Lamitor 25 mg, 50 mg , 100 mg, 200 mg Tablets

Adults and children over 12 years

LAMITOR is indicated as monotherapy or add-on treatment of partial epilepsy with or without secondary generalised tonic-clonic seizures and in primary generalised tonic-clonic seizures.

Children 2 to 12 years

LAMITOR is indicated as add-on treatment of partial epilepsy with or without secondary generalised tonic-clonic seizures not satisfactorily controlled with other antiepileptic medicines. Monotherapy in children under 12 years of age is not recommended until such time as adequate information is made available from controlled trials in this particular target population.

Lennox-Gastaut Syndrome

LAMITOR is indicated as add-on treatment for seizures associated with Lennox-Gastaut Syndrome.

It is important to adhere to the recommended dosages especially in combination therapy with valproate where one-tenth of the normal dose is used. Do not exceed the maximum dosage (see WARNINGS). To ensure a therapeutic dose is maintained the weight of a child must be monitored and the dose reviewed if necessary. If the doses calculated for children according to bodyweight, do not equate to whole tablets, the dose to be administered is that equal to the lower number of whole tablets.

Dosage in monotherapy:

Adults and children over 12 years of age

Initial dose in monotherapy: 25 mg once daily for two weeks, followed by 50 mg once daily for two weeks. The dosage may be increased by a maximum of 50 u2013 100 mg every 1 to 2 weeks until the optimal response is achieved.

Maintenance dose in monotherapy: The usual dose to achieve optimal response is 100 u2013 200 mg per day given in one dose or two divided doses. Some patients have required 500 mg/day of LAMITOR to achieve the desired response.

Adults and Children over 12 years (total daily dose)

Weeks 1 & 2: 25 mg (once daily)

Weeks 3 & 4: 50 mg (once daily)

Maintenance Dose: 100 u2013 200 mg (once a day or two divided doses). To achieve maintenance, doses may be increased by 50 u2013 100 mg every 1 u2013 2 weeks.

The recommended initial dose and subsequent dose escalation should not be exceeded to minimise the risk of skin rash (see WARNINGS).

Dosage in add-on therapy:

Adults and children over 12 years of age

The initial LAMITOR dose in those patients not taking sodium valproate: The initial dose is 50 mg once a day for two weeks, then 100 mg a day, divided into two doses, for two weeks. The dosage may be increased by a maximum of 100 mg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose is 200 u2013 400 mg/day given in two divided doses.

In those patients taking sodium valproate: The initial dose is 25 mg once every other day for two weeks, then 25 mg once a day for two weeks. The dosage may be increased by a maximum of 25 u2013 50 mg a day every 1 or 2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100 u2013 200 mg/day given once a day or in two divided doses.

Children aged 2 to 12 years

The initial LAMITOR dose in those children not taking sodium valproate: The initial dose is 0,6 mg/kg body-weight daily given in two divided doses for two weeks, followed by 1,2 mg/kg daily in 2 divided doses for two weeks. Thereafter, the dose should be increased by a maximum of 1,2 mg/kg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose is 5 u2013 15 mg/kg/day given in two divided doses. A maximum daily dose of 400 mg must not be exceeded.

In those children taking sodium valproate: The initial dose of 0,15 mg/kg once daily for two weeks, followed by 0,3 mg/kg once daily for two weeks. Thereafter the dose is increased by a maximum of 0,3 mg/kg every 1 to 2 weeks until the optimal response is achieved. The usual maintenance dose is 1 u2013 5 mg/kg, which may be given once a day or in two divided doses. A maximum daily dose of 200 mg must not be exceeded.

LAMITOR is contraindicated in the following circumstances:

• Individuals with known hypersensitivity to lamotrigine.
• The safety of LAMITOR in pregnancy and lactation has not been established.
• Renal and hepatic function impairment. Hepatic metabolism followed by renal excretion is the principal route of elimination of lamotrigine and until more information is available, the use of LAMITOR in patients with impairment of hepatic or renal function is contraindicated.
• Patients over the age of 65 years.

Severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multiorgan dysfunction and disseminated intravascular coagulation, usually with fatal outcome. Similar cases have occurred in association with the use of LAMITOR. Patients receiving LAMITOR should be closely monitored and changes in hepatic, renal and clotting parameters looked for. Patients should be warned to consult their doctors immediately if rashes or flu-like symptoms associated with hypersensitivity develop, especially within the first month of starting treatment with LAMITOR. Withdrawal of LAMITOR therapy should be considered if unexplained rashes, fever, flu-like symptoms, drowsiness or worsening of seizure control occur. Dosage recommendations should not be exceeded to minimise the risk of developing rash requiring withdrawal of therapy. Abrupt withdrawal of LAMITOR may provoke rebound seizures. The risk may be reduced by tapering the withdrawal of LAMITOR over a period of two weeks.

