Paclitaxel

ABRAXANE is a microtubule inhibitor indicated for the treatment of: • Metastatic breast cancer, after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. • Locally advanced or metastatic non-small cell lung cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. • Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.

ABRAXANE is a microtubule inhibitor that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. Paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.

• Do not substitute ABRAXANE for other paclitaxel products. • Extravasation: Closely monitor the infusion site for extravasation and infiltration. • Metastatic Breast Cancer (MBC): Recommended dosage of ABRAXANE is 260 mg/m 2 intravenously over 30 minutes every 3 weeks. ( 2. 2 ) • Non-Small Cell Lung Cancer (NSCLC): Recommended dosage of ABRAXANE is 100 mg/m 2 intravenously over 30 minutes on Days 1, 8, and 15 of each 21-day cycle, administer carboplatin on Day 1 of each 21-day cycle immediately after ABRAXANE. • Adenocarcinoma of the Pancreas: Recommended dosage of ABRAXANE is 125 mg/m 2 intravenously over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle, administer gemcitabine on Days 1, 8, and 15 of each 28-day cycle immediately after ABRAXANE.

ABRAXANE is contraindicated in patients with: • Baseline neutrophil counts of < 1,500 cells/mm 3 • A history of severe hypersensitivity reactions to ABRAXANE • Neutrophil counts of < 1,500 cells/mm 3. • Severe hypersensitivity reactions to ABRAXANE.

Boxed warning (severe myelosuppression •): Do not administer ABRAXANE therapy to patients with baseline neutrophil counts of less than 1,500 cells/mm 3. • Monitor for neutropenia, which may be severe and result in infection or sepsis. • Perform frequent complete blood cell counts on all patients receiving ABRAXANE. WARNING: SEVERE MYELOSUPPRESSION. • Sensory neuropathy occurs frequently and may require dose reduction or treatment interruption. • Sepsis occurred in patients with or without neutropenia who received ABRAXANE in combination with gemcitabine, interrupt ABRAXANE and gemcitabine until sepsis resolves, and if neutropenia, until neutrophils are at least 1500 cells/mm 3, then resume treatment at reduced dose levels. • Pneumonitis occurred with the use of ABRAXANE in combination with gemcitabine, permanently discontinue treatment with ABRAXANE and gemcitabine.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (≥ 20%) with single-agent use of ABRAXANE in metastatic breast cancer are alopecia, neutropenia, sensory neuropathy, abnormal ECG, fatigue/asthenia, myalgia/arthralgia, AST elevation, alkaline phosphatase elevation, anemia, nausea, infections, and diarrhea. The most common adverse reactions (≥ 20%) of ABRAXANE in combination with carboplatin for non-small cell lung cancer are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue.

The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4. Use caution when concomitantly administering ABRAXANE with inhibitors or inducers of either CYP2C8 or CYP3A4.

Store the vials in original cartons at 20°C to 25°C (68°F to 77°F). Retain in the original package to protect from bright light.