Expiration date: 09/2025
Structure and Composition:
Tablets. One tablet contains lamotrigine 25, 50 or 100 mg
Excipients: colloidal anhydrous silica magnesium stearate, povidone, sodium carboxymethyl lactose monohydrate MCC
in blisters of 10 pieces. in a stack of cardboard 3 packaging.
Description pharmaceutical form:
Tablets 25 mg: white or almost white biconvex tablets, engraved on one side «L25».
Tablets 50 mg: white or almost white biconvex tablets, engraved on one side «L50».
Tablets 100 mg: white or almost white biconvex tablets, engraved on one side «L100».
Pharmacokinetics:
Rapidly and completely absorbed in the intestine without being substantially primary metabolism in the liver. Maximum plasma concentration is reached 2.5 hours after oral administration. Eating slows down the process of absorption, but does not affect its effectiveness. The pharmacokinetics of single dose not exceeding 450 mg, is linear. The concentration in the saturation stage is pronounced individual character.
Bioavailability - 98%. Binding to plasma proteins - 55% it is unlikely that the displacement of lamotrigine due to proteins may cause toxic effects. The volume of distribution - 0,92-1,22 l / kg body weight.
Metabolism in the liver due to uridine diphosphate glucuronyl. Among all the metabolites predominate N-glucuronides. The moderate, dose-dependent manner, Lamotrigine induces its own metabolism.
Average clearance saturation stage is in healthy adults (39 ± 14) ml / min. Displayed along with the urine in the form of glucuronide conjugate, less than 10% - unchanged. About 2% of active compound and degradation products are displayed, along with stool. The clearance half-life and do not depend on the dosage, T1 / 2 in healthy volunteers - 24-35 h.
Provided with breast milk. Concentration in breast milk is 40-60% of the plasma concentration. In some cases, the drug concentration in the serum of infants whose mothers took the drug during breastfeeding, reaches a therapeutic level.
Clearance recalculated per kg of body weight in children is higher than in adults, is highest under 5 years of age. T1 / 2 is generally shorter than in adults while taking inducers of enzymes of the liver T1 / 2 is equal to 7 hours, and when taking sodium valproate - 45-60 hours.
Clearances lamotrigine in young and elderly patients with epilepsy minimally different from each other.
Description of the pharmacological actions:
Stabilizes the voltage dependent sodium channels of the cell membrane and blocks the release of neurotransmitters, especially glutamate. As activating amino acid glutamate plays a key role in the occurrence of epileptic seizures.
Indications:
epilepsy:
- adults and children over 12 years - as a single agent or in combination with other antiepileptic drugs for the treatment of partial and generalized seizures, including tonic-clonic seizures and seizures with Lennox-Gastaut syndrome
- children over 2 years old - in combination with other antiepileptic drugs for the treatment of partial and generalized seizures, including tonic-clonic seizures and seizures with Lennox-Gastaut syndrome.
Bipolar disorder:
- prevention and treatment, mainly episodes of depression in patients older than 18 years.
Contraindications:
- hypersensitivity to any component of the drug
- pregnancy
- breastfeeding
- Children under 2 years old.
Carefully:
- renal failure (due to the possible cumulation glucuronide metabolite)
- children as a drug of choice for epilepsy monotherapy.
Application of pregnancy and breastfeeding:
Pregnancy: Due to the inhibitory effects of lamotrigine in the dihydrofolate reductase likely to develop malformations of the fetus in the case of the treatment of pregnant women, but the available data are insufficient to determine the degree of safety of lamotrigine for pregnant women. Receiving Lamotrigine is contraindicated during pregnancy, except in cases where the expected benefit to pregnant exceeds the degree of potential risk to the fetus.
Lactation: the number of observations in the period of breastfeeding is limited. Concentration in breast milk lamotrigine is 40-60% of the plasma concentration. A few observations show that the drug concentration in the serum of infants whose mothers took the drug during breastfeeding, up to a therapeutic level. You should carefully weigh the benefits of breast-feeding during treatment and the risk of side effects in the infant.
