BIGBEAR AKADX Acalabrutinib 100mg

I. Basic Information

Generic Name: Acalabrutinib

Brand Names: Calquence, Kangkeqi, AKADX

Dosage Form & Strength: 100 mg/capsule; 60 capsules/box

Target: Bruton's Tyrosine Kinase (BTK) Inhibitor

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

Laos National Drug Administration Approval No.: 06 L 0984/23

Storage Conditions: 20°C–25°C (excursions permitted between 15°C–30°C); protect from light and moisture.

II. Indications

1. Mantle Cell Lymphoma (MCL):

Indicated for adult patients with relapsed or refractory disease who have received at least one prior systemic therapy.

2. Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL):

Indicated as first-line or subsequent therapy for adult patients; may be used as monotherapy or in combination with Obinutuzumab.

III. Mechanism of Action

Acalabrutinib irreversibly binds to the Cys481 residue of BTK, thereby inhibiting the B-cell receptor (BCR) signaling pathway and blocking the proliferation, survival, and migration of malignant B cells. Its active metabolite, ACP-5862, further enhances this inhibitory effect. IV. Dosage and Administration

1. Standard Dosing Regimens

| Indication          | Dosage and Combination Regimen

| MCL             | 100 mg orally every 12 hours, until disease progression or unacceptable toxicity

| CLL/SLL (Monotherapy) | 100 mg orally every 12 hours

| CLL/SLL (Combination) | 100 mg every 12 hours + Obinutuzumab (Start Acalabrutinib in Cycle 1; add Obinutuzumab in Cycle 2; continue for a total of 6 cycles)

2. Key Administration Rules

Administration Method: Swallow capsules whole (do not chew or crush). May be taken with or without food. Take at approximately the same time each day.

Missed Dose Management:

- Missed dose < 3 hours: Take the missed dose immediately.

- Missed dose ≥ 3 hours: Skip the missed dose and take the next scheduled dose as planned. Dose Adjustment:

| Adverse Reaction                       | Management Measures

| ≥Grade 3 Non-hematologic Toxicity      | Suspend → Resume at 100 mg q12h once toxicity resolves to ≤Grade 1; Permanently discontinue upon the 4th occurrence.

| Grade 3 Thrombocytopenia with Bleeding / Grade 4 Neutropenia | Suspend → Resume at a reduced dose or discontinue once resolved.

| Severe Hepatic / Renal Impairment      | 100 mg once daily.

V. Management of Adverse Reactions

Common Adverse Reactions (≥20%)

The table below summarizes adverse reactions with an incidence of ≥20% and corresponding management recommendations:

| Adverse Reaction Type | Incidence | Management Recommendations

| Headache              | 39%       | Symptomatic analgesia (e.g., acetaminophen); avoid precipitating factors.

| Diarrhea              | 31%       | Fluid replacement + Antidiarrheals (e.g., loperamide); assess for potential infection.

| Fatigue               | 28%       | Pacing of activities; optimize sleep duration.

| Myalgia / Arthralgia  | 21%       | Non-pharmacologic therapies (e.g., heat packs/massage); NSAIDs if necessary.

| Bruising / Bleeding   | 21%       | Avoid trauma; monitor coagulation status; for ≥Grade 3 bleeding, suspend medication and provide transfusion support.

Serious Adverse Reactions and Monitoring

1. Infections (Serious infection rate: 20%):

Increased risk of bacterial, viral, and fungal infections, including opportunistic infections (e.g., *Pneumocystis* pneumonia).

Prevention: Prophylactic use of antimicrobial/antiviral agents in high-risk patients; monitor for symptoms such as fever and cough.

2. Bleeding Events (Serious event rate: 0.8%):

Avoid concomitant use of anticoagulants (e.g., warfarin); discontinue medication 3–7 days prior to surgery.

3. Cardiovascular Toxicity:

Atrial fibrillation/flutter (incidence: <5%); monitor for palpitations and syncope; perform periodic ECG assessments.

4. Secondary Primary Malignancies:

Skin cancer is the most common; sun protection and regular skin examinations are recommended. VI. Important Considerations

1. Drug Interactions:

Strong CYP3A Inhibitors (e.g., Ketoconazole): Avoid concomitant use; if necessary, temporarily suspend acalabrutinib.

Strong CYP3A Inducers (e.g., Rifampin): Avoid concomitant use, or increase the acalabrutinib dosage to 200 mg every 12 hours (q12h).

Gastric Acid-Reducing Agents:

Proton Pump Inhibitors (PPIs): Contraindicated.

H2-Receptor Antagonists: Administer acalabrutinib 2 hours prior to taking the H2-receptor antagonist.

Antacids: Maintain an interval of at least 2 hours between doses.

2. Special Populations:

Pregnancy/Lactation: Poses a risk to the fetus; effective contraception is required during treatment and for 1 week after discontinuing the drug.

Elderly Patients (≥65 years): Higher incidence of severe adverse reactions; requires enhanced monitoring.

3. Laboratory Monitoring:

Monthly complete blood count (to assess for anemia/neutropenia).

Periodic assessment of liver and renal function (ALT/AST, creatinine).

Summary: Key Points for Clinical Application

> As a second-generation BTK inhibitor, the treatment regimen for acalabrutinib should adhere to the following principles:

> 1. Genetic Testing: Confirm the specific type of B-cell malignancy (CLL/SLL/MCL) prior to initiating treatment.

> 2. Individualized Dosing:

> Adjust dosage based on baseline liver and renal function.

> Dynamically adjust dosage based on serum phosphorus levels and observed toxicities.

> 3. Management of Multi-System Toxicities:

> Patients at high risk of bleeding should avoid trauma and anticoagulant medications.

> Conduct periodic ophthalmologic screening (due to the risk of retinopathy).

> Prioritize infection prevention over treatment.

*Note: The information above is synthesized from the drug's prescribing information and clinical studies; specific treatment decisions should be made under the guidance of a hematologist.