Abraxane

Q: Who makes Abraxane?

Abraxane is listed by 1 labeler in the FDA NDC directory, including Abraxis BioScience, LLC.

Paclitaxel · Injection, Powder, Lyophilized, For Suspension · Intravenous

Boxed warning. WARNING: SEVERE MYELOSUPPRESSION
• Do not administer ABRAXANE therapy to patients with baseline neutrophil counts of less than 1,500 cells/mm 3 [see Contraindications (4) ].
• Monitor for neutropenia, which may be severe and result in infection or sepsis [see Warnings and Precautions (5.1 , 5.3) ].
• Perform frequent complete blood cell counts on all patients receiving ABRAXANE [see Warnings and Precautions (5.1 , 5.3) ]. WARNING: SEVERE MYELOSUPPRESSION See full prescribing information for complete boxed warning .
• Do not administer ABRAXANE therapy to patients with baseline neutrophil counts of less than 1,500 cells/mm 3 . ( 4 )
• Monitor for neutropenia, which may be severe and result in infection or sepsis. ( 5.1 , 5.3 )
• Perform frequent complete blood cell counts on all patients receiving ABRAXANE. ( 5.1 , 5.3 )

Uses

1 INDICATIONS AND USAGE 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. ( 1.1 )
• 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. ( 1.2 )
• Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine. ( 1.3 ) 1.1 Metastatic Breast Cancer ABRAXANE is indicated for the treatment of 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. 1.2 Non-Small Cell Lung Cancer ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. 1.3 Adenocarcinoma of the Pancreas ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.

Dosage and administration

• Do not substitute ABRAXANE for other paclitaxel products. ( 2.1 )
• Extravasation : Closely monitor the infusion site for extravasation and infiltration. ( 2.1 )
• 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. ( 2.3 )
• 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. ( 2.4 )
• Use in Patients with Hepatic Impairment: ABRAXANE is not recommended for use in patients with AST > 10 × ULN; or bilirubin > 5 × ULN or with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment. For MBC or NSCLC, reduce starting dose in patients with moderate to severe hepatic impairment. ( 2.5 )
• Dose Reductions for Adverse Reactions : Dose reductions or discontinuation may be needed based on severe hematologic, neurologic, cutaneous, or gastrointestinal toxicities. ( 2.6 ) 2.1 Important Administration Instructions DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS. ABRAXANE has different dosage and administration instructions from other paclitaxel products. Closely monitor the infusion site for extravasation or drug infiltration during administration. Limiting the infusion of ABRAXANE to 30 minutes may reduce the risk of infusion-related reactions [see Adverse Reactions (6.2) ] . Consider premedication in patients who have had prior hypersensitivity reactions to ABRAXANE. Do not re-challenge patients who experience a severe hypersensitivity reaction to ABRAXANE [see Contraindications (4) and Warnings and Precautions (5.5) ] . 2.2 Recommended Dosage for Metastatic Breast Cancer After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for ABRAXANE is 260 mg/m 2 administered intravenously over 30 minutes every 3 weeks. 