DARZALEX s.c

/ Janssen

The recommended dose is 1800 mg, administered over approximately 3-5 minutes, in accordance with the appropriate treatment protocol. Refer to the prescribing information for complete details.

Multiple myeloma
* In combination with lenalidomide and dexamethasone or with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
* In combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.
* In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
* in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor.
* As monotherapy is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.
Light chain (AL) amyloidosis
In combination with cyclophosphamide, bortezomib and dexamethasone for the treatment of adult patients with newly diagnosed systemic AL amyloidosis.

Hypersensitivity to the active substance or to any of the excipients

Infusion‑related reactions
Severe and/or serious IRRs, including anaphylactic reactions. Most IRRs occurred following the first injection and were grade 1-2.
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, dyspnoea, hypertension tachycardia and ocular adverse reactions (including choroidal effusion, acute myopia and acute angle closure glaucoma). Pre-medication with antihistamines, antipyretics, and corticosteroids should be considered also, monitoring for IRRs is especially during the first two injections. If an anaphylactic reaction or life-threatening (grade 4) reactions occur, appropriate emergency care should be initiated immediately. Therapy should be discontinued immediately and permanently. To reduce the risk of delayed IRRs, oral corticosteroids should be administered to all patients following injection. 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. If ocular symptoms occur, interrupt treatment and seek immediate ophthalmologic evaluation prior to restarting.
Neutropenia/thrombocytopenia
Daratumumab may increase neutropenia and thrombocytopenia induced by background therapy. Patients with neutropenia should be monitored for signs of infection. Daratumumab delay may be required to allow recovery of blood cell counts. In lower body weight patients receiving Daratumumab subcutaneous formulation, higher rates of neutropenia were observed; however, this was not associated with higher rates of serious infections. No dose reduction is recommended. Consider supportive care with transfusions or growth factors. 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.
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 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.
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 treatment. Manage patients according to current clinical guidelines. In patients who develop reactivation of HBV while on daratumumab, suspend treatment and institute appropriate treatment. Resumption of 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 daratumumab solution for subcutaneous injection in patients with body weight >120 kg.
See prescribing information for full details.

Very common: Upper respiratory tract infection, COVID-19, Pneumonia, Bronchitis, Neutropenia, Thrombocytopenia, Anaemia, Lymphopenia, Leukopenia, Hypokalaemia, Decreased appetite, Insomnia, Peripheral neuropathy, Headache, Cough, Dyspnoea, Diarrhoea, Constipation, Nausea, Abdominal pain, Vomiting, Rash, Musculoskeletal pain, Arthralgia, Muscle spasms, Fatigue, Oedema peripheral, Pyrexia, Asthenia, Daratumumab intravenous.
Common: Urinary tract infection, Sepsis, Hypogammaglobulinemia, Hyperglycaemia, Hypocalcaemia, Dehydration, Dizziness, Paraesthesia, Syncope, Atrial fibrillation, Hypertension, Pulmonary oedema, Pancreatitis, Pruritus, Chills, Injection site reactions, Infusion-related reactions, Daratumumab, subcutaneous.
See prescribing information for full details.

No interaction studies have been performed.
Interference with indirect antiglobulin test (indirect Coombs test)
Daratumumab binds to CD38 on RBCs and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered.
Interference with serum protein electrophoresis and immunofixation tests
Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, where daratumumab interference is suspected, consider using a validated daratumumab-specific IFE assay to distinguish daratumumab from any remaining endogenous M protein in the patient’s serum, to facilitate determination of a complete response.
See prescribing information for full details.

Women of child-bearing potential/Contraception
Women of child-bearing potential should use effective contraception during, and for 3 months after cessation of daratumumab treatment. T
Pregnancy
There are no or limited amount of data from the use of daratumumab in pregnant women. daratumumab is not recommended during pregnancy and in women of childbearing potential not using contraception.
Lactation
It is not known whether daratumumab is excreted into human or animal milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from daratumumab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Symptoms and signs
There has been no experience of overdosage in clinical studies.
Treatment
There is no known specific antidote for daratumumab overdose. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse effects and appropriate symptomatic treatment should be instituted immediately.