Lamotrigine 100 tablets 100 mg blister No. 60

Instructions Lamotrigine 100 tablets 100 mg blister No. 60

Composition

active ingredient: lamotrigine;

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

Excipients: microcrystalline cellulose, colloidal anhydrous silica, povidone, sodium starch glycolate (type A), lactose monohydrate, magnesium stearate.

Dosage form

Pills.

main physicochemical properties: tablets, white or almost white in color, with a biconvex surface, round in shape (Lamotrigine 25), with a score on one side (Lamotrigine 50 and Lamotrigine 100).

Pharmacotherapeutic group

Antiepileptic drugs. Lamotrigine. ATX code N03A X09.

Pharmacological properties

Pharmacodynamics

Lamotrigine is an anticonvulsant drug whose mechanism of action is associated with the blockade of voltage-gated sodium channels of presynaptic neuronal membranes in the phase of slow inactivation and the inhibition of excessive release of glutamate (an amino acid that plays a significant role in the development of an epileptic seizure).

Pharmacokinetics

After oral administration, the drug is rapidly and completely absorbed from the gastrointestinal tract. Maximum plasma concentration is reached after approximately 2.5 hours.

Lamotrigine is extensively metabolized, with the major metabolite being the N-glucuronide. In adults, the elimination half-life averages 29 hours. Lamotrigine has a linear pharmacological profile. It is excreted primarily as metabolites and partially unchanged, primarily in the urine. The elimination half-life is shorter in children than in adults.

Special patient groups.

Children.

Weight-based clearance is higher in children than in adults, with the highest values in children under 5 years of age. The elimination half-life of lamotrigine in children is generally shorter than in adults, with a mean value of approximately 7 hours when co-administered with enzyme inducers such as carbamazepine and phenytoin, and an increase to a mean value of 45-50 hours when co-administered exclusively with valproate.

Elderly patients.

A pharmacokinetic analysis of a population of patients, which included both elderly and young patients with epilepsy, in a single study was reported to show that the clearance of lamotrigine was not changed to a clinically relevant extent. After single doses, apparent clearance decreased by 12% from 35 mL/min/kg in patients aged 20 years to 31 mL/min/kg in patients aged 70 years. The decrease after 48 weeks of treatment was 10% from 41 mL/min in young patients to 37 mL/min in elderly patients. The pharmacokinetics of lamotrigine were reported to have been studied in 12 healthy elderly patients who were given a single 150 mg dose. The mean clearance in elderly patients (0.39 mL/min/kg) is within the range of the mean clearance (0.31 to 0.65 mL/min/kg) obtained in 9 studies conducted in non-elderly adults after receiving a single dose of 30 to 450 mg.

Patients with impaired renal function.

A single 100 mg dose of lamotrigine was administered to 12 volunteers with chronic renal impairment and 6 patients on haemodialysis. The mean CL/F values were 0.42 mL/min/kg (chronic renal impairment), 0.33 mL/min/kg (inter-haemodialysis) and 1.57 mL/min/kg (during haemodialysis) compared with 0.58 mL/min/kg in healthy subjects. The mean plasma elimination half-life was 42.9 hours (chronic renal impairment), 57.4 hours (inter-haemodialysis) and 13.0 hours (during haemodialysis), compared with 26.2 hours in healthy subjects. Lamotrigine was reduced by approximately 20% (5.6 to 35.1) during a 4-hour haemodialysis session. For this group of patients, the initial dose of lamotrigine should be based on the patient's antiepileptic drug regimen; a reduction in the maintenance dose may be effective in patients with significant renal impairment.

Patients with impaired liver function.

