I. Drug Name

Generic Name: Alectinib Hydrochloride Capsules

English Name: Alectinib

Brand Names: Alecensa, Anshengsha, AILEDX

Dosage Form: Oral Capsules

Specification: 150 mg per capsule; 112 capsules per box

Manufacturer: Laos Da Xiong Pharmaceutical Co., Ltd.

Regulatory Approval No.: 09 L1207/24

II. Pharmacological Actions

Pharmacological Classification: Receptor Tyrosine Kinase Inhibitor

Mechanism of Action: Alectinib is a potent, highly selective second-generation Anaplastic Lymphoma Kinase (ALK) inhibitor.

In ALK-positive non-small cell lung cancer (NSCLC), the ALK gene undergoes rearrangement with other genes, producing abnormal fusion proteins that constitutively activate signaling pathways driving tumor cell growth and survival.

Alectinib inhibits tumor cell proliferation and induces apoptosis by suppressing ALK phosphorylation and blocking its downstream signal transduction.

Compared to the first-generation ALK inhibitor crizotinib, alectinib exerts a stronger inhibitory effect on ALK and is effective against various ALK mutations that confer resistance to crizotinib (e.g., L1196M, G1269A, etc.).

Furthermore, its optimized molecular structure significantly enhances its ability to penetrate the blood-brain barrier, enabling effective treatment and prevention of brain metastases.

III. Indications

Alectinib is indicated for the treatment of adult patients with ALK-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC).

It may be used as initial therapy (first-line treatment).

It may also be used in patients whose disease has progressed following treatment with crizotinib, or who are intolerant to crizotinib.

IV. Dosage and Administration

Recommended Dosage: 600 mg (4 capsules of 150 mg each), taken orally twice daily (approximately every 12 hours).

Method of Administration:

Swallow the capsules whole; do not open or dissolve the capsules.

Take with food; high-fat, high-calorie meals can significantly increase drug absorption.

If a dose is missed, do not take the missed dose unless more than 6 hours remain before the next scheduled dose. At the same time, the next scheduled dose should be taken as soon as possible, after which the regular dosing schedule should be resumed. Do not take a double dose at the same time to make up for a missed dose.

If vomiting occurs after taking the medication, do not take a replacement dose; instead, wait until the next scheduled time to take the regular dose.

V. Contraindications

Patients with a history of severe hypersensitivity to Alectinib or to any of its excipients.

VI. Warnings and Precautions

1. Hepatotoxicity:

May cause severe drug-induced liver injury.

ALT, AST, and total bilirubin levels must be monitored prior to initiating treatment; every two weeks during the first two months of treatment; monthly thereafter; and as clinically indicated.

Depending on the severity of the hepatotoxicity, it may be necessary to withhold the drug, reduce the dose, or permanently discontinue treatment.

2. Interstitial Lung Disease (ILD)/Pneumonitis:

Severe, and potentially fatal, ILD/pneumonitis may occur.

In patients presenting with symptoms suggestive of ILD/pneumonitis (e.g., dyspnea, cough, fever, etc.), treatment should be immediately interrupted and an evaluation performed. If confirmed, Alectinib must be permanently discontinued.

3. Bradycardia:

May cause symptomatic bradycardia (slow heart rate).

Heart rate and blood pressure should be monitored regularly during treatment. Avoid concomitant use with medications known to cause bradycardia.

Depending on the severity, it may be necessary to withhold the drug, reduce the dose, or permanently discontinue treatment.

4. Creatine Phosphokinase (CPK) Elevation:

May lead to significant elevations in CPK levels, indicative of muscle injury, and may cause myalgia or muscle inflammation.

CPK levels should be monitored prior to initiating treatment and periodically during treatment. Depending on the degree of elevation, it may be necessary to withhold the drug or reduce the dose.

5. Renal Impairment:

May lead to elevated serum creatinine levels.

Serum creatinine levels should be monitored prior to initiating treatment and periodically during treatment.

6. Anemia:

May cause anemia.

Hemoglobin levels should be monitored prior to initiating treatment and periodically during treatment.

7. Embryo-Fetal Toxicity:

Based on its mechanism of action, Alectinib may cause fetal harm when administered to pregnant women. Women of childbearing potential should use effective contraception during treatment and for at least one week after treatment.

