What Is Sotorasib?
Sotorasib is a targeted cancer medicine for the treatment of certain types of non-small cell lung cancer with a specific genetic mutation called the KRAS G12C mutation. This mutation enables cancer cells to develop and multiply quickly. This medicine blocks the cancer cell’s mutated gene, thus slowing down the cancer cell’s growth.
The FDA (Food and Drug Administration) approved Sotorasib in May 2021. This medicine is for adults with locally advanced or metastatic non-small cell lung cancer with a KRAS G12C mutation who have received at least one prior systemic treatment.
Doctors may recommend Sotorasib for cancer patients whose cancer continues to progress after other treatments. This medicine is available in tablet form, and the patient is monitored for side effects. Testing is required before taking the medicine to ensure the presence of the KRAS G12C mutation in cancer cells.
What Are the Uses of Sotorasib?
Sotorasib is used to treat non-small cell lung cancer (NSCLC) that carries the KRAS G12C genetic mutation. It inhibits the function of the protein KRAS G12C, a major promoter of cancer development in people with this genetic mutation.
The following are particular Sotorasib indications:
Carcinoma of the non-small cell lung (NSCLC) with the KRAS G12C mutation.
Disease development following previous therapy(s).
Individuals who cannot have surgery or get radiation therapy.
How Does Sotorasib Work?
Sotorasib is the first targeted treatment to show clinical efficacy in NSCLC patients with the KRAS G12C mutation. A particular mutant variant of the KRAS protein, frequently present in several forms of cancer, is the target of the small molecule inhibitor Sotorasib (also known as AMG 510). A GTPase protein called KRAS is essential for cell signaling pathways that control cell growth and division. Overactive KRAS proteins can result from mutations in the KRAS gene, which can help cancer develop and spread.
Once it binds to the altered KRAS protein, Sotorasib begins to operate by precisely targeting the amino acid alteration known as KRAS G12C. Due to this interaction, the protein undergoes a conformational change, which hinders downstream signaling pathways that support the survival and proliferation of cancer cells.
Dose and Dosage of Sotorasib
Sotorasib is a medication used to treat non-small cell lung cancer that carries the KRAS G12C mutation.
Oral tablets containing 120 mg (milligrams) and 180 mg are the only available dosage forms for Sotorasib.
Eight 120 mg pills or five 180 mg tablets taken orally once per day with or without meals make up the recommended daily dosage of Sotorasib, which is 960 mg.
It is crucial to take the prescription every day without crushing or chewing the tablets.
Directions
The following are basic guidelines for utilizing Sotorasib:
Sotorasib tablets are available and should be taken once a day, with or without meals.
Sotorasib should be used once a day orally in doses of 960 mg (eight 120 mg pills or five 180 mg tablets).
The pills must not be chewed, crushed, or broken.
Take the missed dosage as soon as it is recalled. Skip the missed dosage and follow the usual dosing plan if it is less than six hours before the next scheduled dose.
If an overdose of Sotorasib occurs, call the doctor or get help immediately.
Sotorasib should be kept at room temperature, away from heat sources, moisture, and direct sunlight.
For Patients
How Effective Is Sotorasib?
In clinical studies, Sotorasib has demonstrated promise in treating non-small cell lung cancer (NSCLC) with the KRAS G12C mutation. In patients with advanced NSCLC with the KRAS G12C mutation who had had at least one prior line of treatment, Sotorasib showed an overall response rate (ORR) of 37.1 percent. The usual time taken for the response was ten months.
Furthermore, the safety profile of Sotorasib was easily managed and well-tolerated by the patients. During the clinical trials conducted on the drug, the most common side effects were diarrhea, exhaustion, nausea, musculoskeletal discomfort, and cough.
The effectiveness of Sotorasib may vary based on the particular features of each patient, including the amount and location of cancer, the existence of other medical disorders, and the patient's general health state.
Things to Inform the Doctor Before Starting Sotorasib:
If a person has an allergy to Sotorasib, other drugs, or any of the substances in Sotorasib tablets, inform the doctor and pharmacist immediately. Get a list of the components from the chemist.
Inform the doctor about any other prescription and over-the-counter drugs, vitamins, dietary supplements, and herbal items they are taking or intend to use.
Sotorasib may interact with the following over-the-counter medicines or herbal supplements: Ranitidine, Cimetidine, Esomeprazole, Famotidine, Lansoprazole, and Omeprazole. When using Sotorasib, inform the doctor about taking these drugs. When using Sotorasib, avoid starting any drugs without first seeing the doctor.
