ESLICARBAZEPINE ASCEND

Posology Adults Eslicarbazepine Ascend may be taken as monotherapy or added to existing anticonvulsant therapy. The recommended starting dose is 400 mg once daily which should be increased to 800 mg once daily after one or two weeks.

Based on individual response, the dose may be increased to 1,200 mg once daily. 1). Special populations Elderly (over 65 years of age) No dose adjustment is needed in the elderly population provided that the renal function is not disturbed.

Due to very limited data on the 1,600 mg monotherapy regimen in the elderly, this dose is not recommended for this population. Renal impairment Caution should be exercised in the treatment of patients, adult and children above 6 years of age, with renal impairment and the dose should be adjusted according to creatinine clearance (CLCR) as follows: − CLCR >60 ml/min: no dose adjustment required.

− CLCR 30-60 ml/min: initial dose of 200 mg (or 5 mg/kg in children above 6 years) once daily or 400 mg (or 10 mg/kg in children above 6 years) every other day for 2 weeks followed by a once daily dose of 400 mg (or 10 mg/kg in children above 6 years).

However, based on individual response, the dose may be increased. − CLCR <30 ml/min: use is not recommended in patients with severe renal impairment due to insufficient data. Hepatic impairment No dose adjustment is needed in patients with mild to moderate hepatic impairment.

2) and use in these patients is, therefore, not recommended. Paediatric population Children above 6 years of age The recommended starting dose is 10 mg/kg/day once daily. Dosage should be increased in weekly or bi-weekly increments of 10 mg/kg/day up to 30 mg/kg/day, based on individual response.

1). Children with a body weight of ≥60 kg Children with a body weight of 60 kg or more should be given the same dose as for adults. The safety and efficacy of eslicarbazepine acetate in children aged 6 years and below has not yet been established.

2 but no recommendation on a posology can be made. Method of administration Oral use. Eslicarbazepine Ascend may be taken with or without food.

Summary of the safety profile In clinical studies (adjunctive therapy treatment and monotherapy), 2,434 patients with partial-onset seizures were treated with eslicarbazepine acetate (1,983 adult patients and 451 paediatric patients) and 51% of those patients experienced adverse reactions.

Adverse reactions were usually mild to moderate in intensity and occurred predominantly during the first weeks of treatment with eslicarbazepine acetate. The risks that have been identified for eslicarbazepine acetate are mainly class-based, dose-dependent undesirable effects.

The most common adverse reactions reported, in placebo controlled adjunctive therapy studies with adult epileptic patients and in an active controlled monotherapy study comparing eslicarbazepine acetate with carbamazepine controlled release, were dizziness, somnolence, headache, and nausea.

The majority of adverse reactions were reported in <3% of subjects in any treatment group. 4). Tabulated list of adverse reactions Adverse reactions associated with eslicarbazepine acetate obtained from clinical studies and post-marketing surveillance are tabulated below.

The following convention has been used for the classification of adverse reactions very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and not known (frequency cannot be estimated from available data). Within each frequency category, adverse reactions are presented in order of decreasing seriousness.

5. PR interval The use of eslicarbazepine acetate is associated with increase in the PR interval. g. AV block, syncope, bradycardia) may occur. Class related adverse reactions Rare adverse reactions such as bone marrow depression, anaphylactic reactions, systemic lupus erythematosus or serious cardiac arrhythmias did not occur during the placebo-controlled studies of the epilepsy program with eslicarbazepine acetate.

However, they have been reported with oxcarbazepine. Therefore, their occurrence after treatment with eslicarbazepine acetate cannot be excluded. There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with the structurally related antiepileptic drugs carbamazepine and oxcarbazepine.

The mechanism by which bone metabolism is affected has not been identified. Paediatric population In placebo-controlled studies involving patients aged from 2 to 18 years with partial-onset seizures […]

Suicidal ideation Suicidal ideation and behaviour have been reported in patients treated with antiepileptic active substances in several indications. A meta-analysis of randomised placebo-controlled trials of antiepileptic medicinal products 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 eslicarbazepine acetate. Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.

Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Nervous system disorders Eslicarbazepine acetate has been associated with some central nervous system adverse reactions, such as dizziness and somnolence, which could increase the occurrence of accidental injury.

Other warnings and precautions If Eslicarbazepine Ascend is to be discontinued it is recommended to withdraw it gradually to minimise the potential of increased seizure frequency. 2% of total population treated with eslicarbazepine acetate in clinical studies in epileptic patients.

Urticaria and angioedema cases have been reported in patients taking eslicarbazepine acetate. Angioedema in the context of hypersensitivity/anaphylactic reaction associated with laryngeal oedema can be fatal. If signs or symptoms of hypersensitivity develop, eslicarbazepine acetate must be discontinued immediately and alternative treatment should be initiated.

Severe cutaneous adverse reactions (SCARS) including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in post-marketing experience with eslicarbazepine acetate treatment.

At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Eslicarbazepine Ascend should be withdrawn immediately and an alternative treatment considered (as appropriate).

If the patients have developed such reactions, treatment with Eslicarbazepine Ascend must not be restarted in these patients at any time. HLA-B* 1502 allele - in Han Chinese, Thai and other Asian populations HLA-B* 1502 in individuals of Han Chinese and Thai origin has been shown to be strongly associated with the risk of developing the severe cutaneous reactions known as Stevens Johnson syndrome (SJS) when treated with carbamazepine.

The chemical structure of eslicarbazepine acetate is similar to that of carbamazepine, and it is possible that patients who are positive for HLA-B*1502 may also be at risk for SJS after treatment with eslicarbazepine acetate. The prevalence of HLA-B*1502 carrier is about 10% in Han Chinese and Thai populations.

Whenever possible, these individuals should be screened for this allele before starting treatment with carbamazepine or chemically-related active substances. If patients of these ethnic origins are tested positive for HLA- B*1502 allele, the use of eslicarbazepine acetate may be considered if the benefits are thought to exceed risks.

g, above 15% in the Philippines and Malaysia), testing genetically at risk populations for the presence of HLA- B*1502 may be considered. HLA-A*3101 allele- European descent and Japanese populations There are some data that suggest HLA-A*3101 is associated with an increased risk of carbamazepine induced cutaneous adverse drug reactions including SJS, TEN, Drug rash with eosinophilia (DRESS), or less severe acute generalized exanthematous pustulosis (AGEP) and maculopapular rash in people of European descent and the Japanese.

The frequency of the HLA-A*3101 allele varies widely between ethnic populations. HLA-A*3101 allele has a prevalence of 2 to 5% in European populations and about 10% in Japanese population. 8%. There are insufficient data supporting a recommendation for HLA-A*3101 screening before starting carbamazepine or chemically-related compounds treatment.

If patients of European descent or Japanese origin are known to be positive for HLA-A*3101 allele, the use of carbamazepine or chemically-related compounds may be considered if the benefits are thought to exceed risks. 5% of patients treated with eslicarbazepine acetate.

Hyponatraemia is asymptomatic in most cases, however, it may be accompanied by clinical symptoms like worsening of seizures, confusion, decreased consciousness. Frequency of hyponatraemia increased with increasing eslicarbazepine acetate dose.

g. diuretics, desmopressin, carbamazepine), serum sodium levels should be examined before and during treatment with eslicarbazepine acetate. Furthermore, serum sodium levels should be determined if clinical signs of hyponatraemia occur.

Apart from this, sodium levels should be determined during routine laboratory examination. If clinically-relevant hyponatraemia develops, eslicarbazepine acetate should be discontinued. PR interval Prolongations in PR interval have been observed in clinical studies with eslicarbazepine acetate.

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g. 1. Second or third degree atrioventricular (AV) block.