I. Basic Drug Information

Generic Name: Acalabrutinib Capsules

Brand Names: Calquence, Kangkeqi, Acalnib

Dosage Form and Strength: Hard capsules; 100 mg/capsule; 30 capsules/box

Manufacturer: Hetero Healthcare Limited

Pharmacological Class: Selective Bruton's Tyrosine Kinase (BTK) Inhibitor

Mechanism of Action: Acalabrutinib and its active metabolite, ACP-5862, covalently bind to the cysteine residue in the active site of BTK, thereby inhibiting BTK enzymatic activity, blocking the B-cell receptor signaling pathway, and inhibiting the proliferation of malignant B cells and tumor growth.

Storage Conditions: Keep tightly closed; store in a dry place protected from light at a temperature below 25°C; keep out of reach of children. Use within 30 days after opening.

II. Indications

1. Mantle Cell Lymphoma (MCL): For adult patients who have received at least one prior therapy.

2. Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL): For adult patients (including both treatment-naïve and relapsed/refractory cases).

3. Combination Therapy: In combination with bendamustine and rituximab, for the treatment of adult patients with treatment-naïve MCL who are not candidates for autologous hematopoietic stem cell transplantation; in combination with obinutuzumab, for the treatment of adult patients with treatment-naïve CLL/SLL.

III. Dosage and Administration

Standard Dosage

Recommended Dose: 100 mg per dose, twice daily, taken orally (may be taken with or without food). Doses should be spaced approximately 12 hours apart. Continue treatment until disease progression or until intolerable toxicity occurs.

Method of Administration: Swallow capsules whole; do not open, crush, or chew.

Missed Dose: If a dose is missed, take the missed dose as soon as possible, provided that the next scheduled dose is ≥3 hours away; if the next scheduled dose is less than 3 hours away, skip the missed dose and do not take a double dose.

Dosage Adjustments for Special Populations

Hepatic Impairment: No dosage adjustment is required for mild impairment (Child-Pugh A); for moderate impairment (Child-Pugh B), reduce the dose to 100 mg once daily; for severe impairment (Child-Pugh C) Avoid Use

Renal Impairment: No dosage adjustment is required for mild to moderate impairment (eGFR 30–89 mL/min); for severe impairment (eGFR < 30 mL/min) or patients undergoing dialysis, individualized dosage adjustments should be made according to a physician's instructions.

Drug Interactions: Avoid concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin); if concomitant use is unavoidable, reduce the dosage to 100 mg once daily. Avoid concomitant use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine). Consumption of grapefruit juice is prohibited.

IV. Adverse Reactions

Common Adverse Reactions (Incidence ≥ 20%)

Headache, diarrhea, fatigue/asthenia, nausea, arthralgia, rash, cough, constipation, vomiting, myalgia.

Serious Adverse Reactions (Require Immediate Medical Attention)

1. Serious Infections: Pneumonia, sepsis, herpes zoster; manifestations include persistent fever, chills, and dyspnea.

2. Bleeding Events: Intracranial hemorrhage, gastrointestinal hemorrhage; manifestations include hematemesis, melena, severe headache, and confusion.

3. Arrhythmias: Atrial fibrillation/flutter; manifestations include palpitations, chest tightness, and dizziness.

4. Second Primary Malignancies: Skin cancer, other hematologic malignancies, etc.

V. Precautions

Bleeding Risk

Monitor for signs of bleeding throughout the course of treatment. Discontinue the medication 3–7 days prior to surgery. Avoid concomitant use with anticoagulant or antiplatelet agents (e.g., aspirin, warfarin).

Infection Control

Rule out active infections (e.g., Hepatitis B, tuberculosis) prior to initiating treatment. Avoid receiving live vaccines during treatment. Seek immediate medical attention if fever (> 38.5°C) develops.

Embryo-Fetal Toxicity

Contraindicated in pregnant women. Women of childbearing potential must use effective contraception during treatment and for 1 week after discontinuing the medication; men must use effective contraception during treatment and for 3 months after discontinuing the medication.

Other Monitoring

Periodically monitor complete blood count (CBC), liver and renal function, and coagulation parameters. Monitor electrocardiograms (ECG) in patients with a history of cardiac disease. VI. Contraindications

Patients with a known hypersensitivity to Acalabrutinib or to any of the excipients contained in the capsule.

Pregnant and lactating women (contraindicated during lactation).

VII. Drug Interactions

CYP3A4 Inhibitors: Concomitant use with strong inhibitors (e.g., ketoconazole, itraconazole) should be avoided; for moderate inhibitors (e.g., erythromycin, fluconazole), a dose reduction is required.

CYP3A4 Inducers: Concomitant use with strong inducers (e.g., rifampin, phenytoin) should be avoided, as this may reduce therapeutic efficacy.

Acid-Reducing Agents: Avoid concomitant use with Proton Pump Inhibitors (PPIs); when used in combination with H2-receptor antagonists, administer Acalabrutinib 2 hours apart; when used in combination with antacids, administer Acalabrutinib at least 2 hours apart.

VIII. Use in Specific Populations

Pediatric Patients: The safety and efficacy in children have not been established.

Geriatric Patients: No significant differences in efficacy have been observed in patients aged ≥65 years; use under the guidance of a physician.

Lactating Women: It is recommended that lactating women either discontinue the medication or discontinue breastfeeding.

Product Specifications

Product Name: Acalabrutinib Capsules 100 mg (30 capsules/box)

Common Name: Acalabrutinib Capsules

Active Ingredient: Acalabrutinib

Dosage Form: Capsule

Specification: 100 mg/capsule; 30 capsules/box

Manufacturer: Hetero Healthcare Limited

Indications: 1. Mantle Cell Lymphoma (MCL): Indicated for adult patients who have received at least one prior therapy.

2. Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL): Indicated for adult patients (including both treatment-naïve and relapsed/refractory cases).

3. Combination Therapy: In combination with bendamustine and rituximab, for the treatment of treatment-naïve adult patients with MCL who are not candidates for autologous hematopoietic stem cell transplantation; in combination with obinutuzumab, for the treatment of treatment-naïve adult patients with CLL/SLL.

Dosage and Administration: Standard Dosage

Recommended Dosage: 100 mg per dose, twice daily, taken orally (may be taken with or without food). Doses should be spaced approximately 12 hours apart. Continue treatment until disease progression or the onset of intolerable toxicity.

Administration: Swallow capsules whole; do not open, crush, or chew.

Missed Dose: If more than 3 hours remain before the next scheduled dose, take the missed dose immediately; if less than 3 hours remain, skip the missed dose. Do not take a double dose.