Composition, form of production and packaging
Tablets are round, flat-cylindrical, pale yellow, with engraving "25" on one side.
1 tab.
lamotrigine 25 mg
Excipients: magnesium carbonate - 27.8 mg, microcrystalline cellulose - 20 mg, povidone - 2.4 mg, pigment light yellow (lactose monohydrate - 0.68 mg, iron oxide yellow - 0.12 mg), crospovidone (polyplazone XL10) - 3.2 mg, magnesium stearate - 0.8 mg.
10 pieces. - blisters (3) - packs of cardboard.
Tablets are round, flat-cylindrical, light-yellow in color, engraved with "50" on one side.
1 tab.
lamotrigine 50 mg
Auxiliary substances: magnesium carbonate - 55.6 mg, microcrystalline cellulose - 40 mg, povidone - 4.8 mg, pigment light yellow (lactose monohydrate - 1.36 mg, iron oxide yellow - 0.24 mg), crospovidone (polyplazone XL10) - 6.4 mg, magnesium stearate - 1.6 mg.
10 pieces. - blisters (3) - packs of cardboard.
Tablets are round, flat-cylindrical, light yellow in color, with engraving "100" on one side.
1 tab.
lamotrigine 100 mg
Auxiliary substances: magnesium carbonate - 111.2 mg, microcrystalline cellulose - 80 mg, povidone - 9.6 mg, pigment light yellow (lactose monohydrate - 2.72 mg, iron oxide yellow - 0.48 mg), crospovidone (polyplazone XL10) - 12.8 mg, magnesium stearate - 3.2 mg.
10 pieces. - blisters (3) - packs of cardboard.
Tablets are round, flat-cylindrical, pale yellow, with engraving "200" on one side.
1 tab.
lamotrigine 200 mg
Excipients: magnesium carbonate 222.4 mg, microcrystalline cellulose 160 mg, povidone 19.2 mg, pigment light yellow (lactose monohydrate 5.44 mg, iron oxide yellow 0.96 mg), crospovidone (polyplazone XL10) 25.6 mg, magnesium stearate 6.4 mg.
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Anticonvulsant drug. Lamotrigine is a blocker of potential-dependent sodium channels, inhibits the pathological release of glutamic acid (an amino acid that plays a key role in the development of epileptic seizures), and also inhibits depolarization caused by glutamate.
PHARMACOKINETICS
Suction
After ingestion lamotrigine is quickly and completely absorbed from the digestive tract, almost without undergoing pre-systemic metabolism with the effect of "first passage". C max in plasma is achieved approximately 2.5 hours after taking the drug. The time to reach C max slightly increases after ingestion, but the degree of absorption remains unchanged. The pharmacokinetics of lamotrigine is linear in the administration of a single dose up to 450 mg. Significant interindividual oscillations of C max in an equilibrium state are observed, but with rare fluctuations in each individual.
Distribution
Lamotrigine binds to plasma proteins by approximately 55%. It is unlikely that the release of the drug from the bond with the protein could lead to the development of a toxic effect.
V d is 0.92-1.22 l / kg.
Metabolism
In the metabolism of lamotrigine, the enzyme uridine-diphosphate-glucuronyltransferase (UDP-glucuronyltransferase) participates. Metabolized to glucuronide.Lamotrigine in a small degree increases its own metabolism depending on the dose.
Excretion
In adults, lamotrigine clearance in the state of equilibrium concentrations averages 39 В± 14 ml / min. It is excreted in the urine in the form of metabolites, less than 10% of the drug is excreted unchanged in urine, about 2% - with feces. Clearance and T 1/2 are dose independent. T 1/2 in adults is an average of 24 hours to 35 hours. T 1/2 of lamotrigine is greatly influenced by co-administered medications.
Pharmacokinetics in special clinical cases
In children, lamotrigine clearance in terms of body weight is higher than in adults (the highest in children under 5 years old). In children, T 1/2 lamotrigine is usually less than in adults. Its mean value is approximately 7 hours with concomitant administration with glucuronizing stimulants such as carbamazepine and phenytoin, and rises to an average of 45-50 hours with a co-administration with valproate.
