The drug should be administered under the guidance of a physician with experience in treating multiple myeloma.
Before each dose of Emplicity, patients should receive premedication.
Dosing regimen
The recommended dose of Emplicity ® in combination with dexamethasone is 10 mg / kg as an intravenous infusion on days 1, 8, 15, 22 during the first two 28-day cycles and every two weeks in subsequent cycles on days 1 and 15. Treatment should continue before the disease progresses or until signs of intolerable toxicity appear. Dexamethasone should be applied as follows:
- On the days of Embrysity® administration, dexamethasone should be taken at 28 mg orally 3-24 hours before the introduction of Emplicity, and 8 mg intravenously 45 - 90 minutes before the introduction of Emplicity.
- On days when Emplicity® is not injected, but a dose of dexamethasone is prescribed, it should be taken at a dose of 40 mg orally.
- The recommended dose of lenalidomide is 25 mg orally once a day on days 1-21 of each 28 day cycle, at least 2 hours after the administration of elotuzumab.
The dosage regimen is shown in Table 1.
Table 1: Recommended scheme for the administration of Embrysity® in combination with lenalidomide and dexamethasone
| Cycle | 1 cycle, 2 administration2 | 1 cycle, 3 and 4 introductions and all subsequent cycles2 |
| Day cycle | 1 | 8 | 15 | 22 | 1 | 8 | 15 | 22 |
| Premedication1 | ˅ | ˅ | ˅ | ˅ | ˅ |
| ˅ |
|
| The drug Emplicity ® (mg / kg) intravenously | 10 | 10 | 10 | 10 | 10 |
| 10 |
|
| Lenalidomide3 (25 mg) orally | Days 1 - 21 | Days 1 - 21 |
| Dexamethasone4 (mg) orally | 28 | 28 | 28 | 28 | 28 | 40 | 28 | 40 |
| Day cycle | 1 | 8 | 15 | 22 | 1 | 8 | 15 | 22 |
1 Premedication with the following drugs is carried out 45-90 minutes before the administration of Emplicity ®: 8 mg of dexamethasone intravenously, the blocker of H1-histamine receptors: diphenhydramine (25-50 mg orally or intravenously) or a similar preparation; blocker of H2-histamine receptors: ranitidine (50 mg intravenously or 150 mg orally) or a similar preparation; paracetamol (650-1000 mg orally).
2 Cycle 28 days
3Not earlier than 2 hours after the introduction of Emplicity ®.
4 Inside dexamethasone (28 mg) 3-24 hours before the administration of Emplicity®.
Instructions for the administration of the drug
Introduction Emplicity ® should be started at a rate of 0.5 ml per minute. With good tolerability, the speed of maintenance can be incremented step by step, as described in Table 2. The maximum rate of administration should not exceed 5 ml per minute.
Table 2: Implicity rate of administration
| Cycle 1, dose 1 | Cycle 1, dose 2 | Cycle 1, dose 3 and 4, And also all subsequent doses |
| Time Interval | Speed | Time Interval | Time Interval | Speed |
| 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 * | - | - |
|
* Maintain this speed until the end of the injection, about 1 hour, depending on the patient's body weight.
Changing the mode of administration
If the administration of one of the drugs is suspended, interrupted or discontinued, therapy with other drugs can be continued on schedule. However, if the use of dexamethasone is suspended or stopped, the use of Emplicity® should be based on a clinical assessment of the risk of developing hypersensitivity reactions.
With the development of infusion reactions of 2 degrees and higher, the introduction of Emplicity ® must be suspended and appropriate treatment is prescribed. After reducing the severity of the infusion reaction to 1 degree and lower, the introduction of Emplicity ® should be resumed at a rate of 0.5 ml per minute and, with good tolerability, gradually increase by 0.5 ml per minute every 30 minutes to the rate at which the infusion reaction. If there is no re-development of infusion reactions, it is possible to continue increasing the rate of administration according to the scheme (see Table 2, Implicity rate of administration).
In patients who previously developed infusion reactions, vital signs should be monitored every 30 minutes within 2 hours after the end of Embrycity® administration.If the infusion reaction develops again, the drug should be discontinued and not restarted on that day. Very severe infusion reactions may require the abolition of Emplicity therapy and emergency therapy.
Suspension of therapy and change in the regimen of therapy with dexamethasone and lenalidomide should be carried out according to clinical indications.
Patients with mild infusions can receive the Emplicity® preparation at a reduced rate of administration and under close medical supervision.
Rules for the preparation of solution
Concentrate and solution for infusion are prepared in aseptic conditions.