Side effect:
Adverse reactions are presented separately for each disease and classified into categories depending on their frequency of occurrence: very common (> 1/10), common (> 1/100, <1/10), sometimes (> 1/1000, <1 / 100), rare (> 1/10000, <1/1000), very rare (<1/10000).
Epilepsy:
From the side of hematopoiesis: rarely - neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis.
On the part of the immune system, allergic reactions: very often - in the first 8 weeks of treatment skin rash (usually maculopapular) disappears after the abolition of lamotrigine rarely - Stevens-Johnson syndrome rarely - hypersensitivity syndrome (fever, lymphadenopathy, facial edema, changes in blood parameters and hepatic function, disseminated intravascular coagulation, and multiple organ failure), toxic epidermal necrolysis (Lyell's syndrome, in some cases, recovery from scarring).
From the nervous system: very often - headache often - irritability, drowsiness, insomnia, dizziness, tremor, nystagmus, ataxia, anxiety sometimes - ataxia, aggression is very rare - increased agitation, hallucinations, darkening and confusion, impaired balance, current deterioration Parkinson's disease, extrapyramidal effects, choreoathetosis, increased seizures.
From a sight organ: very often - diplopia, blurred vision, rarely - conjunctivitis.
On the part of the digestive tract: often - nausea, vomiting rarely - increase in liver enzymes, liver failure.
From the musculoskeletal system: very rarely - a separate lupusopodobnye (or lupus) reaction.
General, dose-dependent: often - fatigue.
With bipolar disorder in addition to the above symptoms are possible:
on the part of the musculoskeletal system: often - arthralgia
dose-dependent: myalgia, back pain.
Drug Interactions:
Sodium valproate competitively blocks liver enzymes and inhibits the metabolism of lamotrigine, nearly doubling the amount of the average value of its T1 / 2, extending it to 70 hours.
Antiepileptics - hepatic enzyme inducers (phenytoin, carbamazepine, phenobarbital, primidone), paracetamol lamotrigine stimulate metabolism and shorten its T1 / 2 to 2 times, i.e. to 14 hours (phenytoin, carbamazepine). Patients taking carbamazepine, lamotrigine administration may cause increased side reactions from the central nervous system: dizziness, ataxia, diplopia, blurred vision and nausea. Reducing the dose of carbamazepine usually leads to the disappearance of complaints.
No effect on the plasma concentrations of other antiepileptic drugs on ethinyl estradiol and levonorgestrel concentration after administration of oral contraceptives.
Lamotrigine does not reduce the clearance of drugs, especially those that are eliminated from the body due to CYP2D6. Clozapine, phenelzine, risperidone, trazodone sertalin and apparently did not affect the clearance of lamotrigine.
Data on the effect of lamotrigine on the pharmacokinetics of other antiepileptic drugs and drug interactions between him and drugs, depending on the CYP450, no.
Compatible with sedative, anxiolytic and antiepileptic agents.
Dosage and administration:
Inside, with liquid squeezed small amounts of water.
Monotherapy epilepsy
Adults and children over 12 years: an initial dose - 25 mg 1 time a day for 2 weeks for the next 2 weeks - 50 mg 1 time a day. Subsequently, every 1-2 weeks the daily dose can be increased to 50-100 mg until until the optimum effect is reached. Generally supporting daily dose - 100-200 mg, distributed to 1 or 2 divided doses. In rare cases, the desired effect is provided by doses of 500 mg per day.
Table 1. Driving increasing doses as monotherapy for adults and children over 12 years
| 1–2 weeks | 3–4 weeks | The recommended maintenance dose |
| 25 mg 1 time per day | 50 mg 1 time per day | 100-200 mg (1 or 2 divided doses). To achieve the maintenance dose every 1-2 weeks increase the dose of 50-100 mg |
Combination therapy of epilepsy
Adults and children over 12 years: patients taking sodium valproate in combination with other antiepileptic drugs or without them, the initial dose of lamotrigine - 25 mg every other day for 2 weeks for the next 2 weeks - daily 25 mg 1 time a day. In the subsequent dose may be increased to 25-50 mg every 1-2 weeks until until the optimum effect is reached. Regular maintenance daily dose - 100-200 mg 1-2 reception.