Clinically significant differences in the clearance of lamotrigine in elderly patients in comparison with young patients were not detected.
In patients with Gilbert's syndrome, the clearance of the drug was reduced by 32%, which, however, did not exceed the limits of normal values ​​for the general population.
INDICATIONS
Epilepsy
- as an additional or monotherapy of epilepsy (partial and generalized seizures, including tonic-clonic convulsions, as well as seizures in the Lennox-Gastaut syndrome) in adults and children over 12 years of age;
- as an additional therapy for epilepsy (partial and generalized seizures, including tonic-clonic seizures, as well as seizures in the Lennox-Gastaut syndrome) in children 2 to 12 years of age (after attaining epilepsy control against combined therapy, concomitant antiepileptic drugs may be withdrawn and the use of lamotrigine is continued as a monotherapy);
- monotherapy of typical absences.
Bipolar disorders
- for the prevention of mood disorders (depression, mania, hypomania, mixed episodes) in adults with bipolar disorders.
DOSING MODE
The drug is taken orally. If the calculated dose of lamotrigine (for example, when administered to children or patients with impaired liver function) can not be divided into a whole number of tablets, then the patient should be given a dose that corresponds to the nearest value of the whole tablet at a lower dosage.
Because of the risk of developing the rash, the initial dose of the drug and the recommended regime for increasing doses should not be exceeded.
Epilepsy
Monotherapy in adults and children over 12 years of age
The initial dose of Convulsan is 25 mg 1 time / day for the first 2 weeks, followed by a dose increase to 50 mg 1 time / day for the next 2 weeks. Then the dose should be increased by 50-100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 100-200 mg / day in 1 or 2 doses. Some patients require the appointment of Convulsan in a dose of 500 mg / day to achieve a therapeutic effect.
Additional therapy in adults and children over 12 years of age
With the simultaneous use of Convulsan with valproic acid preparations in combination with other antiepileptic drugs (PEP) or without them, the initial dose of lamotrigine is 25 mg every other day for the first 2 weeks; in the future - 25 mg 1 time / day for the next 2 weeks. Then the dose should be increased as much as 25-50 mg / day every 1-2 weeks, until the optimal therapeutic effect is achieved. The standard maintenance dose is 100-200 mg / day in 1 or 2 doses.
When Convulsan is used together with antiepileptic drugs or other drugs stimulating the glucuronization of lamotrigine, in combination with or without other PEP (with the exception of valproic acid preparations), the initial dose of Convulsan is 50 mg 1 time / day for the first 2 weeks, then 100 mg / day in 2 divided doses for the next 2 weeks. Then the dose is increased by max. 100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 200-400 mg / day in 2 divided doses. Some patients may require a dose of up to 700 mg / day.
In the joint use of Convulsan with oxcarbazepine in combination with any other inducers or inhibitors of glucuronizia of lamotrigine or without them, the initial dose of lamotrigine is 25 mg 1 time / day for the first 2 weeks, then 50 mg / day in 1 dose during the following 2 weeks. Then the dose increases by max. 50-100 mg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 100-200 mg / day in 1 or 2 doses.
Monotherapy in children aged 2 to 12 years
The initial dose of Convulsan with monotherapy of typical absences is 0.3 mg / kg body weight / day in 1 or 2 doses during the first 2 weeks, followed by a dose increase of up to 0.6 mg / kg / day in 1 or 2 doses for the next 2 weeks. Then the dose should be increased as much as 0.6 mg / kg every 1-2 weeks until the optimal therapeutic effect is achieved. The usual maintenance dose is 1 to 15 mg / kg / day in 1 or 2 doses, although some patients require higher doses.
Additional therapy in children aged 2 to 12 years
With the concomitant use of Convulsan and valproic acid preparations in combination with other PETs or without them, the initial dose of lamotrigine is 0.15 mg / kg 1 time / day for the first 2 weeks, then 0.3 mg / kg 1 time / day for the next 2 weeks . The dose should then be increased by 0.3 mg / kg every 1-2 weeks until the optimal therapeutic effect is achieved. The standard maintenance dose is 1-5 mg / kg / day in 1 or 2 doses. The maximum daily dose is 200 mg.