A single-dose pharmacokinetic study was conducted in patients with varying degrees of hepatic impairment and healthy volunteers. The mean apparent clearance of lamotrigine was 0.31 mL/min/kg, 0.24 mL/min/kg, and 0.10 mL/min/kg in patients with Child-Pugh A, B, and C hepatic impairment, respectively, compared with 0.34 mL/min/kg in healthy subjects. In general, the initial, titration, and maintenance doses should be reduced by approximately 50% for patients with moderate hepatic impairment (Child-Pugh B) and by 75% for patients with severe hepatic impairment (Child-Pugh C). The titration and maintenance doses should be adjusted based on response to treatment.

Indication

Epilepsy.

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 absence seizures.

Bipolar disorders in adults.

Adults (ages 18 and over).

For the prevention of depressive states in patients with bipolar I disorder who predominantly suffer from depressive states.

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

Contraindication

Hypersensitivity to lamotrigine or to any of the other ingredients of the drug.

Interaction with other medicinal products and other types of interactions

Uridine 5'-diphospho (UDP)-glucuronyl transferase (UGT) has been identified as the enzyme responsible for the metabolism of lamotrigine. Therefore, drugs that induce or inhibit glucuronidation may affect the clearance of lamotrigine. Strong or moderate inducers of the cytochrome P450 3A4 enzyme (CYP3A4) known to induce UGT may also increase the metabolism of lamotrigine. There is no evidence that lamotrigine can cause clinically significant stimulation or inhibition of cytochrome P450 oxidative enzymes. Lamotrigine can induce its own metabolism, but this effect is modest and has no significant clinical consequences.

Those drugs that have been shown to have a relevant clinical effect on lamotrigine concentrations are listed in Table 1. Specific dosing recommendations for these drugs are provided in the Dosage and Administration section. Those drugs that have been shown to have little or no effect on lamotrigine concentrations are also listed in Table 1. In general, concomitant use of such drugs is not expected to have any clinical effect. However, caution should be exercised in patients with epilepsy whose disease state is particularly sensitive to fluctuations in lamotrigine concentrations.

Table 1

Effect of other drugs on lamotrigine concentrations

For detailed information on dosage, see the section “General dosage recommendations for special patient groups” in the “Method of administration and dosage” section. For dosage instructions for women taking hormonal contraceptives, see the section “Hormonal contraceptives” in the “Special warnings and precautions for use” section.

Interaction with antiepileptic drugs (AEDs) (see also section “Method of administration and dosage”).

Valproate, which inhibits lamotrigine glucuronidation, slows the metabolism of lamotrigine and increases its mean half-life by approximately 2-fold.

Some AEDs (such as phenytoin, carbamazepine, phenobarbital, and primidone) that induce cytochrome P450 microsomal enzymes induce UTG and accelerate the metabolism of lamotrigine.

Central nervous system adverse reactions, including dizziness, ataxia, diplopia, blurred vision, and nausea, have been reported in patients receiving carbamazepine concomitantly with lamotrigine. These events usually resolve with dose reduction of carbamazepine. Similar effects have been observed in studies of lamotrigine and oxcarbazepine in adult volunteers, but dose reduction has not been studied. It is known that in a study in healthy adult volunteers using a dose of lamotrigine 200 mg and a dose of oxcarbazepine 1200 mg, oxcarbazepine did not alter the metabolism of lamotrigine, and lamotrigine did not alter the metabolism of oxcarbazepine.

It was reported that a study in volunteers found that coadministration of felbamate 1200 mg twice daily and lamotrigine 100 mg twice daily 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 or without gabapentin showed that gabapentin did not alter the baseline clearance of lamotrigine.

It is known that the potential drug interaction between levetiracetam and lamotrigine has been studied by assessing 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 of pregabalin (200 mg 3 times daily). There is no pharmacokinetic interaction between lamotrigine and pregabalin.

It is known that, according to the study, the use of zonisamide (200-400 mg/day) together with lamotrigine (150-500 mg/day) for 35 days for the treatment of epilepsy had no significant effect on the pharmacokinetics of lamotrigine.

