ibrutinib ALIBRU 140mg

[Basic Drug Information]

Generic Name: Ibrutinib Capsules; Ibrutinib

Brand Names: Yike, IMBRUVICA, ALIBRU

English Name: Ibrutinib Capsules

Specification: 140 mg/capsule; 120 capsules/box

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Approval Number (Lao National Drug Administration): 07 L 1373/25

Storage Conditions: Store below 30°C.

Composition:

Active Ingredient: Ibrutinib

Excipients: Microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, magnesium stearate, gelatin empty capsules.

[Indications]

As a single agent, this product is indicated for the treatment of patients with Mantle Cell Lymphoma (MCL) who have received at least one prior therapy.

As a single agent, this product is indicated for the treatment of patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) who have received at least one prior therapy.

As a single agent, this product is indicated for the treatment of patients with Waldenström’s Macroglobulinemia (WM) who have received at least one prior therapy, or as a first-line treatment for patients with WM who are unsuitable for chemo-immunotherapy.

In combination with rituximab, this product is indicated for the treatment of patients with Waldenström’s Macroglobulinemia (WM).

[Dosage and Administration]

Administration: For oral use. Take once daily; the time of administration should be approximately the same each day. Swallow the capsules whole with water; do not open, break, or chew the capsules. Do not take with grapefruit juice.

Recommended Dosage:

For Mantle Cell Lymphoma (MCL), the recommended dose is 560 mg (4 capsules of 140 mg) once daily until disease progression or unacceptable toxicity occurs.

For Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) and Waldenström’s Macroglobulinemia (WM), the recommended dose is 420 mg (3 capsules of 140 mg) once daily until disease progression or unacceptable toxicity occurs. When administered in combination with rituximab, if both medications are given on the same day, it is recommended that this product be administered prior to the rituximab dose.

**Dose Adjustments for Adverse Reactions:** Treatment should be interrupted in the event of any Grade ≥3 non-hematologic toxicity, Grade ≥3 neutropenia with infection or fever, or Grade 4 hematologic toxicity. Once toxicities have resolved to Grade 1 or baseline levels, treatment may be resumed at the starting dose. If the toxicity recurs, the dose should be reduced by 140 mg. If necessary, a further dose reduction of 140 mg may be considered. If the toxicity persists or recurs after two dose reductions, this product should be permanently discontinued.

**Dose Adjustments for Patients with Hepatic Impairment:** The recommended dose for patients with mild hepatic impairment (Child-Pugh Class A) is 140 mg once daily (one capsule). Use of this product should be avoided in patients with moderate or severe hepatic impairment (Child-Pugh Class B and C).

**Missed Doses:** If a dose is missed at the scheduled time, it should be taken as soon as possible on the same day; the patient should then resume taking the medication at the normal scheduled time the following day. Do not take extra doses to make up for a missed dose.

**[Adverse Reactions]**

**Common Adverse Reactions:** These include hemorrhage, infections, cytopenias, interstitial lung disease, atrial fibrillation, leukostasis, hypertension, secondary malignancies, tumor lysis syndrome, etc.

**Mantle Cell Lymphoma:** The most frequently occurring adverse reactions (≥20%) are diarrhea, hemorrhage (e.g., bruising), fatigue, musculoskeletal pain, nausea, upper respiratory tract infection, cough, and rash. The most common Grade 3 or 4 adverse reactions (≥5%) are neutropenia, thrombocytopenia, pneumonia (infectious), and anemia.

**Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma:** The most frequently occurring adverse reactions (≥20%) are neutropenia, thrombocytopenia, anemia, diarrhea, musculoskeletal pain, nausea, rash, bruising, fatigue, pyrexia, and hemorrhage. [Contraindications]

Contraindicated in patients with hypersensitivity (e.g., anaphylaxis and anaphylactoid reactions) to ibrutinib or to any of the excipients.

Contraindicated in patients with moderate to severe hepatic impairment.

Contraindicated in pregnant women.

Contraindicated during breastfeeding.

[Precautions]

Hemorrhage: May increase the risk of bleeding; monitor for signs of bleeding. Avoid concomitant use with Vitamin K antagonists (e.g., warfarin). Suspend administration of this product for at least 3 to 7 days before and after surgery.

Infections: For patients at increased risk of opportunistic infections, consider prophylaxis in accordance with standard medical practice.

Cytopenias: Monitor complete blood counts monthly.

Interstitial Lung Disease (ILD): Monitor for pulmonary symptoms; if symptoms occur, suspend treatment to provide appropriate medical management. If symptoms persist, consider dose adjustment.

Arrhythmias: In patients presenting with signs and/or symptoms of ventricular tachycardia, suspend administration of this product and conduct a comprehensive clinical benefit-risk assessment.

Leukostasis: Consider suspending administration of this product, closely monitor the patient, and provide supportive care as clinically indicated.

Hypertension: Monitor for new-onset hypertension or hypertension that is not adequately controlled following the initiation of treatment; adjust antihypertensive medications as appropriate.

Secondary Malignancies: Other malignancies have occurred in patients treated with this product; monitor patients closely.

Tumor Lysis Syndrome (TLS): Assess baseline risk, take appropriate prophylactic measures, and closely monitor and treat patients as appropriate.

Hepatitis B Virus (HBV) Reactivation: If HBV infection testing results are positive, consultation with a specialist is recommended to monitor and manage the condition in accordance with local medical standards.

[Use in Pregnant and Lactating Women]

Pregnancy and Embryo-Fetal Toxicity: Female patients are advised to avoid pregnancy while taking this product and for 1 month after discontinuing treatment. If this product is used during pregnancy, or if a patient becomes pregnant while taking this product, the patient should be informed of the potential hazard to the fetus.

Lactation: This product may cause serious adverse reactions in nursing infants; breastfeeding should be discontinued during treatment.

[Pediatric Use]

The safety and efficacy of this product in pediatric patients have not been established.

[Geriatric Use]

Anemia (all grades) and Grade ≥3 pneumonia occurred more frequently in elderly patients treated with this product. [Overdosage]

Currently, there is no specific experience regarding the management of Ibrutinib overdose. One healthy subject experienced reversible Grade 4 elevations in liver enzymes following the administration of 1680 mg of the product. Patients who have received a dose exceeding the recommended dosage should be closely monitored and provided with appropriate supportive care.