Osimertinib

Introduction

Osimertinib is a targeted therapy medication used primarily for the treatment of non-small cell lung cancer (NSCLC) with specific mutations. It is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that selectively targets and inhibits EGFR mutations, including the T790M mutation, which can confer resistance to earlier-generation EGFR TKIs.

Uses

Osimertinib is used to treat adults with metastatic non-small cell lung cancer (NSCLC) who have EGFR mutations. It is particularly effective in patients who have developed resistance to first- and second-generation EGFR TKIs due to the T790M mutation. It is also used as a first-line treatment for NSCLC with specific EGFR mutations.

Brand Name	Osimertinib
Type
Weight
Generic	Osimertinib
Manufacturer
Available in	English বাংলা

Mechanism of Action

Osimertinib works by specifically binding to the mutated EGFR receptors on cancer cells, thereby inhibiting their kinase activity. This inhibition prevents the activation of downstream signaling pathways that promote cancer cell growth and proliferation. By targeting both the activating mutations and the resistance mutation (T790M), osimertinib effectively blocks the survival and proliferation of cancer cells.

How Long Does It Take to Work?

The effects of osimertinib can often be observed within a few weeks of starting treatment. Tumor response and clinical improvement may vary, with some patients showing significant benefits in terms of tumor shrinkage and symptom relief within a few cycles of treatment.

Absorption

Osimertinib is well absorbed following oral administration. It reaches peak plasma concentrations within 4 to 6 hours. The drug is absorbed more slowly with food, but it is still recommended to take it consistently with or without food to maintain stable drug levels.

Route of Elimination

Osimertinib is primarily metabolized in the liver. It is eliminated through both hepatic metabolism and renal excretion. The drug and its metabolites are excreted mainly via the feces, with a smaller amount excreted in the urine.

Dosage

The recommended dose of Osimertinib is 80 mg tablet once a day until disease progression or unacceptable toxicity. Osimertinib can be taken with or without food. If a dose of Osimertinib is missed, do not make up the missed dose and take the next dose as scheduled. Disperse tablet in 60 ml (2 ounces) of non-carbonated water only. Stir until tablet is dispersed into small pieces (the tablet will not completely dissolve) and swallow immediately. Do not crush, heat, or ultrasonicate during preparation. Rinse the container with 120 ml to 240 ml (4 to 8 ounces) of water and immediately drink. If administration via nasogastric tube is required, disperse the tablet as above in 15 ml of non-carbonated water, and then use an additional 15 ml of water to transfer any residues to the syringe. The resulting 30 ml liquid should be administered as per the nasogastric tube instructions with appropriate water flushes (approximately 30 ml).

The typical dose of osimertinib for the treatment of NSCLC is 80 mg once daily. Dosage adjustments may be necessary based on individual tolerance, response, and side effects. It is essential to follow the specific dosing instructions provided by a healthcare provider.

Administration

Osimertinib is administered orally in the form of tablets. It should be taken once daily at the same time each day, with or without food. Tablets should be swallowed whole and not chewed or crushed.

Side Effects

Common side effects of osimertinib include diarrhea, rash, dry skin, and nausea. Other potential side effects can include decreased appetite, fatigue, and potential lung inflammation (pneumonitis). Regular monitoring is necessary to manage these side effects effectively.

Toxicity

Severe toxicity can include interstitial lung disease (ILD), which may present with symptoms such as cough, difficulty breathing, and fever. In such cases, treatment with osimertinib should be discontinued, and appropriate medical evaluation should be conducted.

Precautions

Precautions should be taken in patients with a history of interstitial lung disease or pulmonary conditions. Regular monitoring of lung function and symptoms is essential. Liver function should also be monitored, as hepatic impairment may affect drug metabolism.

Interaction

Osimertinib has the potential for drug interactions with other medications that are metabolized by the liver, particularly those affecting CYP3A4 enzymes. Patients should inform their healthcare provider of all medications and supplements they are taking to avoid potential interactions.

Disease Interaction

Patients with significant hepatic impairment may require dose adjustments or closer monitoring due to the impact on osimertinib metabolism. Careful consideration should be given to patients with a history of pulmonary disease due to the risk of ILD.

Drug Interaction

Osimertinib may interact with drugs that affect the CYP3A4 enzyme system. Coadministration with strong CYP3A4 inhibitors or inducers may require dose adjustments. It is important to consult with a healthcare provider regarding potential drug interactions.

Food Interactions

Osimertinib can be taken with or without food. However, taking it with food may slow the rate of absorption, although this does not significantly affect the overall effectiveness of the drug. Maintaining a consistent routine regarding food intake is recommended.

Pregnancy Use

Osimertinib is classified as a Category D drug, indicating that there is evidence of potential risk to the fetus based on human data. It should be used during pregnancy only if the potential benefits outweigh the risks. Women of childbearing potential should use effective contraception while taking osimertinib.

Lactation Use

The safety of osimertinib during lactation is not well established. It is recommended that breastfeeding be avoided during treatment with osimertinib due to potential risks to the nursing infant. Patients should discuss alternative feeding options with their healthcare provider.

Acute Overdose

In case of acute overdose, supportive care should be provided. Symptoms of overdose may include more severe side effects. There is no specific antidote for osimertinib overdose, so management focuses on symptomatic and supportive care.

Contraindication

Osimertinib is contraindicated in patients with a known hypersensitivity to the drug or any of its components. Caution should be used in patients with severe hepatic impairment or those with a history of severe pulmonary conditions.

Use Direction

Patients should follow the prescribed dosage and administration schedule carefully. Osimertinib should be taken once daily at the same time each day. It is important to adhere to the prescribed regimen and attend regular follow-up appointments to monitor for efficacy and side effects.

Storage Conditions

Osimertinib should be stored at room temperature, away from light and moisture. It should be kept in its original container and out of reach of children. The medication should not be used beyond its expiration date.

Volume of Distribution

The volume of distribution for osimertinib is approximately 2.5 L/kg, indicating moderate distribution into tissues beyond the bloodstream. This distribution helps in targeting cancer cells effectively.

Half Life

The half-life of osimertinib is approximately 48 hours. This extended half-life allows for once-daily dosing, providing sustained inhibition of EGFR activity over the course of treatment.

Clearance

Osimertinib is cleared from the body primarily through hepatic metabolism. The drug's clearance rate can be affected by liver function, and dose adjustments may be necessary for patients with impaired hepatic function.

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