iCliniq logo

Ask a Doctor Online Now

HomeHealth articlesnon-small cell lung cancerWhat Is the Use of Adagrasib?

Adagrasib: Dosage, Indications, Effectiveness, and Side Effects

Verified dataVerified data
0

10 min read

Share

Adagrasib is an anticancer drug for treating non-small cell lung cancer (NSCLC).

Written by

Dr. Kinjal Shah

Medically reviewed by

Dr. Abdul Aziz Khan

Published At April 1, 2024
Reviewed AtMay 15, 2024

Overview

Adagrasib is a member of the class of drugs known as antineoplastics (anticancer drugs). It prevents the development of cancer cells, which are subsequently eliminated. Adagrasib, a RAS GTPase (an enzyme involved in DNA synthesis) family inhibitor, received accelerated approval from the Food and Drug Administration (FDA) on December 12, 2022, for adult patients suffering from metastatic or locally advanced non-small cell lung cancer, as identified by an FDA-approved test, who have received at least one prior systemic therapy.

How Does Adagrasib Work?

Adagrasib functions by concentrating on the KRAS G12C mutation, which affects 14 percent of people with non-small cell lung cancer (NSCLC). The G12C mutation traps the protein KRAS, essential for controlling cell growth and division, in an active state and promotes unchecked cell growth and proliferation.

A small chemical inhibitor called Adagrasib binds to the KRAS G12C protein to stop it from activating signaling pathways that support the development of tumors. Other targeted medicines, such as tyrosine kinase inhibitors, which decrease the activity of certain enzymes involved in the development of cancer cells, have a distinct mode of action.

Adagrasib may be able to delay or stop the growth of NSCLC tumors with this particular mutation by obstructing the action of KRAS G12C. Adagrasib has demonstrated anti-tumor solid activity in NSCLC patients with KRAS G12C mutations who have previously undergone systemic treatment, displaying encouraging outcomes in preclinical and clinical investigations.

Dosing and Dosage Form

  1. Depending on the particular clinical trial or indication under study, the dosage and dosage form options for Adagrasib may change. Adagrasib is, however, offered in oral tablet form.

  2. Patients with KRAS G12C mutations and non-small cell lung cancer (NSCLC) are advised to take 600 milligrams (mg) of Adagrasib once a day. However, based on the features and tolerance of each patient, the dosage may be changed.

  3. Adagrasib must only be used under the supervision of a medical professional, and patients must adhere to their provider's recommendations for dosage and administration. Additionally, patients should let their doctor know if they are taking any other drugs or have any illnesses that might interact with Adagrasib or make them more likely to experience negative side effects.

Directions

The following broad rules may be useful to patients:

  1. Adagrasib is a tablet that should be swallowed whole, with or without meals, following the healthcare provider's instructions.

  2. Patients with KRAS G12C mutations and non-small cell lung cancer (NSCLC) are commonly prescribed 600 mg of Adagrasib once a day. However, the exact dose and frequency may change based on the patient's unique features and medical background.

  3. To keep their blood levels of the drug constant, patients should take Adagrasib simultaneously every day.

  4. Avoid crushing, chewing, or breaking the pills since doing so might reduce the medication's efficacy.

Warnings

The following are some significant cautions and warnings related to Adagrasib:

  1. Interstitial Lung Disease (ILD): Adagrasib has the potential to induce interstitial lung disease (ILD), a potentially fatal lung illness that can include breathing problems, a cough, and fever. Patients should immediately report any new or worsening respiratory symptoms to their healthcare provider.

  2. Gastrointestinal (GI) Toxicity: Adagrasib can have gastrointestinal (GI) toxicity, which includes diarrhea, nausea, vomiting, and abdominal discomfort. Patients should immediately report any new or deteriorating GI symptoms to their physician.

  3. Hepatotoxicity: Adagrasib has the potential to harm the liver, which might lead to abnormally high liver function tests or liver failure. Patients should contact their healthcare practitioner immediately if they experience any new or worsening liver dysfunction symptoms, such as yellowing of the skin or eyes, stomach discomfort, or black urine.

  4. Toxicity to the Embryo-Fetus: Adagrasib is toxic to growing fetuses; hence, pregnant women are not advised to take it. During therapy with Adagrasib and for at least a month following the final dosage, women of reproductive potential should utilize effective contraception.

  5. QT Interval Prolongation: Adagrasib may extend the QT interval, which raises the possibility of an irregular cardiac rhythm. Adagrasib therapy should be continuously watched for changes in cardiac rhythm in patients with a history of QT prolongation or who are taking drugs that can do so.

  6. Squamous Cell Carcinoma and Keratoacanthoma: Adagrasib has been linked to the emergence of squamous cell carcinoma (skin cancer) and keratoacanthoma (dome-shaped skin tumor), two types of skin cancer. Patients should contact their healthcare practitioner if any skin lesions develop or change.