2.3 Recommended Dosage for Non-Small Cell Lung Cancer The recommended dose of ABRAXANE is 100 mg/m 2 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 ABRAXANE [see Clinical Studies (14.2) ] . 2.4 Recommended Dosage for Adenocarcinoma of the Pancreas The recommended dose of ABRAXANE is 125 mg/m 2 administered as an intravenous infusion over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle. Administer gemcitabine immediately after ABRAXANE on Days 1, 8, and 15 of each 28-day cycle [see Clinical Studies (14.3) ]. 2.5 Dosage Modifications for Hepatic Impairment For patients with moderate or severe hepatic impairment, reduce the starting dose of ABRAXANE as shown in Table 1. Table 1: Recommendations for Starting Dose in Patients with Moderate and Severe Hepatic Impairment AST = Aspartate Aminotransferase; MBC = Metastatic Breast Cancer; NSCLC = Non-Small Cell Lung Cancer; ULN = Upper limit of normal. a Dosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance. b A dose increase to 260 mg/m 2 for patients with metastatic breast cancer or 100 mg/m 2 for patients with non-small cell lung cancer in subsequent courses should be considered if the patient tolerates the reduced dose for two cycles. c Patients with bilirubin levels above the upper limit of normal were excluded from clinical trials for pancreatic or lung cancer. AST Levels Bilirubin Levels ABRAXANE Dose a MBC NSCLC c Adenocarcinoma of Pancreas c Moderate < 10 x ULN AND > 1.5 to ≤ 3 x ULN 200 mg/m 2 b 80 mg/m 2 b not recommended Severe < 10 x ULN AND > 3 to ≤ 5 x ULN 200 mg/m 2 b 80 mg/m 2 b not recommended > 10 x ULN OR > 5 x ULN not recommended not recommended not recommended 2.6 Dosage Modifications for Adverse Reactions Metastatic Breast Cancer Patients who experience severe neutropenia (neutrophils less than 500 cells/mm 3 for a week or longer) or severe sensory neuropathy during ABRAXANE therapy should have dosage reduced to 220 mg/m 2 for subsequent courses of ABRAXANE. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m 2 . For Grade 3 sensory neuropathy hold treatment until resolution to Grade 1 or 2, followed by a dose reduction for all subsequent courses of ABRAXANE [see Contraindications (4) , Warnings and Precautions (5.1 , 5.2) and Adverse Reactions (6.1) ]. Non-Small Cell Lung Cancer
• Do not administer ABRAXANE on Day 1 of a cycle until absolute neutrophil count (ANC) is at least 1500 cells/mm 3 and platelet count is at least 100,000 cells/mm 3 [see Contraindications (4) , Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].
• In patients who develop severe neutropenia or thrombocytopenia withhold treatment until counts recover to an absolute neutrophil count of at least 1500 cells/mm 3 and platelet count of at least 100,000 cells/mm 3 on Day 1 or to an absolute neutrophil count of at least 500 cells/mm 3 and platelet count of at least 50,000 cells/mm 3 on Days 8 or 15 of the cycle. Upon resumption of dosing, permanently reduce ABRAXANE and carboplatin doses as outlined in Table 2 .
• Withhold ABRAXANE for Grade 3-4 peripheral neuropathy. Resume ABRAXANE and carboplatin at reduced doses (see Table 2 ) when peripheral neuropathy improves to Grade 1 or completely resolves [see Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] .

