sotorasib

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action 

sotorasib is a small molecule inhibitor that explicitly targets the KRAS G12C mutation, a common mutation found in certain types of cancer, including NSCLC. The KRAS G12C mutation leads to uncontrolled cell growth and proliferation. sotorasib works by irreversibly binding to the mutant KRAS protein, inhibiting its signaling activity and interfering with downstream signaling pathways that promote tumor growth. By targeting this specific mutation, sotorasib aims to inhibit the cancer-promoting effects of KRAS G12C and slow down tumor growth. 

Spectrum of Activity 

sotorasib is specifically designed to target and inhibit the KRAS G12C mutation, predominantly found in non-small cell lung cancer (NSCLC). This mutation occurs in approximately 13% of NSCLC cases, making it the most common KRAS mutation in this cancer type. Therefore, sotorasib is primarily indicated for treating NSCLC patients with the KRAS G12C mutation. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All grades 

Decreased hemoglobin (43%) 

Increased AST (39%) 

Musculoskeletal pain (35%) 

Increased alkaline phosphatase (33%) 

Increased urine protein (29%) 

Nausea (26%) 

Hepatoxicity (25%) 

Decreased lymphocytes (48%) 

Diarrhea (42%) 

Increased ALT (28%) 

Decreased calcium (35%) 

Decreased sodium (28%) 

Fatigue (26%) 

Dyspnea (16%) 

Cough (20%) 

Edema (15%) 

Increased activated partial thromboplastin time (aPTT) (23%) 

Decreased albumin (23%) 

Vomiting (17%) 

Constipation (16%) 

Abdominal pain (15%)  

Grade 3 or 4 

Increased ALT (11%) 

Hepatoxicity (12%) 

1-10% 

Grade 3 or 4 

Musculoskeletal pain (8%) 

Diarrhea (5%) 

Dyspnea (2.9%) 

Increased alkaline phosphatase (2.5%) 

Fatigue (2%) 

Cough (1.5%) 

Decreased sodium (1%) 

Arthralgia (1%) 

Nausea (1%) 

Increased AST (9%) 

Pneumonia (7%) 

Increased urine protein (3.9%) 

Decreased lymphocytes (2%) 

Increased aPTT (1.5%) 

Vomiting (1.5%) 

Decreased appetite (1%) 

Abdominal pain (1%) 

<1% 

Grade 3 or 4 

Decreased albumin (0.5%) 

Decreased hemoglobin (0.5%) 

Constipation (0.5%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Hepatic Toxicity: sotorasib can cause liver toxicity. Liver function tests should be monitored regularly during treatment, and caution should be exercised in individuals with pre-existing liver conditions or impaired liver function. 
• Interstitial Lung Disease (ILD) or Pneumonitis: sotorasib has been associated with ILD or pneumonitis, which is inflammation of the lung tissue. Symptoms may include cough, difficulty breathing, or shortness of breath. Patients should be monitored for signs of ILD or pneumonitis, and treatment should be discontinued if severe cases occur. 
• QT Interval Prolongation: sotorasib may cause QT interval prolongation, leading to an irregular heartbeat. Electrocardiograms (ECGs) should be performed before starting treatment and periodically during treatment, especially in patients with pre-existing cardiac conditions or risk factors for QT prolongation. 
• Drug Interactions: sotorasib may interact with other medications, including over-the-counter drugs, prescription medications, and herbal supplements.  
• Pregnancy and Breastfeeding: sotorasib during pregnancy or while breastfeeding is not recommended, as its effects on fetal development and its presence in breast milk are not well-established. Adequate contraception should be used during treatment and for a certain period after the last dose. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

sotorasib (AMG 510) is a targeted therapy medicine for treating non-small cell lung cancer (NSCLC) with a specific mutation called KRAS G12C. Here are some critical aspects of the pharmacology of sotorasib: 

sotorasib is a small molecule inhibitor that targets the KRAS G12C mutation. The KRAS gene plays a critical role in regulating cell growth and division. The G12C mutation in KRAS produces a constitutively active protein that promotes cancer cell growth. sotorasib works by irreversibly binding to the mutant KRAS G12C protein, inhibiting its signaling activity. This inhibition interferes with downstream signaling pathways involved in tumor growth and survival. 

Pharmacodynamics: 

• KRAS G12C Inhibition: sotorasib targets the KRAS G12C mutation, inhibiting its signaling activity. This inhibition interferes with downstream signaling pathways involved in tumor growth, proliferation, and survival. 
• Anticancer Effects: By targeting the KRAS G12C mutation, sotorasib aims to inhibit the cancer-promoting effects of mutant KRAS and slow down tumor growth in NSCLC patients with this specific mutation. 

Pharmacokinetics: 

Absorption 

sotorasib is administered orally in the form of tablets. After oral administration, it is absorbed from the gastrointestinal tract into the bloodstream. The specific details regarding the rate and extent of absorption of sotorasib are not readily available in my training data. 

Distribution 

The distribution of sotorasib in the body is not extensively described in the available information. It is expected to distribute to various tissues, including tumor cells harboring the KRAS G12C mutation. The binding of sotorasib to the target protein KRAS G12C indicates its ability to reach the intended site of action. 

Metabolism 

sotorasib undergoes metabolism primarily in the liver through the cytochrome P450 (CYP) enzyme system, primarily involving CYP3A4. The exact details of the metabolites formed and their activity levels are relatively rare. 

Elimination and Excretion 

The elimination of sotorasib and its metabolites from the body occurs mainly through feces, with a smaller portion eliminated in urine. The specific percentages of excretion through feces and urine are not readily available. 

Adminstartion

Administration: 

• Dosage: The specific dosage of sotorasib and the recommended treatment regimen may vary depending on the individual’s condition and the prescribing healthcare professional’s instructions. It’s essential to follow the prescribed dosage and schedule. 
• Timing: sotorasib tablets are usually taken once daily, with or without food. It’s essential to take the medication simultaneously each day as directed by the healthcare professional. 
• Swallowing: The sotorasib tablets should be swallowed whole with water. Do not chew, crush, or break the tablets unless specifically instructed by your healthcare provider. 
• Missed Dose: If a missed dose, it should be taken as soon as remembered unless it is close to the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule should be resumed. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sotorasib 

Why do we use sotorasib? 

sotorasib (AMG 510) is a targeted therapy for treating non-small cell lung cancer (NSCLC) with a specific mutation known as KRAS G12C. Here are the primary uses of sotorasib: 

• Non-Small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation: sotorasib is primarily indicated for treating NSCLC patients with the KRAS G12C mutation. This mutation is found in a subset of NSCLC cases and is associated with poor prognosis. sotorasib targets and inhibits the KRAS G12C protein, which promotes cancer growth, thereby slowing down tumor growth and improving patient outcomes.