Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Empliciti 300 mg powder for concentrate for solution for infusion
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Elotuzumab may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for
Empliciti contains the active substance elotuzumab, which is a monoclonal antibody, a type of protein designed to recognise and attach to a specific target substance in the body. Elotuzumab attaches to a target protein called SLAMF7. SLAMF7 is found in large amounts on the surface of multiple myeloma cells and on certain cells of your immune system (natural killer cells). When elotuzumab binds to SLAMF7 on the multiple myeloma or natural killer cells, it stimulates your 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 together with lenalidomide and dexamethasone or together with pomalidomide and dexamethasone. Multiple myeloma is a cancer of a type of white blood cell called plasma cells. These cells divide out of control and collect in the bone marrow. This results in damage to 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 you take it
e Empliciti
You should not be given Empliciti if you are allergic to elotuzumab or any of the other ingredients of this medicine (listed in section 6 "Contents of the pack and other information"). Talk to your doctor if you are not sure. Warnings and precautions Infusion related reaction Tell your doctor or nurse straight away if you get any of the infusion related reactions listed at the top of section 4. These side effects mostly occur during or after the infusion of the first dose. You will be monitored for signs of such effects during and after the infusion. Depending on the seriousness of the infusion related reactions, you may require additional treatment to prevent complications and reduce your symptoms, or your infusion of Empliciti may be interrupted. When the symptoms go away or improve, the infusion can be continued more slowly and speeded up 2
gradually if the symptoms do not recur. Your doctor may decide not to continue Empliciti treatment if you have a strong infusion related reaction. Before each infusion of Empliciti, you will be given medicines to reduce infusion related reaction (see section 3 "How to use Empliciti, Medicines given before each infusion"). Before starting treatment with Empliciti, you must also read the package leaflet warnings and precautions of all medicines to be taken in combination with Empliciti for information related to these medicines. When lenalidomide is used, particular attention to pregnancy testing and prevention requirements is needed (see "Pregnancy and breast-feeding" in this section). Children and adolescents Empliciti is not recommended for use in children and adolescents aged under 18 years. Other medicines and Empliciti Tell your doctor if you are taking, have recently taken, or might take any other medicines. Pregnancy and breast-feeding For women taking Empliciti If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You should not use Empliciti if you are pregnant, unless your doctor specifically recommends it. The effects of Empliciti in pregnant women or its possible harm to an unborn baby are unknown. You must use effective contraception while you are being treated with Empliciti and for 120 days after stopping treatment, if there is any chance you could become pregnant. If you become pregnant while using Empliciti, tell your doctor. When Empliciti is given in combination with lenalidomide or pomalidomide, you must follow the pregnancy prevention programme for lenalidomide or pomalidomide respectively (see package leaflet for lenalidomide or pomalidomide). Lenalidomide and pomalidomide are expected to be harmful for an unborn baby. It is not known, whether elotuzumab passes into breast milk or if there is any risk to the breast-fed infant. Elotuzumab will be given in combination with lenalidomide or pomalidomide and breast-feeding should be stopped because of the use of lenalidomide or pomalidomide. For men taking Empliciti You should use a condom while taking Empliciti and for 180 days after stopping treatment to ensure your partner does not become pregnant. Driving and using machines Empliciti is unlikely to affect your ability to drive or use machines. However, if you get an infusion related reaction (fever, chills, high blood pressure see section 4 "Possible side effects"), do not drive, cycle or use machines until the reaction stops. Empliciti contains sodium Tell your doctor if you are on a low-sodium (low-salt) diet before you are given Empliciti. This medicine contains 3.92 mg sodium (main component of cooking/table salt) per 300 mg vial or 5.23 mg sodium per 400 mg vial. This is equivalent to 0.2% or 0.3% respectively, of the recommended maximum daily dietary intake of sodium for an adult. 3.
How to use Empliciti
How much Empliciti is given The amount of Empliciti you will be given will be calculated based on your body weight. 3
How to take it
You will receive Empliciti under the supervision of an experienced healthcare professional. It will be given into a vein (intravenously) as a drip (infusion) over several hours. Empliciti is taken in treatment cycles that are 28 days (4 weeks) long in combination with other medicines used to treat multiple myeloma. When given in combination with lenalidomide and dexamethasone, Empliciti is given as follows: In cycles 1 and 2, once weekly on days 1, 8, 15, and 22. In cycles 3 and beyond, once every 2 weeks on days 1 and 15. When given in combination with pomalidomide and dexamethasone, Empliciti is given as follows: In cycles 1 and 2, once weekly on days 1, 8, 15, and 22. In cycles 3 and beyond, once every 4 weeks on day 1. Your doctor will continue to treat you with Empliciti for as long as the disease improves or remains stable and side effects are tolerable. Medicines given before each infusion You must receive the following medicines before each infusion of Empliciti to help reduce possible infusion related reactions: medicine to reduce an allergic reaction (an anti-histamine) medicine to reduce inflammation (dexamethasone) medicine to reduce pain and fever (paracetamol) If you miss a dose of Empliciti Empliciti is used in combination with other medicines for multiple myeloma. If any medicine in the treatment is delayed, interrupted, or discontinued, your doctor will decide how your treatment should be continued. If you are given too much Empliciti As Empliciti will be given to you by a healthcare professional, it is unlikely you will be given too much. In the unlikely case of an overdose, your doctor will monitor you for side effects. If you stop using Empliciti Stopping your treatment with Empliciti may stop the effect of the medicine. Do not stop treatment unless you have discussed this with your doctor. If you have any further questions on the use of this medicine, ask 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 with you and will explain the risks and benefits of your treatment. The following side effects have been reported in clinical trials with elotuzumab: Infusion related reactions Empliciti has been associated with infusion related reactions (see section 2 "Warnings and precautions"). Tell your doctor or nurse straight away if you feel unwell during infusion. Below is a list of typical symptoms associated with infusion related reactions: Fever Chills High blood pressure Other symptoms may occur as well. Your doctor may consider slowing the Empliciti infusion or interrupting it to manage these symptoms.
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Other side effects Very common (may affect more than 1 in 10 people) Fever Sore throat Pneumonia Weight decrease Low white blood cell count Cough Common cold Headache Diarrhoea Feeling tired or weak Common (may affect up to 1 in 10 people) Chest pain Blood clots in the veins (thrombosis) Painful skin rash with blisters (shingles, zona) Night sweats Mood changes Decreased sensitivity, especially in the skin Allergic reactions (hypersensitivity) Pain in the mouth/throat region/sore throat Uncommon (may affect up to 1 in 100 people) Sudden life-threatening allergic reaction (anaphylactic reaction) Tell your doctor immediately if you get any of the side effects listed above. Do not try to treat your symptoms with other medicines. Reporting of side effects If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine. 5.
How to store it
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 vial label and carton after EXP. The expiry date refers to the last day of that month. Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original package in order to protect from light. After reconstitution, the reconstituted solution should be transferred from the vial to the infusion bag immediately. After dilution, the infusion must be completed within 24 hours of preparation. The product should be used immediately. If not used immediately, the solution for infusion may be stored in the refrigerator (2 °C – 8 °C) for up to 24 hours. Any unused medicine or waste material should be disposed of in accordance with local requirements.
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6.
Contents of the pack and other information
What Empliciti contains
The active substance is elotuzumab. Each vial of powder contains either 300 mg or 400 mg of elotuzumab. After reconstitution, each mL of concentrate contains 25 mg of elotuzumab.
The other ingredients (excipients) are sucrose, sodium citrate (see section 2 "Empliciti contains sodium"), citric acid monohydrate, and polysorbate 80 (E433).
What Empliciti looks like and contents of the pack Empliciti powder for concentrate for solution for infusion (powder for concentrate) is a white to off white whole or fragmented cake provided in a glass vial. Empliciti is available in packs containing 1 vial. Marketing Authorisation 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 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 This leaflet was last revised in May 2022 ——————————————————————————————————————–The following information is intended for healthcare professionals only: Preparation and administration of Empliciti Calculating the dose Calculate the dose (mg) and determine the number of vials needed for the dose (10 mg/kg or 20 mg/kg) based on body weight (bw). More than one vial of Empliciti may be needed to give the total dose for the patient.
The total elotuzumab dose in mg equals the patient's bw in kg multiplied by the elotuzumab dose (10 or 20 mg/kg).
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Reconstitution of vials Aseptically reconstitute each Empliciti vial with a syringe of adequate size and an 18 gauge or smaller needle as shown in Table 1. A slight back pressure may be experienced during administration of the water for injections, which is considered normal. Table 1:
Reconstitution instructions
Strength 300 mg vial 400 mg vial
Amount of water for injections, required for reconstitution 13.0 mL 17.0 mL
Final volume of reconstituted Empliciti in the vial 13.6 mL 17.6 mL
Post-reconstitution concentration 25 mg/mL 25 mg/mL
Hold the vial upright and swirl the solution by rotating the vial to dissolve the lyophilised cake. Then invert the vial a few times in order to dissolve any powder that may be present on top of the vial or the stopper. Avoid vigorous agitation, DO NOT SHAKE. The lyophilised powder should dissolve in less than 10 minutes. After the remaining solids are completely dissolved, allow the reconstituted solution to stand for 5 to 10 minutes. The reconstituted solution is colourless to slightly yellow and clear to very opalescent. Empliciti should be inspected visually for particulate matter and discolouration prior to administration. Discard the solution if any particulate matter or discolouration is observed. Preparation of the solution for infusion The reconstituted solution should be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection or 5% glucose injection to obtain a final infusion concentration range between 1 mg/mL and 6 mg/mL. The volume of sodium chloride 9 mg/mL (0.9%) solution for injection or 5% glucose injection should be adjusted so as to not exceed 5 mL/kg of bw at any given dose of Empliciti. Calculate the volume (mL) of diluent (either sodium chloride 9 mg/mL (0.9%) solution for injection or 5% glucose injection) needed to make up the solution for infusion for the patient. Withdraw the necessary volume for the calculated dose from each vial, up to a maximum of 16 mL from 400 mg vial and 12 mL from 300 mg vial. Each vial contains a slight overfill to ensure sufficient extractable volume. Transfer the withdrawn volumes of all vials needed according to the calculated dose for this patient into one 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 left in the vial. Administration The entire Empliciti infusion should be administered with an infusion set and a sterile, non-pyrogenic, low-protein-binding filter (with a pore size of 0.2-1.2 μm) using an automated infusion pump. Empliciti infusion is compatible with: PVC and polyolefin containers PVC infusion sets polyethersulfone and nylon in-line filters with pore sizes of 0.2 μm to 1.2 μm. Infusion rate for Empliciti 10 mg/kg bw Empliciti at 10 mg/kg bw dose should be initiated at an infusion rate of 0.5 mL/min. If well tolerated, the infusion rate may be increased stepwise as described in Table 2. The maximum infusion rate should not exceed 5 mL/min.
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Table 2:
Infusion rate for Empliciti 10 mg/kg bw Cycle 1, Dose 1
Cycle 1, Dose 2
Cycle 1, Dose 3 and 4 and all subsequent Cycles
*
Time interval
Rate
Time interval
Rate
Rate
0 – 30 min
0.5 mL/min
0 – 30 min
3 mL/min
30 – 60 min
1 mL/min
≥ 30 min
4 mL/min*
≥ 60 min
2 mL/min*
–
–
5 mL/min*
Continue this rate until infusion is completed.
Infusion rate for Empliciti 20 mg/kg bw Empliciti at 20 mg/kg bw dose should be initiated at an infusion rate of 3 mL/min. If well tolerated, the infusion rate maybe increased in a stepwise fashion as described in Table 3. The maximum infusion rate should not exceed 5 mL/min. Patients who have escalated to 5 mL/min at 10 mg/kg bw dose must decrease the rate to 3 mL/min at the first infusion at 20 mg/kg bw. Table 3:
Infusion rate for Empliciti 20 mg/kg bw Dose 1
*
Dose 2 and all subsequent doses
Time interval
Rate
0-30 min
3 mL/min
≥ 30 min
4 mL/min*
Rate 5 mL/min*
Continue this rate until infusion is completed.
The Empliciti infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C − 8°C protected from light. Do not freeze the reconstituted or diluted solution. The solution for infusion may be stored for a maximum of 8 hours of the total 24 hours at 20°C − 25°C and room light. This 8-hour period should be inclusive of the product administration period. Disposal Do not store any unused portion of the infusion solution for reuse. Any unused medicine or waste material should be disposed of in accordance with local requirements.
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Frequently asked questions about Empliciti 300 mg powder for concentrate for solution for infusion
How do I take Empliciti 300 mg powder for concentrate for solution for infusion?
Empliciti 300 mg powder for concentrate for solution for infusion comes as infusion containing 300mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in Empliciti 300 mg powder for concentrate for solution for infusion?
The active substance in Empliciti 300 mg powder for concentrate for solution for infusion is elotuzumab.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Empliciti 300 mg powder for concentrate for solution for infusion, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get Empliciti 300 mg powder for concentrate for solution for infusion without a prescription?
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: elotuzumab
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
Empliciti is indicated in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in adult patients who have received at least one prior therapy (see sections 4.2 and 5.1).
Empliciti is indicated in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy (see sections 4.2 and 5.1).
4.2. Posology and method of administration
Elotuzumab therapy should be initiated and supervised by physicians experienced in the treatment of multiple myeloma.
Premedication for prevention of infusion related reactions (IRRs)
Patients must be administered with the following premedications 45-90 minutes prior to Empliciti infusion (see section 4.4):
▪ Dexamethasone 8 mg intravenous
▪ H1 blocker: diphenhydramine (25-50 mg orally or intravenous) or equivalent H1 blocker.
▪ H2 blocker: ranitidine (50 mg intravenous or 150 mg orally) or equivalent H2 blocker.
▪ Paracetamol (650-1000 mg orally).
Management of IRRs
If a ≥ Grade 2 IRR occurs during Empliciti administration, the infusion must be interrupted. Upon resolution to ≤ Grade 1, Empliciti should be restarted at 0.5 mL/min and may be gradually increased at a rate of 0.5 mL/min every 30 minutes as tolerated to the rate at which the IRR occurred. If there is no recurrence of the IRR, the escalation can be resumed (see Tables 3 and 4).
In patients who experience an IRR, vital signs should be monitored every 30 minutes for 2 hours after the end of the Empliciti infusion. If the IRR recurs, the Empliciti infusion must be stopped and not restarted on that day (see section 4.4). Very severe IRRs (≥ Grade 3) may require permanent discontinuation of Empliciti therapy and emergency treatment.
Posology for administration with lenalidomide and dexamethasone
The length of each treatment cycle is 28 days, see Table 1 for the dosing schedule. Treatment should continue until disease progression or unacceptable toxicity.
The recommended dose of Empliciti is 10 mg/kg body weight (bw) administered intravenously every week, on days 1, 8, 15, and 22 for the first two treatment cycles and every 2 weeks thereafter on days 1 and 15.
The recommended dose of lenalidomide is 25 mg orally once daily on days 1-21 of repeated 28-day cycles, and at least 2 hours after Empliciti infusion when administered on the same day.
The administration of dexamethasone is as follows:
▪ On days that Empliciti is administered, dexamethasone should be given as 28 mg orally once daily between 3 and 24 hours before Empliciti plus 8 mg intravenously between 45 and 90 minutes before Empliciti on days 1, 8, 15, and 22 of repeated 28-day cycles.
▪ 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), dexamethasone should be given 40 mg orally.
Table 1: Recommended dosing schedule of Empliciti in combination with lenalidomide and dexamethasone
Cycle
28-Day Cycles 1 & 2
28-Day Cycles 3+
Day of Cycle
1
8
15
22
1
8
15
22
Premedication
✓
✓
✓
✓
✓
✓
Empliciti (mg/kg bw) intravenously
10
10
10
10
10
10
Lenalidomide (25 mg) orally
Days 1-21
Days 1-21
Dexamethasone (mg) orally
28
28
28
28
28
40
28
40
Day of Cycle
1
8
15
22
1
8
15
22
For additional information concerning lenalidomide and dexamethasone, see the corresponding Summary of Product Characteristics.
Posology for administration with pomalidomide and dexamethasone
The length of each treatment cycle is 28 days, see Table 2 for the dosing schedule. Treatment should continue until disease progression or unacceptable toxicity.
The recommended dose of Empliciti is 10 mg/kg bw administered intravenously every week on days 1, 8, 15, and 22 of each treatment cycle for the first two cycles and then 20 mg/kg bw administered on day 1 of each treatment cycle thereafter.
The recommended dose of pomalidomide is 4 mg orally once daily on days 1-21 of repeated 28-day cycles, and at least 2 hours after Empliciti infusion when administered on the same day.
Administration of dexamethasone for adults ≤ 75 years old and for > 75 years old
▪ On days that Empliciti is administered, patients ≤ 75 years old 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 > 75 years old 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 old and 20 mg orally to patients > 75 years old.
Table 2: Recommended dosing schedule of Empliciti in combination with pomalidomide and dexamethasone
Cycle
28-Day Cycles 1 and 2
28-Day Cycles 3+
Day of Cycle
1
8
15
22
1
8
15
22
Premedication
✓
✓
✓
✓
✓
Empliciti (mg/kg bw) intravenously
10
10
10
10
20
Pomalidomide (4 mg) orally
Days 1-21
Days 1-21
Dexamethasone (mg) intravenously
8
8
8
8
8
Dexamethasone (mg) orally ≤ 75 years old
28
28
28
28
28
40
40
40
Dexamethasone (mg) orally > 75 years old
8
8
8
8
8
20
20
20
Day of Cycle
1
8
15
22
1
8
15
22
For additional information concerning pomalidomide and dexamethasone, see the corresponding Summary of Product Characteristics.
See Method of administration below for instruction on infusion rates.
Dose delay, interruption, or discontinuation
If the dose of one medicine in the regimen is delayed, interrupted, or discontinued, the treatment with the other medicinal products may continue as scheduled. However, if oral or intravenous dexamethasone is delayed or discontinued, the administration of Empliciti should be based on clinical judgment (e.g. risk of hypersensitivity) (see section 4.4).
Special populations
Elderly
No dose adjustment is required for Empliciti in patients over 65 years of age (see section 5.2). Data on the efficacy and safety of Empliciti in patients ≥ 85 years of age are very limited. The dose for dexamethasone in combination with pomalidomide is adjusted according to age. See Administration of dexamethasone for adults ≤ 75 years old and for > 75 years old above.
Renal impairment
No dose adjustment of Empliciti is required for patients with mild (creatinine clearance (CrCl) = 60 - 89 mL/min), moderate (CrCl = 30 - 59 mL/min), severe (CrCl < 30 mL/min) renal impairment or end stage renal disease requiring dialysis (see section 5.2).
Hepatic impairment
No dose adjustment for Empliciti is required for patients with mild hepatic impairment (total bilirubin (TB) ≤ to the upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or TB < 1 to 1.5 × ULN and any AST). Empliciti has not been studied in patients with moderate (TB > 1.5 to 3 × ULN and any AST) or severe (TB > 3 × ULN and any AST) hepatic impairment (see section 5.2).
Paediatric population
There is no relevant use of Empliciti in the paediatric population for the indication of multiple myeloma.
Method of administration
Empliciti is for intravenous use only.
Infusion rate for Empliciti 10 mg/kg bw
The administration of the reconstituted and diluted solution must be initiated at an infusion rate of 0.5 mL/min. If the infusion is well tolerated the infusion rate may be increased in a stepwise fashion as described in Table 3. The maximum infusion rate should not exceed 5 mL/min.
Table 3: Infusion rate for Empliciti 10 mg/kg bw
Cycle 1, Dose 1
Cycle 1, Dose 2
Cycle 1, Dose 3 and 4 and all subsequent Cycles
Time interval
Rate
Time interval
Rate
Rate
0 - 30 min
0.5 mL/min
0 - 30 min
3 mL/min
5 mL/min*
30 - 60 min
1 mL/min
≥ 30 min
4 mL/min*
≥ 60 min
2 mL/min*
-
-
* Continue this rate until infusion is completed.
Infusion rate for Empliciti 20 mg/kg bw
The administration of reconstituted and diluted solution must be initiated at an infusion rate of 3 mL/min. If the infusion is well tolerated, the infusion rate maybe increased in a stepwise fashion as described in Table 4. The maximum infusion rate should not exceed 5 mL/min.
Patients who have escalated to 5 mL/min at 10 mg/kg bw dose must decrease the rate to 3 mL/min at the first infusion at 20 mg/kg bw.
Table 4: Infusion rate for Empliciti 20 mg/kg bw
Dose 1
Dose 2 and all subsequent doses
Time interval
Rate
Rate
0-30 min
3 mL/min
5 mL/min*
≥ 30 min
4 mL/min*
* Continue this rate until infusion is completed.
For instructions on reconstitution and dilution of Empliciti before administration, see section 6.6.
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
The Summary of Product Characteristics for lenalidomide, pomalidomide and dexamethasone used in combination with Empliciti must be consulted before starting therapy.
4.4. Special warnings and precautions for use
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
IRRs
IRRs have been reported in patients receiving elotuzumab (see section 4.8).
Premedication consisting of dexamethasone, H1 blocker, H2 blocker, and paracetamol must be administered prior to Empliciti infusion (see section 4.2 Premedication). The rate of IRRs was much higher in patients who were not premedicated.
If any of the symptoms of IRR reach Grade ≥ 2, Empliciti infusion must be interrupted and appropriate medical and supportive measures instituted. Vital signs should be monitored every 30 minutes for 2 hours after the end of the Empliciti infusion. Once the reaction has resolved (symptoms ≤ Grade 1), Empliciti can be restarted at the initial infusion rate of 0.5 mL/min. If symptoms do not recur, the infusion rate may be gradually escalated every 30 minutes to a maximum of 5 mL/min (see section 4.2 Method of administration).
Very severe IRRs may require permanent discontinuation of Empliciti therapy and emergency treatment. Patients with mild or moderate IRRs may receive Empliciti with a reduced infusion rate and close monitoring (see section 4.2 Method of administration).
Conditions for use of medicinal products used with Empliciti
Empliciti is used in combination with other medicinal products; therefore, the conditions for use applicable to those medicinal products also apply to the combination therapy. The Summary of Product Characteristics for all medicinal products used in combination with Empliciti must be consulted before starting therapy.
Infections
In clinical trials of patients with multiple myeloma, the incidence of all infections, including pneumonia, were higher in patients treated with Empliciti (see section 4.8). Patients should be monitored and infections should be managed with standard treatment.
Second primary malignancies (SPMs)
In a clinical trial of patients with multiple myeloma that compared Empliciti combined with lenalidomide and dexamethasone treatment to lenalidomide and dexamethasone treatment (CA204004), the incidence of SPMs, and specifically of solid tumours and non-melanoma skin cancer, was higher in patient treated with Empliciti (see section 4.8). SPMs are known to be associated with lenalidomide exposure, which was extended in patients treated with Empliciti combined with lenalidomide and dexamethasone vs. lenalidomide and dexamethasone. The rate of haematologic malignancies was the same between the two treatment arms. Patients should be monitored for the development of SPMs.
Excipients
This medicinal product contains 3.92 mg sodium per 300 mg vial or 5.23 mg sodium per 400 mg vial, which is equivalent to 0.2% or 0.3% respectively, of the WHO recommended maximum daily intake of 2 g sodium for an adult.
4.5. Interaction with other medicinal products and other forms of interaction
Pharmacokinetic interaction studies have not been conducted. Empliciti, as a humanised monoclonal antibody, is not expected to be metabolised by cytochrome P450 (CYP) enzymes or other drug metabolising enzymes, inhibition or induction of these enzymes by co-administered medicinal products is not anticipated to affect the pharmacokinetics of Empliciti.
Empliciti may be detected in the serum protein electrophoresis (SPEP) and serum immunofixation assays of myeloma patients and could interfere with correct response classification. The presence of elotuzumab in patient's serum may cause a small peak in the early gamma region on SPEP that is IgGƙ on serum immunofixation. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.
In case of detection of additional peaks on serum immunofixation, the possibility of a biclonal gammopathy should be excluded.
The Summary of Product Characteristics for lenalidomide, pomalidomide and dexamethasone used in combination with Empliciti must be consulted before starting therapy.
4.6. Fertility, pregnancy and lactation
Woman of childbearing potential/Contraception in the males and females
Empliciti should not be used in women of childbearing potential, unless the clinical condition of the woman requires treatment with elotuzumab. Women of childbearing potential should use effective contraception during and for 120 days following treatment.
Male patients must use effective contraception measures during and for 180 days following treatment if their partner is pregnant or of childbearing potential and not using effective contraception.
Pregnancy
There is no human experience with elotuzumab during pregnancy. Elotuzumab will be given in combination with lenalidomide, which is contraindicated during pregnancy. No animal data are present regarding the effect on reproductive toxicity because of the lack of an adequate animal model. Empliciti should not be used during pregnancy unless the clinical condition of the woman requires treatment with elotuzumab.
The Summary of Product Characteristics for all medicinal products used in combination with Empliciti must be consulted before starting therapy. When Empliciti is used with lenalidomide or pomalidomide there is a risk of foetal harm, including severe life-threatening human birth defects associated with these agents and the need to follow requirements regarding pregnancy avoidance, including testing and contraception. Lenalidomide and pomalidomide are present in the blood and sperm of patients receiving the medicine. Refer to the Summary of Product Characteristics for requirements regarding contraception due to presence and transmission in sperm and for additional detail. Patients receiving Empliciti in combination with lenalidomide or pomalidomide should adhere to the pregnancy prevention programme of lenalidomide or pomalidomide respectively.
Breast-feeding
Elotuzumab is not expected to be excreted into human milk. Elotuzumab will be given in combination with lenalidomide or pomalidomide and breast-feeding should be stopped because of the use of lenalidomide or pomalidomide.
Fertility
Studies to evaluate the effect of elotuzumab on fertility have not been performed. Thus, the effect of elotuzumab on male and female fertility is unknown.
4.7. Effects on ability to drive and use machines
On the basis of reported adverse reactions, Empliciti is not expected to influence the ability to drive or use machines. Patients experiencing IRRs should be advised not to drive and use machines until symptoms abate.
4.8. Undesirable effects
Summary of safety profile
The safety data of elotuzumab have been assessed from a total of 682 patients with multiple myeloma treated with elotuzumab in combination with lenalidomide and dexamethasone (451 patients), bortezomib and dexamethasone (103 patients) or pomalidomide and dexamethasone (128 patients) pooled across 8 clinical trials. The majority of adverse reactions were mild to moderate (Grade 1 or 2).
The most serious adverse reaction that may occur during elotuzumab treatment is pneumonia.
The most common adverse reactions (occurring in > 10% of patients) with elotuzumab treatment were IRRs, diarrhoea, herpes zoster, nasopharyngitis, cough, pneumonia, upper respiratory tract infection, lymphopenia and weight decreased.
Tabulated list of adverse reactions
Adverse reactions reported in 682 patients with multiple myeloma who were treated with elotuzumab in 8 clinical trials are presented in Table 5.
These reactions are presented by system organ class and by frequency. Frequencies are defined as:
very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 5: Adverse reactions in patients with multiple myeloma treated with Empliciti
System Organ Class
Adverse reactions
Frequency overall
Grade 3/4 frequency
Infections and infestations
Pneumoniaa
Very common
Common
Herpes zosterb
Common
Uncommon
Upper respiratory tract infection
Very common
Common
Nasopharyngitis
Very common
Not known
Blood and lymphatic system disorders
Lymphopeniac
Very common
Common
Leukopenia
Common
Common
Immune system disorders
Anaphylactic reaction
Uncommon
Uncommon
Hypersensitivity
Common
Uncommon
Psychiatric disorders
Mood altered
Common
Not known
Nervous system disorders
Headache
Very common
Uncommon
Hypoaesthesia
Common
Uncommon
Vascular disorders
Deep vein thrombosis
Common
Common
Respiratory, thoracic and mediastinal
disorders
Coughd
Very common
Uncommon
Oropharyngeal pain
Common
Not known
Gastrointestinal disorders
Diarrhoea
Very common
Common
Skin and subcutaneous tissue disorders
Night sweats
Common
Not known
General disorders and administration site
conditions
Chest pain
Common
Common
Fatigue
Very common
Common
Pyrexia
Very common
Common
Investigations
Weight decreased
Very common
Uncommon
Injury, poisoning and
procedural complications
Infusion related reaction
Common
Uncommon
a The term pneumonia is a grouping of the following terms: pneumonia, atypical pneumonia, bronchopneumonia, lobar pneumonia, bacterial pneumonia, fungal pneumonia, pneumonia influenza, and pneumococcal pneumonia.
b The term herpes zoster is a grouping of the following terms: herpes zoster, oral herpes, and herpes virus infection.
c The term lymphopenia includes the following terms: lymphopenia and lymphocyte count decreased.
d The term cough includes the following terms: cough, productive cough, and upper airway cough syndrome.
Exposure-adjusted rates for adverse reactions (all Grades and Grade 3/4) in CA204004, a clinical trial in patients with multiple myeloma comparing Empliciti combined with lenalidomide and dexamethasone treatment (N = 318) to lenalidomide and dexamethasone treatment (N = 317), is shown in Table 6.
Table 6: CA204004 Exposure-adjusted rates for adverse reactions for Empliciti-treated patients versus lenalidomide and dexamethasone-treated patients [includes multiple occurrences in all treated patients]
Empliciti + Lenalidomide and Dexamethasone
N = 318
Lenalidomide and Dexamethasone
N = 317
All grades
Grade 3/4
All grades
Grade 3/4
Adverse reaction
Event count
Rate (incidence rate/100 patient years)
Event count
Rate (incidence rate/100 patient years)
Event count
Rate (incidence rate/100 patient years)
Event count
Rate (incidence rate/100 patient years)
Diarrhoea
303
59.2
19
3.7
206
49.3
13
3.1
Pyrexia
220
43.0
8
1.6
116
27.7
10
2.4
Fatigue
205
40.0
33
6.4
145
34.7
26
6.2
Cougha
170
33.2
1
0.2
85
20.3
-
-
Nasopharyngitis
151
29.5
-
-
116
27.7
-
-
Upper respiratory tract infection
129
25.2
2
0.4
95
22.7
4
1.0
Lymphopeniab
90
17.6
65
12.7
57
13.6
31
7.4
Headache
88
17.2
1
0.2
40
9.6
1
0.2
Pneumoniac
80
15.6
54
10.5
54
12.9
34
8.1
Leukopenia
70
13.7
19
3.7
65
15.5
21
5.0
Herpes zosterd
51
10.0
5
1.0
24
5.7
3
0.7
Oropharyngeal pain
45
8.8
-
-
17
4.1
-
-
Weight decreased
44
8.6
4
0.8
20
4.8
-
-
Night sweats
31
6.1
-
-
12
2.9
-
-
Chest pain
29
5.7
2
0.4
12
2.9
1
0.2
Deep vein thrombosis
26
5.1
18
3.5
12
2.9
7
1.7
Hypoaesthesia
25
4.9
1
0.2
12
2.9
-
-
Mood altered
23
4.5
-
-
8
1.9
-
-
Hypersensitivity
10
2.0
-
-
4
1.0
1
0.2
a The term cough includes the following terms: cough, productive cough, and upper airway cough syndrome.
b The term lymphopenia includes the following terms: lymphopenia and lymphocyte count decreased.
c The term pneumonia is a grouping of the following terms: pneumonia, atypical pneumonia, bronchopneumonia, lobar pneumonia, bacterial pneumonia, fungal pneumonia, pneumonia influenza, and pneumococcal pneumonia.
d The term herpes zoster is a grouping of the following terms: herpes zoster, oral herpes, and herpes virus infection.
Exposure-adjusted rates for adverse reactions (all Grades and Grade 3/4) in CA204125, a clinical trial in patients with multiple myeloma comparing Empliciti combined with pomalidomide and dexamethasone treatment (N = 60) to pomalidomide and dexamethasone treatment (N = 55), is shown in Table 7.
Table 7: CA204125 Exposure-adjusted rates for adverse reactions for Empliciti-treated patients versus pomalidomide and dexamethasone-treated patients [includes multiple occurrences in all treated patients]
Empliciti + Pomalidomide and Dexamethasone
N = 60
Pomalidomide and Dexamethasone
N = 55
All grades
Grade 3/4
All grades
Grade 3/4
Adverse reaction
Event count
Rate (incidence rate/100 patient years)
Event count
Rate (incidence rate/100 patient years)
Event count
Rate (incidence rate/100 patient years)
Event count
Rate (incidence rate/100 patient years)
Cougha
12
25.2
1
2.1
9
26.2
-
-
Nasopharyngitis
12
25.2
-
-
10
29.1
-
-
Upper respiratory tract infection
9
18.9
-
-
10
29.1
1
2.9
Leukopenia
13
27.3
9
18.9
3
8.7
2
5.8
Lymphopeniab
10
21.0
6
12.6
1
2.9
1
2.9
Pneumoniac
6
12.6
4
8.4
9
26.2
8
23.3
Herpes zosterd
5
10.5
-
-
3
8.7
-
-
Infusion related reaction
2
4.2
1
2.1
1
2.9
-
-
Chest pain
2
4.2
-
-
1
2.9
-
-
Night sweats
1
2.1
-
-
-
0.0
-
-
Hypoaesthesia
1
2.1
-
-
1
2.9
-
-
Mood altered
1
2.1
-
-
1
2.9
-
-
a The term cough includes the following terms: cough, productive cough, and upper airway cough syndrome.
b The term lymphopenia includes the following terms: lymphopenia and lymphocyte count decreased.
c The term pneumonia is a grouping of the following terms: pneumonia, atypical pneumonia, bronchopneumonia, lobar pneumonia, bacterial pneumonia, fungal pneumonia, pneumonia influenza, and pneumococcal pneumonia.
d The term herpes zoster is a grouping of the following terms: herpes zoster, oral herpes, herpes virus infection and ophthalmic herpes zoster.
Description of selected adverse reactions
IRRs
In the clinical trials of patients with multiple myeloma IRRs were reported in approximately 10% of premedicated patients treated with Empliciti combined with lenalidomide and dexamethasone
(N = 318) and 3% of premedicated patients treated with Empliciti combined with pomalidomide and dexamethasone (N = 60) (see section 4.4). The rate of mild to moderate IRRs was > 50% in patients who were not premedicated. All reports of IRR were ≤ Grade 3. Grade 3 IRRs occurred in 1% of patients. In study CA204004, the most common symptoms of an IRR included fever, chills, and hypertension. Five percent (5%) of patients required interruption of the administration of Empliciti for a median of 25 minutes due to IRR, and 1% of patients discontinued due to IRRs. Of the patients who experienced an IRR, 70% (23/33) had the reaction during the first dose. In study CA204125, all of the reported IRRs occurred during the first treatment cycle and were ≤ Grade 2.
Infections
The incidence of infections, including pneumonia, was higher with Empliciti treatment than with control (see section 4.4). In a clinical trial of patients with multiple myeloma (CA204004), infections were reported in 81.4% of patients in the Empliciti combined with lenalidomide and dexamethasone arm (N = 318) and 74.4% in lenalidomide and dexamethasone arm (N = 317). Grade 3-4 infections were noted in 28% and 24.3% of Empliciti combined with lenalidomide and dexamethasone and lenalidomide and dexamethasone treated patients, respectively. Fatal infections were infrequent and were reported in 2.5% of Empliciti combined with lenalidomide and dexamethasone and 2.2% of lenalidomide and dexamethasone treated patients. The incidence of pneumonia was higher in the Empliciti combined with lenalidomide and dexamethasone arm compared to lenalidomide and dexamethasone arm reported at 15.1% vs. 11.7% with a fatal outcome at 0.6% vs. 0%, respectively.
In a clinical trial of patients with multiple myeloma (CA204125), infections were reported in 65% of patients in the Empliciti combined with pomalidomide and dexamethasone arm (N = 60) and 65.5% in the pomalidomide and dexamethasone arm (N = 55). Grade 3-4 infections were noted in 13.3% and 21.8% of Empliciti combined with pomalidomide and dexamethasone and pomalidomide and dexamethasone treated patients, respectively. Fatal infections (i.e. Grade 5 infections) were reported in 5% of Empliciti combined with pomalidomide and dexamethasone and 3.6% of pomalidomide and dexamethasone treated patients.
SPMs
The incidence of SPMs was higher with Empliciti treatment than with control (see section 4.4). In the clinical trial of patients with multiple myeloma (CA204004), invasive SPMs have been observed in 6.9% of patients treated with Empliciti combined with lenalidomide and dexamethasone (N = 318) and 4.1% of patients treated with lenalidomide and dexamethasone (N = 317). SPMs are known to be associated with lenalidomide exposure which was extended in patients treated with Empliciti combined with lenalidomide and dexamethasone vs. lenalidomide and dexamethasone. The rate of haematologic malignancies were the same between the two treatment arms (1.6%). Solid tumours were reported in 2.5% and 1.9% of Empliciti combined with lenalidomide and dexamethasone and lenalidomide and dexamethasone treated patients, respectively. Non-melanoma skin cancer was reported in 3.1% and 1.6% of patients treated with Empliciti combined with lenalidomide and dexamethasone and lenalidomide and dexamethasone, respectively.
There were no SPM events reported in patients treated in the Empliciti combined with pomalidomide and dexamethasone study arm (N = 60) and 1 (1.8%) in patients treated in the pomalidomide and dexamethasone arm (N = 55) in study CA204125.
Deep vein thrombosis
In a clinical trial of patients with multiple myeloma (CA204004), deep vein thromboses were reported in 7.2% of patients treated with Empliciti combined with lenalidomide and dexamethasone (N = 318) and 3.8% of patients treated with lenalidomide and dexamethasone (N = 317). Among, patients treated with aspirin, deep vein thromboses were reported in 4.1% of patients treated with Empliciti combined with lenalidomide and dexamethasone (E-Ld) and 1.4% of patients treated with lenalidomide and dexamethasone (Ld). The rates of deep vein thromboses observed between treatment arms were similar for patients given prophylaxis with low molecular weight heparin (2.2% in both treatment arms), and for patients given vitamin K antagonists the rates were 0% for patients treated with E-Ld and 6.7% for patients treated with Ld.
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity to Empliciti.
Of 390 patients across four clinical trials who were treated with Empliciti and evaluable for the presence of anti-product antibodies, 72 patients (18.5%) tested positive for treatment-emergent anti-product antibodies by an electrochemiluminescent (ECL) assay. Neutralizing antibodies were detected in 19 of 299 patients in CA204004. In the majority of patients, immunogenicity occurred early in treatment and was transient resolving by 2 to 4 months. There was no clear causal evidence of altered pharmacokinetic, efficacy, or toxicity profiles with anti-product antibody development based on the population pharmacokinetic and exposure-response analyses.
Of the 53 patients in CA204125 treated with Empliciti and evaluable for the presence of anti-product antibodies, 19 patients (36%) tested positive, of whom 1 patient tested persistent positive, for treatment-emergent anti-product antibodies by an ECL assay. In these 19 patients, anti-product antibodies occurred within the first 2 months of the initiation of Empliciti treatment. Anti-product antibodies resolved by 2 to 3 months in 18 (95%) of these 19 patients. Neutralizing antibodies were detected in 2 of 53 patients.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
4.9. Overdose
One patient was reported to be overdosed with 23.3 mg/kg bw of elotuzumab in combination with lenalidomide and dexamethasone. The patient had no symptoms, did not require any treatment for the overdose, and was able to continue on elotuzumab therapy.
In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.
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