Nab-Xelpac IV Infusion

✔️ Uses of Nab-Xelpac

• Metastatic Breast Cancer
• Non-Small Cell Lung Cancer (NSCLC)
• Adenocarcinoma of the Pancreas

✔️ How does Nab-Xelpac work?

• Nab-Paclitaxel is a microtubule inhibitor that promotes microtubule assembly from tubulin dimers and stabilizes them by preventing depolymerization.
  • This disrupts the dynamic microtubule reorganization necessary for cell division.
  • Results in abnormal microtubule bundles and multiple asters during mitosis, leading to cancer cell death.

✔️ Side Effects of Nab-Xelpac

Most Common Adverse Reactions (≥20%):

• Metastatic Breast Cancer: Alopecia, neutropenia, sensory neuropathy, anemia, nausea, fatigue, infections, diarrhea.
• NSCLC (with carboplatin): Anemia, thrombocytopenia, alopecia, nausea, fatigue.
• Pancreatic Adenocarcinoma (with gemcitabine): Neutropenia, thrombocytopenia, peripheral neuropathy, diarrhea.

Serious Adverse Reactions:

• Myelosuppression (e.g., neutropenia, thrombocytopenia).
• Peripheral neuropathy.
• Severe hypersensitivity.

✔️ Overdose Management of Nab-Xelpac

• No specific antidote.
• Symptoms include bone marrow suppression, neurotoxicity, and mucositis.
• Supportive care and close monitoring are recommended.

✔️ Important Notes for Safe Use

• Specialized Equipment: No special solution containers or DEHP-free administration sets are necessary.
• Inspect the Reconstituted Solution: Ensure the suspension is milky and homogenous without visible particles before use.
• Avoid Shaking: This can create excessive foam and compromise the suspension.
• Foaming: If foam develops during preparation, allow time for it to dissipate before proceeding.

✔️ Hepatic Impairment: Comprehensive Dosing Guide for Paclitaxel Protein-Bound (Nab-Paclitaxel)

• AST >10x ULN or bilirubin >5x ULN: Avoid use regardless of indication.

✔️ Non-Small Cell Lung Cancer (NSCLC): Comprehensive Dosing Guide for Paclitaxel Protein-Bound (Nab-Paclitaxel)

First-line treatment for advanced or metastatic NSCLC, in combination with carboplatin, in patients not candidates for surgery or radiation.

Standard Dose:

• Paclitaxel protein-bound: 100 mg/m² IV over 30 minutes on Days 1, 8, and 15 of a 21-day cycle.
• Carboplatin: AUC 6 mg·min/mL IV on Day 1 of each cycle, administered immediately after paclitaxel.

Dose Modifications:

• Hematologic Toxicities:
  • Do not administer on Day 1 until ANC ≥1500/mm³ and platelets ≥100,000/mm³.
  • For Day 8 or 15, withhold treatment if ANC <500/mm³ or platelets <50,000/mm³.
  • Resume at a reduced dose when ANC ≥500/mm³ and platelets ≥50,000/mm³.
• Peripheral Neuropathy (Grade 3 or 4): Withhold dose; resume at reduced levels after improvement to Grade 1.

Permanent Dose Reductions:

Neutropenic fever or delayed cycle >7 days:

• First occurrence: Reduce paclitaxel to 75 mg/m² and carboplatin to AUC 4.5 mg·min/mL.
• Second occurrence: Reduce paclitaxel to 50 mg/m² and carboplatin to AUC 3 mg·min/mL.
• Third occurrence: Discontinue treatment.

Platelets <50,000/mm³:

• First occurrence: Reduce paclitaxel to 75 mg/m² and carboplatin to AUC 4.5 mg·min/mL.
• Second occurrence: Discontinue treatment.

✔️ Breast Cancer: Comprehensive Dosing Guide for Paclitaxel Protein-Bound (Nab-Paclitaxel)

For metastatic breast cancer after failure of prior combination chemotherapy or relapse within 6 months of adjuvant therapy.

Standard Dose: 260 mg/m² IV over 30 minutes every 3 weeks.

