Daratumumab


Concise Prescribing Info
Indications/Uses
Multiple myeloma.
Dosage/Direction for Use
Adult : IV Monotherapy or combination therapy with lenalidomide and dexamethasone (4-week cycle regimen): For weeks 1-8: 16 mg/kg once weekly; for weeks 9-24: 16 mg/kg every 2 weeks; for weeks 25 onwards: 16 mg/kg every 4 weeks until disease progression. Combination therapy with bortezomib and dexamethasone (3-week cycle regimen): For weeks 1-9: 16 mg/kg once weekly; for weeks 10-24: 16 mg/kg every 3 weeks; for weeks 25 onwards: 16 mg/kg every 4 weeks until disease progression. Combination therapy with bortezomib, melphalan and prednisone (6-week cycle regimen): For weeks 1-6: 16 mg/kg once weekly; for weeks 7-54: 16 mg/kg every 3 weeks; for weeks 55 onwards: 16 mg/kg every 4 weeks until disease progression. Combination therapy with bortezomib, thalidomide and dexamethasone in newly diagnosed patient eligible for ASCT: Induction: For weeks 1-8: 16 mg/kg once weekly; for weeks 9-16: 16 mg/kg every 2 weeks. Consolidation (following ASCT): 16 mg/kg every 2 weeks for 4 doses. Doses to be given via infusion at initial rate of 50 mL/hour for weeks 1-2 and 100 mL/hour for the subsequent weeks. Rate may be increased by increments of 50 mL/hour every hour if no infusion reactions occur. Max rate: 200 mL/hour. Pre- and post-infusion medications may be administered. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Dosage Details
Intravenous
Multiple myeloma
Adult: As monotherapy in relapse or refractory case or in combination with lenalidomide and dexamethasone (4-week cycle regimen): For weeks 1-8: 16 mg/kg once weekly; for weeks 9-24: 16 mg/kg every 2 weeks (total of 8 doses); for weeks 25 onwards: 16 mg/kg every 4 weeks until disease progression. In combination with bortezomib and dexamethasone (3-week cycle regimen): For weeks 1-9: 16 mg/kg once weekly; for weeks 10-24: 16 mg/kg every 3 weeks (total of 5 doses); for weeks 25 onwards: 16 mg/kg every 4 weeks until disease progression. In combination with bortezomib, melphalan and prednisone (6-week cycle regimen): For weeks 1-6: 16 mg/kg once weekly; for weeks 7-54: 16 mg/kg every 3 weeks (total of 16 doses); for weeks 55 onwards: 16 mg/kg every 4 weeks until disease progression. In combination with bortezomib, thalidomide and dexamethasone in newly diagnosed patient eligible for autologous stem cell transplant (ASCT): Induction: For weeks 1-8: 16 mg/kg once weekly; for weeks 9-16: 16 mg/kg every 2 weeks (total of 4 doses). Consolidation (re-initiation following ASCT): 16 mg/kg every 2 weeks for 4 doses. Doses to be given via infusion at initial rate of 50 mL/hour for weeks 1-2 (1st dose may be given as single or split dose), if no reactions occur, initial rate for week 3 onwards may be given at 100 mL/hour. Rate may be increased by increments of 50 mL/hour every hour in the absence of infusion reactions. Max rate: 200 mL/hour. Pre- and post-infusion medications may be administered. Dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Reconstitution
Dilute 1st dose to 1 L, and 2nd and subsequent doses to 500 mL using 0.9% NaCl inj (refer to product guideline for specific instructions on dilution).
Contraindications
History of hypersensitivity to daratumumab.
Special Precautions
Patients with chronic infections, history of recurring infections or underlying conditions that may develop infections. Pregnancy and lactation.
Adverse Reactions
Significant: Neutropenia, thrombocytopenia, severe infusion reactions (e.g. anaphylactic reactions, bronchospasm, hypoxia, dyspnoea, hypertension, laryngeal oedema, pulmonary oedema).
Blood and lymphatic system disorders: Anaemia, lymphopenia.
Cardiac disorders: Atrial fibrillation.
Gastrointestinal disorders: Diarrhoea, constipation, nausea, vomiting.
General disorders and administration site conditions: Fatigue, pyrexia, chills.
Infections and infestations: Influenza.
Metabolism and nutrition disorders: Decreased appetite, peripheral oedema.
Musculoskeletal and connective tissue disorders: Muscle spasms, back pain, arthralgia, pain in extremity, musculoskeletal chest pain.
Nervous system disorders: Headache, peripheral sensory neuropathy.
Respiratory, thoracic and mediastinal disorders: Pneumonia, upper respiratory tract infection, cough, nasal congestion.
Potentially Fatal: Rarely, hepatitis B virus reactivation.
Patient Counseling Information
This drug may cause fatigue, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor CBC periodically. Perform blood typing and screening, hepatitis B virus (HBV) screening prior to therapy. Monitor for infusion-related reactions; signs or symptoms of HBV reactivation, bleeding, infection.
Lab Interference
May interfere with protein electrophoresis and immunofixation assays which may affect the determination of complete response in patient with IgG kappa myeloma protein. May cause positive result in indirect antiglobulin test (indirect Coombs test) and may persist up to 6 months after last dose.
Action
Description: Daratumumab is a human monoclonal antibody that targets CD38, a cell surface glycoprotein expressed on multiple myeloma cells. It binds to CD38 protein resulting to inhibition of growth of CD38 expressing tumour cells by inducing apoptosis directly through Fc mediated cross linking as well as by immune-mediated tumour cell lysis through complement dependent cytotoxicity, antibody dependent cell mediated cytotoxicity and antibody dependent cellular phagocytosis.
Pharmacokinetics:
Distribution: Crosses placenta. Volume of distribution: 4.7±1.3 L (monotherapy); 4.4±1.5 L (combination therapy).
Excretion: Elimination half-life: 18±9 days.
Storage
Store between 2-8°C. Do not freeze. Protect from light.
ATC Classification
L01XC24 - daratumumab ; Belongs to the class of monoclonal antibodies, other antineoplastic agents. Used in the treatment of cancer.
References
Anon. Daratumumab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/04/2020.

Buckingham R (ed). Daratumumab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/04/2020.

Darzalex (Vetter Pharma Fertigung GmbH & Co.KG). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 08/04/2020.

Darzalex 20 mg/mL Concentrate for Solution for Infusion (Janssen Biologics BV). European Medicines Agency [online]. Accessed 20/05/2020.

Darzalex Injection, Solution, Concentrate (Janssen Biotech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/04/2020.

Joint Formulary Committee. Daratumumab. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/04/2020.

Disclaimer: This information is independently developed by MIMS based on Daratumumab from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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