Lamotrigine

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Lamotrigine: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Drug interactions
14. Analogs
15. Terms and conditions of storage
16. Terms of dispensing from pharmacies
17. Reviews
18. Price in pharmacies

Latin name: Lamotrigine

ATX code: N03AX09

Active ingredient: lamotrigine (Lamotrigine)

Manufacturer: Ozone, LLC (Russia)

Description and photo update: 2019-10-07

Prices in pharmacies: from 199 rubles.

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Lamotrigine is an antiepileptic drug.

Release form and composition

Dosage form - tablets: round flat-cylindrical shape, white or white with a yellowish tinge, with a risk on one side and with bevels on both sides (10-50 or 100 tablets in a can, in a cardboard box 1 can; 10, 25, 30 or 50 tablets in blister packs, in a cardboard box 1-3, 5 or 10 packs. Each pack also contains instructions for the use of Lamotrigine).

Composition of 1 tablet:

active substance: lamotrigine - 25, 50, 100 or 200 mg;
auxiliary components (25/50/100/200 mg): sodium carboxymethyl starch - 2.85 / 5.7 / 11.4 / 22.8 mg; lactose monohydrate (milk sugar) - 41.95 / 83.9 / 167.8 / 335.6 mg; povidone-K25 - 4.75 / 9.5 / 19/38 mg; microcrystalline cellulose - 19/38/76/152 mg; magnesium stearate - 0.95 / 1.9 / 3.8 / 7.6 mg; colloidal silicon dioxide - 0.5 / 1/2/4 mg.

Pharmacological properties

Pharmacodynamics

According to the results of pharmacological studies, lamotrigine is a blocker of voltage-gated sodium channels, while the effect of the drug itself is determined by the magnitude of the electric charge and produces a self-potentiating effect.

Lamotrigine helps to suppress the continuously repetitive firing of neurons and inhibits the release of glutamate (belongs to the neurotransmitters that play a key role in the occurrence of epileptic seizures). There is an assumption that these effects contribute to the anticonvulsant activity of the substance. At the same time, the mechanisms by which lamotrigine has a therapeutic effect in bipolar disorder have not been established, but its interaction with voltage-gated sodium channels is most likely important.

Pharmacokinetics

Lamotrigine is absorbed from the intestine quickly and in full, practically does not undergo first-pass first pass metabolism. The time to reach the maximum plasma concentration is approximately 2.5 hours after oral administration. The value of this indicator after eating increases slightly, while the degree of absorption does not change. Pharmacokinetic processes with a single dose of up to 450 mg (the maximum investigated dose) are linear. The maximum concentration of a substance in an equilibrium state has significant fluctuations, but individual variation is rarely observed.

The substance binds to blood plasma proteins by about 55%. It is unlikely that the release of a substance from its bond with proteins can cause toxic effects. The volume of distribution is in the range from 0.92 to 1.22 l / kg.

The enzyme UDP-glucuronyltransferase (uridine diphosphate glucuronyltransferase) is involved in the metabolism of the substance. To a small extent, depending on the dose, lamotrigine increases its own metabolism. There is no evidence that the substance affects the pharmacokinetics of other antiepileptic drugs. There is also no evidence that an interaction is possible between lamotrigine and other drugs that are metabolized by the cytochrome P _{450 system}.

The clearance of lamotrigine at equilibrium concentrations in healthy adults averages 39 ± 14 ml / min. Metabolism is accompanied by the formation of glucuronides, which are subsequently excreted by the kidneys.

Up to 10% of the dose is excreted unchanged by the kidneys, about 2% through the intestines.

The value of clearance and half-life does not depend on the dose. In healthy adults, the half-life is on average 24–35 hours. In Gilbert's syndrome, there is a decrease in drug clearance by 32% in comparison with the control group. However, this does not go beyond the normal range for the general population. Drugs taken simultaneously have a great influence on the half-life of a substance.

Depending on the drugs used in combination with lamotrigine, a change in the average half-life (T _1/2) is possible:

drugs-inducers of glucuronidation (phenytoin, carbamazepine): T _1/2 decreases to about 14 hours;
valproate: T _1/2 increases to an average of 70 hours.

The clearance of lamotrigine in children based on body weight is higher than in adult patients; it is highest in children under 5 years of age. The elimination half-life of a substance is usually shorter in children than in adults. Its average value is approximately 7 hours with simultaneous use with drugs that induce glucuronidation (carbamazepine, phenytoin), the indicator increases to an average of 45-50 hours against the background of combined use with valproate.

The starting dose of lamotrigine in patients with impaired renal function is calculated according to the standard antiepileptic drug regimen. A dose reduction may be required only for patients with a significant decrease in renal function.

Necessary adjustment of initial, increasing and maintenance doses for patients with impaired liver function:

moderate (Child-Pugh class B): about 50%;
severe (Child-Pugh class C): about 75%.

