Latrigin

Latrigine is an anticonvulsant drug.

Indications Latrigina

It is used to treat epilepsy in adolescents aged 12 years and over and in adults – as monotherapy or as an additional agent (for example, for seizures of a generalized or partial nature; this includes seizures of the tonic-clonic type and seizures caused by LGS).

It is also used to treat bipolar disorders in adults – to prevent the development of stages of emotional disorders in such people (usually these are episodes of depression).

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Release form

The release occurs in tablet form, 10 pieces inside a blister cell. In a separate package - 3 blister plates.

Pharmacodynamics

The drug blocks the activity of potential-dependent Na channels inside presynaptic neuronal membranes at the stage of slow inactivation. In addition, it slows down the release of excess neurotransmitters (mainly from 2-aminopentanedioic acid - an excitatory amino acid that is an important participant in the processes of forming epileptic seizures).

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Pharmacokinetics

After oral administration, the drug is completely and very quickly absorbed in the gastrointestinal tract. Peak plasma levels of the substance are observed after 2.5 hours. The period of reaching this indicator may be extended if the drug is taken with food (the degree of absorption remains the same).

Liver metabolism involves the enzyme glucuronyl transferase, which forms the N-glucuronide element. The half-life is 29 hours.

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Dosing and administration

Taken orally, regardless of food intake. Swallow the tablets without chewing.

If the dosage of the drug prescribed does not correspond to the active component indicators in the table, it is necessary to reduce the dose to 0.5 tablets or a whole one.

Re-initiation of the therapeutic course.

When prescribing a repeat course to people who have discontinued therapy, it is necessary to clearly determine the need to increase the maintenance dose, because there is a risk of rash due to a high initial dosage and failure to comply with the recommended dosage increase scheme. The longer the interval between the time of use of the previous dose, the more carefully it is necessary to monitor the regimen of increasing the dose to maintenance values. After the interval after the end of drug use exceeds the half-life by 5 times, the dosage of lamotrigine can be increased to the maintenance level - taking into account the data recommended by the application scheme.

Do not restart the treatment if the treatment was stopped due to a rash from previous treatment with lamotrigine. In such a situation, the probable benefit of the drug should be weighed against the expected risk before deciding to re-use it.

For epilepsy in adolescents from 12 years of age and adults.

Monotherapy.

The initial dose of the drug is equal to a single dose of 25 mg per day for 14 days. During the next 14 days, 50 mg/day is taken, and then the dose can be increased every 1-2 weeks by 50-100 mg until the optimal effect is achieved. The standard maintenance dose is 100-200 mg/day (it is taken in 1-2 doses). There are also patients who need to take 0.5 g of the drug per day.

Combination treatment.

People taking valproate (either as monotherapy or with other anticonvulsants) are required to take 25 mg of the drug every other day for 14 days, and then take the same dose daily for the next 14 days. The dosage is then increased every 1-2 weeks (by no more than 25-50 mg/day) until the optimal medicinal effect is achieved. The standard maintenance dose is 100-200 mg/day (taken in 1-2 doses).

For people taking other anticonvulsants or other drugs (liver enzyme inducers) with or without other anticonvulsants (sodium valproate is an exception), the initial dose of Latrigine is a single dose of 50 mg/day for 14 days. Then, 100 mg is taken per day in 2 doses (for 2 weeks). Later, the dose is increased every 1-2 weeks (maximum by 0.1 g) until the desired medicinal effect is achieved. In general, the maintenance dose is 0.2-0.4 g/day, taken in 2 doses. Some patients may need to take 700 mg per day.

People taking other drugs that weakly induce or inhibit liver enzymes should first take 25 mg once a day (for 2 weeks), and later 50 mg per day (also for 14 days). The dosage is then increased at intervals of 1-2 weeks (by no more than 0.05-0.1 g/day) until the desired medicinal effect is achieved. The maintenance dose is often 0.1-0.2 g/day (taken 1-2 times).