Dosage forms and strengths

For injectable suspension, for intravenous use: white to yellow, sterile lyophilized powder containing 100 mg of paclitaxel formulated as albumin-bound particles in single-dose vial for reconstitution. For injectable suspension: white to yellow, sterile, lyophilized powder containing 100 mg of paclitaxel formulated as albumin-bound particles in single-dose vial for reconstitution. ( 3 )

Contraindications

4 CONTRAINDICATIONS ABRAXANE is contraindicated in patients with:
• Baseline neutrophil counts of < 1,500 cells/mm 3 [see Warnings and Precautions (5.1) ]
• A history of severe hypersensitivity reactions to ABRAXANE [see Warnings and Precautions (5.5) ]
• Neutrophil counts of < 1,500 cells/mm 3 . ( 4 )
• Severe hypersensitivity reactions to ABRAXANE. ( 4 )

Warnings and precautions

• Sensory neuropathy occurs frequently and may require dose reduction or treatment interruption. ( 5.2 )
• 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. ( 5.3 )
• Pneumonitis occurred with the use of ABRAXANE in combination with gemcitabine; permanently discontinue treatment with ABRAXANE and gemcitabine. ( 5.4 )
• Severe hypersensitivity reactions with fatal outcome have been reported. Do not rechallenge with this drug. ( 4 , 5.5 )
• Exposure and toxicity of paclitaxel can be increased in patients with hepatic impairment, consider dose reduction and closely monitor patients with hepatic impairment. ( 2.5 , 5.6 )
• ABRAXANE contains albumin derived from human blood, which has a theoretical risk of viral transmission. ( 5.7 )
• ABRAXANE can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.8 , 8.1 , 8.3 ) 5.1 Severe Myelosuppression Severe myelosuppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC), 47% of patients with non-small cell lung cancer (NSCLC), and 38% of patients with pancreatic cancer. Monitor for severe neutropenia and thrombocytopenia by performing complete blood cell counts frequently, including prior to dosing on Day 1 (for MBC) and Days 1, 8, and 15 (for NSCLC and for pancreatic cancer). Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1,500 cells/mm3 [see Contraindications (4) ] . In the case of severe neutropenia (<500 cells/mm 3 for seven days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with either MBC or NSCLC. In patients with MBC, resume treatment with every-3-week cycles of ABRAXANE after ANC recovers to a level >1,500 cells/mm 3 and platelets recover to a level >100,000 cells/mm 3 . In patients with NSCLC, resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm 3 and platelet count of at least 100,000 cells/mm 3 on Day 1 or to an ANC of at least 500 cells/mm 3 and platelet count of at least 50,000 cells/mm 3 on Days 8 or 15 of the cycle [see Dosage and Administration (2.6) ]. In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm 3 or platelets are less than 50,000 cells/mm 3 and delay initiation of the next cycle if the ANC is less than 1500 cells/mm 3 or platelet count is less than 100,000 cells/mm 3 on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended [see Dosage and Administration (2.6) ]. 5.2 Severe Neuropathy Sensory neuropathy is dose- and schedule-dependent [see Adverse Reactions (6.1) ] . If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to Grade 1 or 2 for metastatic breast cancer or until resolution to ≤ Grade 1 for NSCLC and pancreatic cancer followed by a dose reduction for all subsequent courses of ABRAXANE [see Dosage and Administration (2.6) ] . 5.3 Sepsis Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine. Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis. If a patient becomes febrile (regardless of ANC) initiate treatment with broad spectrum antibiotics. For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC ≥ 1500, then resume treatment at reduced dose levels [see Dosage and Administration (2.6) ] . 5.4 Pneumonitis Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine. Monitor patients for signs and symptoms of pneumonitis and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis. After ruling out infectious etiology and upon making a diagnosis of pneumonitis, permanently discontinue treatment with ABRAXANE and gemcitabine. 5.5 Severe Hypersensitivity Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported. Do not rechallenge patients who experience a severe hypersensitivity reaction to ABRAXANE with this drug [see Contraindications (4) ] . Cross-hypersensitivity between ABRAXANE and other taxane products has been reported and may include severe reactions such as anaphylaxis. Closely monitor patients with a previous history of hypersensitivity to other taxanes during initiation of ABRAXANE therapy. 5.6 Use in Patients with Hepatic Impairment The exposure and toxicity of paclitaxel can be increased in patients with hepatic impairment. Closely monitor patients with hepatic impairment for severe myelosuppression. ABRAXANE is not recommended in patients who have total bilirubin >5 x ULN or AST >10 x ULN. In addition, ABRAXANE is not recommended in patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment (total bilirubin >1.5 x ULN and AST ≤10 x ULN). Reduce the starting dose for patients with moderate or severe hepatic impairment [see Dosage and Administration (2.5) , Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ] . 5.7 Albumin (Human) ABRAXANE contains albumin (human), a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries a remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote.

