Lamictal

/ GSK

Adults and children over 12 years: Monotherapy: Initially 25 mg once a day for 2 weeks, followed by 50 mg once a day for 2 weeks. Increase by maximum of 50-100 mg every 1-2 weeks until optimum response. The usual maintenance dose is 100-200 mg daily given once or in 2 divided doses. Some patients have required 500 mg/day to achieve the desired response.
Add-on-therapy: In patients taking valproate with/without any other anti-epileptic drug (AED), the initial dose is 25 mg every alternate day for 2 weeks, followed by 25 mg once a day for 2 weeks. Thereafter the dose should be increased by a maximum of 25-50 mg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100-200 mg/day given once a day or in 2 divided doses. In those patients taking enzyme inducing AED’s with/without other AED’s (except valproate), the initial dose is 50 mg once a day for 2 weeks, followed by 100 mg/day given in 2 divided doses for 2 weeks. The dose should be increased by a maximum of 100 mg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 200-400 mg/day in 2 divided doses. Some patients have required 700 mg/day to achieve the desired response. In patients taking AED.
Children aged 2-12 years: In patients taking valproate with/without any other AED, the initial lamotrigine dose is 0.15 mg/kg bodyweight/day given once a day for two weeks, followed by 0.3 mg/kg/day once a day for two weeks. Thereafter, the dose should be increased by a maximum of 0.3 mg/kg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1-5 mg/kg/day given once a day or in two divided doses, with a maximum of 200 mg/day.
In those patients taking concomitant AEDs or other medications that induce lamotrigine glucuronidation with/without other AEDs (except valproate), the initial lamotrigine dose is 0.6 mg/kg bodyweight/day given in two divided doses for two weeks, followed by 1.2 mg/kg/day for two weeks. Thereafter, the dose should be increased by a maximum of 1.2 mg/kg every 1-2 weeks until the optimal response is achieved.  The usual maintenance dose to achieve optimal response is 5-15 mg/kg/day given in two divided doses, with a maximum of 400 mg/day.
In patients taking other medications that do not significantly inhibit or induce lamotrigine glucuronidation, the initial lamotrigine dose is 0.3 mg/kg bodyweight/day given once a day or in two divided doses for two weeks, followed by 0.6 mg/kg/day given once a day or in two divided doses for two weeks. Thereafter, the dose should be increased by a maximum of 0.6 mg/kg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1 to 10 mg/kg/day given once a day or in two divided doses, with a maximum of 200 mg/day. To ensure a therapeutic dose is maintained the weight of a child must be monitored and the dose reviewed as weight changes occur.
For full details see prescribing information.

Monotherapy: in adults and children over 12 years of age: Simple partial seizures, complex partial seizures, secondary generalized tonic-clonic seizures, primary generalized tonic-clonic seizures. Monotherapy in children under 12 years of age is not recommended.
Add-on-therapy: in adults and children over 2 years of age: Simple partial seizures, complex partial seizures, secondary generalized tonic-clonic seizures.

Lamotrigine is contra-indicated in individuals with known hypersensitivity to lamotrigine or any other ingredient of the product.