Emplicity ® is compatible with the following types of infusion equipment:
- Glass bottles, polyvinylchloride (PVC) and polyolefin bags for infusions;
- Polyvinyl chloride (PVC) systems for intravenous administration with an automatic infusion pump;
- Polyethersulfone (pore size: 0.2 - 1.2 μm) and nylon (pore size: 0.2 μm) flow filters for infusion systems.
Partially used bottles with the drug should be disposed of, according to local recommendations.
Rules for the preparation of solution
- The dosage of the drug is determined taking into account the patient's weight - 10 mg / kg. Based on the dose given to the patient, the number of vials of the preparation required for administration is determined. For the preparation of a single dose for administration per patient, more than 1 vial may be required.
- Remove the protective plastic lid from the vial. The vial is wiped with a sterile cotton wool soaked in alcohol.
- The contents of each vial are dissolved in water for injection as indicated in Table 3 using a suitable syringe (needle size 18 or smaller).
Table 3: Instructions for dissolution dilution of Emplicity®
| Dosage | Amount of sterile water for injection | The final volume of dissolved Emplicity® in the vial (including the volume occupied by the lyophilizate) | Concentration after dissolution |
| Bottle 300 mg | 13.0 ml | 13.6 ml | 25 mg / ml |
| Bottle 400 mg | 17.0 ml | 17.6 ml | 25 mg / ml |
- To reduce foaming, add water slowly, holding the piston of the syringe with your fingers. The spray of the solvent is directed strictly to the wall of the vial (and not to the lyophilizate).
- Gently stir in circular movements, holding the bottle vertically. Then flip the vial to dissolve the whole powder, which may be in the top of the vial or on the plug. DO NOT BURST.
- The lyophilizate must dissolve within 10 minutes. After complete dissolution, leave the resulting solution for another 5-10 minutes before further dilution.
- The resulting concentrate is a clear or highly opalescent liquid from colorless to light yellow in color. Do not use a solution of a different color or containing foreign particles. Vials with changed color or particles are discarded.
- After dissolution, the necessary volume of concentrate from each vial is taken for the calculated dose, but not more than -16 ml from a vial of 400 mg and 12 ml from a 300 mg vial. Further dilution is carried out in a vial of a sterile infusion system with 230 ml of a 0.9% sodium chloride solution for infusion or a sterile 5% dextrose solution for infusion. The volume of a 0.9% solution of sodium chloride for infusion or a sterile 5% dextrose solution for infusion is selected so that the concentration of elotuzumab in the solution is not more than 5 ml / kg of the body weight of the patient at any administered dose of the drug.
- The prepared solution is mixed by carefully turning the infusion container. Do not shake the bottle before use! Prepared mortar should not be frozen.
- Before administration, it is necessary to visually check the prepared solution of the preparation for the presence of mechanical inclusions and discoloration. Emplicity® solution is a clear or strongly opalescent solution, from colorless to light yellow in color.
- The drug should be injected through a sterile infusion system with a low protein binding capacity with a sterile, pyrogen-free flow filter (pore size 0.2 - 1.2 μm) and an automatic infusion pump.
Introduction Emplicity ® should be started at a rate of 0.5 ml per minute. If the administration is well tolerated, the infusion rate can be gradually increased as indicated in Table 2. The maximum infusion rate should not exceed 5 mL per minute.
- The drug can not be administered as a quick intravenous injection or as a bolus injection.
- Do not mix Emplicity® with other medications in one vial or infusion system and do not inject it simultaneously with other infusion medications.
- After each dose of Emplicity®, the infusionsystem with a sterile 0.9% isotonic sodium chloride solution for infusion or a sterile 5% dextrose solution for infusion. From the point of view of microbiological purity, the prepared solution should be used immediately. Otherwise, the prepared solution can be stored in the dark place for up to 24 hours at a temperature of 2-8 ° C. (Of the indicated 24 hours, the solution of the preparation can be at room temperature (20-25 ° C) and daylight for no more than 8 hours, including the time required to administer the drug). Prepared mortar should not be frozen!
- The unused residue of Emplicity® in the vial and the empty vial must be destroyed.
Elderly patients
In clinical studies, there was no difference in safety and efficacy between patients 65 years of age or older and younger patients (less than 65 years). Data on the efficacy and safety of the drug in patients older than 85 years are limited.
Impaired renal function
In clinical studies, the pharmacokinetics of elotuzumab in combination therapy did not differ significantly in patients with normal renal function,in patients with severe renal dysfunction that did not require dialysis, and in patients with terminal stage of renal dysfunction that required dialysis. In patients with impaired renal function of varying severity, as well as in patients requiring dialysis, correction of the Emplicity dose is not required.
Impaired liver function
In patients with mild hepatic impairment, correction of the Emplicity dose is not required. In patients with impaired liver function of moderate or severe degree, no clinical studies have been performed.