Description
Release form
Pale yellow to yellow brown tablets, square with rounded corners, one side flat with an extruded GSEC7 inscription, the other multifaceted with a convex square with an extruded number 25.
Packing
10 pcs. – blisters (3) – packs of cardboard.
Pharmacological action
Antiepileptic drug. Lamotrigine is a voltage-gated sodium channel blocker. In neuronal culture, it causes a voltage-dependent blockade of continuously repeating impulses and suppresses the pathological release of glutamic acid (an amino acid that plays a key role in the development of epileptic seizures), and also inhibits the depolarization caused by glutamate.
Lamictal’s effectiveness in preventing mood disorders in patients with bipolar disorders has been demonstrated in two basic clinical studies. As a result of a combined analysis of the results, it was found that the duration of remission, defined as the time before the first episode of depression and before the first episode of mania / hypomania / mixed after stabilization, was longer in the lamotrigine group compared with placebo. The duration of remission is more pronounced for depression.
Pharmacokinetics
Absorption
After oral administration, lamotrigine is rapidly and completely absorbed from the gastrointestinal tract, practically without undergoing a presystemic metabolism of the first passage. Cmax in plasma is reached approximately 2.5 hours after taking the drug. The time to reach Cmax slightly increases after eating, but the degree of absorption remains unchanged. The pharmacokinetics of lamotrigine is linear when taking a single dose of up to 450 mg (the largest dose studied). Significant interindividual Cmax fluctuations are observed in the equilibrium state, but with rare fluctuations in each individual person.
Distribution of
Lamotrigine binds to plasma proteins by approximately 55%. It is unlikely that the release of the drug from binding to the protein could lead to the development of a toxic effect. Vd is 0.92-1.22 L / kg.
Metabolism
The metabolism of lamotrigine involves the enzyme uridine diphosphate glucuronyl transferase (UDP-glucuronyl transferase). Lamotrigine slightly increases its own metabolism depending on the dose. However, there is no evidence that lamotrigine affects the pharmacokinetics of other antiepileptic drugs and that interaction is possible between lamotrigine and other drugs metabolized by the P450 cytochrome system.
Excretion of
In healthy adults, clearance of lamotrigine at a state of equilibrium concentrations averages 39 ± 14 ml / min. Lamotrigine is metabolized to glucuronides, which are excreted by the kidneys. Less than 10% of the drug is excreted by the kidneys unchanged, about 2% – through the intestines. Ground clearance and T1 / 2 are dose independent. T1 / 2 in healthy adults is on average from 24 hours to 35 hours. Patients with Gilbert’s syndrome showed a decrease in clearance of the drug by 32% compared with the control group, which, however, did not go beyond the normal values for the general population. T1 / 2 lamotrigine is greatly influenced by co-medication. The average T1 / 2 decreases to approximately 14 hours when taken concomitantly with drugs that stimulate glucuronidation, such as carbamazepine and phenytoin, and rises to an average of up to 70 hours when taken together with valproate.
Pharmacokinetics in special clinical cases
In children, lamotrigine clearance, based on body weight, is higher than in adults, it is highest in children under 5 years of age. In children, T1 / 2 of lamotrigine is usually less than in adults. Its average value is approximately 7 hours when taken concomitantly with drugs that stimulate glucuronidation, such as carbamazepine and phenytoin, and increases on average up to 45-50 hours when taken together with valproate.
No clinically significant differences in lamotrigine clearance were found in elderly patients compared with younger patients.
In case of impaired renal function, the initial dose of lamotrigine is calculated in accordance with the standard antiepileptic drug regimen. Dose reduction may be required only with a significant decrease in renal function.
Initial, incremental, and maintenance doses should be reduced by approximately 50% in patients with moderate hepatic impairment (Child Pugh class B) and 75% in patients with severe hepatic impairment (Child Pugh class C ) The dose increase and maintenance dose should be adjusted depending on the clinical effect.
Indications
Epilepsy
for adults and children over 12 years old
epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures with Lennox-Gastaut syndrome) as part of combination therapy or monotherapy.
for children 3 to 12 years old
epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures with Lennox-Gastaut syndrome) as part of combination therapy. After achieving control of epilepsy in combination therapy, concomitant antiepileptic drugs can be canceled and lamotrigine continued in monotherapy with
monotherapy of typical absences.