For Patients

What Is Non-small-Cell Lung Cancer?

  1. The majority of occurrences of lung cancer, between 80 and 85 percent, are caused by non-small cell lung cancer (NSCLC). As its name implies, the small cells typically found in lung tissue are not included in the NSCLC subtype of lung cancer. Instead, it often develops from the epithelial cells that border the lung's significant airways.

  2. Adenocarcinoma (globular tissue cancer), squamous cell carcinoma, and giant cell carcinoma are a few of the several forms of NSCLC. The most frequent kind, accounting for around 40 percent of all NSCLC cases, is adenocarcinoma, whereas squamous cell carcinoma makes up roughly 25 percent to 30 percent of cases. Less often occurring, accounting for 10 percent to 15 percent of cases, is large cell carcinoma.

  3. Coughing, chest discomfort, exhaustion, and shortness of breath are typical signs of NSCLC.

Learn More About Adagrasib

Before Starting Adagrasib

  1. Those with allergies, including allergies to the chemicals in Adagrasib tablets, should notify their doctor and pharmacist. An ingredient list should be obtained from the chemist.

  2. Inform the doctor and chemist about any other prescription and over-the-counter medications, vitamins, herbal items, nutritional supplements, and any drugs that are now taking or intend to take. The doctor might need to adjust the medication doses or watch for negative side effects.

  3. Tell the physician if ever had long QT syndrome, a rare cardiac illness that can result in erratic heartbeat, fainting, or unexpected death, any other type of irregular heartbeat, heart failure, liver or kidney issues, breathing or lung issues, or other than lung cancer.

  4. It should be mentioned to the doctor if one is pregnant or intends to become pregnant.

  5. Breastfeeding mothers should inform the doctor and discuss it. During therapy and one week following the last dosage, the doctor might advise against breastfeeding.

  6. Patients should be aware that this medicine may lower both male and female fertility. A person should discuss the dangers of taking Adagrasib with her doctor.

  7. Inform the surgeon or dentist about the history of taking Adagrasib.

When and Why to Take Adagrasib?

  1. Adagrasib is a drug used to treat certain non-small cell lung cancer (NSCLC) subtypes with the KRAS G12C genetic mutation. People with cancer who cannot be physically removed or have progressed after earlier therapy typically take this medicine.

  2. Adagrasib should be taken on an empty stomach one hour before or two hours after a meal. It is typically used once daily.

  3. A healthcare professional decides whether to prescribe a patient Adagrasib after reviewing their medical history and doing the necessary tests to see if their cancer carries the particular genetic mutation that Adagrasib is designed to target. It is crucial to adhere to the dose recommendations and any additional instructions the healthcare professional gives.

How Effective Is Adagrasib?

In clinical studies, Adagrasib has shown promise in treating non-small cell lung cancer (NSCLC) with KRAS G12C mutations. Adagrasib showed an objective response rate (ORR) of 45.3 percent in phase II clinical study, with a median duration of response of 11.1 months, in patients with NSCLC who had progressed despite previous therapy. Adagrasib demonstrated an ORR of 32 percent in patients with previously treated NSCLC with KRAS G12C mutations in a different clinical study, with a median time to response of 10 months.

These findings imply that Adagrasib may be a useful therapeutic option for NSCLC patients with a KRAS G12C mutation. However, it is crucial to remember that Adagrasib reactions may differ depending on the individual.

What Are the Side Effects of Adagrasib?

Adagrasib's typical adverse effects include the following:

  1. Nausea.

  2. Diarrhea.

  3. Fatigue.

  4. Reduced appetite.

  5. Rash.

  6. Cough.

  7. Breathing difficulty.

  8. Joint or muscle ache.

Though less common, the following adverse effects are more dangerous:

  1. Coughing, dyspnea, and other respiratory problems can be brought on by interstitial lung disease (ILD), which damages the lungs.

  2. Cardiac incidents like heart attacks or irregular heartbeats.

  3. Liver issues include high liver enzymes or failing liver.

  4. Extremely severe skin responses, including Stevens-Johnson syndrome or toxic epidermal necrolysis.

What Should Be Done if a Dose Is Missed?

Adagrasib should be taken as soon as remembered if a dosage is missed. If the next dosage is due, skip the missed one and continue with the normal dosing plan. Do not adjust the dosage to make up for missed time. Adagrasib side effects are more likely if used in excess.

What Should Be Done to Treat an Adagrasib Overdose?

Adagrasib overdose has no known particular antidote; thus therapy will concentrate on symptom management and supportive care. This could entail giving fluids and electrolytes to prevent dehydration, monitoring vital signs, including blood pressure and heart rate, and giving drugs to reduce nausea and vomiting.

How to Store Adagrasib?

