What Is Lamotrigine?

Lamotrigine Tablets, Indications for Epilepsy: Monotherapy for children over 12 years of age and adults: 1. Simple partial seizures 2. Complex partial seizures 3. Secondary generalized tonicity-clonic seizures 4. Original Primary systemic tonicity-Clonic seizures are currently not recommended as monotherapy in children under twelve, as data for controlled trials in this particular target population are not yet available. Add-on therapy for children over two years of age and adults: 1. Simple partial seizures 2. Complex partial seizures 3. Secondary generalized tonicity-clonic seizures 4. Primary generalized tonicity-clonics Seizures can also be used to treat seizures with Lennox-Gastaut syndrome.

Drug Name: Lamotrigine

Drug type: Prescription drugs, medicines for medical workers' injuries
Use classification: Sodium channel regulators

Lamotrigine Tablets Ingredients

Chemical name: 3,5-diamino-6- (2, 3-dichlorophenyl) -as-triazine Chemical structural formula:

Molecular formula C ₉ H ₇ N ₅ Cl ₂
Molecular weight: 256.09

Lamotrigine Tablet Properties

This product is a light yellow square round tablet. Each tablet of 500mg: embossed "GSEE1" on one side, polyhedron on the other side, "50"; 100mg tablets: "GSEE5" on one side, polyhedron on the other side, "100".

Lamotrigine Tablets Specifications

(1) 50mg; (2) 100mg.