Side effects

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 [see Adverse Reactions (6.1) ] . 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 [see Adverse Reactions (6.1) ]. The most common serious adverse reactions of ABRAXANE 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 ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%). The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%). The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%). In a randomized open-label trial of ABRAXANE in combination with gemcitabine for pancreatic adenocarcinoma [see Clinical Studies (14.3) ] , the most common (≥ 20%) selected (with a ≥ 5% higher incidence) adverse reactions of ABRAXANE are neutropenia, fatigue, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, pyrexia, vomiting, decreased appetite, rash, and dehydration [see Adverse Reactions (6.1) ] . The most common serious adverse reactions of ABRAXANE (with a ≥ 1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and vomiting (4%). The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are peripheral neuropathy (8%), fatigue (4%), and thrombocytopenia (2%). The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%). The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%).
• The most common adverse reactions (≥ 20%) 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. ( 6.1 )
• The most common adverse reactions (≥ 20%) in NSCLC are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue. ( 6.1 )
• The most common (≥ 20%) adverse reactions of ABRAXANE in adenocarcinoma of the pancreas are neutropenia, fatigue, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, pyrexia, vomiting, decreased appetite, rash, and dehydration. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Metastatic Breast Cancer Table 6 shows the frequency of important adverse reactions in the randomized comparative trial for the patients who received either single-agent ABRAXANE or paclitaxel injection for the treatment of metastatic breast cancer. Table 6: Adverse Reactions in the Randomized Metastatic Breast Cancer Study on an Every-3-Weeks Schedule a Paclitaxel injection patients received premedication. b Includes treatment-related events related to hypersensitivity (e.g., flushing, dyspnea, chest pain, hypotension) that began on a day of dosing. c Severe events are defined as at least Grade 3 toxicity. Percent of Patients ABRAXANE 260 mg/m 2 over 30 min (n=229) Paclitaxel Injection 175 mg/m 2 over 3 h a (n=225) Bone Marrow Neutropenia < 2.0 x 10 9 /L 80 82 < 0.5 x 10 9 /L 9 22 Thrombocytopenia < 100 x 10 9 /L 2 3 < 50 x 10 9 /L <1 <1 Anemia < 11 g/dL 33 25 < 8 g/dL 1 <1 Infections 24 20 Febrile Neutropenia 2 1 Neutropenic Sepsis <1 <1 Bleeding 2 2 Hypersensitivity Reaction b All 4 12 Severe c 0 2 Cardiovascular Vital Sign Changes During Administration Bradycardia <1 <1 Hypotension 5 5 Severe Cardiovascular Events c 3 4 Abnormal ECG All Patients 60 52 Patients with Normal Baseline 35 30 Respiratory Cough 7 6 Dyspnea 12 9 Sensory Neuropathy Any Symptoms 71 56 Severe Symptoms c 10 2 Myalgia / Arthralgia Any Symptoms 44 49 Severe Symptoms c 8 4 Asthenia Any Symptoms 47 39 Severe Symptoms c 8 3 Fluid Retention/Edema Any Symptoms 10 8 Severe Symptoms c 0 <1 Gastrointestinal Nausea Any Symptoms 30 22 Severe Symptoms c 3 <1 Vomiting Any Symptoms 18 10 Severe Symptoms c 4 1 Diarrhea Any Symptoms 27 15 Severe Symptoms c <1 1 Mucositis Any Symptoms 7 6 Severe Symptoms c <1 0 Alopecia 90 94 Hepatic (Patients with Normal Baseline) Bilirubin Elevations 7 7 Alkaline Phosphatase Elevations 36 31 AST (SGOT) Elevations 39 32 Injection Site Reaction <1 1 Other Adverse Reactions Hematologic Disorders Neutropenia was dose dependent and reversible. Among patients with metastatic breast cancer in the randomized trial, neutrophil counts declined below 500 cells/mm 3 (Grade 4) in 9% of the patients treated with a dose of 260 mg/m 2 compared to 22% in patients receiving paclitaxel injection at a dose of 175 mg/m 2 . Pancytopenia has been observed in clinical trials. Infections Infectious episodes were reported in 24% of the patients treated with ABRAXANE. Oral candidiasis, respiratory tract infections and pneumonia were the most frequently reported infectious complications.

