About This Tool

The Rozlytrek (entrectinib) dose calculator is a clinical support resource for healthcare professionals. It determines the appropriate initial dose or subsequent dose reduction based on patient type (adult or pediatric), body surface area (BSA), hepatic function, and concomitant use of CYP3A inhibitors, as outlined in the prescribing information.

Outputs

Upon calculation, the tool provides the following information:

• Recommended Dose: The calculated dose in milligrams (mg) to be administered orally once daily.
• Formulation Guidance: A practical suggestion on how to achieve the recommended dose using available 100 mg and 200 mg capsules.
• Dose Adjustment Rationale: If the dose is modified, the tool specifies the reason, such as moderate hepatic impairment or drug interaction.
• Toxicity Reduction Schedule: In the dose reduction mode, it shows the next recommended dose levels based on the current dose.

How to Use

For Initial Dosing:

1. Select the patient type: "Adult (≥ 12 years)" or "Pediatric (< 12 years)".
2. For pediatric patients, enter their weight and height to enable Body Surface Area (BSA) calculation.
3. Specify the patient's hepatic function using the Child-Pugh classification.
4. Indicate if the patient is taking a concomitant strong or moderate CYP3A inhibitor or inducer.
5. Click "Calculate Dose" to see the recommended initial dosing schedule.

For Dose Reduction Due to Toxicity:

1. Check the box for "Calculate Next Dose Reduction for Toxicity".
2. Select the patient's current daily dose from the dropdown menu.
3. Click "Calculate Dose" to view the subsequent dose reduction steps.

Dosing Overview

Standard dosing for Rozlytrek depends on the patient population:

• Adults: The recommended dose is 600 mg orally once daily.
• Pediatric Patients (<12 years): The recommended dose is 300 mg/m² orally once daily, calculated based on BSA. The dose is rounded to the nearest 100 mg.

Dose Adjustments:

• Moderate Hepatic Impairment (Child-Pugh B): The starting dose is reduced by 50%.
• Concomitant Strong or Moderate CYP3A Inhibitors: The starting dose is reduced by 50%.

Switching

There are no specific guidelines provided in this tool for switching between entrectinib and other therapies. Clinicians should refer to the full prescribing information and exercise clinical judgment when transitioning patients to or from Rozlytrek, considering the half-life of previous medications and potential for drug interactions.

Missed Dose

If a dose of Rozlytrek is missed, the patient should take it as soon as they remember. However, if the next scheduled dose is due within 12 hours, the patient should skip the missed dose and resume their regular schedule. Patients should not take two doses at the same time to make up for a missed dose.

Safety Alerts

This tool incorporates key safety parameters that impact dosing:

• Severe Hepatic Impairment (Child-Pugh C): Rozlytrek is not recommended for use in patients with severe hepatic impairment. The tool will display a warning if this option is selected.
• Strong/Moderate CYP3A Inducers: Co-administration should be avoided as it may decrease entrectinib plasma concentrations and reduce efficacy. The tool provides a warning against this combination.
• Dose Reduction for Toxicity: For adverse reactions, the dose is typically reduced in steps (e.g., from 600 mg to 400 mg, then to 200 mg for adults). If toxicity persists, treatment may need to be discontinued.

Frequently Asked Questions (FAQ)

• Why are weight and height required for pediatric patients but not adults?
  Pediatric dosing is based on Body Surface Area (BSA), which is calculated using the patient's height and weight. Adult dosing is a fixed 600 mg daily and does not require a BSA calculation.
• What is Body Surface Area (BSA)?
  BSA is a measurement of the total surface area of the human body. It is often used in oncology to calculate chemotherapy doses more accurately than by body weight alone.
• What happens if a patient has moderate hepatic impairment and is also taking a strong CYP3A inhibitor?
  The dose is reduced by 50% one time. For an adult, the standard 600 mg dose would be reduced to 300 mg. The 50% reduction is not applied twice.
• How does the "Dose Reduction for Toxicity" mode work?
  It follows the dose reduction schedule outlined in the prescribing information. For adults, the steps are 600 mg → 400 mg → 200 mg. For pediatrics, the steps are 300 mg/m² → 200 mg/m² → 100 mg/m². The tool shows the next step(s) based on the patient's current dose.
• What are the available capsule strengths for Rozlytrek?
  Rozlytrek is available as 100 mg and 200 mg capsules. The tool's formulation output is based on combining these strengths.
• Why can't I calculate an initial dose and a toxicity reduction at the same time?
  These are two distinct clinical scenarios. The tool requires you to select one mode: either calculating a patient's initial "starting" dose or determining the next dose reduction for a patient already on therapy who has experienced toxicity.
• Why is Rozlytrek not recommended in severe hepatic impairment (Child-Pugh C)?
  The pharmacokinetics of entrectinib have not been studied in patients with severe hepatic impairment, and its safety in this population is unknown. Therefore, its use is not recommended.
• Is this calculator a substitute for the official prescribing information?
  No. This tool is for educational purposes only and should not replace clinical judgment or the full, official prescribing information. Always verify calculations and consult the complete product label.

References

• ROZLYTREK (entrectinib) US Prescribing Information. Genentech, Inc. FDA.
• Dosing and Administration for ROZLYTREK. Genentech USA, Inc.
• Rozlytrek (entrectinib) European Public Assessment Report (EPAR). European Medicines Agency.
• Entrectinib - NCI Drug Dictionary. National Cancer Institute.