Drug Detail:Lumakras (Sotorasib)
Generic Name: SOTORASIB 120mg
Dosage Form: tablet, coated
Drug Class: Miscellaneous antineoplastics
Patient Selection
Select patients for treatment of locally advanced or metastatic NSCLC with LUMAKRAS based on the presence of KRAS G12C mutation in tumor or plasma specimens [see Clinical Studies (14)]. If no mutation is detected in a plasma specimen, test tumor tissue.
Information on FDA-approved tests for the detection of KRAS G12C mutations is available at: http://www.fda.gov/CompanionDiagnostics.
Recommended Dosage and Administration
The recommended dosage of LUMAKRAS is 960 mg (three 320 mg tablets or eight 120 mg tablets) orally once daily until disease progression or unacceptable toxicity.
Take the daily dose of LUMAKRAS at the same time each day with or without food [see Clinical Pharmacology (12.3)]. Swallow tablets whole. Do not chew, crush or split tablets. If a dose of LUMAKRAS is missed by more than 6 hours, take the next dose as prescribed the next day. Do not take 2 doses at the same time to make up for the missed dose.
If vomiting occurs after taking LUMAKRAS, do not take an additional dose. Take the next dose as prescribed the next day.
Administration to Patients Who Have Difficulty Swallowing Solids
Disperse tablets in 120 mL (4 ounces) of non-carbonated, room-temperature water without crushing. No other liquids should be used. Stir or swirl the cup for approximately 3 minutes until tablets are dispersed into small pieces (the tablets will not completely dissolve) and drink immediately or within 2 hours. The appearance of the mixture may range from pale yellow to bright yellow. Swallow the tablet dispersion. Do not chew pieces of the tablet. Rinse the container with an additional 120 mL (4 ounces) of water and drink. If the mixture is not consumed immediately, stir the mixture again to ensure that tablets are dispersed.
Dosage Modifications for Adverse Reactions
LUMAKRAS dose reduction levels are summarized in Table 1. Dosage modifications for adverse reactions are provided in Table 2.
If adverse reactions occur, a maximum of two dose reductions are permitted. Discontinue LUMAKRAS if patients are unable to tolerate the minimum dose of 240 mg once daily.
| Dose Reduction Level | Dose |
|---|---|
| First dose reduction | 480 mg (four 120 mg tablets) once daily |
| Second dose reduction | 240 mg (two 120 mg tablets) once daily |
| Adverse Reaction | Severity* | Dosage Modification |
|---|---|---|
| ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal | ||
|
||
| Hepatotoxicity [see Warnings and Precautions (5.1)] | Grade 2 AST or ALT with symptoms or Grade 3 to 4 AST or ALT |
|
| AST or ALT > 3 × ULN with total bilirubin > 2 × ULN in the absence of alternative causes |
|
|
| Interstitial Lung Disease (ILD)/ pneumonitis [see Warnings and Precautions (5.2)] | Any Grade |
|
| Nausea or vomiting despite appropriate supportive care (including anti-emetic therapy) [see Adverse Reactions (6.1)] |
Grade 3 to 4 |
|
| Diarrhea despite appropriate supportive care (including anti-diarrheal therapy) [see Adverse Reactions (6.1)] |
Grade 3 to 4 |
|
| Other adverse reactions [see Adverse Reactions (6.1)] |
Grade 3 to 4 |
|
Coadministration of LUMAKRAS with Acid-Reducing Agents
Avoid coadministration of proton pump inhibitors (PPIs) and H2 receptor antagonists with LUMAKRAS. If treatment with an acid-reducing agent cannot be avoided, take LUMAKRAS 4 hours before or 10 hours after administration of a local antacid [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
