I. Basic Drug Information

Generic Name: Capivasertib

Approved Name in China: Capivasertib Tablets

Brand Names: Truqap, ALICAPASE, Quankede

Dosage Form & Strength: 200 mg per tablet; 64 tablets per box

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Approval Number (Lao National Drug Administration): 07 L 1133/24

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

II. Indications

Used in combination with fulvestrant (Faslodex) for the treatment of the following patients:

Adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer;

Patients confirmed—via an FDA-approved test—to harbor alterations in the PIK3CA/AKT1/PTEN genes (at least one);

Patients with disease progression following prior therapy: progression on or after at least one endocrine therapy in the metastatic setting, or recurrence within 12 months of completing adjuvant therapy.

Mutation status must be confirmed via genetic testing prior to administration; otherwise, use is contraindicated.

III. Mechanism of Action

Capivasertib is a highly selective AKT kinase inhibitor:

Target: Inhibits the three AKT isoforms (AKT1/2/3), thereby blocking the aberrant activation of the PI3K/AKT/mTOR signaling pathway;

Action: Inhibits tumor cell proliferation, survival, and metastasis, and reverses resistance to endocrine therapy;

Synergistic Effect: When used in combination with fulvestrant (an estrogen receptor degrader), it provides a dual blockade of tumor growth signals.

IV. Dosage and Administration

1. Standard Dosing Regimen

Dosage: 400 mg (two 200 mg tablets or an equivalent combination), taken orally twice daily (at 12-hour intervals);

Treatment Cycle: Take continuously for 4 days → discontinue for 3 days (weekly cycle);

Administration: Swallow tablets whole (do not crush or chew); may be taken with or without food. 2. Dosage Adjustment Guidelines

Table 1: Dosage Adjustments Based on Adverse Reactions

| Type of Adverse Reaction | Management Measures

| Hyperglycemia (Grade ≥3) | Suspend treatment → Resume after blood glucose control is achieved → First dose reduction to 320 mg; second dose reduction to 200 mg

| Diarrhea (Grade ≥3) | Suspend until resolution → Resume at a reduced dose level (400 mg → 320 mg → 200 mg)

| Severe Skin Reactions | Suspend treatment → Resume at a reduced dose after recovery; if accompanied by systemic symptoms (e.g., DRESS syndrome), permanently discontinue treatment

| Other Grade 3/4 Toxicities | Suspend until toxicity resolves to Grade ≤1 → Resume at a reduced dose; if toxicity recurs a second time, permanently discontinue treatment

Maximum Dose Reduction Steps: 400 mg → 320 mg → 200 mg → If still not tolerated, permanently discontinue treatment.

3. Management of Drug Interactions

| Concomitant Medication | Dosage Adjustment

| Strong CYP3A Inhibitors (e.g., Ketoconazole) | Avoid concomitant use; if use is essential → Reduce dose to 320 mg twice daily

| Moderate CYP3A Inhibitors (e.g., Fluconazole) | Reduce dose to 320 mg twice daily

| CYP3A Inducers (e.g., Rifampin) | Strictly contraindicated (significantly reduces plasma drug concentrations)

V. Adverse Reactions

Common Adverse Reactions (Incidence ≥20%)

Gastrointestinal System: Diarrhea (>50%), Nausea (>30%), Vomiting (>20%), Stomatitis;

Metabolic Abnormalities: Increased random blood glucose (>60%), Increased fasting blood glucose (>40%), Increased triglycerides (>30%);

Hematologic Toxicities: Lymphopenia (>40%), Decreased hemoglobin (>35%), Neutropenia (>25%);

Other: Skin reactions (rash, dryness), Fatigue, Increased creatinine. **Severe Risk Warning (Requires Urgent Intervention)**

| **Risk Type** | **Key Symptoms & Management**

| **Hyperglycemic Crisis** | Ketoacidosis (thirst, polyuria, fruity-scented breath) → Suspend medication + Insulin therapy; monitor electrolytes.

| **Severe Diarrhea** | Dehydration, electrolyte imbalance → Fluid replacement + Antidiarrheals (e.g., Loperamide); hospitalization if necessary.

| **Cutaneous Hypersensitivity** | Erythema Multiforme (EM), DRESS Syndrome → Permanently discontinue medication + Dermatologic consultation.

| **Hepatotoxicity** | Jaundice, elevated AST/ALT → Suspend medication and monitor liver function.

**VI. Contraindications and Precautions**

**Absolute Contraindications**

Patients with known hypersensitivity to Capivasertib components;

Pregnancy (known teratogenic risk; confirmed in animal studies).

**Key Precautions**

**1. Hyperglycemia Monitoring:**

Measure fasting glucose (FG) and HbA1c prior to treatment; monitor FG weekly in patients with obesity or diabetes.

Seek immediate medical attention if symptoms occur; initiate insulin therapy if necessary.

**2. Diarrhea Management:**

Have antidiarrheal medication available from the start of treatment; increase fluid intake if watery stools occur.

**3. Contraception Requirements:**

**Females:** Use effective contraception during treatment and for at least 1 month after discontinuing the medication.

**Males:** Use effective contraception during treatment and for at least 4 months after discontinuing the medication (due to the longer spermatogenesis cycle).

**4. Hepatic and Renal Impairment:**

**Mild Hepatic Impairment** (Child-Pugh A) or **Mild Renal Impairment** (creatinine clearance ≥ 30 mL/min): No dose adjustment required.

**Moderate to Severe Hepatic Impairment** (Child-Pugh B/C): Contraindicated.

**Note:** The information above is compiled based on FDA/EMA-approved prescribing information and integrated clinical study data. Specific medication use must strictly adhere to a physician's instructions, and regular monitoring of blood glucose, liver enzymes, and skin reactions is required.