Lamictin Range 2mg. 5mg. 25mg. 50mg. 100mg. 200mg Tablet

EPILEPSY: Adults and adolescents (over 12 years of age): LAMICTIN 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: LAMICTIN 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: LAMICTIN is indicated as add-on treatment for seizures associated with Lennox-Gastaut syndrome. BIPOLAR DISORDER (Adults 18 years of age and over): LAMICTIN is indicated for the prevention of mood episodes in patients with bipolar disorder, predominantly by preventing depressive episodes.

It is important to adhere to the recommended dosages especially in combination therapy with valproate where one-tenth to one-fifth of the normal dose is used. Do not exceed the maximum dosage (see section 4.4). General Dosing Recommendations: Administration: LAMICTIN Dispersible Tablets should be dispersed in a small volume of water (at least enough to cover the whole tablet). The tablets may also be chewed, or swallowed whole with a little water, if preferred.

If a calculated dose of LAMICTIN (e.g. for use in children and patients with hepatic impairment) does not equate to whole tablets, the dose to be administered should be equal to the lower number of whole tablets. Restarting Therapy: Prescribers should assess the need for escalation to maintenance dose when restarting LAMICTIN in patients who have discontinued LAMICTIN for any reason, since the risk of serious rash is associated with high initial doses and exceeding the recommended dose escalation for LAMICTIN (see section 4.4). The greater the interval of time since the previous dose, the more consideration should be given to escalation to the maintenance dose. When the interval since discontinuing LAMICTIN exceeds five half-lives (see section 5.2), LAMICTIN should generally be escalated to the maintenance dose according to the appropriate schedule. It is recommended that LAMICTIN not be restarted in patients who have discontinued due to rash associated with prior treatment with LAMICTIN.

EPILEPSY: When concomitant antiepileptic medicines are withdrawn to achieve LAMICTIN monotherapy or other AEDs/medicines are added-on to treatment regimes containing LAMICTIN, consideration should be given to the effect this may have on lamotrigine pharmacokinetics (see section 4.5). To ensure a therapeutic dose is maintained, the weight of a child must be monitored, and the dose reviewed as weight changes occur. If a calculated dose of LAMICTIN (e.g. for use in children and patients with hepatic impairment) does not equate to whole tablets the dose to be administered should be equal to the lower number of whole tablets.

Dosage in epilepsy monotherapy: Adults and adolescents (over 12 years of age): The initial dose in monotherapy is 25 mg once a day for 2 weeks, followed by 50 mg once a day for 2 weeks. Thereafter, the dose should be increased by a maximum of 50 mg - 100 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 as two divided doses. Some patients have required 500 mg/day of LAMICTIN to achieve the desired response.

Dosage in epilepsy add-on therapy: Adults and adolescents (over 12 years of age): In those patients taking concomitant antiepileptic drugs (AEDs) or other medications (see section 4.5) that induce lamotrigine glucuronidation with/without other AEDs (except valproate), the initial LAMICTIN dose is 50 mg once a day for 2 weeks, followed by 100 mg/day given in two divided doses for 2 weeks. Thereafter, 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 given in two divided doses. In those patients taking sodium valproate with/without any other AED, the initial LAMICTIN dose is 25 mg every alternate day for two weeks, followed by 25 mg once a day for two 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 two divided doses.

In those patients taking oxcarbazepine 1 200 mg daily, without any other inducers or inhibitors of lamotrigine glucuronidation, the initial LAMICTIN dose is 25 mg once a day for 2 weeks, followed by 50 mg once a day for 2 weeks. Thereafter, the dose should be increased by a maximum of 50 - 100 mg every 1 - 2 weeks until optimal response is achieved, or a dose of 200 mg is reached. The usual maintenance dose to achieve an optimal response is 100 - 200 mg/day given once a day or as two divided doses.

