Lamotrin

Lamotrin is an anticonvulsant and contains lamotrigine.

[1]

Indications of the lamotrina

Among the indications:

• treatment of epilepsy. In children from 12 years and adults: in combination or for monotherapy of generalized or partial forms of epileptic seizures (also of tonic-clonic type), and with it seizures that develop against the background of the Lennox-Gastaut syndrome. Children 2-12 years with the above violations - as an additional drug;
• Monotherapy with typical forms of small epileptic seizures;
• treatment in adult bipolar disorders. Prevention of the development of stages of emotional disorders in people with bipolar disorder is mainly prevention of manifestations of depression.

[2], [3], [4]

Release form

Produced in tablets with a volume of 25, 50 or 100 mg. One blister contains 10 tablets. Inside the package, 1, 3 or 6 blister plates are placed.

[5]

Pharmacodynamics

Lamotrigine is a derivative of phenyltriazine. This anticonvulsant, which acts on the body by blocking the potential-dependent sodium channels inside the presynaptic neuronal walls, as well as suppressing the excessive amount of released neurotransmitters with excitatory activity. In general, it is glutamate - an amino acid, which is one of the main causative agents of epilepsy.

[6], [7], [8], [9]

Pharmacokinetics

After oral administration, the drug is completely and quickly absorbed inside the digestive tract. In this case, the peak of the plasma concentration of the substance is observed after 2.5 hours. When you take your medicine with food, the peak period is longer, but food does not affect the degree of absorption.

Synthesis with a plasma protein reaches 55%. The active ingredient undergoes an intensive metabolism process, and the main product of its decomposition is N-glucuronide. The half-life of the substance in an adult is 29 hours, and in children this period is shorter.

Decay products are mainly excreted through the kidneys (unchanged - less than 10%), and 2% of the substance is excreted with feces.

[10], [11], [12]

Dosing and administration

The scheme of admission in the treatment of epilepsy in children from 12 years old, as well as adults.

Monotherapy:

• 1-2 weeks - once for 25 mg of medication per day;
• 3-4 weeks - once for 50 mg of medicine per day;
• maintenance dosages - per day for 100-200 mg (once or split in half). Achievement of the required dose occurs by gradually increasing the daily value every 1-2 weeks by 50-100 mg, until the desired effect is obtained. Sometimes the size of such a daily dose can be up to 500 mg.

In combination with sodium valproate (not including other additional drugs):

• 1-2 weeks - 25 mg every other day (or 12.5 mg per day);
• 3-4 weeks - 25 mg once a day;
• maintenance treatment - per day for 100-200 mg (once or split in half). Achievement of the desired dose occurs by increasing it every 1-2 weeks by 25-50 mg.

In combination with carbamazepine, phenytoin, primidone, as well as phenobarbital or other inducers of liver enzymes (sodium valproate is not used):

• 1-2 weeks - once for 50 mg per day;
• 3-4 weeks - divided into 2 daily dosages of 100 mg;
• maintenance dose - for a day for 200-400 mg (2 methods), is achieved with a gradual increase in the value of not more than 100 mg every 1-2 weeks. Individual cases required the use of 700 mg of a daily dose.

In combination with other drugs that have no significant effect (inhibition / induction) on liver enzymes (sodium valproate is not used):

• 1-2 weeks - once a day for 25 mg;
• 3-4 weeks - for a single dose of 50 mg per day;
• Supportive treatment - for a day of 100-200 mg (single or 2-way). To achieve the required value, it is necessary by gradually increasing the dosage after 1-2 weeks at 50-100 mg.

The scheme for eliminating epileptic seizures in children 2-12 years of age.

Monotherapy with the typical form of small seizures:

• 1-2 weeks - 0.3 mg / kg per day (once or in 2 doses);
• 3-4 weeks - 0.6 mg / kg per day (once or 2 times a day);
• Supporting - per day for 1-10 mg / kg (single or two-time intake). You can obtain the desired value by gradually increasing the size by 0.6 mg / kg every 1-2 weeks. Sometimes patients need stronger doses. Maximum of 200 mg per day is allowed.

In combination with sodium salt (without reference to other additional drugs):

• 1-2 weeks - per day (single dose) at 0.15 mg / kg;
• 3-4 weeks - per day (once) at 0.3 mg / kg;
• maintenance treatment - per day for 1-5 mg / kg (single or two-time intake). Achievement is carried out by gradual increase of the value by 0.3 mg / kg after 1-2 weeks. For a day you can take no more than 200 mg.