Drug interactions

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. ( 7 )

Use in specific populations

• Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available human data on ABRAXANE use in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of paclitaxel formulated as albumin-bound particles to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at doses approximately 2% of the daily maximum recommended human dose on a mg/m 2 basis (see Data ). Advise females of reproductive potential of the potential risk to a fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development studies, intravenous administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy, on gestation days 7 to 17 at doses of 6 mg/m 2 (approximately 2% of the daily maximum recommended human dose on a mg/m 2 basis) caused embryo-fetal toxicities, as indicated by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduction in fetal body weight, and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles. 8.2 Lactation Risk Summary There are no data on the presence of paclitaxel in human milk, or its effect on the breastfed child or on milk production. In animal studies, paclitaxel and/or its metabolites were excreted into the milk of lactating rats (see Data ). Because of the potential for serious adverse reactions in a breastfed child from ABRAXANE, advise lactating women not to breastfeed during treatment with ABRAXANE and for two weeks after the last dose. Data Animal Data Following intravenous administration of radiolabeled paclitaxel to rats on days 9 to 10 postpartum, concentrations of radioactivity in milk were higher than in plasma and declined in parallel with the plasma concentrations. 8.3 Females and Males of Reproductive Potential Based on animal studies and mechanism of action, ABRAXANE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to starting treatment with ABRAXANE. Contraception Females Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with ABRAXANE and for at least six months after the last dose of ABRAXANE. Males Based on findings in genetic toxicity and animal reproduction studies, advise males with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with ABRAXANE and for at least three months after the last dose of ABRAXANE [see Use in Specific Populations (8.1) and Nonclinical Toxicology (13.1) ]. Infertility Females and Males Based on findings in animals, ABRAXANE may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Pharmacokinetics, safety, and antitumor activity of ABRAXANE were assessed in an open-label, dose escalation, dose expansion study (NCT01962103) in 96 pediatric patients aged 1.4 to < 17 years with recurrent or refractory pediatric solid tumors. The maximum tolerated dose (MTD) normalized for body surface area (BSA) was lower in pediatric patients compared to adults. No new safety signals were observed in pediatric patients across these studies. Paclitaxel protein-bound exposures normalized by dose were higher in 96 pediatric patients (aged 1.4 to < 17 years) as compared to those in adults. 8.5 Geriatric Use Of the 229 patients in the randomized study who received ABRAXANE for the treatment of metastatic breast cancer, 13% were at least 65 years of age and < 2% were 75 years or older. This study of ABRAXANE did not include a sufficient number of patients with metastatic breast cancer who were 65 years and older to determine whether they respond differently from younger patients. A subsequent pooled analysis was conducted in 981 patients receiving ABRAXANE 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 ABRAXANE 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 ABRAXANE 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.

Pregnancy

8.1 Pregnancy Risk Summary Based on its mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available human data on ABRAXANE use in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of paclitaxel formulated as albumin-bound particles to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at doses approximately 2% of the daily maximum recommended human dose on a mg/m 2 basis (see Data ). Advise females of reproductive potential of the potential risk to a fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In embryo-fetal development studies, intravenous administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy, on gestation days 7 to 17 at doses of 6 mg/m 2 (approximately 2% of the daily maximum recommended human dose on a mg/m 2 basis) caused embryo-fetal toxicities, as indicated by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduction in fetal body weight, and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles.

Pediatric use

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Pharmacokinetics, safety, and antitumor activity of ABRAXANE were assessed in an open-label, dose escalation, dose expansion study (NCT01962103) in 96 pediatric patients aged 1.4 to < 17 years with recurrent or refractory pediatric solid tumors. The maximum tolerated dose (MTD) normalized for body surface area (BSA) was lower in pediatric patients compared to adults. No new safety signals were observed in pediatric patients across these studies. Paclitaxel protein-bound exposures normalized by dose were higher in 96 pediatric patients (aged 1.4 to < 17 years) as compared to those in adults.

Geriatric use

8.5 Geriatric Use Of the 229 patients in the randomized study who received ABRAXANE for the treatment of metastatic breast cancer, 13% were at least 65 years of age and < 2% were 75 years or older. This study of ABRAXANE did not include a sufficient number of patients with metastatic breast cancer who were 65 years and older to determine whether they respond differently from younger patients. A subsequent pooled analysis was conducted in 981 patients receiving ABRAXANE 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 ABRAXANE 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 ABRAXANE 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 ABRAXANE 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.

