Dosage and Administration of Sotorasib: Dosing Guidelines, Dose Modifications, Use in Special Popula

KRAS mutations have long been considered a major challenge in cancer research, remaining difficult to target for many years. The launch of Sotorasib has changed this landscape, offering a new treatment option for patients with KRAS mutations, particularly those with non-small cell lung cancer (NSCLC).

Recommended Adult Dosage of Sotorasib

Non-Small Cell Lung Cancer / Colorectal Cancer

Administer 960 mg orally once daily until disease progression or unacceptable toxicity occurs.

Precautions for Sotorasib Administration

(I) Precautions Before Administration

Patient Selection

Prior to administration, select patients based on the presence of a KRASG12C mutation in tumor or plasma samples. If the mutation is not detected in a plasma sample, tumor tissue should be tested.

(II) Precautions During Administration

Timing and Method of Administration

Sotorasib should be taken at the same time each day, with or without food.

Method of Ingestion

Swallow the tablet whole. Do not chew, crush, or split the tablet.

Administration for Patients with Difficulty Swallowing

a. Disperse the tablet in 120 mL (4 ounces) of non-carbonated room temperature water without crushing. Do not use other liquids.

b. Stir until the tablet disperses into small pieces (the tablet will not completely dissolve). Administer immediately or within 2 hours. The mixture may appear pale yellow to bright yellow.

c. Swallow the dispersed liquid. Do not chew the tablet fragments.

d. Rinse the container with an additional 120 mL (4 ounces) of water and drink.

e. If not administered immediately, stir again to ensure the tablet is evenly dispersed.

Missed Dose

If more than 6 hours have passed since the missed dose, take the next dose as prescribed the following day. Do not take two doses at the same time to make up for the missed dose.

Vomiting

If vomiting occurs after taking the dose, do not take an additional dose. Take the next dose as prescribed the following day.

Monitoring Recommendations for Sotorasib

Hepatic Monitoring

Monitoring Parameters

Liver function tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin.

Monitoring Frequency

Monitor before initiating Sotorasib, every 3 weeks during the first 3 months of treatment, then once monthly thereafter, or as clinically indicated. More frequent monitoring is recommended for patients who develop elevated transaminases and/or bilirubin.

Respiratory Monitoring

Monitor for new or worsening pulmonary symptoms that may indicate interstitial lung disease (ILD) or pneumonitis.

Dose Modifications for Sotorasib

(I) Dose Reduction for Adverse Reactions

First Dose Reduction: Administer Sotorasib 480 mg orally once daily.

Second Dose Reduction: Administer Sotorasib 240 mg orally once daily.

(II) Dose Modifications for Specific Adverse Reactions

Interstitial Lung Disease (ILD)/Pneumonitis

Any Grade: Suspend Sotorasib if ILD/pneumonitis is suspected. Permanently discontinue Sotorasib if ILD/pneumonitis is confirmed.

Nausea or Vomiting Despite Appropriate Supportive Care (Including Antiemetic Therapy)

Grade 3–4: Suspend Sotorasib until resolved to Grade 1 or less or baseline. Resume treatment at the next lower dose level.

Diarrhea Despite Appropriate Supportive Care (Including Antidiarrheal Therapy)

Grade 3–4: Suspend Sotorasib until resolved to Grade 1 or less or baseline. Resume treatment at the next lower dose level.

Other Adverse Reactions

Grade 3–4: Suspend Sotorasib until resolved to Grade 1 or less or baseline. Resume treatment at the next lower dose level.

Dosage Adjustments for Special Populations Taking Sotorasib

(I) Dosage Adjustment for Patients with Renal Impairment

No relevant data are currently available.

(II) Dosage Adjustment for Patients with Hepatic Impairment

Management of Hepatotoxicity

If Grade 2 AST or ALT Elevation with Symptoms, or Grade 3–4 AST or ALT Elevation Occurs

Suspend dosing until recovery to Grade 1 or less or baseline. Resume treatment at the next lower dose.

First Dose Reduction: Administer Sotorasib 480 mg orally once daily.

Second Dose Reduction: Administer Sotorasib 240 mg orally once daily.

If AST or ALT Elevation > 3 × Upper Limit of Normal (ULN) with Total Bilirubin Elevation > 2 × ULN, in the Absence of Another Clear Cause

Permanently discontinue Sotorasib.