Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.


Infusion-related reactions
DARZALEX 120MG/ML S.C. 1,800MG solution for subcutaneous injection can cause severe and/or serious IRRs, including anaphylactic reactions. In clinical studies, approximately 11% (52/490) 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 less than 1% of patients (see section 4.8).

The median time to onset of IRRs following DARZALEX 120MG/ML S.C. 1,800MG injection was 3.7 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, 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) (see section 4.8).

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 120MG/ML S.C. 1,800MG therapy should be discontinued immediately and permanently (see sections 4.2 and 4.3).

To reduce the risk of delayed IRRs, oral corticosteroids should be administered to all patients following DARZALEX 120MG/ML S.C. 1,800MG injection (see section 4.2). 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. If ocular symptoms occur, interrupt DARZALEX and seek immediate ophthalmologic evaluation prior to restarting DARZALEX (see section 4.2).

Neutropenia/thrombocytopenia
DARZALEX 120MG/ML S.C. 1,800MG may increase neutropenia and thrombocytopenia induced by background therapy (see section 4.8).
Complete blood cell counts should be monitored periodically during treatment according to manufacturer’s prescribing information for background therapies. Patients with neutropenia should be monitored for signs of infection. DARZALEX 120MG/ML S.C. 1,800MG delay may be required to allow recovery of blood cell counts. In lower body weight patients receiving DARZALEX 120MG/ML S.C. 1,800MG subcutaneous formulation, higher rates of neutropenia were observed; however, this was not associated with higher rates of serious infections. No dose reduction of DARZALEX 120MG/ML S.C. 1,800MG 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 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 section 4.5). 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 section 4.5). 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 120MG/ML S.C. 1,800MG. HBV screening should be performed in all patients before initiation of treatment with DARZALEX 120MG/ML S.C. 1,800MG.
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 120MG/ML S.C.
1,800MG 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 120MG/ML S.C. 1,800MG, suspend treatment with DARZALEX 120MG/ML S.C. 1,800MG and institute appropriate treatment.
Resumption of DARZALEX 120MG/ML S.C. 1,800MG 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 120MG/ML S.C. 1,800MG solution for subcutaneous injection in patients with body weight >120 kg (see sections 4.2 and 5.2).

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 Driving

4.7   Effects on ability to drive and use machines

DARZALEX 120MG/ML S.C. 1,800MG 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.