Those taking anticonvulsants with unclear interactions with Lamotrigine should use the same regimen as when combining lamotrigine and valproate.

For adults with bipolar disorder.

It is necessary to follow the below transition regimen when using. This includes a scheme of increasing the dosage until the stabilization portion is reached (over 6 weeks), and then stopping the use of other psychotropic or anticonvulsant drugs (if there is a medicinal need).

It is also necessary to consider the need for additional treatment that will prevent the development of manic episodes, because there is no precise data on the effective use of drugs for the treatment of manic syndrome.

Dose escalation schedule to stabilization maintenance dose (per day) in adults with bipolar disorder:

• additional course using liver enzyme inhibitors (including valproate): days 1-14 – 25 mg of the drug every other day; days 15-28 – 25 mg daily; days 29-35 – 50 mg/day in 1-2 doses; days 36-42 – the stabilization dose is 0.1 g/day (in 1-2 doses). No more than 0.2 g is allowed per day;
• an additional course using liver enzyme inducers for people who do not take inhibitors (carbamazepine, primidone, phenytoin, phenobarbital or other inducer drugs): days 1-14 - 1 time per day 50 mg; days 15-28 - 0.1 g per day (in 2 doses); days 29-35 - 0.2 g per day (in 2 doses); days 36-42 - the stabilization dose is 0.3 g / day (in 2 doses). It is allowed to increase it to 0.4 g / day in the 7th week;
• monotherapy with lamotrigine or additional use in individuals taking other drugs that do not have clinically significant suppression/induction of liver enzymes: days 1-14 - 1-time intake of 25 mg per day; days 15-28 - 50 mg per day (1-2 doses); days 29-35 - use in 1-2 doses of 100 mg per day; days 36-42 - stabilization dose - take in 1-2 doses of 200 mg per day (in the range of 100-400 mg).

After receiving the required maintenance stabilization dose, the use of other psychotropic drugs can be stopped according to the following schemes:

• when subsequently discontinuing agents that inhibit liver enzymes (valproate): in the 1st week, double the stabilization dose (but not exceeding the limit of 0.1 g/week) – for example, from 0.1 g/day to 0.2 g/day; over the course of 8-21 days, it is necessary to maintain a dosage of 0.2 g/day (divide into 2 doses);
• when further discontinuing the intake of liver enzyme inducing agents (taking into account the initial dose): there are 3 schemes:

1. first 7 days – 0.4 g; second 7 days – 0.3 g; from the 15th day – 0.2 g;
2. first 7 days – 0.3 g; second 7 days – 225 mg; from the 15th day – 150 mg;
3. first 7 days – 0.2 g; second 7 days – 150 mg; from the 15th day – 0.1 g;

• with subsequent withdrawal of other drugs that do not have clinically significant induction/inhibition of liver enzymes: maintaining the dosage that was determined during the increase (200 mg/day), which is divided into 2 doses (within 100-400 mg).

People who use anticonvulsants whose interaction with Lamotrigine has not been studied should follow a regimen in which the existing dosage of lamotrigine is maintained and adjusted based on the clinical picture.

Dose adjustment of lamotrigine in people with bipolar disorder when using other drugs in addition.

Schemes for additional administration of liver enzyme inhibitors (valproate) taking into account the initial dose of lamotrigine:

1. stabilization dose of lamotrigine – 0.2 g/day; first 7 days – 0.1 g; from the 8th day onwards – maintenance dosage of 0.1 g/day;
2. stabilization – 0.3 g/day; first 7 days – 150 mg; from the 8th day onwards – maintenance of 150 mg/day;
3. stabilization – 0.4 g/day; first 7 days – 0.2 g; from the 8th day onwards – maintaining the dose of 0.2 g/day.

Schemes for additional administration of liver enzyme inducers to individuals not using valproates, taking into account the initial dose:

1. stabilization – 0.2 g/day; days 1-7 – 200 mg; days 8-14 – 300 mg; from the 15th day – 400 mg;
2. stabilization – 150 mg/day; days 1-7 – 150 mg; days 8-14 – 225 mg; from the 15th day – 300 mg;
3. stabilization – 100 mg/day; days 1-7 – 100 mg; days 8-14 – 150 mg; from the 15th day – 200 mg.

