IntravenousHER2-positive metastatic breast cancer, HER2-positive unresectable breast cancerAdult: For the treatment of patients who have received 2 or more previous anti-HER2-based regimens: 5.4 mg/kg once every 3 weeks (21-day cycle) via IV infusion until disease progression or unacceptable toxicity. Administer the initial dose as a 90-minute IV infusion, if well tolerated, subsequent doses may be given as a 30-minute infusion. Antiemetics may be given based on local medical practices as per patient tolerance for prophylaxis or management. Dose reduction, dosing interruption or discontinuation may be required according to individual safety and tolerability. Recommended therapeutic indications may vary between countries (refer to specific product guidelines).
IntravenousHER2-positive locally advanced gastric adenocarcinoma, HER2-positive locally advanced gastrooesophageal junction adenocarcinoma, HER2-positive metastatic gastric adenocarcinoma, HER2-positive metastatic gastrooesophageal junction adenocarcinomaAdult: For the treatment of patients who have received 2 or more prior regimens, including a trastuzumab-based regimen: 6.4 mg/kg once every 3 weeks (21-day cycle) via IV infusion until disease progression or unacceptable toxicity. Administer the initial dose as a 90-minute IV infusion, if well tolerated, subsequent doses may be given as a 30-minute infusion. Antiemetics may be given based on local medical practices as per patient tolerance for prophylaxis or management. Dose reduction, dosing interruption or discontinuation may be required according to individual safety and tolerability. Recommended therapeutic indications may vary between countries (refer to specific product guidelines).
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Check the vial to ensure that the appropriate product will be reconstituted. Reconstitute each 100 mg vial with 5 mL of sterile water for inj to make a final concentration of 20 mg/mL. Gently swirl to mix; do not shake. Further dilute the calculated volume of the reconstituted solution in an infusion bag containing 100 mL of 5% dextrose in water. Gently invert the bag to mix; do not shake. Protect the infusion bag from light.
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May result in particulate formation with 0.9% NaCl solution.
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Hypersensitivity. Pregnancy and lactation.
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Verify the vial label to ensure that trastuzumab deruxtecan is being prepared and administered; trastuzumab deruxtecan is not interchangeable with conventional trastuzumab, trastuzumab emtansine, or other trastuzumab biosimilars. Elderly. Moderate to severe hepatic and renal impairment.
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Significant: Neutropenia, including febrile neutropenia; decreased LVEF, increased risk of left ventricular dysfunction.
Blood and lymphatic system disorders: Anaemia, thrombocytopenia, leucopenia, lymphopenia.
Eye disorders: Dry eye.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, abdominal pain, stomatitis, dyspepsia, intestinal obstruction.
General disorders and administration site conditions: Fatigue, fever, peripheral oedema, infusion-related reactions.
Immune system disorders: Antibody development.
Investigations: Increased AST, ALT, serum bilirubin and serum alkaline phosphatase.
Metabolism and nutrition disorders: Decreased appetite, hypokalaemia, dehydration.
Nervous system disorders: Headache, dizziness.
Respiratory, thoracic and mediastinal disorders: Epistaxis, dyspnoea, cough, upper respiratory tract infection, pneumonia.
Skin and subcutaneous tissue disorders: Alopecia, rash, pruritus, cellulitis.
Potentially Fatal: Interstitial lung disease (ILD) and pneumonitis.
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IV: Z (Risk of oligohydramnios resulting in neonatal complications. If unavoidable, closely monitor the amniotic fluid status.)
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This drug may cause dizziness, if affected, do not drive or operate machinery.
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Obtain human epidermal growth factor receptor 2 (HER2) status. Evaluate pregnancy status before treatment initiation. Monitor CBC prior to treatment initiation, before each administration, and as clinically indicated; LVEF by standard cardiac function testing (echocardiogram or multigated acquisition [MUGA] scan) prior to initiation of therapy, regularly during treatment, and as necessary. Assess for signs and symptoms of infusion reactions and ILD or pneumonitis. Obtain radiographic imaging for suspected ILD, preferably a CT scan.
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Description:
Mechanism of Action: Trastuzumab deruxtecan, an antineoplastic agent, is a human epidermal growth factor receptor type 2 (HER2)-directed antibody-drug conjugate composed of a humanised anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab, covalently linked to deruxtecan or DXd (an exatecan derivative and a topoisomerase I inhibitor), via a tetrapeptide-based cleavable linker. The antibody portion binds to the surface of certain tumour cells; thereafter, the trastuzumab deruxtecan complex then undergoes internalisation and intracellular linker cleavage by lysosomal enzymes that are upregulated in cancer cells. This results in the release of the membrane-permeable DXd causing DNA damage and eventual apoptotic cell death.
Pharmacokinetics:
Distribution: Volume of distribution: Central compartment: 2.77 L (trastuzumab deruxtecan); 27.4 L (DXd). Plasma protein binding: Approx 97% (DXd).
Metabolism: Trastuzumab deruxtecan undergoes intracellular cleavage by lysosomal enzymes to release the DXd. The humanised HER2 IgG1 monoclonal antibody is degraded via catabolic pathways into small peptides and amino acids, while the DXd is metabolised via oxidative pathways mainly by CYP3A4.
Excretion: Elimination half-life: Approx 7 days.
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Intact vials: Store between 2-8°C. Reconstituted solution: Stable for up to 24 hours when stored between 2-8°C from the time of reconstitution. Diluted solution for infusion: Store below 30°C for up to 4 hours (including preparation and infusion) or between 2-8°C for up to 24 hours. Do not shake the reconstituted or diluted solutions. Do not freeze. Protect from light. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
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L01FD04 - trastuzumab deruxtecan ; Belongs to the class of HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors. Used in the treatment of cancer.
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Anon. Fam-Trastuzumab Deruxtecan-nxki. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/09/2022. Anon. Fam-Trastuzumab Deruxtecan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/09/2022. Enhertu 100 mg Powder for Concentrate for Solution for Infusion (Daiichi Sankyo UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 02/09/2022. Enhertu Lyophilized Powder for Solution for Injection (Daiichi Sankyo, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/09/2022. Enhertu Powder for Concentrate for Solution for Infusion 100 mg (AstraZeneca Singapore Pte Ltd). MIMS Singapore. http://www.mims.com/singapore. Accessed 13/09/2022. Enhertu Powder for Concentrate for Solution for Infusion 100 mg (Daiichi Sankyo Hong Kong Limited). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 02/09/2022. Joint Formulary Committee. Trastuzumab Deruxtecan. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/09/2022.
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