With the simultaneous use of Convulsan with antiepileptic drugs or other drugs stimulating glucuronization of lamotrigine, in combination with or without other PEP (with the exception of valproic acid preparations), the initial dose of lamotrigine is 0.6 mg / kg / day in 2 doses for the first 2 weeks, in Further - 1.2 mg / kg / day in 2 divided doses for the next 2 weeks. Then the dose should be increased as much as 1.2 mg / kg / day every 1-2 weeks until the optimal therapeutic effect is achieved.The standard maintenance dose is 5-15 mg / kg per day in 2 divided doses. The maximum daily dose is 400 mg.
When Convulsan is used together with oxcarbazepine without any other inducers or inhibitors of lamotrigine glucuronin, the initial dose of lamotrigine is 0.3 mg / kg / day in 1 or 2 doses for the first 2 weeks, then 0.6 mg / kg / day in 1 or 2 reception for the next 2 weeks. Then the dose is increased by a maximum of 0.6 mg / kg every 1-2 weeks, until the optimal therapeutic effect is achieved. The standard maintenance dose is 1-10 mg / kg / day in 1 or 2 doses. The maximum dose is 200 mg / day.
To be sure that a therapeutic dose is maintained, it is necessary to monitor the weight of the child's body and adjust the dose of the drug as it changes. Accurate dosing during initial therapy with Convulsan in 5 mg tablets is not possible if the child's body weight is less than 17 kg.
Most likely, children between the ages of 2 and 6 years will need the largest maintenance doses.
With the withdrawal of concomitant antiepileptic drugs for switching to monotherapy with Convulsan, or when administered with other drugs or PEP, Convulsan should take into account that this may affect the pharmacokinetics of lamotrigine.
Bipolar disorders in adults
It is necessary to follow a transitional dosing regimen that includes increasing the dose of lamotrigine for 6 weeks to a maintenance stabilizing dose (Table 1), after which other psychotropic and / or antiepileptic drugs may be withdrawn if there are indications (Table 2).
Table 1. Recommended scheme of increasing doses to achieve a maintenance daily stabilizing dose for bipolar disorders in adults.
Combination therapy with inhibitors of glucuronization of lamotrigine (eg, with valproic acid preparations)
1-2 weeks 3-4 weeks 5 weeks Supportive stabilizing dose (from 6 weeks)
12.5 mg (25 mg every other day) 25 mg once a day 50 mg / day (in 1 or 2 doses) 100 mg / day (in 1 or 2 doses), the maximum dose is 200 mg / day
Combination therapy with lamotrigine glucuronin inducers in patients not taking inhibitors, such as valproic acid preparations. This regimen should be used with phenytoin, carbamazepine, phenobarbital, primidone or other inducers of lamotrigine glucuronization
1-2 weeks 3-4 weeks 5 weeks Supportive stabilizing dose (from 6 weeks)
50 mg 1 time / day 100 mg / day (in 2 divided doses) 200 mg / day (in 2 divided doses) 300 mg at week 6, if necessary, increase the dose to 400 mg at week 7 of therapy (in 2 divided doses)
Convulsant Monotherapy or complementary therapy in patients taking lithium preparations, bupropion, olanzapine, oxcarbazepine, or other drugs that do not exert a significant inducing or inhibitory effect on glucuronization of lamotrigine
1-2 weeks 3-4 weeks 5 weeks Supportive stabilizing dose (from 6 weeks)
25 mg 1 time / day 50 mg / day (in 1 or 2 doses) 100 mg / day (in 1 or 2 doses) 200 mg (100 mg to 400 mg) / day in 1 or 2 doses
Note: Patients receiving PEP, pharmacokinetic interaction of which with lamotrigine is not studied, it is necessary to use the regimen of doses as recommended for lamotrigine in combination with valproic acid preparations.
The maintenance stabilizing dose varies depending on the clinical effect.