Table 1: Recommended treatment regimen for adults and adolescents over 12 years of age Treatment regimen Weeks 1 + 2 Weeks 3 + 4 Maintenance Dose Monotherapy 25 mg (once a day) 50 mg (once a day) 100 - 200 mg (once a day or two divided doses) To achieve maintenance, doses may be increased by 50 - 100 mg every 1 - 2 weeks Treatment regimen Weeks 1 + 2 Weeks 3 + 4 Maintenance Dose Add-on therapy with valproate regardless of any concomitant medications 12,5 mg (given as 25 mg alternate on days) 25 mg (once a day) 100 - 200 mg (once a day or two divided doses) To achieve maintenance, doses may be increased by 25 - 50 mg every 1 - 2 weeks Add-on therapy without valproate This dosage regimen should be used with: Phenytoin, Carbamazepine, Phenobarbitone, Primidone, or with other inducers of lamotrigine glucuronidation (see section 4.5). 50 mg (once a day) 100 mg (two divided doses) 200 - 400 mg (two divided doses) To achieve maintenance, doses may be increased by 100 mg every 1 - 2 weeks With oxcarbazepine without inducers or inhibitors of lamotrigine glucuronidation 25 mg (once a day) 50 mg (once a day) 100 - 200 mg (once a day or two divided doses) To achieve maintenance, doses may be increased by 50 - 100 mg every 1 - 2 weeks In patients taking AEDs where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for LAMICTIN with concurrent valproate should be used. The recommended initial dose and subsequent dose escalation should not be exceeded to minimise the risk of skin rash (see section 4.4).

Children aged 2 to 12 years: To ensure a therapeutic dose is maintained 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 should be equal to the lower number of whole tablets. In those patients taking concomitant AEDs or other medications (see section 4.5) that induce lamotrigine glucorindation with/without other AEDs (except valproate), the initial LAMICTIN dose is 0,6 mg/kg bodymass/day given in two divided doses for 2 weeks, followed by 1,2 mg/kg/day for 2 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 once a day or in two divided doses. A maximum daily dose of 400 mg must not be exceeded.

In those patients taking sodium valproate with/without any other AED, the initial LAMICTIN dose is 0,15 mg/kg bodymass/day given once a day for 2 weeks, followed by 0,3 mg/kg/day given once a day for 2 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. A maximum daily dose of 200 mg must not be exceeded.

In patients taking oxcarbazepine without any inducers or inhibitors of lamotrigine glucuronidation, the initial lamotrigine dose is 0,3 mg/kg bodyweight/day given once a day or in two divided doses for 2 weeks, followed by 0,6 mg/kg/day given once a day or in two divided doses for 2 weeks. Thereafter, the dose should be increased by a maximum of 0,6 mg/kg every 1 - 2 weeks until an optimal response is achieved, or dose of 200 mg is reached. The usual maintenance dose to achieve optimal response is 1 - 10 mg/kg/day given once a day or in two divided doses, with a maximum of 200 mg/day.

Table 2: Recommended treatment regimen for children aged 2 - 12 years (total daily dose in mg/kg bodyweight/day) Treatment regimen Weeks 1 + 2 Weeks 3 + 4 Maintenance Dose Add-on therapy with valproate regardless of any other concomitant medication 0,15 mg/kg* (once a day) 0,3 mg/kg (once a day) 0,3 mg/kg increments every 1 - 2 weeks to achieve a maintenance dose of 1 - 5 mg/kg (once a day or two divided doses) to a maximum of 200 mg/day. Add-on therapy without valproate This dosage regimen should be used with: Phenytoin, Carbamazepine, Phenobarbitone, Primidone, or with other inducers of lamotrigine glucuronidation (see section 4.5). 0,6 mg/kg (two divided doses) 1,2 mg/kg (two divided doses) 1,2 mg/kg increments every 1 - 2 weeks to achieve a maintenance dose of 5 - 15 mg/kg (once a day or two divided doses) to a maximum of 400 mg/day. With oxcarbazepine without inducers or inhibitors of lamotrigine glucuronidation 0,3 mg/kg (one or two divided doses) 0,6 mg/kg (one or two divided doses) 0,6 mg/kg increments every one to two weeks to achieve a maintenance dose of 1 - 10 mg/kg (once a day or two divided doses) to a maximum of 200 mg/day. In patients taking AEDs where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for LAMICTIN with concurrent valproate should be used.

** If the calculated daily dose in patients taking valproate is 1 - 2 mg, then 2 mg LAMICTIN may be taken on alternate days for the first two weeks. If the calculated daily dose is less than 1 mg, then LAMICTIN should not be administered. DO NOT attempt to give partial quantities of the LAMICTIN dispersible tablets. ** If the calculated dose of LAMICTIN cannot be achieved using whole tablets, the dose should be rounded down to the nearest whole tablet. The recommended initial dose and subsequent dose escalation should not be exceeded to minimise the risk of skin rash (see section 4.4). Patients aged 2 - 6 years may require a maintenance dose at the higher end of the recommended range. Dosage in seizures associated with Lennox-Gastaut syndrome: The doses used for seizures associated with Lennox-Gastaut syndrome correspond to the dosing guidelines outlined above for both adults and children aged 2 - 12 years. Children aged less than 2 years: LAMICTIN has not been studied as monotherapy in children less than 2 years of age or as add-on therapy in children less than 1 month of age. The safety and efficacy of LAMICTIN as add-on therapy of partial seizures in children aged 1 month to 2 years has not been established. Therefore, LAMICTIN is not recommended in children less than 2 years of age. BIPOLAR DISORDER: Because of the risk of rash, the initial dose and subsequent dose escalation should not be exceeded (see section 4.4). The following transition regimen should be followed. The transition regimen involves escalating the dose of LAMICTIN to a maintenance stabilisation dose over six weeks (see Table 3) after which other psychotropic and/or anti-epileptic medicines can be withdrawn, if clinically indicated (see Table 4).

