Index of drugs

Epilepsy. Adults and adolescents ≥13 years old: combination therapy or monotherapy for partial and generalized seizures, including tonic-clonic seizures; attacks associated with Lennox-Gastaut syndrome - the drug is used in combination therapy, but can be used as the first antiepileptic drug included in the treatment of Lennox-Gastaut syndrome.Children from 2 to 12 years old: combined treatment of partial and generalized seizures, including tonic-clonic seizures and seizures associated with Lennox-Gastaut syndrome; monotherapy in typical attacks of the unconscious.Bipolar disorder. Adults (≥ 18 years): prevention of episodes of depression in patients with bipolar I disorder who have depression episodes. Lamotrigine is not indicated for the immediate treatment of mania or depression episodes.

1 tabl contains 25 mg, 50 mg or 100 mg of lamotrigine (and 0.68 mg, 1.36 mg or 2.72 mg lactose, respectively).

Antiepileptic medicine. Lamotrigine is a voltage-gated sodium channel blocker dependent on the application and voltage. It inhibits frequent neuron discharges and inhibits the release of glutamate. Lamotrigine quickly and completely absorbed after oral administration, reaching C_max after 2.5 h. In about 55% bound to plasma proteins. It is metabolized by means of UDP-glucuronyl transferase. It is excreted in the urine, mainly in the form of metabolites. Only about 2% of the derivatives of lamotrigine are excreted in the faeces. Medium T_0,5 is about 33 h. T_0,5 is reduced to approximately 14 h after administration of glucuronidation inducing drugs (eg, carbamazepine, phenytoin), whereas it is prolonged to approximately 70 hours when lamotrigine is co-administered with valproate. T_0,5 In children, lamotrigine is shorter than in adult patients: when T-inducers are used concomitantly_0,5 is about 7 hours, while in the case of concomitant use valproate extends to about 45-50 h.

Hypersensitivity to the active substance or to any of the excipients.

The use of lamotrigine is associated with the risk of severe skin reactions, usually occurring during the first 8 weeks of treatment. In patients who develop a rash, if no other cause of this complication has been established, the drug should be discontinued. It is not recommended to restart treatment with lamotrigine if it was interrupted due to a rash. The risk of severe skin reactions is greater in children. In addition, it appears to be associated with large initial doses of lamotrigine and exceeding the recommended rate of increasing the dose of lamotrigine and with the simultaneous use of valproate. Lamotrigine should be used with caution in patients with a history of hypersensitivity to other antiepileptic agents, as these patients are at higher risk of developing a rash. The rash was observed as one of the symptoms of hypersensitivity syndrome - in case of hypersensitivity symptoms (even in the absence of a clear rash), if another etiology of symptoms can not be determined, treatment with lamotrigine should be discontinued. All patients treated with lamotrigine should be monitored for signs of suicidal ideation and behavior. This is especially true for patients with bipolar disorder, young adults and patients with history of suicidal behavior or thoughts. If a patient develops symptoms of bipolar disorder (new symptoms or suicidal thoughts or behaviors occur), a change in management should be considered, including the option to stop treatment with lamotrigine. Caution should be exercised when using lamotrigine in combination with oral contraceptives. Lamotrigine is a weak inhibitor of dihydrofolate reductase and therefore it is possible to interfere with folate metabolism during long-term therapy. Caution should be exercised when administering lamotrigine to patients with renal insufficiency (the possibility of glucuronide metabolite accumulation).There have been reports that severe seizures, including epileptic status, may lead to rhabdomyolysis, multi-organ failure and disseminated intravascular coagulation, sometimes with fatal outcome; similar cases occurred in connection with the use of lamotrigine. During therapy, a paradoxical increase in the frequency of epileptic seizures is possible. In patients with more than one type of seizure, the benefits of controlling one type of seizure should be weighed against any worsening of other types of seizures. Symptoms of myoclonic seizures may be impaired after the use of lamotrigine. Response to treatment may be less when using lamotrigine in combination with hepatic enzyme inducers. The efficacy of lamotrigine in the treatment of typical childhood seizures may not be maintained in all patients. Data on the use of lamotrigine in the treatment of epilepsy in children under 2 years of age are limited - use is not recommended. There are no data on the effect of lamotrigine on growth, sexual maturation, cognitive and behavioral development of children. The use of lamotrigine in the treatment of bipolar disorder in patients under 18 years is not recommended, due to the lack of data on safety and efficacy. In addition, the use of antidepressants is associated with an increased risk of suicidal thoughts and behavior in children and adolescents with depressive disorders and other psychiatric disorders. Due to the content of lactose in tablets, they should not be used in patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

