EmPLICITI

Package leaflet: Information for the user

Empliciti 300 mg powder for concentrate for solution for infusion, 400 mg powder for concentrate for solution for infusion

elotuzumab
Read this entire leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Empliciti is and what it is used for
2. What you need to know before using Empliciti
3. How to use Empliciti
4. Possible side effects
5. How to store Empliciti
6. Contents of the pack and other information

1. What Empliciti is and what it is used for

Empliciti contains the active substance elotuzumab, which is a monoclonal antibody, a type of protein
designed to recognise and bind to a specific target substance in the body. Elotuzumab binds to a
target protein called SLAMF7. SLAMF7 is present in large amounts on the surface of multiple myeloma
cells and on certain immune system cells (natural killer cells). When elotuzumab binds to SLAMF7 on
multiple myeloma cells or on natural killer cells, it stimulates the immune system to attack and destroy
the multiple myeloma cells.
Empliciti is used to treat multiple myeloma (a cancer of the bone marrow) in adults.
Empliciti will be given to you in combination with lenalidomide and dexamethasone or in combination
with pomalidomide and dexamethasone. Multiple myeloma is a cancer that affects a type of white blood
cell called plasma cells. These cells divide uncontrollably and accumulate in the bone marrow. This
damages the bones and kidneys.
Empliciti is used if your cancer has not responded to, or has come back after, certain treatments.

2. What you need to know before using Empliciti

Do not use Empliciti

• if you are allergic to elotuzumab or to any of the other ingredients of this medicine (listed in section 6 "Contents of the pack and other information"). If you are in doubt, consult your doctor.

Warnings and precautions
Infusion-related reactions
Inform your doctor or nurse immediately if you experience any of the infusion-related reactions listed at the beginning of section 4. These adverse effects mostly occur during or after the first dose infusion. You will be monitored for signs of these effects during and after the infusion.
Depending on the severity of the infusion-related reactions, additional treatments may be required to prevent complications and reduce symptoms, or the Empliciti infusion may need to be interrupted. Once symptoms disappear or improve, the infusion may continue at a slower rate and may be gradually increased if symptoms do not recur. Your doctor may decide to discontinue your treatment with Empliciti in case of a severe infusion-related reaction.
Before each Empliciti infusion, you will be given medications to reduce the risk of an infusion-related reaction (see section 3 "How to use Empliciti, Medicines administered before each infusion").
Before starting treatment with Empliciti, you should also read the warnings and precautions in the package leaflets of all medicines you are taking in combination with Empliciti, to obtain information about those medicines. If lenalidomide is used, particular attention must be paid to requirements regarding pregnancy testing and pregnancy prevention (see "Pregnancy and breastfeeding" in this section).
Children and adolescents
The use of Empliciti is not recommended in children and adolescents under 18 years of age.
Other medicines and Empliciti
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
For women taking Empliciti
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Do not use Empliciti if you are pregnant unless specifically recommended by your doctor. The effects of Empliciti in pregnant women or the potential harm to the fetus are unknown.

• If there is any possibility that you could become pregnant, you must use effective contraception during treatment with Empliciti and for 120 days after the end of treatment.
• If you become pregnant during treatment with Empliciti, inform your doctor.

When Empliciti is administered in combination with lenalidomide or pomalidomide, you must follow the pregnancy prevention programme for lenalidomide or pomalidomide, respectively (see the package leaflet for lenalidomide or pomalidomide). Lenalidomide and pomalidomide are expected to be harmful to the fetus.
It is not known whether elotuzumab passes into breast milk or whether there is a risk to the breastfed infant. Elotuzumab will be administered in combination with lenalidomide or pomalidomide; breastfeeding must be discontinued due to the use of lenalidomide or pomalidomide.
For men taking Empliciti
While you are taking Empliciti and for 180 days after stopping treatment, you must use a condom to ensure that your partner does not become pregnant.
Driving and using machines
It is unlikely that Empliciti will negatively affect your ability to drive or operate machinery. However, if you experience an infusion-related reaction (fever, chills, high blood pressure; see section 4 "Possible side effects"), do not drive, ride a bicycle, or operate machinery until the reaction has resolved.
Empliciti contains sodium
If you are on a low-sodium diet (a low-salt diet), inform your doctor before receiving Empliciti. This medicine contains 3.92 mg of sodium (the main component of table salt) per 300 mg vial or 5.23 mg of sodium per 400 mg vial. This corresponds to 0.2% or 0.3% of the maximum recommended daily dietary intake of sodium for an adult, respectively.

