DARZALEX

DARZALEX should be administered by a healthcare professional, in an environment where resuscitation facilities are available. Pre- and post-infusion medicinal products should be administered to reduce the risk of infusion-related reactions (IRRs) with daratumumab.

See below “Recommended concomitant medicinal products”, “Management of infusion-related reactions” and section

Summary of the safety profile The most frequent adverse reactions of any grade (≥ 20% patients) were IRRs, fatigue, nausea, diarrhoea, constipation, pyrexia, dyspnoea, cough, neutropenia, thrombocytopenia, anaemia, oedema peripheral, asthenia, peripheral neuropathy, upper respiratory tract infection, musculoskeletal pain and COVID-19.

Serious adverse reactions were sepsis, pneumonia, bronchitis, upper respiratory tract infection, pulmonary oedema, influenza, pyrexia, dehydration, diarrhoea and atrial fibrillation. Tabulated list of adverse reactions Table 6 summarises the adverse reactions that occurred in patients receiving DARZALEX.

The data reflects exposure to DARZALEX (16 mg/kg) in 2066 patients with multiple myeloma including 1910 patients who received DARZALEX in combination with background regimens and 156 patients who received DARZALEX as monotherapy. Post-marketing adverse reactions are also included.

9%). 0 x 109/L, and platelets > 50 x 109/L without transfusion). 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) and very rare (<1/10,000). Within each frequency groupingadverse reactions are presented in the order of decreasing seriousness.

Table 6:

Adverse reactions in multiple myeloma patients treated with DARZALEX 16 mg/kg Incidence (%) System organ class Adverse reaction Frequency Any grade Grade 3-4 Upper respiratory tract infectiona 46 4 COVID-19a, d 23 6 Bronchitisa 17 2 Pneumoniaa Very common 19 11 Urinary tract infection 8 1 Sepsisa 4 4 Cytomegalovirus infectiona Common 1 <1* Infections and infestations Hepatitis B Virus reactivationb Uncommon - - Neutropeniaa 44 39 Thrombocytopeniaa 31 19 Anaemiaa 27 12 Lymphopeniaa 14 11 Blood and lymphatic system disorders Leukopeniaa Very common 12 6 Anaphylactic reactionb Rare - - Immune system disorders Hypogammaglobulinaemiaa Common 3 <1* Decreased appetite 12 1 Hypokalaemiaa Very common 10 3 Hyperglycaemia 7 3 Hypocalcaemia 6 1 Metabolism and nutrition disorders Dehydration Common 3 1* Psychiatric disorders Insomnia Very common 16 1* Peripheralneuropathya 35 4 Headache 12 <1* Paraesthesia 11 <1 Dizziness Very common 10 <1* Nervous system disorders Syncope Common 2 2* Cardiac disorders Atrial fibrillation Common 4 1 Vascular disorders Hypertensiona Very common 10 5 Cougha 25 < 1* Dyspnoeaa Very common 21 3 Respiratory, thoracic and mediastinal disorders Pulmonary oedemaa Common 1 < 1 Constipation 33 1 Diarrhoea 32 4 Nausea 26 2* Vomiting 16 1* Abdominal paina Very common 14 1 Gastrointestinal disorders Pancreatitisa Common 1 1 Rash Very common 13 1*Skin and subcutaneous tissue disorders Pruritus Common 7 < 1* Musculoskeletal paina,e 37 4 Arthralgia 14 1 Musculoskeletal and connective tissue disorders Muscle spasms Very common 14 < 1* Oedema peripherala a 27 1 Fatigue 26 4 Pyrexia 23 2 Asthenia Very common 21 2 General disorders and administration site conditions Chills Common 9 < 1* Injury, poisoning and procedural complications Infusion-related reactionc Very common 40 4 * No grade 4 a Indicates grouping of terms b Post-marketing adverse reaction c Infusion-related reaction includes terms determined by investigators to be related to infusion, see below d Incidence is based on a subset of patients who received at least one dose of study treatment on or after 01 February 2020 (the start of the COVID-19 pandemic) from studies MMY3003, MMY3006, MMY3008 and MMY3013, and all daratumumab treated patients from studies MMY3014, MMY3019, and SMM3001 (N=1177).

4. Posology Dosing schedule in combination with lenalidomide and dexamethasone (4-week cycle regimen) and for monotherapy The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule in table 1.

Table 1:

DARZALEX dosing schedule in combination with lenalidomide and dexamethasone (Rd) (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).

1 and the corresponding Summary of Product Characteristics. Dosing schedule in combination with bortezomib, melphalan and prednisone (6-week cycle regimens) The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule in table 2.

Table 2:

DARZALEX dosing schedule in combination with bortezomib, melphalan and prednisone ([VMP]; 6-week cycle dosing regimen) Weeks Schedule Weeks 1 to 6 weekly (total of 6 doses) Weeks 7 to 54a every three weeks (total of 16 doses) Week 55 onwards until disease progressionb every four weeks a First dose of the every-3-week dosing schedule is given at Week 7 b First dose of the every-4-week dosing schedule is given at Week 55 Bortezomib is given twice weekly at weeks 1, 2, 4 and 5 for the first 6-week cycle, followed by once weekly at weeks 1, 2, 4 and 5 for eight more 6-week cycles.

1. Dosing schedule in combination with bortezomib, thalidomide and dexamethasone (4- week cycle regimens) for treatment of newly diagnosed patients eligible for autologous stem cell transplant (ASCT) The recommended dose is DARZALEX 16 mg/kg body weight administered as an intravenous infusion according to the following dosing schedule in table 3.

1.