Empliciti 300 mg and 400 mg powder for concentrate for solution for infusion

Name change of the manufacturing site responsible for product batch release in the EU, Swords Laboratories located in Ireland, by adding “Unlimited Company” at the end of the current legal entity name.

Update the ATC code for elotuzumab from L01XC23 to L01FX08 as per the WHO publication.

To update the SmPC section 5.1 with final overall survival data from study CA204-004. No changes to the PIL text but 'Date of Revision' updated to reflect overall product informationupdate

To update the SmPC section 5.1 with final overall survival data from study CA204-004

SmPC update for the Empliciti extension of indication in relapsed and refractory multiple myeloma - the approved indication reads:

4.1     Therapeutic indications

​​“Empliciti is indicated in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy (see sections 4.2 and 5.1).”

Section 10 DATE OF REVISION OF THE TEXT: Updated to 28 Feb to reflect overall product information update to the patient leaflet (addition of alternative batch release site)
 

Section 7 - New Marketing Authorisation Holder address

4.8     Undesirable effects

Table 3:           Adverse reactions in patients with multiple myeloma treated with Empliciti

Hypoaesthesia

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

5.2     Pharmacokinetic properties

The pharmacokinetics (PK) of elotuzumab was studied in patients with multiple myeloma. Elotuzumab exhibits nonlinear PK with decrease in clearance with increase in dose from 0.5‑20 mg/kg.

Absorption

Elotuzumab is dosed via intravenous route and therefore is immediately and completely bioavailable.

Distribution

The geometric meanMean volume of distribution of elotuzumab at 10 mg/kg (in combination with lenalidomide and dexamethasone) at steady state ranged from is 6.02 L (CV: 22.1%)36 mL/kg to 70 mL/kg (2.3‑4.6 L for a typical patient) and was independent from the dose in a dose range of 0.5 mg/kg to 20 mg/kg.

Biotransformation

The metabolic pathway of elotuzumab has not been characterized. As an IgG monoclonal antibody, elotuzumab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Elimination

The geometric mean total clearance ofFollowing a single dose of 10 mg/kg, the elotuzumab at 10 mg/kg (in combination with lenalidomide and dexamethasone) at steady state is 0.194 L/day (CV: 62.9%)clearance was 13.2 mL/day/kg. Elotuzumab exhibits nonlinear pharmacokinetics with clearance of elotuzumab decreasing from 17.5 to 5.8 mL/day/kg with an increase in dose from 0.5 to 20 mg/kg, suggesting target‑mediated clearance, resulting in greater than proportional increases in Area under the Concentration time curve (AUC). Upon discontinuation of elotuzumab in combination with lenalidomide and dexamethasone, concentrations of elotuzumab will decrease to approximately 3% (approximately 97% washout as estimated by 5 half‑lives) of the population predicted steady‑state maximal serum concentration by 3 months

10.     DATE OF REVISION OF THE TEXT

14 July 2017