Take Sotorasib either four hours before or ten hours after taking an antacid if a person is taking both.
Inform the doctor if one has or has previously had lung or breathing issues other than lung cancer or liver illness.
If pregnant or intend to become pregnant, inform the doctor right away. Sotorasib should not be used by women who are pregnant or trying to get pregnant.
If used during pregnancy, Sotorasib may be dangerous to the unborn child. Effective birth control should be utilized throughout therapy and for one week following the final dosage of Sotorasib.
Since it can enter breast milk, Sotorasib poses a risk to breastfeeding infants. Sotorasib should not be taken by nursing mothers, or they should discuss discontinuing it while taking the medicine.
Side Effects of Sotorasib
Vomiting.
Nausea.
Constipation.
Reduced appetite.
Fatigue.
Discomfort in the muscle or bone.
Stomach ache.
Arthritic rash (rash related to an immune disorder).
Certain adverse effects can be quite harmful. If any of these symptoms are encountered, seek emergency care:
Black urine, yellowing of the skin or eyes, easier bruising or bleeding, loss of appetite, low energy, or pain in the right side of the stomach region.
Breathing difficulty, coughing, or fever.
Other side effects of Sotorasib are possible. Contact the doctor immediately if one experiences any unusual issues while taking this medication.
How to Take Sotorasib?
Take Sotorasib exactly as prescribed by the healthcare provider. Wait to change the dose or stop taking Sotorasib after consulting the healthcare provider.
Sotorasib is taken orally, usually once a day. The recommended dose is 960 mg, taken with or without food.
Swallow the Sotorasib tablet whole with a glass of water.
If the dose of Sotorasib is missed, take it as soon as remembered. However, if it is less than six hours before the next scheduled dose, the missed dose can be skipped. Resume the regular dosing schedule. Refrain from taking extra doses to make up for a missed dose.
If one experiences any side effects or concerns about using Sotorasib, talk to the healthcare provider as soon as possible.
The healthcare provider will monitor the patient’s response to Sotorasib and adjust the dose or treatment schedule as needed. Be sure to keep all the appointments with the healthcare provider.
Store Sotorasib tablets at room temperature, away from heat and moisture.
Missed Dose
Take the missed dosage as soon as it is recalled. Skip the missed dosage and follow the usual dosing plan if it is less than six hours before the next scheduled dose. If you unintentionally take too much Sotorasib, call the doctor or get help immediately.
Sotorasib Overdose
Sotorasib side effects, such as diarrhea, lethargy, nausea, musculoskeletal discomfort, and cough, are more likely to occur in an overdose. It must be managed by medical personnel, depending on the severity of the overdose.
How to Store Sotorasib?
Sotorasib should be kept between 68°F (degrees Fahrenheit) and 77°F (20 and 25 degrees Celsius) in a dry environment. Sotorasib should be stored according to the following advice:
Keep it in its original container until it is time to take the medicine.
Keep Sotorasib away from heat, moisture, and direct sunlight.
Keep children and pets away from the drug.
Never freeze Sotorasib.
Dispose of any unused or expired medicine in accordance with local legislation.
Before using Sotorasib, it is crucial to constantly verify the expiration date and not use it if it has passed.
For Doctors
Pharmacology
Mechanism of Action:
By activating the protein and promoting effectors in the MAP kinase pathway, GTP normally binds to KRAS.
KRAS is deactivated, and GTP hydrolyzes to GDP.
KRAS G12C mutations prevent GTP from being hydrolyzed, leaving it active.
With KRAS G12C mutations, Sotorasib binds to the cysteine residue, keeping the protein inactive.
As the natural type, KRAS lacks the cysteine residue that Sotorasib targets, so off-target effects are avoided. One to three percent of solid tumors, three percent of colorectal and appendix cancers, and 13 % of non-small cell lung cancers have this mutation.
Absorption
Sotorasib is absorbed at 960 mg (milligrams) once daily, with a Cmax (maximum plasma concentration) of 7.50 g/mL, a median Tmax (time to reach maximum plasma concentration) of 2.0 hours, and an AUC0–24 h (area under the plasma concentration–time curve from zero to 24 hours) of 65.3 h*g/mL.
Volume of Distribution
The Sotorasib distribution volume is 211 liters.
Involving Proteins
In plasma, Sotorasib is 89 percent protein-bound.
Metabolism
The two main metabolic pathways for Sotorasib are conjugation and CYP3As.
