Lamictal, pills 25mg, 30pcs

Composition

>of 1 tab. contains: Active ingredients: lamotrigine – 25 mg

Auxiliary substances:

lactose monohydrate – 24.7 mg,

microcrystalline cellulose-24.7 mg,

sodium carboxymethyl starch-2.5 mg,

povidone-2.5 mg,

magnesium stearate-0.4 mg,

iron oxide yellow (E 172) – 0.2 mg

Pharmacological action

Anticonvulsant. It blocks potential-dependent sodium channels, stabilizes neuronal membranes, and inhibits the release of glutamic acid, which plays a key role in the development of epileptic seizures.

Indications

Partial and generalized seizures, including tonic-clonic and associated with Lennox-Gastaut syndrome (in adults and children), bipolar disorders in adults over 18 years of age with predominantly depressive phases.

Use during pregnancy and lactation

Since lamotrigine is a weak inhibitor of dihydrofolate reductase, there is at least a theoretical risk of developing birth defects in the fetus when taking the drug during pregnancy. There is insufficient data to assess the safety of lamotrigine in pregnancy. Currently, information on the use of lamotrigine in lactation is incomplete. Lamotrigine is detected in breast milk at concentrations of 40-60% of its plasma concentration. In some breastfed infants, the plasma concentration of lamotrigine reaches therapeutic levels.

Contraindications

Hypersensitivity. Caution should be used in patients with renal insufficiency.

Side effects

The available information on adverse events 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 in general, it is necessary to take into account the information in both sections.

The adverse events presented below are listed according to the anatomical and physiological classification and frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), common (≥1/100,

Epilepsy

Skin and subcutaneous fat disorders:  very often-skin rash; rarely-Stevens-Johnson syndrome, very rarely-toxic epidermal necrolysis.

In double-blind clinical trials in adults 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 macular-papular nature, usually appears within the first 8 weeks after the start of therapy and disappears after discontinuation of the drug.

Rare cases of severe, potentially life-threatening skin lesions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome), have been reported. Although in most cases the withdrawal of the drug reversed the development of symptoms, some patients remained permanently scarred, and in rare cases fatal outcomes associated with taking the drug were reported.

The overall risk of developing a rash was largely associated with a high initial dose of lamotrigine and exceeding the recommended rate of increase in lamotrigine doses, as well as with concomitant use of valproic acid. The development of rash was also considered as a manifestation of hypersensitivity syndrome associated with various systemic manifestations.

Hematopoietic and lymphatic system disorders:  very rarely – hematological disorders (neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis), lymphadenopathy. Hematological disorders and lymphadenopathy may or may not be associated with hypersensitivity syndrome.

From the immune system:  very rarely – hypersensitivity syndrome (including symptoms such as fever, lymphadenopathy, facial swelling, blood and liver disorders, DIC syndrome, multiple organ failure). The rash is also considered 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 syndrome and multiple organ failure. It is important to note that early signs of hypersensitivity (i. e. fever, lymphadenopathy) may occur even if there are no obvious signs of rash. If such symptoms develop, the patient should be immediately examined by a doctor and, unless another cause of the development of symptoms is established, lamotrigine should be discontinued.

From the side of the psyche:  often-aggressiveness, irritability; very rarely-tics, hallucinations, confusion.

From the central nervous system:  with monotherapy: very often – headache; often-drowsiness, insomnia, dizziness, tremor; infrequently-ataxia; rarely-nystagmus. In combination therapy: very often – drowsiness, ataxia, headache, dizziness; often-nystagmus, tremor, insomnia; very rarely-aseptic meningitis, agitation, gait instability, movement disorders, worsening of Parkinson’s disease symptoms, extrapyramidal disorders, choreoathetosis, increased frequency of seizures. There are reports that lamotrigine may worsen the extrapyramidal symptoms of parkinsonism in patients with concomitant Parkinson’s disease, and in some cases cause extrapyramidal symptoms and choreathetosis in patients without previous disorders.

From the side of the senses:  with monotherapy:  infrequently – diplopia, blurred vision; in combination therapy: very often-diplopia, blurred vision; rarely-conjunctivitis.

From the digestive system:  in monotherapy: often – nausea, vomiting, diarrhea; in combination therapy: very often-nausea, vomiting; often-diarrhea.