With the simultaneous use of Convulsan and other PEPs that inhibit glucuronidation of lamotrigine (eg valproic acid preparations), the initial dose of lamotrigine is 25 mg every other day for the first 2 weeks, then 25 mg 1 time / day for the next 2 weeks, at week 5 The dose should be increased to 50 mg / day in 1-2 doses.Stabilizing dose at 6 weeks is 100 mg / day in 1-2 divided doses. The maximum daily dose is 200 mg.
With the simultaneous use of Convulsan and other PEPs stimulating the glucuronization of lamotrigine (eg, phenytoin, carbamazepine, phenobarbital, primidone), in patients who do not receive lamotrigine glucuronin inhibitors (eg, valproic acid preparations), the initial dose of lamotrigine is 50 mg 1 time per day during the first 2 weeks, then 100 mg / day in 2 divided doses for the next 2 weeks, at 5 weeks the dose should be increased to 200 mg / day in 2 divided doses. At 6 weeks, the dose may be increased to 300 mg / day, but the stabilizing dose for achieving the optimal therapeutic effect is 400 mg / day in 2 divided doses and is prescribed starting from week 7.
In monotherapy with Convulsan or with the concomitant use of Convulsan with lithium preparations, bupropion, olanzapine, oxcarbazepine, or other drugs that are not inducers or inhibitors of glucuronization of lamotrigine, the initial dose of lamotrigine is 25 mg 1 time / day for the first 2 weeks, then 50 mg / day in 1 or 2 doses for the next 2 weeks. The dose should be increased to 100 mg / day at week 5. Stabilizing dose at 6 weeks is 200 mg / day in 1-2 divided doses.
After reaching a daily maintenance stabilizing dose, other psychotropic drugs can be canceled.
Table 2. Supportive stabilizing daily dose for the treatment of bipolar disorders after withdrawal of concomitant psychotropic or antiepileptic drugs.
After the abolition of inhibitors of glucuronization of lamotrigine, for example, preparations of valproic acid
1 week 2 weeks 3 weeks and more
Double the stabilizing dose, not exceeding 100 mg / week, i.e. maintaining a stabilizing dose of 100 mg / day increases at 1 week to 200 mg / day Save a dose of 200 mg / day in 2 divided doses
After the abolition of the inductors, the glucuronization of lamotrigine is dependent on the initial dose. This regimen should be used when using phenytoin, carbamazepine, phenobarbital, primidon, or other inducers of lamotrigine glucuronization
1 week 2 weeks 3 weeks and more
400 mg 300 mg 200 mg
300 mg 225 mg 150 mg
200 mg 150 mg 100 mg
After the abolition of other psychotropic or antiepileptic drugs in patients not taking inducers or inhibitors of glucuronization of lamotrigine (including lithium, bupropion, olanzapine, oxcarbazepine)
1 week 2 weeks 3 weeks and more
Maintain the stabilizing dose achieved during the regimen (200 mg / day in 2 divided doses from 100 mg to 400 mg).
Note: Patients receiving PEP, whose pharmacokinetic interaction with lamotrigine is not currently known, is recommended dosing regimen, as when taking lamotrigine with valproic acid preparations
If necessary, the dose may be increased to 400 mg / day.
After withdrawal of additional therapy with lamotrigine glucuronide inhibitors (eg, valproic acid drugs), the stabilizing initial dose of lamotrigine is doubled and maintained at this level.
After the withdrawal of additional therapy inductors glucuronization of lamotrigine (including phenytoin, carbamazepine, phenobarbital, primidone), the dose of lamotrigine gradually decreases within 3 weeks, depending on the initial maintenance dose.
After the withdrawal of concomitant psychotropic or antiepileptic drugs that do not have a significant pharmacokinetic interaction with lamotrigine (eg, lithium, bupropion, olanzapine, oxcarbazepine), the stabilizing dose of Convulsan achieved during the enhancement regimen should be maintained.
There is no clinical experience in correcting the daily doses of lamotrigine in patients with bipolar disorders after the addition of other drugs. However, based on studies on drug interactions, the following recommendations can be made (Table 3).
Table 3. Correction of daily doses of lamotrigine in patients with bipolar disorder after adherence to therapy with other drugs.
