Zebinix 800mg tablets

Change to section 2 - interactions with other medicines, food or drink

Change to section 2 - pregnancy, breast feeding and fertility

Change to section 4 - possible side effects

Change to MA holder contact details

Change to section 4.6 - Pregnancy and lactation

Change to section 4.8 - Undesirable effects

revised contact details of local representatives

Summary of Product Characteristics

Section 4.2 Posology and method of administration

Under the heading Method of administration

Switching preparations

The text below has been deleted:

“Since comparative bioavailability data for the tablet and the suspension formulation are not available, switching patients from one formulation to the other should be done with caution.”

Previous text has been replaced with the following:

“Based on comparative bioavailability data for the tablet and the suspension formulations, switching   patients from one formulation to the other can be done.”

Section 4.8 Undesirable effects

Addition of following text under Paediatric population heading:

Long-term safety data in the paediatric population obtained from open label extensions of the phase III study was consistent with the known safety profile of the product with no new findings of concern.

Amendment of the following paragraph under Paediatric population heading:

“and hyponatraemia” was added to the following sentence “Dizziness; somnolence; vertigo; asthenia; gait disturbance; tremor; ataxia; balance disorder; vision blurred; diarrhoea; and rash and hyponatraemia were less common in children than in adults.

The sentence “Hyponatraemia was only reported in adult population.” was removed.

Section 5.1Pharmacodynamic properties

The following amendments were made to content under the Paediatric population heading:

1st paragraph:

“Study 208 included 2 additional subsequent long-term, open-label extensions (1 year in part II and 2 years in part III) and Study 305 included 4 subsequent long-term, open-label extension periods (1 year in Parts II, III and IV and 2 years in Part V).”

2^nd and 3^rd paragraph:

“In the phase II study” was changed to “double-blind period of the phase II study”

The following text was added:

“In the subsequent 1-year open-label extension (Part II) of the phase III study (ITT set N=225) the total responder rate was 46.7% (steadily increasing from 44.9% (weeks 1-4) to 57.5% (weeks > 40)). The total median standardised seizure frequency was 6.1 (decreasing from 7.0 (weeks 1-4) to 4.0 (weeks > 40), resulting in a median relative change compared to the baseline period of -46.7%). The median relative change was larger in the previous placebo group (-51.4%) than in the previous ESL group (-40.4%). The proportion of patients with exacerbation (increase of ≥25%) compared to the baseline period was 14.2%.

In the subsequent 3 open-label extensions (ITT set N=148), the overall responder rate was 26.6% when compared to baseline Parts III–V (i.e. the last 4 weeks in part II). The total median standardised seizure frequency was 2.4 (resulting in a median relative change from Baseline Part III–V of -22.9%). The overall median relative decrease in Part I was greater in patients treated with ESL (-25.8%) than in patients treated with placebo (-16.4%). The overall proportion of patients with exacerbation (increase of ≥25%) compared to Baseline Parts III–V was 25.7%.

Of the 183 patients who completed parts I and II of the study, 152 patients were enrolled into part III. Of these, 65 patients had received ESL and 87 patients had received placebo during the double-blind part of the study. 14 patients (9.2%) completed open-label treatment with ESL through Part V. The most common reason for withdrawal during any part of the study was sponsor request (30 patients in part III [19.7% of the patients who entered part III], 9 in part IV [9.6% of the patients who entered part IV], and 43 in part V [64.2% of the patients who entered Part V]).

Taking into consideration the limitations of open label uncontrolled data, the long-term response to eslicarbazepine acetate in the open-label parts of the study was overall maintained.”

Update of sections 4.4 and 4.8 of the SmPC to add information on urticaria, angioedema and severe cutaneous adverse reactions (SCARS) including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) as adverse drug reactions with unknown frequency, based on recent post-marketing safety data on Zebinix treatment.