Lamotrigine is contra-indicated in individuals with known hypersensitivity to lamotrigine or any other ingredient of the product.
Skin Rash: here have been reports of adverse skin reactions, which have generally occurred mild within the first 8 weeks after initiation of lamotrigine treatment. The majority of rashes are mild and self limiting, however serious rashes requiring hospitalisation and discontinuation of lamotrigine have also been reported. These have included potentially life threatening rashes such as Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In adults enrolled in studies utilising the current lamotrigine dosing recommendations the incidence of serious skin rashes is approximately 1 in 500 in epilepsy patients. Approximately half of these cases have been reported as SJS (1 in 1000). In clinical trials with lamotrigine in patients with bipolar disorder, the incidence of serious rash is approximately 1 in 1000. The risk of serious skin rash in children is higher than in adults. Available data from a number of studies with lamotrigine suggest the incidence of rashes associated with hospitalisation in epileptic children is from 1 in 300 to 1 in 100. In children, the initial presentation of a rash can be mistaken for an infection. Physicians should consider the possibility of a drug reaction in children that develop symptoms of rash and fever during the first eight weeks of therapy. Additionally the overall risk of rash appears to be strongly associated with:
High initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine therapy. Concomitant use of valproate. Caution is also required when treating patients with a history of allergy or rash to other anti-epileptic drugs as the frequency of non-serious rash after treatment with lamotrigine was approximately three times higher in these patients than in those without such history. All patients (adults and children) who develop a rash should be promptly evaluated and lamotrigine withdrawn immediately unless the rash is clearly not drug related. It is recommended that lamotrigine not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk. Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema, abnormalities of the blood and liver and aseptic meningitis. The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation (DIC) and multi-organ failure. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs and symptoms are present the patient should be evaluated immediately and lamotrigine discontinued if an alternative aetiology cannot be established.
Aseptic meningitis was reversible on withdrawal of the drug in most cases, but recurred in a number of cases on re-exposure to lamotrigine. Re-exposure resulted in a rapid return of symptoms that were frequently more severe. Lamotrigine should not be restarted in patients who have discontinued due to aseptic meningitis associated with prior treatment of lamotrigine.
Suicide risk: Symptoms of depression and /or bipolar disorder may occur in patients with epilepsy, and there is evidence that patients with epilepsy and bipolar disorder have an elevated risk for suicidality. Twenty-five to 50% of patients with bipolar disorder attempt suicide at least once, and may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking medications for bipolar disorder, including lamotrigine Suicidal ideation and behaviour have been reported in patients treated with AEDs in several indications, including epilepsy and bipolar disorder. A meta-analysis of randomised placebo-controlled trials of AEDs (including lamotrigine) has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for lamotrigine. Therefore patients should be monitored for signs of suicidal ideation and behaviours. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. For full details see prescribing information.

The undesirable effects have been divided into epilepsy and bipolar specific sections based on the data currently available. However, both sections should be consulted when considering the overall safety profile of lamotrigine. Adverse reactions identified through post-marketing surveillance are included in the Epilepsy section. The following convention has been utilised for the classification of undesirable effects:- Very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1000 to < 1/100); rare (> 1/10,000 to < 1/1000); very rare (< 1/10,000).
EPILEPSY
Skin and subcutaneous tissue disorders: Very common: Skin rash. Rare: Stevens-Johnson syndrome. Very rare: Toxic epidermal necrolysis.
In double-blind, add-on clinical trials in adults, skin rashes occurred in up to 10% of patients taking lamotrigine and in 5% of patients taking placebo. The skin rashes led to the withdrawal of lamotrigine treatment in 2% of patients. The rash, usually maculopapular in appearance, generally appears within eight weeks of starting treatment and resolves on withdrawal of lamotrigine.
Rarely, serious potentially life threatening skin rashes, including Stevens Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome) have been reported. Although the majority recover on drug withdrawal, some patients experience irreversible scarring and there have been rare cases of associated death. The overall risk of rash, appears to be strongly associated with:-
High initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine therapy.
Concomitant use of valproate. Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms.
For full details see prescribing information.

For full details see prescribing information.

Fertility: Administration of lamotrigine did not impair fertility in animal reproductive studies. There is no experience of the effect of lamotrigine on human fertility.
Pregnancy: Postmarketing data from several prospective pregnancy registries have documented outcomes in over 2000 women exposed to lamotrigine monotherapy during the first trimester of pregnancy. Overall, these data do not suggest a substantial increase in the risk for major congenital malformations, although data from a limited number of registries have reported an increase in the risk of isolated oral cleft malformations. A case control study did not demonstrate an increased risk of oral clefts compared to other defects following exposure to lamotrigine. The data on use of lamotrigine in polytherapy combinations are insufficient to assess whether the risk of malformation associated with other agents is affected by concomitant lamotrigine use. As with other medicines, lamotrigine should only be used during pregnancy if the expected benefits outweigh the potential risk. Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There have been reports of decreased lamotrigine levels during pregnancy. Appropriate clinical management of pregnant women during lamotrigine therapy should be ensured.
Lactation: Lamotrigine has been reported to pass into breast milk in highly variable concentrations, resulting in total lamotrigine levels in infants of up to approximately 50% of the mother’s. Therefore, in some breast-fed infants, serum concentrations of lamotrigine may reach levels at which pharmacological effects occur.The potential benefits of breast feeding should be weighed against the potential risk of adverse effects occurring in the infant.

Symptoms and signs: Acute ingestion of doses in excess of 10 – 20 times the maximum therapeutic dose, have been reported. Overdose has resulted in symptoms including nystagmus, ataxia, impaired consciousness and coma.
Treatment: In the event of overdose, the patient should be admitted to hospital and given appropriate supportive therapy as clinically indicated or as recommended by the national poisons centre, where available.