- Approval Id
- a9b154b4f9b9a46a
- Drug Approval Emc Name
- Eslicarbazepine Milpharm 800 mg tablets
- Drug Name
- Eslicarbazepine Milpharm 800 mg tablets
- Company Name
- Aurobindo Pharma - Milpharm Ltd.
- Company Address
- Odyssey Business Park, Ares Block, West End Road, South Ruislip, Middlesex, HA4 6QD
- Company Website
- http://www.aurobindo.com
- Company Telephone
- + 44 (0)208 845 8811
- Company Fax
- +44 (0)208 845 8795
- Company Medical Info Email
- [email protected]
- Company Customer Care Direct Line
- +44 (0)208 845 8811
- Company Medical Info Fax
- +44 (0)208 845 8795
- Atc Code
- N03AF04
- Legal Category
- Prescription only medicine
- Authorisation Holder
- 7. Marketing authorisation holder Milpharm Limited Ares Block, Odyssey Business Park, West End Road, Ruislip, HA4 6QD United Kingdom
- Authorisation Number
- 8. Marketing authorisation number(s) PL 16363/0825
- Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 28/03/2024
- Instruction Authorisation Holder
- 7. Marketing authorisation holder Milpharm Limited Ares Block, Odyssey Business Park, West End Road, Ruislip, HA4 6QD United Kingdom
- Instruction Authorisation Number
- 8. Marketing authorisation number(s) PL 16363/0825
- Instruction Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 28/03/2024
- Instruction Composition
- 2. Qualitative and quantitative composition Each tablet contains 800 mg of eslicarbazepine acetate. For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- 3. Pharmaceutical form Tablet White to off white, oblong shape, approximately 19 x 9.8 mm, biconvex, uncoated tablet, debossed with 'E' and 'T' on either side of the score line on one side and '800' on the other side. The tablet can be divided into equal doses.
- Instruction Clinical Particulars
- 4. Clinical particulars 4.1 Therapeutic indications Eslicarbazepine is indicated as: • monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy; • adjunctive therapy in adults, adolescents and children aged above 6 years with partial-onset seizures with or without secondary generalisation. 4.2 Posology and method of administration Posology Adults Eslicarbazepine 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 Some patients on monotherapy regimen may benefit from a dose of 1,600 mg once daily (see section
- Instruction Pharmacology
- 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antiepileptics, carboxamide derivatives, ATC code: N03AF04 Mechanism of action The precise mechanisms of action of eslicarbazepine acetate are unknown. However, in vitro electrophysiological studies indicate that both eslicarbazepine acetate and its metabolites stabilise the inactivated state of voltage-gated sodium channels, precluding their return to the activated state and thereby preventing repetitive neuronal firing. Pharmacodynamic effects Eslicarbazepine acetate and its active metabolites prevented the development of seizures in nonclinical models predictive of anticonvulsant efficacy in man. In humans, the pharmacological activity of eslicarbazepine acetate is primarily exerted through the active metabolite eslicarbazepine. Clinical efficacy Adult population The efficacy of eslicarbazepine acetate as adjunctive therapy has been demonstrated in four phase III double-blind placebo-controlled studies in 1,703 randomized adult patients with partial epilepsy refractory to treatment with one to three concomitant antiepileptic medicinal products. Oxcarbazepine and felbamate were not allowed as concomitant medicinal products in these studies. Eslicarbazepine acetate was tested at doses of 400 mg (in -301 and -302 studies only), 800 mg and 1,200 mg, once daily. Eslicarbazepine acetate 800 mg once daily and 1,200 mg once daily were significantly more effective than placebo in reducing seizure frequency over a 12-week maintenance period. The percentage of subjects with ≥50% reduction (1581 analyzed) in seizure frequency in the phase III studies was 19.3% for placebo, 20.8% for eslicarbazepine acetate 400 mg, 30.5% for