Empliciti^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Bristol-Myers Squibb Company (USA)

Manufactured By

Bristol-Myers Squibb Holdings Pharma LLC (USA)

Labeled By

CATALENT ANAGNI, S.R.L. (Italy)

Quality Control Release

BRISTOL-MYERS SQUIBB CRUISERATH BIOLOGICS (Ireland)

ATC Code

L01FX08 (Elotuzumab)

Active Substance

Elotuzumab (Rec.INN registered with WHO)

Dosage Forms

	Empliciti®	Lyophilisate for the preparation of a concentrate for the preparation of an infusion solution 300 mg: vial. 1 pc.
		Lyophilisate for the preparation of a concentrate for the preparation of an infusion solution 400 mg: vial. 1 pc.

Dosage Form, Packaging, and Composition

Lyophilisate for the preparation of a concentrate for the preparation of an infusion solution as a porous mass or powder from white to almost white.

* packaging is carried out with an overfill of 40 mg (13.3%), which is necessary to guarantee the complete extraction of the declared dosage.
The extractable amount of elotuzumab in 1 vial is 300 mg.

Excipients : sodium citrate dihydrate – 16.6 mg, citric acid monohydrate – 2.44 mg, sucrose – 510 mg, polysorbate 80 – 3.4 mg.

Colorless glass vials (1) – cardboard packs with first-opening stickers.

Lyophilisate for the preparation of a concentrate for the preparation of an infusion solution as a porous mass or powder from white to almost white.

* packaging is carried out with an overfill of 40 mg (10%), which is necessary to guarantee the complete extraction of the declared dosage.
The extractable amount of elotuzumab in 1 vial is 400 mg.

Excipients : sodium citrate dihydrate – 21.5 mg, citric acid monohydrate – 3.17 mg, sucrose – 660 mg, polysorbate 80 – 4.4 mg.

Colorless glass vials (1) – cardboard packs with first-opening stickers.

Clinical-Pharmacological Group

Antitumor drug. Monoclonal antibodies

Pharmacotherapeutic Group

Antineoplastic agent, monoclonal antibodies

Pharmacological Action

Elotuzumab is a human immunostimulatory monoclonal IgG1 antibody that specifically binds to the SLAMF7 protein (signaling lymphocytic activation molecule family member 7). SLAMF7 is highly expressed on myeloma cells regardless of the type of cytogenetic abnormalities. SLAMF7 is also expressed on natural killer cells, normal plasma cells, and other immune cells, including some T-cells, monocytes, B-cells, and dendritic cells. SLAMF7 is not detected on healthy tissue cells and hematopoietic stem cells.

Elotuzumab directly activates natural killer cells via SLAMF7 and Fc receptors, thereby enhancing their anti-myeloma activity in vitro. Elotuzumab also binds to SLAMF7 on myeloma cells, facilitating their interaction with natural killer cells and the destruction of myeloma cells via antibody-dependent cellular cytotoxicity. In preclinical studies, Elotuzumab demonstrated synergistic activity when used in combination with lenalidomide.

Pharmacokinetics

Elotuzumab has nonlinear pharmacokinetics; the clearance of the drug decreases from 17.5 to 5.8 ml/day/kg as the dose increases from 0.5 to 20 mg/kg. This suggests that clearance is target-mediated, leading to a more than proportional increase in AUC. The V_d of elotuzumab approaches the volume of the intravascular space and is independent of the drug dose. According to population pharmacokinetic analysis, the typical value for the central volume of distribution is 4.04 L. When elotuzumab is administered at a dose of 10 mg/kg, the blood concentration of the drug decreases to approximately 3% of the previously achieved maximum C_ss.

In mouse xenograft models, the maximum therapeutic efficacy of the drug was observed at an elotuzumab plasma concentration of 70 µg/ml. In humans, the use of elotuzumab at a dose of 10 mg/kg ensures the achievement of a C_ss greater than 70 µg/ml in plasma.

The metabolism of elotuzumab has not been characterized. As expected, during catabolism, monoclonal antibodies are degraded into small peptides and amino acids.

The clearance of elotuzumab increases with increasing body weight, which is the basis for body weight-based dosing.