Dose Modifications:

• Severe neutropenia (<500/mm³) or severe sensory neuropathy: Reduce dose to 220 mg/m².
• Recurrence of severe toxicities: Reduce dose to 180 mg/m².
• Grade 3 sensory neuropathy: Hold treatment until resolved to ≤Grade 1 or 2, then reduce dose for subsequent cycles.

✔️ Pancreatic Cancer: Comprehensive Dosing Guide for Paclitaxel Protein-Bound (Nab-Paclitaxel)

First-line treatment of metastatic adenocarcinoma of the pancreas in combination with gemcitabine.

Standard Dose:

• Paclitaxel protein-bound: 125 mg/m² IV infused over 30–40 minutes on Days 1, 8, and 15 of a 28-day cycle.
• Gemcitabine: 1000 mg/m² IV infused over 30–40 minutes immediately after paclitaxel on the same days.

Dose Modifications:

• First dose reduction:
  • Paclitaxel: 100 mg/m²
  • Gemcitabine: 800 mg/m²
• Second dose reduction:
  • Paclitaxel: 75 mg/m²
  • Gemcitabine: 600 mg/m²
• Discontinue treatment if additional reductions are required.

Hematologic Toxicities:

• Cycle Day 1:
  • ANC <1500/mm³ or platelets <100,000/mm³: Delay doses until recovery.
• Cycle Days 8 or 15:
  • ANC 500 to <1000/mm³ or platelets 50,000 to <75,000/mm³: Reduce dose level by 1.
  • ANC <500/mm³ or platelets <50,000/mm³: Withhold doses.

Non-Hematologic Toxicities:

• Febrile Neutropenia (Grade 3 or 4): Withhold doses until fever resolves and ANC ≥1500/mm³; resume at the next lower dose level.
• Peripheral Neuropathy (Grade 3 or 4): Withhold paclitaxel until improved to ≤Grade 1, then resume at a reduced dose.
• Mucositis or Diarrhea (Grade 3): Withhold doses until improved to ≤Grade 1, then resume at the next lower dose.
• Cutaneous Toxicity (Grade 2 or 3): Reduce paclitaxel dose; discontinue treatment if toxicity persists.

✔️ General Monitoring & Considerations

• Hematologic: Monitor ANC and platelet counts before and during treatment cycles.
• Peripheral Neuropathy: Assess for new or worsening symptoms.
• Non-Hematologic Toxicities: Manage symptoms with dose delays or reductions.
• Renal Impairment: No adjustment is needed for CrCl ≥30 mL/min. Limited data for CrCl <30 mL/min.

✔️ Administration Instructions: Nab-Xelpac

Preparation for IV Use:

Reconstitution:

• Aseptically reconstitute the vial by injecting 20 mL of 0.9% NaCl (normal saline) over 1 minute.
• Allow the fluid to flow gently along the inner wall of the vial to avoid foaming.

Mixing:

• Swirl or invert the vial gently to mix; do not shake.
• The resulting suspension should be milky and homogenous, free from visible particulates.

Handling Foam:

• If foaming occurs during reconstitution, allow the solution to stand for at least 15 minutes to let the foam subside.

Final Preparation:

• Withdraw the required volume of the reconstituted suspension (5 mg/mL) and transfer it into a sterile IV bag.
• The IV bag can be PVC or non-PVC; specialized DEHP-free containers are not required.

IV Administration:

• Infuse the prepared suspension intravenously over 30 minutes.
• Do not use an in-line filter during the infusion process.

✔️ Pregnancy & Lactation:

• Pregnancy: Category D (fetal harm reported in animal studies).
• Lactation: Discontinue drug or breastfeeding due to potential risks to the infant.

✔️ Geriatric Use: Nab-Xelpac

• Older patients may experience more adverse effects (e.g., diarrhea, dehydration, fatigue).

✔️ Renal Impairment: Nab-Xelpac

• No adjustments for mild to moderate impairment.
• Insufficient data for severe impairment.

