Prescribing information For Healthcare Professionals Only

Darzalex®

20 mg/ml Concentrate
for Solution for Infusion and 1,800 mg Solution for Injection.

PRESCRIBING INFORMATION

Active Ingredient(s):

Daratumumab

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

Indications(S): 

Newly diagnosed multiple myeloma: In combination with lenalidomide/dexamethasone or bortezomib/melphalan/prednisone in adults, ineligible for autologous stem cell transplant: in combination with bortezomib, thalidomide and dexamethasone in adults, eligible for autologous stem cell transplant.

Relapsed/Refractory multiple myeloma: Monotherapy for adults whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on last therapy. In combination with lenalidomide/dexamethasone or bortezomib/dexamethasone in adults who have received ≥ one prior therapy.

Dosage & Administration:

Administration by healthcare professional where resuscitation facilities available, intravenous (IV) infusion or subcutaneous (SC) injection. For SC injection, resuscitation facilities required only for first dose. Adult Dose: IV dose 16 mg/kg body. Dilute with sodium chloride 0.9% solution for injection and administer by intravenous infusion. SC dose: Inject 15 mL DARZALEX solution for SC injection into the subcutaneous tissue of the abdomen approximately 7.5 cm to the right or left of the navel over approximately 3‑5 minutes according to dosing schedule. Patients > 120 kg, flat-dose 1,800 mg SC, efficacy not established. For SC injection, no dose adjustments based on body weight recommended. Check the vial labels to ensure that the appropriate formulation (IV or SC formulation) and dose is being given as prescribed. For dose and schedule of medicinal products administered with DARZALEX, refer to SmPC 4.1 and the corresponding SmPC for other products. Refer to SmPC for further details.


Recommended concomitant medications for management of infusion/ injection-related reactions (IRRs): administer pre- IV infusion/ SC injection medicinal products 1-3 hours prior to administration (corticosteroids, antipyretics and antihistamines). For SC injections, pre-medications can be given orally from the first dose. When dexamethasone is background‑regimen specific corticosteroid, this dose will serve as pre‑medication on infusion days. If dexamethasone given on infusion day, do not take additional background regimen specific corticosteroids (e.g. prednisone). Post-IV infusion/ SC injection medicinal products should be administered to reduce the risk of delayed IRRs: administer oral corticosteroid. If the patient experiences no major IRRs after the first three SC injections, post-injection corticosteroids (excluding any background regimen corticosteroids) may be discontinued. Consider bronchodilators and inhaled corticosteroids in patients with history of chronic obstructive pulmonary disorder. Darzalex Infusion: Any grade/severity IRRs, interrupt Darzalex infusion immediately and manage symptoms. Re-starting Darzalex infusion: reduce infusion rate (refer to SmPC); Grade 4 IRRs (or third occurrence of Grade 3) – permanently discontinue. No dose reductions of Darzalex recommended.  Consider anti‑viral prophylaxis for prevention of herpes zoster virus reactivation.
Children: No data available. 
Elderly/Renal impairment/Hepatic impairment: No dose adjustments.

Contraindications:

Hypersensitivity to active substance or excipients.

Special warnings & Precautions:

IRRs: can cause serious IRRs including anaphylactic reactions. Majority occurred following first IV infusion/SC injection. Monitor for IRRs throughout the IV infusion, continue monitoring post- IV infusion until symptoms resolve. For SC injection, median time to onset of IRRs was 3.7 hours following injection, monitor IRRs especially in the first and second SC injection. Darzalex solution for SC injection should never be injected into areas where the skin is red, bruised, tender, hard or areas where there are scars. During treatment with Darzalex SC injection, do not administer other medicinal products for subcutaneous use at the same site as Darzalex.  Both IV and SC Darzalex: if an anaphylactic reaction or life‑threatening (Grade 4) IRR occurs, initiate appropriate emergency resuscitation immediately and discontinue Darzalex immediately and permanently.
Neutropenia/Thrombocytopenia: Darzalex may increase neutropenia and thrombocytopenia induced by background therapy; monitor for infections & periodic complete blood cell counts (refer to relevant SmPCs); consider supportive care. Indirect Antiglobulin Test (Indirect Coombs Test): Daratumumab binds to CD38; may mask detection of antibodies to minor antigens; ABO and Rh blood typing not impacted.

Interference may occur up to 6 months post-treatment. Type and screen patients prior to starting daratumumab; consider phenotyping; red blood cell genotyping not affected by daratumumab. Inform blood transfusion centres when appropriate. If emergency transfusion required, give non-cross-matched ABO/RhD-compatible RBCs. Hepatitis B virus (HBV) reactivation: Fatal cases reported in patients treated with Darzalex. Perform HBV screening before initiation of treatment. Suspend treatment in patients who develop reactivation of HBV while on Darzalex. Patient’s with body weight >120 kg, potential for reduced efficacy. Infusion contains sodium. SC injection contains sorbitol.

Side Effects:

Very common: IRRs, pneumonia, bronchitis, upper respiratory tract infection, anaemia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, decreased appetite, peripheral sensory neuropathy, paraesthesia, headache, hypertension, cough, dyspnoea, nausea, diarrhoea, constipation, vomiting, back pain, muscle spasms, fatigue, pyrexia, peripheral oedema, asthenia. SC only: insomnia, arthralgia.
Common: urinary tract infection, influenza, sepsis, hyperglycemia, hypocalcemia, dehydration, atrial fibrillation, pulmonary oedema, pancreatitis, chills. SC only: dizziness, musculoskeletal chest pain, rash, pruritus, injection site erythema/reactions.
Serious side effects: HBV reactivation (uncommon), anaphylactic reaction (rare).
Refer to SmPC for other side effects.

Pregnancy:

Effective contraception during and for 3 months after treatment in women of child-bearing potential. Do not use during pregnancy unless benefits outweigh potential risks to foetus.

Lactation:

Not known if daratumumab is excreted into breast milk.

Interactions:

No studies performed. Not anticipated to alter drug-metabolising enzymes. Daratumumab binds to CD38 on RBCs and interferes with compatibility testing (including antibody screening and cross matching). Interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. However, Kell-negative units should be supplied after ruling out/identifying alloantibodies using DTT-treated RBCs. Alternatively, consider phenotyping or genotyping prior to starting treatment. Daratumumab detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays; can impact determination of complete response and disease progression in some patients. Consider using a validated daratumumab-specific IFE assay to facilitate determination of a complete response in patients with persistent very good partial response.
Refer to SmPC for full details of interactions.

LEGAL CATEGORY: POM

PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS

Presentations Pack Sizes Marketing Authorisation Number(s) Basic Nhs Costs
5 ml vial (100mg daratumumab) X 1 EU/1/16/1101/001 £360
20 ml vial (400mg daratumumab) X 1 EU/1/16/1101/002 £1,440
15 ml vial (1800 mg daratumumab) X 1 EU/1/16/1101/004 £4320

MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV. Turnhoutseweg 30, B-2340 Beerse, Belgium

FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK.

Prescribing information last revised: July 2020

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