Dose escalation and maintenance dose should be determined by clinical response.

The efficacy of lamotrigine in preventing mood disorders in patients with bipolar disorder has been documented in two basic clinical studies. According to the results of the combined analysis of the obtained results, it was found that the duration of remission, which was defined as the time before the onset of the first episode of depression and before the first episode of hypomania / mania / mixed episode of mania and hypomania after stabilization, in the lamotrigine group, compared with placebo, is longer.

For depression, the duration of remission is more pronounced.

Indications for use

epilepsy (generalized and partial seizures, including tonic-clonic seizures, as well as seizures in patients with Lennox-Gastaut syndrome): adults - as monotherapy or as part of a combination treatment; children 3–12 years old - as part of a combination treatment, after achieving control of the disease, concomitant antiepileptic drugs are canceled, and Lamotrigine is continued as monotherapy;
bipolar disorder: the drug is used in adults to prevent mood disorders (depression, hypomania, mania, mixed episodes); the use of lamotrigine for the treatment of acute depressive or manic episodes is not indicated.

Contraindications

Absolute:

lactase deficiency, glucose-galactose malabsorption, lactose intolerance;
under 3 years of age - in the treatment of epilepsy, or up to 18 years - in the treatment of bipolar affective disorder;
individual intolerance to the components of the drug.

Relative (Lamotrigine tablets are used under medical supervision):

dysfunction of the kidneys and liver;
pregnancy and lactation.

Lamotrigine, instructions for use: method and dosage

Lamotrigine is intended for oral administration. The tablets should be swallowed whole without chewing or breaking. If the calculated dose cannot be divided by the whole number of tablets of the lower dosage, it should be adjusted to the nearest value of the whole tablet of the lower dosage.

If Lamotrigine is resumed, the physician should assess the need to increase the maintenance dose in patients who, for any reason, interrupt the drug intake, since with high initial doses and exceeding the recommended dose, the likelihood of a severe rash increases. The longer the period of time has passed since the last dose, the more caution is required when increasing the dose to a maintenance dose. If, after stopping the intake, a time has passed in excess of five half-lives, then the dose of Lamotrigine must be increased to a maintenance one according to the appropriate scheme.

You should not resume therapy with lamotrigine in patients in whom the discontinuation of treatment was associated with the appearance of a rash, unless the potential benefit of such treatment is higher than the possible risks.

Epilepsy

Monotherapy

The initial dose for children from 12 years of age and adults is 25 mg once a day for two weeks with a further increase in a single dose to 50 mg over the same period. Then, every 1-2 weeks, the dose is increased by a maximum of 50-100 mg until the optimal therapeutic effect is achieved. This is usually provided with a maintenance daily dose of 100-200 mg in 1 or 2 divided doses. Some patients may require a daily dose of 500 mg.

The initial daily dose of Lamotrigine for patients 3–12 years old with typical absences is 0.3 mg / kg in 1 or 2 doses for two weeks with a further increase in the single dose by 2 times over the same period. Then every 1-2 weeks the daily dose is increased by a maximum of 0.6 mg / kg until the optimal therapeutic effect is achieved. The calculation method allows relatively accurate dosage of the drug in children weighing 40 kg. The usual daily maintenance dose is in the range of 1-10 mg / kg in 1 or 2 divided doses, although higher doses may be needed.

Combination therapy

The initial dose of Lamotrigine in children from 12 years of age and adults who are already receiving valproic acid in combination with other antiepileptic drugs or without them is 25 mg every other day for two weeks, then, during the same period, take 25 mg 1 time per day … Then, every 1–2 weeks, the daily dose is increased by a maximum of 25–50 mg until the optimal therapeutic effect is achieved. The usual daily maintenance dose is 100-200 mg in 1 or 2 divided doses.

The initial dose of lamotrigine in patients receiving concomitant therapy with antiepileptic drugs or other drugs that induce glucuronidation of lamotrigine, with / without other antiepileptic drugs (except valproate), is 50 mg once a day for two weeks, then for the same period apply 100 mg per day in 2 divided doses. Then, every 1–2 weeks, the dose is increased by a maximum of 100 mg until the optimal therapeutic effect is achieved. The usual daily maintenance dose is from 200 to 400 mg in 2 divided doses, in some cases it is necessary to use Lamotrigine at a dose of 700 mg per day.

The initial dose of Lamotrigine in patients taking other drugs that do not have a significant effect on the inhibition / induction of lamotrigine glucuronidation is 25 mg once a day for two weeks, then, over the same period, 50 mg is taken once a day. Then, every 1-2 weeks, the dose is increased by a maximum of 50-100 mg until the optimal therapeutic effect is achieved. The usual daily maintenance dose is 100 to 200 mg in 1 or 2 divided doses.