LAMICTIN is contraindicated in individuals with known hypersensitivity to lamotrigine.

Severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multi-organ dysfunction and disseminated intravascular coagulation, usually with fatal outcome. Similar cases have occurred in association with the use of LAMICTIN. It is recommended that the medical practitioner closely monitor patients (including hepatic, renal and clotting parameters) who acutely develop any combination of unexplained rash, fever, flu-like symptoms, drowsiness or worsening of seizure control, especially within the first month of starting treatment with LAMICTIN. Exceeding the recommended dose at the initiation of LAMICTIN therapy may be associated with an increased incidence of rash requiring withdrawal of therapy. Abrupt withdrawal of lamotrigine may provoke rebound seizures, in patients with epilepsy. Unless safety concerns (e.g. rash) require an abrupt withdrawal, the dose of LAMICTIN should be gradually decreased over a period of 2 weeks. To ensure that a therapeutic dose is maintained in children, 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 should be equal to the lower number of whole tablets (see section 4.2).

Skin Reactions: There have been reports of adverse skin reactions, which have predominantly occurred within the first 8 weeks after initiation of LAMICTIN treatment. The majority of rashes are mild and self-limiting; however serious, potentially life-threatening skin rashes including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis have been reported especially in children and in patients (adults and children) who also used valproate (see section 4.8). Cases have however been reported after prolonged treatment (6 months). Skin reactions in all clinical studies occurred in adults in approximately 10% and in children 17%. In patients on concomitant valproate, skin reactions occurred in 21% of adults and in 34% of children, of whom 12% and 17% respectively withdrew from treatment. Although the majority recover on withdrawal of LAMICTIN, some patients experience irreversible scarring and there have been cases of associated death. In adults enrolled in studies utilising the current LAMICTIN 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). The risk of serious skin rashes in children is higher than in adults. Available data suggest the incidence of rashes which needed hospitalisation in children is from 1 in 300 to 1 in 100. In clinical trials with LAMICTIN in patients with bipolar disorder, the incidence of serious rash is approximately 1 in 1000. In children, the initial presentation of a rash can be mistaken for an infection; medical practitioners should consider the possibility of a 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 LAMICTIN and exceeding the recommended dose escalation of LAMICTIN (see section 4.2).
• Concomitant use of valproate, which increases the mean half-life of LAMICTIN nearly two-fold (see section 5.2 and 4.2).

Caution is also required when treating patients with a history of allergy or rash to other anti-epileptic medicines, as the frequency of non-serious rash after treatment with LAMICTIN was approximately three times higher in these patients than in those without such history. 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 LAMICTIN withdrawn immediately unless the rash is clearly not related to LAMICTIN treatment. It is recommended that LAMICTIN not be restarted in patients who have discontinued due to rash associated with prior treatment with LAMICTIN. Rash has also been reported as part of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); also known as hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, pruritis, facial oedema, abnormalities of the blood, liver, and kidney aseptic meningitis and thrombocytopenia. The syndrome shows a wide spectrum of clinical severity and may lead to disseminated intravascular coagulation 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 LAMICTIN discontinued if an alternative aetiology cannot be immediately established. Aseptic meningitis was reversible on withdrawal of the LAMICTIN in most cases but recurred in a number of cases on re-exposure to LAMICTIN. Re-exposure resulted in a rapid return of symptoms that were frequently more severe. LAMICTIN should not be restarted in patients who have discontinued due to aseptic meningitis associated with treatment of LAMICTIN.

Haemophagocytic lymphohistiocytosis (HLH): HLH has occurred in patients taking LAMICTIN (see section 4.8). HLH is a syndrome of pathological immune activation, which can be life threatening, characterised by clinical signs and symptoms such as fever, rash, neurological symptoms, hepatosplenomegaly, lymphadenopathy, cytopenias, high serum ferritin, hypertriglyceridaemia and abnormalities of liver function and coagulation. Symptoms occur generally within 4 weeks of treatment initiation. Immediately evaluate patients who develop these signs and symptoms and consider a diagnosis of HLH. LAMICTIN should be discontinued unless an alternative aetiology can be established.

