Recommended Dosing when EMPLICITI Is Used in Combination with Lenalidomide and Dexamethasone

The recommended dosage of EMPLICITI is 10 mg/kg administered intravenously every week for the first two cycles (28-day cycle) and every 2 weeks thereafter in conjunction with the recommended dosing of lenalidomide and low-dose dexamethasone as described below. Continue treatment until disease progression or unacceptable toxicity.

Refer to the dexamethasone and lenalidomide prescribing information for additional information.

Administer premedications before each dose of EMPLICITI [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].

Administer dexamethasone as follows:

•

On days that EMPLICITI is administered, give dexamethasone 28 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 and 22 of cycle 3 and all subsequent cycles), give 40 mg orally.

The recommended dosing is presented in Table 1.

Recommended Dosing when EMPLICITI Is Used in Combination with Pomalidomide and Dexamethasone

The recommended dosage of EMPLICITI is 10 mg/kg administered intravenously every week for the first two cycles (28-day cycle). Starting at cycle 3 (28-day cycle), administer EMPLICITI 20 mg/kg intravenously every 4 weeks. Administer EMPLICITI in conjunction with pomalidomide and low-dose dexamethasone as described below (Table 2). Continue treatment until disease progression or unacceptable toxicity.

Refer to the dexamethasone and pomalidomide prescribing information for additional information.

Administer premedications before each dose of EMPLICITI [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].

Administer dexamethasone as follows:

•

​On days that EMPLICITI is administered, for patients 75 years or younger 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 older than 75 years 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 or younger and 20 mg orally to patients older than 75 years.

The recommended dosing is presented in Table 2.

Premedication

Dose Modifications

If the dose of one drug in the regimen is delayed, interrupted, or discontinued, the treatment with the other drugs may continue as scheduled. However, if dexamethasone is delayed or discontinued, base the decision whether to administer EMPLICITI on clinical judgment (i.e., risk of hypersensitivity).

If a Grade 2 or higher infusion reaction occurs during EMPLICITI administration, interrupt the infusion and institute appropriate medical and supportive measures. Upon resolution to Grade 1 or lower, restart EMPLICITI at 0.5 mL per minute and gradually increase at a rate of 0.5 mL per minute every 30 minutes as tolerated to the rate at which the infusion reaction occurred. Resume the escalation regimen if there is no recurrence of the infusion reaction (see Table 3 and Table 4).

In patients who experience an infusion reaction, monitor vital signs every 30 minutes for 2 hours after the end of the EMPLICITI infusion. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart on that day [see Warnings and Precautions (5.1)]. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.

Dose delays and modifications for dexamethasone, pomalidomide and lenalidomide should be performed as recommended in their Prescribing Information.

Administration

Administer the entire EMPLICITI infusion with an infusion set and a sterile, nonpyrogenic, low-protein-binding filter (with a pore size of 0.2 to 1.2 micrometer) using an automated infusion pump.

Initiate EMPLICITI infusion at a rate of 0.5 mL per minute for 10 mg/kg dose. The infusion rate may be increased in a stepwise fashion as described in Table 3 if no infusion reactions develop. The maximum infusion rate should not exceed 5 mL per minute.

Initiate EMPLICITI infusion rate at 3 mL per minute for 20 mg/kg dose. The infusion rate may be increased in a stepwise fashion as described in Table 4 if no infusion reactions develop. The maximum infusion rate should not exceed 5 mL per minute.

Patients who have escalated to 5 mL/min at 10 mg/kg dose must decrease the rate to 3 mL/min at the first infusion at 20 mg/kg.

Adjust the infusion rate following a Grade 2 or higher infusion reaction [see Dosage and Administration (2.4)].

Do not mix EMPLICITI with, or administer as an infusion with, other medicinal products. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of EMPLICITI with other agents.

Reconstitution and Preparation