The initial daily dose of Lamotrigine in children 3-12 years old, taking valproate with / without other antiepileptic drugs, is 0.15 mg / kg in 1 dose for two weeks, then during the same period - 0.3 mg / kg in 1 reception. Then, until the optimal therapeutic effect is achieved, the daily dose is increased every 1–2 weeks by a maximum of 0.3 mg / kg. The usual daily maintenance dose is 1–5 mg / kg in 1 or 2 divided doses, the maximum is 200 mg per day.

The initial daily dose of lamotrigine in children 3-12 years old who receive antiepileptic drugs or other drugs that induce glucuronidation of lamotrigine, in combination with or without other antiepileptic drugs (except for valproates), is 0.6 mg / kg in 2 divided doses for two weeks, then during the same period - 1.2 mg / kg per day in 2 divided doses. Then every 1–2 weeks the dose is increased by a maximum of 1.2 mg / kg until the optimal therapeutic effect is achieved. The usual daily maintenance dose is 5-15 mg / kg in 2 divided doses, the maximum is 400 mg per day.

The initial daily dose of lamotrigine in patients taking other drugs that do not have a significant effect on the inhibition / induction of glucuronidation of lamotrigine is 0.3 mg / kg in 1 or 2 doses for two weeks, then, during the same period, the dose is increased to 0.6 mg / kg in 1 or 2 divided doses. Then, until the optimal therapeutic effect is achieved, the dose is increased by a maximum of 0.6 mg / kg every 1-2 weeks. The usual daily maintenance dose is 1 to 10 mg / kg in 1 or 2 divided doses, the maximum is 200 mg per day.

Children 3–6 years of age are likely to need a maintenance dose that is at the upper end of the recommended range. It is necessary to control the child's body weight and, if it changes, dose adjustment.

If the calculated daily dose in patients taking valproate is 1–2 mg, Lamotrigine can be prescribed at a dose of 2 mg every other day for the first two weeks. If the calculated daily dose is less than 1 mg, Lamotrigine is not prescribed.

The use of the drug in children under 2 years of age as monotherapy or in children under 1 month of age as an adjunctive therapy has not been studied. In children from 1 month to 2 years, the effectiveness and safety of Lamotrigine as an adjunctive therapy for partial seizures has not been established.

Children under 3 years old are not allowed to use solid dosage forms.

Bipolar disorder

When using Lamotrigine, it is necessary to follow a transitional dosing regimen, which includes increasing the dose of the drug over 6 weeks to a supporting stabilizing one, after which, if indicated, other psychotropic and / or antiepileptic drugs can be canceled.

Combined use with lamotrigine glucuronidation inhibitors (eg, valproate)

The initial dose is 25 mg every other day for two weeks, then, over the same period, 1 time per day, 25 mg. In the fifth week, the dose is increased to 50 mg per day in 1 or 2 divided doses.

For optimal therapeutic benefits, the usual target daily dose is 100 mg in 1 or 2 divided doses. Depending on the clinical effect, the dose may be increased to a maximum of 200 mg.

Combination therapy with lamotrigine glucuronidation inducers in patients not taking inhibitors (such as valproate)

This dosing regimen should be used when used with phenytoin, phenobarbital, carbamazepine, primidone and other inducers of lamotrigine glucuronidation.

The initial dose is 50 mg once a day for two weeks, then during the same period the drug is taken in a daily dose of 100 mg in 2 divided doses. In the fifth week, the dose is increased to 200 mg per day in 2 divided doses, at the sixth, an increase to 300 mg per day is possible. To achieve optimal therapeutic effect, the usual target daily dose is 400 mg in 2 divided doses, it is prescribed starting from the seventh week of therapy.

Monotherapy or combination therapy in patients taking drugs that do not have a significant inducing or inhibitory effect on lamotrigine glucuronidation

The initial dose is 25 mg once a day for two weeks, then during the same period the drug is taken at 50 mg per day in 1 or 2 doses. In the fifth week, the daily dose is increased to 100 mg in 1 or 2 doses. To achieve optimal therapeutic effect, the usual target daily dose is 200 mg (in clinical trials, doses in the range of 100-400 mg were used) in 1 or 2 doses. Once the target daily maintenance stabilizing dose has been reached, other psychotropic drugs may be withdrawn.

Maintenance stabilizing total daily dose of lamotrigine in the treatment of bipolar affective disorder after concomitant psychotropic and antiepileptic drugs have been discontinued:

therapy after discontinuation of combined treatment with inhibitors of lamotrigine glucuronidation, for example valproate: the target stabilizing dose immediately after discontinuation of valproate should be doubled and maintained at this level;
therapy after discontinuation of combined treatment with inducers of lamotrigine glucuronidation, depending on the initial maintenance dose: the regimen is used when using carbamazepine, phenytoin, primidone, phenobarbital or other inducers of lamotrigine glucuronization; the dose should be gradually reduced over three weeks after the withdrawal of these drugs;
therapy after the cancellation of psychotropic drugs that do not have an inhibitory / inducing effect on the glucuronidation of lamotrigine: dose adjustment is not carried out, the dose should remain at the level achieved during the increase regimen.