Lamotrigine Tablets Usage and Dosage

[u] How to take [/ u]
This product should be swallowed whole with a small amount of water.
To ensure that the therapeutic dose is maintained, the patient's weight should be monitored and the dose should be checked when the weight changes.
If the calculated dose of lamotrigine (for children and patients with impaired liver function) is not the whole number, the lower dose should be used for the whole number.
When other combined anti-epileptic drugs are discontinued and treated with this product alone or other anti-epileptic drugs are added to the additive treatment plan of this product, the effect of the above changes on the pharmacokinetics of lamotrigine should be considered interaction).
[u] Monotherapy dose [/ u]
Adults and children over 12 years:
The initial dose of this product is 25 mg once daily for two weeks; then 50 mg once daily for two weeks. Thereafter, the dose is increased every 1-2 weeks, the maximum increase is 50-100mg, until the best effect is achieved. The maintenance dose that usually achieves the best effect is 100-200mg / day, which is administered once or twice daily. However, some patients need to take 500mg of lamotrigine daily to achieve the desired effect.
The recommended dose escalation methods for adults and children over 12 years of age are shown in the following table:
1 + 2 weeks 3 + 4 weeks usually maintain a dose of 25mg (once daily) 50mg (once daily) 100-200mg (once or twice daily)
In order to achieve maintenance, the daily dose can be increased by 50-100mg every 1-2 weeks
To reduce the risk of rash, do not exceed the above table for the initial dose and subsequent dose increments (see [Cautions]).
[u] Dosage of Additive Therapy [/ u]
Adults and children over 12 years:
For patients taking sodium valproate, whether or not they are taking other antiepileptic drugs, the initial dose of this product is 25 mg, taken every other day for two weeks; 25 mg once daily for the next two weeks. Thereafter, the dose should be increased every 1-2 weeks, with a maximum increase of 25-50 mg until the best effect is achieved. The maintenance amount that usually achieves the best effect is 100-200mg daily, taken once or twice.
For those patients with anti-epileptic drugs induced by a combination of enzymes, whether or not they are taking other anti-epileptic drugs (except sodium valproate), the initial dose of this product is 50 mg once daily for two weeks; each subsequent two weeks Take 100mg daily in two divided doses. Thereafter, the dose was increased every 1-2 weeks, with a maximum increase of 100 mg until the best effect was achieved. The maintenance amount that usually achieves the best effect is 200-400mg per day, divided into two doses. Some patients need to take 700mg of this product daily to achieve the desired effect.
In patients using other drugs that do not significantly inhibit or induce lamotrigine glucuronidation (see [Drug Interactions]), the initial dose of this product is 25 mg once daily for two weeks; each subsequent two weeks 50mg once daily. Thereafter, a dose level is increased every 1-2 weeks, with an increase of 50-100 mg / day, and the subsequent dose should be increased to achieve the best effect. The optimal maintenance amount is usually 100-200mg / day, once or twice a day.
The recommended dose escalation methods for adults and children over 12 years of age are shown in the following table:
Concomitant drugs 1 + 2 weeks 3 + 4 weeks The usual maintenance dose of sodium valproate plus / without other antiepileptic drugs 12.5mg (25mg, every other day) 25mg (once a day) 100-200mg (once a day or in two) (Serving twice) In order to achieve maintenance, it can be increased by 25-50mg every 1-2 weeks
Enzyme-induced antiepileptic drugs * with / without other 50mg (once a day) 100mg (taken twice) 200-400mg (every two times) In order to achieve maintenance, 100mg can be added every 1-2 weeks
Antiepileptic drugs (except sodium valproate)
Others that do not significantly inhibit or induce lamotrigine glucose 25mg (once a day) 50mg (once a day) 100-200mg (once or twice a day) may be increased by 50-1-2 every 1-2 weeks in order to achieve maintenance 100mg
Therapeutic dose escalation schemes for alkylated drugs * such as phenytoin, carbamazepine, phenobarbital, and apoxenone Note: If the pharmacokinetic interactions of antiepileptics and lamotrigine used by patients are unclear The recommended dose when lamotrigine is used in combination with sodium valproate should be used, and the dose should be gradually increased to achieve the best effect.
To reduce the risk of rash, do not exceed the above table for the initial dose and subsequent dose increments (see [Cautions]).
Children (2-12 years):
For patients taking sodium valproate with or without any other antiepileptic drugs, the initial dose of this product is 0.15 mg / kg / day, once daily for two weeks; daily for the next two weeks, 0.3 each time mg / kg. Thereafter, the dose should be increased every 1-2 weeks with a maximum increase of 0.3 mg / kg until the best effect is achieved. The best maintenance effect is usually 1-5mg / kg / day, taken in single or divided doses.
Patients who take antiepileptic drugs (AEDs) or other drugs that induce lamotrigine glucuronidation (see [Drug Interactions]), with or without other antiepileptic drugs (except sodium valproate). The initial dose was 0.6 mg / kg / day, divided into two doses for two consecutive weeks; the next two weeks, the dose was 1.2 mg / kg / day, divided into two divided doses. Thereafter, the dose should be increased every 1-2 weeks, with a maximum increase of 1.2 mg / kg until the best effect is achieved. The maintenance amount that usually achieves the best effect is 5-15mg / kg / day, divided into two doses.
To obtain an effective maintenance dose, the child's weight must be monitored and the dose re-evaluated based on changes in body weight.