Patients receiving antiepileptic drug which is an inducer of liver enzymes (phenytoin, carbamazepine, phenobarbital, primidone), in combination with other antiepileptic drugs, or without them, but not receiving sodium valproate, the initial daily dose of lamotrigine - 50 mg 1 time per day for 2 the following week for 2 weeks - 100 mg per day, 2 doses. Further dose can be increased by not more than 100 mg every 1-2 weeks until the optimum effect. Regular maintenance daily dose - 200-400 mg 1-2 reception. In rare cases, a 700 mg daily.
In the case of treatment of antiepileptic drugs, a pharmacokinetic interaction with lamotrigine is unknown, the dose of lamotrigine should be increased for smaller doses of the scheme described for taking sodium valproate.
Table 2. Driving increasing dose in combination therapy for adults and children over 12 years
| The additional therapeutic agent | 1–2 weeks | 3–4 weeks | The recommended maintenance dose |
| Valproate ± other antiepileptic drugs | 12.5 mg (through day 25 mg) | 25 mg (1 per day) | 100-200 mg (1-2 doses). The maintenance dose is selected, increasing the daily dose of 25-50 mg every 1-2 weeks |
| Antiepileptics-inducer of liver enzymes (phenytoin, carbamazepine, phenobarbital, primidone) ± other medication (no valproate) | 50 mg (1 per day) | 100 mg (1 or 2 doses) | 200-400 mg (2 receptions). The maintenance dose is selected, increasing the dose to 100 mg every 1-2 weeks |
| Antiepileptic agent does not react with lamotrigine | The dose of lamotrigine to improve the scheme for valproate | ||
For children ages 2 to 12 years, receiving sodium valproate, in combination with other antiepileptic drugs or without an initial daily dose of lamotrigine - 0.15 mg / kg body weight one time daily for two weeks for the following 2 weeks - on 0 3 mg / 1 kg body weight per day. Further, the dose may be increased to 0.3 mg / kg every 1-2 weeks until until the optimum effect is reached. Regular maintenance daily dose - 1-5 mg / kg for 1-2 reception. The maximum daily dose should not exceed 200 mg.
Babies receiving antiepileptic drug-inducer of liver enzymes (phenytoin, carbamazepine, phenobarbital, primidone) in combination with other antiepileptic drugs or without them, but not taking sodium valproate, the initial lamotrigine daily dose - 0.6 mg / kg in 2 divided doses per day for two weeks for the following 2 weeks - 1.2 mg / kg per day in 2 divided doses. Further, every 1-2 weeks the dose can be increased by not more than 1.2 mg / kg until until it reaches an optimal effect. Regular maintenance daily dose - 5-15 mg / kg in 2 divided doses. The maximum daily dose should not exceed 400 mg.
In the case of treatment of antiepileptic drugs, a pharmacokinetic interaction with lamotrigine is unknown, the dose of lamotrigine should be increased for smaller doses of the scheme described for taking sodium valproate.
Table 3. Driving increasing dose in combination therapy of children from 2 to 12 years
| The additional therapeutic agent | 1–2 weeks | 3–4 weeks | The recommended maintenance dose |
| Valproate ± other antiepileptic drugs | 0.15 mg / kg (1 per day) | 0.3 mg / kg (1 per day) * | The daily dose is increased every 1-2 weeks to 0.3 mg / kg, until reaching the maintenance dose of 1-5 mg / kg (1-2 doses). The maximum dose - 200 mg daily |
| Antiepileptics-inducer of liver enzymes (phenytoin, carbamazepine, phenobarbital, primidone) ± other medication (no valproate) | 0.6 mg / kg (2 doses) | 1.2 kg (2 doses) | The daily dose is increased every 1-2 weeks to 1.2 mg / kg, until reaching the maintenance dose is 5-15 mg / kg (1-2 doses). The maximum dose - 400 mg daily |
| Antiepileptic agent does not react with lamotrigine | The dose of lamotrigine to improve the scheme for valproate | ||
* - A dose increase spend whole tablets (see general instructions for dispensing.).
