LuciOsim Osimertinib Tablets

Product Name: LuciOsim

Chinese Name: Osimertinib

English Name: Osimertinib

[Summary]

Osimertinib is a novel EGFR-TKI; the concentration required for its irreversible binding to certain EGFR mutants (T790M, L858R, and Exon 19 deletion) is approximately 9-fold lower than that required for the wild-type EGFR. Following oral administration of Osimertinib, two pharmacologically active metabolites (AZ7550 and AZ5104, accounting for approximately 10% of the parent compound) are detected in plasma; their inhibitory profiles are similar to that of Osimertinib. The potency of AZ7550 is comparable to that of Osimertinib, whereas AZ5104 demonstrates greater activity against EGFR Exon 19 deletion and T790M mutations (approximately 8-fold) as well as against the wild-type EGFR (approximately 15-fold). *In vitro* studies indicate that, at clinically relevant concentrations, Osimertinib also inhibits the activity of HER2, HER3, HER4, ACK1, and BLK.

[Indications]

Osimertinib is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed on or after prior therapy with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and whose tumors harbor the EGFR T790M mutation, as detected by a validated test.

[Specification] 80 mg/tablet; 30 tablets/box

[Dosage and Administration]

The recommended dose of Osimertinib is 80 mg once daily, administered until disease progression or until unacceptable toxicity occurs.

If a dose of Osimertinib is missed, the missed dose should be taken unless the next scheduled dose is due within 12 hours.

Osimertinib should be taken at the same time each day and may be taken with or without food.

Dose Adjustment

Dose interruption or reduction may be required based on individual patient safety and tolerability. If dose reduction is required, the dose should be reduced to 40 mg once daily. [Contraindications]

Hypersensitivity to the active substance or to any of the excipients.

Osimertinib must not be administered concomitantly with St. John’s wort (see [Drug Interactions]).

[Adverse Reactions]

The most common adverse reactions (≥20%) were diarrhea (42%), rash (41%), dry skin (31%), nail toxicity (25%), and fatigue.

[Warnings and Precautions]

1. Interstitial Lung Disease (ILD)

Severe, life-threatening, or fatal interstitial lung disease (ILD) or ILD-like adverse reactions (e.g., non-infectious pneumonia) have been observed in patients treated with osimertinib. Patients presenting with acute onset and/or unexplained worsening of respiratory symptoms (dyspnea, cough, fever) should be carefully evaluated to rule out ILD. Osimertinib treatment should be suspended while the etiology of these symptoms is being investigated. If ILD is confirmed, osimertinib should be permanently discontinued, and appropriate treatment measures should be initiated.

2. QTc Interval Prolongation

QTc interval prolongation has been observed in patients treated with osimertinib. QTc interval prolongation may lead to an increased risk of ventricular arrhythmias (e.g., Torsades de Pointes) or sudden death. Osimertinib should be avoided in patients with congenital long QT syndrome, if possible. Patients with congestive heart failure, electrolyte abnormalities, or those taking medications known to prolong the QTc interval should undergo periodic monitoring of electrocardiograms (ECGs) and electrolytes. Osimertinib should be temporarily withheld in patients who are found to have a QTc interval >500 ms on at least two independent ECGs, until the QTc interval...

3. Altered Cardiac Contractility

Cardiac function monitoring, including assessment of Left Ventricular Ejection Fraction (LVEF) at baseline and during treatment, should be considered for patients with known cardiovascular risk factors or conditions that may affect LVEF. Cardiac monitoring, including LVEF assessment, should be considered for patients who develop signs and symptoms suggestive of a cardiac event during osimertinib treatment. 4. Effects on Ability to Drive and Use Machines

Osimertinib has no or negligible influence on the ability to drive and use machines.

[Osimertinib Use in Pregnant and Lactating Women]

Contraception in Males and Females

Women of childbearing potential should avoid becoming pregnant while taking osimertinib. Such patients should continue to use effective contraception for the following periods after completing osimertinib treatment: at least 2 months for women, and at least 4 months for men. Following co-administration with osimertinib, a risk of decreased exposure to hormonal contraceptives cannot be ruled out.

Pregnancy

There are currently no data, or very limited data, on the use of osimertinib in pregnant women. Animal studies suggest that osimertinib has reproductive toxicity (embryo-fetal mortality, retarded embryo-fetal growth, and neonatal mortality). Based on its mechanism of action and preclinical data, osimertinib may cause fetal harm when administered to pregnant women. Osimertinib should not be used during pregnancy unless the patient's clinical condition necessitates treatment with osimertinib.

Breastfeeding

It is not known whether osimertinib or its metabolites are excreted in human milk. Furthermore, there is currently insufficient information regarding the excretion of osimertinib or its metabolites in animal milk. However, osimertinib and its metabolites were detected in nursing offspring, and adverse effects on offspring growth and survival were observed. Therefore, a risk to the breastfed infant cannot be excluded. Consequently, breastfeeding should be discontinued during treatment with osimertinib.

Fertility

There are currently no data regarding the effects of osimertinib on human fertility. Results from animal studies suggest that osimertinib has effects on female and male reproductive organs and may impair fertility.

[Storage]

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).