature of decreased lamotrigine levels when co-administered with oxcarbazepine.

In a study of 61 healthy adult volunteers receiving 200 mg of lamotrigine and 1200 mg of oxcarbazepine, oxcarbazepine did not alter the metabolism of lamotrigine, and lamotrigine did not alter the metabolism of oxcarbazepine. Therefore, recommendations for adjunctive therapy with lamotrigine without valproate and without inducers of lamotrigine glucuronidation should be followed in patients receiving concomitant oxcarbazepine therapy (see section 4.2).

In a study in healthy volunteers, it was found that the simultaneous use of felbamate at a dose of 1200 mg twice a day and lamotrigine at a dose of 100 mg twice a day for 10 days had no clinically significant effect on the pharmacokinetics of the latter.

A retrospective analysis of plasma levels in patients receiving lamotrigine with/without gabapentin showed that gabapentin did not alter the baseline clearance of lamotrigine.

The potential drug interaction between levetiracetam and lamotrigine was studied by evaluating the serum concentrations of both drugs in placebo-controlled clinical trials. According to these data, the substances do not alter the pharmacokinetics of each other.

Steady-state plasma concentrations of lamotrigine are not altered by co-administration with pregabalin (200 mg 3 times daily). There is no pharmacokinetic interaction between lamotrigine and pregabalin.

Topiramate does not affect the plasma concentration of lamotrigine. The use of lamotrigine on

15% increases the concentration of topiramate in blood plasma.

According to the study, the use of zonisamide (200–400 mg per day) together with lamotrigine (150–500 mg per day) for 35 days for the treatment of epilepsy had no significant effect on the pharmacokinetics of lamotrigine.

Concomitant administration of lacosamide (200, 400 or 600 mg/day) had no effect on lamotrigine plasma concentrations in placebo-controlled clinical trials in patients with partial onset seizures.

In a pooled analysis of data from three placebo-controlled clinical trials investigating the adjunctive use of perampanel in patients with partial-onset seizures and primary generalized tonic-clonic seizures, the highest dose of perampanel studied (12 mg/day) resulted in a less than 10% increase in lamotrigine clearance. This effect on lamotrigine metabolism is not considered clinically significant.

Although there have been reports of changes in plasma concentrations of other antiepileptic drugs, controlled studies have shown that lamotrigine does not affect the plasma concentrations of concomitant antiepileptic drugs. In vitro studies have shown that lamotrigine does not displace other antiepileptic drugs from their protein binding.

Interaction with other psychotropic substances.

Coadministration of 100 mg/day of lamotrigine and 2 g of lithium gluconate twice daily for 6 days in 20 patients did not alter the pharmacokinetics of lithium.

Multiple oral doses of bupropion had no statistically significant effect on the pharmacokinetics of lamotrigine in a study of 12 patients, only resulting in a slight increase in lamotrigine glucuronide levels.

In studies in healthy adult volunteers, 15 mg of olanzapine reduced the area under the concentration-time curve (AUC) and Cmax of lamotrigine by an average of 24% and 20%, respectively. Such a pronounced effect is rarely observed in clinical practice. A dose of 200 mg of lamotrigine had no effect on the pharmacokinetics of olanzapine.

Multiple oral doses of lamotrigine 400 mg/day had no clinically significant effect on the pharmacokinetics of risperidone given as a single 2 mg dose in a study of 14 healthy adult volunteers. When risperidone 2 mg was coadministered with lamotrigine, 12 of 14 volunteers experienced somnolence compared to 1 of 20 volunteers receiving risperidone alone. No cases of somnolence were observed with lamotrigine alone.

In vitro experiments have shown that the formation of the primary metabolite of lamotrigine, 2-N-glucuronide, is minimally affected by amitriptyline, bupropion, clonazepam, fluoxetine, haloperidol or lorazepam. In vitro studies also suggest that clozapine, fluoxetine, phenelzine, risperidone, sertraline or 62-trazodone are unlikely to affect the clearance of lamotrigine. Studies of the metabolism of bufuralol in human liver microsomes suggest that lamotrigine does not reduce the clearance of drugs that are primarily metabolised by CYP 2D6. In vitro studies also suggest that clozapine, phenelzine, risperidone, sertraline and trazodone do not affect the clearance of lamotrigine.

Interaction with hormonal contraceptives.

Effect of hormonal contraceptives on the pharmacokinetics of lamotrigine.