Plasma lamotrigine concentrations were not affected by co-administration with lacosamide (200, 400 or 600 mg/day) in placebo-controlled clinical trials in patients with partial-onset seizures. In three placebo-controlled clinical trials of additional co-administration of perampanel with lamotrigine in patients with partial-onset and primary generalized tonic-clonic seizures, the highest dose of perampanel tested (12 mg/day) increased lamotrigine clearance by less than 10%.

Although there have been reports of changes in plasma concentrations of other antiepileptic drugs, available data suggest that lamotrigine does not affect the plasma concentrations of concomitant antiepileptic drugs. In vitro studies have shown that lamotrigine does not affect the binding of other antiepileptic drugs to serum proteins.

Interaction with other psychotropic substances (see also section "Method of administration and dosage").

It is known that concomitant administration of 100 mg/day of lamotrigine and 2 g of lithium gluconate, administered 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, with only a slight increase in lamotrigine glucuronide levels. It is known that in a study in adult volunteers, 15 mg of olanzapine reduced the area under the concentration-time curve (AUC) and maximum concentration (Cmax) of lamotrigine by an average of 24% and 20%, respectively. Lamotrigine at a dose of 200 mg does not affect the pharmacokinetics of olanzapine. Multiple oral doses of lamotrigine 400 mg/day have no clinically significant effect on the pharmacokinetics of risperidone when administered as a single 2 mg dose. Somnolence has been reported when risperidone 2 mg was co-administered with lamotrigine. Available data indicate that no cases of somnolence have been reported with lamotrigine alone.

It is known that in a clinical study involving 18 adult patients with bipolar disorder who received lamotrigine (≥ 100 mg/day) and aripiprazole with a gradual dose increase from 10 mg/kg to 30 mg/kg over 7 days and then for another 7 days, an approximately 10% decrease in Cmax and AUC of lamotrigine was observed.

In vitro studies have shown that the formation of the primary metabolite of lamotrigine, the N-glucuronide, is only minimally affected by amitriptyline, bupropion, clonazepam, fluoxetine, haloperidol or lorazepam. Studies of the metabolism of bufuralol in human liver microsomes indicate that lamotrigine does not reduce the clearance of drugs that are primarily metabolized by CYP 2D6.

In vitro studies suggest that lamotrigine clearance is not affected by clozapine, phenelzine, risperidone, sertraline or trazodone.

Interaction with hormonal contraceptives.

Effect of hormonal contraceptives on the pharmacokinetics of lamotrigine.

There is evidence that the combination of "ethinylestradiol 30 mcg/levonorgestrel 150 mcg" increases the excretion of lamotrigine by approximately 2-fold, which in turn causes a decrease in the area under the curve AUC and Cmax of lamotrigine, on average by 52% and 39%, respectively. With a one-week break in contraceptive use (the so-called contraceptive-free week), the concentration of lamotrigine in the blood serum gradually increased, reaching a concentration that was approximately 2-fold higher than with concomitant use of the drugs (see the section "Method of administration and dosage" and the section "Special instructions for use").

The effect of lamotrigine on the pharmacokinetics of hormonal contraceptives.

It is known that in women, a fixed dose of lamotrigine 300 mg did not affect the pharmacokinetics of ethinylestradiol, which is part of a combined oral contraceptive pill. There was a persistent slight increase in the elimination of levonorgestrel, which in turn caused a decrease in the AUC and Cmax of levonorgestrel by an average of 19% and 12%, respectively. Measurements of serum levels of follicle-stimulating hormone and luteinizing hormone and estradiol during the study showed suppression of ovarian hormonal activity in some women, although measurements of serum progesterone levels revealed that there were no hormonal symptoms of ovulation in any of the women. The effect of changes in serum follicle-stimulating hormone and luteinizing hormone levels and the slight increase in levonorgestrel excretion on ovarian ovulatory activity is unknown (see section “General dosage recommendations for special patient groups” in the “Dosage and administration” section for dosage in women taking hormonal contraceptives and section “Hormonal contraceptives” in the “Special warnings and precautions for use” section). It is known that the effect of lamotrigine at daily doses above 300 mg has not been studied. It has been reported that studies of other hormonal contraceptives have also not been conducted.