In patients using other drugs that do not significantly inhibit or induce lamotrigine glucuronidation (see [Drug Interactions]), the initial dose of this product is 0.3 mg / kg / day, once or twice daily. Take it for two weeks, then 0.6 mg / kg / day, once or twice a day for two weeks. Thereafter, the dose was increased every 1-2 weeks, and the maximum daily increase was 0.6 mg / kg / day until the best effect was achieved. The optimal maintenance effect is usually 1-10 mg / kg daily, taken once or twice daily, with a maximum daily dose of 200 mg.
The recommended dose escalation method (total daily mg / kg / day) for children (2-12 years old) in combination therapy is shown in the following table:
Concomitant drugs 1 + 2 weeks 3 + 4 weeks The usual maintenance dose of sodium valproate plus / without other antiepileptic drugs 0.15mg / kg ** (once a day) 0.3mg / kg (once a day) may be every 1-2 Increase by 0.3mg / kg weekly to achieve a maintenance amount of 1-5mg / kg (once or twice daily)
Enzyme-induced antiepileptic drugs * with / without other 0.6mg / kg (taken in two doses) 1.2mg / kg (taken in two doses) can be increased by 1.2mg / kg for 1-2 weeks to achieve a maintenance amount of 5-15mg / kg (served twice)
Antiepileptic drugs (except sodium valproate)
Others do not significantly inhibit or induce lamotrigine 0.3 mg / kg (once or twice) 0.6 mg / kg (once or twice) In order to achieve a maintenance amount of 1-10 mg / kg, increase 0.6 every 1-2 weeks mg / kg (1 time or 2 times)
Therapeutic dose escalation regimen for glucuronidated drugs is a maximum daily dose of 200 mg
* Such as phenytoin, carbamazepine, phenobarbital, and apoxenone Note: If the pharmacokinetic interactions of antiepileptic drugs and lamotrigine with patients are not clear, lamotrigine and The recommended dose when sodium valproate is used in combination, and then gradually increase the dose to achieve the best effect.
** Note: If the daily dose is 1-2mg, 2mg of this product should be taken in the first two weeks, once every other day. If the calculated dose is less than 1mg, this product should not be taken.
To reduce the risk of rash, do not exceed the above table for the initial dose and subsequent dose increments (see [Cautions]).
Patients 2-6 years old:
The amount of maintenance required can be at the upper end of the recommended dosage range.
Children younger than 2 years:
Children under 2 years of age do not have sufficient information to use this product, so lamotrigine tablets are not recommended for children under 2 years of age.
General recommendations for lamotrigine for specific patient populations. Women taking hormonal contraceptives (a) Women who have already taken hormonal contraceptives start lamotrigine:
Although oral contraceptives can increase the clearance of lamotrigine (see [Precautions] and [Drug Interactions]), the recommended lamotrigine need not be used solely based on the patient's use of hormonal contraceptives Dose escalation guidelines are adjusted. The dose should be increased according to whether lamotrigine is used in combination with sodium valproate (an enzyme inhibitor of lamotrigine); or whether it is used in combination with an enzyme inducer of lamotrigine; or whether lamotrigine is used in In the absence of valproate or lamotrigine glucuronidation, dose escalation was performed in accordance with the proposed guidelines (see Table 1 for patients with epilepsy).
(b) Patients who have taken a maintenance dose of lamotrigine but have not taken a lamotrigine gluconate inducer have started taking a hormonal contraceptive:
The maintenance dose of lamotrigine needs to be increased in most cases, and may be increased by up to 2 times (see [Cautions] and [Drug Interactions]). It is recommended that the lamotrigine dose be increased at a rate of 50-100 mg / day from the beginning of the hormonal contraceptives, depending on the individual clinical response. Unless the clinical response supports a larger dose increase, the dose increase should not exceed this rate.
(c) Withdrawal of hormonal contraceptives in patients who have taken a maintenance dose of lamotrigine but have not taken a lamotrigine gluconate inducer:
The maintenance dose of lamotrigine needs to be reduced by up to 50% in most cases (see [Cautions] and [Drug Interactions]). It is recommended that the daily dose of lamotrigine be gradually reduced at a rate of 50-100 mg per week (at a rate not exceeding 25% of the total daily dose per week) and lowered for more than 3 weeks, unless the clinical response shows otherwise.
[u] Combined with atazanavir / ritonavir [/ u]
Although atazanavir / ritonavir has been shown to reduce the plasma concentration of lamotrigine (see [Drug Interactions]), it is not necessary to simply treat atazanavir / ritonavir based on the patient. Adjustments to the recommended lamotrigine dose escalation guidelines were made. Dose escalation should be based on whether lamotrigine is used in sodium valproate (an enzyme inhibitor of lamotrigine); or whether lamotrigine is used as an inducer of glucuronidation; or lamotrigine Whether to add in the absence of sodium valproate or lamotrigine glucuronidation inducers, and follow the guidelines given for dose escalation. In patients who have taken a maintenance dose of lamotrigine and have not been treated with an inducer of glucosidification, if atazanavir / ritonavir is added, the dose of lamotrigine needs to be increased. Zanavir / ritonavir treatment requires a reduction in the lamotrigine dose.
[u] Dose for patients with impaired liver function [/ u]
Lamotrigine's initial, escalating, and maintenance doses should be reduced by approximately 50% and 75% in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) liver impairment, respectively. Increasing and maintaining doses should be adjusted for clinical efficacy.
[u] Dose for patients with impaired renal function [/ u]
Patients with impaired renal function should be cautious when taking lamotrigine. For patients with advanced renal failure, the initial dose of lamotrigine should follow the medication regimen when combined with other antiepileptic drugs. For patients with significantly impaired renal function, the maintenance dose should be reduced (see [Precautions]). For more information about pharmacokinetics, see [Pharmacokinetics].
Adverse reactions