In a study of 16 female volunteers taking lamotrigine with a combination of ethinylestradiol 30 mcg/levonorgestrel 150 mcg, an increase in lamotrigine excretion by approximately 2-fold was observed, which in turn caused a decrease in AUC and Cmax of lamotrigine by an average of 52 and 39%, respectively. Serum lamotrigine concentrations gradually increased during the one-week break, reaching concentrations closer to the end of the one-week break that were on average approximately 2-fold higher than with concomitant use of the drugs (see section "Special instructions for use"). No dose adjustment of lamotrigine is recommended when hormonal contraceptives are used simultaneously, but the maintenance dose of lamotrigine should be increased or decreased when starting or stopping hormonal contraceptives (see section "Method of administration and dosage").

The effect of lamotrigine on the pharmacokinetics of hormonal contraceptives.

In a study of 16 female volunteers, a continuous dose of lamotrigine 300 mg did not affect the pharmacokinetics of ethinylestradiol, a component of a combined oral contraceptive. There was a sustained, small increase in the clearance of levonorgestrel, which in turn resulted in a mean decrease in the AUC and Cmax of levonorgestrel of 19% and 12%, respectively. Measurement of serum levels of follicle-stimulating hormone, luteinizing hormone and estradiol during the study showed suppression of ovarian hormonal activity in some women, although

Results of serum progesterone measurements revealed the absence of any hormonal symptoms of ovulation in all 16 women.

The effect of changes in serum levels of follicle-stimulating and luteinizing hormones and a slight increase in levonorgestrel excretion on ovarian ovulatory activity is unknown (see section 4.4). The effect of lamotrigine at daily doses above 300 mg has not been studied. Other hormonal contraceptives have also not been studied.

Interaction with other drugs.

In a study of 10 male volunteers, lamotrigine was administered concomitantly with rifampicin, resulting in increased clearance and decreased half-life of lamotrigine due to induction of hepatic enzymes responsible for glucuronidation. Patients receiving concomitant rifampicin therapy should be treated with the same regimen recommended for lamotrigine and appropriate inducers of glucuronidation.

In studies in healthy volunteers, lopinavir/ritonavir approximately halved the plasma concentrations of lamotrigine by inducing glucuronidation. Patients already taking lopinavir/ritonavir should be treated with the same regimen recommended for lamotrigine and glucuronidation inducers.

In studies in healthy volunteers, the use of atazanavir/ritonavir (300 mg/100 mg) reduced the AUC and Cmax of lamotrigine in plasma (at a dose of 100 mg) by an average of 32 and 6%, respectively.

In vitro data on the effects of lamotrigine on organic cation transporter 2 (OCT 2) have shown that lamotrigine, but not the N(2)-glucuronide metabolite, is an inhibitor of OCT 2 at potentially clinically relevant concentrations. These data demonstrate that lamotrigine is a more potent inhibitor of OCT 2 than cimetidine, with IC50 values of 53.8 µM and 186 µM, respectively (see section 4.4).

The clinical significance of these findings is not yet fully established, but should still be considered when the patient is taking drugs that are OCT 2 substrates (e.g. metformin, gabapentin, varenicline).

Interaction with the involvement of laboratory tests.

Lamotrigine has been reported to interact with tests used to rapidly detect certain drugs in urine, resulting in false-positive results, particularly for phencyclidine. An alternative and more specific chemical method should be used to confirm positive results.

Application features

Special precautions.

Skin rashes.

In adults taking lamotrigine in studies using current dosing recommendations, the incidence of severe skin rashes is approximately 1 in 500 patients with epilepsy. Approximately half of these cases were diagnosed as Stevens-Johnson syndrome (1 in 1000 cases).

The incidence of severe skin rashes in patients with bipolar disorder is 1 in 1,000.

Children are at higher risk of developing serious skin rashes than adults.

According to research, the frequency of rashes leading to hospitalization in children varies from 1 in 300 to 1 in 100 patients.

In children, the first signs of skin rashes may be mistaken for infection, so doctors should pay attention to the possibility of developing an adverse reaction to the drug in children who develop rashes and fever during the first 8 weeks of therapy.

The overall risk of skin rashes appears to be closely related to the use of lamotrigine at high initial doses and exceeding the recommended dose escalation schedule for lamotrigine therapy, as well as to the concomitant use of valproate.

Lamotrigine should be used with caution in patients with a history of allergy or rash to other antiepileptic drugs, as the incidence of moderate rash after treatment with lamotrigine in this group of patients was 3 times higher than in the group without such a history.

