Osimertinib is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer. It is specifically effective in patients whose tumors harbor EGFR-activating mutations, including the T790M resistance mutation. The drug works by selectively inhibiting mutant EGFR receptors responsible for uncontrolled cancer cell growth. Osimertinib has improved selectivity compared to earlier EGFR inhibitors, resulting in fewer adverse effects on normal cells. It demonstrates strong activity against both primary lung tumors and metastatic disease. Notably, osimertinib can cross the blood–brain barrier and treat central nervous system metastases. The drug is administered orally once daily, improving patient compliance. It has a favorable pharmacokinetic profile with a long half-life. Osimertinib has significantly improved progression-free and overall survival rates. It is now considered a standard first-line therapy for EGFR-mutated non-small cell lung cancer.
BRAND NAMES
Osimertinib is marketed under the brand name Tagrisso. It is manufactured by AstraZeneca and is widely used in the treatment of non-small cell lung cancer. The drug is specifically indicated for patients with EGFR mutation–positive tumors. It is approved for both first-line therapy and resistant disease. Tagrisso is available only as an oral formulation.
MECHANISM OF ACTION
Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor. It irreversibly binds to EGFR mutations, including the T790M resistance mutation. This binding inhibits EGFR signaling pathways responsible for tumor growth and survival. The drug shows high selectivity for mutant EGFR over wild-type EGFR. This selectivity helps reduce damage to normal cells.
PHARMACOKINETICS
Absorption: Osimertinib is well absorbed after oral administration with good bioavailability.
Distribution: It is extensively distributed in tissues and highly protein bound in plasma.
Metabolism: The drug is metabolized mainly by CYP3A4 and CYP3A5 enzymes.
Excretion: Elimination occurs primarily via feces and partially via urine.
It has a long elimination half-life allowing once-daily dosing.
PHARMACODYNAMICS
Osimertinib inhibits EGFR phosphorylation and downstream signaling pathways. This leads to decreased tumor cell proliferation and increased apoptosis. The drug is effective against both systemic and central nervous system metastases. Sustained inhibition of mutant EGFR improves disease control. Its targeted action results in improved progression-free survival.
ADMINISTRATION
Osimertinib is administered orally as a tablet. It should be taken once daily at the same time each day. The tablet must be swallowed whole with water. It can be taken with or without food. Treatment is continued until disease progression or unacceptable toxicity occurs.
DOSAGE AND STRENGTH
The recommended dose of osimertinib is 80 mg once daily. It is available in tablet strengths of 40 mg and 80 mg. Dose reduction may be necessary in patients experiencing severe adverse effects. Temporary interruption may be required in certain toxicities. Dosage adjustments are guided by patient tolerance.
DRUG INTERACTIONS
Strong CYP3A inducers can reduce osimertinib plasma concentrations and decrease effectiveness. CYP3A inhibitors may increase drug levels and toxicity risk. Concomitant use with QT-prolonging drugs increases the risk of cardiac arrhythmias. Caution is required when used with cardiac medications. A thorough medication review is recommended before therapy.
FOOD INTERACTIONS
Food does not significantly affect the absorption of osimertinib. It may be taken with or without meals. High-fat foods do not alter its pharmacokinetic profile. Patients are advised to maintain consistent dosing habits. No specific dietary restrictions are required.
CONTRAINDICATIONS
Osimertinib is contraindicated in patients with known hypersensitivity to the drug. Caution is advised in patients with pre-existing cardiac conditions. Those with a history of interstitial lung disease require close monitoring. Use during pregnancy is contraindicated due to fetal harm. Breastfeeding should be discontinued during therapy.
SIDE EFFECTS
Gastrointestinal Issues: Diarrhea and inflammation or sores in the mouth (stomatitis).
Skin and Nail Effects: Rash, dry skin, itching, and nail changes such as redness, pain, brittleness, or separation from the nail bed.
General Symptoms: Fatigue, reduced appetite, nausea, and constipation.
Musculoskeletal Pain: Back pain, muscle aches, and joint pain.
Blood Count Changes: Decreased white blood cells (leukopenia, neutropenia) and platelets (thrombocytopenia), increasing infection and bleeding risk.
Anemia: Reduced red blood cell count leading to weakness and fatigue.
OVERDOSE
Overdose of osimertinib may worsen its known side effects. Gastrointestinal symptoms such as diarrhea and vomiting may become severe. Cardiac toxicity including QT prolongation can occur. There is no specific antidote for overdose. Management is supportive and based on symptoms.
TOXICITY
Serious toxicity includes interstitial lung disease and pneumonitis. Cardiac toxicity such as cardiomyopathy has been reported. Severe QT prolongation may lead to life-threatening arrhythmias. Rare hematological abnormalities may occur. Regular monitoring is essential to prevent severe outcomes.
