LAMOTRIGINE BRISTOL LABS

Posology Lamotrigine tablets should be swallowed whole, and should not be chewed or crushed. If the calculated dose of lamotrigine (for example for treatment of children with epilepsy or patients with hepatic impairment) does not equate to whole tablets, the dose to be administered is that equal to the lower number of whole tablets.

4). The greater the interval of time since the previous dose, the more consideration should be given to escalation to the maintenance dose. 2), lamotrigine should generally be escalated to the maintenance dose according to the appropriate schedule.

It is recommended that Lamotrigine Tablets 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. Epilepsy The recommended dose escalation and maintenance doses for adults and adolescents aged 13 years and above (Table 1) and for children and adolescents aged 2 to 12 years (Table 2) are given below.

4). 5). 5), the treatment regimen as recommended for lamotrigine with concurrent valproate should be used. 6 mg/kg every one to […]

The undesirable effects for epilepsy and bipolar disorder indications are based on available data from controlled clinical studies and other clinical experience and are listed in the table below. Frequency categories are derived from controlled clinical studies (epilepsy monotherapy (identified by†) and bipolar disorder (identified by §)).

Where frequency categories differ between clinical trial data from epilepsy and bipolar disorder the most conservative frequency is shown. However, where no controlled clinical trial data are available, frequency categories have been obtained from other clinical experience.

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), not known (cannot be estimated from the available data).

System Organ Class Adverse Event Frequency Haematological abnormalities1 including neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis, Haemophagocytic lymphohistiocytosis (HLH) Very rareBlood and lymphatic system disorders Lymphadenopathy1 , Pseudolymphoma Not known Hypersensitivity syndrome2 (including such symptoms as, fever, lymphadenopathy, facial oedema, abnormalities of the blood and liver, disseminated intravascular coagulation, multi organ failure).

4) Rare Nervous System Disorders Unsteadiness, movement disorders, worsening of Parkinson's disease 3, extrapyramidal effects, choreoathetosis†, increase in seizure frequency Very Rare Diplopia†, blurred vision† UncommonEye disorders Conjunctivitis Rare Gastrointestinal disorders Nausea†, vomiting†, diarrhoea†, dry mouth§ Common Hepatobiliary disorders Hepatic failure, hepatic dysfunction4, increased liver function tests Very rare Skin and Skin rash5†§ Very common Alopecia, photosensitivity reaction Uncommon Stevens–Johnson Syndrome§ Rare Toxic epidermal necrolysis Very rare subcutaneous tissue disorders Drug Reaction with Eosinophilia and Systemic Symptoms Very rare Arthralgia§ CommonMusculoskeletal and connective tissue disorders Lupus-like reactions Very rare Renal and urinary disorders Tubulointerstitial nephritis, Tubulointerstitial nephritis and uveitis syndrome Not known General disorders and administration site conditions Tiredness†, pain§, back pain§ Common Description of selected adverse reactions 1 Haematological abnormalities and lymphadenopathy may or may not be associated with the Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / hypersensitivity syndrome (see Special warnings and precautions for use and Immune system disorders).

Skin rash:

There have been reports of adverse skin reactions, which have generally occurred 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.

8). In adults enrolled in studies utilizing 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 Stevens–Johnson syndrome (1 in 1000).

In clinical trials in patients with bipolar disorder, the incidence of serious rash is approximately 1 in 1000. The risk of serious skin rashes is higher in children than in adults. 8). In children, the initial presentation of a rash can be mistaken for an infection; physicians should consider the possibility of a reaction to lamotrigine treatment in children that develop symptoms of rash and fever during the first eight weeks of therapy.

2). 2). Caution is also required when treating patients with a history of allergy or rash to other antiepileptic 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.

HLA-B*1502 allele in individuals of Asian (primarily Han Chinese and Thai) origin has been shown to be associated with the risk of developing SJS/TEN when treated with lamotrigine. If these patients are known to be positive for HLA-B*1502, use of lamotrigine should be carefully considered.

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 to lamotrigine treatment. It is recommended that lamotrigine should not be restarted in patients who have discontinued due to rash associated with their prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk.

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