Bipolar disorder
for adults (18 years of age and older)
prevention of mood disorders (depression, mania, hypomania, mixed episodes) in patients with bipolar affective disorders.
Contraindications
hypersensitivity to lamotrigine or any component of the drug.
Use in cases of impaired liver function
Impaired liver function
Initial, increasing, and maintenance doses should be reduced by approximately 50% and 75% in patients with moderate (stage B) and severe (stage C) degrees of impaired liver function, respectively. Increasing and maintenance doses should be adjusted according to the clinical effect.
Use for impaired renal function
Impaired renal function
Patients with renal failure lamotrigine should be prescribed with caution. In patients with severe renal failure, the initial dose of lamotrigine is calculated in accordance with the standard regimen for patients with a significant decrease in renal function, a maintenance dose reduction may be recommended.
Use in children
It is possible to use according to some indications and in doses established taking into account the age of the patient.
Lamotrigine is not indicated for bipolar disorders in children and adolescents under 18 years of age. The safety and effectiveness of lamotrigine in bipolar disorder in patients of this age group have not been evaluated.
Use in elderly patients
Elderly patients (over 65 years old)
The pharmacokinetics of lamotrigine in this age group are practically the same as in other adult patients, therefore, a change in the dosage regimen is not required.
Special instructions
Skin rash
There is evidence of the development of skin rashes, which usually occurred within the first 8 weeks after starting treatment with Lamictal. In most cases, skin rashes are mild and go away on their own, but at the same time, serious cases have sometimes been noted that require hospitalization of the patient and the removal of Lamiktal (for example, Stevens-Johnson syndrome and Lyell syndrome).
Severe skin reactions in adults taking LamictalВ® in accordance with generally accepted recommendations develop with a frequency of approximately 1 in 500 patients with epilepsy. In about half of these cases, Stevens-Johnson syndrome (1 in 1000) was recorded. In patients with bipolar disorders, the frequency of severe skin rashes according to clinical studies is approximately 1 in 1000 patients.
In children, the risk of developing severe skin rashes is higher than in adults. According to reports, the frequency of skin rashes requiring hospitalization in children with epilepsy, ranged from 1 in 300 to 1 in 100 children.
In children, the initial manifestations of a rash may be mistaken for an infection, so the possibility of children’s reactions to the drug, which manifests itself in the development of a rash and fever in the first 8 weeks of therapy, should be taken into account.
In addition, the total risk of developing a rash is significantly associated with a high initial dose of Lamiktal and exceeding the recommended rate of increase, as well as with the combined use of valproate with drugs.
Caution is necessary when prescribing to patients with a history of allergic reactions or a rash in response to taking other antiepileptic drugs, since the development of a rash (not classified as serious) was observed in patients with such a history 3 times more often with lamotrigine than in patients with unburdened history.
If a rash is found, all patients (adults and children) should be examined immediately by a doctor. Lamotrigine should be stopped immediately unless it is obvious that the development of the rash is not associated with taking the drug. It is not recommended to resume taking lamotrigine in cases where its previous appointment was canceled due to the development of a skin reaction, unless the expected therapeutic effect of the drug does not exceed the risk of side effects.
It has been reported that a rash may be part of a hypersensitivity syndrome associated with various systemic manifestations, including fever, lymphadenopathy, swelling of the face, and blood and liver disorders. The severity of the syndrome varies widely and in rare cases can lead to the development of DIC and multiple organ failure. It should be noted that early manifestations of hypersensitivity syndrome (i.e., fever, lymphadenopathy) can occur even if there are no obvious manifestations of a rash. With the development of such symptoms, the patient should be immediately examined by a doctor and, unless another cause for the symptoms is established, lamotrigine should be withdrawn.
Aseptic meningitis
The development of aseptic meningitis is reversible when the drug is discontinued in most cases and resumes in a number of cases when reassigned. Repeated prescribing leads to a quick return of symptoms, which are often more severe. Lamotrigine is not reassigned to patients in whom discontinuation of treatment has been associated with aseptic meningitis.
