Lamitor^® (Tablets) Instructions for Use

Marketing Authorization Holder

Torrent Pharmaceuticals, Ltd. (India)

Contact Information

TORRENT PHARMACEUTICALS LTD. (India)

ATC Code

N03AX09 (Lamotrigine)

Active Substance

Lamotrigine (Rec.INN registered by WHO)

Dosage Forms

	Lamitor®	Tablets 25 mg: 30 or 50 pcs.
		Tablets 50 mg: 30 or 50 pcs.
		Tablets 100 mg: 30 or 50 pcs.

Dosage Form, Packaging, and Composition

* – non-proprietary international name recommended by WHO; in the Russian Federation, the international name spelling – Lamotrigine – is adopted.

10 pcs. – blister packs (5) – cardboard packs.

Clinical-Pharmacological Group

Anticonvulsant drug

Pharmacotherapeutic Group

Antiepileptic drugs; other antiepileptic drugs

Pharmacological Action

Anticonvulsant (antiepileptic) drug.

Blocker of voltage-gated sodium channels. It causes blockade of impulse discharges in neuronal culture and inhibits the excessive release of glutamate (an amino acid that plays a key role in generating epileptic seizures) along with the inhibition of glutamate-induced effector impulses.

Pharmacokinetics

Absorption

After oral administration, Lamotrigine is rapidly and completely absorbed from the gastrointestinal tract. C_max in blood plasma is observed 2.5±1.5 hours after oral administration. The time to reach C_max is somewhat prolonged if the drug is taken after a meal, but the extent of absorption remains unchanged. The pharmacokinetics are linear up to a dose of 450 mg – the maximum single dose that has been studied. There are significant individual differences in the C_max values of the drug, but individual concentrations vary very little.

Distribution

Binding to plasma proteins is approximately 55%.

Metabolism

It is metabolized in the liver with the formation mainly of glucuronides.

Excretion

T_1/2 in healthy adults is 24-35 hours.

The average clearance values in healthy individuals are 39±14 ml/min.

Lamotrigine is excreted from the body in the urine as glucuronides. Less than 10% is excreted unchanged in the urine. Only 2% of metabolites are excreted in the feces.

Pharmacokinetics in special clinical cases

The T_1/2 of lamotrigine largely depends on concomitant drug therapy.

The T_1/2 of lamotrigine decreases to 14 hours when combined with drugs that induce the activity of cytochrome P₄₅₀ isoenzymes, such as carbamazepine and phenytoin, and increases on average to about 70 hours in case of concomitant use with sodium valproate.

The T_1/2 of lamotrigine in children is usually shorter than in adults. The T_1/2 in children is approximately 7 hours when taken with drugs that induce isoenzyme activity, such as carbamazepine, phenytoin, phenobarbital, and primidone. The T_1/2 increases to 45-55 hours when taken concomitantly with sodium valproate.

Studies of the pharmacokinetics of lamotrigine in single doses in patients with kidney disease indicate that the pharmacokinetic parameters change insignificantly, but the concentrations of the main metabolite in the form of a glucuronide increase almost 8 times due to decreased renal clearance.

Indications

Lamitor^® is recommended as monotherapy and adjunctive therapy for adults and children over 12 years of age

• Simple partial seizures;
• Complex partial seizures;
• Secondarily generalized tonic-clonic seizures;
• Primarily generalized tonic-clonic seizures;
• Typical absences;
• Atypical absences;
• Myoclonic seizures;
• Seizures resistant to other antiepileptic drugs of any type.

Lamitor^® is also used as adjunctive therapy for children aged 2 to 12 years.

ICD codes

Dosage Regimen

The initial dose of Lamitor^® for adults and children over 12 years of age not taking sodium valproate but taking other antiepileptic drugs that induce isoenzymes is 50 mg once daily for the first 2 weeks and 100 mg/day (in 2 doses) for the next 2 weeks. Then the dose should be increased to 200-400 mg/day (in 2 doses).

The initial dose of Lamitor^® for patients taking sodium valproate in combination with other antiepileptic drugs that induce isoenzymes is 25 mg every other day for the first 2 weeks and then 25 mg once daily for the next 2 weeks. Then the dose should be increased to achieve the optimal therapeutic effect. The maintenance dose is 100-200 mg (in 1 or 2 doses).

The initial dose of Lamitor^® for children from 2 to 12 years old not taking sodium valproate but taking other antiepileptic drugs that induce isoenzymes is 2 mg/kg/day (in 2 doses) for the first 2 weeks and 5 mg/kg/day (in 2 doses) for the next 2 weeks. The maintenance dose is 5-15 mg/kg/day (in 2 doses).

The initial dose of Lamitor^® for children taking sodium valproate in combination with other antiepileptic drugs that induce isoenzymes is 0.2 mg/kg once daily for the first 2 weeks, then 0.5 mg/kg once daily for the next 2 weeks. Then the dose should be increased to achieve the optimal therapeutic effect. The maintenance dose is 1-5 mg/kg (in 1 or 2 doses).

