Darzalex Faspro Special Precautions

Infusion-related reactions: DARZALEX FASPRO can cause severe and/or serious infusion-related reactions (IRRs), including anaphylactic reactions. In clinical trials, approximately 9% (77/898) of patients experienced an infusion-related reaction. Most IRRs occurred following the first injection and were Grade 1-2 (see Adverse Reactions). IRRs occurring with subsequent injections were seen in 1% of patients.
The median time to onset of IRRs following DARZALEX FASPRO was 3.2 hours (range 0.07-83 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, hypotension and blurred vision. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia and ocular adverse events (including choroidal effusion, acute myopia and acute angle closure glaucoma) (see Adverse Reactions).
Pre-medicate patients with antihistamines, antipyretics and corticosteroids. Patients should be 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, institute appropriate emergency care and permanently discontinue DARZALEX FASPRO.
To reduce the risk of delayed IRRs, administer oral corticosteroids to all patients following DARZALEX FASPRO injections. Patients with a history of chronic obstructive pulmonary disease may require additional post-injection medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease. If ocular symptoms, interrupt DARZALEX FASPRO infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO (see Dosage & Administration).
Neutropenia/Thrombocytopenia: Daratumumab 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 FASPRO dose delay may be required to allow recovery of blood cell counts. In lower body weight patients receiving DARZALEX FASPRO subcutaneous formulation, higher rates of neutropenia were observed; however, this was not associated with higher rates of serious infections. No dose reduction of DARZALEX FASPRO 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 administration. It should be recognized 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.
Type and screen patients prior to starting DARZALEX FASPRO. 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 notify blood transfusion centers 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. 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 (HBV) reactivation, in some cases fatal, has been reported in patients treated with daratumumab. HBV screening should be performed in all patients before initiation of treatment with DARZALEX FASPRO.
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 FASPRO 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 FASPRO, suspend treatment with DARZALEX FASPRO and any concomitant steroids, chemotherapy, and institute appropriate treatment. Resumption of DARZALEX FASPRO treatment in patients whose HBV reactivation is adequately controlled should be discussed with physicians with expertise in managing HBV.
Body weight (>120 kg): There is a potential for reduced efficacy with DARZALEX FASPRO solution for subcutaneous injection in patients with body weight >120 kg.
Excipients: 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 FASPRO 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.