Lumakras Special Precautions

Hepatotoxicity: LUMAKRAS can cause hepatotoxicity and increased alanine aminotransferase (ALT) or increased aspartate aminotransferase (AST) which may lead to drug-induced liver injury and hepatitis.
In the pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg [see Clinical Trials Experience under Adverse Reactions], hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥3). Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.
In this pool safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg, 17% of patients who received LUMAKRAS had increased ALT/increased AST; of which 9% were Grade ≥3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS. LUMAKRAS was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥3).
In this pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg, a total of 40% patients with recent (≤3 months) immunotherapy prior to starting LUMAKRAS had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS, with or without corticosteroid treatment.
In the pooled safety population of patients with CRC who received LUMAKRAS 960 mg in combination with panitumumab [see Clinical Trials Experience under Adverse Reactions], hepatotoxicity occurred in 15% of patients, of which 4.8% were Grade 3. A total of 7% of patients who received LUMAKRAS had increased ALT or increased AST, of which 0.8% were Grade 3. The median time to first onset of increased ALT or increased AST was 10 weeks (range: 2 to 22). Increased ALT or increased AST leading to dose interruption occurred in 2.4% of patients. A total of 3.2% of patients who received LUMAKRAS had hyperbilirubinemia, of which 2.4% were Grade 3. The median time to first onset of hyperbilirubinemia was 12 weeks (range: 0, 29).
Hyperbilirubinemia leading to dose interruption occurred in 1.6% of patients. Among patients with hepatotoxicity, 21% received corticosteroids.
Monitor liver function tests (ALT, AST, alkaline phosphatase and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS based on severity of the adverse reaction [see Posology under Dosage & Administration and Clinical Trials Experience under Adverse Reactions]. Consider administering systemic corticosteroids for the management of hepatotoxicity.
Interstitial Lung Disease (ILD)/Pneumonitis: LUMAKRAS can cause ILD/pneumonitis that can be fatal.
In the pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg [see Clinical Trials Experience under Adverse Reactions], ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥3, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1 to 36.7 weeks). LUMAKRAS was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS-treated patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified [see Posology under Dosage & Administration and Clinical Trials Experience under Adverse Reactions].
In the pooled safety population of patients with CRC who received LUMAKRAS 960 mg in combination with panitumumab, 1 patient experienced a Grade 1 event of ILD/pneumonitis [see Clinical Trials Experience under Adverse Reactions].
Effects on Ability to Drive and Use Machines: LUMAKRAS has no or negligible influence on the ability to drive and use machines.