In combination with phenobarbital, phenytoin, primidone and carbamazepine or other inducers of liver enzymes (without the use of sodium salt):

• 1-2 weeks - a two-time drug intake per day in the amount of 0.6 mg / kg;
• 3-4 weeks - at 1.2 mg / kg per day (two-time use);
• maintenance dosage - per day for 5-15 mg / kg (2-time intake). This value can be obtained by gradually increasing the dose after 1-2 weeks at 1.2 mg / kg. For a day is allowed not more than 400 mg of medication.

In combination with other medicines that have no noticeable effect (by inhibition / induction) on liver enzymes (without sodium salt):

• 1-2 weeks - a single or two-time intake of 0.3 mg / kg of medication per day;
• 3-4 weeks - 0.6 mg / kg per day (1-2 administration);
• maintenance value - 1-10 mg / kg per day (1-2-time intake). It can be obtained by gradually increasing the daily dose (after 1-2 weeks) by 0.6 mg / kg. For a day is allowed to take no more than 200 mg of drugs.

(For people who take anticonvulsants with an unknown interaction with lamotrigine, a treatment regimen suitable for combination with valproate is recommended).

We recommend the following scheme for increasing the dosage of lamotrin to obtain a stabilizing daily value during treatment of adults suffering from bipolar disorders.

As an additional remedy together with inhibitors of liver enzymes, as well as with valproate:

• 1-2 weeks - 25 mg every other day;
• 3-4 weeks - daily for 25 mg (once);
• Week 5 - every day for 50 mg (1-2 doses);
• Week 6 (stabilizing dosage) - 100 mg (single or two-time administration). The maximum for the day is 200 mg.

As a complementary medicine, together with inducers of liver enzymes (without combination with valproate and other inhibitors) - such as primidone, carbamazepine, phenytoin, as well as phenobarbital or other inducers of lamotrigine glucuronization processes:

• 1-2 weeks - once a day for 50 mg;
• 3-4 weeks - 100 mg (in 2 applications) per day;
• Week 5 - 200 mg per day (with 2 methods);
• 6th week (stabilizing) - per day with 2 300 mg (6th week), with possible, if necessary, increase in the value to 400 mg (week 7), and also in 2 doses.

In monotherapy or in combination with drugs that do not have a significant effect (induction or inhibition) on the function of liver enzymes:

• 1-2 weeks - once a day, 25 mg;
• 3-4 weeks - 50 mg each (1-2 applications);
• 5-th week - for a day of 100 mg (once or in 2 doses);
• 6-th week (stabilizing) - for a day for 200 mg (for 1 reception or split in half). Also, the use of dosages in the range of 100-400 mg was noted.

(In this case, the stabilizing value may vary depending on the medication provided).

Dimensions of the stabilizing dosage of drugs in the treatment of bipolar disorders with the subsequent cancellation of the additional anticonvulsants or psychotropic drugs.

With the subsequent abolition of the use of inhibitors of liver enzymes (eg, valproate):

• Week 1 - increase in the stabilizing value by half, with a week not more than 100 mg (for example, a week increase from 100 to 200 mg per day);
• 2-3 weeks - maintenance of this value (200 mg per day, if necessary, it is allowed to increase the dose to 400 mg) with the use of 2 doses.

With the subsequent termination of the intake of inducers of liver enzymes (dose-dependent regimens) - carbamazepine, primidone, as well as phenytoin with phenobarbital and others:

• dosage of the first week - 400 mg; The second week - 300 mg; 3rd week - 200 mg;
• dosage of the first week - 300 mg; The second week - 225 mg; 3rd week - 150 mg;
• dosage of the first week - 200 mg; The second week - 150 mg; The 3rd week - 100 mg.

With the subsequent elimination of other drugs that have no significant effect on the process of glucuronization of the active substance (suppression / induction):

• for the entire period of therapy (3 weeks), the maintenance daily dosage is 200 mg (two-time intake). Variations of this value are possible within the limits of 100-400 mg.

Change in the size of doses of the drug for people with bipolar disorders when combined with other drugs.

In combination with inhibitors of liver enzymes (valproate); the dosage of lamotrigine is taken into account:

• maintenance value: 200 mg per day; 1st week - 100 mg per day; 2 nd and from 3 rd week - maintenance of the value established in the first week (100 mg / day);
• maintaining a value of 300 mg per day; in the first week - 150 mg per day; in the second and third weeks, the dosage of the first week (150 mg / day) is maintained;
• maintenance value: 400 mg per day; in the first week - 200 mg per day; in the second and third weeks, it is required to maintain a dose of the first week (200 mg per day).

