Infusion related reactions: Infusion related reactions (IRRs) were reported in approximately half of all patients treated with DARZALEX. Monitor such patients throughout the infusion and the post infusion period.
The majority of IRRs occurred at the first infusion. Four percent of all patients had an IRR at more than one infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnoea, hypertension, laryngeal oedema and pulmonary oedema. Symptoms predominantly included nasal congestion, cough, throat irritation, chills, vomiting and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus and hypotension (see ADVERSE REACTIONS).
Patients should be pre-medicated with antihistamines, antipyretics and corticosteroids to reduce the risk of IRRs prior to treatment with DARZALEX. DARZALEX infusion should be interrupted for IRRs of any severity. Medical management/supportive treatment for IRRs should be instituted as needed. The infusion rate should be reduced when re-starting the infusion (see DOSAGE & ADMINISTRATION).
To reduce the risk of delayed IRRs, oral corticosteroids should be administered to all patients following DARZALEX infusions. Additionally the use of post-infusion medications (e.g. inhaled corticosteroids, short and long acting bronchodilators) should be considered for patients with a history of chronic obstructive pulmonary disease to manage respiratory complications should they occur (see DOSAGE & ADMINISTRATION).
DARZALEX therapy should be permanently discontinued in the event of life-threatening IRRs.
Neutropenia/Thrombocytopenia: DARZALEX may increase neutropenia and thrombocytopenia induced by background therapy (see ADVERSE REACTIONS).
Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. DARZALEX delay may be required to allow recovery of blood cell counts. No dose reduction of DARZALEX is recommended. Consider supportive care with transfusions or growth factors.
Interference with Indirect Antiglobulin Test (Indirect Coombs Test): Daratumumab binds to CD38 found at low levels on red blood cells (RBCs) and may result in a positive indirect Coombs test. Daratumumab-mediated positive indirect Coombs test may persist for up to 6 months after the last daratumumab infusion. It should be recognised that daratumumab bound to RBCs may mask detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted.
Patients should be typed and screened prior to starting daratumumab treatment. Phenotyping may be considered prior to starting daratumumab treatment as per local practice. Red blood cell genotyping is not impacted by daratumumab and may be performed at any time.
In the event of a planned transfusion blood transfusion centres should be notified of this interference with indirect antiglobulin tests (see INTERACTIONS). If an emergency transfusion is required, non-cross matched ABO/RhD-compatible RBCs can be given per local blood bank practices.
Interference with determination of Complete Response: Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both, the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein (see INTERACTIONS). This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
Excipients: Each 5 mL and 20 mL vial of DARZALEX contains 0.4 mmol and 1.6 mmol (9.3 mg and 37.3 mg) sodium, respectively. This should be taken into consideration by patients on a controlled sodium diet.
Effects on Ability to Drive and Use Machines: DARZALEX has no or negligible influence on the ability to drive and use machines. However, fatigue has been reported in patients taking daratumumab and this should be taken into account when driving or using machines.