Lamotrigine Tablets Adverse Reactions

Classification of adverse reactions:
Very common (> 1/10);
Common (> 1/100 and <1/10);
Uncommon (> 1/1000 and <1/100);
Rare (> 1/10000 and <1/1000);
Very rare (<1/10000).
[u] Skin and subcutaneous tissue lesions [/ u]
Very common: rash.
Rare: Stevens-Johnson syndrome.
Very rare: toxic epidermal necrolysis.
In an adult double-blind, additional clinical trial, the incidence of rash was as high as 10% in patients taking lamotrigine and 5% in patients taking placebo. 2% of patients discontinued lamotrigine due to a rash. This rash is usually maculopapular in appearance and usually appears 8 weeks before the start of treatment. It disappears after stopping lamotrigine (see [Precautions]).
Rare, severe, and potentially life-threatening rashes have been reported, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (LyeLL syndrome). Although most patients can recover after discontinuation, some patients have experienced irreversible scars, and rare cases related to death have occurred (see [Cautions]).
Reports of severe rashes, such as in adults and children over 12 years old, are about 1: 1000. Children under 12 years of age are more at risk than adults. Studies have shown that children under the age of 12 have a rash and require hospitalization at a rate of 1: 300 to 1: 100 (see [Precautions]).
The child's initial rash may be mistaken for an infection; in the first 8 weeks of treatment with this product, if the child develops a rash and fever symptoms, the doctor should consider the possibility of a drug reaction.
In addition, the overall risk of rash is related to the following factors:
-The starting dose of lamotrigine is high and the subsequent increasing dose exceeds the recommended incremental dose (see [Dosage and Administration]).
-Simultaneously apply sodium valproate (see [Dosage and Administration]).
It has also been reported that rash is part of an allergic syndrome, with multiple forms of systemic symptoms (see Immune System Disorders).
[u] Blood and lymphatic disorders [/ u]
Very rare: Hematological abnormalities (including neutropenia, leukocytopenia, anemia. Thrombocytopenia, pancytopenia and very rare aplastic anemia and agranulocytosis), lymphadenopathy. Hematological abnormalities and lymphadenopathy may or may not be associated with allergic syndromes (see Immune System Disorders).
[u] Immune system disorder [/ u]
Very rare: allergic syndrome ** (including symptoms such as fever, lymphadenopathy, facial edema, abnormal blood and liver function, rare diffuse intravascular coagulation (DIC), and multiple organ failure)
**: There are also reports that the rash is part of an allergic syndrome with many forms of systemic symptoms, including fever. Lymphadenopathy, facial edema, and abnormal blood and liver function. The severity of the clinical response to this syndrome varies widely; rare is diffuse intravascular coagulation (DIC) and multiple organ failure. Even if the rash is not obvious, it is important to pay attention to the early manifestations of allergic reactions (such as fever, lymphadenopathy). If symptoms and signs appear, the patient should be advised to seek medical attention immediately. If signs and symptoms of early reactions appear, the patient should be evaluated immediately; if no other cause can be determined, this product should be discontinued.
[u] Disorders of the mental system [/ u]
Common: Aggressive behavior.
Very rare: unstable standing, hallucinations, and confusion.
[u] Disorders of the nervous system [/ u]
In clinical trials of monotherapy is very common: headache.
Common: lethargy, insomnia, dizziness, tremor.
Uncommon: Ataxia.
Rare: nystagmus.
In other clinical applications <is very common: lethargy, ataxia, headache, dizziness.
Common: nystagmus, tremor, insomnia.
Very rare: aseptic meningitis, excitement, restlessness, movement disorders, exacerbation of Parkinson's disease, extrapyramidal effects, chorea of hand-foot movements in chorea, and increased frequency of disease attacks.
There have been reports of patients who already have Parkinson's disease, taking this product to aggravate their Parkinson's symptoms, and in patients without potential disease, there have been individual reports of extrapyramidal effects and chorea of choppy feet in chorea.
[u] Eye abnormalities [/ u]
In clinical trials of monotherapy Rarely: diplopia, blurred vision.
It is very common in other clinical applications : diplopia, blurred vision.
Rare: conjunctivitis.
[u] Gastrointestinal disorders [/ u]
In clinical trials of monotherapy Common: nausea, vomiting, diarrhea.
In other clinical applications is very common: nausea, vomiting.
Common: Diarrhea.
[u] Hepatobiliary abnormalities [/ u]
Very rare: elevated liver function tests, abnormal liver function, and liver failure.
The appearance of liver dysfunction is usually associated with allergic reactions, but there have been reports of individual cases with no obvious signs of allergies.
[u] Muscle, bone, and connective tissue disorders [/ u]
Very rare: Lupus-like reaction.
[u] General disorders and site reactions [/ u]
Common: Fatigue.

Lamotrigine Tablets Contraindications

It is contraindicated in patients who are allergic to lamotrigine and any ingredients in this product.

