Empliciti 300 mg powder for concentrate for solution for infusion.

Empliciti 400 mg powder for concentrate for solution for infusion.

Empliciti 300 mg powder for concentrate for solution for infusion

Each val contains 300 mg elotuzumab*.

Empliciti 400 mg powder for concentrate for solution for infusion

Each vial contains 400 mg elotuzumab.

After reconstitution, each mL of concentrate contains 25 mg elotuzumab.

* Elotuzumab is produced in NS0 cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

Powder for concentrate for solution for infusion (powder for concentrate).

The powder is white to off white whole or fragmented cake.

Empliciti is indicated in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in adult patients who have received at least one prior therapy (see sections 4.2 and 5.1).

Elotuzumab therapy should be initiated and supervised by physicians experienced in the treatment of multiple myeloma.

Premedication for prevention of infusion reaction

Patients must be administered with the following premedications 45-90 minutes prior to Empliciti infusion (see section 4.4):

Dexamethasone 8 mg intravenous

H1 blocker: diphenhydramine (25-50 mg orally or intravenous) or equivalent H1 blocker.

H2 blocker: ranitidine (50 mg intravenous or 150 mg orally) or equivalent H2 blocker.

Paracetamol (650-1000 mg orally).

Management of infusion reaction

If a ≥ Grade 2 infusion reaction occurs during Empliciti administration, the infusion must be interrupted. Upon resolution to ≤ Grade 1, Empliciti should be restarted at 0.5 mL/min and may be gradually increased at a rate of 0.5 mL/min every 30 minutes as tolerated to the rate at which the infusion reaction occurred. If there is no recurrence of the infusion reaction, the escalation can be resumed (see Table 2).

In patients who experience an infusion reaction, vital signs should be monitored every 30 minutes for 2 hours after the end of the Empliciti infusion. If the infusion reaction recurs, the Empliciti infusion must be stopped and not restarted on that day (see section 4.4). Very severe infusion reactions (≥ Grade 3) may require permanent discontinuation of Empliciti therapy and emergency treatment.

Posology for administration with lenalidomide and dexamethasone

The dosing schedule is presented in Table 1.

Treatment should continue until disease progression or unacceptable toxicity.

The recommended dose of Empliciti is 10 mg/kg administered intravenously every week (28-day cycle), on days 1, 8, 15, and 22 for the first two cycles and every 2 weeks thereafter on days 1 and 15.

The recommended dose of lenalidomide is 25 mg orally once daily on days 1-21 of repeated 28-day cycles, and at least 2 hours after Empliciti infusion when administered on the same day.

The administration of dexamethasone is as follows:

• On days that Empliciti is administered, dexamethasone should be given as 28 mg orally once daily between 3 and 24 hours before Empliciti plus 8 mg intravenously between 45 and 90 minutes before Empliciti on days 1, 8, 15, and 22 of repeated 28-day cycles.

• On days that Empliciti is not administered but a dose of dexamethasone is scheduled (Days 8 and 22 of cycle 3 and all subsequent cycles), dexamethasone should be given 40 mg orally.

Table 1: Recommended dosing schedule of Empliciti in combination with lenalidomide and dexamethasone

For additional information concerning lenalidomide and dexamethasone, see the corresponding Summary of Product Characteristics.

See Method of administration below for instruction on infusion rates.

Dose delay, interruption, or discontinuation

If the dose of one medicine in the regimen is delayed, interrupted, or discontinued, the treatment with the other medicinal products may continue as scheduled. However, if oral or intravenous dexamethasone is delayed or discontinued, the administration of Empliciti should be based on clinical judgment (e.g. risk of hypersensitivity) (see section 4.4).

Special populations

Paediatric population

There is no relevant use of Empliciti in the paediatric population for the indication of multiple myeloma.

Elderly

No dose adjustment is required for elotuzumab in patients over 65 years of age (see section 5.2). Data on the efficacy and safety of elotuzumab in patients ≥ 85 years of age are very limited.

Renal impairment

No dose adjustment of Empliciti is required for patients with mild (CrCl = 60 - 89 mL/min), moderate (CrCl = 30 - 59 mL/min), severe (CrCl < 30 mL/min) renal impairment or end stage renal disease requiring dialysis (see section 5.2).

Hepatic impairment

No dose adjustment for Empliciti is required for patients with mild hepatic impairment (total bilirubin [TB] ≤ to the upper limit of normal [ULN] and AST > ULN or TB < 1 to 1.5 × ULN and any AST). Empliciti has not been studied in patients with moderate (TB > 1.5 to 3 × ULN and any AST) or severe (TB > 3 × ULN and any AST) hepatic impairment (see section 5.2).

Method of administration

Empliciti is for intravenous use only.

The administration of the reconstituted and diluted solution must be initiated at an infusion rate of 0.5 mL/min. If the infusion is well tolerated the infusion rate may be increased in a stepwise fashion as described in Table 2. The maximum infusion rate should not exceed 5 mL/min.

Table 2: Infusion rate for Empliciti

* Continue this rate until infusion is completed, approximately 1 hour based on patient weight.

For instructions on reconstitution and dilution of Empliciti before administration, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

The Summary of Product Characteristics for all medicinal products used in combination with Empliciti must be consulted before starting therapy.

Infusion reaction

Infusion reactions have been reported in patients receiving elotuzumab (see section 4.8).

Premedication consisting of dexamethasone, H1 blocker, H2 blocker, and paracetamol must be administered prior to Empliciti infusion (see section 4.2 Premedication). The rate of infusion reactions was much higher in patients who were not premedicated.

If any of the symptoms of infusion reaction reach Grade ≥ 2, Empliciti infusion must be interrupted and appropriate medical and supportive measures instituted. Vital signs should be monitored every 30 minutes for 2 hours after the end of the Empliciti infusion. Once the reaction has resolved (symptoms ≤ Grade 1), Empliciti can be restarted at the initial infusion rate of 0.5 mL/min. If symptoms do not recur, the infusion rate may be gradually escalated every 30 minutes to a maximum of 5 mL/min (see section 4.2 Method of administration).

Very severe infusion reactions may require permanent discontinuation of Empliciti therapy and emergency treatment. Patients with mild or moderate infusion reactions may receive Empliciti with a reduced infusion rate and close monitoring (see section 4.2 Method of administration).

Conditions for use of medicinal products used with Empliciti

Empliciti is used in combination with other medicinal products; therefore, the conditions for use applicable to those medicinal products also apply to the combination therapy. The Summary of Product Characteristics for all medicinal products used in combination with Empliciti must be consulted before starting therapy.

Infections

In clinical trials of patients with multiple myeloma, the incidence of all infections, including pneumonia, were higher in patients treated with Empliciti (see section 4.8). Patients should be monitored and infections should be managed with standard treatment.

Second primary malignancies (SPMs)

In a clinical trial of patients with multiple myeloma that compared Empliciti combined with lenalidomide and dexamethasone treatment to lenalidomide and dexamethasone treatment (Study 1), the incidence of SPMs, and specifically of solid tumours and non-melanoma skin cancer, was higher in patient treated with Empliciti (see section 4.8). SPMs are known to be associated with lenalidomide exposure, which was extended in patients treated with Empliciti combined with lenalidomide and dexamethasone vs. lenalidomide and dexamethasone. The rate of haematologic malignancies was the same between the two treatment arms. Patients should be monitored for the development of SPMs.