Liver and biliary tract disorders:  very rarely-increased activity of liver enzymes, impaired liver function, liver failure. Liver function disorders usually develop in combination with symptoms of hypersensitivity, but in isolated cases they were also observed in the absence of obvious signs of hypersensitivity.

Muscle and connective tissue disorders:  very rarely – lupus-like syndrome.

Other services:  often – fatigue.

Bipolar affective disorder

To assess the overall safety profile of lamotrigine, the following adverse events should be taken into account along with those characteristic of epilepsy.

Skin and subcutaneous fat disorders:  very common-skin rash; rarely-Stevens-Johnson syndrome. When evaluating all studies (controlled and uncontrolled) on the use of Lamictal in patients with bipolar affective disorder, skin rash occurred in 12% of all patients treated with lamotrigine, while the frequency of skin rash in controlled studies alone was 8% in patients treated with Lamictal® and 6% in patients treated with placebo.

From the central nervous system:  very often – headache; often-agitation, drowsiness, dizziness.

Muscle and connective tissue disorders:  often-arthralgia.

From the digestive system:  often – dryness of the oral mucosa.

Other services:  often-pain, back pain.

Composition

UDP-glucuronyltransferase interaction is the main enzyme that metabolizes lamotrigine. There are no data on the ability of lamotrigine to cause clinically significant induction or inhibition of microsomal liver enzymes. Therefore, the interaction between lamotrigine and drugs metabolized by cytochrome P450 isoenzymes is unlikely. Lamotrigine can induce its own metabolism, but this effect is moderate and has no clinical significance.

Effect of other drugs on lamotrigine glucuronidation.

The effect of other oral contraceptives and hormone replacement therapy has not been studied, although they may have a similar effect on the pharmacokinetic parameters of lamotrigine.

Interaction with the PEP

Valproic acid, which inhibits lamotrigine glucuronidation, reduces its metabolic rate and extends its average T_1/2 by almost 2 times.

Some antiepileptic drugs (such as phenytoin, carbamazepine, phenabarbital, and primidone) that induce microsomal liver enzymes accelerate lamotrigine glucuronidation and metabolism. CNS adverse events, including dizziness, ataxia, diplopia, blurred vision, and nausea, have been reported in patients who started taking carbamazepine with lamotrigine therapy. These symptoms usually resolved after reducing the dose of carbamazepine.A similar effect was observed when taking lamotrigine and oxcarbazepine in healthy volunteers, the result of dose reduction was not studied.

When lamotrigine 200 mg and oxcarbazepine 1200 mg are co-administered, neither oxcarbazepine nor lamotrigine interfere with each other’s metabolism.

Concomitant use of felbamate 1200 mg 2 times / day and lamotrigine 100 mg 2 times / day did not lead to clinically significant changes in the pharmacokinetics of lamotrigine.

When lamotrigine and gabapentin were co-administered, the apparent clearance of lamotrigine did not change.

Possible drug interactions of levetiracetam and lamotrigine were investigated when evaluating the serum concentrations of both drugs in placebo-controlled clinical trials. These data indicate that lamotrigine and levetiracetam do not affect each other’s pharmacokinetics.

There was no effect of pregabalin at a dose of 200 mg 3 times / day on the equilibrium concentrations of lamotrigine, i. e. pregabalin and lamotrigine do not interact pharmacokinetically with each other.

The use of topiramate did not lead to a change in the concentration of lamotrigine in plasma. However, lamotrigine use resulted in a 15% increase in topiramate concentrations.

Taking zonizamide (200-400 mg/day) during the clinical program together with lamotrigine (150-500 mg/day) did not change the pharmacokinetic parameters of lamotrigine.

Studies have shown that lamotrigine does not affect the plasma concentrations of other antiepileptic drugs.

The results of in vitro studies showed that lamotrigine does not displace other antiepileptic drugs from binding to plasma proteins.

Interaction when used in combination with other psychotropic drugs

Lamotrigine at a dose of 100 mg / day does not cause a violation of the pharmacokinetics of anhydrous lithium gluconate (2 g 2 times/day for 6 days) when administered together.

Multiple oral use of bupropion has no statistically significant effect on the pharmacokinetics of a single dose of lamotrigine and causes a slight increase in the AUC of lamotrigine glucuronide.