Lamotrigine Tablets Precautions

[u] rash [/ u]
There have been reports of adverse skin reactions, which generally occurred 8 weeks before the start of treatment with lamotrigine. Most rashes are mild and self-limiting. However, it has rarely been serious. Life-threatening rashes, including Stevens-Johnson syndrome and reports of toxic epithelial necrosis (TEN) (see [Adverse Reactions]).
Severe rashes such as SJS syndrome occur in adults and children over 12 years old at a rate of about 1: 1000. Children under 12 years of age are more at risk than adults. Studies have shown that children under 12 years of age develop a rash and require hospitalization at a rate of 1: 300-1: 100 (see [Adverse Reactions]).
The child's initial rash may be mistaken for an infection; in the first 8 weeks of treatment with this product, if the child develops a rash and fever symptoms, the doctor should consider the possibility of a drug reaction.
In addition, the overall risk of rash is related to the following factors:
-The initial dose of lamotrigine is too high and the subsequently increased dose exceeds the recommended dose (see [Dosage and Administration]).
-Simultaneously apply sodium valproate (see [Dosage and Administration]).
It should also be noted that patients who have a history of allergies or rashes with other antiepileptic drugs, who have received lamotrigine, are about three times more likely to develop a non-serious rash than patients without such a history.
All patients (adults and children) who develop a rash should be evaluated promptly and lamotrigine be discontinued unless a rash can be diagnosed that is not related to this drug. For patients who discontinued this product due to a rash during previous treatment, it is not recommended to re-use this product for treatment, unless the expected benefits outweigh the potential risks.
It has also been reported that the rash is part of an allergic syndrome and is accompanied by various forms of systemic symptoms, including fever and lymphadenopathy. Facial edema and abnormalities in blood and liver. The severity of the clinical response to this syndrome varies widely; rare is diffuse intravascular coagulation (DIC) and multiple organ failure. Even if the rash is not obvious, it is important to pay attention to the early manifestations of allergic reactions (such as fever, lymphadenopathy). If symptoms and signs appear, the patient should be advised to seek medical attention immediately. If signs and symptoms of early reactions appear, the patient should be evaluated immediately; if no other cause can be determined, this product should be discontinued.
[u] Risk of suicide [/ u]
Patients with epilepsy may also have symptoms of depression and / or bipolar disorder, and there is evidence that patients with epilepsy and bipolar disorder have an increased risk of suicide.
25-50% of patients with bipolar disorder have attempted suicide at least once and can experience worsening depressive symptoms and / or suicidal ideation and behavior (suicidal behavior) regardless of whether they are taking bipolar disorder medications, including lamotrigine.
There have been reports of suicidal ideation and behavior in patients with several indications treated with AEDs, including epilepsy and bipolar disorder. A meta-analysis of a randomized, blank-controlled clinical trial of AEDs, including lamotrigine, showed a slightly increased risk of suicidal ideation and behavior. The mechanism for this type of risk is unknown, and the possibility of lamotrigine growth risk cannot be ruled out with the currently available data.
Therefore, patients should be monitored for suicidal thoughts and signs of behavior. Patients (and their caregivers) should consider seeking medical advice and help for signs of suicidal ideation and behavior.
[u] Hormonal contraceptives [/ u]
[u] Effects of hormonal contraceptives on the efficacy of lamotrigine triazine tablets [/ u]
Studies have shown that ethinyl estradiol / levonorgestrel (30mcg / 150mcg) mixture can increase the clearance of lamotrigine by about two times, leading to a decrease in the level of lamotrigine (see [Drug Interactions]). After a gradual increase in dose, to maintain maximum efficacy, the maintenance dose (up to 2 times) of lamotrigine needs to be increased in most cases. Among women who have not taken lamotrigine glucuronidation inducers but have taken a hormonal contraceptive (including a 1-week inactive drug period) (eg, "drug-free period"), during a week when the active drug is not used The level of lamotrigine increased temporarily. The lamotrigine concentration increased significantly before the week when the active drug was not used or when the dose of lamotrigine increased. For medication instructions, please see "Recommendations, Dosage, and Usage of Lamotrigine Tablets in Specific Patients."
Clinicians should properly manage women who start or stop using hormonal contraceptives during lamotrigine treatment, and adjust the dosage of lamotrigine when necessary in most cases.
Other oral contraceptives and hormone replacement therapy (HRT) have not been studied, although these drugs may have similar effects on the pharmacokinetic parameters of lamotrigine.
[u] Effects of lamotrigine on the efficacy of hormonal contraceptives [/ u]
Drug interaction studies in 16 healthy volunteers have shown that levonorgestrel clearance is moderate when lamotrigine and a hormonal contraceptive (ethinylestradiol / levonorgestrel mixture) are taken at the same time Elevated, serum FSH and LH also changed (see [Drug Interactions]). The effect of these changes on ovulation activity in the ovary is unknown. However, the possibility that these changes may lead to a reduction in the contraceptive effect of some patients taking both hormonal drugs and lamotrigine tablets cannot be ruled out. Therefore, patients should be advised to report any changes to the menstrual cycle, such as sudden bleeding, to the doctor as soon as possible.
[u] Dihydrofolate reductase [/ u]
This product is a weak inhibitor of dihydrofolate reductase, so it may interfere with folate metabolism during long-term treatment. However, after long-term administration in humans for up to one year, lamotrigine did not cause significant changes in hemoglobin concentration, average cell volume, and folate concentration in serum or red blood cells: the administration of lamotrigine for five years had no significant effect on the folate concentration of red blood cells. .
[u] renal failure [/ u]
In a single-dose study of patients with advanced renal failure, plasma lamotrigine concentrations did not change significantly. However, accumulation of glucuronic acid metabolites can be expected; therefore, caution should be used in patients with renal failure.
[u] Liver failure [/ u]
In patients with severe hepatic impairment (Child-Pugh Class C), the initial and maintenance doses should be reduced by 75%. Patients with severe liver dysfunction should be used with caution.
[u] Patients taking other lamotrigine formulations [/ u]
This product should not be used in patients who are taking other lamotrigine-containing preparations for treatment without consulting a doctor.
[u] epilepsy [/ u]
When combined with other antiepileptic drugs, sudden discontinuation of this product can cause seizures. Unless sudden discontinuation is required due to safety considerations (such as a rash), the dose of this product should be gradually reduced to discontinuation within two weeks.
It has been reported in the literature that severe seizures, including status epilepticus, can cause rhabdomyolysis, multiple organ disorders, and diffuse intravascular coagulation (DIC), which can sometimes be fatal. Similar events occurred with lamotrigine.
[u] Impact on ability to drive and operate machines [/ u]
Two volunteer studies have shown that lamotrigine has no different effects on the coordination of subtle visual movements, eye movements, body swing, and subjective sedation than placebo.
In clinical trials of lamotrigine, adverse neurological events such as dizziness and diplopia have been reported. Therefore, patients should understand how this product may affect them before driving and operating machines.