  1. The recommended storage range for Adagrasib is 68°Fahrenheit (F) to 77°Fahrenheit (20°Celsius to 25°Celsius). Store in its built in container, with the lid securely fastened, out of direct sunlight, heat, and moisture.

  2. Adagrasib should not be stored in the bathroom or other locations where it could be exposed to moisture or humidity. Additionally, avoid putting it in the freezer or refrigerator because these temperatures might compromise the medication's stability and efficacy.

  3. Adagrasib should not be shared with others. It ought to be kept out of the reach of kids and animals.

  4. Dispose of any unused or expired medication responsibly by local laws and regulations.

Avoid Self-Medication

Only use this medication if a pharmacist or doctor has prescribed it. Do not suggest the drug to others; never accept someone else's prescription. Some people may even respond worse to drugs than others. Therefore, when using medications, adhere to the instructions given by the healthcare provider.

For Doctors:

Indications

Adagrasib is recommended for treating non-small cell lung cancer (NSCLC) that carries the KRAS G12C mutation, a particular sort of genetic change. It is prescribed to individuals with advanced or metastatic NSCLC who have had at least one previous systemic treatment.

Adagrasib should only be used under the supervision of a medical professional with training in the management of NSCLC because it is not recommended for the treatment of other cancers or genetic abnormalities.

Dosing

Adagrasib should be administered orally once a day with or without meals at a dose of 120 mg for the treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutations.

Dose Considerations

Depending on a person's unique circumstances, such as kidney or liver function, age, and other medical issues, dosage modifications may be required. Adagrasib is sold as a capsule and needs to be consumed whole with water. Avoid crushing, chewing, or breaking the capsule since doing so may reduce the medication's effectiveness and raise the possibility of adverse effects.

Pharmacology

Pharmacodynamics

Adagrasib's exposure-response relationship and pharmacodynamic response time course remain unclear. Adagrasib usage has the potential to extend QTc intervals. The rise in QTc depends on concentration. The mean QTc change from baseline (QTcF) in individuals receiving 600 milligrams of Adagrasib twice daily was 18 milliseconds at the mean steady-state maximum concentration. Adagrasib usage may potentially result in severe gastrointestinal side effects, hepatotoxicity, and pneumonitis or interstitial lung disease.

Mechanism of Action

  • KRAS is activated in healthy cells by binding to guanosine triphosphate (GTP), which encourages activation and intracellular signal transmission of the MAP kinase pathway. KRAS is deactivated when GTP is degraded to guanosine diphosphate (GDP). This mechanism controls cell development using an "on''/"off" scheme.

  • Cysteine is substituted for Gly12 in KRAS (KRAS G12C), which prevents GTP hydrolysis and keeps KRAS active. Consequently, this mutation causes unchecked cellular growth and proliferation, as well as malignant transformation.

  • Adagrasib is a covalent inhibitor of KRAS G12C that binds to and locks KRAS G12C in an inactive, guanosine diphosphate-bound state with irreversible and selective binding.

  • Adagrasib treatment decreases tumor cell proliferation and viability with negligible off-target action in tumors with KRAS G12C mutations.

Pharmacokinetics:

Absorption

Between 400 mg and 600 mg (0.67 to 1 times the authorized therapeutic dosage), Adagrasib's AUC and Cmax rise in a dose-proportional way. Adagrasib attained a steady state with a 6-fold accumulation at the indicated dose in eight days. Adagrasib has a Tmax of around six hours. A high-fat and high-calorie lunch (900–1000 calories, 50 percent of which were from fat) was administered. However, it had no clinically meaningful impact on the pharmacokinetics of Adagrasib. Adagrasib can enter the central nervous system and has a high oral bioavailability.

Dimensions of Dispersion

The apparent volume of distribution for Adagrasib is 248.85 United States liquid gallon (USLgal).

Protein Binding

Adagrasib binds 98 percent of human plasma proteins in vitro (experimentally outside the body).

Metabolism

Following a single dose, CYP3A4 is primarily responsible for Adagrasib's metabolism. Adagrasib suppresses CYP3A4 after many doses, thus, other enzymes such as CYP2C8, CYP1A2, CYP2B6, CYP2C9, and CYP2D6 participate in its steady-state metabolism.

Route of Elimination

Adagrasib is expelled from the body through urine and feces. In individuals who received a single dosage of radiolabeled Adagrasib, 4.5 percent of the dose was recovered in urine, and two percent remained unaltered. In comparison, 75 percent of the dose was recovered in feces.

Half-Life

The terminal elimination half-life of Adagrasib is 23 hours.

