Prescribing information For Healthcare Professionals Only

Darzalex®

20 mg/ml concentrate
for solution for infusion

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 bortezomib, melphalan and prednisone in adults ineligible 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. 
Dilute with sodium chloride 0.9% solution for injection and administer by intravenous infusion using incremental escalation of infusion rate only if previous infusion well-tolerated. 
Adults: Newly diagnosed multiple myeloma: Combination with bortezomib, melphalan and prednisone (6 week cycle): 16 mg/kg body weight weekly for 6 weeks followed by every 3 weeks up to Week 54, then every 4 weeks from Week 55, until disease progression. Relapsed/Refractory multiple myeloma: Monotherapy and combination with lenalidomide (4 week cycle): 16 mg/kg body weight weekly for 8 weeks followed by every 2 weeks up to Week 24, then every 4 weeks from Week 25. Combination with bortezomib (3 week cycle): 16 mg/kg body weight weekly for 9 weeks followed by every 3 weeks up to Week 24, then every 4 weeks from Week 25. Refer to SmPC for further details.


Recommended concomitant medications for management of infusion-related reactions (IRRs): To reduce risk, administer pre-infusion medications to all patients 1-3 hours prior to every infusion: i.e corticosteroid (monotherapy: methylprednisolone (or equivalent) iv then iv or oral from second infusion; combination: dexamethasone (or equivalent) iv then iv or oral following second infusion) plus oral antipyretics and oral or intravenous antihistamine. If dexamethasone given on infusion day, do not take additional background regimen specific corticosteroids (e.g. prednisone). To reduce the risk of delayed IRRs administer post-infusion oral corticosteroid: monotherapy e.g. mg methylprednisolone on each of two days following all infusions; combination: mg methylprednisolone the day after infusion, but may not be needed if dexamethasone or prednisone continued. Consider short/long acting bronchodilators and inhaled corticosteroids in patients with history of obstructive pulmonary disorder. Any grade/severity IRRs, interrupt Darzalex® immediately and manage symptoms. Re-starting Darzalex®: reduce infusion rate (refer to SmPC); Grade 4 IRRs - (or third occurence of Grade 3) - permanently discontinue. No dose reductions of DARZALEX® recommended. For haematological toxicity dose delay may be required to allow recovery of blood cell counts. 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: Symptoms predominantly include nasal congestion, cough, throat irritation, chills, vomiting and nausea; can cause serious IRRs including anaphylactic reactions. Monitor for IRRs throughout the infusion. For any Grade of IRR, continue monitoring post-infusion until symptoms resolve. Majority occurred at first infusion; interrupt Darzalex® for any severity IRRs (see also Dosage and Administration). Institute medical management/supportive treatment as needed. 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): 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. Contains sodium.

Side Effects:

Very common: IRRs, pneumonia, upper respiratory tract infection, anaemia, neutropenia, thrombocytopenia, lymphopenia, peripheral sensory neuropathy, headache, hypertension, cough, dyspnoea, nausea, diarrhoea, vomiting, muscle spasms, fatigue, pyrexia, peripheral oedema.
Common: influenza, atrial fibrillation, pulmonary oedema.  
Other side effects: 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. Daratumumab detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays; can impact determination of complete response and disease progression in some patients. Considerusing 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

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: August 2018

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