BIGBEAR ENASIDX Enasidenib 100mg

I. Basic Drug Information

Brand Name: Idhifa, ENASIDX

Generic Name: Enasidenib

Dosage Form & Strength: 50 mg/tablet (30 tablets/box); 100 mg/tablet (30 tablets/box)

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

Laos National Drug Administration Approval No.: 10 L 1227/24

Laos National Drug Administration Approval No.: 10 L 1040/23

Storage Conditions: 20°C–25°C (excursions permitted between 15°C–30°C); protect from light and moisture; keep the original desiccant in the bottle.

II. Indications

Patient Population: Adult patients confirmed to harbor an IDH2 mutation via an FDA/NMPA-approved diagnostic test.

Specific Disease:

Relapsed or Refractory Acute Myeloid Leukemia (AML):

Must harbor an IDH2 mutation (e.g., R140Q, R172K, R172S).

III. Mechanism of Action

Target Inhibition: Selectively inhibits the mutated IDH2 enzyme, thereby blocking the production of the oncogenic metabolite 2-hydroxyglutarate (2-HG).

Cellular Effects: Reduces 2-HG levels → restores abnormal hematopoietic cell differentiation → induces apoptosis in leukemia cells.

IV. Dosage and Administration

Standard Regimen

Recommended Dosage: 100 mg orally once daily (taken with or without food), continued until disease progression or unacceptable toxicity occurs.

Key Requirements:

Swallow tablets whole; do not crush or chew.

Take the medication at approximately the same time each day.

Continue treatment for at least 6 months to assess efficacy. **Management of Special Situations**

| Scenario                      | Management Measures

| Missed Dose                   | Take as soon as possible (if >12 hours remain until the next scheduled dose, skip the missed dose)

| Vomiting                      | Take one replacement dose on the same day

| Concomitant Use with Strong CYP3A4 Inhibitors | Monitor for toxicity; dose reduction may be required (follow physician's instructions)

**Dose Adjustments for Toxicity**

**Differentiation Syndrome (Fever/Dyspnea/Hypoxia):**

Immediately administer IV Dexamethasone (10 mg every 12 hours); for severe cases, suspend Enasidenib until symptoms resolve.

**Grade ≥3 Non-hematologic Toxicity:**

Suspend treatment → Resume at a reduced dose of 50 mg/day once toxicity resolves to Grade ≤1 → Permanently discontinue if toxicity recurs.

**Tumor Lysis Syndrome (TLS):**

Prophylactic hydration and uric acid-lowering therapy; monitor electrolytes and renal function.

**V. Adverse Reactions**

**Common (≥20%)**

**Gastrointestinal:** Nausea (50%), Diarrhea (43%), Vomiting (34%), Decreased Appetite (34%);

**Laboratory Abnormalities:** Increased Bilirubin (81%), Hypocalcemia (74%), Hypokalemia (41%);

**Systemic:** Fatigue (37%), Edema (21%).

**Serious Adverse Reactions**

**1. Differentiation Syndrome (14%):**

Most frequently occurs within 1 day to 5 months of treatment initiation; mortality rate is 10%.

**2. Non-infectious Leukocytosis (12%):** Requires monitoring of white blood cell counts.

**3. Hepatotoxicity:** Increased Bilirubin (81%); monitor liver function periodically.

**4. QT Interval Prolongation:** Monitor ECG prior to and during treatment.

**VI. Contraindications and Warnings**

**Contraindications:**

Pregnancy (risk of teratogenicity); Breastfeeding (discontinue breastfeeding for ≥2 months after the last dose).

Hypersensitivity to any component of the product.

**Boxed Warning:** Differentiation Syndrome (requires urgent corticosteroid treatment). VII. Drug Interactions

| Concomitant Drug Type      | Representative Drug(s) | Risks and Management

| OATP1B1/BCRP Substrates | Rosuvastatin           | ↑ Plasma concentration → Dose reduction and toxicity monitoring required

| P-gp Substrates           | Digoxin                | ↑ Exposure → Dose adjustment required

| Strong CYP3A4 Inducers    | Rifampin, Phenytoin    | ↓ Enasidenib efficacy → Avoid concomitant use

VIII. Use in Specific Populations

Pregnancy/Lactation:

Contraception is required during treatment and for ≥2 months after the last dose (for both men and women); discontinue breastfeeding during treatment.

Hepatic/Renal Impairment:

Mild to Moderate: No dose adjustment required; Severe (Child-Pugh C or eGFR < 30): Use with caution; data are limited.

Pediatric Patients: Safety has not been established.

Geriatric Patients: No dose adjustment required.

IX. Clinical Efficacy Data

Key Trial (n=199; IDH2-mutated R/R AML):

Complete Remission (CR) Rate: 19%; Complete Remission with Partial Hematologic Recovery (CRh) Rate: 4%;

Median Duration of Remission: 8.2 months (CR), 9.6 months (CRh);

34% of transfusion-dependent patients became transfusion-independent following treatment.

X. Patient Information

Monitoring Requirements:

Baseline: IDH2 mutation testing, ECG, complete blood count (CBC), liver and renal function tests, electrolytes;

During Treatment: Monitor CBC and liver function every 2 weeks for the first 3 months, then once monthly thereafter.

Indications for Immediate Medical Attention:

Fever accompanied by difficulty breathing, bone pain, and/or edema (suggestive of Differentiation Syndrome);

Decreased urine output and/or muscle cramps (suggestive of Tumor Lysis Syndrome).

This prescribing information is based on the latest clinical evidence; specific medication use should be strictly in accordance with a physician's instructions.

Important Note: Avoid consuming grapefruit or starfruit during treatment (as they affect CYP3A4 metabolism); avoid driving or operating heavy machinery if neurological symptoms (such as dizziness or hallucinations) occur.