Bipolar disorder
In the case of bipolar disorders lamotrigine administered to prevent episodes of depression. In the case of short-term treatment maintenance dose of lamotrigine should be increased gradually over 6 weeks, as long as the patient's condition has stabilized, after that, with appropriate clinical picture of the disease can stop taking psychotropic and / or other antiepileptic drug.
To prevent episodes of mania may require adjuvant therapy, because efficacy of lamotrigine in the case of mania and manic states is mixed.
Table 4. The scheme supports the selection of the daily dose in the treatment of adults 18 years or older with bipolar disorder
| Therapy | 1–2 weeks | 3–4 weeks | 5 weeks | The recommended maintenance dose | ||
| Valproate ± other antiepileptic drugs | 12.5 mg (25 mg every other day) | 25 mg (1 per day) | 50 mg (1-2 times daily) | 100 mg (1-2 times daily). The maximum dose - 200 mg | ||
| Antiepileptics-inducer of liver enzymes (phenytoin, carbamazepine, phenobarbital, primidone) ± other medication (no valproate) | 50 mg (1 per day) | 100 mg (2 doses) | 200 mg (for 2 doses) | 300 mg at week 6, the maximum dose for the 7th week may be 400 mg (2 doses) | ||
| Antiepileptic agent does not react with lamotrigine | 25 mg (1 per day) | 50 mg (1 or 2 times daily) | 100 mg (1 or 2 times daily) | 200 mg (1 or 2 times daily) | (The usual dose of 100-400 mg) | |
In the case of treatment of antiepileptic drugs, does not interact with lamotrigine, Lamolepa dose should be increased by the scheme referred to valproate | ||||||
A dosage administered in combination with inhibitors of liver enzymes, such as sodium valproate
For patients receiving liver enzyme inhibitor such as sodium valproate, lamotrigine initial dose - 25 mg / kg every other day for two weeks for the next 2 weeks - 25 mg / kg one time a day. At 5 weeks the daily dose should be increased to 50 mg, is allocated on a 1-2 reception. Typically, to achieve optimum therapeutic effect is required dose of 100 mg per day (1-2 doses) supporting daily dose - 5.1 mg / kg for 1-2 reception. The maximum daily dose should not exceed 200 mg.
B. Dosage when administered in conjunction with a liver enzyme inducers, such as phenobarbital and carbamazepine, sodium valproate but without
For patients taking antiepileptic drug-inducer of liver enzymes (carbamazepine, phenobarbital), but not taking sodium valproate, the initial daily dose of lamotrigine - 50 mg 1 time a day for 2 weeks then, over the next 2 weeks - 100 mg per day 2 reception. At 5 weeks the daily dose should be increased to 200 mg (2 receptions). At 6 weeks, the daily dose may reach 300 mg per daily dose 7 weeks, distributed into 2 doses, may reach 400 mg.
B. Dosage monotherapy and when administered in conjunction with drugs to which the pharmacological interaction with lamotrigine is either unknown, or possibly any,
In the case of treatment an antiepileptic agent, a pharmacokinetic interaction with lamotrigine is unknown, or possibly any, as well as initial monotherapy lamotrigine daily dose - 25 mg 1 time per day in the first two weeks for the next 2 weeks - 50 mg in 2 divided doses. After 5 weeks the dose was increased to 100 mg. Typically, the optimal daily dose - 200 mg in 1-2 reception. The maximum dose can be 400 mg / day.
After reaching an effective maintenance dose of psychotropic drugs canceled as follows.