The addition of lamotrigine glucuronine inhibitors (eg, valproic acid preparations) depending on the initial dose of lamotrigine
Current stabilizing dose of lamotrigine (mg / day) 1 week 2 weeks 3 weeks and more
200 mg 100 mg Save the dose of 100 mg / day
300 mg 150 mg Save a dose of 150 mg / day
400 mg 200 mg Save a dose of 200 mg / day
Accession lamotrigine glucuronidation inducers (including phenytoin, carbamazepine, phenobarbital, primidone) in patients not treated with valproic acid formulations, depending on the initial dose of lamotrigine
Current anti lamotrigine dose (mg / day) 1 Week 2 Week 3 Week further
200 mg 200 mg 300 mg 400 mg
150 mg 150 mg 225 mg 300 mg
100 mg 100 mg 150 mg 200 mg
Accession other psychotropic or antiepileptic drugs with insignificant lamotrigine pharmacokinetic interaction with (e.g., drugs lithium, bupropion, olanz pin, oxcarbazepine)
Current anti lamotrigine dose (mg / day) 1 Week 2 Week 3 Week further
Maintain stabilizing dose achieved during the raising mode (200 mg / day range of doses from 100 mg to 400 mg)
Note: patients taking AEDs character pharmacokinetic interaction with lamotrigine is currently not known, it is recommended dosing regimen, when receiving with lamotrigine formulations of valproic acid.
Upon termination Konvulsanom therapy in patients with bipolar disorder can be revoke Konvulsan immediately without tapering.
In the case of reintroduction of lamotrigine physician must evaluate the need to improve the maintenance dose in patients who had stopped taking the drug for any reason, since high initial doses and exceeding the recommended doses are associated with a risk of severe rash. The more time has passed after the last dose, the dose should be increased to support more cautious. If the time after stopping is greater than 5 half-lives, the lamotrigine dosage should be increased to support according to the corresponding scheme.
Lamotrigine therapy should not be reopened for patients, discontinuation of treatment with lamotrigine which was associated with the appearance of rash, unless the potential benefits of this therapy clearly exceeds the potential risk.
In appointing Konvulsana women already taking hormonal contraceptives, there is no need for correction of the recommended doses of lamotrigine modes increase.
In the appointment of hormonal contraceptives to patients already receiving maintenance doses Konvulsana and not receiving inducers of lamotrigine glucuronidation, you may need to increase the maintenance dose of lamotrigine, but not more than 2 times, depending on the individual clinical response.
Upon termination of hormonal contraceptives by patients already receiving maintenance doses Konvulsana and receiving inductors glucuronidation of lamotrigine may require dose reduction lamotrigine 2 times depending on the individual clinical effect.
Correct dosing regimen inElderly patients (over 65 years) is not required.
In human liver average (class B Child-Pugh) and severe (grade C in Child-Pugh) start, and increasing maintenance dose should be reduced by approximately 50% and 75% respectively. Increasing and maintenance doses should be adjusted depending on clinical response.
Patients with a significant reduction in renal function can be recommended maintenance dose reduction.
SIDE EFFECT
Of adverse reaction information is divided into 2 sections: adverse reactions in patients with epilepsy and adverse reactions in patients with bipolar disorder. However, considering the safety profile of lamotrigine in general must take into account the details of both sections.
Use the following conditional classification of the incidence of adverse reactions: very common (> 1/10), common (> 1/100, <1/10), sometimes (> 1/1000, <1/100), rare (> 1/10 000 <1/1000), very rare (<1/10 000).
In patients with epilepsy
Dermatological reactions: monotherapy: very often - skin rash; in other types of clinical use: very often - skin rash; rarely - Stevens-Johnson syndrome; very seldom - toxic epidermal necrolysis.
Rash, mainly maculopapular character usually appears during the first 8 weeks after initiation of therapy and after the drug passes.
There are reports of rare cases of severe, potentially life-threatening skin lesions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome). Although in most cases to remove the drug occurred regression of symptoms, some patients remained irreversible scarring and, in rare cases have been reported deaths associated with taking the drug. The overall risk of rash development has largely been associated with a high initial dose of lamotrigine and exceeding the recommended rate increasing doses of lamotrigine with concomitant administration of valproic acid formulations. Development of the rash was also seen as a manifestation of a hypersensitivity syndrome associated with a variety of systemic manifestations.
