Enhertu Dosage/Direction for Use

Enhertu should be prescribed by a physician and administered under the supervision of a healthcare professional experienced in the use of anticancer medicinal products. 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.
Enhertu should not be substituted with trastuzumab or trastuzumab emtansine.
Patient selection: HER2-positive breast cancer: Patients treated with trastuzumab deruxtecan for breast cancer should have documented HER2-positive tumour status, defined as a score of 3+ by immunohistochemistry (IHC) or a ratio of ≥2.0 by in situ hybridization (ISH) or by fluorescence in situ hybridization (FISH) assessed by a CE-marked in vitro diagnostic (IVD) medical device. If a CE-marked IVD is not available, the HER2 status should be assessed by an alternate validated test.
HER2-low breast cancer: Patients treated with trastuzumab deruxtecan should have documented HER2-low tumour status, defined as a score of IHC 1+ or IHC 2+/ISH-, as assessed by a CE-marked IVD medical device. If a CE-marked IVD is not available, the HER2 status should be assessed by an alternate validated test (see Pharmacology: Pharmacodynamics under Actions).
Gastric cancer: Patients treated with trastuzumab deruxtecan for gastric or gastroesophageal junction cancer should have documented HER2-positive tumour status, defined as a score of 3+ by immunohistochemistry (IHC) or a ratio of ≥2 by in situ hybridization (ISH) or by fluorescence in situ hybridization (FISH), assessed by a CE-marked in vitro diagnostic (IVD) medical device. If a CE-marked IVD is not available, the HER2 status should be assessed by an alternate validated test.
Posology: Breast cancer: 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.
Gastric cancer: The recommended dose of Enhertu is 6.4 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 (see Adverse Reactions). Enhertu should be permanently discontinued in case of severe infusion reactions.
Premedication: Enhertu is emetogenic (see Adverse Reactions), 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 provided in Tables 5 and 6. (See Tables 5 and 6.)
Enhertu dose should not be re-escalated after a dose reduction is made.

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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.
Special populations: 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 (see Pharmacology: Pharmacokinetics under Actions). The potential need for dose adjustment in patients with severe renal impairment or end-stage renal disease cannot be determined as severe renal impairment was an exclusion criterion in clinical studies. A higher incidence of Grade 1 and 2 ILD/pneumonitis leading to an increase in discontinuation of therapy has been observed in patients with moderate renal impairment. In patients with moderate renal impairment at baseline who received Enhertu 6.4 mg/kg, a higher incidence of serious adverse reactions was observed compared to those with normal renal function. Patients with moderate or severe renal impairment should be monitored carefully for adverse reactions including ILD/pneumonitis (see Precautions).
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. The potential need for dose adjustment in patients with total bilirubin >1.5 times ULN, irrespective of AST value, cannot be determined due to insufficient data; therefore, these patients should be monitored carefully (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Paediatric 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.
Method of administration: Enhertu is for intravenous use. It must be reconstituted and diluted by a healthcare professional and administered as an intravenous infusion. Enhertu must not be administered as an intravenous push or bolus.
For instructions on reconstitution and dilution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.