Lamotrigine tablets for pregnant and lactating women

Fertility:
In animal reproduction experiments, this product does not harm fertility.
The effect of this product on human fertility has not been experienced.
Teratogenicity:
This product is a weak dihydrofolate reductase inhibitor. When pregnant mothers are treated with folic acid inhibitors, there is theoretically a risk of fetal teratogenesis. However, in animal reproductive toxicity studies, lamotrigine doses did not have teratogenic effects when they exceeded human therapeutic doses.
During pregnancy:
There is insufficient data on the use of lamotrigine in humans during pregnancy and its safety cannot be evaluated. Lamotrigine should not be used during pregnancy or weigh the pros and cons.
Lactation:
There is limited information on the use of lamotrigine during lactation. Preliminary data show that lamotrigine can enter milk, and its concentration can usually reach 40 to 60% of the plasma concentration. In a small number of infants known to be breastfed, the plasma concentration of lamotrigine reaches a level where pharmacological effects can occur.

Lamotrigine tablets for children

For monotherapy and supplementary therapy for children over 12 years old, see [ Dosage and Administration ]:
Children from 2 to 12 years;
Due to inadequate data from the corresponding studies in children, it is not possible to recommend doses for monotherapy for children under twelve years of age. Adding therapy see [ Dosage and Administration ]
Children under 2 years: see [ Dosage and Administration ]

Lamotrigine

The pharmacokinetics of lamotrigine in the elderly are not significantly different from those in the young, so no dose adjustment of the recommended protocol is needed.

Lamotrigine tablets drug interactions

UDP-glucuronyltransferase has been identified as an enzyme responsible for lamotrigine metabolism. There is no evidence that lamotrigine can induce or inhibit clinically significant liver oxidative drug metabolism enzymes, and there is no possibility of interaction between lamotrigine and drugs metabolized by cytochrome P450 enzymes. Lamotrigine can induce its own metabolism, but this effect is limited and has no obvious clinical significance.
Table: Effects of other drugs on lamotrigine glucuronidation