Table 5. Supporting daily doses for the treatment of bipolar disorder after canceling simultaneously used psychotropic or antiepileptics
| Therapy | 1 week, mg | Week 2 mg | On the third week, mg | (Maximum dose = 400 mg per day) | |||||
| After the abolition of the liver enzyme inhibitor, such as valproate | Dose increased twice, not more than 100 mg per week, i.e. in the first week dosage should amount to 200 mg per day | It is necessary to assign an adjusted dose (200mg per day) | |||||||
| After canceling inductor liver enzymes (e.g. carbamazepine), depending on the initial dose of | 400 | 300 | 200 | ||||||
| 300 | 225 | 150 | |||||||
| 200 | 150 | 100 | |||||||
| After the abolition of psychotropic or antiepileptics are likely not providing the pharmacokinetic effect on lamotrigine (eg lithium, bupropion) | Be administered adjusted dose (200 mg per day) | (Recommended dose - 100-400 mg per day) | |||||||
After the abolition of antiepileptic drug, does not interact with lamotrigine, Lamolepa dose should be increased by the scheme referred to valproate | |||||||||
A. After the abolition of the liver enzyme inhibitor (eg valproate), designated in combination, stabilizing the initial dose of lamotrigine should be doubled and continue to prescribe valproate after cancellation.
B. After the abolition of the inductor of the liver enzymes (such as carbamazepine), appointed in a combination of lamotrigine dose should be gradual over 3 weeks, reduce.
B. After the cancellation of psychotropic and antiepileptic drugs (eg lithium, bupropion), a pharmacokinetic interaction with lamotrigine is unknown, it is necessary to continue the appointment of the dose selected in the escalation.
Adjustment of the daily dose of lamotrigine in the treatment of bipolar disorders after the introduction of additional drugs in spite of the lack of clinical experience in titrated doses of lamotrigine after the introduction of additional drugs, it is recommended to appoint below these doses, established on the basis of the results of the study of drug-drug interactions (see Table 6..).
Table 6. Adjusting the dose of lamotrigine in bipolar disorders after administration of additional drugs
| Initial dose Lamolepa mg per day | Week 1 mg per day | Week 2 mg daily | From week 3 mg per day | |
| ????????? ????????? ?????? (???????? ?????????), ? ??????????? ?? ????????? ???? ???????? | 200 | 100 | Reduced dose reached at week 1 (100 mg daily) | ||
| 300 | 150 | Reduced dose achieved in the 1st week (150 mg daily) | |||
| 400 | 200 | Reduced dose achieved in the 1st week (200mg per day) | |||
| Liver enzyme inducers (such as carbamazepine), depending upon the initial dose Lamolepa (without valproate) | 200 | 200 | 300 | 400 | |
| 150 | 150 | 225 | 300 | ||
| 100 | 100 | 150 | 200 | ||
| Psychotropic or antiepileptic drugs with unknown pharmacokinetic interactions with Lamolepom (eg lithium, bupropion) | Dose escalation reached during dose (200mg daily) in the range of 100-400 mg | ||||
Antiepileptic drugs with unknown pharmacokinetic interaction with lamotrigine: see with valproate.. | |||||
Cancellation of lamotrigine in the treatment of bipolar disorders:
lamotrigine discontinuation of treatment does not require a gradual reduction of the dose.
Children's age (<18 years): efficacy and safety in this age group has not been studied, so the recommendations for dosage does not exist.
In the case where the calculated dose includes incomplete tablet should be administered a dose of an integer tablets.
Increasing age (> 65 years): dose adjustment for age is not required, since The pharmacokinetics of the drug were not significantly different from that observed in the young population.
Hepatic impairment: the average degree of severity of hepatic failure (stage B according to Child-Pugh) starting and maintenance doses, and dose titration should be 50% below normal in Step C (according to Child-Pugh), ie to-severe - 75% lower. Growing and maintenance dose depends on the patient's clinical response.
Renal impairment: caution should be exercised when administering the drug in renal failure. In end-stage renal failure the initial dose of lamotrigine dosage regimen depends on other antiepileptic drugs with a significant decrease in renal function reduced maintenance dose may be sufficient.
Overdose:
Symptoms: nystagmus, ataxia, headache, drowsiness, vomiting, impairment of consciousness up to coma.