From hemopoiesis system:very rarely - neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis. Hematologic abnormalities may or may not be associated with the hypersensitivity syndrome.
Immune system:very rarely - hypersensitivity syndrome (including symptoms such as fever, lymphadenopathy, facial edema, disorders of the blood and liver, disseminated intravascular coagulation, multiorgan disorder). The rash is also seen as part of a hypersensitivity syndrome. Importantly, early manifestations of hypersensitivity (i.e. fever, lymphadenopathy) may occur even in the absence of obvious signs of rash. The patient should seek medical advice immediately and, if not installed another cause of symptoms, lamotrigine should be discontinued during the development of these symptoms.
CNS:in monotherapy: very often - irritability, headache; often - drowsiness, insomnia, dizziness, tremors; sometimes - ataxia, aggression; very rarely - tics, hallucinations, confusion; in other types of clinical applications: often - headache, dizziness; often - irritability, nystagmus, tremor, ataxia, drowsiness, insomnia; sometimes - aggressive; very rarely - tics, hallucinations, confusion, agitation, unsteadiness, movement disorders, worsening of Parkinson's disease, extrapyramidal disorder, choreoathetosis, increase in the frequency of seizures.
From the senses: very often - diplopia, blurred vision; rarely - conjunctivitis.
From the digestive system:in monotherapy: often - nausea; in other types of clinical applications: often - nausea, diarrhea.
On the part of hepato-biliary system: very rarely - increased levels of liver enzymes, abnormal liver function, hepatic failure. Disturbances of liver function usually develop the symptoms in combination with hyperreactivity, but in a few cases noted in the absence of overt signs of hypersensitivity.
Other: often - fatigue; very rarely - a lupus-like syndrome.
In patients with bipolar disorder
Dermatological reactions: very often - skin rash; rarely - Stevens-Johnson syndrome.
On the part of the central nervous system : very often - headache; often - agitation, drowsiness, dizziness.
On the part of the musculoskeletal system: often - arthralgia, back pain.
Other: often - pain.
CONTRAINDICATIONS
- Children under 2 years;
- Hypersensitivity to lamotrigine or to any component of the drug.
With caution is prescribed for kidney failure.
PREGNANCY AND LACTATION
Konvulsan should be administered during pregnancy only if the expected therapeutic benefit to the mother outweighs the potential risk to the fetus. Physiological changes, developing during pregnancy may affect lamotrigine levels and / or therapeutic effect. It has been reported to reduce the concentration of lamotrigine during pregnancy.
Lamotrigine is excreted in breast milk and is determined in breast milk in concentrations of 40-60% of the concentrations in maternal plasma. The appointment Konvulsana lactation should be weighed the potential benefits of breast-feeding and the potential risk of adverse effects in a child.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution is prescribed for kidney failure.
Patients with a significant reduction in renal function can be recommended maintenance dose reduction.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In human liver average (class B Child-Pugh) and severe (grade C in Child-Pugh) start, and increasing maintenance dose should be reduced by approximately 50% and 75% respectively. Increasing and maintenance doses should be adjusted depending on clinical response.
APPLICATION FOR CHILDREN
Contraindications: Children under 2 years old.
APPLICATION IN ELDERLY PATIENTS
A correction mode in elderly patients (over 65 years) is not required.
SPECIAL INSTRUCTIONS
In children, the risk of serious skin rashes is higher than in adults. According to available data rate of skin rash that required hospitalization in children with epilepsy, ranged from 1 to 300 to 1 in 100 children.
In children, the initial manifestations of rash can be mistaken for an infection, so you should take into account the possibility of children's reactions to the drug, manifested development of rash and fever during the first 8 weeks of therapy.
Furthermore, the overall risk of rash is largely associated with a high initial dose and Konvulsana exceeding the recommended speed increase it, as well as the combined use of drugs with valproic acid.