There is no clinical experience in correcting daily doses of Lamotrigine after adding other drugs. However, based on drug interaction studies, the following recommendations can be followed:

the addition of inhibitors of glucuronidation of lamotrigine (for example, valproate): the current stabilizing dose is reduced by 2 times;
adding inducers of lamotrigine glucuronidation in patients who do not receive valproate: this regimen should be used when using carbamazepine, phenytoin, primidone, phenobarbital or other inducers of lamotrigine glucuronidation; during the first week, the current stabilizing dose is not changed, from the second week it is increased by 50%, from the third - a repeated increase is carried out, thus, the dose exceeds the initial stabilizing dose by 2 times;
the addition of other drugs that do not have a significant inducing / inhibitory effect on the glucuronidation of lamotrigine: dose adjustment is not required.

When conducting clinical studies, it was found that abrupt withdrawal of Lamotrigine did not cause an increase in the severity, frequency or change in the nature of adverse reactions, in comparison with placebo. Therefore, patients can cancel the drug immediately, without gradually reducing its dose.

General recommendations for the use of Lamotrigine in special categories of patients

Combined use with hormonal contraceptives

use of lamotrigine in patients already receiving hormonal contraceptives: it is recommended to consider the use of continuous contraceptives or other non-hormonal methods of contraception. The regimen should be consistent with the directions, depending on whether lamotrigine is added to inhibitors or inducers of its glucuronidation;
the use of hormonal contraceptives by patients already receiving maintenance doses of lamotrigine and not taking inducers of its glucuronidation: an increase in the maintenance dose of lamotrigine is usually necessary, but not more than 2 times. In the case of the appointment of hormonal contraceptives, it is recommended to increase the daily dose by 50-100 mg every week (depending on the clinical picture). It is not recommended to exceed these figures if the woman's clinical condition does not require a further increase in the dose. Against the background of the use of contraceptives, including 7 days of inactive treatment, control of serum lamotrigine levels should be carried out during the third week of active treatment, that is, from 15 to 21 days of the menstrual cycle. It is recommended to consider the use of continuous contraceptives or other non-hormonal methods of contraception;
discontinuation of hormonal contraceptives by patients who are already receiving maintenance doses of lamotrigine and are not receiving inducers of its glucuronidation: usually a dose reduction is necessary, but not more than 50%. If the woman's clinical condition does not require otherwise, it is recommended to gradually decrease the daily dose of Lamotrigine every week by 50-100 mg (the rate of decrease is not more than 25% of the daily dose per week) for more than three weeks.

Combined use with ritonavir

An increase in the dose of lamotrigine should be carried out on the basis of recommendations, based on whether it is added to therapy with inhibitors or inducers of glucuronidation, or used in their absence.

In patients who are already taking maintenance doses of lamotrigine and do not use inducers of its glucuronidation, the dose of the drug while using atazanavir in combination with ritonavir may need to be increased, and if canceled, it will need to be reduced.

Impaired liver and kidney function

The initial, increasing and maintenance doses of the drug with moderate and severe hepatic impairment should be reduced by 50 and 75%, respectively. Correction of increasing and maintenance doses should be carried out depending on the clinical effect.

Lamotrigine tablets for renal failure should be used with caution. Initial doses of the drug in patients with end-stage renal failure should be calculated in accordance with the dosage regimen for patients taking antiepileptic drugs. Patients with a significant decrease in renal function may be advised to reduce maintenance doses.

Side effects

There are reports of adverse reactions in patients with epilepsy and bipolar disorder. When considering the safety profile of a drug as a whole, information relating to both diseases should be taken into account.

Disorders registered mainly in the course of clinical trials in patients with epilepsy (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare):

skin and subcutaneous tissue: very often - skin rash; rarely - Stevens-Johnson syndrome; very rarely - toxic epidermal necrolysis;
immune system: very rarely - hypersensitivity syndrome (including fever, facial swelling, lymphadenopathy, multiple organ failure, disseminated intravascular coagulation syndrome);
blood and lymphatic system: very rarely - hematological disorders (including neutropenia, anemia, leukopenia, pancytopenia, thrombocytopenia, aplastic anemia, agranulocytosis), lymphadenopathy (these disorders may or may not be associated with hypersensitivity syndrome);
psyche: often - irritability, aggressiveness; very rarely - hallucinations, tics, confusion;
nervous system (with monotherapy with the drug): very often - headache; often - tremors, insomnia, drowsiness, dizziness; infrequently - ataxia; rarely - an increase in the frequency of seizures (recorded only in patients with epilepsy), nystagmus;
digestive system (with monotherapy with the drug): often - vomiting, nausea, diarrhea;
organ of vision (with monotherapy with the drug): infrequently - blurred vision, diplopia;
musculoskeletal and connective tissue: very rarely - lupus-like syndrome;
liver and biliary tract: very rarely - increased activity of liver enzymes, liver failure, liver dysfunction;
general disorders: often - fatigue.

