About This Calculator

The Tagrisso (osimertinib) Dose Calculator is an educational resource for healthcare professionals to determine appropriate dosing based on the FDA-approved prescribing information. It covers initial dosing, dose modifications for adverse reactions, and adjustments for drug-drug interactions, helping to ensure patient safety and therapeutic efficacy.

Outputs

The tool provides a clear, actionable recommendation based on the user's selected scenario. Outputs include:

• Recommended Dose: The calculated dose in milligrams (e.g., 80 mg, 40 mg, 160 mg).
• Required Action: A directive such as "Start treatment," "Reduce dose," "Withhold treatment," or "Permanently discontinue."
• Clinical Rationale: A brief explanation for the recommendation, referencing key safety or efficacy considerations from the product label.

How to Use

To use the calculator, follow these steps:

1. Select the Primary Scenario: Choose whether you are calculating an initial dose, adjusting for an adverse reaction, or accounting for a concomitant medication.
2. Provide Scenario-Specific Details: If adjusting for an adverse event, select the specific reaction and the patient's current dose. If adjusting for a drug interaction, select the class of interacting medication.
3. Calculate: The tool will process the inputs and display the recommended dosing regimen and management plan.

Dosing Overview

The dosing of Tagrisso is tailored to the clinical situation:

• Standard Dose: The recommended dose for most indications is 80 mg orally once daily, with or without food.
• Dose Reduction: For management of certain adverse reactions, the dose can be reduced to 40 mg once daily. If further dose reduction is required, treatment should be permanently discontinued.
• Dose Increase: When co-administered with a strong CYP3A inducer, the Tagrisso dose should be increased to 160 mg once daily.

Switching

There are no specific guidelines in the prescribing information for switching between other targeted therapies and Tagrisso. Any transition in treatment should be managed by an experienced oncologist, considering factors such as the half-life of the previous drug, the patient's clinical status, and potential for overlapping toxicities. Always refer to the most current clinical guidelines and prescribing information.

Missed Dose

If a patient misses a dose of Tagrisso, they 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 the regular dosing schedule. Patients must be instructed not to take a double dose to make up for a missed one.

Safety Alerts

Dose modifications are critical for managing toxicities. Key safety concerns requiring dose interruption, reduction, or discontinuation include:

• Interstitial Lung Disease (ILD)/Pneumonitis: Permanently discontinue Tagrisso if ILD/Pneumonitis is diagnosed.
• QTc Interval Prolongation: Withhold treatment for QTc >500 msec. Resume at a reduced dose (40 mg) once QTc normalizes.
• Cardiomyopathy: Withhold treatment for a symptomatic decline in left ventricular ejection fraction (LVEF). Treatment may be resumed at a reduced dose if LVEF recovers within 4 weeks.
• Keratitis: Withhold treatment and seek an urgent ophthalmology consultation.
• Drug Interactions: Avoid co-administration with strong CYP3A inducers where possible. If unavoidable, increase the Tagrisso dose to 160 mg/day. Monitor closely when used with strong CYP3A inhibitors.

FAQ

What is the standard starting dose of Tagrisso?

The standard recommended starting dose is 80 mg taken orally once a day.

How is the Tagrisso dose adjusted for a Grade 3 adverse reaction?

For a Grade 3 or greater adverse reaction (other than the specific events listed), treatment should be withheld for up to 3 weeks. If the reaction improves to Grade 0-2, treatment can be resumed at a reduced dose of 40 mg once daily.

What should I do if my patient is starting a strong CYP3A inducer like rifampin?

The Tagrisso dose should be increased to 160 mg once daily. After the inducer is discontinued for 3 weeks, the Tagrisso dose should be returned to 80 mg once daily.

Should Tagrisso be stopped for a QTc interval over 500 msec?

Yes, Tagrisso should be withheld if the QTc interval is greater than 500 msec on at least two separate ECGs. It can be resumed at a 40 mg dose once the QTc returns to less than 481 msec or baseline.

Can I resume Tagrisso after it was stopped for cardiomyopathy?

If LVEF recovers to baseline levels within 4 weeks of withholding treatment, Tagrisso may be resumed at a reduced dose of 40 mg daily. If it does not recover, permanent discontinuation is required.

What is the lowest recommended dose of Tagrisso?

The lowest dose is 40 mg once daily. If a patient cannot tolerate this dose, the medication should be permanently discontinued.

Does this calculator apply to pediatric patients?

No. The safety and effectiveness of Tagrisso have not been established in pediatric patients. This calculator is for adult patients only.

What is the recommendation for co-administration with a strong CYP3A inhibitor?

Co-administration should be avoided if possible. If it's unavoidable, patients should be monitored more frequently for Tagrisso-related adverse reactions. The prescribing information does not recommend a specific dose adjustment.

References

1. TAGRISSO® (osimertinib) Prescribing Information. U.S. Food and Drug Administration.
2. Tagrisso (osimertinib) Summary of Product Characteristics. European Medicines Agency.
3. TagrissoHCP.com. Official AstraZeneca Website for Healthcare Professionals.
4. Drugs@FDA: FDA-Approved Drugs - TAGRISSO (osimertinib).