lludx Ibrutinib Capsules 140mg

[Drug Name]

Generic Name: Ibrutinib Capsules

Brand Names: Yike, IMBRUVICA, lludx

English Name: Ibrutinib Capsules

Pinyin: Yibutini Jiaonang

Specification: 140 mg/capsule; 90 capsules/box

Manufacturer: Bigbear Pharmaceutical Laos

Drug Approval Number: 07 L0991/23

[Composition]

Active Ingredient: Ibrutinib

Chemical Name: 1-{(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl}prop-2-en-1-one

Molecular Formula: C₂₅H₂₄N₆O₂

Molecular Weight: 440.50

[Indications]

1. Mantle Cell Lymphoma (MCL): As a single agent for adult patients with MCL who have received at least one prior therapy.

2. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): As a single agent or in combination therapy for adult patients with CLL/SLL (including patients with 17p deletion).

3. Waldenström’s Macroglobulinemia (WM):

As a single agent for patients with WM who have received at least one prior therapy, or as first-line therapy for patients with WM who are unsuitable for chemoimmunotherapy;

In combination with rituximab for the treatment of patients with WM.

4. Chronic Graft-versus-Host Disease (cGVHD): For adults and pediatric patients aged ≥1 year with cGVHD who have failed one or more lines of systemic therapy.

[Dosage and Administration]

Administration

For oral use. Take once daily at approximately the same time each day. Swallow the capsule whole with warm water; do not open, break, or chew the capsule. Do not take with grapefruit juice.

Recommended Dosage (Adults)

1. Mantle Cell Lymphoma (MCL): 560 mg (4 capsules × 140 mg) once daily, until disease progression or unacceptable toxicity. 2. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): 420 mg (3 capsules × 140 mg) once daily, until disease progression or unacceptable toxicity.

3. Waldenström’s Macroglobulinemia (WM): 420 mg (3 capsules × 140 mg) once daily, until disease progression or unacceptable toxicity.

4. Chronic Graft-versus-Host Disease (cGVHD): 420 mg (3 capsules × 140 mg) once daily, until disease progression or unacceptable toxicity.

Pediatric Dosage (Chronic Graft-versus-Host Disease [cGVHD], 1 to <12 years of age)

240 mg/m² once daily (maximum 420 mg).

Dosage Adjustments (Adverse Reactions)

1. Grade ≥3 non-hematologic toxicity, Grade ≥3 neutropenia with infection/fever, or Grade 4 hematologic toxicity: Withhold treatment; resume at the original dose once toxicity resolves to Grade ≤1 or returns to baseline. If toxicity recurs, reduce the dose by 140 mg; if a second recurrence occurs, reduce the dose by another 140 mg; if toxicity recurs again, permanently discontinue the drug.

2. Hepatic Impairment:

Mild (Child-Pugh A): 140 mg once daily;

Moderate/Severe (Child-Pugh B/C): Contraindicated.

3. Missed Dose: Take the missed dose as soon as possible on the same day; resume the regular schedule the following day. Do not take a double dose.

[Adverse Reactions]

Common Adverse Reactions (≥20%)

Hematologic: Neutropenia, thrombocytopenia, anemia;

Non-hematologic: Diarrhea, hemorrhage (ecchymosis), fatigue, musculoskeletal pain, nausea, upper respiratory tract infection, cough, rash.

Grade 3/4 Adverse Reactions (≥5%)

Neutropenia, thrombocytopenia, pneumonia, anemia, atrial fibrillation, diarrhea, fatigue. Important Adverse Reactions

1. Hemorrhage: Fatal hemorrhage (intracranial, gastrointestinal, post-operative); approximately 50% of patients experience bleeding of varying grades (petechiae, ecchymoses); avoid warfarin; use anticoagulants/antiplatelet agents with caution; discontinue medication 3–7 days prior to surgery.

2. Infection: Fatal/non-fatal infections (pneumonia, sepsis); 14%–29% are Grade ≥3; remain vigilant for PML and *Pneumocystis* pneumonia.

3. Arrhythmias: Atrial fibrillation/flutter (7%; 2.8% are Grade 3), ventricular arrhythmias (1%); monitor ECG; provide symptomatic treatment.

4. Interstitial Lung Disease (ILD): Monitor for cough/dyspnea; discontinue medication and administer corticosteroids; permanently discontinue treatment if necessary.

5. Tumor Lysis Syndrome (TLS): Prophylaxis recommended for patients with high tumor burden; monitor electrolytes and renal function.

6. Hepatitis B Reactivation: Screen for HBV prior to treatment; for positive patients, monitor closely and administer antiviral therapy.

Post-marketing Adverse Reactions

Hepatic failure, interstitial lung disease, Stevens-Johnson syndrome, angioedema, brittle nails, panniculitis, hepatitis B reactivation.

[Contraindications]

Patients with hypersensitivity to ibrutinib or any of its excipients;

Patients with moderate to severe hepatic impairment (Child-Pugh B/C).

[Precautions]

1. Bleeding Risk: Monitor for signs of bleeding; avoid warfarin, fish oil, and high-dose Vitamin E.

2. Infection Control: Prophylaxis against opportunistic infections; promptly evaluate and treat patients presenting with fever or signs of infection.

3. Hematologic Monitoring: Perform monthly complete blood counts (CBC); promptly manage any cytopenias.

4. Cardiovascular Monitoring: Periodically monitor blood pressure and perform ECGs; assess thrombotic risk in patients with atrial fibrillation and initiate anticoagulation if necessary.

5. Hepatic and Renal Function: Periodically monitor liver function; no dose adjustment is required for patients with renal impairment.

6. Vaccinations: Avoid live vaccines during treatment; inactivated vaccines may be administered. [Use in Specific Populations]

Pregnant and Lactating Women

Pregnancy: Animal studies indicate teratogenicity; contraindicated during pregnancy; women of childbearing potential must use effective contraception during treatment and for 1 month after discontinuing the drug; men must use effective contraception during treatment and for 3 months after discontinuing the drug.

Lactation: Breastfeeding should be discontinued during treatment (the drug may be excreted in breast milk).

Pediatric Use

CLL/SLL/MCL/WM: Safety and efficacy have not been established; cGVHD: May be used in patients ≥1 year of age, dosed according to body weight.

Geriatric Use

No dose adjustment is required; patients ≥65 years of age may be at increased risk for anemia and severe pneumonia; enhanced monitoring is recommended.

[Drug Interactions]

CYP3A Inhibitors

Strong Inhibitors (e.g., ketoconazole, itraconazole, clarithromycin): Avoid concomitant use.

Moderate Inhibitors (e.g., fluconazole, erythromycin): Reduce dose to 140 mg once daily.

CYP3A Inducers

Strong Inducers (e.g., rifampin, carbamazepine, phenytoin): Avoid concomitant use.

Anticoagulants/Antiplatelet Agents

Increased risk of bleeding; concomitant use with warfarin is contraindicated; use with caution with rivaroxaban, aspirin, or clopidogrel.

[Pharmacology]

Mechanism of Action: Irreversibly inhibits Bruton's tyrosine kinase (BTK), thereby blocking B-cell receptor signaling and inhibiting the proliferation, survival, migration, and adhesion of tumor cells.

Pharmacokinetics: Peak plasma concentrations are reached 1–2 hours after oral administration; elimination half-life is 4–6 hours; primarily metabolized in the liver (via CYP3A4) and excreted via feces; exposure is increased 2.7-fold in patients with mild hepatic impairment, and 8.2–9.8-fold in patients with moderate to severe hepatic impairment.

[Storage]

Store in a tightly sealed container at a temperature not exceeding 30°C.