✔️ Hepatic Impairment: Nab-Xelpac

• Dose adjustments are required for moderate impairment.
• Avoid severe hepatic dysfunction.

✔️ Pediatric Use: Nab-Xelpac

• Safety and efficacy not established.

✔️ Drug Interactions: Nab-Xelpac

• CYP2C8 and CYP3A4 inhibitors (e.g., ketoconazole, fluoxetine): May increase paclitaxel levels.
• CYP2C8 and CYP3A4 inducers (e.g., rifampicin, phenytoin): May decrease paclitaxel levels.
• Avoid combinations that can further suppress bone marrow or increase the risk of neurotoxicity.

✔️ Contraindications

• Baseline neutrophil count <1,500 cells/mm³.
• Severe hypersensitivity to paclitaxel or its components.
• Pregnancy (Category D): Can cause fetal harm.

✔️ Pregnancy and Lactation Considerations for Nab-Paclitaxel

Pregnancy: Category D

• Nab-Paclitaxel can cause fetal harm when administered to pregnant women.
• Animal Studies:
  • In rats, exposure to doses lower than the maximum recommended human dose (based on body surface area) resulted in:
    • Embryo-fetal toxicities: Increased intrauterine mortality, resorptions, and reduced live fetuses.
    • Malformations: Structural abnormalities in the fetus.

Human Data:

• No well-controlled studies have been conducted in pregnant women.
• If used during pregnancy, or if a patient becomes pregnant while receiving treatment, the patient must be informed of the potential hazards to the fetus.

Recommendations for Women of Childbearing Potential:

• Use effective contraception during treatment and for 6 months after completing therapy.
• Consider pregnancy testing before starting treatment.

Lactation

Excretion in Milk:

• Paclitaxel and/or its metabolites are excreted in the milk of lactating rats.
• It is unknown whether paclitaxel is excreted into human breast milk.

Potential Risks to Infants:

• Given the potential for serious adverse reactions in nursing infants, including myelosuppression, neuropathy, or other toxicities, breastfeeding is not recommended during treatment.

Either discontinue breastfeeding or discontinue Nab-Paclitaxel, depending on the critical need for the drug in the mother’s treatment plan.

Patient Counseling Points

Pregnancy:

• Emphasize the importance of avoiding pregnancy and the potential risks to the fetus.
• If pregnancy occurs, discuss the option of continued treatment versus discontinuation based on the severity of the cancer and patient preference.

Lactation:

• Counsel patients to either stop breastfeeding or seek alternative feeding methods for infants if Nab-Paclitaxel is required for treatment.

✔️ Safety Precautions and Risk Management for Paclitaxel Protein-Bound (Nab-Paclitaxel)

1. Myelosuppression

• Risk: Causes significant myelosuppression, including neutropenia, anemia, and thrombocytopenia.
• Monitoring:
  • Regularly monitor Complete Blood Count (CBC) before each treatment cycle.
  • Adjust or withhold doses in cases of severe hematologic toxicity (refer to Dosage Modifications for specific thresholds).
• Management: Prompt intervention with dose delays or reductions based on ANC and platelet levels to prevent complications like febrile neutropenia.

2. Sensory Neuropathy

• Risk: Frequent occurrence, particularly peripheral neuropathy. Severe cases may require treatment interruption or dose reduction.
• Monitoring: Assess for symptoms of tingling, numbness, or pain in extremities regularly.
• Management:
  • Grade 3 or 4 neuropathy: Withhold treatment until symptoms improve to ≤Grade 1. Resume therapy at a reduced dose.

3. Sepsis

• Incidence: Occurs in 5% of patients, with or without neutropenia.
  • Risk Factors: The presence of biliary obstruction or biliary stent increases the risk of severe or fatal sepsis.
• Monitoring: Watch for signs of infection (e.g., fever, chills) and treat promptly.
• Prevention: Close monitoring in high-risk patients, including those with biliary stents or hepatic compromise.

if coadministered, monitor closely

✔️ Storage Conditions

Store the vials in original cartons at 20°C to 25°C. Retain in the original package to protect from bright light.