eslicarbazepine acetate 800 mg and 35.3% for eslicarbazepine acetate 1,200 mg daily. The efficacy of eslicarbazepine acetate as monotherapy has been demonstrated in a double-blind, active controlled (carbamazepine controlled release) study, involving 815 randomized adult patients with newly diagnosed partial-onset seizures. Eslicarbazepine acetate was tested at once-daily doses of 800 mg, 1,200 mg and 1,600 mg. The doses of the active comparator, carbamazepine controlled release, were 200 mg, 400 mg and 600 mg, twice-daily. All subjects were randomized to the lowest dose level and only if a seizure occurred subjects were to be escalated to the next dose level. From the 815 randomized patients, 401 patients were treated with eslicarbazepine acetate once-daily [271 patients (67.6%) remained at dose of 800 mg, 70 patients (17.5%) remained at dose of 1,200 mg and 60 patients (15.0%) were treated with 1,600 mg]. In the primary efficacy analysis, in which drop-outs were considered as non-responders, 71.1% subjects were classified as seizure free in the eslicarbazepine acetate group and 75.6% in the carbamazepine controlled release group during the 26 week evaluation period (average risk difference -4.28%, 95% confidence interval: [-10,30; 1,74]. The treatment effect observed during the 26-week evaluation period was maintained over 1 year of treatment with 64.7 % eslicarbazepine acetate subjects and 70.3 % carbamazepine controlled release subjects classified as seizure free (average risk difference -5.46%, 95% confidence interval: [-11.88; 0.97]. In the analysis of treatment failure (seizure risk) based on time to event analysis (Kaplan-Meier analysis and Cox regression), the Kaplan-Meier estimates of seizure risk at the end of the evaluation period was 0.06 with carbamazepine and 0.12 with eslicarbazepine acetate and by the end of 1 year with an additional increased risk to 0.11 with carbamazepine and 0.19 with eslicarbazepine acetate (p=0.0002). At 1 year, the probability for subjects to withdraw due to either adverse reactions or lack of efficacy was 0.26 for eslicarbazepine acetate and 0.21 for carbamazepine controlled release. The efficacy of eslicarbazepine acetate as conversion to monotherapy was evaluated in 2 double-blind, randomized controlled studies in 365 adult patients with partial-onset seizures. Eslicarbazepine acetate was tested at doses of 1,200 mg and 1,600 mg once-daily. Seizure-free rates during the entire 10-week monotherapy period were 7.6% (1,600 mg) and 8.3 % (1,200 mg) in one study and 10.0% (1,600 mg) and 7.4 % (1,200 mg) in the other study, respectively. Elderly population The safety and efficacy of eslicarbazepine acetate as adjunctive therapy for partial seizures in elderly patients were evaluated in one non-controlled study, with a duration of 26 weeks, in 72 elderly (aged ≥ 65 years). The data shows that the incidence of adverse reactions in this population (65.3 %) is similar to the general population enrolled in the double-blind epilepsy studies (6
- Instruction Pharmaceutical Particulars
- 6. Pharmaceutical particulars 6.1 List of excipients sodium starch glycolate (Type-A) crospovidone (Type-A) silica, colloidal anhydrous povidone (K-90) magnesium stearate 6.2 Incompatibilities None 6.3 Shelf life 3 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container The tablets are marketed in blister pack (i.e Clear PVC– Aluminium foil blister). Pack size of 30 and 60 tablets. Not all pack sizes may be marketed 6.6 Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- Instruction Content
- ## Composition
2. Qualitative and quantitative composition Each tablet contains 800 mg of eslicarbazepine acetate. For the full list of excipients, see section 6.1.
## Pharmaceutical Form
3. Pharmaceutical form Tablet White to off white, oblong shape, approximately 19 x 9.8 mm, biconvex, uncoated tablet, debossed with 'E' and 'T' on either side of the score line on one side and '800' on the other side. The tablet can be divided into equal doses.