Male patients should use condoms during treatment and for at least three months after treatment.

VII. Adverse Reactions

Very Common (>10%) Serious and/or Major Adverse Reactions:

Gastrointestinal: Constipation, nausea, diarrhea, vomiting.

Systemic: Fatigue, edema (peripheral edema, facial edema).

Musculoskeletal: Myalgia, back pain, arthralgia (often associated with elevated CPK).

Hematologic and Lymphatic: Anemia.

Nervous System: Headache.

Skin and Subcutaneous Tissue: Rash.

Laboratory Abnormalities: Elevated CPK, elevated ALT/AST, elevated bilirubin, elevated creatinine, elevated blood glucose, hypocalcemia, lymphopenia.

Common but Serious Adverse Reactions:

Liver injury, ILD/pneumonitis, bradycardia, severe muscle pain.

VIII. Drug Interactions

Strong CYP3A Inhibitors (e.g., clarithromycin, itraconazole, ritonavir):

Co-administration significantly increases alecetinib plasma concentrations, thereby increasing the risk of adverse reactions.

Avoid co-administration. If co-administration is unavoidable, closely monitor for adverse reactions to alecetinib.

Strong CYP3A Inducers (e.g., rifampin, carbamazepine, St. John's wort):

Co-administration significantly decreases alecetinib plasma concentrations, potentially compromising efficacy.

Avoid co-administration.

CYP3A Substrates:

Alecetinib is a moderate inducer of CYP3A; it may decrease the plasma concentrations of drugs metabolized by CYP3A (e.g., midazolam, hormonal contraceptives), potentially leading to a loss of efficacy for these drugs.

When co-administering, closely monitor the efficacy of these substrate drugs and consider increasing their dosage or selecting alternative medications.

IX. Use in Specific Populations

Pregnant Women: May cause fetal harm. Advise pregnant women of the potential risk to the fetus.

Lactating Women: It is recommended to discontinue breastfeeding during treatment and for one week after the last dose. Pediatric Patients: Safety and efficacy have not been established.

Geriatric Patients: In patients aged 65 years and older, no overall significant differences in safety were observed compared to younger patients.

Patients with Hepatic/Renal Impairment:

Hepatic Impairment: No dose adjustment is required for patients with mild hepatic impairment. For patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment, the recommended dose should be reduced to 450 mg, taken twice daily.

Renal Impairment: No dose adjustment is required for patients with mild to moderate renal impairment. Data regarding use in patients with severe renal impairment or those requiring dialysis are limited; therefore, caution is advised.

X. Overdosage

Symptoms: Expected symptoms include an exacerbation of adverse reactions, such as muscle pain, hepatotoxicity, etc.

Management: The drug should be discontinued immediately; supportive care and symptomatic treatment should be initiated.

XI. Clinical Pharmacology

Pharmacokinetics: Alectinib is well absorbed following oral administration, reaching peak plasma concentrations approximately 4 hours after dosing. High-fat meals increase exposure (AUC) by approximately 3.1-fold; therefore, the drug must be taken with food. In vivo, it is primarily metabolized into its active metabolite, M4. Fecal excretion is the primary route of elimination.

XII. Patient Counseling Information

1. Genetic Testing: Patients must understand that ALK gene testing is mandatory prior to initiating treatment.

2. Administration with Food: The medication must be taken with a meal to ensure optimal efficacy.

3. Regular Monitoring: Patients must understand the importance of regular monitoring of liver function, CPK levels, heart rate, renal function, and complete blood counts.

4. Muscle Symptoms: Patients should report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by fever or malaise.

5. Pulmonary Symptoms: Patients should immediately report any new onset or worsening of breathing difficulties, coughing, etc.

6. Heart Rate Monitoring: Patients should report any instances of dizziness, fainting (syncope), or palpitations.

7. Contraception Requirements: Patients of reproductive potential must understand and strictly adhere to contraception requirements, and should be aware that hormonal contraceptives may be ineffective.

Final Reminder: Please strictly follow the specific instructions provided by your attending physician and pharmacist. If you have any questions or experience any discomfort during the course of treatment, please communicate immediately with your healthcare team.