In combination with inducers of liver enzymes (carbamazepine, phenytoin, primidone, phenobarbital or other drugs from this category) without the use of valproate; the dose rate of lamotrin is taken into account:

• maintenance value: 200 mg per day; in the first week - 200 mg; in the second week - 300 mg; beginning with the third week - 400 mg;
• maintenance norm: 150 mg / day; in the first week - 150 mg; in the second week - 225 mg; starting from the 3rd week - 300 mg;
• maintenance dose: 100 mg / day; in the first week - 100 mg; in the second week - 150 mg; beginning with the third week - 200 mg.

In combination with drugs that do not have a significant inhibitory or inducing action against liver enzymes:

• During the entire course, the dosage should be maintained at 200 mg per day.

[16], [17]

Use of the lamotrina during pregnancy

The existing post-marketing information of several registered registries, in which 2000+ pregnant women (1 trimester), who received lamotrigine monotherapy, showed that there was no significant increase in the likelihood of many congenital malformations in development. But there are also limited registries that have demonstrated that there is a high probability of developing an isolated cleft in the oral cavity.

The current information on the course of controlled trials does not show an increase in the likelihood of developing a cleft in the mouth compared to other congenital disorders after using lamotrigine. If treatment with the use of medication can not be avoided, it is recommended to take it at the lowest effective dosages.

At the moment, there is little information about the use of lamotrigine in combination with other drugs during pregnancy, so it can not be determined whether this substance affects the likelihood of developmental defects that are associated with other medicines.

Like other drugs, Lamotrin is prescribed to pregnant women only when the probability of a beneficial effect for a woman exceeds the possibility of a negative reaction in the fetus.

Since lamotrigine has a slight inhibitory effect on dihydrofolate reductase and can reduce folate, in theory it can increase the likelihood of disorders in embryonic development. Therefore, it is necessary to consider the need for folic acid during the period of pregnancy planning or in its early stages.

Contraindications

Contraindications are intolerance lamotrigine or other substances contained in the drug, and in addition, children's age less than 2 years.

[13]

Side effects of the lamotrina

As a result of using the medicine, the following side effects may develop:

• subcutaneous tissue and skin: itching, rashes on the skin, Lyell's syndromes or Stevens-Johnson syndrome;
• lymph and hematopoiesis: pancito-, neutro-, thrombocyto- or leukopenia, agranulocytosis, anemia (or its aplastic form), as well as lymphadenopathy;
• Immune system organs: facial swelling, hematopoietic or hepatic function disorders, hypersensitivity syndrome (also fever condition), multiple organ failure, and in addition, DIC syndrome;
• mental disorders: a feeling of aggressiveness or irritability, the appearance of hallucinations or tics, and confusion;
• organs of the National Assembly: dizziness and headaches, insomnia or drowsiness, development of ataxia, tremors, nystagmus. In addition, serous meningitis, loss of balance, anxiety, motor disorders, increased motor paralysis, extrapyramidal syndromes, frequent seizures and choreoathetosis;
• visual organs: development of conjunctivitis or diplopia, as well as the appearance of a veil before the eyes;
• organs of the digestive system: diarrhea, vomiting, dry mouth mucous and nausea;
• liver: a disorder of the hepatic function, an increase in the values of functional liver samples, as well as liver failure;
• connective tissues, as well as the structure of bones and muscles: the development of arthralgia or the appearance of signs of SLE;
• Other disorders: pain in the back, increased fatigue.

[14], [15]

Overdose

There is evidence of an acute overdose due to the use of drugs in values that exceed the maximum permissible level of 10-20 times (including fatalities).

The symptoms are headaches with dizziness, nystagmus, vomiting, a feeling of drowsiness, development of ataxia. In addition, a disorder of consciousness, a state of coma, severe attacks of epilepsy, as well as widening of the teeth inside the QRS complex (conduction delay begins inside the cardiac ventricles).

To reduce the absorption of drugs, you should do gastric lavage, and then give the patient enterosorbents. After this, hospitalization for intensive care is required to provide the necessary supportive and symptomatic treatment.

[18], [19], [20]

Interactions with other drugs

It was revealed that UDFGT is an enzyme involved in the metabolism of lamotrigine. There are no reliable facts that the active ingredient of Lamotrin is capable of inhibiting or stimulating oxidative hepatic enzymes that are involved in drug metabolism processes within medically significant limits. Also, the probability of its interaction with drugs, whose metabolism is carried out with the help of hemoprotein 450 enzymes, is also low. At the same time, lamotrigine is able to independently induce its metabolism, although this action is rather weak and does not have a noticeable clinical significance.

Combination with anticonvulsants.