If a skin rash develops, the patient (both adults and children) should be evaluated immediately and the drug discontinued unless there is evidence that the skin rash is not related to the drug. It is not recommended to restart lamotrigine if it has been discontinued due to a rash from previous treatment with lamotrigine. In such cases, the decision to re-administer the drug should be based on the expected benefits of treatment and the potential risks.

Skin rashes have also been reported as part of a hypersensitivity syndrome, which is accompanied by various systemic symptoms including fever, lymphadenopathy, facial edema, changes in blood counts and liver function tests, and aseptic meningitis (see section 4.8). The syndrome can vary in severity and can occasionally lead to disseminated intravascular coagulation and multiorgan failure. It is important to note that early signs of hypersensitivity (e.g. fever and lymphadenopathy) may occur even in the absence of skin rashes. If such symptoms occur, the patient should be evaluated immediately and, in the absence of other causes, the drug should be discontinued.

In most cases, aseptic meningitis is reversible upon discontinuation of the drug, but in some cases it may recur with re-administration of lamotrigine. Re-administration of lamotrigine causes a rapid return of symptoms, often of a more severe nature. Lamotrigine should not be re-administered to patients who have been discontinued due to aseptic meningitis during previous administration.

Due to the potential for cross-reactions, special caution should be exercised when using lamotrigine in patients with known hypersensitivity to carbamazepine and phenytoin.

Photosensitivity reactions have also been reported with lamotrigine (see section 4.8). In a few cases, the reaction occurred with high doses (400 mg or more), after dose increases or rapid titration. If a patient with signs of photosensitivity (e.g. severe sunburn) is suspected of having photosensitivity related to lamotrigine, discontinuation of treatment should be considered. If continued treatment with lamotrigine is considered clinically warranted, the patient should be advised to avoid exposure to sunlight and artificial ultraviolet light and to take protective measures (e.g. use of protective clothing and sunscreen).

Suicidal risk.

People with epilepsy may experience symptoms of depression and/or bipolar disorder. There is also evidence that people with epilepsy and bipolar disorder are at increased risk of suicide.

Between 25% and 50% of patients with bipolar disorder have at least one suicide attempt and may experience worsening depressive symptoms and/or the emergence of suicidal thoughts and behavior (suicidality) regardless of whether they have used medications for the treatment of bipolar disorder, including Lamictal®.

Suicidal ideation and behavior have been reported in patients treated with antiepileptic drugs for a variety of indications, including epilepsy. A meta-analysis of randomized, placebo-controlled clinical trials of antiepileptic drugs, including lamotrigine, has shown a small increased risk of suicidal ideation and behavior. The mechanism of this increased risk is unknown, but available data do not exclude the possibility of an increased risk with lamotrigine. Therefore, patients should be closely monitored for signs of suicidal ideation and behavior. If such signs occur, medical attention should be sought.

Patients treated with lamotrigine for bipolar disorder should be observed closely for clinical worsening (including new symptoms) and for suicidality, particularly at the beginning of treatment or at the time of dose changes. Some patients with a history of suicidal behavior or intent, younger patients, and patients who have demonstrated a significant degree of suicidal ideation prior to initiation of treatment may be at increased risk of suicidal thoughts or suicide attempts, which may require close monitoring during treatment.

Patients (and caregivers of patients) should be warned about the need to monitor for any worsening of their condition (including the appearance of new symptoms) and/or the emergence of suicidal thoughts/behavior or self-harm and to seek medical advice immediately if these symptoms occur.

In this case, the situation should be assessed and appropriate changes made to the therapeutic regimen, including possible discontinuation of treatment in patients with clinical worsening (including the appearance of new symptoms) and/or the appearance of suicidal thoughts/behavior, especially if these symptoms are severe, develop suddenly and are not part of pre-existing symptoms.

Hormonal contraceptives.

The effect of hormonal contraceptives on the efficacy of lamotrigine.

Studies have shown that the combination of ethinylestradiol 30 mcg/levonorgestrel 150 mcg increases the excretion of lamotrigine by approximately 2-fold, which in turn reduces lamotrigine levels. In most cases, an increase (by titration) of the maintenance dose of lamotrigine (by 2-fold) is necessary to obtain the maximum therapeutic effect. In women who are not taking drugs that induce lamotrigine glucuronidation and are already taking hormonal contraceptives (with a week's break between courses), a gradual temporary increase in lamotrigine levels may be observed during the week's break. This increase will be greater if the lamotrigine dose is increased the day before or during the week's break. Therefore, women who start or stop taking oral contraceptives should be under constant medical supervision, and in most cases they will need to adjust the dose of lamotrigine.