Treatment: a stationary conducting supportive and symptomatic therapy may require gastric lavage and administration of activated charcoal.
Special instructions:
Evidence for inducing and inhibitory effects of lamotrigine for oxidation enzymes in the liver at clinically relevant values ??are absent. The ability of the drug to induce its own metabolism is low and probably has no clinical significance.
Do not assign Lamolep simultaneously with other containing lamotrigine, drugs.
If Lamolep provides good control of epilepsy, treatment with other antiepileptic drugs can be stopped.
The objective criterion for the effectiveness of treatment is the ability to reduce the frequency of spikes in the EEG at 78-98%.
In the first 8 weeks of treatment may develop skin reactions. Skin rashes, usually are mild, disappear spontaneously, but may be severe and requiring hospitalization and discontinuation of lamotrigine eg Stevens-Johnson syndrome and toxic epidermal necrolysis. High initial doses and accelerating the pace prescribed increasing doses of lamotrigine and concomitant use of valproate contribute to the appearance of skin rash. To avoid the appearance of a skin rash should be strictly observe the specified dosage and rate of their increase.
Children are more likely to develop severe skin reactions (incidence requiring hospitalization of children is 1: 300-1: 100).
Early symptoms of an allergic rash easily confused with an infectious rash, so if high fever and rash occur in the first 8 weeks of treatment, we must assume the development of drug reaction.
It is important to remember that early manifestations of hypersensitivity (for example fever, lymphadenopathy) may occur without a rash. When a rash of each patient, regardless of age, should be immediately and thoroughly evaluated and lamotrigine stop treatment if symptoms develop can not be explained by another cause.
The appearance of the rash may be accompanied by a variety of systemic manifestations of hypersensitivity (fever, lymphadenopathy, facial edema, reactions on the part of the liver and hematopoietic system). The severity of hypersensitivity reactions may be different, and sometimes can be disseminated intravascular coagulopathy (CAAC) and the functional failure of multiple organs. It should be borne in mind that the early signs of hypersensitivity (e.g. fever, lymphadenopathy) are not always accompanied by skin rash.
Disturbances of liver function are usually part of a hypersensitivity syndrome, however, is not always accompanied by other symptoms of hypersensitivity.
Prolonged treatment lamotrigine can alter the metabolism of folic acid, as Lamotrigine is a weak inhibitor of dihydrofolate reductase. In this long, 12-month treatment lamotrigine does not significantly affect the level of hemoglobin, mean corpuscular volume, folic acid concentrations in plasma and erythrocytes, after 5 years of treatment - the concentration of folic acid.
If lactose intolerance should be aware that Lamolepa tablet contains 25 mg of lactose monohydrate 16.35 mg tablet 50 mg - 32.5 mg tablet and 100 mg - 65 mg.
Despite the fact that with oral contraceptives lamotrigine does not affect the concentration of ethinyl estradiol and levonorgestrel, changes during the menstrual cycle in lamotrigine therapy taking oral contraceptives requires attention of the attending physician.
In the treatment of patients with kidney failure on hemodialysis, it should be borne in mind that during a 4-hour dialysis excreted an average of 20% of lamotrigine is output.
Epilepsy: abrupt discontinuation of lamotrigine treatment provoke epileptic seizures, up to status epilepticus. Therefore, except in special cases (such as the appearance of skin rash), requiring immediate treatment discontinuation, withdrawal of the drug should be carried out gradually, with a smooth, for 2 weeks, dose reduction.
Severe seizures and status epilepticus may lead to rhabdomyolysis, multiple organ dysfunction and disseminated intravascular coagulopathy, sometimes fatal. Similar cases have occurred in connection with the use of lamotrigine.
Bipolar disorder: bipolar disorder is characterized by the tendency of patients to suicide, so the treatment of people with an increased tendency to suicide should be accompanied by careful monitoring of the patient.
During treatment it is prohibited to drive and engage in activities that require high concentration and psychomotor speed reactions.