Adverse reactions from systems and organs according to post-marketing use data:

psyche: very rarely - nightmares;
nervous system: very often - dizziness, ataxia, drowsiness, headache; often - tremor, nystagmus, insomnia; rarely - aseptic meningitis; very rarely - increased frequency of seizures, movement disorders, agitation, worsening symptoms of Parkinson's disease, choreoathetosis, extrapyramidal disorders, gait instability;
digestive system: very often - vomiting, nausea; often - diarrhea;
organ of vision: very often - blurred vision, diplopia; rarely - conjunctivitis.

In double-blind additional clinical trials, skin rash occurred in 10% of adult patients taking lamotrigine and in 5% of patients in the placebo group. In 2% of cases, the appearance of a skin rash led to the discontinuation of the drug. The rash, predominantly maculopapular in nature, appears mainly during the first 8 weeks from the moment the drug is started and disappears after its withdrawal.

There are reports of rare cases of severe, potentially life-threatening skin lesions, including Stevens-Johnson and Lyell syndromes. Although symptoms usually reversed when the drug was discontinued, some patients had permanent scars. There are reports of rare cases of death. Also, the development of rash was considered as a manifestation of hypersensitivity syndrome associated with various systemic manifestations.

Lamotrigine therapy can lead to a worsening of signs of parkinsonism in patients with pre-existing Parkinson's disease, and in isolated cases - to extrapyramidal symptoms and choreoathetosis in patients without previous disorders.

Hepatic dysfunction usually appears in combination with symptoms of hypersensitivity, however, in isolated cases, they develop in the absence of obvious signs of hypersensitivity.

Adverse events reported mainly in clinical trials in patients with bipolar disorder:

skin and subcutaneous tissue (according to clinical studies): very often - skin rash; rarely - Stevens-Johnson syndrome;
psyche (according to post-marketing use): very rarely - nightmares;
nervous system (according to clinical studies): very often - headache; often - drowsiness, agitation, dizziness;
musculoskeletal and connective tissue (according to clinical studies): often - arthralgia;
digestive system: often - xerostomia;
general disorders (according to clinical studies): often - pain, including back pain.

Overdose

In the case of taking doses 10–20 times higher than the maximum therapeutic dose, fatal cases have been reported.

The main symptoms are: widening of the QRS interval (lengthening of intraventricular conduction time), nystagmus, ataxia, epileptic seizure, impaired consciousness and coma.

Therapy: hospitalization and supportive symptomatic treatment are indicated in accordance with the recommendations of the national poison control center or the clinical picture.

special instructions

There is information about the development of adverse reactions from the skin, which may appear during the first eight weeks after starting the use of Lamotrigine. In most cases, rashes are characterized by a mild course and go away on their own, but sometimes hospitalization and drug withdrawal are required. Potentially life-threatening skin reactions such as Stevens-Johnson syndrome and Lyell's syndrome (toxic epidermal necrolysis) may develop.

In adult patients with epilepsy, severe skin reactions when lamotrigine is used in accordance with generally accepted recommendations occur in about one in 500 cases. Stevens-Johnson syndrome is reported in approximately 50% of patients with similar reactions.

According to clinical studies, the incidence of severe skin rashes in bipolar disorder is approximately 1 in 1000 patients. Children are more likely to develop severe skin rashes than adults. The incidence of skin rashes requiring hospitalization is 1 case per 100–300 sick children.

The initial manifestations of a rash in children can be mistaken for an infection, so the likelihood of a reaction to lamotrigine must be considered. The overall risk of this disorder is largely associated with the following factors:

high initial dose of the drug and exceeding the recommended rate of increasing the dose;
combined use with valproate.

With a burdened history of allergic reactions or in cases of a rash in response to the use of other antiepileptic drugs, therapy requires caution. This is due to the fact that in patients with such a history, the incidence of rash (not classified as serious) was observed three times more often with the appointment of lamotrigine than in patients with an uncomplicated history.

Patients of all age groups need immediate medical evaluation if a rash is detected. Therapy is immediately discontinued, unless it is obvious that the occurrence of a rash is not associated with taking Lamotrigine.

It is not recommended to resume the use of the drug if its previous therapy was canceled due to the development of a skin reaction, with the exception of patients in whom the expected therapeutic effect exceeds the likelihood of side effects.

There is evidence that the rash may be part of a hypersensitivity syndrome associated with a variety of systemic manifestations, including fever, lymphadenopathy, facial swelling, and liver and blood disorders. The severity of the syndrome can vary widely, in rare cases it leads to the development of multiple organ failure and DIC syndrome. It should be noted that the early manifestation of hypersensitivity syndrome (in the form of lymphadenopathy, fever) can also be observed in cases where there are no obvious manifestations of the rash. If such symptoms appear, the patient should immediately seek the advice of a doctor. If no other cause of the onset of skin symptoms is identified, Lamotrigine is discontinued.

