Lamictal
Pregnancy
Risk associated with antiepileptic drugs in general
Women capable of childbearing should consult with specialists.
If a woman is planning a pregnancy, the need for treatment with antiepileptic drugs should be reconsidered. In women undergoing treatment for epilepsy, sudden cessation of antiepileptic therapy should be avoided because this may lead to a recurrence of seizures, which can have serious consequences for the woman and the unborn child. In offspring of mothers treated with antiepileptic drugs, the risk of congenital malformations increases by 2-3 times compared with the expected incidence of about 3% in the general population. The most frequently recorded defects are cleft lip, heart and vascular defects, and neural tube developmental defects. Multiple therapy with antiepileptic drugs is associated with a higher risk of congenital malformations than monotherapy; therefore, monotherapy should be used whenever possible.
Risk associated with taking lamotrigine
Lamotrigine has a weak inhibitory effect on dihydrofolic acid reductase and therefore, theoretically, may lead to an increased risk of impaired embryonic and fetal development due to decreased folic acid levels. You should consider taking folic acid during pregnancy planning and in the early stages of pregnancy.
Post-marketing surveillance data from several prospective pregnancy registries documented the pregnancy outcomes of approximately 8,700 women receiving monotherapy with the drug in the first trimester of pregnancy. Overall, the findings do not support a general increase in the risk of congenital malformations. Although there are reports from a limited number of pregnancy registries of an increased risk of oral malformations, a completed case-control study did not show an increased risk of oral malformations compared with other major malformations following lamotrigine use.
There are insufficient data from the use of the drug in combination therapy to assess whether the risk of malformations is associated with other drugs used in combination with lamotrigine.
Just like other drugs, the drug should be prescribed during pregnancy only if the expected therapeutic benefit outweighs the potential risk.
Physiological changes during pregnancy may affect lamotrigine levels and/or its therapeutic effect. There have been reports of decreased lamotrigine plasma levels during pregnancy with a possible risk of loss of seizure control. After delivery, lamotrigine levels may increase rapidly with a risk of dose-related adverse reactions. Therefore, lamotrigine serum levels should be monitored before, during and after pregnancy, as well as immediately after delivery. If necessary, adjust the dose to maintain lamotrigine serum levels at the same level as before pregnancy, or adjust the dose based on clinical response. In addition, dose-related adverse reactions should be monitored after delivery.
Breastfeeding period
Lamotrigine is excreted into breast milk to varying degrees; total lamotrigine concentrations in breastfed infants may be approximately 50% of the lamotrigine concentrations reported in the mother. Therefore, in some breastfed infants, serum concentrations of lamotrigine may reach levels at which pharmacological effects occur.
It is necessary to balance the potential benefits of breastfeeding with the potential risk of adverse reactions in the child.
If a woman taking the drug decides to breastfeed, the baby should be monitored for any adverse reactions.
Fertility
Animal reproductive studies with lamotrigine have not shown any impairment of fertility.
No studies have been conducted on the effects of lamotrigine on human fertility.
Release form and composition
Lamictal is available in the following forms:
- Tablets: with rounded corners, square, yellowish-brown, light (10 pieces in blisters, 3 blisters in a cardboard pack);
- Soluble/chewable tablets: elongated, biconvex (at a dose of 5 mg) or square with rounded corners (at a dose of 25 and 100 mg), white or almost white, sometimes with small inclusions, with the aroma of black currant (10 pieces in blisters, 3 blisters in a cardboard box).
The active ingredient is lamotrigine (25, 50 or 100 mg tablets and 5, 25 or 100 mg chewable tablets).
Auxiliary components:
- Tablets: microcrystalline cellulose, lactose monohydrate, magnesium stearate, povidone, sodium starch glycolate type A, yellow iron oxide E172;
- Chewable tablets: low-substituted hydroxypropylcellulose, sodium starch glycolate type A, calcium carbonate, sodium saccharin, magnesium stearate, povidone K30, aluminum magnesium silicate, blackcurrant flavor.
Indications for use
Lamictal is prescribed to adults and children over 12 years of age as part of combination treatment or as monotherapy for epilepsy (generalized and partial seizures).
In children 3-12 years old, the drug is used for epilepsy as part of a combination treatment (when control of epilepsy is achieved, concomitant antiepileptic drugs can be discontinued, and Lamictal is continued in monotherapy), and as monotherapy for short primary generalized epileptic seizures (typical absence seizures).
In patients with bipolar affective disorder aged 18 years and older, lamotrigine is used to prevent mood disorders (mania, hypomania, depression, mixed episodes).
Overdose
There is information about a single use of doses of Lamictal that exceeded the maximum permissible by 10-20 times, while the symptoms of overdose were: ataxia , nystagmus , impaired consciousness coma is also possible .
If an overdose is detected, it is necessary to hospitalize the patient and prescribe supportive treatment according to the general condition or recommendations of the toxicological service.
