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Hypersensitivity and Other Administration Reactions: Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX SC. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX SC [see Postmarketing Experience under Adverse Reactions].
Systemic Reactions: In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX SC as monotherapy or as part of a combination therapy, 9% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3:1%). Systemic administration-related reactions occurred in 8% of patients with the first injection, 0.3% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 140 systemic administration-related reactions that occurred in 77 patients, 121 (86%) occurred on the day of DARZALEX SC administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.
Severe reactions include hypoxia, dyspnea, hypertension, and tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension and blurred vision.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen and corticosteroids [see Recommended Concomitant Medications under Dosage & Administration]. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX SC. Consider administering corticosteroids and other medications after the administration of DARZALEX SC depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions [see Recommended Concomitant Medications under Dosage & Administration].
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX SC and seek immediate ophthalmologic evaluation prior to restarting DARZALEX SC.
Local Reactions: In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 0.7%. The most frequent (>1%) injection-site reaction was injection site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX SC. Monitor for local reactions and consider symptomatic management.
Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis: Serious or fatal cardiac adverse reactions occurred in patients with light chain (AL) amyloidosis who received DARZALEX SC in combination with bortezomib, cyclophosphamide and dexamethasone [see Clinical Trials Experience under Adverse Reactions]. Serious cardiac disorders occurred in 16% and fatal cardiac disorders occurred in 10% of patients. Patients with NYHA Class IIIA or Mayo Stage IIIA disease may be at greater risk. Patients with NYHA Class IIIB or IV disease were not studied.
Monitor patients with cardiac involvement of light chain (AL) amyloidosis more frequently for cardiac adverse reactions and administer supportive care as appropriate
Neutropenia: Daratumumab may increase neutropenia induced by background therapy [see Clinical Trials Experience under 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. Consider withholding DARZALEX SC until recovery of neutrophils. In lower body weight patients receiving DARZALEX SC, higher rates of Grade 3-4 neutropenia were observed.
Thrombocytopenia: Daratumumab may increase thrombocytopenia induced by background therapy [see Clinical Trials Experience under Adverse Reactions].
Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX SC until recovery of platelets.
Interference with Serological Testing: Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks 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 [see Effects of Daratumumab on Laboratory Tests under Interactions].
Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX SC. Type and screen patients prior to starting DARZALEX SC [see Important Dosing Information under Dosage & Administration].
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 Effects of Daratumumab on Laboratory Tests under Interactions]. This interference can impact the determination of complete response and of disease progression in some DARZALEX SC-treated 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 SC.
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 SC 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 SC, suspend treatment with DARZALEX SC and any concomitant steroids, chemotherapy, and institute appropriate treatment. Resumption of DARZALEX SC 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 Machine: Not applicable.
Use in Pregnancy: Embryo-Fetal Toxicity: Based on the mechanism of action, DARZALEX SC can cause fetal harm when administered to a pregnant woman. DARZALEX SC may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX SC and for 3 months after the last dose [see Pregnancy and Females and Males of Reproductive Potential under Use in Pregnancy & Lactation].
The combination of DARZALEX SC with lenalidomide, thalidomide or pomalidomide is contraindicated in pregnant women, because lenalidomide, thalidomide or pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide or pomalidomide prescribing information on use during pregnancy.