Excretion:
74 percent of the drug Sotorasib is excreted in feces, while 6 percent is excreted in the urine.
The unmodified parent molecule makes up 53 percent of the dosage found in the feces and one percent of the dose found in the urine.
Half-Life
The terminal elimination half-life of Sotorasib is 5.5 +/- 1.8 hours.
Clearance
At a steady state, Sotorasib has an apparent clearance of 26.2 liters per hour.
Management of Toxicity
Depending on the toxicity and the circumstances surrounding each patient, Sotorasib's clinical and non-clinical side effects may require different management strategies. The following are some basic toxicity management guidelines:
Managing Clinical Toxicity:
When mild to severe side effects like diarrhea or nausea occur, supportive care techniques like water or anti-nausea medication are frequently used to control them.
Treatment options for more severe side effects, such as pneumonitis or elevated liver enzymes, may include stopping Sotorasib usage and/or administering corticosteroids or other immunosuppressive drugs.
Healthcare professionals must regularly evaluate patients for negative side effects and modify therapy as necessary.
Management of Non-clinical Toxicity
Similar to clinical toxicity, non-clinical toxicity management is based on the degree of toxicity and the circumstances of each patient.
Patients may need to be watched for indications of DNA (deoxyribonucleic acid) damage or an increased risk of developing cancer if Sotorasib is determined to have genotoxic potential.
Treatment options for liver toxicity may include monitoring liver function tests, modifying doses as needed, or stopping the medicine altogether.
It may be important to refrain from using Sotorasib in pregnant women or those attempting to get pregnant in situations of developmental toxicity.
Warnings and Precautions
When taking Sotorasib, the following warnings and precautions are crucial to remember:
Interstitial Lung Disease (ILD): Sotorasib may result in interstitial lung disease (ILD), a severe and potentially deadly illness. ILD symptoms might include fever, coughing, and shortness of breath. Sotorasib therapy should be stopped after ILD is detected, and suitable medical attention should be given.
Hepatotoxicity: Sotorasib has the potential to damage the liver, which might result in liver failure. When taking Sotorasib, liver function tests should be performed frequently, and the medication should be stopped if liver damage is detected.
Embryo-Fetal Toxicity: Sotorasib can damage a growing baby and should not be taken during pregnancy unless the possible advantages outweigh the dangers due to embryo-fetal toxicity. Patients should use reliable birth control while using Sotorasib and for at least a month after finishing the medication.
QT Prolongation: Sotorasib has the potential to extend QT, which may result in an irregular heartbeat. When using Sotorasib, patients with a history of QT prolongation or other risk factors for this illness should be constantly monitored.
Rash: Sotorasib may result in a serious rash. Sotorasib therapy should be stopped, and proper medical attention should be given if a severe rash appears.
Photosensitivity: Sotorasib has the potential to cause photosensitivity, which might result in a painful sunburn. With Sotorasib therapy, patients should stay out of the sun and wear sunscreen and protective clothing.
Result: Sotorasib may result in alterations in eyesight or eye discomfort, among other eye issues.
Usage in Certain Populations: As the safety and effectiveness of Sotorasib have not been demonstrated in patients with moderate or severe renal impairment, these patients should use it with caution.
Contraindications:
Hypersensitivity: Those with a known allergy to the medication or its ingredients should not use Sotorasib.
Strong CYP3A4 Inhibitors: Sotorasib should not be administered to individuals who are using strong CYP3A4 inhibitors since these medications can raise the blood concentration of Sotorasib and increase the risk of side effects.
Pregnancy: Due to the possibility of damage to a developing baby, Sotorasib is not recommended for use in pregnant women.
Breastfeeding: Because it is unknown if Sotorasib is secreted in human milk and might affect a nursing child, the medicine is contraindicated for breastfeeding women.
Severe Hepatic Impairment: Those with severe hepatic impairment shouldn't take Sotorasib because it hasn't been thoroughly researched in this group and may worsen their liver damage.
Other Specifications:
Pregnancy: Sotorasib should not be used during pregnancy due to the risk to the fetus. Effective contraception should be used by women who are sexually active during their Sotorasib therapy and for at least one month following the final dosage.
Lactation: It is unknown if Sotorasib is secreted in breast milk during lactation. Therefore, breastfeeding should be avoided while receiving Sotorasib medication due to the risk of damage to a nursing newborn.
Pediatrics: The safety and efficacy of Sotorasib in pediatric patients under 18 have not been demonstrated. Sotorasib is not advised for usage in this demographic until further information is known.