Scheme for additional administration of drugs that do not have a noticeable inducing or depressing effect on liver enzymes: maintaining the dosage that was obtained after using the dose increase regimen – 200 mg/day (within 100-400 mg).

Women using hormonal contraceptives.

Initiation of lamotrigine therapy in women already using hormonal contraception.

Although oral contraceptives increase the clearance rate of lamotrigine, there is no need to change the dosage regimen when combined with contraception alone. The dose is increased in the specified regimen only when Latrigine is added to an inhibitor or inducer of liver enzymes (also when added without valproates or inducers of liver enzymes).

Initiation of hormonal contraception in women already taking lamotrigine in maintenance doses and not taking liver enzyme inducers.

Often, it is necessary to double the maintenance dose of lamotrigine. It is recommended that from the beginning of the use of hormonal contraception, the dose of Latrigine is increased by 50-100 mg/day every 7 days (taking into account the patient's response to therapy). In the process of increasing the dose, the specified limit must not be exceeded (this happens only if there is such a need in accordance with the clinical response of the patient).

Discontinuation of hormonal contraceptive therapy in women already taking lamotrigine in maintenance doses but not taking liver enzyme inducers.

Often, a reduction of up to 50% of the maintenance dose of lamotrigine is required. The daily dosage of the drug should be reduced gradually - weekly by 50-100 mg (maximum 25% of the total weekly dose) for 3 weeks. Exceptions may be cases where an unusual individual clinical response is observed.

For liver failure.

The starting dose, dose escalation, and maintenance dose should be reduced by approximately 50% in people with moderate disease (Child-Pugh score B) or by 75% in people with severe disease (Child-Pugh score C). The dose escalation and maintenance dose may be adjusted based on drug effect.

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Use Latrigina during pregnancy

The test results show that there is no significant increase in the risk of many birth defects in the first trimester, but some testing has shown that there is an increased risk of an anomaly called an isolated cleft in the oral cavity. Control tests have not shown an increased risk of an isolated cleft in the oral cavity compared to other adverse effects of lamotrigine use.

There is too little information on the combined use of lamotrigine to draw a clear conclusion that the drug affects the likelihood of developmental abnormalities associated with other drugs. Latrigine can be prescribed to a pregnant woman only in a situation where the likelihood of helping the woman from its use is higher than the risk of complications in the fetus.

Physiological changes during pregnancy can affect lamotrigine levels or its medicinal effect. There is evidence of decreased levels of the substance in pregnant women. In this regard, pregnant women who are treated with lamotrigine should be under regular medical supervision.

There is evidence that the drug can pass into breast milk in varying concentrations, reaching values in the infant that correspond to 50% of the maternal values. Because of this, in some breastfed infants, serum drug levels can reach values at which drug effects may develop.

Therefore, it is necessary to take into account the risk of adverse reactions in the infant and correlate it with the need for breastfeeding during the treatment period.

Contraindications

Main contraindications: hypersensitivity to the drug components and children under 12 years of age (for epilepsy therapy). It is also prohibited to prescribe to children under 18 years of age to eliminate bipolar disorders, because there is no information on the use of drugs in this group of patients.

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Side effects Latrigina

The use of drugs to treat epilepsy may lead to the following side effects:

