Nab-Xelpac IV Infusion

Nab-Paclitaxelis 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.

Metastatic Breast Cancer: After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for Nab-Paclitaxel is 260 mg/m² administered intravenously over 30 minutes every 3 weeks.

Non-Small Cell Lung Cancer: The recommended dose of Nab-Paclitaxel is 100 mg/m² administered as an intravenous infusion 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 Nab-Paclitaxel.

Adenocarcinoma Of The Pancreas: The recommended dose of Nab-Paclitaxel is 125 mg/m² administered as an intravenous infusion over 30-40 minutes on Days 1, 8 and 15 of each 28-day cycle. Administer gemcitabine immediately after Nab-Paclitaxel on Days 1, 8 and 15 of each 28-day cycle.

Dosage In Patients With Hepatic Impairment: For patients with mild hepatic impairment (total bilirubin greater than ULN and less than or equal to 1.5 x ULN and aspartate aminotransferase [AST] less than or equal to 10 x ULN), no dose adjustments are required, regardless of indication.

Do not administer Nab-Paclitaxel to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment. Do not administer Nab-Paclitaxel to patients with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN regardless of indication as these patients have not been studied.

The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. Caution should be exercised when administering Nab-Xelpac concomitantly with medicines known to inhibit (e.g., ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) or induce (e.g., rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine) either CYP2C8 or CYP3A4.

Nab-Paclitaxel should not be used in patients who have baseline neutrophil counts of <1,500 cells/mm³. Patients who experience a severe hypersensitivity reaction to Nab-Paclitaxel should not be rechallenged with the drug.

The most common adverse reactions ( ≥20%) with single-agent use of Nab-Xelpac 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 Nab-Xelpac in combination with carboplatin for non-small cell lung cancer are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue.

The most common serious adverse reactions of Nab-Xelpac in combination with carboplatin for non-small cell lung cancer are anemia (4%) and pneumonia (3%).

The most common adverse reactions resulting in permanent discontinuation of Nab-Xelpac are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%).

The most common adverse reactions resulting in dose reduction of Nab-Xelpac are neutropenia (24%), thrombocytopenia (13%), and anemia (6%).

The most common adverse reactions leading to withholding or delay in Nab-Xelpac dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%).

Pregnancy Category D. Nab-Paclitaxel can cause fetal harm when administered to a pregnant woman. Administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy at doses lower than the maximum recommended human dose, based on body surface area, caused embryo-fetal toxicities, including intrauterinemortality, increased resorptions, reduced numbers of live fetuses, and malformations.

There are no adequate and well-controlled studies in pregnant women receiving Nab-Paclitaxel. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving Nab-Paclitaxel

It is not known whether paclitaxel is excreted in human milk. Paclitaxel and/or its metabolites were excreted into the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: The safety and effectiveness of Nab-Xelpac in pediatric patients have not been evaluated.

Geriatric Use: Of the 229 patients in the randomized study who received Nab-Xelpac for the treatment of metastatic breast cancer, 13% were at least 65 years of age and < 2% were 75 years or older. No toxicities occurred notably more frequently among patients who received Nab-Xelpac.

A subsequent pooled analysis was conducted in 981 patients receiving Nab-Xelpac monotherapy for metastatic breast cancer, of which 15% were 65 years of age or older and 2% were 75 years of age or older. A higher incidence of epistaxis, diarrhea, dehydration, fatigue and peripheral edema was found in patients 65 years of age or older.

Of the 514 patients in the randomized study who received Nab-Xelpac and carboplatin for the first-line treatment of non-small cell lung cancer, 31% were 65 years or older and 3.5% were 75 years or older. Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients 65 years or older compared to patients younger than 65 years old. No overall difference in effectiveness, as measured by response rates, was observed between patients 65 years or older compared to patients younger than 65 years old.

Of the 431 patients in the randomized study who received Nab-Xelpac and gemcitabine for the first-line treatment of pancreatic adenocarcinoma, 41% were 65 years or older and 10% were 75 years or older. No overall differences in effectiveness were observed between patients who were 65 years of age or older and younger patients. Diarrhea, decreased appetite, dehydration and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old. Clinical studies of Nab-Xelpac did not include sufficient number of patients with pancreatic cancer who were 75 years and older to determine whether they respond differently from younger patients.

Patients With Hepatic Impairment: The exposure to paclitaxel may be higher in patients with hepatic impairment than in patients with normal hepatic function. Reduce  Nab-Xelpac starting dose in patients with moderate to severe hepatic impairment. Do not administer Nab-Xelpac to patients with total bilirubin > 5 x ULN or AST> 10 x ULN. Do not administer to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment.

Patients With Renal Impairment: Adjustment of the starting Nab-Xelpac dose is not required for patients with mild to moderate renal impairment (estimated creatinine clearance ≥ 30 to < 90 mL/min). There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min).

There is no known antidote for Nab-Xelpac overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, sensory neurotoxicity, and mucositis.

Cytotoxic Chemotherapy

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