Correctly mastering the usage and dosage of Vepdegestrant is fundamental to ensuring efficacy and safety. This article systematically reviews the core medication points in three aspects.

I. Standard Administration and Basic Requirements

1. Patient Eligibility Screening:

(1) This drug is indicated for the treatment of adult patients with ER‑positive, HER2‑negative, advanced or metastatic breast cancer harboring ESR1 gene mutations.

(2) Before initiation, the presence of an ESR1 mutation must be confirmed using an FDA‑authorized test (typically with a plasma specimen) – this is a prerequisite for therapy.

2. Recommended Standard Dose:

(1) For eligible patients, the recommended fixed regimen is 200 mg orally once daily.

(2) Treatment should continue until disease progression or unacceptable toxicity occurs; patients should not discontinue arbitrarily.

3. Important Administration Instructions:

(1) To ensure adequate absorption, each dose must be taken with food.

(2) Tablets should be swallowed whole; do not chew, crush, dissolve, or split before ingestion.

(3) Do not take tablets that are broken, cracked, or visually abnormal.

4. Management of Missed Doses or Vomiting:

(1) If vomiting occurs after a dose, or if a dose is missed, do not take an additional or make‑up dose on the same day.

(2) The patient should simply take the next dose at the regularly scheduled time the following day; never take a double dose to compensate.

II. Dose Adjustments for Adverse Reactions

1. General Dose‑Reduction Principle:

(1) When an adverse reaction requires management, the recommended initial dose reduction is from 200 mg to 100 mg orally once daily.

(2) If the patient remains intolerant after reduction to 100 mg, permanent discontinuation should be considered.

2. Adjustments for Non‑Cardiac Reactions:

For adverse reactions other than QTc prolongation, management is guided by the severity grade according to clinical judgment.

3. Adjustments for Cardiac‑Related Reactions:

(1) QTc interval prolongation is an adverse reaction requiring close monitoring.

(2) If QTc exceeds 480 ms or increases by >60 ms from baseline, withhold the dose; after recovery, therapy may be resumed at the original dose.

(3) For QTc >500 ms, stricter measures apply: if a reversible cause is identified and corrected, resume at the original dose; if no reversible cause is found, restart at the reduced dose (100 mg).

III. Dose Adjustments for Drug‑Drug Interactions

1. Coadministration with Strong CYP3A Inhibitors:

(1) Strong CYP3A inhibitors significantly increase Vepdegestrant plasma concentrations, raising the risk of adverse events.

(2) Therefore, concomitant use should be avoided whenever possible.

(3) If co‑administration is unavoidable, reduce the Vepdegestrant dose from 200 mg to 100 mg.

(4) After the inhibitor is discontinued for 3‑5 half‑lives, the dose may be restored to 200 mg.

2. Coadministration with Strong CYP3A Inducers:

(1) Strong CYP3A inducers lower Vepdegestrant plasma levels, potentially reducing therapeutic efficacy.

(2) Concomitant use should also be avoided. If unavoidable, increase the dose from 200 mg to 300 mg.

(3) After the inducer is withdrawn for 7‑14 days, the dose may be returned to 200 mg.

3. Other Medications Requiring Special Attention:

(1) This drug may increase plasma concentrations of certain P‑glycoprotein (P‑gp) or UGT1A9 substrates; use with caution.

(2) For such substrate drugs where even a modest increase in concentration may lead to severe adverse reactions, co‑administration should be avoided.