Clinical worsening and suicide risk: There is evidence that patients with bipolar disorder and with epilepsy, have an elevated risk for suicidality. This risk may continue during treatment. Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic medicines (AEDs), including LAMICTIN in several indications, including epilepsy and bipolar disorder. A meta-analysis of randomised placebo-controlled trials of AEDs (including LAMICTIN) has also shown an increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known. 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. Patients receiving LAMICTIN for bipolar disorder should be closely monitored for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes. Certain patients, such as those with a history of suicidal behaviour or thoughts, young adults, and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, may be at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. Patients (and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing LAMICTIN, in patients who experience clinical worsening (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour, especially if these symptoms are severe, abrupt in onset, or were not part of the patientu2019s presenting symptoms.

Uridine 5u2019 - diphospho (UDP) - glucuronyl transferases (UGTs) have been identified as the enzymes responsible for metabolism of lamotrigine. Medicines that induce or inhibit glucuronidation may, therefore, affect the apparent clearance of lamotrigine. Strong or moderate inducers of the cytochrome P450 3A4 (CYP3A4) enzyme, which are also known to induce UGTs, may also enhance the metabolism of lamotrigine. There is no evidence that lamotrigine causes clinically significant induction or inhibition of cytochrome P450 enzymes. Lamotrigine may induce its own metabolism, but the effect is modest and unlikely to have significant clinical consequences. Those medicines that have been demonstrated to have a clinically relevant impact on lamotrigine concentration are outlined in Table below. Specific dosing guidance for these medicines is provided in section 4.2. In addition, this table lists those medicines which have been shown to have little or no effect on the concentration of lamotrigine. Coadministration of such medicines would generally not be expected to result in any clinical impact. However, consideration should be given to patients whose epilepsy is especially sensitive to fluctuations in concentrations of lamotrigine.

Effects of medicines on the concentration of lamotrigine): Medicines that increase the concentration of lamotrigine (doubling of lamotrigine half-life) Medicines that decrease the concentration of lamotrigine (halving lamotrigine half-life) Medicines have little or no that effect on the concentration of lamotrigine Valproate Atazanavir/ritonavir* Carbamazepine Aripiprazole Ethinyloestradiol/levonorgestrel combination ** Bupropion Phenytoin Felbamate Phenobarbitone Phenytoin Primidone Gabapentin Oxcarbazepine Rifampicin Lacosamide Levetiracetam Lithium Olanzapine Oxcarbazepine Paracetamol Perampanel Topiramate

Pregnancy: Safety of LAMICTIN in pregnancy and lactation has not been established. Use during pregnancy: There is some evidence of an increased risk of oral cleft malformations following exposure to LAMICTIN in pregnancy. The decision to use LAMICTIN during pregnancy should be taken by the physician following assessment of the benefit/risk profile. A large amount of data on pregnant women exposed to LAMICTIN monotherapy during the first trimester of pregnancy (more than 8700) do not suggest a substantial increase in the risk for major congenital malformations, including oral clefts. Animal studies have shown developmental toxicity (see section 5.3). If therapy with LAMICTIN is considered necessary during pregnancy, the lowest possible therapeutic dose is recommended. Lamotrigine has a slight inhibitory effect on dihydrofolic acid reductase and could therefore theoretically lead to an increased risk of embryofoetal damage by reducing folic acid levels. Intake of folic acid when planning pregnancy and during early pregnancy may be considered. Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There have been reports of decreased lamotrigine plasma levels during pregnancy with a potential risk of loss of seizure control. After birth, lamotrigine levels may increase rapidly with a risk of dose-related adverse events. Therefore, lamotrigine serum concentrations should be monitored before, during and after pregnancy, as well as shortly after birth. If necessary, the dose should be adapted to maintain the lamotrigine serum concentration at the same level as before pregnancy or adapted according to clinical response. In addition, dose-related undesirable effects should be monitored after birth.

Breastfeeding: The decision to breastfeed should be taken in by the mother in consultation with the physician. The potential benefits of breastfeeding should be weighed against the potential risk of adverse effects occurring in the infant. 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 mothersu2019.

In clinical trials with LAMICTIN adverse events of a neurological character such as dizziness and diplopia have been reported. Therefore, patients should see how LAMICTIN therapy affects them before driving or operating machinery.

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 LAMICTIN. The following convention has been utilised for the classification of undesirable effects: Very common (> 1/10), common (> 1/100, 1/1 000, 1/10 000, < 1/1 000), very rare (< 1/10 000).