3. How to use Empliciti

How much Empliciti you will be given
The amount of Empliciti you will be given is calculated based on your body weight.
How Empliciti is administered
You will receive Empliciti under the supervision of an experienced healthcare professional. It will be given to you intravenously (by intravenous infusion) as a slow drip over several hours.
Empliciti is administered in treatment cycles lasting 28 days (4 weeks), in combination with other medicines used for the treatment of multiple myeloma.
When given in combination with lenalidomide and dexamethasone, Empliciti is administered as follows:

• In cycles 1 and 2, once weekly on days 1, 8, 15, and 22.
• In cycle 3 and onwards, once every 2 weeks on days 1 and 15.
  When given in combination with pomalidomide and dexamethasone, Empliciti is administered as follows:
• In cycles 1 and 2, once weekly on days 1, 8, 15, and 22.
• In cycle 3 and onwards, once every 4 weeks on day 1.
  Your doctor will continue treating you with Empliciti for as long as your disease improves or remains stable and side effects are manageable.

Medicines given before each infusion
Before each Empliciti infusion, you must receive the following medicines to help reduce possible infusion-related reactions:

• A medicine to reduce an allergic reaction (an antihistamine)
• A medicine to reduce inflammation (dexamethasone)
• A medicine to reduce pain and fever (paracetamol)

If you miss an infusion of Empliciti
Empliciti is used in combination with other medicines for multiple myeloma. If there is a delay, interruption, or suspension of any of the treatment medicines, your doctor will decide how to continue the treatment.
If you are given more Empliciti than you should have
Since Empliciti will be administered by a healthcare professional, it is unlikely that you will receive more than you should. In the unlikely event of an overdose, your doctor will monitor you for any side effects.
If you stop treatment with Empliciti
Stopping treatment with Empliciti may interrupt the medicine’s effect. Do not stop treatment without first discussing it with your doctor.
If you have any doubts about how to use this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Your doctor will discuss these side effects with you and explain the risks and benefits of the treatment.
The following side effects have been reported in clinical studies with elotuzumab:

Infusion-related reactions
Empliciti has been associated with infusion-related reactions (see section 2 "Warnings and precautions").
Tell your doctor or nurse immediately if you feel unwell during the infusion.
Below is a list of typical symptoms associated with infusion-related reactions:

• fever
• chills
• high blood pressure

Other symptoms may also occur. To manage these symptoms, your doctor might consider slowing down or stopping the Empliciti infusion.

Other side effects

Very common (may affect more than 1 in 10 people)

• fever
• sore throat
• pneumonia
• weight loss
• reduced number of white blood cells
• cough
• common cold
• headache
• diarrhoea
• feeling of tiredness or weakness

Common (may affect up to 1 in 10 people)

• chest pain
• blood clots in veins (thrombosis)
• painful skin rash with blisters (herpes zoster, shingles)
• night sweats
• mood changes
• decreased sensation, especially in the skin
• allergic reactions (hypersensitivity)
• mouth/throat area pain/sore throat

Uncommon (may affect up to 1 in 100 people)

• sudden potentially life-threatening allergic reaction (anaphylactic reaction)

Tell your doctor immediately if you experience any of the side effects listed above. Do not try to treat these symptoms with other medicines.

Reporting of side effects
If you get any side effects, including any not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Empliciti

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label of the vial and on the
carton after Exp. The expiry date refers to the last day of that month.
Store in the refrigerator (2°C - 8°C).
Do not freeze.
Keep in the original packaging to protect the medicine from light.
After reconstitution, the reconstituted solution must be immediately transferred from the vial
into the infusion bag.
After dilution, the infusion must be completed within 24 hours of preparation. The product should
be used immediately. If not used immediately, the infusion solution can be stored in the refrigerator (2°C - 8°C) for up to 24 hours.
Any unused medicine and waste material arising from this medicine must be disposed of in accordance
with local regulations.

6. Package contents and other information

What Empliciti contains

• The active substance is elotuzumab. Each vial of powder contains 300 mg or 400 mg of elotuzumab. After reconstitution, each mL of concentrate contains 25 mg of elotuzumab.
• The other components (excipients) are sucrose, sodium citrate (see section 2 "Empliciti contains sodium"), citric acid monohydrate, and polysorbate 80 (E433).

Description of the appearance of Empliciti and contents of the pack
Empliciti powder for concentrate for solution for infusion (powder for concentrate) is a solid
white to almost white cake, intact or fragmented, supplied in a glass vial.
Empliciti is available in packs containing 1 vial.
Marketing Authorization Holder
Bristol-Myers Squibb Pharma EEIG
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland
Manufacturer
CATALENT ANAGNI S.R.L.
Loc. Fontana del Ceraso snc
Strada Provinciale 12 Casilina, 41
03012 - ANAGNI (FR)
Italy
Swords Laboratories Unlimited Company t/a Bristol-Myers Squibb Cruiserath Biologics
Cruiserath Road, Mulhuddart
Dublin 15, D15 H6EF
Ireland
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.

The following information is intended exclusively for healthcare professionals:

Preparation and administration of Empliciti
Dose calculation
Calculate the dose (mg) and determine the number of vials required for the dose (10 mg/kg or
20 mg/kg) based on body weight (bw). More than one Empliciti vial may be needed to administer the total dose to the patient.

• Total elotuzumab dose in mg equals patient's body weight in kg multiplied by the elotuzumab dose (10 or 20 mg/kg).

Reconstitution of the vial
Under aseptic conditions, reconstitute each Empliciti vial using an appropriately sized syringe and an 18-gauge or smaller needle, as shown in Table 1. A slight resistance may be felt during the administration of water for injections, which is considered normal.
Table 1: Reconstitution instructions

Keep the vial in an upright position and mix the solution by rotating the vial to dissolve the lyophilized cake. Then invert the vial several times to dissolve any powder that may be present on the upper part of the vial or on the cap. Avoid vigorous shaking; DO NOT SHAKE. The lyophilized powder should dissolve within less than 10 minutes.
After the solid residues have completely dissolved, allow the reconstituted solution to stand for 5–10 minutes. The reconstituted solution is colourless to pale yellow and ranges from transparent to very opalescent. Prior to administration, Empliciti must be visually inspected for particulate matter and discoloration. If particulate matter or discoloration is observed, discard the solution.

Preparation of infusion solution
The reconstituted solution must be diluted with sodium chloride 9 mg/mL (0.9%) injection or 5% glucose injection to achieve a final infusion concentration between 1 mg/mL and 6 mg/mL. The volume of 9 mg/mL (0.9%) sodium chloride injection or 5% glucose injection must be adjusted so that the total volume does not exceed 5 mL/kg of body weight at any administered dose of Empliciti.

Calculate the volume (mL) of diluent (9 mg/mL (0.9%) sodium chloride injection or 5% glucose injection) required to prepare the infusion solution for the patient. Withdraw the required volume for the calculated dose from each vial, up to a maximum of 16 mL from the 400 mg vial and 12 mL from the 300 mg vial. Each vial is slightly overfilled to ensure sufficient extractable volume.

Transfer the withdrawn volumes from all vials required for the patient's calculated dose into a single infusion bag made of polyvinyl chloride or polyolefin containing the calculated volume of diluent. Gently mix the infusion by manual rotation. Do not shake.
Empliciti is for single use only. Discard any unused portion remaining in the vial.

Administration
The entire Empliciti infusion must be administered using an infusion set and a sterile, pyrogen-free, low-protein-binding filter (with a pore size of 0.2–1.2 µm) with an automated infusion pump.
Empliciti infusion is compatible with:

• PVC and polyolefin containers
• PVC infusion sets
• In-line filters made of polyethersulfone and nylon with pore sizes ranging from 0.2 µm to 1.2 µm.

Empliciti infusion rate at 10 mg/kg body weight
Empliciti at a dose of 10 mg/kg body weight should be initiated at an infusion rate of 0.5 mL/min. If well tolerated, the infusion rate may be gradually increased as described in Table 2. The maximum infusion rate must not exceed 5 mL/min.

Table 2: Empliciti infusion rate at 10 mg/kg body weight

Empliciti 20 mg/kg bw infusion rate
Empliciti at a dose of 20 mg/kg bw must be initiated at an infusion rate of 3 mL/min. If
the infusion is well tolerated, the infusion rate may be gradually increased as described
in Table 3. The maximum infusion rate must not exceed 5 mL/min.
Patients who increased the rate to 5 mL/min at the 10 mg/kg bw dose must reduce the
rate to 3 mL/min at the first infusion of the 20 mg/kg bw dose.
Table 3: Empliciti 20 mg/kg bw infusion rate

The Empliciti infusion solution must be used immediately. If not used immediately,
the storage times and conditions prior to use are under the responsibility of the user and
usually should not exceed 24 hours at 2°C − 8°C, protected from light. Do not freeze the reconstituted or diluted solution. The infusion solution may be stored for a maximum of 8 hours within the total 24-hour period at 20°C − 25°C and under normal lighting conditions.
This 8-hour period must include the product administration time.
Disposal
Do not store unused infusion solution for later use. Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.