Olanzapine at a dose of 15 mg reduces the AUC and_cmax of lamotrigine by an average of 24% and 20%, respectively, which is clinically insignificant. Lamotrigine 200 mg did not alter the pharmacokinetics of olanzapine.

Repeated use of lamotrigine at a dose of 400 mg / day did not have a clinically significant effect on the pharmacokinetics of risperidone after a single dose of 2 mg in healthy volunteers. At the same time, drowsiness was observed: in 12 out of 14 patients with combined lamotrigine and risperidone; in 1 out of 20 patients with risperidone alone; in none of the patients with lamotrigine alone.

Inhibition of lamotrigine action by amitriptyline, bupropion, clonazepam, fluoxetine, haloperidol, or lorazepam has minimal effect on the formation of the primary lamotrigine metabolite 2-N-glucuronide.

A study of the metabolism of bufuralol by microsomal liver enzymes isolated from humans suggests that lamotrigine does not reduce the clearance of drugs that are mainly metabolized by CYP2D6 isoenzymes. The results of in vitro studies also suggest that clozapine, phenelzine, risperidone, sertraline, or trazodone are unlikely to affect lamotrigine clearance.

Interaction with hormonal contraceptives

1. Effect of hormonal contraceptives on lamotrigine pharmacokinetics

Combined oral contraceptives containing 30 mcg of ethinyl estradiol and 150 mcg of levonorgestrel cause an approximately twofold increase in lamotrigine clearance (after oral use), which leads to a decrease in lamotrigine AUC and_cmax by an average of 52% and 39%, respectively. During the week free from taking the active drug, an increase in plasma lamotrigine concentration is observed, while the lamotrigine concentration measured at the end of this week before the next dose is on average 2 times higher than during active therapy.

2. Effect of lamotrigine on the pharmacokinetics of hormonal contraceptives

During steady-state concentrations, lamotrigine at a dose of 300 mg does not affect the pharmacokinetics of ethinyl estradiol, a component of the combined oral contraceptive. There is a slight increase in the clearance of the second component of the oral contraceptive, levonorgestrel, which leads to a decrease in the AUC and_cmax of levonorgestrel by 19% and 12%, respectively. Measurement of serum FSH, LH, and estradiol levels during this study revealed a slight decrease in ovarian hormone suppression in some women, although measurement of plasma progesterone levels in none of the 16 women revealed hormonal evidence of ovulation. The effect of a moderate increase in levonorgestrel clearance and changes in plasma concentrations of FSH and LH on ovulatory activity of the ovaries has not been established. The effect of other doses of lamotrigine (other than 300 mg / day) has not been studied and studies involving other hormonal drugs have not been conducted.

Interaction with other drugs

Rifampicin increases lamotrigine clearance and reduces its T_1/2 by inducing microsomal liver enzymes responsible for glucuronidation. In patients taking rifampicin as concomitant therapy, the lamotrigine regimen should be consistent with the regimen recommended for concomitant use of lamotrigine and glucuronidation-inducing agents.

When lopinavir/ritonavir was used, a decrease of approximately 50% in the plasma lamotrigine concentration was observed, possibly due to the induction of glucuronidation. In patients receiving concomitant treatment with lopinavir/ritonavir, a lamotrigine dosage regimen with concomitant glucuronidation inducers should be recommended.

In a study in healthy volunteers, taking atazanavir/ritonavir (300 mg/100 mg) resulted in a decrease in the AUC and_{cmax values} of lamotrigine (at a single dose of 100 mg) by approximately 32% and 6%, respectively.

The results of in vitro studies have shown that lamotrigine is an inhibitor of cationic carriers of organic substrates in potentially clinically significant concentrations. These data show that lamotrigine is a more potent inhibitor (half of the inhibitory concentration (IC50) varies from 53.8 nmol / L to 186 nmol/L, respectively) than cimetidine.

Interaction, including laboratory parameters

Lamotrigine has been reported to interfere with some rapid urinalysis methods to detect illegal drugs that may lead to false positive results, especially when phencyclidine (a dissociative anesthetic) is detected. A more specific alternative chemical method should be used to confirm a positive result.

How to take, course of use and dosage

Inside.

Epilepsy: adults and children over 12 years of age who did not receive sodium valproate, the initial dose is 25 mg once a day for 2 weeks, then 50 mg once a day for 2 weeks, then the dose is increased by 50-100 mg every 1-2 weeks until the optimal therapeutic effect is achieved.

