Darzalex Special Precautions

Infusion-related reactions: DARZALEX can cause serious IRRs, including anaphylactic reactions. These reactions can be life-threatening and fatal outcomes have been reported.
Monitor patients throughout the infusion and the post-infusion period.
In clinical trials, 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. Four percent of patients had an IRR at more than one infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, and hypertension, laryngeal edema, pulmonary edema, myocardial infarction, and ocular adverse reactions (including choroidal effusion, acute myopia and acute angle closure glaucoma). Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision (see Adverse Reactions).
Pre-medicate patients with antihistamines, antipyretics and corticosteroids to reduce the risk of IRRs prior to treatment with DARZALEX. Interrupt DARZALEX infusion for IRRs of any severity and institute medical management/supportive treatment as needed. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. If an anaphylactic reaction or life threatening (Grade 4) IRR occurs, permanently discontinue administration of DARZALEX and institute appropriate emergency care (see Dosage & Administration).
To reduce the risk of delayed IRRs, administer oral corticosteroids to all patients following all DARZALEX infusions. Additionally consider the use of post-infusion medications (e.g. inhaled corticosteroids, short and long acting bronchodilators) for patients with a history of chronic obstructive pulmonary disease to manage respiratory complications should they occur. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX (see Dosage & Administration).
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 dose 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 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.
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.
Hepatitis B Virus (HBV) reactivation: Hepatitis B virus (HBV) 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 any concomitant steroids, chemotherapy, 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.
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.