Adverse Reactions

Side effects noted when prescribing Lamitor^® as monotherapy

From the central nervous system dizziness, headache, drowsiness, sleep disturbance, increased fatigue.

From the digestive system nausea.

Allergic reactions maculopapular skin rash (2%), most often noted in the first 4 weeks after starting treatment and disappears after drug withdrawal. In some cases – Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis.

Side effects noted when prescribing Lamitor^® as adjunctive therapy to standard antiepileptic drugs

From the central nervous system dizziness, headache, drowsiness, imbalance, increased fatigue, irritability, aggressiveness, tremor, confusion.

From the organ of vision diplopia, blurred vision.

From the hematopoietic system neutropenia, leukopenia.

From the digestive system nausea, vomiting, dyspeptic symptoms.

Contraindications

• Severe liver dysfunction;
• Hypersensitivity to lamotrigine and other components of the drug.

Use in Pregnancy and Lactation

The drug should not be prescribed during pregnancy and lactation, except in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus and child.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction.

Use in Renal Impairment

In patients with end-stage renal disease, accumulation of the glucuronide metabolite should be expected. Therefore, caution should be exercised when prescribing to such patients if necessary.

Pediatric Use

The initial dose of Lamitor^® for children from 2 to 12 years old not taking sodium valproate but taking other antiepileptic drugs that induce isoenzymes is 2 mg/kg/day (in 2 doses) for the first 2 weeks and 5 mg/kg/day (in 2 doses) for the next 2 weeks. The maintenance dose is 5-15 mg/kg/day (in 2 doses).

The initial dose of Lamitor^® for children taking sodium valproate in combination with other antiepileptic drugs that induce isoenzymes is 0.2 mg/kg once daily for the first 2 weeks, then 0.5 mg/kg once daily for the next 2 weeks. Then the dose should be increased to achieve the optimal therapeutic effect. The maintenance dose is 1-5 mg/kg (in 1 or 2 doses).

Special Precautions

Information on the use of Lamitor^® in elderly patients is limited. Therefore, the drug should be prescribed with caution to this category of patients.

Overdose of Lamitor^® may lead to the development of skin rash (in this situation, the drug should be discontinued).

In some cases, when prescribing the drug, severe skin rash (including Stevens-Johnson syndrome) may develop. Such reactions develop more often in children. Lamitor^® should be discontinued at the first signs of rash. The risk of developing such complications increases when Lamitor^® is prescribed simultaneously with sodium valproate and if the dose of Lamitor^® used exceeds the recommended initial and maximum daily dose.

If a skin rash develops, the use of the drug should be stopped immediately.

When using Lamitor^®, the development of such hypersensitivity symptoms (in some cases up to a fatal outcome) as fever, malaise, cold symptoms, drowsiness, lymphadenopathy, facial swelling, and in very rare cases – liver dysfunction, hematopoiesis disorders (leukopenia and thrombocytopenia) is possible. In most patients, these symptoms disappear after discontinuation of Lamitor^®.

If a rash, chills, cold symptoms, drowsiness, or worsening control of seizures (especially during the first month) occurs during the use of the drug, liver function tests, kidney function parameters, and blood clotting should be monitored.

Abrupt withdrawal of Lamitor^® may lead to an increase in seizures. The dose of Lamitor^® should be reduced gradually over 2 weeks.

In patients with end-stage renal disease, accumulation of the glucuronide metabolite should be expected. Therefore, caution should be exercised when prescribing to such patients if necessary.

Effect on the ability to drive vehicles and operate machinery

The possibility of driving vehicles and working with moving mechanisms while taking Lamitor^® is decided individually, taking into account the clinical situation.

Overdose

Symptoms nystagmus, ataxia, dizziness, drowsiness, headache, nausea, loss of consciousness, coma.

Treatment gastric lavage, intake of activated charcoal. If necessary, symptomatic therapy is carried out.

Drug Interactions

With simultaneous use with antiepileptic drugs that induce liver isoenzymes (phenytoin, carbamazepine, phenobarbital, primidone), the metabolism of Lamitor^® is enhanced, which may require an increase in its dose.

Sodium valproate, which competes with lamotrigine for metabolizing liver isoenzymes, inhibits its metabolism. There is no data that Lamitor^® is capable of inducing or inhibiting liver isoenzymes that metabolize other drugs. Lamitor^® may induce its own metabolism, but this effect is very insignificant and does not cause serious clinical manifestations.

Although some patients experience changes in the plasma concentrations of other antiepileptic drugs, controlled studies have not confirmed the effect of Lamitor^® on the plasma levels of concurrently taken antiepileptic drugs. Data from in vitro studies indicate that Lamitor^® does not compete with other antiepileptic drugs for plasma protein binding sites.

Storage Conditions

The drug should be stored in a place protected from light and moisture at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.