## Clinical Particulars
4. Clinical particulars 4.1 Therapeutic indications Eslicarbazepine is indicated as: • monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy; • adjunctive therapy in adults, adolescents and children aged above 6 years with partial-onset seizures with or without secondary generalisation. 4.2 Posology and method of administration Posology Adults Eslicarbazepine 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 Some patients on monotherapy regimen may benefit from a dose of 1,600 mg once daily (see section
## Pharmacological Properties
5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Antiepileptics, carboxamide derivatives, ATC code: N03AF04 Mechanism of action The precise mechanisms of action of eslicarbazepine acetate are unknown. However, in vitro electrophysiological studies indicate that both eslicarbazepine acetate and its metabolites stabilise the inactivated state of voltage-gated sodium channels, precluding their return to the activated state and thereby preventing repetitive neuronal firing. Pharmacodynamic effects Eslicarbazepine acetate and its active metabolites prevented the development of seizures in nonclinical models predictive of anticonvulsant efficacy in man. In humans, the pharmacological activity of eslicarbazepine acetate is primarily exerted through the active metabolite eslicarbazepine. Clinical efficacy Adult population The efficacy of eslicarbazepine acetate as adjunctive therapy has been demonstrated in four phase III double-blind placebo-controlled studies in 1,703 randomized adult patients with partial epilepsy refractory to treatment with one to three concomitant antiepileptic medicinal products. Oxcarbazepine and felbamate were not allowed as concomitant medicinal products in these studies. Eslicarbazepine acetate was tested at doses of 400 mg (in -301 and -302 studies only), 800 mg and 1,200 mg, once daily. Eslicarbazepine acetate 800 mg once daily and 1,200 mg once daily were significantly more effective than placebo in reducing seizure frequency over a 12-week maintenance period. The percentage of subjects with ≥50% reduction (1581 analyzed) in seizure frequency in the phase III studies was 19.3% for placebo, 20.8% for eslicarbazepine acetate 400 mg, 30.5% for eslicarbazepine acetate 800 mg and 35.3% for eslicarbazepine acetate 1,200 mg daily. The efficacy of eslicarbazepine acetate as monotherapy has been demonstrated in a double-blind, active controlled (carbamazepine controlled release) study, involving 815 randomized adult patients with newly diagnosed partial-onset seizures. Eslicarbazepine acetate was tested at once-daily doses of 800 mg, 1,200 mg and 1,600 mg. The doses of the active comparator, carbamazepine controlled release, were 200 mg, 400 mg and 600 mg, twice-daily. All subjects were randomized to the lowest dose level and only if a seizure occurred subjects were to be escalated to the next dose level. From the 815 randomized patients, 401 patients were treated with eslicarbazepine acetate once-daily [271 patients (67.6%) remained at dose of 800 mg, 70 patients (17.5%) remained at dose of 1,200 mg and 60 patients (15.0%) were treated with 1,600 mg]. In the primary efficacy analysis, in which drop-outs were considered as non-responders, 71.1% subjects were classified as seizure free in the eslicarbazepine acetate group and 75.6% in the carbamazepine controlled release group during the 26 week evaluation period (average risk difference -4.28%, 95% confidence interval: [-10,30; 1,74]. The treatment effect observed during the 26-week evaluation period was maintained over 1 year of treatment with 64.7 % eslicarbazepine acetate subjects and 70.3 % carbamazepine controlled release subjects classified as seizure free (average risk difference -5.46%, 95% confidence interval: [-11.88; 0.97]. In the analysis of treatment failure (seizure risk) based on time to event analysis (Kaplan-Meier analysis and Cox regression), the Kaplan-Meier estimates of seizure risk at the end of the evaluation period was 0.06 with carbamazepine and 0.12 with eslicarbazepine acetate and by the end of 1 year with an additional increased risk to 0.11 with carbamazepine and 0.19 with eslicarbazepine acetate (p=0.0002). At 1 year, the probability for subjects to withdraw due to either adverse reactions or lack of efficacy was 0.26 for eslicarbazepine acetate and 0.21 for carbamazepine controlled release. The efficacy of eslicarbazepine acetate as conversion to monotherapy was evaluated in 2 double-blind, randomized controlled studies in 365 adult patients with partial-onset seizures. Eslicarbazepine acetate was tested at doses of 1,200 mg and 1,600 mg once-daily. Seizure-free rates during the entire 10-week monotherapy period were 7.6% (1,600 mg) and 8.3 % (1,200 mg) in one study and 10.0% (1,600 mg) and 7.4 % (1,200 mg) in the other study, respectively. Elderly population The safety and efficacy of eslicarbazepine acetate as adjunctive therapy for partial seizures in elderly patients were evaluated in one non-controlled study, with a duration of 26 weeks, in 72 elderly (aged ≥ 65 years). The data shows that the incidence of adverse reactions in this population (65.3 %) is similar to the general population enrolled in the double-blind epilepsy studies (6
## Pharmaceutical Particulars
6. Pharmaceutical particulars 6.1 List of excipients sodium starch glycolate (Type-A) crospovidone (Type-A) silica, colloidal anhydrous povidone (K-90) magnesium stearate 6.2 Incompatibilities None 6.3 Shelf life 3 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container The tablets are marketed in blister pack (i.e Clear PVC– Aluminium foil blister). Pack size of 30 and 60 tablets. Not all pack sizes may be marketed 6.6 Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