The maintenance dose is 100-200 mg / day in 1 or 2 doses (some patients require a dose of 500 mg / day).

Overdose

A single dose of 10-20 times the maximum therapeutic dose has been reported. Overdose was manifested by the following symptoms: nystagmus, ataxia, impaired consciousness and coma.

Treatment: hospitalization and maintenance therapy are recommended in accordance with the clinical picture or recommendations of the national toxicology center.

Special instructions

Skin rash

There are data on the development of skin rashes, which were usually observed within the first 8 weeks after the start of Lamictal treatment. In most cases, skin rashes are mild and go away on their own, but sometimes serious cases have been reported that require hospitalization of the patient and discontinuation of Lamictal (for example, Stevens-Johnson syndrome and Lyell’s syndrome).

Severe skin reactions in adults taking Lamictal® in accordance with generally accepted recommendations develop with a frequency of approximately 1 in 500 patients with epilepsy. Approximately half of these cases have Stevens-Johnson syndrome (1 in 1000). In patients with bipolar disorder, the incidence of severe skin rashes is approximately 1 in 1000 patients, according to clinical studies.

Children have a higher risk of developing severe skin rashes than adults. According to available data, the incidence of skin rashes requiring hospitalization in children with epilepsy ranged from 1 in 300 to 1 in 100 children.

In children, the initial rash may be mistaken for an infection, so you should take into account the possibility of a reaction of children to the drug, manifested by the development of rash and fever in the first 8 weeks of therapy.

In addition, the overall risk of developing a rash is largely associated with a high initial dose of Lamictal and exceeding the recommended rate of increase, as well as with combined use with valproates.

Caution is necessary when prescribing to patients with a history of allergic reactions or rash in response to other antiepileptic drugs, since the incidence of rash (not classified as serious) in patients with such a history was observed 3 times more often when lamotrigine was prescribed than in patients with an unencumbered history.

If a rash is detected, all patients (adults and children) should be immediately examined by a doctor. Lamotrigine should be discontinued immediately, unless it is obvious that the development of a rash is not related to 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 the rash may be part of a hypersensitivity syndrome associated with various systemic manifestations, including fever, lymphadenopathy, facial swelling, and blood and liver disorders. The severity of the syndrome varies widely and in rare cases can lead to the development of DIC syndrome and multiple organ failure. It should be noted that early manifestations of hypersensitivity syndrome (i. e. fever, lymphadenopathy) can occur even if there is no obvious rash. If such symptoms develop, the patient should be immediately examined by a doctor and, unless another cause of the symptoms is established, lamotrigine should be discontinued.

Aseptic meningitis

The development of aseptic meningitis is reversible when the drug is discontinued in most cases and resumes in some cases with repeated use. Repeated use leads to a rapid return of symptoms, which are often more severe. Lamotrigine should not be re-administered to patients whose discontinuation of treatment has been associated with aseptic meningitis.

Hormonal contraceptives

1. Effect of hormonal contraceptives on lamotrigine pharmacokinetics

The combination drug ethinyl estradiol/levonorgestrel (30 mcg/150 mcg) has been shown to increase lamotrigine clearance approximately 2-fold, 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. Women who are no longer taking lamotrigine glucuronidation inducers and are taking hormonal contraceptives, whose treatment regimen includes a week of taking an inactive drug (or a one-week break in taking a contraceptive), will experience a gradual transient increase in lamotrigine concentration during this time period. The increase in concentration will be more pronounced if the next increase in the dose of lamotrigine is carried out immediately before or during the period of taking an inactive drug.

Health professionals should develop clinical management skills for women who start or stop taking hormonal contraceptives during lamotrigine treatment, as this may require adjusting the lamotrigine dose.

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-use of lamotrigine and a combined hormonal contraceptive (ethinyl estradiol/levonorgestrel) leads to a moderate increase in levonorgestrel clearance and changes in FSH and LH concentrations. The effect of these changes on ovulatory activity of the ovaries is unknown. However, the possibility cannot be excluded that in some patients taking lamotrigine and hormonal contraceptives, these changes may 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. sudden bleeding.