In children of patients using antiepileptic therapy in pregnancy, the occurrence of congenital malformations is 2-3 times more frequent than in the general population. The most frequently reported developmental defects are cleft lip, cardiovascular defects and neural tube dysfunction. There is a risk of a moderate increase in the incidence of cleft palate or lips in offspring of mothers who have taken lamotrigine in the first trimester of pregnancy. The use of antiepileptic therapy should be considered if the woman plans to become pregnant. Sudden discontinuation of antiepileptic therapy should be avoided, as it may lead to seizures with serious consequences for both the mother and the unborn child. Combined antiepileptic therapy is associated with a higher risk of congenital malformations of the fetus than monotherapy, therefore, if possible, monotherapy should be used. If treatment with lamotrigine is necessary in pregnancy, the lowest therapeutic dose is recommended. In pregnant women, the concentration of lamotrigine may be reduced. The levels of lamotrigine in the blood should be monitored before pregnancy, during pregnancy and in the postpartum period. If necessary, the dose should be adjusted to maintain the lamotrigine level in the blood at pre-pregnancy levels or according to the clinical response. In addition, after the delivery, the patient should be monitored for any dose-related adverse reactions. Lamotrigine may lead to folic acid deficiency - folate intake should be considered for women planning pregnancy and early pregnancy. Lamotrigine is excreted in human milk. In some breast-fed infants, levels of lamotrigine in the blood may reach values ​​with pharmacological effects. You should assess whether the expected benefit of breastfeeding outweighs the potential risk of side effects in your child. If the infant is breastfed, it should be monitored for adverse reactions to lamotrigine.

Epilepsy. Very common: headache, dizziness, drowsiness, ataxia, diplopia, blurred vision, nausea, vomiting, skin rash. Common: aggression, irritability, nystagmus, tremor, insomnia, diarrhea, fatigue. Rarely: conjunctivitis. Very rare: neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis, hypersensitivity syndrome (rash, fever, lymphadenopathy, facial edema, hematological abnormalities, abnormalities in liver function tests, disseminated intravascular coagulation, multiple organ dysfunction) , confusion, hallucinations, tics, agitation, unsteady gait, movement disorders, worsening of Parkinson's symptoms, extrapyramidal symptoms, choreoathetosis, increased frequency of epileptic seizures, liver failure, abnormal liver function,increases in liver function tests, Stevens-Johnson syndrome, toxic epidermal necrolysis, and epidural syndrome. Severe skin reactions in rare cases were fatal. Frequency unknown: lymphadenopathy, aseptic meningitis, alopecia, drug erosion with eosinophilia and general symptoms (DRESS).Bipolar disorder. Very common: skin rash, headache. Common: agitation, drowsiness, dizziness, dry mouth, joint pain, back pain, pain. Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis. Not known: drug eruptions with eosinophilia and general symptoms (DRESS). In patients using antiepileptic drugs in various indications, cases of suicidal ideation and behavior have been reported; the risk also occurs when using lamotrigine. Reductions in bone mineral density, osteopenia, osteoporosis and fractures have been observed in patients using lamotrigine for a long time.

Orally. Do not exceed the initial dose and subsequently increased doses to minimize the risk of rash. When re-starting treatment with lamotrigine in patients who discontinue its use, the need to gradually increase the dose to the maintenance dose should be assessed. The longer the break from the last dose, the more attention should be paid to gradually increasing the dose to the maintenance dose. If the time from discontinuation of lamotrigine exceeds 5-fold the half-life of the drug, the appropriate dose escalation regimen should be used up to the maintenance dose. It is recommended that re-initiation of therapy with lamotrigine should not be initiated in patients who discontinued treatment due to a rash if the potential benefit does not clearly outweigh the risks associated with the use of the drug. If a previously used anti-epileptic medicine is discontinued to switch to monotherapy with lamotrigine or if other medicines are added to lamotrigine, the possible effect of these changes on the pharmacokinetics of lamotrigine should be considered.