Hormonal contraceptives
1. The effect of hormonal contraceptives on the pharmacokinetics of lamotrigine
It was shown that the combined preparation of ethinyl estradiol / levonorgestrel (30 Ојg / 150 Ојg) increases the clearance of lamotrigine approximately 2 times, which leads to a decrease in its plasma level. When it is prescribed, to achieve the maximum therapeutic effect, it is necessary to increase the maintenance doses of lamotrigine, but not more than 2 times. In women who are no longer taking lamotrigine glucuronidation inducers and taking hormonal contraceptives, the treatment regimen of which includes a week of inactive drug administration (or a week-long break in contraceptive intake), a gradual transient increase in lamotrigine concentration will be observed during this period of time. The increase in concentration will be expressed more if the next increase in the dose of lamotrigine will be carried out immediately before or during the administration of the inactive drug.
Medical professionals must master the clinical skills of women who, with treatment with lamotrigine, start or stop taking hormonal contraceptives, as this may require dose adjustment of lamotrigine.
Other oral contraceptives and hormone replacement therapy have not been studied, although they may similarly affect the pharmacokinetic parameters of lamotrigine.
2. Effect of lamotrigine on the pharmacokinetics of hormonal contraceptives
Co-administration of lamotrigine and combined hormonal contraceptives (ethinyl estradiol / levonorgestrel) leads to a moderate increase in clearance of levonorgestrel and changes in the concentration of FSH and LH. The effect of these changes on the ovulatory activity of the ovaries is unknown. However, we cannot exclude the possibility that in some patients taking lamotrigine and hormonal contraceptives, these changes can cause a decrease in the effectiveness of contraceptives. Patients should be informed about the need to immediately inform the doctor about changes in the nature of the menstrual cycle, i.e. about sudden bleeding.
Dihydrofolate reductase
Lamotrigine is a weak inhibitor of dihydrofolate reductase, and therefore, with prolonged therapy, the drug may affect folate metabolism. However, it was shown that even with prolonged use, lamotrigine did not cause serious changes in the hemoglobin content, the average volume of red blood cells, the concentration of folate in serum (when taken up to 1 year) or red blood cells (when taken up to 5 years).
Effect of lamotrigine on the cationic carrier of organic substrates
Lamotrigine is an inhibitor of tubular secretion by acting on the cationic carrier of proteins. This can lead to increased plasma concentrations of certain drugs that are excreted mainly through the kidneys. Co-administration of lamotrigine and substrates with a narrow therapeutic range, such as dofetilide, is not recommended.
Renal failure
A single dose of lamotrigine in patients with severe renal failure did not reveal significant changes in lamotrigine concentration. However, the accumulation of a glucuronide metabolite is very likely therefore, caution must be exercised in the treatment of patients with renal failure.
Patients taking other drugs containing lamotrigine
If the patient receives any other drug containing lamotrigine, he should not take LamictalВ® without consulting a doctor.
Epilepsy
Abrupt withdrawal of lamotrigine, like other PEPs, can trigger seizures. If a sudden cessation of therapy is not a safety requirement (for example, if a rash appears), the dose of lamotrigine should be reduced gradually over a period of 2 weeks. There are reports in the literature that severe seizures, including status epilepticus, can lead to rhabdomyolysis, multiple organ dysfunctions, and disseminated vascular coagulation, sometimes with a fatal outcome. Similar cases were observed in the treatment of lamotrigine patients.
Suicidal risk
Symptoms of depression and / or bipolar disorder may occur in patients with epilepsy. Patients with epilepsy and concomitant bipolar disorder are at high risk for suicide. In 25-50% of patients with bipolar disorder, at least one suicidal attempt was observed in such patients, there may be an aggravation of suicidal thoughts and suicidal behavior (suicidality) while taking medications to treat bipolar disorder, including lamotrigine, as well as without treatment.
