40/15 PRODUCT DETAILS 

Drug Name-                EMPLICITI

Active Ingredient-      Elotuzumab

 Approved date         11/30/2015                                                                                       

FDA approved use-  To treat people with multiple myeloma who have received one or                                      three prior medications

HIGHLIGHTS OF PRESCRIBING INFORMATION -

These highlights do not include all the information needed to use                                    EMPLICITI safely and effectively.

See full prescribing information for EMPLICITI. EMPLICITI? (elotuzumab) for injection, for intravenous use

Initial U.S. Approval: 2015

INDICATIONS AND USAGE-

 EMPLICITI is a SLAMF7-directed immunostimulatory antibody indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

ADVERSE REACTIONS-

 Most common adverse reactions (20% or higher) are fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, pneumonia.

CONTRAINDICATIONS-

 None 

WARNINGS AND PRECAUTIONS-

 Infusion reactions: Premedication is required. Interrupt EMPLICITI for Grade 2 or higher and permanently discontinue for severe infusion reaction.

 Monitor for fever and other signs of infection and treat promptly.

 Second Primary Malignancies (SPM): Higher incidences of SPM were observed in a controlled clinical trial of patients with multiple myeloma receiving EMPLICITI. 

Hepatotoxicity: Monitor liver function and stop EMPLICITI if hepatotoxicity is suspected.

 Interference with determination of complete response: EMPLICITI can interfere with assays used to monitor M-protein. This interference can impact the determination of complete response.

DOSAGE AND ADMINISTRATION-

With lenalidomide and dexamethasone: 10 mg/kg administered intravenously every week for the first two cycles and every 2 weeks thereafter until disease progression or unacceptable toxicity.

Premedicate with dexamethasone, diphenhydramine, ranitidine and acetaminophen.

DOSAGE FORMS AND STRENGTHS-

 For Injection: 300 mg or 400 mg lyophilized powder in a single-dose vial for reconstitution. 

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Infusion Reactions -                                                                                           EMPLICITI may cause infusion reactions. Advise patients to contact their healthcare provider if they experience signs and symptoms of infusion reactions, including fever, chills, rash, or breathing problems within 24 hours of infusion

 Advise patients that they will be required to take the following oral medications prior to EMPLICITI dosing to reduce the risk of infusion reaction

 Dexamethasone orally as prescribed  H1 blocker: diphenhydramine or equivalent (if oral) H2 blocker: ranitidine or equivalent (if oral)

Acetaminophen (650-1000 mg orally)

Pregnancy -                                                                                                                     Advise patients that lenalidomide has the potential to cause fetal harm and has specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm. Lenalidomide is only available through a REMS program

. Infections-                                                                                                                  Inform patients of the risk of developing infections during treatment with EMPLICITI, and to report any symptoms of infection 

Second Primary Malignancies -                                                                                  Inform patients of the risk of developing SPM during treatment with EMPLIC

 Hepatotoxicity -

Inform patients of the risk of hepatotoxicity during treatment with EMPLICITI and to report any signs and symptoms associated with this event to their healthcare provider for evaluation 

Manufactured by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA U.S. License No. 1713

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                             Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7) protein

2. Pharmacodynamics-                                                                                                  Cardiac Electrophysiology-                                                                                      EMPLICITI does not prolong the QT interval to any clinically relevant extent in combination with lenalidomide and dexamethasone at the recommended dose or as monotherapy (at a dose 2 times the recommended dose).

3 Pharmacokinetics-                                                                                                   Elotuzumab exhibits nonlinear pharmacokinetics (PK) resulting in greater than proportional increases in area under the concentration-time curve (AUC) indicative of target-mediated clearance.

The administration of the recommended 10 mg/kg EMPLICITI regimen in combination with lenalidomide/dexamethasone is predicted to result in geometric mean (CV%) steady-state trough concentrations of 194 ?g/mL (52%).

Elimination: The clearance of elotuzumab decreased from a geometric mean (CV%) of 17.5 (21.2%) to 5.8 (31%) mL/day/kg with an increase in dose from 0.5 (i.e., 0.05 times the recommended dosage) to 20 mg/kg (i.e., 2 times the recommended dosage).

Specificific Populations-                                                                                                 Clinically significant differences were not observed in the pharmacokinetics of elotuzumab based on age (37-88 years), gender, race, baseline LDH, albumin, renal impairment ranging from mild to severe (creatinine clearance (CLcr) 15 to 89 mL/min) renal impairment, end-stage renal disease (CLcr less than 15 mL/min) with or without hemodialysis, and mild (NCI-CTEP) hepatic  impairment.

The pharmacokinetics of elotuzumab in patients with moderate to severe hepatic impairment is unknow

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                      There are no studies with EMPLICITI with pregnant women to inform any drug associated risks.

Animal reproduction studies have not been conducted with elotuzumab. EMPLICITI is administered in combination with lenalidomide and dexamethasone.

Lenalidomide can cause embryo-fetal harm and is contraindicated for use in pregnancy. Refer to the lenalidomide and dexamethasone prescribing information for additional information.

Lenalidomide is only available through a REMS program.

The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

2 Lactation Risk Summary -                                                                                           There is no information on the presence of EMPLICITI in human milk, the effect on the breast fed infant, or the effect on milk production.

Because of the potential for serious adverse reactions in breast-fed infants from elotuzumab administered with lenalidomide/dexamethasone, breastfeeding is not recommended. Refer to the lenalidomide and dexamethasone prescribing information for additional information

3 Females and Males of Reproductive Potential -                                                     Pregnancy Testing -                                                                                                      Refer to the lenalidomide labeling for pregnancy testing requirements prior to initiating treatment in females of reproductive potential.

When EMPLICITI is used with lenalidomide, there is a risk of fetal harm, including severe life threatening human birth defects associated with lenalidomide, and the need to follow requirements regarding pregnancy avoidance, including testing.

Contraception Refer to the lenalidomide labeling for contraception requirements prior to initiating treatment in females of reproductive potential and males.

Lenalidomide is present in the blood and semen of patients receiving the drug. Refer to the lenalidomide full prescribing information for requirements regarding contraception and the 12 prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information

4 Pediatric Use-                                                                                                                  Safety and effectiveness have not been established in pediatric patients.

5 Geriatric Use-                                                                                                                 Of the 646 patients across treatment groups in the randomized trial in multiple myeloma, 57% were 65 years of age or older; the number of patients 65 years or older was similar between treatment groups.

No overall differences in efficacy or safety were observed between patients 65 years or older and younger patients (less than 65 years of age).

 OVERDOSAGE-                                                                                                            The dose of EMPLICITI at which severe toxicity occurs is not known. EMPLICITI does not appear to be removed by dialysis as determined in a study of patients with renal impairment. In case of overdosage, monitor patients closely for signs or symptoms of adverse reactions and institute appropriate symptomatic treatment.