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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.
Infusion-related reactions: Concentrate for solution for IV infusion: DARZALEX can cause serious IRRs, including anaphylactic reactions (see Adverse Reactions).
All patients should be monitored throughout the infusion for IRRs. For patients that experience any Grade IRRs, continue monitoring post-infusion until symptoms resolve.
In clinical studies, IRRs were reported in approximately half of all patients treated with DARZALEX.
The majority of IRRs occurred at the first infusion and were Grade 1-2 (see Adverse Reactions). 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 and medical management/supportive treatment for IRRs should be instituted as needed. For patients with Grade 1, 2, or 3 IRRs, the infusion rate should be reduced when re-starting the infusion. If an anaphylactic reaction or life-threatening (Grade 4) infusion reaction occurs, appropriate emergency resuscitation should be initiated immediately. DARZALEX therapy should be discontinued immediately and permanently (see Dosage & Administration and Contraindications).
To reduce the risk of delayed IRRs, oral corticosteroids should be administered to all patients following DARZALEX infusions. Additionally the use of post-infusion medicinal products (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).
Solution for SC injection: DARZALEX solution for subcutaneous injection can cause severe and/or serious IRRs, including anaphylactic reactions. In clinical studies, approximately 9% (74/832) 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 1% of patients (see Adverse Reactions).
The median time to onset of IRRs following DARZALEX injection was 3.2 hours (range 0.15-83 hours). The majority of IRRs occurred on the day of treatment. Delayed IRRs have occurred in 1% of patients.
Signs and symptoms of IRRs may include respiratory symptoms, such as nasal congestion, cough, throat irritation, allergic rhinitis, wheezing as well as pyrexia, chest pain, pruritus, chills, vomiting, nausea, and hypotension. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnoea, hypertension and tachycardia (see Adverse Reactions).
Patients should be pre-medicated with antihistamines, antipyretics, and corticosteroids as well as monitored and counselled regarding IRRs, especially during and following the first and second injections. If an anaphylactic reaction or life-threatening (grade 4) reactions occur, appropriate emergency care should be initiated immediately. DARZALEX therapy should be discontinued immediately and permanently (see Dosage & Administration and Contraindications).
To reduce the risk of delayed IRRs, oral corticosteroids should be administered to all patients following DARZALEX injection (see Dosage & Administration). Patients with a history of chronic obstructive pulmonary disease may require additional post-injection medicinal products to manage respiratory complications. The use of post-injection medicinal products (e.g. short- and long-acting bronchodilators and inhaled corticosteroids) should be considered for patients with chronic obstructive pulmonary disease (see Dosage & Administration).
Neutropenia/Thrombocytopenia: DARZALEX may increase neutropenia and thrombocytopenia induced by background therapy (see Adverse Reactions).
Complete blood cell counts should be monitored periodically during treatment according to prescribing information for background therapies. Patients with neutropenia should be monitored 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.
Solution for SC injection: In lower body weight patients receiving DARZALEX subcutaneous formulation, higher rates of neutropenia were observed; however, this was not associated with higher rates of serious infections.
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.
Hepatitis B virus (HBV) reactivation: Hepatitis B virus reactivation, in some cases fatal, has been reported in patients treated with DARZALEX. HBV screening should be performed in all patients before initiation of treatment with DARZALEX.
For patients with evidence of positive HBV serology, monitor for clinical and laboratory signs of HBV reactivation during, and for at least six months following the end of DARZALEX treatment. Manage patients according to current clinical guidelines. Consider consulting a hepatitis disease expert as clinically indicated.
In patients who develop reactivation of HBV while on DARZALEX, suspend treatment with DARZALEX and institute appropriate treatment. Resumption of DARZALEX treatment in patients whose HBV reactivation is adequately controlled should be discussed with physicians with expertise in managing HBV.
Body weight (> 120 kg): Solution for SC injection: There is a potential for reduced efficacy with DARZALEX solution for subcutaneous injection in patients with body weight > 120 kg (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Excipients: Concentrate for solution for IV infusion: 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 corresponds to 0.46% and 1.86% of the WHO recommended maximum daily intake of 2 g sodium for an adult, respectively.
Solution for SC injection: This medicinal product contains sorbitol (E420). Patients with hereditary fructose intolerance (HFI) should not be given this medicinal product.
This medicinal product also contains less than 1 mmol (23 mg) sodium per dose, that is to say essentially 'sodium-free'.
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.