Other oral contraceptives and hormone replacement drugs have not been studied, but they may similarly affect the pharmacokinetics of lamotrigine.

The effect of lamotrigine on the efficacy of hormonal contraceptives.

A clinical interaction study in 16 healthy volunteers showed a slight increase in the excretion of levonorgestrel and changes in serum levels of follicle-stimulating hormone and luteinizing hormone when lamotrigine was administered with a hormonal contraceptive (combination of ethinylestradiol 30 mcg/levonorgestrel 150 mcg). The effect of these changes on ovarian ovulation is unknown. It is possible that in some patients taking lamotrigine and hormonal contraceptives simultaneously, these changes may lead to a decrease in the effectiveness of the latter. Therefore, patients should be promptly informed of changes in their menstrual cycle, such as breakthrough bleeding.

Effect of lamotrigine on OCT 2 substrates.

Lamotrigine is an inhibitor of renal tubular secretion via organic cation transporters. This may result in increased plasma levels of some drugs that are primarily excreted via the above route. Therefore, the use of lamotrigine with OCT 2 substrates with a narrow therapeutic index, such as dofetilide, is not recommended.

Dihydrofolate reductase.

Lamotrigine is a weak inhibitor of dihydrofolate reductase, so with prolonged use

It may affect folate metabolism. However, long-term use of lamotrigine did not produce any significant changes in hemoglobin, mean red blood cell volume, serum and red blood cell folate concentrations over 1 year, or red blood cell folate concentrations over 5 years.

Kidney failure.

In single-dose studies in patients with end-stage renal disease, lamotrigine plasma concentrations were not significantly altered. However, accumulation of the glucuronide metabolite is possible. Therefore, caution should be exercised when treating patients with renal impairment.

Patients with liver dysfunction.

Caution should be exercised when treating patients with impaired liver function with Lamal®.

Patients taking other medications containing lamotrigine.

Lamotrigine is not prescribed to patients who are already taking any other medication containing lamotrigine.

ECG of Brugada syndrome.

Arrhythmogenic ST-T abnormalities and typical ECG features of Brugada syndrome have been reported in patients treated with lamotrigine. Lamotrigine should be used with caution in patients with Brugada syndrome.

Hemophagocytic lymphohistiocytosis (HLH).

Patients should be informed of the symptoms associated with GLH; they should be advised to seek immediate medical attention if they experience these symptoms while taking lamotrigine. Patients who develop these symptoms should be carefully evaluated for the diagnosis of GLH. Lamotrigine should be discontinued immediately if an alternative etiology for these symptoms cannot be established.

Child development.

There are no data on the effects of lamotrigine on growth, puberty, or the development of cognitive, emotional, and behavioral functions.

Epilepsy.

As with other antiepileptic drugs, abrupt discontinuation of lamotrigine may result in an increase in seizure frequency. Unless the patient's condition requires abrupt discontinuation, such as rash, the dose of lamotrigine should be tapered gradually over a period of at least 2 weeks.

According to the literature, severe epileptic seizures can cause rhabdomyolysis, multiple organ failure, and disseminated intravascular coagulation syndrome, sometimes with fatal outcome. Similar cases are possible during treatment with lamotrigine.

There may be a clinically significant worsening in seizure frequency rather than improvement. In patients with more than 1 seizure type, improvement in control of one seizure type should be carefully weighed against worsening control of another seizure type. Treatment with lamotrigine may exacerbate myoclonic seizures.

There is evidence that the response to treatment with combinations of enzyme inducers is weaker than to treatment with combinations of non-enzyme inducing antiepileptic drugs. The reason for this is unknown.

When treating children with typical minor epileptic seizures, the effect is not achieved in all patients.

Bipolar disorders.

Children and adolescents.

Antidepressant treatment is associated with an increased risk of suicidal ideation and behavior in children and adolescents with major depressive disorder and other psychiatric disorders.

Fertility.

The use of lamotrigine in animal reproductive studies did not impair fertility.

There are no data on the effect of lamotrigine on fertility in humans.

Teratogenicity.

Lamotrigine is a weak inhibitor of dihydrofolate reductase. There is a theoretical risk of congenital malformations if a woman is treated with folate inhibitors during pregnancy. However, reproductive toxicology studies of lamotrigine in animals at doses exceeding the human therapeutic dose have not revealed a teratogenic effect.

Use during pregnancy or breastfeeding

Risk associated with the use of antiepileptic drugs in general.

Women of childbearing potential should seek medical advice. When planning pregnancy, the need for antiepileptic treatment should be reconsidered. Women with epilepsy who are already being treated should avoid abrupt discontinuation of antiepileptic therapy, as this may lead to an exacerbation of seizures and have serious consequences for both the woman and the child.