The weight of a child must be monitored and the dose reviewed as weight changes occur. If the doses calculated for children, according to bodyweight, do not equate to whole tablets, the dose to be administered is that equal to the lower number of whole tablets.

Skin Reactions

Adverse skin reactions have been reported, which have generally occurred within the first 8 weeks of starting LAMITOR. Although the majority of rashes usually resolve when LAMITOR is discontinued, irreversible scarring and cases of associated death have been reported. A mild rash may subside even with continuation of LAMITOR therapy; however, close monitoring is essential. Less frequently, serious and potentially life-threatening skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported especially in children and in patients using valproate (see SIDE-EFFECTS AND SPECIAL PRECAUTIONS). Isolated cases have been reported after prolonged treatment (6 months).

The estimated incidence of serious skin rashes in adults is 1 in 1 000. The risk is higher in children than in adults. Some children may require hospitalisation because of the seriousness of skin rashes.

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.

The overall risk of rash appears to be strongly associated with:

• High initial doses of LAMITOR and exceeding the recommended dose escalation of LAMITOR (see DOSAGE AND DIRECTIONS FOR USE).
• Concomitant use of valproate, which increases the mean half-life of LAMITOR nearly two-fold (see DOSAGE AND DIRECTIONS FOR USE).

As it cannot be predicted reliably which rashes will prove to be life-threatening, all patients (adults and children) who develop a rash should be promptly evaluated and LAMITOR withdrawn immediately unless the rash is clearly not drug related. Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, pruritus, facial oedema, abnormalities of the blood and liver and thrombocytopenia. The syndrome shows a wide spectrum of clinical severity and may lead to disseminated intravascular coagulation and multiorgan failure. It is important 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 LAMITOR therapy discontinued if an alternative aetiology cannot be immediately established.

Enzyme-inducing agents (such as phenytoin, carbamazepine, phenobarbitone and primidone) enhance the metabolism of LAMITOR leading to an increased clearance and subsequent reduction of the elimination half-life of LAMITOR. Concomitant use of valproic acid increases the half-life and plasma concentrations of LAMITOR due to competition for hepatic glucuronidation. Plasma concentrations of valproic acid may decrease slightly when LAMITOR is added.

No evidence was shown that LAMITOR affects the plasma concentration of concomitant antiepileptic drugs. LAMITOR does not displace other antiepileptic drugs from protein binding sites.

There is no evidence that LAMITOR causes clinically significant induction or inhibition of hepatic oxidative drug-metabolising enzymes. LAMITOR may induce its own metabolism but the effect is modest and unlikely to have significant clinical consequences. LAMITOR does not seem to affect plasma concentrations of ethinyloestradiol and levonorgestrel following the administration of the oral contraceptive pill. However, as with the introduction of other chronic therapy in patients taking oral contraceptives, any change in the menstrual bleeding pattern should be reported to the patientu2019s physician.

The safety of LAMITOR in pregnancy and lactation has not been established.

Not provided in the text.

Very common (> 1/10), Common (> 1/100 and u2264 1/10), Uncommon (> 1/1000 and u2264 1/100), Rare (> 1/10 000 and u2264 1/1000), Very rare (u2264 1/10 000)

Blood and lymphatic system disorders

Very rare: Blood dyscrasias including anaemia, eosinophilia, leucopenia or thrombocytopenia

Immune system disorder

Very rare: Hypersensitivity syndrome. Symptoms such as fever, malaise, influenza-like symptoms, drowsiness, lymphadenopathy, facial oedema and rarely, hepatic dysfunction, leucopenia and thrombocytopenia have been reported in conjunction with rashes as part of a hypersensitivity syndrome (see WARNINGS).

Skin and subcutaneous tissue disorders

Very common: Skin rash

Rare: Stevens-Johnson Syndrome, photosensitivity

Very rare: Toxic epidermal necrolysis

Severe skin rashes, including Stevens-Johnson Syndrome have been reported, especially in children. The skin rash usually occurs within 8 weeks of starting LAMITOR and resolves on withdrawal of LAMITOR (see WARNINGS).

Nervous system disorders

Very common: Headache

Common: Tiredness, insomnia, drowsiness, dizziness, anxiety, confusion, depression, irritability, nystagmus, tremor and ataxia

Uncommon: Increased seizures, coordination abnormalities

Eye disorders

Very common: Vision abnormalities, including blurred vision, diplopia

Respiratory, thoracic and mediastinal disorders

Rare: Angio-oedema (trouble in breathing, swelling of face, mouth, hands or feet)

Gastrointestinal disorders

Common: Nausea and vomiting

Symptoms and signs

Acute ingestion of doses in excess of 10 u2013 20 times the maximum therapeutic doses has been reported. Overdose has resulted in symptoms including nystagmus, ataxia, impaired consciousness and coma.

Treatment

In the event of overdosage, the patient should be admitted to hospital and given appropriate supportive therapy. Gastric lavage should be performed if indicated.