Summary of the safety profile: The safety data described as follows reflects exposure to DARZALEX (16 mg/kg) in 820 patients with multiple myeloma including 526 patients from two Phase III active-controlled trials who received DARZALEX in combination with either lenalidomide (DRd; n = 283; Study MMY3003) or bortezomib (DVd; n = 243; Study MMY3004) and five open-label, clinical trials in which patients received DARZALEX either in combination with pomalidomide (DPd; n = 103), in combination with lenalidomide (n = 35) or as monotherapy (n = 156).
The most frequent adverse reactions (>20%) in individual randomised controlled studies were infusion reactions, fatigue, nausea, diarrhoea, muscle spasms, pyrexia, cough, dyspnoea, neutropenia, thrombocytopenia and upper respiratory tract infection. In addition, in combination with bortezomib, peripheral oedema and peripheral sensory neuropathy were frequently reported. Serious adverse reactions were pneumonia, upper respiratory tract infection, influenza, pyrexia, diarrhoea, atrial fibrillation.
Tabulated list of adverse reactions: Table 7 summarises the adverse drug reactions that occurred in patients receiving DARZALEX.
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 grouping, where relevant, adverse reactions are presented in order of decreasing seriousness. (See Table 7.)
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Infusion related reactions: In clinical trials (monotherapy and combination treatments; N = 820) the incidence of any grade infusion-related reactions was 46% with the first infusion of DARZALEX, 2% with the second infusion, and 3% with subsequent infusions. Less than 1% of patients had a Grade 3 infusion related reaction with second or subsequent infusions.
The median time to onset of a reaction was 1.4 hours (range: 0.02 to 72.8 hours). The incidence of infusion interruptions due to reactions was 42%. Median durations of infusion for the 1st, 2nd and subsequent infusions were 7, 4.3 and 3.5 hours respectively.
Severe (Grade 3) infusion related reactions included bronchospasm, dyspnoea, laryngeal oedema, pulmonary oedema, hypoxia, and hypertension. Other adverse infusion-related reactions (any Grade, ≥5%) were nasal congestion, cough, chills, throat irritation, vomiting and nausea.
In patients receiving DARZALEX combination therapy, Grade 3 or 4 infections were reported with DARZALEX combinations and background therapies (DVd: 21%, Vd: 19%; DRd: 27%, Rd: 23%; DPd: 28%). Pneumonia was the most commonly reported severe (Grade 3 or 4) infection across studies. Discontinuations from treatment were reported in 2% to 5% of patients. Fatal infections were reported in 0.8% to 2% of patients across studies, primarily due to pneumonia and sepsis.
There is a theoretical risk of haemolysis. Continuous monitoring for this safety signal will be performed in clinical studies and post-marketing safety data.
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.