Epilepsy. Adults and adolescents ≥13 years old. monotherapy: initially 25 mg once a day for the first 2 weeks, then 50 mg once a day for the Next 2 weeks. Then the dose should be increased by a maximum of 50-100 mg every 1-2 weeks until an optimal therapeutic response is obtained. Maintenance dose: 100-200 mg per day in 1 dose or in 2 divided doses. Some patients require a daily dose of 500 mg to achieve the desired therapeutic response.Combination therapy with valproate (an inhibitor of lamotrigine metabolism), regardless of other concomitant medications: initially 25 mg every other day for the first 2 weeks, then 25 mg once a day for the next 2 weeks. Then the dose should be increased by a maximum of 25-50 mg every 1-2 weeks until an optimal therapeutic response is obtained. Maintenance dose: 100-200 mg per day in 1 dose or in 2 divided doses.Combination therapy with inducers of lamotrigine metabolism (eg with phenytoin, carbamazepine, phenobarbital, primidone and rifampicin, lopinavir / ritonavir), without valproate: initially 50 mg once daily for the first 2 weeks, then 100 mg daily in 2 divided doses for the next 2 weeks. Then the dose should be increased by a maximum of 100 mg every 1-2 weeks until an optimal therapeutic response is obtained. Maintenance dose: 200-400 mg per day in 2 divided doses. Some patients require 700 mg / day to achieve the desired therapeutic response.Combination therapy with drugs without affecting the metabolism of lamotrigine (no valproate and no inducers of metabolism of lamotrigine): initially 25 mg once a day for the first 2 weeks, then 50 mg once a day for the next 2 weeks. Then the dose should be increased by a maximum of 50-100 mg every 1-2 weeks until an optimal therapeutic response is obtained. Maintenance dose: 100-200 mg per day in 1 or 2 divided doses. In the case of combination therapy with antiepileptic medicinal products whose effects on the pharmacokinetics of lamotrigine are not known, a treatment regimen is recommended as for patients taking valproate.Children from 2 to 12 years old: Monotherapy in typical attacks of the unconscious: 0.3 mg / kg initially. daily in 1 or 2 doses divided by the first 2 weeks, then 0.6 mg / kg daily in 1 or 2 doses divided for a further 2 weeks. Then the dose should be increased by a maximum of 0.6 mg / kg. daily for 1-2 weeks until an optimal therapeutic response is obtained. Maintenance dose: 1-10 mg / kg daily in 1 or 2 divided doses.Some patients require a dose of up to 15 mg / kg to achieve the desired therapeutic response. per day.Combination therapy with valproate(an inhibitor of lamotrigine metabolism), regardless of other concomitant medications: initially 0.15 mg / kg once a day for the first 2 weeks, then 0.3 mg / kg once a day for the next 2 weeks. Then the dose should be increased by a maximum of 0.3 mg / kg. daily for 1-2 weeks until an optimal therapeutic response is obtained. Maintenance dose: 1-5 mg / kg daily in 1 or 2 divided doses. Do not exceed the 200 mg dose per day.Combination therapy with inducers of lamotrigine metabolism (eg with phenytoin, carbamazepine, phenobarbital, primidone, as well as rifampicin, lopinavir / ritonavir), without valproate: initially 0.6 mg / kg daily in 2 doses divided by the first 2 weeks, then 1.2 mg / kg daily in 2 doses divided for a further 2 weeks. Then the dose should be increased by a maximum of 1.2 mg / kg. daily for 1-2 weeks until an optimal therapeutic response is obtained. Maintenance dose: 5-15 mg / kg daily in 2 divided doses. Do not exceed the 400 mg dose a day.Combination therapy with drugs without affecting the metabolism of lamotrigine (no valproate and no inducers of metabolism of lamotrigine): 0.3 mg / kg initially. daily in 1 or 2 doses divided by the first 2 weeks, then 0.6 mg / kg daily in 1 or 2 doses divided for a further 2 weeks. Then the dose should be increased by a maximum of 0.6 mg / kg. daily for 1-2 weeks until an optimal therapeutic response is obtained. Maintenance dose: 1-10 mg / kg daily in 1 or 2 divided doses. Do not exceed the 200 mg dose per day. In the case of combination therapy with antiepileptic medicinal products whose effects on the pharmacokinetics of lamotrigine are not known, a treatment regimen such as for patients taking valproate is recommended. In order to be sure that the therapeutic dose is properly selected, the child's body weight should be controlled and the dose should be recalculated if changes occur in the body weight. It is likely that patients aged 2-6 will require a maintenance dose at the upper limit of the recommended dose range. If seizure control is obtained in combination therapy, the concomitant use of antiepileptic drugs may be discontinued and patients may continue treatment with only lamotrigine. There are limited data on