ALIVINEKLA Venetoclax

I. Basic Information

Drug Name: Venetoclax

Brand Names: Venclexta, Venclyxto, ALIVINEKLA

Dosage Form & Strength: 100 mg per tablet; 120 tablets per box

Pharmacological Class: BCL-2 Inhibitor (Targeting Apoptosis Proteins)

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Approval Number (Lao National Drug Administration): 11 L 127/24

II. Indications

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

Patients with CLL harboring a 17p deletion (who have received at least one prior therapy);

Second-line treatment for CLL/SLL in combination with rituximab or obinutuzumab.

2. Acute Myeloid Leukemia (AML):

Newly diagnosed AML patients aged ≥75 years or those ineligible for intensive chemotherapy, in combination with azacitidine, decitabine, or low-dose cytarabine.

3. Mantle Cell Lymphoma (MCL) (Approved in select countries):

Monotherapy for relapsed/refractory MCL (with dose escalation up to 800 mg/day).

III. Mechanism of Action

Selectively inhibits the BCL-2 protein (an anti-apoptotic protein), thereby promoting apoptosis in cancer cells. In CLL, SLL, and AML cells, BCL-2 overexpression leads to drug resistance; Venetoclax acts to reverse this process. IV. Dosage and Administration

1. Standard Dose Escalation Schedule (for Prevention of Tumor Lysis Syndrome)

CLL/SLL (5-week escalation):

| Treatment Week | Daily Dose

| Week 1         | 20 mg

| Week 2         | 50 mg

| Week 3         | 100 mg

| Week 4         | 200 mg

| From Week 5    | 400 mg

AML (3–4 day rapid escalation):

Day 1: 100 mg → Day 2: 200 mg → Day 3: 400 mg → From Day 4: 400 mg (in combination with azacitidine/decitabine) or 600 mg (in combination with low-dose cytarabine).

2. Key Administration Requirements

Administration: Once daily; swallow tablets whole with a meal (do not chew or crush).

Hydration Requirements:

Drink 1.5–2 liters of water daily for 2 days prior to the first dose and throughout the dose escalation period (to prevent Tumor Lysis Syndrome).

Missed Dose Management:

≤ 8 hours: Take the missed dose immediately; > 8 hours: Skip the missed dose and resume the original schedule the following day.

V. Warnings and Precautions

1. Tumor Lysis Syndrome (TLS):

High-risk populations: Patients with high tumor burden or renal impairment. 

Preventive Measures:

Assess risk prior to administration (monitor electrolytes and uric acid); 

Pre-hydration + anti-hyperuricemia agents (e.g., allopurinol);

High-risk patients require hospitalization for monitoring.

2. Neutropenia:

Incidence ≥ 20%; regular monitoring of complete blood counts is required; use Granulocyte Colony-Stimulating Factor (G-CSF) or interrupt treatment if necessary.

3. Risk of Infection:

Avoid administration of live vaccines (e.g., measles, varicella vaccines). 

Maintain vigilance for serious infections, such as pneumonia and sepsis.

4. Embryo-Fetal Toxicity:

Contraindicated in pregnant women; patients of reproductive potential must use effective contraception during treatment and for 30 days following the last dose. 5. Hepatic and Renal Impairment:

Dose adjustment is required for patients with moderate to severe hepatic or renal impairment.

VI. Adverse Reactions

Common Adverse Reactions (≥20%)

| System Class     | Manifestation

| Hematologic System | Neutropenia, Anemia, Thrombocytopenia

| Digestive System | Diarrhea, Nausea, Vomiting, Constipation

| Infections            | Upper Respiratory Tract Infection, Pneumonia, Sepsis

| General Symptoms     | Fatigue, Fever, Edema

Serious Adverse Reactions

TLS (Tumor Lysis Syndrome), Severe Neutropenia (with fever), Serious Infections (Sepsis), Hemorrhage.

VII. Drug Interactions

Contraindicated Combinations:

Strong CYP3A Inhibitors (e.g., Ketoconazole, Clarithromycin): Contraindicated during the dose ramp-up phase; dose reduction is required during the maintenance phase.

Combinations to Avoid:

Strong CYP3A Inducers (e.g., Carbamazepine, Phenytoin): May decrease Venetoclax plasma concentrations; 

P-gp Substrates (e.g., Digoxin): Administer at least 6 hours apart.

Dietary Restrictions: Grapefruit, Starfruit, Seville Oranges (inhibit CYP3A, increasing the risk of toxicity).

VIII. Use in Specific Populations

Pregnant Women: Contraindicated (risk of fetal malformations).

Lactating Women: Breastfeeding is prohibited for at least 1 week after discontinuing the drug.

Male Fertility: May temporarily reduce sperm quality.

Geriatric Patients: AML patients aged ≥75 years require close monitoring.

IX. Storage Conditions

Protect from light; store at a temperature below 30°C (86°F).

Summary Points

> Key Takeaways:

> Dose ramp-up is critical for safety; be especially vigilant for Tumor Lysis Syndrome (TLS);

> Swallow tablets whole with food; avoid grapefruit and starfruit;

> Monitor complete blood counts, electrolytes, and signs of infection during treatment;

> Patients of reproductive potential must use effective contraception for 30 days after the last dose.

Consult a professional pharmacist for more detailed prescribing information.