It is known that in a study involving 10 male volunteers taking rifampicin, the excretion rate was increased and the half-life of lamotrigine was reduced due to the induction of hepatic enzymes responsible for glucuronidation.

For patients receiving concomitant rifampicin therapy, the treatment regimen recommended for lamotrigine and related glucuronidation inducers should be used (see section 4.2).

In studies in healthy volunteers, lopinavir/ritonavir approximately halved the plasma concentration of lamotrigine by inducing glucuronidation.

For patients receiving concomitant lopinavir/ritonavir therapy, the treatment regimen recommended for concomitant use of lamotrigine with appropriate glucuronidation inducers should be used (see section 4.2).

The use of atazanavir/ritonavir (300 mg/100 mg) reduces the AUC and Cmax of lamotrigine in plasma (at a dose of 100 mg) by an average of 32% and 6%, respectively (see the subsection “General dosage recommendations for special patient groups” in the “Method of administration and dosage” section).

According to studies in healthy volunteers, the use of paracetamol at a dosage of 1 g (four times a day) reduced the AUC and Cmin of lamotrigine in blood plasma by an average of 20% and 25%, respectively.

In vitro studies of the effects of lamotrigine on organic cation transporter 2 (OCT 2) have demonstrated that lamotrigine, but not the N(2)-glucuronide metabolite, is an inhibitor of OCT 2 at potentially clinically relevant concentrations. Lamotrigine is an inhibitor of OCT 2 with IC50 values of 53.8 μM and 186 μM, respectively (see section 4.4).

Interactions affecting laboratory test results.

Lamotrigine has been reported to interfere with tests used for the rapid detection of certain drugs in urine, resulting in false-positive results, particularly for phencyclidine. An alternative, more specific chemical method should be used to confirm positive results.

Application features

Skin rashes

A skin rash may occur within the first 8 weeks of treatment with lamotrigine. In most cases, the rash is mild and resolves without treatment, but severe skin reactions requiring hospitalisation and discontinuation of the drug have been reported. These include potentially life-threatening rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS); also known as hypersensitivity syndrome (HSS) (see section 4.8).

Patients who have experienced Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms (DRESS) after taking lamotrigine should not be re-administered with lamotrigine. In adults who participated in studies following current dosing recommendations for lamotrigine, the incidence of severe skin rashes is known to be approximately 1 in 500 patients with epilepsy. Approximately half of these cases were diagnosed as Stevens-Johnson syndrome (1 in 1,000). 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. Studies with lamotrigine have shown that the incidence of rashes leading to hospitalisation 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 be aware of the possibility of 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 rash appears to be closely related to high initial doses of lamotrigine and exceeding the recommended dose escalation schedule for lamotrigine therapy (see section 4.2), as well as to concomitant use of valproate (see section 4.2).

Lamotrigine should be prescribed with caution to 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.

The HLA-B*1502 allele in individuals of Asian (predominantly Chinese and Thai) descent is associated with an increased risk of Stevens-Johnson syndrome/toxic epidermal necrolysis with lamotrigine. If a patient tests positive for the HLA-B*1502 allele, the decision to use lamotrigine should be carefully considered.

Skin rashes have been reported as a manifestation of DRESS syndrome, also known as hypersensitivity syndrome. This condition is accompanied by various systemic symptoms, including fever, lymphadenopathy, facial swelling, abnormal blood counts, liver and kidney function, and aseptic meningitis (see section 4.8). The syndrome can vary in severity and can rarely lead to disseminated intravascular coagulation and multiorgan failure. 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 promptly and, unless otherwise indicated, lamotrigine should be discontinued.