Suicidal thoughts and suicidal behavior have been observed in patients taking PEP for several reasons, including epilepsy and bipolar disorder. A meta-analysis of randomized, placebo-controlled PEP studies (including lamotrigine) showed a slight increase in suicidal risk. The mechanism of this action is unknown, and the available data do not exclude the possibility of increasing the risk of suicide with lamotrigine. Therefore, patients should be closely monitored for suicidal thoughts and behavior. Patients and carers should be informed of the need for medical advice if such symptoms occur.
Bipolar Affective Disorder
Children and adolescents under the age of 18
Antidepressant treatment is associated with an increased risk of suicidal thoughts and behavior in children and adolescents with major depression and other mental disorders.
Clinical worsening in patients with bipolar affective disorder
In patients with bipolar disorder receiving lamotrigine, it is necessary to carefully monitor the symptoms of clinical worsening (including the appearance of new symptoms) and suicidality, especially at the beginning of treatment and at the time of a dose change. Patients who have a history of suicidal thoughts or suicidal behavior, young patients and patients who have identified a significant degree of suicidal thoughts before starting therapy, are at high risk for suicidal thoughts or suicidal behavior, such patients should be under strict observation during treatment.
Patients (and individuals caregivers) should be warned about the need to monitor any deterioration in the patient’s condition (including the appearance of new symptoms) and / or the emergence of suicidal thoughts / behavior or thoughts of self-harm and should seek medical attention immediately if these symptoms are present.
In this case, the situation should be assessed and appropriate changes made to the treatment regimen, including the possibility of drug withdrawal in patients who have clinical deterioration (including the appearance of new symptoms) and / or the appearance of suicidal thoughts / behavior, especially if these symptoms are severe, with a sudden onset and not previously noted.
Impact on driving ability and driving
Two studies with healthy volunteers showed that the effect of lamotrigine on the exact visual-motor coordination, eye movements and subjective sedative effect did not differ from the placebo effect. There are reports of side effects of neurological lamotrigine, such as dizziness and diplopia. Therefore, before sitting behind the wheel of a car or operating machinery, patients should evaluate the effect of lamotrigine on their condition.
Since the effect of all antiepileptic drugs has individual variability, then patients should consult their doctor about the possibility of driving a car.
Composition
1 tab. contains:
Active ingredients:
lamotrigine – 25 mg
Excipients:
lactose monohydrate – 24.7 mg,
microcrystalline cellulose – 24.7 mg,
carboxymethyl starch sodium – 2.5 mg,
srldylmidone 2.5 mg,
strontium – iron oxide yellow (E172) – 0.2 mg.
Dosage and Administration
Inside.
Epilepsy: adults and children over 12 years of age who have not received sodium valproate, an initial dose of 25 mg 1 time per day for 2 weeks, then 50 mg 1 time per day for 2 weeks, then the dose is increased by 50-100 mg every 1-2 weeks to achieve the optimal therapeutic effect.
Maintenance dose – 100-200 mg / day in 1 or 2 doses (some patients require a dose of 500 mg / day).
Side effects
The available adverse event information is divided into 2 parts: adverse events in patients with epilepsy and adverse events in patients with bipolar affective disorder. However, when considering the safety profile of lamotrigine as a whole, the information in both sections must be taken into account.
The adverse events presented below are listed based on the anatomical and physiological classification and frequency of occurrence. The frequency of occurrence is determined as follows: very often (? 1/10), often (? 1/100,
Epilepsy
on the part of the skin and subcutaneous fat: very often – skin rash rarely – Stevens-Johnson syndrome, very rarely – toxic epidermal necrolysis.
In double-blind adult clinical trials, where lamotrigine was used as a combination therapy, the incidence of skin rash in patients taking lamotrigine was 10%, and in patients taking placebo, 5%. In 2% of cases, the occurrence of a skin rash caused the withdrawal of lamotrigine. The rash, mainly of a maculopapular nature, usually appears within the first 8 weeks from the start of therapy and disappears after discontinuation of the drug.
There are reports of rare cases of the development of severe, potentially life-threatening skin lesions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome). Although in most cases when the drug was canceled, the symptoms reversed, some patients had irreversible scars, and in rare cases, deaths associated with taking the drug were recorded.