According to some reports, children and adults taking Lamotrigine have an increased risk of aseptic meningitis. In such cases, therapy is canceled. Most often, after discontinuation of the drug, the symptoms of aseptic meningitis disappear, but in some patients, with repeated administration of Lamotrigine, they resumed. The drug should not be re-administered to patients in whom the withdrawal of therapy was associated with aseptic meningitis.

It was found that against the background of combined use with the combined drug ethinylestradiol + levonorgestrel (30 + 150 mcg), the clearance of lamotrigine approximately doubles, which leads to a decrease in its plasma level. In such cases, to achieve the maximum therapeutic effect, an increase in the maintenance doses of Lamotrigine is required, but not more than 2 times. In women who no longer take glucuronidation inducers of the substance and use hormonal contraceptives according to a scheme that includes a week of taking an inactive drug (or a break in taking a contraceptive for 7 days), a gradual transient increase in the concentration of lamotrigine will be observed during this interval. The value of this indicator will be higher in cases whereif the next increase in the dose of Lamotrigine is carried out immediately before or during the period of taking an inactive drug.

Health care providers should have the clinical skill of managing women who start / stop using hormonal contraceptives while taking Lamotrigine, as in these cases, a dosage adjustment may be required.

Other hormone replacement therapy and the use of oral contraceptives have not been studied, although their effect on the pharmacokinetics of lamotrigine is possible.

Simultaneous use with combined hormonal contraceptives (containing ethinyl estradiol and levonorgestrel) leads to a moderate increase in the clearance of levonorgestrel, and can also cause changes in the concentration of luteinizing and follicle-stimulating hormones. How these changes affect ovulatory activity of the ovaries has not been established. However, it is impossible to exclude the possibility that in some cases these changes may lead to a decrease in the effectiveness of contraceptives. If the nature of the menstrual cycle changes (that is, with the development of sudden bleeding), you should immediately consult a doctor.

Lamotrigine is one of the weak inhibitors of dihydrofolate reductase, therefore, with its long-term administration, there is a risk of impaired folate metabolism. At the same time, it was found that lamotrigine does not lead to significant changes in the concentration of hemoglobin, folates, erythrocytes of serum of average volume (when used up to 1 year) and does not reduce the concentration of folates in erythrocytes (when used up to 5 years).

Lamotrigine is an inhibitor of tubular secretion (due to the effect on the cationic protein carrier). Because of this, an increase in plasma concentrations of some drugs is possible, the excretion of which is carried out mainly by the kidneys. The combined use of Lamotrigine with substrates with a narrow therapeutic range, for example, with dofetilide, is not recommended.

When treating patients with renal insufficiency, caution is necessary, since there is a possibility of accumulation of the glucuronide metabolite.

Patients who are already receiving any other medicinal products containing lamotrigine cannot use the drug without consulting a doctor.

With the abrupt withdrawal of Lamotrigine, like other antiepileptic drugs, seizures may develop. If there is no compelling reason for abrupt discontinuation of the drug (for example, the requirement of safety when a rash appears), the dose should be reduced gradually over 2 weeks. There is evidence in the literature that severe convulsive seizures, including status epilepticus, can cause the development of rhabdomyolysis, disseminated intravascular coagulation and multiple organ dysfunctions, sometimes with a fatal outcome. Such cases have been reported with Lamotrigine therapy.

Patients with epilepsy may present with symptoms of depression and / or bipolar disorder. Patients with epilepsy and comorbid bipolar disorder are at high risk of suicide.

In bipolar disorder, 25–50% of cases have at least one suicide attempt; in such patients, against the background of the use of drugs for the treatment of bipolar disorder, including Lamotrigine, as well as without treatment, the aggravation of suicidal thoughts and suicidal behavior is possible.

The emergence of suicidal behavior / thoughts was noted in patients taking antiepileptic drugs for several indications, including epilepsy and bipolar disorder. According to a meta-analysis of randomized placebo-controlled trials of such drugs, there is a slight increase in suicidal risk. The mechanism of this effect has not been established, and the available data on the likelihood of an increase in the risk of suicide with the use of Lamotrigine do not exclude. For this reason, the condition of such patients should be carefully monitored for the appearance of suicidal thoughts and behavior. If you experience these symptoms, you should seek the advice of a doctor.

In children and adolescents with major depression and other psychiatric disorders, antidepressant use is associated with an increased likelihood of suicidal thoughts / behavior.

