Acalabrutinib: Detailed Product Information

Product Name: Acalabrutinib Capsules

Other Chinese Names: Aketini, Acalabrutinib, Kangkekei

English Name: Acalabrutinib Capsules

Brand Names: Calquence / LuciAcal

Specification: 100 mg × 60 capsules per box

Manufacturer: Lucius Pharmaceutical (Laos) Co., Ltd.

Laos National Drug Approval Number: 03 L 1314/25

I. Indications

1. Mantle Cell Lymphoma (MCL): Indicated for adult patients with relapsed or refractory disease who have received at least one prior therapy.

2. Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): Indicated for adult patients; may be used as monotherapy or in combination with Obinutuzumab.

II. Dosage and Administration

1. Recommended Dosage

Standard Adult Dose: 100 mg orally, once every 12 hours, taken with or without food.

Combination Therapy Regimen: When used in combination with Obinutuzumab, initiate Acalabrutinib in Cycle 1, and add Obinutuzumab starting in Cycle 2, for a total of 6 cycles.

Missed Dose: If a dose is missed by ≤3 hours, take the missed dose; otherwise, skip the missed dose. Do not take a double dose to make up for a missed dose.

2. Dosage Adjustments

Concomitant Use with CYP3A Inhibitors:

Strong Inhibitors (e.g., Itraconazole): Avoid use; if short-term use is necessary, temporarily interrupt Acalabrutinib treatment.

Moderate Inhibitors: Reduce the dose to 100 mg once daily.

Hepatic or Hematologic Toxicity: Interrupt or permanently discontinue treatment based on the severity of the toxicity (e.g., Grade 3 non-hematologic toxicity, or Grade 4 neutropenia lasting >7 days).

III. Adverse Reactions

1. Common Adverse Reactions (≥20%)

Hematologic: Anemia (46%), Thrombocytopenia (44%), Neutropenia (36%). Digestive System: Diarrhea (31%), Nausea (19%), Vomiting (13%).

Nervous System: Headache (39%), Dizziness (6%).

2. Serious Adverse Reactions

Bleeding Risk: Including intracranial hemorrhage and gastrointestinal bleeding (incidence: 8%).

Infection: Bacterial, viral, or fungal infections; requires monitoring and prophylaxis (e.g., pneumonia, sepsis).

Cardiotoxicity: Atrial fibrillation/flutter (rare, but requires vigilance).

IV. Drug Interactions

1. CYP3A Inhibitors/Inducers:

Strong Inducers (e.g., Rifampin): Concomitant use should be avoided; if unavoidable, increase the dosage to 200 mg every 12 hours.

2. Gastric Acid Suppressants:

Proton Pump Inhibitors (e.g., Omeprazole): Significantly reduce plasma drug concentrations; it is recommended to switch to H2 antagonists or antacids (administered with a 2-hour interval).

V. Pharmacological Mechanism

Target: Irreversibly inhibits Bruton's tyrosine kinase (BTK), blocks the B-cell receptor (BCR) signaling pathway, and inhibits the proliferation of malignant B cells.

Selectivity: Inhibitory activity against BTK (IC50 = 3 nM) is significantly higher than that against other kinases such as EGFR and ITK, thereby reducing off-target effects.

VI. Clinical Data

1. Pivotal Trial (ACE-LY-004, Phase II):

Overall Response Rate (ORR): 81% (Complete Response Rate [CR] = 48%).

Survival: Median Progression-Free Survival (PFS) of 22 months; 36-month duration of response rate of 41.9%.

2. Efficacy in CLL/SLL: Significantly reduces the risk of disease progression and prolongs survival.

VII. Precautions and Contraindications

Contraindications: Contraindicated in patients with hypersensitivity to any of the components, as well as in pregnant or breastfeeding women.

Monitoring Requirements:

Monitor complete blood counts monthly during treatment.

Patients with hepatic impairment require periodic monitoring of transaminase levels.

Sun Protection Advice: May increase the risk of skin cancer; sun protection measures should be employed. VIII. Dosage Form and Storage

Dosage Form: Capsules (100 mg/capsule); 60 capsules/bottle.

Storage: Store at 15–30°C, protected from light and moisture.

Summary: As a second-generation BTK inhibitor, acalabrutinib has emerged as a key therapeutic option for MCL and CLL/SLL, distinguished by its high selectivity and safety profile. Clinicians should pay particular attention to the management of bleeding, infections, and drug interactions.