the efficacy and safety of lamotrigine in the combined treatment of partial seizures in children from 1 month to 2 years of age; no data on children under 1 month of age - lamotrigine is not recommended for children <2 years old.Bipolar disorder. During the introduction of lamotrigine, the dose should be gradually increased in order to stabilize the maintenance dose within 6 weeks. Then, if there are clinical indications, other psychotropic and / or anti-epileptic drugs may be discontinued.Adults (≥ 18 years old). Monotherapy with lamotrigine or combination therapy with drugs without affecting the metabolism of lamotrigine (without valproate and without inducers of metabolism of lamotrigine): initially 25 mg once daily for the first 2 weeks. Then 50 mg daily in 1 dose or 2 doses divided for a further 2 weeks. Then 100 mg daily in 1 dose or in 2 doses divided over the next week. The target stabilizing dose (from the 6th week of treatment) is usually 200 mg per day in 1 dose or in 2 divided doses. Doses in the range of 100-400 mg per day were used in clinical trials.Combination therapy with valproate (an inhibitor of lamotrigine metabolism), regardless of other concomitant medications: initially 25 mg every other day for the first 2 weeks. Then 25 mg once a day for the next 2 weeks. Then 50 mg daily for 1 dose or 2 doses divided for the next week. The target stabilizing dose (from the sixth week of treatment) is usually 100 mg per day in 1 dose or in 2 divided doses. Depending on the clinical response, a maximum dose of 200 mg per day may be used.Combination therapy with inducers of lamotrigine metabolism (eg with phenytoin, carbamazepine, phenobarbital, primidone and also rifampicin and lopinavir / ritonavir), without valproate: initially 50 mg once daily for the first 2 weeks. Then 100 mg daily in 2 divided doses for the next 2 weeks. Then 200 mg daily in 2 doses divided over the next week. The target stabilizing dose (from the sixth week of treatment) is usually 300 mg per day. The dose of 400 mg per day given in 2 doses can be used from the 7th week of treatment.In the case of combination therapy with antiepileptic medicinal products whose effects on the pharmacokinetics of lamotrigine are not known, a treatment regimen is recommended as for patients taking valproate.Removal of concurrently used medicines. When the target maintenance dose of lamotrigine is reached, other psychotropic or anti-epileptic drugs can be discontinued. Withdrawal of valproate: the maintenance dose of lamotrigine should be doubled (but not increased by more than 100 mg in 1 week) and maintained after discontinuation of valproate: the current maintenance dose of lamotrigine (before discontinuation) 100 mg per day - 1 week (start of withdrawal) 200 mg daily, 2 weeks and the next remain at 200 mg daily in 2 divided doses; the current maintenance dose of lamotrigine 200 mg per day - 1 week 300 mg daily, 2 weeks 400 mg daily, 3 weeks and then remain at a dose of 400 mg per day. Inhibition of the metabolite inducer lamotrigine (eg phenytoin, carbamazepine, phenobarbital, primidone): the dose of lamotrigine should be gradually decreased, depending on the initial dose, for 3 weeks after discontinuation of the glucuronidation inducer: the current maintenance dose of lamotrigine 400 mg per day - 1 week. 400 mg daily, 2 weeks 300 mg daily, from 3 weeks 200 mg daily; current maintenance dose of 300 mg lamotrigine daily - 1 week 300 mg daily, 2 week 225 mg daily, from 3 weeks 150 mg daily; current maintenance dose of lamotrigine 200 mg daily - 1 week 200 mg daily, 2 weeks 150 mg daily, from 3 weeks 100 mg daily. Drug discontinuation, with no significant pharmacokinetic interaction with lamotrigine (eg lithium, bupropion): the target dose of lamotrigine achieved in the dose escalation phase (200 mg per day, dose range 100-400 mg per day) should be maintained during discontinuation of another drug. In patients taking medicines with unknown pharmacokinetic interactions with lamotrigine, a treatment regimen is recommended as for patients taking valproate.Adjusting the daily dose of lamotrigine after the addition of other drugs used to treat bipolar disorder. Attachment of valproate - depending on the initial dose of lamotrigine: the current maintenance dose of lamotrigine 200 mg per day - 1 week 100 mg daily, from the second week maintenance of a dose of 100 mg per day; current maintenance dose of lamotrigine 300 mg daily - 1 week 150 mg daily, from the second week maintenance of a dose of 150 mg per day; current maintenance dose of lamotrigine 400 mg daily - 1 week 200 mg daily, from the second week maintenance of a dose of 200 mg per day. Attachment of glucuronidation inducers of lamotrigine in patients not taking valproate - depending on the initial dose of