Nab-Paclitaxel [Nanoparticle Albumin-Bound Paclitaxel]

• Approved Indications:
• Breast Cancer: Treatment of locally advanced or metastatic breast cancer, especially in patients who have failed combination chemotherapy or relapsed within 6 months of adjuvant chemotherapy.
• Non-Small Cell Lung Cancer (NSCLC): First-line treatment in combination with carboplatin for patients with locally advanced or metastatic disease.
• Pancreatic Cancer: Treatment of metastatic adenocarcinoma of the pancreas in combination with gemcitabine.
• Off-Label Uses:
• Investigational use in other solid tumors, including ovarian, bladder, and esophageal cancers, based on clinical trials.

• Adults:
• Breast Cancer: 260 mg/m² administered intravenously over 30 minutes every 3 weeks.
• NSCLC: 100 mg/m² administered intravenously over 30 minutes on days 1, 8, and 15 of a 21-day cycle in combination with carboplatin.
• Pancreatic Cancer: 125 mg/m² administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days in combination with gemcitabine.
• Pediatrics: Safety and efficacy have not been established.
• Elderly: No specific dosage adjustment recommended; monitor for toxicity.
• Renal Impairment: No dose adjustment necessary.
• Hepatic Impairment: Use with caution; dose reduction is recommended in moderate to severe hepatic impairment.
• Administration: Intravenous infusion.
• Dose Modifications: Adjustments may be required based on toxicity such as neutropenia or peripheral neuropathy.

Nab-paclitaxel consists of paclitaxel bound to albumin nanoparticles, facilitating enhanced delivery to tumor cells via albumin receptor (gp60) mediated transport and binding to the tumor extracellular matrix protein SPARC. Paclitaxel stabilizes microtubules by promoting tubulin polymerization and preventing depolymerization. This disrupts mitotic spindle function, leading to cell cycle arrest at the G2/M phase and triggering apoptosis, thereby exerting cytotoxic effects against rapidly dividing cancer cells.

• Absorption: Administered intravenously with complete bioavailability.
• Distribution: Widely distributed; enhanced tumor delivery via albumin receptor-mediated transcytosis.
• Metabolism: Extensively metabolized in the liver primarily by CYP2C8 and CYP3A4 enzymes.
• Elimination: Mainly biliary excretion into feces; minor renal excretion.
• Half-life: Approximately 27 hours.
• Onset of Action: Therapeutic effects develop after initial dosing cycles; cytotoxicity is cumulative.

• Pregnancy Category: FDA Category D — evidence of fetal risk exists; use only if benefits outweigh risks.
• Lactation: Paclitaxel is excreted in human milk; breastfeeding is not recommended during treatment due to potential harm to the infant.
• Data: Limited human data; exercise caution.

• Primary Class: Antineoplastic agent
• Subclass: Taxane; antimicrotubule agent
• Formulation: Nanoparticle albumin-bound paclitaxel (solvent-free formulation)

• Known hypersensitivity to paclitaxel, albumin, or formulation excipients.
• Severe neutropenia or bone marrow suppression.
• Severe hepatic impairment without dose adjustment.

• Hypersensitivity: Severe allergic reactions, including anaphylaxis, may occur. Emergency treatment facilities must be available.
• Myelosuppression: Monitor for neutropenia; perform regular complete blood counts.
• Peripheral Neuropathy: Monitor for symptoms; dose modification may be necessary.
• Hepatic Impairment: Use caution; monitor liver function tests.
• Cardiac Effects: Rare reports of arrhythmias and myocardial ischemia.

• Common:
• Hematologic: neutropenia, anemia, thrombocytopenia.
• Neurologic: peripheral neuropathy (numbness, tingling).
• Gastrointestinal: nausea, vomiting, diarrhea, mucositis.
• Musculoskeletal: arthralgia, myalgia.
• Dermatologic: alopecia, rash.
• Serious:
• Hypersensitivity reactions.
• Severe neutropenia leading to infection.
• Hepatotoxicity.
• Rare cardiac toxicity.
• Timing: Usually begins after the first cycle and may worsen with cumulative dosing.

• CYP3A4 and CYP2C8 inhibitors (e.g., ketoconazole): Increase paclitaxel levels, increasing toxicity risk.
• CYP3A4 and CYP2C8 inducers (e.g., rifampin): Decrease paclitaxel levels, reducing efficacy.
• Concurrent myelosuppressive drugs: Increased risk of bone marrow suppression.
• Drug-Food and Drug-Alcohol: No significant interactions reported; avoid excessive alcohol due to liver considerations.

• Recognition of nab-paclitaxel as preferred taxane formulation due to lower solvent-related toxicity.
• Updated dosing recommendations in hepatic impairment to reduce toxicity.
• Inclusion in standard combination regimens for pancreatic cancer treatment in international guidelines.
• Emphasis on neuropathy monitoring and early dose adjustment in clinical practice guidelines.

• Store between 20°C and 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Protect from light and freezing.
• Keep in original packaging until use.
• Do not refrigerate.
• Ready-to-use formulation; no reconstitution needed.
• Use immediately after opening; do not store diluted solutions.