In case of bipolar disorder during therapy with Lamotrigine, careful monitoring of symptoms of clinical deterioration (including the appearance of new symptoms) and suicidality is required, especially at the beginning of use and when the dose is changed. Patients with a history of suicidal thoughts / behavior, young patients and patients with identified suicidal thoughts, to a large extent before the start of treatment, are considered to be at high risk of suicidal behavior / thoughts, and their condition should be strictly monitored.

The patient should be monitored for any worsening of the condition (including the appearance of new symptoms) and / or the appearance of suicidal thoughts / behavior or thoughts of harming oneself. In such cases, you should immediately seek medical help to assess the situation and, if necessary, adjust the dosage regimen. Some patients with clinical deterioration, especially with severe symptoms, with sudden onset and / or in the absence of a burdened history of such conditions, require Lamotrigine to be discontinued.

There is no data on the effect of Lamotrigine on growth, puberty, behavioral, cognitive and emotional changes in children.

Influence on the ability to drive vehicles and complex mechanisms

There is evidence of neurological adverse drug reactions, including dizziness and diplopia. In this regard, an individual assessment of the effect of Lamotrigine on the patient is required. The question of the ability to drive vehicles during therapy should be decided by a doctor.

Application during pregnancy and lactation

Lamotrigine during pregnancy / lactation should be used with caution and only in cases where the expected therapeutic benefit is higher than the existing risk.

If possible, preference should be given to monotherapy, since combination therapy with antiepileptic drugs during pregnancy is associated with a higher risk of congenital malformations (in the form of a cleft lip, malformations of the cardiovascular system and defects in the development of the neural tube) than monotherapy.

The use of Lamotrigine can theoretically lead to an increase in the likelihood of impaired development of the embryo and fetus, which is associated with a decrease in folic acid levels. In this regard, during pregnancy planning, it is necessary to consider the possibility of taking folic acid.

Lamotrigine passes into breast milk to varying degrees. If a decision is made to breastfeed the child against the background of treatment, then careful monitoring should be established for his condition to identify unwanted reactions.

Pediatric use

Contraindication:

epilepsy: up to 3 years;
bipolar disorder: up to 18 years of age.

With impaired renal function

Prescribing Lamotrigine for impaired renal function requires caution.

For violations of liver function

Prescribing Lamotrigine for impaired hepatic function requires caution.

Drug interactions

The drug interaction of Lamotrigine has been studied only when used in adult patients.

It has been established that UDP-glucuronyltransferase, the main enzyme that metabolizes lamotrigine, is responsible for the metabolic process. There is no evidence of the ability of lamotrigine to lead to clinically significant induction or inhibition of microsomal liver enzymes. Therefore, the development of interactions with drugs metabolized by cytochrome P ₄₅₀ isoenzymes is unlikely. Lamotrigine is able to induce its own metabolism, while this effect is moderately expressed and has no clinically significant consequences.

The degree of influence of other drugs on the glucuronidation of lamotrigine:

powerful inhibitors: valproic acid;
powerful inducers: rifampicin, carbamazepine, phenytoin, phenobarbital, primidone, atazanavir / ritonavir, lopinavir / ritonavir, ethinyl estradiol / levonorgestrel combination drug;
agents that have a slight effect: zonisamide, olanzapine, pregabalin, levetiracetam, oxcarbazepine, gabapentin, felbamate, topiramate, bupropion, lithium preparations.

Valproates, which inhibit the glucuronidation of lamotrigine, reduce the rate of its metabolism and lengthen its average half-life by about 2 times. In this regard, when combined therapy requires a dose adjustment of Lamotrigine.

Some antiepileptic drugs (such as carbamazepine, phenytoin, primidone, phenobarbital), inducing microsomal liver enzymes, accelerate the glucuronidation of lamotrigine and its metabolism, which requires correction of the dosage regimen.

There is information about the occurrence of adverse events from the central nervous system against the background of combined use with carbamazepine, such as dizziness, ataxia, diplopia, blurred vision and nausea. The development of a similar effect was observed in healthy volunteers with simultaneous therapy with oxcarbazepine; the result of dose reduction has not been studied.

In the literature there is information that when combined with oxcarbazepine, the concentration of lamotrigine decreases. However, it has been established that these drugs do not disturb each other's metabolism. In this regard, it is necessary to use the dosing regimen as when using lamotrigine as part of combination therapy without inducers of its glucuronidation and valproate.

The use of topiramate does not lead to a change in the plasma concentration of lamotrigine, but the concentration of topiramate increases by 15%.

Repeated intake of 400 mg of lamotrigine per day of a clinically significant effect on the pharmacokinetics of risperidone after administration of a single dose of 2 mg to healthy volunteers does not. At the same time, drowsiness was noted:

combined use: 12 out of 14 patients;
monotherapy with risperidone: in 1 in 20 patients;
lamotrigine monotherapy: no cases reported.

Against the background of simultaneous use with aripiprazole in patients with bipolar affective disorder, a change in some pharmacokinetic parameters was noted, but this effect is not clinically significant.

