OYSIENDX Osimertinib tablets

[Product Name] Osimertinib Mesylate Tablets

[English Name] Osimertinib Tablets

[Other Names] Osimertinib / AZD-9291 / Tagrisso

[Specification] 80 mg × 30 tablets/box

[Manufacturer] Bigbear Pharmaceutical Laos

[Overview]

Osimertinib is a novel EGFR-TKI that binds irreversibly to certain EGFR mutants (T790M, L858R, and exon 19 deletions) at concentrations approximately 9-fold lower than those required for the wild-type receptor. 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 similar to that of Osimertinib, whereas AZ5104 demonstrates greater activity against EGFR exon 19 deletions and T790M mutations (approximately 8-fold) as well as the wild-type receptor (approximately 15-fold). *In vitro* studies have shown 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) whose disease has progressed during or after treatment with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and who have tested positive for the EGFR T790M mutation.

[Dosage and Administration]

The recommended dose of Osimertinib is 80 mg once daily, administered until disease progression or the development of intolerable toxicity.

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

Dosing may be interrupted or reduced based on individual patient safety and tolerability. If dose reduction is required, the dosage 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 receiving osimertinib. Patients presenting with acute onset and/or unexplained worsening of pulmonary 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 receiving osimertinib. QTc interval prolongation may lead to an increased risk of ventricular arrhythmias (e.g., Torsades de Pointes) or sudden death. If possible, osimertinib should be avoided in patients with congenital long QT syndrome. 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. In patients who develop a QTc interval >500 ms on at least two separate ECGs, osimertinib should be temporarily withheld until the QTc interval...

3. Alterations in Cardiac Contractility

For patients with known cardiovascular risk factors and conditions that may affect Left Ventricular Ejection Fraction (LVEF), monitoring of cardiac function—including assessment of LVEF at baseline and during treatment—should be considered. For patients who develop signs and symptoms suggestive of cardiac events during treatment with Osimertinib, cardiac monitoring—including assessment of Left Ventricular Ejection Fraction (LVEF)—should be considered.

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 Pregnancy and Lactation]

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. The risk of decreased exposure to hormonal contraceptives when co-administered with Osimertinib cannot be ruled out.

Pregnancy

There are currently no data, or very limited data, on the use of Osimertinib in pregnant women. Animal studies have indicated 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.

Lactation

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).