Zorifertinib AZD3759

I. Basic Drug Information

Generic Name: Zorifertinib

English Name: Zorifertinib (Trade Name: AZD3759)

Dosage Form: Oral Tablets (Strength: 100 mg/tablet)

Manufacturer: Indar Pharmaceutical

Pharmacological Mechanism: An Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor that selectively targets and inhibits EGFR-sensitizing mutations (including T790M). It demonstrates significant penetration of the blood-brain barrier and is indicated for the treatment of lung cancer with central nervous system (CNS) metastases.

II. Indications

Advanced Non-Small Cell Lung Cancer (NSCLC):

EGFR T790M Mutation-Positive: Second-line treatment following failure of first-line EGFR-TKI therapy (e.g., gefitinib). 

With CNS Metastases: Demonstrates significant efficacy in patients with brain metastases or leptomeningeal metastases.

III. Dosage and Administration

Dosing Regimen

Oral administration of 300 mg (3 tablets) once daily. May be taken with or without food.

A split-dosing regimen is recommended: 200 mg (2 tablets) taken twice daily.

During treatment, the dosage may be temporarily suspended or reduced based on the individual patient's safety and tolerability.

Specific dosage reduction scheme: First reduction to 200 mg once daily; if still not tolerated, the dosage may be further reduced to 100 mg once daily.

Important Note: Patients must strictly adhere to their physician's instructions regarding medication use. Do not arbitrarily alter the dosage or discontinue the medication on your own. Report any discomfort experienced during treatment to your physician immediately.

Key Considerations

Timing of Administration: May be taken either before or after meals; however, a fixed daily administration time should be established.

Missed Doses: If a dose is missed, take the missed dose immediately provided that more than 12 hours remain before the next scheduled dose; otherwise, skip the missed dose and do not take a double dose. IV. Adverse Reactions

Common Adverse Reactions (Incidence ≥ 20%)

| Adverse Reaction Type | Specific Manifestations                               | Incidence

| Skin Toxicity         | Rash, dry skin, fissuring, desquamation             | 53.3%–83.3%

| Hepatic Abnormalities | Elevated Aspartate Aminotransferase (AST)           | 60%

| Bilirubin Abnormalities | Elevated blood bilirubin                            | 33.3%

| Other                 | Oral ulcers, pruritus, fatigue, diarrhea            | 18%–33.3%

Serious Adverse Reactions

1. Interstitial Lung Disease (ILD): Incidence is approximately 1.5%; immediate discontinuation of the drug and corticosteroid treatment are required.

2. Hepatotoxicity: Grade ≥ 3 elevation of AST/ALT (6.7%); regular monitoring of liver function is required.

3. Severe Cutaneous Reactions: Such as Stevens-Johnson syndrome (rare).

V. Contraindications

1. Hypersensitivity to Zolitinib or any of its excipients.

2. Active interstitial lung disease.

3. Pregnancy and lactation (animal studies indicate potential fetal risk).

VI. Precautions

1. Liver Function Monitoring:

- Monitor ALT/AST/bilirubin levels prior to treatment and every 4 weeks thereafter; adjust dosage in cases of abnormality.

2. Warning for Pulmonary Symptoms:

- New-onset cough or dyspnea requires immediate CT examination to rule out ILD.

3. Drug Interactions:

Potent CYP3A4 Inhibitors (e.g., Ketoconazole): Increase Zolitinib plasma concentrations; avoid concomitant use or reduce Zolitinib dosage by 50%.

CYP3A4 Inducers (e.g., Rifampin): Reduce therapeutic efficacy; require substitution with an alternative medication or an increase in Zolitinib dosage.

4. Special Populations:

Elderly Patients: No dosage adjustment is required, but close monitoring for toxicity is necessary. 

Pediatric Patients: Safety and efficacy have not been established.

VII. Storage and Packaging

Storage: Store in a cool, dry place (temperature ≤ 30°C), protected from light and moisture.

Packaging: 100 mg/tablet; 90 tablets/bottle (Shelf life: 3 years). Summary: Zorifertinib represents a crucial second-line treatment option for patients with advanced Non-Small Cell Lung Cancer (NSCLC) harboring the EGFR T790M mutation and presenting with CNS metastases; however, strict monitoring of hepatic and pulmonary function, as well as skin toxicity, is required. Prior to administration, genetic testing must be performed to confirm mutation status, and individualized dosage adjustments should be implemented throughout the course of treatment.

Note: The information provided above is compiled from the product's package insert and clinical studies. Specific usage should strictly adhere to a physician's instructions and reference the latest clinical guidelines.

Product Specifications

Product Name: Zorifertinib Tablets 100mg × 90 Tablets (Zorifertinib / AZD3759)

Generic Name: Zorifertinib

Composition: Zorifertinib Tablets

Dosage Form: Tablets

Specification: 100mg × 90 Tablets

Manufacturer: Indar Pharmaceutical

Indications: Used for the treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC), particularly those with metastases to the Central Nervous System (CNS).

Dosage and Administration: Oral administration of 300mg (3 tablets) once daily. May be taken with or without food.

Fractionated dosing is recommended: 200mg (2 tablets) taken twice daily.