Dihydrofolate Reductase

Lamotrigine is a weak inhibitor of dihydrofolate reductase, and therefore the drug may affect folate metabolism during long-term therapy. However, it was shown that even with prolonged use, lamotrigine did not cause serious changes in hemoglobin content, average red blood cell volume, serum folate concentration (when taken for up to 1 year) or red blood cells (when taken for up to 5 years).

Effect of lamotrigine on the cationic carrier of organic substrates

Lamotrigine is an inhibitor of tubular secretion by affecting the cationic transporter of proteins. This can lead to an increase in plasma concentrations of certain drugs, which are mainly excreted through the kidneys. Concomitant use of lamotrigine and substrates with a narrow therapeutic range, such as dofetilide, is not recommended.

Kidney failure

A single use of lamotrigine to patients with severe renal insufficiency did not reveal significant changes in lamotrigine concentration. However, accumulation of the glucuronide metabolite is very likely, so caution should be exercised when treating patients with renal insufficiency.

Patients taking other medications containing lamotrigine

If the patient is receiving any other drug containing lamotrigine, then he should not take Lamictal® without consulting a doctor.

Epilepsy

Abrupt discontinuation of lamotrigine, as well as other AEDs, can trigger the development of seizures. If abrupt discontinuation of therapy is not a safety requirement (for example, if a rash occurs), the lamotrigine dose should be reduced gradually over 2 weeks. There are reports in the literature that severe seizures, including status epilepticus, can lead to the development of rhabdomyolysis, multiple organ disorders, and disseminated intravascular coagulation, sometimes with fatal outcomes. Similar cases were observed in the treatment of patients with lamotrigine.

Suicide 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 of suicide. 25-50% of patients with bipolar disorder have experienced at least one suicide attempt; these patients may experience an increase in suicidal thoughts and suicidal behavior (suicidality) while taking medications for the treatment of bipolar disorder, including lamotrigine, or without treatment.

Suicidal thoughts and suicidal behavior have been reported in patients treated with AEDs for several indications, including epilepsy and bipolar disorder. A meta-analysis of randomized placebo-controlled studies of PEP (including lamotrigine) showed a small increase in suicide risk. The mechanism of this action is unknown, and the available data do not exclude the possibility of an increased risk of suicide when using lamotrigine. Therefore, patients should be closely monitored for suicidal thoughts and behaviors. Patients and caregivers should be informed about the need for medical advice if such symptoms occur.

Bipolar affective disorder

Children and adolescents under 18 years of age

Treatment with antidepressants is associated with an increased risk of suicidal thoughts and behavior in children and adolescents with major depression and other psychiatric disorders.

Clinical deterioration in patients with bipolar affective disorder

In patients with bipolar disorder receiving lamotrigine, the symptoms of clinical deterioration (including the appearance of new symptoms) and suicidality should be carefully monitored, especially at the beginning of the course of treatment and at the time of dose change. Patients who have a history of suicidal thoughts or suicidal behavior, young patients, and patients who have been found to have significantly suicidal thoughts before starting therapy are at high risk for suicidal thoughts or suicidal behavior, and such patients should be closely monitored during treatment.

Patients (and caregivers) should be warned to monitor for any deterioration in patients ‘ condition (including the appearance of new symptoms) and/or the appearance of suicidal thoughts/behaviors or thoughts of self-harm, and should seek medical attention immediately if these symptoms are present.

In this case, the situation should be evaluated and appropriate changes made to the treatment regimen, including the possibility of discontinuing the drug in patients who have a clinical deterioration (including the appearance of new symptoms) and/or the appearance of suicidal thoughts/behaviors, especially if these symptoms are severe, with a sudden onset and have not previously been noted.

Influence on the ability to drive motor vehicles and manage mechanisms

Two studies conducted in healthy volunteers showed that the effect of lamotrigine on accurate visual-motor coordination, eye movement, and subjective sedation was no different from that of placebo. There are reports of neurological side effects of lamotrigine, such as dizziness and diplopia. Therefore, before getting behind the wheel of a car or operating mechanisms, patients should evaluate the effect of lamotrigine on their condition.

Since the effects of all antiepileptic drugs vary individually, patients should consult their doctor about the possibility of driving a car.

Form of production

Tablets are pale yellow to yellow-brown in color, square with rounded corners, one side is flat with the inscription “GSEC7” squeezed out, the other is polyhedral with a convex square with the number “25”squeezed out.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Lamotrigine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets