DARZALEX 1,800 mg solution for injection *

  • Company:

    Janssen Sciences Ireland
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    No Recent Update
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    Product subject to medical prescription which may not be renewed (A)
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    This medicinal product is subject to additional monitoring.

    *Additional information is available within the SPC or upon request to the company

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 24 June 2021

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IRE & NI Darzalex_SC_1800 mg_PIL- C05_21Jun21-clean_1624533841.pdf

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects

Updated on 24 June 2021

File name

IE&NI_Darzalex-SC-1800 mg SmPC-43 -44-clean-21Jun21_1624533721.pdf

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.1     Therapeutic indications

 

Multiple Myeloma

DARZALEX is indicated:

  • in combination with lenalidomide and dexamethasone or with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
  • in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.
  • in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
  • in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one prior therapy containing a proteasome inhibitor and lenalidomide and were lenalidomide‑refractory, or who have received at least two prior therapies that included lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or after the last therapy (see section 5.1).
  • in as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.
     
    AL Amyloidosis
    DARZALEX is indicated in combination with cyclophosphamide, bortezomib and dexamethasone for the treatment of adult patients with newly diagnosed systemic light chain (AL) amyloidosis.
     
    4.2     Posology and method of administration
     
    Posology
     
    Multiple Myeloma
    Dosing schedule in combination with lenalidomide or pomalidomide (4‑week cycle regimen) and for monotherapy
    The recommended dose is 1 800 mg of DARZALEX solution for subcutaneous injection administered over approximately 3‑5 minutes according to the following dosing schedule in Table 1.
     

Table 1:      DARZALEX dosing schedule in combination with lenalidomide and dexamethasone (Rd), pomalidomide and dexamethasone (Pd) (4‑week cycle dosing regimen) and monotherapy

Weeks

Schedule

Weeks 1 to 8

weekly (total of 8 doses)

Weeks 9 to 24a

every two weeks (total of 8 doses)

Week 25 onwards until disease progressionb

every four weeks

a    First dose of the every-2-week dosing schedule is given at Week 9

b    First dose of the every-4-week dosing schedule is given at Week 25

 

Dexamethasone should be administered at 40 mg/week (or a reduced dose of 20 mg/week for patients >75 years).

 

For dose and schedule of medicinal products administered with DARZALEX solution for subcutaneous injection, see section 5.1 and the corresponding Summary of Product Characteristics.

 

Table 3:      DARZALEX dosing schedule in combination with bortezomib, thalidomide and dexamethasone ([VTd]; 4‑week cycle dosing regimen)

Treatment phase

Weeks

Schedule

Induction

Weeks 1 to 8

weekly (total of 8 doses)

Weeks 9 to 16a

every two weeks (total of 4 doses)

Stop for high dose chemotherapy and ASCT

Consolidation

Weeks 1 to 8b

every two weeks (total of 4 doses)

a       First dose of the every-2-week dosing schedule is given at Week 9

b      First dose of the every-2-week dosing schedule is given at Week 1 upon re-initiation of treatment following ASCT

 

Dexamethasone should be administered at 40 mg on Days 1, 2, 8, 9, 15, 16, 22 and 23 of Cycles 1 and 2, and at 40 mg on Days 1-2 and 20 mg on subsequent dosing days (Days 8, 9, 15, 16) of Cycles 3-4. Dexamethasone 20 mg should be administered on Days 1, 2, 8, 9, 15, 16 in Cycles 5 and 6.

 

For dose and schedule of medicinal products administered with DARZALEX solution for subcutaneous injection, see section 5.1 and the corresponding Summary of Product Characteristics.

 

Dosing schedule in combination with bortezomib (3‑week cycle regimen)

The recommended dose is 1 800 mg of DARZALEX solution for subcutaneous injection administered over approximately 3‑5 minutes according to the following dosing schedule in Table 4.

 

Table 4:      DARZALEX dosing schedule in combination with bortezomib and dexamethasone (Vd) (3‑week cycle dosing regimen)

Weeks

Schedule

Weeks 1 to 9

weekly (total of 9 doses)

Weeks 10 to 24a

every three weeks (total of 5 doses)

Week 25 onwards until disease progressionb

every four weeks

a    First dose of the every-3-week dosing schedule is given at Week 10

b       First dose of the every-4-week dosing schedule is given at Week 25

 

Dexamethasone should be administered at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 bortezomib treatment cycles or a reduced dose of 20 mg/week for patients >75 years, underweight (BMI <18.5), poorly controlled diabetes mellitus or prior intolerance to steroid therapy.

 

For dose and schedule of medicinal products administered with DARZALEX solution for subcutaneous injection, see section 5.1 and the corresponding Summary of Product Characteristics.

 

AL Amyloidosis

Dosing schedule in combination with bortezomib, cyclophosphamide and dexamethasone (4‑week cycle regimens)

The recommended dose is 1 800 mg of DARZALEX solution for subcutaneous injection administered over approximately 3‑5 minutes according to the following dosing schedule in Table 5.

 

Table 5:      DARZALEX dosing schedule for AL amyloidosis in combination with bortezomib, cyclophosphamide and dexamethasone ([VCd];4‑week cycle dosing regimen)a

Weeks

Schedule

Weeks 1 to 8

weekly (total of 8 doses)

Weeks 9 to 24b

every two weeks (total of 8 doses)

Week 25 onwards until disease progressionc

every four weeks

a    In the clinical trial, DARZALEX was given until disease progression or a maximum of 24 cycles (~2 years) from the first dose of study treatment.

b    First dose of the every-2-week dosing schedule is given at Week 9

c    First dose of the every-4-week dosing schedule is given at Week 25

 

For dose and schedule of medicinal products administered with DARZALEX solution for subcutaneous injection, see section 5.1 and the corresponding Summary of Product Characteristics.

4.4     Special warnings and precautions for use

 

Infusion‑related reactions

DARZALEX solution for subcutaneous injection can cause severe and/or serious IRRs, including anaphylactic reactions. In clinical studies, approximately 119% (5274/490832) of patients experienced an IRR. Most IRRs occurred following the first injection and were Grade 1‑2. IRRs occurring with subsequent injections were seen in less than 1% of patients (see section 4.8).

 

The median time to onset of IRRs following DARZALEX injection was 3.73.2 hours (range 0.15‑83 hours). The majority of IRRs occurred on the day of treatment. Delayed IRRs have occurred in less than 1% of patients.

 

4.5     Interaction with other medicinal products and other forms of interaction

 

Clinical pharmacokinetic assessments with daratumumab intravenous or subcutaneous formulations and lenalidomide, pomalidomide, thalidomide, bortezomib, melphalan, prednisone, carfilzomib, cyclophosphamide and dexamethasone indicated no clinically‑relevant drug‑drug interaction between daratumumab and these small molecule medicinal products.

 

4.8     Undesirable effects

Summary of the safety profile

The most frequent adverse reactions of any grade (≥20% patients) with daratumumab (either intravenous or subcutaneous formulations) when administered either as monotherapy or combination treatment were IRRs, fatigue, nausea, diarrhoea, constipation, pyrexia, cough, neutropenia, thrombocytopenia, anaemia, oedema peripheral, peripheral sensory neuropathy and upper respiratory tract infection. Serious adverse reactions were pneumonia, bronchitis, upper respiratory tract infection, sepsis, pulmonary oedema, influenza, pyrexia, dehydration, diarrhoea, and atrial fibrillation and syncope.

 

With the exception of IRRs (see Table 5 below), tThe safety profile of the DARZALEX subcutaneous formulation (evaluated in 260 and 258 patients treated with the subcutaneous and intravenous formulations respectively) from the Phase III study MMY3012 was similar to that of the known safety profile of the intravenous formulation with the exception of a lower rate of IRRs. In the Phase III study MMY3012, Nneutropenia is was the only adverse reaction reported at ≥ 5% higher frequency for DARZALEX subcutaneous formulation compared to intravenous daratumumab (Grade 3 or 4: 13% vs 8%, respectively).

 

Tabulated list of adverse reactions

Table 56 summarises the adverse reactions that occurred in patients receiving DARZALEX subcutaneous formulation or intravenous formulation of daratumumab.

 

The data reflects exposure to DARZALEX subcutaneous formulation (1 800 mg) in 490 639 patients with multiple myeloma (MM). The data includesing 260 patients from a Phase III active‑controlled trial (Study MMY3012) who received DARZALEX solution for subcutaneous injection as monotherapy and 149 patients from a Phase III active-controlled trial (MMY3013) who received DARZALEX subcutaneous formulation in combination with pomalidomide and dexamethasone (D-Pd). andThe data also reflects three open‑label, clinical studies in which patients received DARZALEX solution for subcutaneous injection either as monotherapy (N=31, MMY1004 and MMY1008) and MMY2040 in which patients received DARZALEX solution for subcutaneous injection in combination with either bortezomib, melphalan and prednisone (D‑VMP, n=67), lenalidomide and dexamethasone (D‑Rd, n=65) or bortezomib, lenalidomide and dexamethasone (D‑VRd, n=67). Additionally, data reflect exposure to 193 patients with newly diagnosed AL amyloidosis from a Phase III active-controlled trial (Study AMY3001) in which patients received DARZALEX subcutaneous formulation in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd).

 

Table 56:    Adverse reactions in multiple myeloma and AL amyloidosis patients treated with intravenous daratumumab or subcutaneous daratumumab

 

 

System Organ Class

Adverse reaction

Frequency

Incidence (%)

Any Grade

Grade 3-4

Infections and infestations

Upper respiratory tract infectiona

Very Common

Very Common

Very Common

3837%

2%

BronchitisaPneumoniaa

14%17

2%10

PneumoniaaBronchitisa

14%

9%1

Urinary tract infection

Common

Common

Common

7%6

1%

Influenza

4%

1%#

Sepsisa

4%

3%

Cytomegalovirus infectiona

Common

Uncommon

<11%

<1#<1%#

Hepatitis B Virus reactivationa

<1%

<1%

Blood and lymphatic system disorders

Neutropeniaa

Very Common

Very Common

Very Common

Very Common

Very Common

40%39

33%

Thrombocytopeniaa

30%29

18%17

Anaemiaa

27%

12%

Lymphopeniaa

13%14

11%

Leukopeniaa

11%

6%

Immune system disorders

Anaphylactic reactionb

Rare

-

-

Metabolism and nutrition disorders

Decreased appetite

Very Common

10%

1%

Hyperglycaemia

Common

Common

Common

6%

3%

Hypocalcaemia

5%

1%

Dehydration

2%

1%#

Psychiatric disorders

Insomnia

Very Common

14%15

1%#

Nervous system disorders

Peripheral sensory neuropathy

Very Common

Very Common

26%

3%

Headache

1110%

<1%#

Dizziness

Common

Common

9%

<1%#

Paraesthesia

9%

<1%

Syncope

3

2#

Cardiac disorders

Atrial fibrillation

Common

3%

1%

Vascular disorders

Hypertensiona

Very Common

10%9

5%4

Respiratory, thoracic and mediastinal disorders

Cougha

Very Common

Very Common

22%21

<1%#

Dyspnoeaa

18%

2%

Pulmonary oedemaa

Common

1%

<1%

Gastrointestinal disorders

Diarrhoea

Very Common

Very Common

Very Common

Very Common

29%

3%4

Constipation

28%

1%

Nausea

23%22

1%#

Vomiting

14%

1%#

Pancreatitisa

Common

1%

<1%

Skin and subcutaneous tissue disorders

Rash

Very Common

9%10

<1%#

Pruritus

Common

5%6

<1%#

Musculoskeletal and connective tissue disorders

Back pain

Very Common

Very Common

Very Common

17%16

2%

Muscle spasms

12%11

<1%#

Arthralgia

10%

<1%#

Musculoskeletal chest pain

Common

6%

<1%#

General disorders and administration site conditions

Fatigue

Very Common

Very Common

Very Common

Very Common

23%

3%4

Oedema peripherala

22%

1%

Pyrexia

22%21

1%

Asthenia

18%

2%

Chills

Injection site erythemae

Common

Common

Common

9%8

4%

<1%#

0

Injection site reactionsd,e

8%

0

Injury, poisoning and procedural complications

Infusion‑related reactionsc

 

 

 

Daratumumab intravenousf

Very Common

39%

5%

Daratumumab subcutaneouse

Very Common

11%9

1%#

 

 

Significant changes to Sections 5.1 and 5.2

Clinical pharmacokinetic assessments with daratumumab intravenous or subcutaneous formulations and lenalidomide, pomalidomide, thalidomide, bortezomib, melphalan, prednisone, carfilzomib, cyclophosphamide and dexamethasone indicated no clinically‑relevant drug‑drug interaction between daratumumab and these small molecule medicinal products.

 

4.8     Undesirable effects

Summary of the safety profile

The most frequent adverse reactions of any grade (≥20% patients) with daratumumab (either intravenous or subcutaneous formulations) when administered either as monotherapy or combination treatment were IRRs, fatigue, nausea, diarrhoea, constipation, pyrexia, cough, neutropenia, thrombocytopenia, anaemia, oedema peripheral, peripheral sensory neuropathy and upper respiratory tract infection. Serious adverse reactions were pneumonia, bronchitis, upper respiratory tract infection, sepsis, pulmonary oedema, influenza, pyrexia, dehydration, diarrhoea, and atrial fibrillation and syncope.

 

With the exception of IRRs (see Table 5 below), tThe safety profile of the DARZALEX subcutaneous formulation (evaluated in 260 and 258 patients treated with the subcutaneous and intravenous formulations respectively) from the Phase III study MMY3012 was similar to that of the known safety profile of the intravenous formulation with the exception of a lower rate of IRRs. In the Phase III study MMY3012, Nneutropenia is was the only adverse reaction reported at ≥ 5% higher frequency for DARZALEX subcutaneous formulation compared to intravenous daratumumab (Grade 3 or 4: 13% vs 8%, respectively).

 

Tabulated list of adverse reactions

Table 56 summarises the adverse reactions that occurred in patients receiving DARZALEX subcutaneous formulation or intravenous formulation of daratumumab.

 

The data reflects exposure to DARZALEX subcutaneous formulation (1 800 mg) in 490 639 patients with multiple myeloma (MM). The data includesing 260 patients from a Phase III active‑controlled trial (Study MMY3012) who received DARZALEX solution for subcutaneous injection as monotherapy and 149 patients from a Phase III active-controlled trial (MMY3013) who received DARZALEX subcutaneous formulation in combination with pomalidomide and dexamethasone (D-Pd). andThe data also reflects three open‑label, clinical studies in which patients received DARZALEX solution for subcutaneous injection either as monotherapy (N=31, MMY1004 and MMY1008) and MMY2040 in which patients received DARZALEX solution for subcutaneous injection in combination with either bortezomib, melphalan and prednisone (D‑VMP, n=67), lenalidomide and dexamethasone (D‑Rd, n=65) or bortezomib, lenalidomide and dexamethasone (D‑VRd, n=67). Additionally, data reflect exposure to 193 patients with newly diagnosed AL amyloidosis from a Phase III active-controlled trial (Study AMY3001) in which patients received DARZALEX subcutaneous formulation in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd).

 

Table 56:    Adverse reactions in multiple myeloma and AL amyloidosis patients treated with intravenous daratumumab or subcutaneous daratumumab

 

 

System Organ Class

Adverse reaction

Frequency

Incidence (%)

Any Grade

Grade 3-4

Infections and infestations

Upper respiratory tract infectiona

Very Common

Very Common

Very Common

3837%

2%

BronchitisaPneumoniaa

14%17

2%10

PneumoniaaBronchitisa

14%

9%1

Urinary tract infection

Common

Common

Common

7%6

1%

Influenza

4%

1%#

Sepsisa

4%

3%

Cytomegalovirus infectiona

Common

Uncommon

<11%

<1#<1%#

Hepatitis B Virus reactivationa

<1%

<1%

Blood and lymphatic system disorders

Neutropeniaa

Very Common

Very Common

Very Common

Very Common

Very Common

40%39

33%

Thrombocytopeniaa

30%29

18%17

Anaemiaa

27%

12%

Lymphopeniaa

13%14

11%

Leukopeniaa

11%

6%

Immune system disorders

Anaphylactic reactionb

Rare

-

-

Metabolism and nutrition disorders

Decreased appetite

Very Common

10%

1%

Hyperglycaemia

Common

Common

Common

6%

3%

Hypocalcaemia

5%

1%

Dehydration

2%

1%#

Psychiatric disorders

Insomnia

Very Common

14%15

1%#

Nervous system disorders

Peripheral sensory neuropathy

Very Common

Very Common

26%

3%

Headache

1110%

<1%#

Dizziness

Common

Common

9%

<1%#

Paraesthesia

9%

<1%

Syncope

3

2#

Cardiac disorders

Atrial fibrillation

Common

3%

1%

Vascular disorders

Hypertensiona

Very Common

10%9

5%4

Respiratory, thoracic and mediastinal disorders

Cougha

Very Common

Very Common

22%21

<1%#

Dyspnoeaa

18%

2%

Pulmonary oedemaa

Common

1%

<1%

Gastrointestinal disorders

Diarrhoea

Very Common

Very Common

Very Common

Very Common

29%

3%4

Constipation

28%

1%

Nausea

23%22

1%#

Vomiting

14%

1%#

Pancreatitisa

Common

1%

<1%

Skin and subcutaneous tissue disorders

Rash

Very Common

9%10

<1%#

Pruritus

Common

5%6

<1%#

Musculoskeletal and connective tissue disorders

Back pain

Very Common

Very Common

Very Common

17%16

2%

Muscle spasms

12%11

<1%#

Arthralgia

10%

<1%#

Musculoskeletal chest pain

Common

6%

<1%#

General disorders and administration site conditions

Fatigue

Very Common

Very Common

Very Common

Very Common

23%

3%4

Oedema peripherala

22%

1%

Pyrexia

22%21

1%

Asthenia

18%

2%

Chills

Injection site erythemae

Common

Common

Common

9%8

4%

<1%#

0

Injection site reactionsd,e

8%

0

Injury, poisoning and procedural complications

Infusion‑related reactionsc

 

 

 

Daratumumab intravenousf

Very Common

39%

5%

Daratumumab subcutaneouse

Very Common

11%9

1%#

 

 

Significant changes to Sections 5.1 and 5.2

Clinical pharmacokinetic assessments with daratumumab intravenous or subcutaneous formulations and lenalidomide, pomalidomide, thalidomide, bortezomib, melphalan, prednisone, carfilzomib, cyclophosphamide and dexamethasone indicated no clinically‑relevant drug‑drug interaction between daratumumab and these small molecule medicinal products.

 

Updated on 17 June 2021

File name

IRE & NI Darzalex_SC_1800 mg_PIL- C04 20 May 21-CLEAN_1623952801.pdf

Reasons for updating

  • Change to section 6 - date of revision
  • Change to information for healthcare professionals

Updated on 17 June 2021

File name

IE&NI_Darzalex-SC-1800 mg SmPC-C05-047-Clean-approved (1)_1623952723.pdf

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.4       Special warnings and precautions for use

 

Traceability

In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded.

 

Section 4.8

 

Infections

In patients receiving DARZALEX combination therapy, Grade 3 or 4 infections were reported as follows:

Relapsed/refractory patient studies: DVd: 21%, Vd: 19%; DRd: 287%, Rd: 23%; DPd: 28%

Newly diagnosed patient studies: D‑VMP: 23%, VMP: 15%; DRd: 32%, Rd: 23%; D-VTd: 22%, VTd: 20%.

 

Updated on 13 January 2021

File name

IRE Darzalex_SC_1800 mg_PIL- C03_ 03 Dec 2020-041-CLEAN_1610574544.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 13 January 2021

File name

Darzalex SC-1800 mg SmPC-C04-041-CLEAN-approved_1610574149.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.8 Undesirable effects

Infections and infestations

Pneumoniaa

Very Common

16

10

Bronchitisa

17

2

Upper respiratory tract infectiona

41

3

Urinary tract infection

Common

8

1

Influenza

5

1*

Sepsisa

4

4

Cytomegalovirus infectiona

1

<1*

Hepatitis B Virus reactivationb

Uncommon

-

-

Updated on 20 August 2020

File name

Darzalex SC-1800 mg SmPC-C03-038-Clean-approved_1597916790.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.8     Undesirable effects

 

 

Summary of the safety profile

The most frequent adverse reactions of any grade (≥20 % patients) with daratumumab (either intravenous or subcutaneous formulations) when administered either as monotherapy or combination treatment were IRRs, fatigue, nausea, diarrhoea, constipation, pyrexia, cough, neutropenia, thrombocytopenia, anaemia, oedema peripheral, peripheral sensory neuropathy and upper respiratory tract infection. Serious adverse reactions were pneumonia, bronchitis, upper respiratory tract infection, sepsis, pulmonary oedema, influenza, pyrexia, dehydration, diarrhoea and atrial fibrillation.

 

…………………

 

System Organ Class

Adverse reaction

Frequency

Incidence (%)

Any Grade

Grade 3-4

Infections and infestations

Upper respiratory tract infectiona

Very Common

38%

2%

Bronchitisa

Very Common

14%

2%

Pneumoniaa

Very Common

14%

9%

Urinary tract infection

Common

7%

1%

Influenza

Common

4%

1%#

Sepsisa

Common

4%

3%

 

 

………………………..

 

Infections

In patients receiving DARZALEX subcutaneous formulation as monotherapy, incidence of infections was similar between DARZALEX subcutaneous formulation (52.9%) versus intravenous daratumumab groups (50.0%). Additionally, Grade 3 or 4 infections also occurred at similar frequencies between DARZALEX subcutaneous formulation (11.7%) and intravenous daratumumab (14.3%). Most infections were manageable and rarely led to treatment discontinuation. Pneumonia was the most commonly reported severe (Grade 3 or 4) infection across studies.

 

In patients receiving intravenous daratumumab combination therapy, Grade 3 or 4 infections were reported with intravenous daratumumab combinations and background therapies (as follows:

Relapsed/refractory patient studies: DVd: 21%, Vd: 19%; DRd: 27%, Rd: 23%; D‑VMP: 23%, VMP: 15%; DPd: 28%

Newly diagnosed patient studies: D‑VMP: 23%, VMP: 15%; DRd: 32%, Rd: 23%; D‑VTd: 22%, VTd: 20%.).

Pneumonia was the most commonly reported severe (Grade 3 or 4) infection across studies. In active controlled studies, Ddiscontinuations from treatment due to infections were reportedoccurred in 1-4% to 5% of patients. Fatal infections were generally balanced between the intravenous daratumumab containing regimens and active control arms (<2%) in the controlled studies and were primarily due to pneumonia and sepsis.

In patients receiving intravenous daratumumab combination therapy, fatal infections (Grade 5) were reported as follows:

Relapsed/refractory patient studies: DVd: 1%, Vd: 2%; DRd: 2%, Rd: 1%; DPd: 2%

Newly diagnosed patient studies: D-VMP: 1%, VMP: 1%; DRd: 2%, Rd: 2%; DVTd: 0%, VTd: 0%.

Key: D=daratumumab; Vd=bortezomib-dexamethasone; Rd=lenalidomide-dexamethasone; Pd=pomalidomide-dexamethasone; VMP=bortezomib-melphalan-prednisone; VTd=bortezomib-thalidomide-dexamethasone.

 

 

………………….

 

Elderly patients

Of the 3207 patients who received daratumumab (n=490 subcutaneous; n=2717 intravenous) at the recommended dose, 38% were 65 to 75 years of age, and 17% were 75 years of age or older. No overall differences in effectiveness were observed based on age. The incidence of serious adverse reactions was higher in older than in younger patients. Among patients with relapsed and refractory multiple myeloma (n=1827), the most common serious adverse reactions that occurred more frequently in elderly (≥65 years of age) were pneumonia and sepsis. Among patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (n=777), the most common serious adverse reaction that occurred more frequently in elderly (≥75 years of age) was pneumonia.

Updated on 20 August 2020

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IRE-Darzalex_SC_1800 mg _PIL_C02-038-Clean-approved_1597916672.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

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Common (may affect up to 1 in 10 people):

  • irregular heart beat (atrial fibrillation)
  • build up of fluid in the lungs making you short of breath
  • flu
  • urinary tract infection
  • severe infection throughout the body (sepsis)
  • dehydration
  • high level of sugar in the blood
  • low level of calcium in the blood
  • inflamed pancreas

Updated on 23 July 2020

File name

Darzalex SC-1800 mg SmPC-C02-Clean-11 June 2020_1595490378.pdf

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

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5.1          Pharmacodynamic properties

Immunogenicity

In patients treated with subcutaneous daratumumab in clinical trials, less than 1% of patients developed treatment-emergent anti-daratumumab antibodies. The incidence of treatment‑emergent anti‑daratumumab antibodies for DARZALEX subcutaneous formulation treatment was low, with 1 out of 451 patients tested positive for anti‑drug antibodies. The 1 patient in monotherapy that was positive for anti‑daratumumab antibody also had transient neutralising antibodies. There were no treatment‑emergent anti‑daratumumab antibody positive patients in combination therapies study. The anti‑daratumumab antibodies and neutralising antibodies did not appear to impact daratumumab exposures.

 

However, the employed assay has limitations in detecting anti‑daratumumab antibodies in the presence of high concentrations of daratumumab. Therefore, the incidence of antibody development might not have been reliably determined.

Updated on 23 July 2020

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EDM Updated on 10 July 2020

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EDM Updated on 10 July 2020

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Darzalex RMP Blood Lab Card June 2020 Update_1594373944.pdf

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EDM Updated on 10 July 2020

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Updated on 11 June 2020

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Updated on 11 June 2020

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Darzalex SC_1800 mg-SmPC-C01-03Jun2020_1591882259.pdf

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New SmPC for new Product June 2020