In most cases, aseptic meningitis resolves after discontinuation of the drug, but in some cases it may recur when lamotrigine is re-administered. 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.

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).

Hemophagocytic lymphohistiocytosis (HLH)

GLH has been reported in patients taking lamotrigine (see section 4.8). GLH is characterised by signs and symptoms such as fever, rash, neurological symptoms, hepatosplenomegaly, lymphadenopathy, cytopenias, increased serum ferritin, hypertriglyceridaemia and abnormal liver and coagulation functions. Symptoms usually occur within 4 weeks of initiation of treatment.

Patients should be informed about the symptoms associated with GLH and advised to seek immediate medical attention if these symptoms occur during treatment with lamotrigine.

Patients who develop these signs and symptoms should be evaluated promptly and a diagnosis of GLH should be considered. Lamotrigine therapy should be discontinued immediately if another cause for the symptoms cannot be identified.

Suicidal risk

Patients with epilepsy may experience symptoms of depression and/or bipolar disorder, and there is evidence that patients 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. They may experience worsening depressive symptoms and/or the emergence of suicidal thoughts and behavior (suicidality) whether or not they have used medications for bipolar disorder, including lamotrigine.

Suicidal ideation and behavior have been reported in patients treated with antiepileptic drugs for a variety of indications, including epilepsy. A meta-analysis of antiepileptic drugs, including lamotrigine, has shown a small increased risk of suicidal ideation and behavior. The mechanism of this risk is unknown, but available data do not exclude the possibility of an increased risk with lamotrigine. Therefore, patients should be closely monitored for suicidal ideation and behavior. Patients and caregivers should seek medical advice if such signs appear.

Clinical deterioration in bipolar disorder

Patients taking lamotrigine for bipolar disorder should be closely monitored for clinical worsening (including the appearance of new symptoms) or suicidality, especially at the beginning of treatment or during dose changes.

Patients with a history of suicidal behaviour or thoughts, or who have demonstrated a significant degree of suicidal ideation prior to initiation of treatment, are at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment.

Patients and caregivers should be warned about the need to monitor for any worsening of their condition (including the appearance of new symptoms) and/or the appearance of suicidal thoughts/attempts or tendencies to self-harm, and to seek medical help promptly if these symptoms occur.

In this case, the situation should be assessed and appropriate changes made to the therapeutic regimen, and if necessary, treatment should be discontinued 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, have a sudden onset, and are not part of a pre-existing condition.

Hormonal contraceptives

Data have been obtained that the combination of "ethinylestradiol 30 mcg/levonorgestrel 150 mcg" increases the excretion of lamotrigine by approximately 2-fold, which in turn reduces the level of lamotrigine (see section "Interaction with other medicinal products and other types of interactions"). To obtain the maximum therapeutic effect, in most cases it is necessary to increase (by titration) the maintenance dose of lamotrigine (by 2-fold). In women who are not yet using drugs that induce lamotrigine glucuronidation and are already using hormonal contraceptives with a week-long break between courses (the so-called contraceptive-free week), a gradual temporary increase in lamotrigine levels may be observed during the week-long break. This increase will be greater if the dose of lamotrigine is increased a few days before or during the week-long break (for detailed information on dosage, see the subsection "General dosage recommendations for special patient groups" in the section "Method of administration and dosage"). Therefore, women who start taking oral contraceptives or who finish a course of oral contraceptives should be under constant medical supervision and in most cases will require a dose adjustment 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 effectiveness of hormonal contraceptives

A clinical interaction study in 16 healthy volunteers has been reported to show a slight increase in levonorgestrel excretion 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) (see section 4.5).

The effect of these changes on ovarian ovulation is unknown. However, it cannot be ruled out that in some patients taking lamotrigine and hormonal contraceptives, these changes may lead to a decrease in the effectiveness of the latter. Therefore, patients should promptly report any changes in their menstrual cycle, such as breakthrough bleeding.