• lesions of the subcutaneous layers together with the skin: rashes are often observed (usually maculopapular type), occasionally – Stevens-Johnson syndrome, and isolated cases – TEN, against the background of which scars can form. The risk of rash is usually due to taking large doses of lamotrigine at the initial stage, ignoring the standard scheme for increasing dosages, and in addition to this, taking it together with valproate. In addition, there is an opinion that the rash is an element of intolerance syndrome, accompanied by various general manifestations. Rarely, skin lesions (TEN or Stevens-Johnson syndrome) have led to death;
• dysfunction of the lymph and hematopoietic system: lymphadenopathy or hematological disorders (such as anemia (sometimes of the aplastic type), leuko-, thrombocyto- or neutropenia, as well as agranulocytosis) are observed sporadically. Hematological abnormalities can sometimes be caused by hypersensitivity syndrome;
• immune disorders: intolerance syndrome is occasionally detected, expressed in the form of lymphadenopathy, fever, hematological disorders, swelling of the face, skin rash (of varying severity), liver problems, disseminated intravascular coagulation, and multiple organ failure. Early signs of increased sensitivity (including lymphadenopathy or fever) can develop even in the absence of skin rash. If a patient develops such signs, he should be examined immediately and, if other symptoms are not detected, the drug should be discontinued;
• mental disorders: feelings of irritability and aggressiveness are often observed. Hallucinations, tics and a feeling of confusion are noted sporadically;
• reactions of the nervous system: headaches are often observed. A little less often - nystagmus, dizziness, tremor, a feeling of drowsiness or insomnia. Sometimes the development of ataxia is detected. A feeling of anxious excitement aseptic form of meningitis, movement disorders and loss of balance, extrapyramidal symptoms, exacerbation of shaking palsy, increased frequency of epileptic seizures and choreoathetosis occur sporadically;
• damage to the visual organs: blurred vision and diplopia are often observed. Conjunctivitis occasionally develops;
• gastrointestinal disorders: vomiting, diarrhea or nausea are often observed;
• disorders of the hepatobiliary system: liver failure, problems with liver function, and increased activity of liver transaminases are noted sporadically. Problems with liver function are often an intolerance reaction, although cases have been recorded that did not have visible symptoms of hypersensitivity;
• lesions of the musculoskeletal system with connective tissues: lupus-like manifestations occur sporadically;
• systemic disorders: increased fatigue often appears.

Side effects of taking pills for bipolar disorder:

• lesions in the subcutaneous tissue area along with the skin: most often, rashes appear. Stevens-Johnson syndrome develops occasionally;
• reactions in the nervous system: headaches most often occur. A feeling of drowsiness or anxious excitement, as well as dizziness, often occurs;
• manifestations in the area of connective tissues and the musculoskeletal system: arthralgia often develops;
• systemic symptoms: pain often appears (particularly in the back area).

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Overdose

There are reports of cases of acute poisoning (taking doses that exceeded the maximum medicinal dose by 10-20 times). In this case, there was a disturbance of consciousness, nystagmus with ataxia and a state of coma.

In case of drug intoxication, the victim must be hospitalized to receive adequate supportive treatment.

Interactions with other drugs

Medicines containing valproic acid inhibit the metabolism of lamotrigine, increasing the half-life of the substance to 70 hours.

Primidone with carbamazepine and phenytoin with paracetamol and phenobarbital increase the rate of drug metabolism, halving the half-life of lamotrigine. Combined use with carbamazepine increases the incidence of some adverse effects (ataxia, blurred vision, dizziness, and diplopia with nausea), which disappear after reducing the dose of carbamazepine.

As a result of the combined administration of 100 mg/day lamotrigine and anhydrous lithium gluconate (2 g twice daily) over a 6-day period, no changes in the pharmacokinetic parameters of lithium were observed.

Repeated administration of bupropion has little effect on the pharmacokinetic properties of lamotrigine, slightly increasing the levels of its breakdown product, lamotrigine glucuronide.

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Storage conditions

Latrigine is stored in a place inaccessible to small children. The maximum storage temperature is 25°C.

Special instructions

Reviews

Latrigine receives mostly positive reviews from patients. With a slow increase in dosage, no side effects are observed. At the same time, many point out that the drug has a fairly stable antidepressant effect, as well as a weak antimanic effect. In addition, the drug reduces the feeling of irritability.

Among the disadvantages, there are patients who had to stop taking the drug due to the appearance of rashes.

Shelf life

Latrigine is allowed to be used for 2 years from the date of release of the drug.