Upon detection of a rash all patients (adults and children) should be immediately examined by a doctor. Acceptance of lamotrigine should be discontinued immediately except in cases where it is obvious that the development of the rash is not related to the drug intake. It is not recommended to resume receiving lamotrigine when his previous appointment was canceled due to the development of skin reactions, unless the expected therapeutic effect of the drug is less than the risk of side effects.
Lamotrigine is a weak inhibitor of dihydrofolate reductase, and therefore the drug during long-term therapy may affect the metabolism of folate. However, it was shown that lamotrigine did not induce significant changes in hemoglobin, mean cell volume, serum folate concentrations (at reception for up to 1 year) or erythrocytes (at reception for up to 5 years).
If a patient receives any other preparation containing lamotrigine, it should not take Konvulsan without consulting a doctor.
Abrupt withdrawal receiving Konvulsana as other probes, can trigger the development of seizures. If abrupt discontinuation of therapy is not a security requirement (for example, the appearance of the rash), the dose of lamotrigine should be reduced gradually over a period of 2 weeks.
It has been reported that severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multiorgan violations and DIC are sometimes fatal.Similar cases were observed in the treatment of Konvulsanom.
The possibility of suicide attempt is a characteristic feature of bipolar disorder, therefore the treatment of such patients should be under close supervision.
Impact on the ability to drive vehicles and manage mechanisms
It is not recommended during treatment to engage in potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE
Reported single application Konvulsana a dose exceeding the maximum therapeutic 10-20 times . At the same time we observed the following symptoms: nystagmus, ataxia, impaired consciousness and coma.
Treatment: gastric lavage, hospitalization and symptomatic therapy.
DRUG INTERACTION
Middle T 1/2 is reduced to approximately 14 hours with concomitant administration with drugs that stimulate glucuronidation, such as carbamazepine and phenytoin, and rises to an average of 70 hours at coadministered with valproate. No data on the ability of lamotrigine cause clinically significant inhibition or induction of hepatic oxidative enzymes. In this regard, the interaction between lamotrigine and drugs metabolized by cytochrome P450 enzyme system, is unlikely. Lamotrigine can stimulate its own metabolism but the effect is moderate and does not have clinically significant consequences.
Table 4. Effect of other drugs on glucuronidation of lamotrigine.
Drugs that have a pronounced inhibitory effect on the glucuronidation of lamotrigine Formulations providing a pronounced stimulating effect on the glucuronidation of lamotrigine formulations, no significant suppressive or stimulatory effect on glucuronidation lamotrigine,
valproic acid drugs carbamazepine, phenytoin, primidone, phenobarbital, rifampin combined preparation ethinylestradiol / levonorgestrel drugs lithium, bupropion, olanzapine, oxcarbazepine
Effect of other oral contraceptives and hormone replacement therapy are not studied, though they may have on the obnoe impact on the pharmacokinetic profile of lamotrigine.
Valproic acid formulations which inhibit glucuronidation of lamotrigine reduce its rate of metabolism and lengthen its average T 1/2 is almost 2 times.
Certain antiepileptics (such as phenytoin, carbamazepine, phenobarbital and primidone), which stimulate liver metabolising enzyme system, accelerate glucuronidation of lamotrigine and its metabolism. Reported on the development of undesirable effects the central nervous system, include dizziness, ataxia, diplopia, blurred vision and nausea in patients taking carbamazepine who started on the background Konvulsanom therapy. These symptoms usually resolve after reduction of the dose of carbamazepine. A similar effect was observed in the appointment of lamotrigine and oxcarbazepine in healthy volunteers, a result of reduced doses has not been studied.
Lamotrigine does not displace other antiepileptic drugs from binding with plasma proteins.
When simultaneous administration of lamotrigine at 200 mg oxcarbazepine and a dose of 1200 mg or oxcarbazepine, lamotrigine or not violate the metabolism of each other.
Lamotrigine 100 mg / day does not disturb the pharmacokinetics of anhydrous lithium gluconate (2 g 2 times / day for 6 days) with their combined use.
Multiple dose bupropion inside has no statistically significant effect on the pharmacokinetics of a single dose of lamotrigine and causes a slight increase in AUC