Effect of lamotrigine on organic cation transporter 2 (OCT2) substrates

Lamotrigine is an inhibitor of renal tubular secretion via organic cation transporters (see section 4.5). This may lead to 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 long-term use of lamotrigine may affect folate metabolism. However, long-term use of lamotrigine does 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. Caution should be exercised when administering the drug to patients with renal impairment.

Patients taking other medications containing lamotrigine

Lamotrigine should not be taken by patients who are already being treated with any other medicine containing lamotrigine without consulting a doctor.

Brugada is a type of ECG

Arrhythmogenic ST-T abnormalities and typical Brugada ECGs have been observed in patients treated with lamotrigine. Therefore, careful consideration should be given to such treatment before lamotrigine is used in patients with Brugada syndrome.

Development in children

There is no information on the effects of lamotrigine on growth, puberty, or cognitive, emotional, and behavioral development in children.

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 at least 2 weeks.

Published data suggest that severe seizures may cause rhabdomyolysis, multiple organ failure, and disseminated intravascular coagulation syndrome, sometimes with fatal outcome. Similar events may occur with lamotrigine treatment. Significant clinical worsening in seizure frequency may occur 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. Lamotrigine treatment may exacerbate myoclonic seizures.

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

Bipolar disorder

Children (under 18 years of age)

Antidepressant treatment is associated with an increased risk of suicidal ideation and behavior in children (under 18 years of age) with major depressive disorder and other psychiatric disorders.

Fertility

Lamotrigine is known to have no effect on fertility in animal reproduction studies. There are no data on the effects of lamotrigine on fertility in humans.

Teratogenicity

Lamotrigine is a weak inhibitor of dihydrofolate reductase. There is a theoretical risk of birth defects in humans if a woman is treated with folate inhibitors during pregnancy. However, animal reproductive toxicology studies with lamotrigine at doses less than the human dose of 400 mg/day [based on body surface area (mg/m2)] have shown developmental toxicity (increased mortality, decreased body weight, increased structural changes, neurobehavioral abnormalities) but have not revealed a teratogenic effect.

The medicine contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take it.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.

Use during pregnancy or breastfeeding

Risk associated with the use of antiepileptic drugs in general.

Women of childbearing potential should seek specialist advice. Treatment with antiepileptic drugs should be considered when planning pregnancy. In women receiving treatment for epilepsy, abrupt withdrawal of antiepileptic drugs should be avoided as this may lead to recurrence of seizures, which may have serious consequences for the woman and the foetus. In all cases, monotherapy should be preferred, as the use of combination AED therapy may be associated with an increased risk of congenital malformations compared with monotherapy, depending on the AED used.

Risk associated with the use of lamotrigine.

Pregnancy.

A large amount of data on pregnant women exposed to lamotrigine monotherapy during the first trimester of pregnancy (more than 8700) do not indicate a significant increased risk of serious congenital malformations, including cleft palate. Animal studies have shown embryofetal toxicity.

If lamotrigine therapy is considered necessary during pregnancy, it is recommended that it be used at the lowest possible therapeutic dose.

Lamotrigine has a weak inhibitory effect on dihydrofolate reductase and therefore, theoretically, may increase the risk of fetal malformations by reducing folic acid levels (see section 4.4). Therefore, the need for folic acid intake should be considered when planning and in early pregnancy.

Physiological changes during pregnancy may affect lamotrigine levels and/or its therapeutic effect. There have been reports of decreased lamotrigine levels during pregnancy, potentially increasing the risk of loss of seizure control. Lamotrigine levels may increase rapidly after delivery, with the potential for dose-related adverse reactions. Therefore, serum lamotrigine levels should be monitored before, during and after pregnancy. If necessary, the lamotrigine dose should be modified to maintain serum lamotrigine concentrations at pre-pregnancy levels or adjusted accordingly.