EPILEPSY: Skin and subcutaneous tissue disorders: Very common: skin rash Rare: Erythema multiforme, Stevens-Johnson syndrome Very rare: toxic epidermal necrolysis In double-blind, add-on clinical trials, skin rashes occurred in up to 10% of patients taking LAMICTIN and in 5% of patients taking placebo. The skin rashes led to the withdrawal of LAMICTIN treatment in 2% of patients. The rash, usually maculopapular in appearance, generally appears within 8 weeks of starting treatment and resolves on withdrawal of lamotrigine (see section 4.4).

Serious, potentially life-threatening skin rashes, including angioedema, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Although the majority recover on withdrawal, some patients experience irreversible scarring and there have been rare cases of associated death (see section 4.4). The overall risk of rash appears to be strongly associated with high initial doses of LAMICTIN and exceeding the recommended dose escalation of LAMICTIN therapy (see section 4.2). Rash has also been reported as part of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); also known as hypersensitivity syndrome associated with a variable pattern of systemic symptoms (see section 4.4).

Blood and lymphatic system disorders: Very rare: haematological abnormalities (including, anaemia, neutropenia, leucopenia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocystosis), lymphadenopathy Haematological abnormalities and lymphadenopathy may or may not be associated with a DRESS /Hypersensitivity Syndrome (see section 4.4 Immune system disorders*).

Immune system disorders: Very rare: DRESS/ hypersensitivity syndrome* including such symptoms as, fever, lymphadenopathy, facial oedema, abnormalities of the blood, liver, and kidney, *Rash has also been reported as part of a hypersensitivity syndrome which shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation and multiorgan 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 LAMICTIN discontinued if an alternative aetiology cannot be established (see section 4.4).

Psychiatric disorders: Common: aggression, irritability Very rare: tics, hallucinations, confusion Nervous system disorders: Very common: headache Common: somnolence, insomnia, dizziness, tremor, vertigo, parasthesia Uncommon: ataxia Rare: nystagmus Eye disorders: Uncommon: diplopia, blurred vision Gastrointestinal disorders: Common: nausea, vomiting, diarrhoea Hepato-biliary disorders: Very rare: increased liver function tests, hepatic dysfunction, hepatic failure Hepatic dysfunction usually occurs in association with hypersensitivity reactions, but isolated cases have been reported without overt signs of hypersensitivity. Musculoskeletal and connective tissue disorders: Very rare: lupus-like reactions General disorders and administration site conditions: Common: tiredness.

BIPOLAR DISORDER: The undesirable effects below should be considered alongside those seen in epilepsy for an overall safety profile of LAMICTIN. Skin and subcutaneous tissue disorders: Very Common: skin rash Rare: Erythema multiforme, Stevens-Johnson Syndrome When all bipolar disorder studies (controlled and uncontrolled) conducted with LAMICTIN are considered, skin rashes occurred in 12% of patients on LAMICTIN. Whereas, in controlled clinical trials with bipolar disorder patients, skin rashes occurred in 8% of patients taking LAMICTIN and in 6% of patients taking placebo.

Nervous system disorders: Very Common: headache Common: agitation, somnolence, dizziness Musculoskeletal and connective tissue disorders: Common: arthralgia General disorders and administration site conditions: Common: pain, back pain.

Post-marketing Data: Blood and lymphatic system disorders: haemophagocytic lymphohistiocytosis (see section 4.4), pseudolymphoma Immune system disorders: hypogammaglobulinaemia Psychiatric disorders: nightmares Nervous system disorders: somnolence, headache, ataxia, dizziness, nystagmus, tremor, insomnia, aseptic meningitis (see section 4.4), agitation, unsteadiness, worsening of Parkinsonu2019s disease, extrapyramidal effects, choreoathetosis, and in epilepsy only, increase in seizure frequency. LAMICTIN may worsen Parkinsonian symptoms in patients with pre-existing Parkinsonu2019s disease and reports of extrapyramidal effects and choreoathetosis in patients without this underlying condition. Eye disorders: conjunctivitis Skin and subcutaneous disorders: alopecia Renal and Urinary disorders: Tubulointerstitial nephritis* *may occur in association with uveitis.

Symptoms and signs: Ingestion of doses in excess of 10 - 20 times the maximum therapeutic dose has been reported, including fatal cases. Overdose has resulted in symptoms including nystagmus, ataxia, impaired consciousness, grand mal convulsion and coma. QRS broadening (intraventricular conduction delay) has also been observed in overdose patients (see section 4.8).

Treatment: In the event of overdosage, 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.