Toxicity

Adagrasib has been linked to both clinical and non-clinical toxicity, which can impact many human organs and systems. Here are some instances of Adagrasib's clinical and non-clinical toxicity:

Clinical Toxicity:

  1. Respiratory: Dyspnea (shortness of breath), pneumonia (lung infection), and cough.

  2. Gastrointestinal: Constipation, stomach discomfort, diarrhea, and other digestive symptoms.

  3. Cardiovascular: Reduced ejection fraction, high blood pressure, and prolonged QT interval.

  4. Hematologic Conditions: Anemia, thrombocytopenia, and neutropenia.

  5. Dermatologic: Pruritus, rash, and dry skin.

  6. Musculoskeletal: Back discomfort, myalgia, and arthralgia.

Non-clinical Toxicity:

  1. Hepatic: Increased liver enzyme levels, failing liver.

  2. Renal: Creatinine elevation, renal, and ophthalmic failure.

  3. Ocular: Eye inflammation, ulceration, and alterations in vision.

  4. Reproductive and Developmental Toxicity: Teratogenic effects, fetal death, and decreased fertility.

Contraindications

Adagrasib is contraindicated in several circumstances, when using it could endanger the patient.

Here are a few instances of Adagrasib's contraindications:

  1. Hypersensitivity: Adagrasib should not be administered to individuals with drug hypersensitivity or its ingredients.

  2. Pregnancy and Breastfeeding: Adagrasib should not be used during pregnancy since it may affect the developing fetus. Breastfeeding is not advised while using Adagrasib since it is unknown if the drug goes into breast milk.

  3. Severe Hepatic Impairment: Adagrasib has not been evaluated in patients with severe hepatic impairment. Hence, it is not advised to be used in this group.

Before beginning Adagrasib medication, addressing any medical issues or worries with the healthcare practitioner is important.

Drug Interactions

Other drugs and Adagrasib can interact, which may reduce a drug's efficacy or raise the possibility of adverse effects. The following are some instances of medications and Adagrasib that may interact:

  1. The CYP3A enzyme metabolizes Adagrasib; hence, taking strong CYP3A inhibitors can raise its plasma concentrations and increase its toxicity risk. Strong CYP3A inhibitors include clarithromycin, ketoconazole, Itraconazole, and Ritonavir. The dosage of Adagrasib should be decreased if co-administration is required.

  2. Strong CYP3A inducers can reduce the plasma concentrations of Adagrasib and the therapeutic efficacy of the drug. Strong CYP3A inducers include drugs like Carbamazepine, Phenytoin, and Rifampin. Adagrasib dosage needs to be raised if co-administration is required.

  3. Adagrasib is a substrate of the P-glycoprotein (P-gp), and using P-gp inhibitors can raise plasma concentrations of the drug and increase the danger of toxicity. Verapamil, Quinidine, and Cyclosporine are a few examples of P-gp inhibitors. The dosage of Adagrasib should be decreased if co-administration is required.

  4. Adagrasib can lengthen the QT interval, and taking other medicines that do the same can raise the chance of developing arrhythmias. Drugs that extend QT include Quinidine, Amiodarone, and Haloperidol. ECG (echocardiogram) monitoring and vigilance should be employed when co-administration is required.

Other Specifications

The following supplementary guidelines pertain to the usage of Adagrasib in geriatric, lactating, and pregnant patients:

Pregnant Women: Adagrasib is categorized as pregnancy category D, which means that when given to a pregnant woman, it may damage the fetus. Pregnant women should not use it unless the possible advantages outweigh the hazards to the fetus. For at least a week following the final dosage of Adagrasib, women of reproductive age should utilize reliable contraception.

Lactating Women: It is unknown if Adagrasib is secreted in breast milk. Nursing mothers should refrain from breastfeeding while taking Adagrasib and for a week after the last dose since there might be negative effects on the unborn child.

Patients Who Are Elderly: Although Adagrasib has not been explicitly researched in elderly patients, they may be more vulnerable to side effects due to changes in their metabolism, renal function, and other processes as they age. Based on individual parameters such as renal function and comorbidities, dose changes may be indicated for senior individuals.

Source Article IclonSourcesSource Article Arrow
Dr. Abdul Aziz Khan
Dr. Abdul Aziz Khan

Medical oncology

Tags:

non-small cell lung cancer
Community Banner Mobile
By subscribing, I agree to iCliniq's Terms & Privacy Policy.

Source Article ArrowMost popular articles

Ask your health query to a doctor online

Medical oncology

*guaranteed answer within 4 hours

Disclaimer: No content published on this website is intended to be a substitute for professional medical diagnosis, advice or treatment by a trained physician. Seek advice from your physician or other qualified healthcare providers with questions you may have regarding your symptoms and medical condition for a complete medical diagnosis. Do not delay or disregard seeking professional medical advice because of something you have read on this website. Read our Editorial Process to know how we create content for health articles and queries.

This website uses cookies to ensure you get the best experience on our website. iCliniq privacy policy