1. Enhertu Summary of Product Characteristics. 23 February 2024.

Abbreviated Prescribing Information

Enhertu (Trastuzumab deruxtecan) 100 mg powder for concentrate for solution for infusion. Reg. no. 1C 15005/67 (NBC).

Therapeutic indications: Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti -HER2-based regimens.

Pharmacodynamic properties: Pharmacotherapeutic group: Antineoplastic agents, HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors, ATC code: L01FD04.

Mechanism of action: Enhertu, trastuzumab deruxtecan, is a HER2-targeted antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1 attached to deruxtecan, a topoisomerase I inhibitor (DXd) bound by a tetrapeptide-based cleavable linker. The antibody-drug conjugate is stable in plasma. The function of the antibody portion is to bind to HER2 expressed on the surface of certain tumour cells. After binding, the trastuzumab deruxtecan complex then undergoes internalization and intracellular linker cleavage by lysosomal enzymes that are upregulated in cancer cells. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death. DXd, an exatecan derivative, is approximately 10 times more potent than SN-38, the active metabolite of irinotecan.

Posology and method of administration:

Posology: The recommended dose of Enhertu is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. The initial dose should be administered as a 90-minute intravenous infusion. If the prior infusion was well tolerated, subsequent doses of Enhertu may be administered as 30-minute infusions. The infusion rate of Enhertu should be slowed or interrupted if the patient develops infusion-related symptoms. Enhertu should be permanently discontinued in case of severe infusion reactions.

Premedication: Enhertu is emetogenic, which includes delayed nausea and/or vomiting. Prior to each dose of Enhertu, patients should be premedicated with a combination regimen of two or three medicinal products (e.g., dexamethasone with either a 5-HT3 receptor antagonist and/or an NK1 receptor antagonist, as well as other medicinal products as indicated) for prevention of chemotherapy-induced nausea and vomiting.

Dose modifications: Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of Enhertu per guidelines.

Delayed or missed dose: If a planned dose is delayed or missed, it should be administered as soon as possible without waiting until the next planned cycle. The schedule of administration should be adjusted to maintain a 3-week interval between doses. The infusion should be administered at the dose and rate the patient tolerated in the most recent infusion. Elderly, No dose adjustment of Enhertu is required in patients aged 65 years or older. Limited data are available in patients ≥ 75 years of age.

Renal impairment: No dose adjustment is required in patients with mild (creatinine clearance [CLcr] ≥ 60 and < 90 mL/min) or moderate (CLcr ≥ 30 and < 60 mL/min) renal impairment.

Hepatic impairment: No dose adjustment is required in patients with total bilirubin ≤ 1.5 times upper limit of normal (ULN), irrespective of aspartate transaminase (AST) value.

Pediatric population: The safety and efficacy of Enhertu in children and adolescents below the age of 18 years have not been established. No data are available.

Contraindications: Hypersensitivity to the active substance or to any of the excipients.

Special warnings and precautions for use: In order to prevent medicinal product errors, it is important to check the vial labels to ensure that the medicinal product being prepared and administered is Enhertu (trastuzumab deruxtecan) and not trastuzumab or trastuzumab emtansine.

Interstitial lung disease/pneumonitis: Cases of interstitial lung disease (ILD), and/or pneumonitis, have been reported with Enhertu. Fatal outcomes have been observed.

Neutropenia: Cases of neutropenia, including febrile neutropenia with a fatal outcome, were reported in clinical studies of Enhertu.

Left ventricular ejection fraction decrease: Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies.

Interaction with other medicinal products and other forms of interaction: Co-administration with ritonavir, an inhibitor of OATP1B, CYP3A and P-gp, or with itraconazole, a strong inhibitor of CYP3A and P-gp, resulted in no clinically meaningful (approximately 10-20% increase in exposures of trastuzumab deruxtecan or the released topoisomerase I inhibitor, DXd. No dose adjustment is required during co-administration of trastuzumab deruxtecan with medicinal products that are inhibitors of CYP3A or OATP1B or P-gp transporters.

Fertility, pregnancy, and lactation: Women of childbearing potential should use effective contraception during treatment with Enhertu and for at least 7 months following the last dose. There are no available data on the use of Enhertu in pregnant women. Administration of Enhertu to pregnant women is not recommended, and patients should be informed of the potential risks to the fetus before they become pregnant. It is not known if trastuzumab deruxtecan is excreted in human milk. Therefore, women should not breast-feed during treatment with Enhertu or for 7 months after the last dose.

Undesirable effects: The most common adverse reactions were nausea (74.6%), fatigue (56.5%), vomiting (41.6%), alopecia (37.5%), neutropenia (34.6%), constipation (34.6%), anemia (34.2%), decreased appetite (32.4%), diarrhea (28.5%), transaminases increased (26.1%), musculoskeletal pain (25.7%), thrombocytopenia (24.0%) and leukopenia (23.5%), The most common National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE v.5.0) Grade 3 or 4 adverse reactions were neutropenia (16.5%), anemia (9.4%), fatigue (8.1%), leukopenia (6.3%), nausea (5.8%), thrombocytopenia (5.0%), lymphopenia (4.8%), transaminase es increased (3.6%), hypokalemia (3.5%), vomiting (2.6%), diarrhea (2.0%), decreased appetite (1.7%), pneumonia (1.4%)and ejection fraction decreased (1.1%). Grade 5 adverse reactions occurred in 1.3% of patients, including ILD (1.0%).

Overdose: The maximum tolerated dose of trastuzumab deruxtecan has not been determined. In clinical studies, single doses higher than 8.0 mg/kg have not been tested. In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions and appropriate symptomatic treatment initiated.

Shelf life: Unopened vial, This medicine should not be used after the expiry date EXP shown on the pack. Reconstituted solution, Chemical and physical in-use stability has been demonstrated for up to 24 hours at 2ºC to 8 ºC. Diluted solution, It is recommended that the diluted solution be used immediately.

Special precautions for storage: Store in a refrigerator (2 ºC - 8 ºC). Do not freeze.

FULL PRESCRIBING INFORMATION IS AVAILABLE UPON REQUEST

Enhertu Summary of Product Characteristics. 23 February 2024.
โปรดอ่านรายละเอียดเพิ่มเติมในเอกสารกํากับยา
MARKETING AUTHORISATION HOLDER: DAIICHI SANKYO (THAILAND) LTD.
24th Fl., United Center Bldg., 323, Silom Rd., Silom, Bangrak, Bangkok, 10500, Thailand
TH-ENT-0001 03/24
Document No. TH-17371

ความถูกต้องของโฆษณานี้เป็นความรับผิดชอบของผู้โฆษณามิได้ดําเนินการโดยสํานักงานคณะกรรมการอาหารและยา
ยาใหม่ใช้เฉพาะโรงพยาบาล เลขทะเบียนยาที่ 1C 15005/67 (NBC)
ใบอนุญาตโฆษณาเลขที่ ฆศ.2-1849/2567