Overdosage

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

Description

11 DESCRIPTION ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) is paclitaxel formulated as albumin-bound nanoparticles with a mean particle size of approximately 130 nanometers. Paclitaxel exists in the particles in a non-crystalline, amorphous state. Paclitaxel is a microtubule inhibitor. The chemical name for paclitaxel is 5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2 R ,3 S )- N -benzoyl-3-phenylisoserine. The empirical formula is C 47 H 51 NO 14 and the molecular weight is 853.91. Paclitaxel has the following structural formula: Paclitaxel is a white to off-white crystalline powder. It is highly lipophilic, insoluble in water, and melts at approximately 216°C to 217°C. ABRAXANE is supplied as a white to yellow, sterile, lyophilized powder for reconstitution with 20 mL of 0.9% Sodium Chloride Injection, USP prior to intravenous infusion. Each single‑dose vial contains 100 mg of paclitaxel (bound to human albumin) and approximately 900 mg of human albumin (containing sodium caprylate and sodium acetyltryptophanate). Each milliliter (mL) of reconstituted suspension contains 5 mg paclitaxel formulated as albumin‑bound particles. ABRAXANE is free of solvents. Structural Formula for Paclitaxel

Mechanism of action

12.1 Mechanism of Action 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.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) is a white to yellow, sterile lyophilized powder supplied as: NDC : 68817-134-50 100 mg of paclitaxel in a single-dose vial, individually packaged in a carton. 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. Abraxane is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1

Storage

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. Abraxane is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1

Patient information

Advise the patient to read the approved patient labeling (Patient Information). Severe Myelosuppression
• Patients must be informed of the risk of low blood cell counts and severe and life-threatening infections and instructed to contact their healthcare provider immediately for fever or evidence of infection [see Warnings and Precautions (5.1) , (5.3) ]. Severe Neuropathy
• Patients must be informed that sensory neuropathy occurs frequently with ABRAXANE and patients should advise their healthcare providers of numbness, tingling, pain, or weakness involving the extremities [see Warnings and Precautions (5.2) ]. Pneumonitis
• Instruct patients to contact their healthcare provider immediately for sudden onset of dry persistent cough, or shortness of breath [see Warnings and Precautions (5.4) ] . Severe Hypersensitivity
• Instruct patients to contact their healthcare provider for signs of an allergic reaction, which could be severe and sometimes fatal [see Warnings and Precautions (5.5) ]. Common Adverse Reactions
• Explain to patients that alopecia, fatigue/asthenia, and myalgia/arthralgia occur frequently with ABRAXANE.
• Instruct patients to contact their healthcare providers for persistent vomiting, diarrhea, or signs of dehydration [see Adverse Reactions (6) ] . Embryo-Fetal Toxicity
• ABRAXANE injection can cause fetal harm. Advise patients to avoid becoming pregnant while receiving this drug. Females of reproductive potential should use effective contraception during treatment with ABRAXANE and for at least six months after the last dose of ABRAXANE [see Warnings and Precautions (5.8) and Use in Specific Populations (8.1 , 8.3) ].
• Advise male patients with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with ABRAXANE and for at least three months after the last dose of ABRAXANE [see Use in Specific Populations (8.3) ]. Lactation
• Advise patients not to breastfeed while taking ABRAXANE and for two weeks after receiving the last dose [see Use in Specific Populations (8.2) ] . Infertility
• Advise males and females of reproductive potential that ABRAXANE may impair fertility [see Use in Specific Populations (8.3) ].

Label text from the FDA structured product label by Abraxis BioScience, LLC (revised Oct 31, 2022). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Paclitaxel in 1 product

Abraxane NDC products (1)

NDC	Strength & form	Labeler	Type
68817-134	Paclitaxel 100 mg/20mL Injection, Powder, Lyophilized, For Suspension	Abraxis BioScience, LLC	NDA

Frequently asked questions

What is Abraxane used for?

What are the side effects of Abraxane?

Who makes Abraxane?

Abraxane is listed by 1 labeler in the FDA NDC directory, including Abraxis BioScience, LLC.