The overall risk of developing a rash was largely associated with a high initial dose of lamotrigine and exceeding the recommended ramp-up doses of lamotrigine, as well as with the concomitant use of valproic acid. The development of the rash was also seen as a manifestation of hypersensitivity syndrome associated with various systemic manifestations.
From the hemopoietic organs and lymphatic system: very rarely – hematological disorders (neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis), lymphadenopathy. Hematologic disorders and lymphadenopathy may or may not be associated with hypersensitivity syndrome.
On the part of the immune system: very rarely – hypersensitivity syndrome (including symptoms such as fever, lymphadenopathy, swelling of the face, disorders of the blood and liver function, DIC, multiple organ failure). The rash is also seen as part of a hypersensitivity syndrome associated with various systemic manifestations, including fever, lymphadenopathy, facial swelling, blood disorders, and liver function. The syndrome occurs with varying degrees of severity and can in rare cases lead to the development of DIC and multiple organ failure. It is important to note that early manifestations of hypersensitivity (i.e., fever, lymphadenopathy) can occur even in the absence of obvious signs of a rash. With the development of such symptoms, the patient should be immediately examined by a doctor and, unless another reason for the development of symptoms is established, lamotrigine should be canceled.
From the psyche: often – aggressiveness, irritability very rarely – tics, hallucinations, confusion.
From the side of the central nervous system: with monotherapy: very often – headache often – drowsiness, insomnia, dizziness, tremor infrequently – ataxia rarely – nystagmus. As part of combination therapy: very often – drowsiness, ataxia, headache, dizziness often – nystagmus, tremor, insomnia very rarely – aseptic meningitis, agitation, instability of gait, motor disorders, worsening symptoms of Parkinson’s disease, extrapyramidal disorders, choreoathetosis, increased frequency of convulsions seizures. There are reports that lamotrigine can worsen the extrapyramidal symptoms of Parkinsonism in patients with concomitant Parkinson’s disease, and in rare cases cause extrapyramidal symptoms and choreathetosis in patients without previous disorders.
From the sensory organs: with monotherapy: infrequently – diplopia, blurred vision as part of combination therapy: very often – diplopia, blurred vision rarely – conjunctivitis.
From the digestive system: with monotherapy: often – nausea, vomiting, diarrhea as part of combination therapy: very often – nausea, vomiting often – diarrhea.
From the liver and biliary tract: very rarely – increased activity of liver enzymes, impaired liver function, liver failure. Violations of liver function usually develop in combination with symptoms of hypersensitivity, but in isolated cases were noted in the absence of obvious signs of hypersensitivity.
From the side of muscle and connective tissue: very rarely – lupus-like syndrome.
Other: often – fatigue.
Bipolar Affective Disorder
To assess the overall safety profile of lamotrigine, the adverse events listed below should be taken into account along with those characteristic of epilepsy.
From the skin and subcutaneous fat: very often – a skin rash is rare – Stevens-Johnson syndrome. When evaluating all studies (controlled and uncontrolled) to study the use of Lamiktal in patients with bipolar affective disorder, a skin rash occurred in 12% of all patients receiving lamotrigine, while the frequency of skin rash in only controlled studies was 8% in patients receiving Lamictal®. and in 6% of patients receiving placebo.
From the side of the central nervous system: very often – headache often – agitation, drowsiness, dizziness.
From the side of muscle and connective tissue: often – arthralgia.
From the digestive system: often – dry oral mucosa.
Other: often – pain, back pain.
Overdose
Single dose administration exceeding maximal therapeutic doses of 10-20 times has been reported. Overdose was manifested by the following symptoms: nystagmus, ataxia, impaired consciousness and coma.
Treatment: Hospitalization and supportive care are recommended in accordance with the clinical picture or recommendations of the National Toxicology Center.
Shelf life
3 years
Deystvuyushtee substance
lamotrigine
prescription
Prescription
tablets Dosage form
Possible product names
LAMIKTAL 0,025 N30 TABLE
Lamiktal 25mg Tab. X30
Lamiktal 25mg No. 30
LAMIKTAL 25MG. No. 30 TAB.
lamictal tab. 25mg x 30
GlaxoSmithKline, UK