Indications

In combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one or more prior therapies.

ICD codes

Dosage Regimen

Administer Empliciti^® as an intravenous infusion only. Do not administer as an intravenous push or bolus.

Calculate the dose based on the patient’s actual body weight. Use the 10 mg/kg dose for all cycles when combined with lenalidomide and dexamethasone.

Initiate treatment with a 28-day cycle. Administer the dose on Days 1, 8, 15, and 22 for Cycles 1 and 2. For Cycle 3 and all subsequent cycles, administer the dose on Days 1 and 15.

Continue treatment until disease progression or unacceptable toxicity occurs.

Premedicate with dexamethasone (orally, 8 mg), an H1 blocker (diplenhydramine 25-50 mg or equivalent), an H2 blocker (ranitidine 50 mg or equivalent), and an antipyretic (acetaminophen 650-1000 mg) 45 to 90 minutes prior to every Empliciti infusion.

Reconstitute the lyophilisate with the appropriate volume of Sterile Water for Injection. Gently swirl the vial until the powder is completely dissolved. Do not shake.

Further dilute the reconstituted solution in 230 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection in a PVC or non-PVC polyolefin infusion bag.

Administer the infusion using a 0.2 to 1.2 micron in-line or sterile filter.

For the first infusion (Cycle 1, Day 1), infuse the total volume at a rate of 0.5 mL/min. If no infusion reactions occur, gradually increase the rate to a maximum of 2 mL/min.

For all subsequent infusions, infuse the total volume at a rate of 2 mL/min if the previous infusion was tolerated.

Monitor patients closely during the infusion for potential infusion reactions. Interrupt the infusion for any reaction and manage as clinically indicated.

Adverse Reactions

Infections and infestations very common – herpes zoster, upper respiratory tract infections.

From the hematopoietic system very common – lymphopenia.

Allergic reactions common – hypersensitivity reactions; uncommon – anaphylactic reaction.

Psychiatric disorders common – mood changes.

From the nervous system very common – headache; common – hypoesthesia.

From the cardiovascular system common – deep vein thrombosis.

From the respiratory system very common – nasopharyngitis, cough (including productive cough and cough due to upper respiratory tract infection), pneumonia; common – oropharyngeal pain.

From the digestive system very common – diarrhea.

From the skin and subcutaneous tissues common – night sweats.

Other very common – fatigue, fever, weight loss; common – infusion reactions, chest pain.

Contraindications

Hypersensitivity to elotuzumab; moderate and severe hepatic impairment; presence of contraindications to the use of drugs in the combination therapy; pregnancy, breastfeeding period; age under 18 years.

Use in Pregnancy and Lactation

The use of elotuzumab during pregnancy is contraindicated.

During treatment, women of childbearing potential are advised to use contraception.

Due to the potential risk of serious adverse reactions in the child, the use of elotuzumab during breastfeeding is contraindicated.

Use in Hepatic Impairment

In patients with mild hepatic impairment, dose adjustment is not required.

In moderate and severe hepatic impairment, the use of elotuzumab is contraindicated.

Use in Renal Impairment

In patients with varying degrees of renal impairment, as well as in patients requiring dialysis, dose adjustment is not required.

Pediatric Use

Contraindicated in patients under 18 years of age.

Geriatric Use

No data.

Special Precautions

Elotuzumab may cause infusion reactions. Infusion reactions were observed in clinical studies in approximately 10% of patients receiving therapy with elotuzumab, lenalidomide, and dexamethasone. The most common adverse reactions were fever, chills, and hypertension.

In clinical studies involving patients with multiple myeloma, the incidence of infections, including pneumonia, was higher among patients receiving elotuzumab therapy. Patients should be monitored and standard therapy should be used to treat infectious diseases.

The incidence of secondary malignancies was higher in patients receiving elotuzumab therapy compared to the control group. It is known that secondary malignancies are associated with lenalidomide exposure, which was noted over a longer period of time in patients receiving combination therapy with elotuzumab, lenalidomide, and dexamethasone compared to patients receiving therapy with lenalidomide and dexamethasone. Patients should be monitored for the development of secondary malignancies.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.