+ Dosage guidelines can be found in [Usage and Dosage]-General recommendations for lamotrigine for special patient populations + Other oral contraceptives and HRT treatments have not been studied, although the pharmacokinetics of these drugs on lamotrigine The effects of the learning parameters may be similar. See [Usage and Dosage]-General recommendations for lamotrigine for special patient populations (women taking hormonal contraceptives) and [Precautions]
For the interaction between hormonal contraceptives and AEDs, see [Dosage and Administration]
Certain antiepileptic drugs that induce liver drug metabolism enzymes (eg, phenytoin, carbamazepine, phenobarbital, and polimetone) can induce lamotrigine metabolism by enhancing lamotrigine metabolism. Valproate inhibits glucuronidation of lamotrigine and reduces lamotrigine metabolism. The average half-life of lamotrigine is nearly doubled. (See [Precautions] and [Dosage and Administration]). Patients who are taking carbamazepine have reported CNS reactions after taking lamotrigine, including nausea, blurred vision, dizziness, diplopia, and ataxia. These reactions usually disappear after reducing the dose of carbamazepine. In the lamotrigine and oxcarbazepine studies performed by healthy adult volunteers, the results were similar, but no dose reduction studies were conducted.
In a healthy volunteer study, pharmacokinetics of lamotrigine with lamotrigine (100 mg twice daily for 10 consecutive days) (1200 mg twice daily) There appears to be no clinically relevant effect in science.
Based on a retrospective analysis of the plasma levels of patients receiving lamotrigine tablets, whether with or without gabapentin, gabapentin did not alter the apparent clearance of lamotrigine.
The potential drug-drug interaction between levetiracetam and lamotrigine was evaluated in placebo-controlled clinical trials by evaluating serum concentrations. These data indicate that lamotrigine has no effect on the pharmacokinetics of levothiracetam, and that levothiracetam does not affect the pharmacokinetics of lamotiracetam.
The steady-state trough serum concentration of lamotrigine was not affected by the concomitant use of pregabalin (200 mg, 3 times a day). There is no pharmacokinetic interaction between lamotrigine and pregabalin.
Topiramate did not cause changes in lamotrigine plasma concentrations. Taking lamotrigine tablets resulted in a 15% increase in topiramate concentration.
In studies of patients with epilepsy, taking zonisamide (200 to 400 mg / day) with lamotrigine tablets (150 to 500 mg / day) did not show significant pharmacokinetics of lamotrigine influences.
Although changes in plasma concentrations of other antiepileptic drugs have been reported, controlled studies have shown that there is no evidence that lamotrigine affects the plasma concentrations of concomitant antiepileptic drugs. Evidence from in vitro studies suggests that lamotrigine has not replaced other antiepileptic drugs from protein-binding sites.
In a study of healthy adult volunteers, lamotrigine was administered at a dose of 200 mg and oxcarbazepine was administered at a dose of 1200 mg. Oxcarbazepine did not change the metabolism of lamotrigine, and lamotrigine did not cause Metabolism of Carbazepine.
Interaction with other psychotropic drugs (see [Dosage and Administration])
Twenty healthy subjects received 100 mg / day of lamotrigine and combined with 2 g of anhydrous glucose lithium salt twice daily for 6 consecutive days without any effect on the pharmacokinetics of lithium salt.
Twelve subjects had multiple doses of oral bupropion and had no significant effect on the pharmacokinetics of single-dose oral lamotrigine tablets, but the AUC of lamotrigine glucuronic acid slightly increased.
In a steady-state pharmacokinetic mutual study of healthy adult volunteers, a daily dose of 15 mg of olanzapine reduced the AUC and Cmax of lamotrigine 200 mg per day by an average of 24% and 20%, respectively. The effect of this magnitude is generally considered to be of no clinical significance. Lamoxan 200 mg daily has no effect on the pharmacokinetics of olanzapine.
In 14 healthy adult volunteers, multiple oral doses of 400 mg of lamotrigine daily did not have a clinically significant effect on the pharmacokinetics of a single dose of 2 mg of risperidone. After 2mg of risperidone and lamotrigine, 12 of 14 volunteers reported drowsiness, compared to only 1 of 20 subjects reported after risperidone was administered alone Drowsiness was not reported when lamotrigine tablets were administered alone.
In vitro experiments show that the main metabolite of lamotrigine is 2-N-glucuronic acid, which is used in combination with sodium valproate, bupropion, clonazepam, amitriptyline, haloperidol, and lauracil It can inhibit the production of this metabolite when hatching at the same time. Sodium valproate is known to reduce lamotrigine clearance in the body, and in these experiments, the effect of co-administration of bupropion on lamotrigine was second only to sodium valproate; however, Twelve healthy volunteers who took oral bupropion acetam repeatedly did not have a statistically significant effect on the pharmacokinetics of a single dose of lamotrigine at a low dose (100 mg), only causing lamotrigine glucosamine The acid metabolite AUC increased slightly. These phenomena suggest that the risk of clinical interactions with amitriptyline, clonazepam, haloperidol, or lorazepam is almost impossible. In vitro experiments also suggest that clozapine, phenelzine, risperidone, sertraline, triazolone or fluoxetine do not affect the clearance of lamotrigine. Metabolic data of bupropionol via human liver mitochondria suggest that lamotrigine does not reduce the elimination of drugs that are metabolized primarily by CYP2D6 enzymes.
Interaction with hormonal contraceptives Hormonal contraceptives affect the pharmacokinetics of lamotrigine. In a study of 16 female volunteers, a combined oral contraceptive pill consisting of 30mcg ethinylestradiol and 150mcg levonorgestrel The clearance of oral administration of lamotrigine was increased by about two times, resulting in an average reduction of AUC and Cmax of lamotrigine of 52% and 39%, respectively. The lamotrigine serum concentration gradually increased during the 1 week without the active drug (eg, "week without the contraceptive"), and the average lamotrigine serum concentration before the weekend without the active drug was about The concentration during the combined medication was 2 times higher. See [Usage and Dosage]-General recommendations for lamotrigine for special patient populations (women taking hormonal contraceptives) and [Precautions]-a hormonal contraceptive.
Effect of lamotrigine on the pharmacokinetics of hormonal contraceptives In a study of 16 female volunteers, lamotrigine was administered at a steady state dose of 300 mg to the pharmacokinetics of the ethinylestradiol component of the combined oral contraceptive pill The kinetics have no effect. A modest increase in clearance was observed for oral administration of levonorgestrel, and the average AUC and Cmax of levonorgestrel decreased by 19% and 12%, respectively. Measurements of serum FSH, LH, and estradiol during the study showed that some women lost their inhibitory effects on ovarian hormone activity, but serum progesterone measurement results showed no evidence of ovulation hormones in 16 subjects. The effect of a moderate increase in levonorgestrel clearance and changes in serum FSH and LH on ovarian ovulation activity is unknown (see [Cautions]). The effect of lamotrigine above 300 mg / day has not been studied, and no other estrogen preparations have been studied.
Interactions with other drugs In a study of 10 male volunteers, rifampicin increased lamotrigine clearance and shortened the half-life of lamotrigine by inducing liver enzymes responsible for glucuronidation. Patients treated with rifampicin at the same time should use the recommended treatment regimen of lamotrigine combined with glucuronidation inducer (see [Dosage and Administration]).
In a study with healthy volunteers, lopinavir / ritonavir almost halved the plasma concentration of lamotrigine, most likely due to the induction of gluconic acid. In patients receiving concomitant therapy with lopinavir / ritonavir, the recommended lamotrigine treatment regimen and concomitant inducer of glutaration should be used (see [Dosage and Administration]).
In a study of healthy adult volunteers, atazanavir / ritonavir (300mg / 100mg) reduced the plasma AUC and Cmax of lamotrigine (100mg, single dose) by an average of 32% and 6% (see "Usage and dosage-general dosing recommendations for lamotrigine in specific patient populations").