lamotrigine: the current maintenance dose of lamotrigine 100 mg per day - 1 week 100 mg daily, 2 weeks 150 mg daily, from 3 weeks 200 mg per day; current maintenance dose of lamotrigine 150 mg daily - 1 week 150 mg daily, 2 week 225 mg daily, from 3 weeks 300 mg daily; current maintenance dose of lamotrigine 200 mg daily - 1 week 200 mg daily, 2 weeks 300 mg daily, from 3 weeks 400 mg daily. Inclusion of other drugs without significant interactions with lamotrigine (eg lithium, bupropion): maintenance of the target dose achieved in the phase of increasing the dose of lamotrigine - 200 mg (range 100-400 mg) per day. In patients taking medicines with unknown pharmacokinetic interactions with lamotrigine, a treatment regimen is recommended as for patients taking valproate. The drug is not recommended for use in patients <18 years in the treatment of bipolar disorder.Special groups of patients: Women using hormonal contraceptivesa) initiation of hormonal contraception in patients taking lamotrigine in maintenance doses and not taking additional drugs inducing metabolism of lamotrigine: even a 2-fold increase in the maintenance dose of lamotrigine may be necessary (by 50-100 mg per day in a week, depending on the individual response) women); consideration should be given to measuring the levels of lamotrigine before and after the start of hormonal contraception to confirm maintenance of the initial concentration of lamotrigine and if necessary the dose should be adjusted; if you are taking a product that requires a weekly break - ie "week without tablets", you should monitor the concentration of lamotrigine in the third week of your hormonal treatment (ie from day 15 to day 21), contraception should be considered without a week's delay in taking the tablets as first-line treatment; b) discontinuation of hormonal contraception in patients taking lamotrigine in maintenance doses andnoIf you take additional medication that induces metabolism of lamotrigine: you may need to reduce the maintenance dose of lamotrigine by up to 50% (by 50-100 mg a day, every week in 3 weeks); consideration should be given to measuring the levels of lamotrigine before and after the end of hormonal contraception; if you are taking a product that requires one week's interruption - i.e."week without tablets", you should monitor the concentration of lamotrigine in the third week of the use of the hormonal drug (ie from the 15th to the 21st day of the cycle); samples for the determination of lamotrigine concentrations after total discontinuation of hormonal contraceptives should not be taken within the first week after discontinuation of the contraceptive pill; c) initiation of treatment with lamotrigine in patients already taking hormonal contraception - without special regimens, recommended dosage regimens should be used; d.) initiating and terminating hormonal contraception in patients who are taking maintenance doses of lamotrigine and using agents that induce lamotrigine metabolism: adjusting the recommended maintenance dose of lamotrigine may not be necessary.Use with atazanavir / ritonavir or with lopinavir / ritonavir. Incorporation of lamotrigine into existing atazanavir / ritonavir or lopinavir / ritonavir therapy should not require modification of the recommended dose regimen of lamotrigine. In patients who do not receive glucuronidation inducers and use maintenance doses of lamotrigine, it may be necessary to increase the dose of lamotrigine when adding atazanavir / ritonavir or lopinavir / ritonavir, or to reduce the dose if atazanavir / ritonavir or lopinavir / ritonavir is discontinued. Blood levels of lamotrigine should be monitored before and during the 2 weeks after adding or discontinuing atazanavir / ritonavir or lopinavir / ritonavir to determine the need to change the dose of lamotrigine.Elderly patients: no dose adjustment is needed.Patients with impaired liver function: initial dose, increase dose and maintenance dose in patients with moderate hepatic impairment (Child-Pugh B) should be reduced by about 50%, while in patients with severe hepatic impairment (Child-Pugh C) - by about 75 %. Doses during the rise and maintenance doses should be adjusted to the clinical response.Patients with impaired renal function: in patients with end-stage renal disease, starting doses of lamotrigine should be dependent on the type of concomitant anti-epileptic medicine; reduced maintenance dose can be effective in patients with severe renal impairment.Way of giving. The tablets should be swallowed whole; do not chew, do not crush. If the calculated dose of lamotrigine (eg in children or patients with hepatic impairment) does not correspond to the number of whole tablets, the dose corresponding to the smaller number of whole tablets should be administered.