Side effects
When using Lamictal, the following side effects from systems and organs are possible:
- Digestive system: often – vomiting, nausea, diarrhea; rarely - impaired liver function, increased liver function tests, liver failure;
- Musculoskeletal system: often – low back pain, arthralgia; rarely – lupus-like syndrome;
- Skin and subcutaneous tissue: often – rash (usually maculopapular in nature); rarely - Lyell's syndrome, exudative erythema multiforme;
- Immune system: rarely - hypersensitivity, manifested by fever, facial swelling, lymphadenopathy, hematological disorders, liver damage, multiple organ failure, disseminated intravascular coagulation (DIC);
- Hematopoietic and lymphatic system: rarely - leukopenia, thrombocytopenia, aplastic anemia, neutropenia, anemia, pancytopenia, agranulocytosis;
- Central nervous system: often - headache, anxiety, irritability, dizziness, fatigue, insomnia, drowsiness, ataxia, tremor, nystagmus, imbalance; sometimes – aggressiveness; rarely - agitation, confusion, hallucinations, tics, motor and extrapyramidal disorders, imbalance, increased frequency of seizures, choreoathetosis;
- Sense organs: often – blurred vision, diplopia, conjunctivitis;
- Other: withdrawal syndrome due to abrupt cessation of taking Lamictal (increased seizures).
Reviews of Lamictal
Reviews about Lamictal are very varied and do not provide a clear positive or negative answer about the effectiveness and safety of its use. The thing is that the diseases for which lamotrigine require individual selection of both the drugs themselves and their dosages.
Those people who are suitable for this drug speak of Lamictal as a fairly effective drug. The most common side effect is skin rash
Drug interactions
Paracetamol and antiepileptic drugs (carbamazepine, primidone, phenytoin, phenobarbital) accelerate the metabolism of Lamictal and shorten its half-life by 2 times.
Valproate slows the metabolism of lamotrigine and increases its half-life to 45-55 hours in children and up to 70 hours in adults.
With the simultaneous use of carbamazepine and lamotrigine, diplopia, ataxia, nausea, dizziness and blurred vision are possible, which disappear when the dose of carbamazepine is reduced.
When Lamictal (100 mg per day) is added to treatment with anhydrous lithium gluconate (2 g twice daily for 6 days), the pharmacokinetics of lithium do not change.
Bupropion, repeated after a single dose, does not have a significant effect on the pharmacokinetics of the drug.
Pharmacodynamics and pharmacokinetics
The mechanism of action of Lamictal is to block voltage-gated sodium channels , stabilize neuronal membranes and inhibit the release of glutamic acid , which plays a primary role in the formation of epileptic seizures .
Absorption of lamotrigine from the intestine is complete and fairly rapid. Plasma Cmax occurs approximately 2.5 hours after oral administration. Tmax increases slightly with food intake, although the level of absorption does not change.
An internal dose of up to 450 mg is characterized by linear pharmacokinetics.
The registered connection with plasma proteins is about 55%, with a volume of distribution of 0.92–1.22 l/kg.
Metabolic transformations of lamotrigine take place with the participation of the enzyme glucuronyl transferase . The pharmacokinetics of other antiepileptic drugs are not affected by lamotrigine .
The clearance of lamotrigine in adults averages 39±14 ml/min.
Metabolism continues to glucuronides , which are excreted from the body in the urine. Less than 10% of the drug is also excreted unchanged in the urine, approximately 2% in the feces. T1/2 and clearance of the drug do not depend on the oral dose taken.
The clearance of lamotrigine , in relation to body weight, is higher in childhood, especially in patients under 5 years of age. Also, in children, compared to adults, T1/2 is usually shorter.
There is evidence that confirms the absence of significant differences in creatinine in elderly and young patients.
The average clearance coefficient of lamotrigine when taken by patients with chronic kidney failure (CKD) and patients on hemodialysis is 0.42 ml/min/kg (with chronic kidney disease), 0.33 ml/min/kg (when taken between hemodialysis sessions ) and 1.57 ml/min/kg (during hemodialysis ). In proportion to this, the average T1/2 is observed at 42.9/57.4/13 hours.
Over the course of 4 hours of hemodialysis, approximately 20% of lamotrigine . In this regard, for kidney pathologies, the initial dosage of lamotrigine is calculated according to the standard regimen for the use of antiepileptic drugs. serious pathologies of kidney function
The average clearance coefficient of lamotrigine when taken by patients with mild, moderate and severe hepatic (Child-Pugh stages A, B and C), respectively, is 0.31/0.24/0.1 ml/min/kg.
Initial, escalating, and maintenance dosages should be reduced by approximately 50% for moderate liver failure (stage B) and by approximately 75% for severe liver failure (stage C). In the future, initial and increasing doses of the drug must be adjusted according to the observed clinical effect.