Lamotrigine Tablets Overdose

Symptoms and signs:
There have been reports of acute intake exceeding 10 to 20 times the maximum therapeutic dose. Overdose can cause symptoms such as nystagmus, ataxia, impaired consciousness, and coma.
Disposal:
Once an overdose occurs, the patient should be hospitalized and given appropriate supportive care; if necessary, gastric lavage should be performed.

Lamotrigine Tablets Pharmacology and Toxicology

1. Mechanism of pharmacological action:
The results of pharmacological studies suggest that lamotrigine is a sodium channel blocker that blocks the compliance of voltage applications. In cultured nerve cells, it produces a continuous repetitive discharge of application and voltage compliance blocks, while inhibiting pathological glutamate release (this amino acid plays a key role in the formation of seizures) and also inhibits Burst of glutamate-induced action potential.
Pharmacodynamics:
In tests evaluating the effects of the drug on the central nervous system, healthy volunteers took 240 mg of lamotrigine, and the results were no different from those of placebo; however, 1000 mg of phenytoin and 10 mg of diazepam significantly impaired the coordination of fine visual movement and eye movements, increasing the body The swing and subjective sedation effect.
600mg150mg300mg
3.

Carcinogenicity:

2.5450mg
55%0.921.22L/kg
39±14mL/min 10%2%2435UDPGilbert32%
P450
1470([])
12574550([])
1265761226-38150mg37%(0.39mL/min/kg)30-450mg9(0.310.65mL/min/kg) (1213)2035mL/min7031mL/min12%4841mL/min37mL/min10%
8
2412(Child-Pugh )ABC0.310.240.10mL/min/kg0.34mL/min/kgBC([])

30/

36 months.

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