It was found experimentally that incubation with bupropion, amitriptyline, clonazepam, lorazepam or haloperidol has a minimal inhibitory effect on the formation of the primary metabolite of lamotrigine 2-N-glucuronide. It can be assumed that phenelzine, clozapine, sertraline, fluoxetine, trazodone or risperidone are also unlikely to affect the metabolism of lamotrigine.

The use of combined oral contraceptives containing ethinyl estradiol at a dose of 30 μg and levonorgestrel at a dose of 150 μg in studies in 16 female volunteers caused an increase in the clearance of lamotrigine approximately 2 times (after its oral administration), which led to a decrease in AUC (area under the curve " concentration - time ") lamotrigine on average by 52%, and C _max(maximum concentration of the substance) - on average by 39%. During the seven-day break from the moment of taking the active drug, an increase in the plasma concentration of lamotrigine was noted, while the value of this indicator, measured at the end of this week before the introduction of the next dose, was higher than during the period of active therapy, on average 2 times. The use of hormonal contraceptives does not require correction of the regimen of increasing doses of lamotrigine, however, most often, at the beginning or when taking hormonal contraceptives, a change (up or down) of the maintenance dose of lamotrigine is required.

Lamotrigine has no effect on the pharmacokinetics of ethinyl estradiol. There is a slight increase in the clearance of levonorgestrel, which leads to a decrease in its C _max and AUC by 12 and 19%, respectively. Measurement of serum concentrations of follicle-stimulating and luteinizing hormones and estradiol during the study in some women revealed a slight decrease in suppression of hormonal activity of the ovaries, although when measuring the plasma concentration of progesterone in none of the 16 women, hormonal confirmation of ovulation was not detected. The effect of a moderate increase in levonorgestrel clearance and changes in plasma concentrations of follicle-stimulating and luteinizing hormones on ovarian activity has not been established.

Studies with the inclusion of other hormonal drugs have not been conducted, the effect of lamotrigine doses exceeding 300 mg per day has not been studied.

Rifampicin, when used in a study involving 10 male volunteers, led to an increase in the clearance of lamotrigine and a decrease in its half-life due to the induction of microsomal liver enzymes responsible for glucuronidation. Patients who are prescribed rifampicin as concomitant therapy should adhere to the appropriate lamotrigine dosing regimen.

In healthy volunteers, according to the results of a study of the use of lopinavir / ritonavir, a decrease in the plasma concentration of lamotrigine by about 50% was noted, which may be associated with the induction of glucuronidation. In combination therapy, the appropriate dosing regimen should be observed.

In studies in healthy volunteers, the use of atazanavir / ritonavir (300/100 mg) for 9 days led to a decrease in the C _max and AUC values of lamotrigine (when used in a single dose of 100 mg) by about 6 and 32%, respectively. In combination therapy, the appropriate dosing regimen must be observed.

It was found that lamotrigine, and not its metabolite 2-N-glucuronide, is an inhibitor of the transport system of organic cations OCT2 at clinically significant concentrations. Thus, lamotrigine is a more potent OCT2 inhibitor than cimetidine. Combined use with drugs with renal excretion, which are OCT2 substrates (for example, varenicline, metformin and gabapentin), may cause an increase in the plasma concentration of these drugs. The clinical significance of this phenomenon has not been precisely determined, however, caution should be exercised when using lamotrigine with the above drugs.

Lamotrigine interferes with some rapid urinalysis tests for illegal drugs that can cause false positives, especially in the case of phencyclidine. Therefore, a more specific alternative chemical method must be used to confirm a positive result.

Analogs

Analogues of Lamotrigine are: Lamictal, Lamolep, Seizar, Lamotrigine Canon, Vero-Lamotrigine, Konvulsan, Lameptil, Lamotrix, etc.

Terms and conditions of storage

Store at temperatures up to 25 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Lamotrigine

Reviews of Lamotrigine are mostly positive. It is noted that the effect of therapy develops gradually. In some cases, they indicate the occurrence of side effects, in particular, memory impairment. However, the drug is most often used as part of a complex treatment, therefore, it is impossible to reliably confirm the connection of this disorder with taking Lamotrigine.

The price of Lamotrigine in pharmacies

The approximate price of Lamotrigine for a pack of 30 tablets is: dosage 25 mg - 187-210 rubles, dosage 50 mg - 264-298 rubles, dosage 100 mg - 498-595 rubles.

Lamotrigine: prices in online pharmacies

Drug name

Price

Pharmacy

Lamotrigine 25 mg tablets 30 pcs.

199 RUB

Buy

Lamotrigine 50 mg tablets 30 pcs.

292 r

Buy

Lamotrigine 100 mg tablets 30 pcs.

461 r

Buy

Lamotrigine Canon 100 mg tablets 30 pcs.

505 RUB

Buy

Lamotrigine Canon 100mg tablets 30 pcs.

644 r

Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!