Valproate, which largely inhibits microsomal hepatic enzymes, inhibits the metabolism of lamotrigine, and also extends about half its half-life.

Such anticonvulsants as primidon, phenobarbital and carbamazepine with phenytoin, which induce microsomal hepatic enzymes, increase the metabolic rate of lamotrigine.

There is information about the development of negative reactions from the central nervous system, including diplopia, nausea, dizziness, ataxia and blurred vision when the drug is combined with carbamazepine. After lowering the dosage of the last symptoms, the symptoms usually go away. A similar effect was observed when testing the combination of lamotrin with oxcarbazepine (a drug that does not induce or inhibit liver enzymes), although according to existing information, none of them has any effect on the metabolism of another.

Anticonvulsants, such as levetiracetam, zonisamide with gabapentin, and in addition felbamate with thoriimate and preagabalin, which do not exert an inducing or inhibitory effect on liver enzymes, do not affect the pharmacokinetic properties of lamotrigine. It, in turn, does not affect the pharmacokinetic characteristics of pregabalin with levetiracetam. When combined with lamotrigine, the index of topiramate increases (by 15%).

Although there is evidence of a change in the plasma indices of other anticonvulsants, the information provided by the testing demonstrates that lamotrigine does not affect the plasma level of concomitant anticonvulsant drugs. In vitro tests revealed that the active substance of Lamotrin does not affect the synthesis of other anticonvulsants with the plasma protein.

Combination with other psychotropic drugs.

Interactions with substances that do not induce or inhibit hepatic enzymes (such as aripiprazole, olanzapine, and bupropion with lithium).

In the treatment of bipolar disorders, the combination of lamotrigine with aripiprazole led to a decrease in peak and AUC values (about 10%) of the former. But it is believed that such an impact will not have a noticeable clinical effect.

Simultaneous use with olanzapine reduces peak and AUC lamotrigine, respectively, by 20%, and 24% (mean). The effect of this strength of expression is very rare in clinical practice. Lamotrigine does not affect the pharmacokinetic properties of olanzapine.

With multiple use of bupropion inside, there is no noticeable medicinal effect on the properties of lamotrigine, only a slight increase in lamotrigine glucuronide is possible.

In the case of a combination of the active substance with lithium gluconate, the properties of the latter remain unchanged.

Multiple use of lamotrigine orally does not have a significant clinical effect on the characteristics of risperidone. The combined use of these medicines can cause a feeling of drowsiness.

In vitro testing revealed that only substances such as bupropion, fluoxetine, amitriptyline, and also haloperidol with lorazepam only slightly influence the formation of the primary product of the decay of the active component of the drug, N-glucuronide.

The study of the processes of metabolism of bufuralol inside the hepatic microsomes made it possible to reveal that lamotrigine does not decrease the drug clearance rate, which is mainly metabolized with the participation of the element CYP 2D6. Tests in vitro suggest that the coefficient of cleansing lamotrigine substances such as phenelzine, trazodone, as well as sertraline with risperidone and clozapine, do not work.

Combination with hormonal contraception.

There is evidence that the combined use of ethinylestradiol (30 μg dose) with levonorgestrel (150 μg dose), which cause pronounced induction of liver enzymes, can approximately double the lamotrigine excretion. Because of this, the indicator of the latter decreases, and with a weekly interval in the use of contraceptives, it begins to increase again (for a time and gradually).

In combination with oral contraception lamotrigine does not affect the performance of ethinyl estradiol and insignificantly reduces the level of levonorgestrel inside the plasma. There is no information on how these changes affect the process of ovulation.

Combination with other drugs.

Medications that largely induce liver enzymes (such as rifampicin and in addition lopinavir with ritonavir, as well as atazanavir with ritonavir).

In combination with rifampicin, excretion rates increase and the half-life of lamotrigine decreases, since induction of liver enzymes responsible for the glucuronization process occurs.

Lopinavir with ritonavir approximately halves the level of lamotrigine inside the plasma - thanks to the induction of the glucuronization process.

People who take lopinavir with ritonavir, as well as rifampicin, need to use a regimen that is suitable for the concomitant use of lamotrigine along with appropriate induction drugs for the glucuronization process.

The combination with atazanavir and ritonavir (in doses of 300 and 100 mg) lowers the peak level and lamotrigine AUC of the plasma inside (the dosage of 100 mg) by 6% and 32% (on average), respectively.

[21], [22], [23],

Storage conditions

The medicine is stored in standard conditions for medicines, inaccessible to children. Temperature values - no more than 25 ° С.

[24]

Shelf life

Lamotrin is allowed to be used within 3 years of the release of the medicine.

[25]