About This Information

This section provides supporting clinical context for the Enhertu (trastuzumab deruxtecan) Dosing Calculator. It explains the tool's outputs, intended use, and key dosing considerations based on the official prescribing information. This information is intended for educational purposes and should not replace clinical judgment or the full prescribing information.

Calculator Outputs Explained

The calculator provides four key outputs to guide the preparation and administration of an Enhertu infusion:

• Total Calculated Dose (mg): The patient-specific total dose of trastuzumab deruxtecan, calculated by multiplying the patient's body weight in kilograms by the selected dose level (mg/kg).
• Vials Required: The number of 100 mg single-dose vials needed to prepare the total calculated dose. This is determined by rounding up to the nearest whole vial.
• Reconstitution Volume (mL): The total volume of reconstituted solution (20 mg/mL) that must be withdrawn from the vials to obtain the total calculated dose.
• Dilution: The standard instruction to dilute the withdrawn volume in a 100 mL intravenous bag of 5% Dextrose Injection (D5W) prior to administration.

How to Use the Calculator

Follow these steps to determine the correct dosing parameters for a patient:

1. Enter Patient Body Weight: Input the patient's current body weight. You can toggle between kilograms (kg) and pounds (lbs); the tool will handle the conversion automatically.
2. Select Dose Level: Choose the appropriate dose from the dropdown menu, which includes the standard dose (5.4 mg/kg) and subsequent dose reduction levels. A custom mg/kg value can also be entered.
3. Calculate and Review: Click "Calculate" to see the results. The tool will automatically update if you change any input values.
4. Verify: Always cross-reference the calculated results with the official prescribing information and institutional protocols before preparing or administering the drug.

Dosing Overview

Enhertu is administered as an intravenous (IV) infusion every 3 weeks (21-day cycle). The recommended standard dosage is 5.4 mg/kg. The first infusion should be administered over 90 minutes. If well-tolerated, subsequent infusions may be administered over 30 minutes. Dosing is based on actual body weight and should be recalculated for each cycle if the patient's weight has changed by more than 10%.

Dose Reduction Levels

Dose modifications are required for managing certain adverse reactions. The standard dose reduction schedule is as follows:

• Standard Dose: 5.4 mg/kg
• First Dose Reduction: 4.4 mg/kg
• Second Dose Reduction: 3.2 mg/kg

Treatment should be discontinued in patients who are unable to tolerate a dose of 3.2 mg/kg.

Switching and Dose Modifications

The term "switching" in the context of Enhertu typically refers to dose level adjustments due to toxicities. Management of adverse reactions may require treatment interruption or dose reduction. The decision to resume treatment at the same or a reduced dose level, or to permanently discontinue, depends on the type and severity (grade) of the adverse reaction. Refer to the "Safety Alerts" section below for specific guidance on common toxicities.

Missed Dose

If a planned dose is missed, it should be administered as soon as possible. The schedule for subsequent administrations should be adjusted to maintain a 3-week interval between doses. The infusion rate should be managed according to the guidance for the dose being administered (i.e., 90 minutes for the first-ever dose, 30 minutes for subsequent doses if tolerated).

Safety Alerts & Dose Modification Guide

Enhertu has a boxed warning for Interstitial Lung Disease (ILD)/pneumonitis and Embryo-Fetal Toxicity. Dose modifications are critical for patient safety.

Interstitial Lung Disease (ILD) / Pneumonitis

• Grade 1 (asymptomatic): Interrupt treatment. May resume at the same dose or a reduced dose once recovered to Grade 0.
• Grade 2 or higher (symptomatic): Permanently discontinue Enhertu.

Neutropenia

• Grade 3: Interrupt until recovery to ≤Grade 2, then resume at the same dose level.
• Grade 4: Interrupt until recovery to ≤Grade 2, then resume with one dose level reduction.

Left Ventricular Dysfunction

• LVEF <40% or >20% absolute decrease from baseline: Withhold treatment. If confirmed on repeat LVEF assessment after 3 weeks, permanently discontinue.
• LVEF 40-45% and 10-20% absolute decrease: Withhold treatment. If confirmed, resume with one dose level reduction.

Frequently Asked Questions (FAQ)

What is the concentration of Enhertu after reconstitution?

After reconstituting a 100 mg vial with 5 mL of Sterile Water for Injection, the resulting concentration is 20 mg/mL.

Why is the number of vials rounded up?

Vials are for single use only. To obtain the precise total dose, you must use the minimum number of vials required, which often means rounding up. For example, a total dose of 240 mg requires three 100 mg vials.

Can I use a different diluent than D5W?

No. The prescribing information specifies that the reconstituted Enhertu solution must be diluted in a 100 mL infusion bag of 5% Dextrose Injection (D5W). Do not use Sodium Chloride solution.

What should I do if the patient's weight changes significantly?

The dose of Enhertu should be recalculated prior to each cycle if the patient's body weight has changed by more than 10% from the previous assessment. Use the new weight to calculate the dose.

The calculator provides a "Custom Dose" option. When would this be used?

The custom dose option is for investigational use or specific institutional protocols that may differ from the standard approved dosing. It should only be used under the direction of a qualified oncologist and in accordance with relevant trial or institutional guidelines.

How are the dose reduction levels determined?

The dose reduction levels (4.4 mg/kg and 3.2 mg/kg) are established in the clinical trials and approved in the prescribing information as the standard decrements for managing treatment-related toxicities.

What is the maximum dose of Enhertu?

The prescribing information does not specify an absolute maximum dose, as dosing is strictly weight-based. However, clinical decisions should always guide treatment, especially for patients at extremes of body weight.

Is this calculator a substitute for the official Prescribing Information (PI)?

No. This calculator is an educational tool designed to simplify dosing calculations. It is not a substitute for clinical judgment or the full, official Prescribing Information, which must be consulted before prescribing or administering Enhertu.

References

• ENHERTU® (trastuzumab deruxtecan) Prescribing Information. AstraZeneca and Daiichi Sankyo, Inc. Revised: 04/2024.
• Enhertu HCP Official Website. AstraZeneca & Daiichi Sankyo.
• Enhertu European Medicines Agency (EMA) Summary of Product Characteristics.
• National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. (Specific guidelines require login).