The risk of birth defects is higher with combination antiepileptic therapy compared to monotherapy, so monotherapy should be used wherever possible.

Risk associated with the use of lamotrigine.

Pregnancy period.

Postmarketing data from a study involving over 8,700 women exposed to lamotrigine as monotherapy during the first trimester of pregnancy have been obtained. Overall, these data did not indicate a significant increase in the risk of most birth defects, but a limited number of registries have reported an increased risk of the birth defect isolated cleft palate. Other data are not yet available to support this. Animal studies have shown developmental toxicity.

If lamotrigine therapy is necessary during pregnancy, the lowest possible therapeutic dose should be used.

Lamotrigine has a weak inhibitory effect on dihydrofolate reductase and therefore could theoretically increase the risk of fetal malformations by reducing folic acid levels. Therefore, the need for folic acid supplementation should be considered during planning and early pregnancy.

Physiological changes during pregnancy may affect lamotrigine levels and/or its therapeutic effect. There have been cases of decreased lamotrigine levels during pregnancy. Therefore, pregnant women taking lamotrigine should be given appropriate treatment. Additionally, patients should be monitored postpartum.

Breastfeeding period.

The concentration of lamotrigine in the infant's plasma can reach up to 50% of the maternal concentration.

Therefore, the benefits of breastfeeding should be weighed against the potential risk of adverse effects in the infant. If a woman decides to breastfeed while taking lamotrigine, the infant should be monitored for adverse effects such as sedation, rash, and poor weight gain.

Ability to influence reaction speed when driving vehicles or other mechanisms

Two studies in volunteers found that the effects of lamotrigine on visual coordination, eye movement, body control and subjective sedation were no different from those of placebo. Dizziness and diplopia have been reported with lamotrigine, so patients should first assess their own response to lamotrigine treatment before driving or operating machinery. Since there is an individual response to antiepileptic drugs, the patient should consult a doctor regarding the specifics of driving in these cases.

Method of administration and doses

Lamal® tablets should be swallowed whole, without chewing or breaking.

If the dose of lamotrigine (for example, in children or in adult patients with impaired liver function) does not correspond to the dose of a whole tablet, then the smallest dose that corresponds to a whole tablet should be prescribed.

Epilepsy.

In monotherapy.

Adults and children aged 13 years and over (see Table 2).

The initial dose of Lamal® is 25 mg once daily for 2 weeks, then the drug is taken at a dose of 50 mg per 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 per day in 1–2 doses. For some patients, an increase in the dose to 500 mg per day may be necessary.

Children aged 2 to 12 years (see Table 3).

The initial dose of Lamal® for the treatment of typical minor epileptic seizures is 0.3 mg/kg/body weight per day in 1–2 doses per day for 2 weeks, then 0.6 mg/kg/body weight per day in 1–2 doses per day for the next 2 weeks. The dose should then be increased by 0.6 mg/kg every 1–2 weeks until the optimal effect is achieved. The usual maintenance dose is 1–15 mg/kg/day in 1–2 doses. Some patients may require a higher dose. The maximum maintenance dose is 200 mg/day.

Due to the risk of rashes, the initial dose should not be exceeded and the rate of its increase should not be accelerated.

With combination therapy.

Adults and children aged 13 years and over (see Table 2).

For patients taking valproate (including in combination with other antiepileptic drugs), the initial dose of Lamal® is 25 mg every other day for 2 weeks, then 25 mg every day for the next 2 weeks. After that, the dose should be increased (maximum by 25-50 mg/day) every 1-2 weeks until the optimal therapeutic effect is achieved. The usual maintenance dose is 100-200 mg per day in 1-2 doses.

For patients taking other antiepileptic drugs or other drugs that induce lamotrigine glucuronidation, with or without other antiepileptic drugs (except sodium valproate), the initial dose of Lamal® is 50 mg once daily for 2 weeks, then 100 mg daily in 2 divided doses for 2 weeks. The dose should then 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 daily in 2 divided doses. Some patients may require an increase in dose to 700 mg daily.

For patients taking other drugs that do not significantly induce or inhibit lamotrigine glucuronidation (see section "Interaction with other drugs and other forms of interaction"), the initial dose of Lamictal® is 25 mg once daily for 2 weeks, then 50 mg once daily for the next 2 weeks. After that, the dose should be increased (maximum by 50-100 mg per day) every 1-2 weeks until the optimal therapeutic effect is achieved.