Posology : מינונים

4.2    Posology and method of administration

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


Premedication for prevention of infusion related reactions (IRRs)
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 IRRs
If a ≥ Grade 2 IRR 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 IRR occurred. If there is no recurrence of the IRR, the escalation can be resumed (see Tables 3 and 4).

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

Posology for administration with lenalidomide and dexamethasone
The length of each treatment cycle is 28 days, see Table 1 for the dosing schedule.
Treatment should continue until disease progression or unacceptable toxicity.

The recommended dose of Empliciti is 10 mg/kg body weight (bw) administered intravenously every week, on days 1, 8, 15, and 22 for the first two treatment 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
Cycle         28-Day Cycles 1 & 2               28-Day Cycles 3+
Day of Cycle     1        8       15        22      1       8     15       22 
Premedication                  ✓        ✓       ✓         ✓      ✓               ✓ 
Empliciti (mg/kg bw) intravenously       10       10      10        10     10             10 

Lenalidomide (25 mg) orally                     Days 1-21                        Days 1-21 

Dexamethasone (mg) orally            28       28      28        28     28       40    28       40 
Day of Cycle     1        8       15        22      1       8     15       22 
For additional information concerning lenalidomide and dexamethasone, see the corresponding prescribing information leaflets.
Posology for administration with pomalidomide and dexamethasone
The length of each treatment cycle is 28 days, see Table 2 for the dosing schedule.
Treatment should continue until disease progression or unacceptable toxicity.

The recommended dose of Empliciti is 10 mg/kg bw administered intravenously every week on days 1, 8, 15, and 22 of each treatment cycle for the first two cycles and then 20 mg/kg bw administered on day 1 of each treatment cycle thereafter.

The recommended dose of pomalidomide is 4 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.

Administration of dexamethasone for adults ≤ 75 years old and for > 75 years old ▪    On days that Empliciti is administered, patients ≤ 75 years old give dexamethasone 28 mg orally between 3 and 24 hours before Empliciti plus 8 mg intravenously between 45 and 90 minutes before Empliciti and for patients > 75 years old give dexamethasone 8 mg orally between 3 and 24 hours before Empliciti plus 8 mg intravenously between 45 and 90 minutes before Empliciti.
▪    On days that Empliciti is not administered but a dose of dexamethasone is scheduled (Days 8, 15 and 22 of cycle 3 and all subsequent cycles), give 40 mg orally to patients  75 years old and 20 mg orally to patients > 75 years old.

Table 2:  Recommended dosing schedule of Empliciti in combination with pomalidomide and dexamethasone
Cycle     28-Day Cycles 1 and 2            28-Day Cycles 3+
Day of Cycle    1       8      15     22      1       8     15       22 
Premedication                    ✓       ✓      ✓      ✓       ✓ Empliciti (mg/kg bw) intravenously         10     10      10     10     20 Pomalidomide (4 mg) orally                     Days 1-21                     Days 1-21 Dexamethasone (mg) intravenously           8       8      8       8      8 Dexamethasone (mg) orally  75 years old      28     28      28     28     28      40     40       40 Dexamethasone (mg) orally > 75 years old      8       8      8       8      8      20     20       20 
Day of Cycle    1       8      15     22      1       8     15       22 

For additional information concerning pomalidomide and dexamethasone, see the corresponding prescribing information leaflets.

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

Elderly
No dose adjustment is required for Empliciti in patients over 65 years of age (see section 5.2). Data on the efficacy and safety of Empliciti in patients ≥ 85 years of age are very limited. The dose for dexamethasone in combination with pomalidomide is adjusted according to age. See Administration of dexamethasone for adults ≤ 75 years old and for > 75 years old above.

Renal impairment
No dose adjustment of Empliciti is required for patients with mild (creatinine clearance (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 aspartate aminotransferase (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).

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

Method of administration
Empliciti is for intravenous use only.

Infusion rate for Empliciti 10 mg/kg bw
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 3. The maximum infusion rate should not exceed 5 mL/min.

Table 3:          Infusion rate for Empliciti 10 mg/kg bw
Cycle 1, Dose 1                                Cycle 1, Dose 2                   Cycle 1, Dose 3 and 4 and all subsequent Cycles
Time interval           Rate           Time interval               Rate                           Rate 0 - 30 min         0.5 mL/min            0 - 30 min                3 mL/min 30 - 60 min        1 mL/min              ≥ 30 min                 4 mL/min*                    5 mL/min* ≥ 60 min          2 mL/min*                  -                        - *       Continue this rate until infusion is completed.

Infusion rate for Empliciti 20 mg/kg bw
The administration of reconstituted and diluted solution must be initiated at an infusion rate of 3 mL/min. If the infusion is well tolerated, the infusion rate may be increased in a stepwise fashion as described in Table 4. The maximum infusion rate should not exceed 5 mL/min.
Patients who have escalated to 5 mL/min at 10 mg/kg bw dose must decrease the rate to 3 mL/min at the first infusion at 20 mg/kg bw.

Table 4:          Infusion rate for Empliciti 20 mg/kg bw
Dose 1                                            Dose 2 and all subsequent doses 
Time interval                           Rate                                         Rate 0-30 min                          3 mL/min
5 mL/min*
≥ 30 min                         4 mL/min*
*       Continue this rate until infusion is completed.

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