Paclitaxel Protein Bound

Paclitaxel protein-bound is used to treat pancreatic cancer, breast cancer, and locally advanced or metastatic non-small cell lung cancer (NSCLC).

Paclitaxel protein-bound is available under the following different brand names: Abraxane.

Dosages of Paclitaxel Protein Bound:

Dosage Forms and Strengths

Injection, Lyophilized Powder for Reconstitution

• 100 mg/vial

Dosage Considerations – Should be Given as Follows:

Pancreatic Cancer

• Indicated for metastatic adenocarcinoma of the pancreas as first-line treatment in combination with gemcitabine
• 125 mg/m² intravenously (IV) infused over 30-40 minutes on Days 1, 8 and 15 of each 28-day cycle
• Administer gemcitabine 1000 mg/m² IV infused over 30-40 minutes immediately after paclitaxel protein bound on Days 1, 8 and 15 of each 28-day cycle

Dosage modifications (pancreatic cancer)

• 1st dose reduction: 100 mg/m² (paclitaxel); 800 mg/² (gemcitabine)
• 2nd dose reduction: 75 mg/² (paclitaxel); 600 mg/² (gemcitabine)
• Discontinue if additional dose reduction required

Dosage modifications (pancreatic cancer – hematologic toxicities)

• Cycle Day 1: ANC less than 1500/mm³ or platelets less than 100,000/mm³ - Delay doses until recovery
• Cycle Day 8: ANC 500 to less than 1000/mm³ or platelets 50,000 to less than 75,000/mm³ - Reduce 1 dose level
• Cycle Day 8: ANC less than 500/mm³ or platelets less than 50,000/mm³ - Withhold doses
• Cycle Day 15: ANC 500 to less than 1000/mm³ or platelets 50,000 to less than 75,000/mm³ - Reduce 1 dose level from Day 8
• Cycle Day 15: ANC less than 500/mm³ or platelets less than 50,000/mm³ - Withhold doses
• Cycle Day 15 (if Day 8 doses withheld): ANC greater than 1000/mm³ or platelets 75,000/mm³ or greater - Reduce 1 dose level from Day 1
• Cycle Day 15 (if Day 8 doses withheld): ANC 500 to less than 1000/mm³ or platelets 50,000 to less than 75,000/mm³ - Reduce 2 dose levels from Day 1
• Cycle Day 15 (if Day 8 doses withheld): ANC less than 500/mm³ or platelets less than 50,000 /mm³ - Withhold doses

Breast Cancer

• Microtubule inhibitor 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 contraindicated
• 260 mg/m² IV infused over 30 minutes every 3 weeks

Dosage modifications (breast cancer)

• Severe neutropenia (less than 500 cells/mm³) or severe sensory neuropathy: Decrease dose to 220 mg/m²
• Recurrence of severe neutropenia or severe sensory neuropathy: Decrease dose to 180 mg/m²
• Grade 3 sensory neuropathy: Hold treatment until resolution to grade 1 or 2, followed by a dose reduction for all subsequent courses

Non-Small Cell Lung Cancer

• Indicated for 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
• 100 mg/m² IV infused over 30 minutes on Days 1, 8, and 15 of each 21-day cycle, PLUS
• Carboplatin AUC 6 mg/minute/mL IV on Day 1 of each 21-day cycle immediately after paclitaxel protein-bound infusion

Dosage modifications (NSCLS)

• Do not administer on Day 1 of a cycle until ANC is at least 1500 cells/mm³ and platelet count is at least 100,000 cells/mm³
• Severe neutropenia or thrombocytopenia: Withhold treatment until counts recover to an ANC of at least 1500 cells/mm³ and platelet count of at least 100,000 cells/mm³ on Day 1 or an ANC of at least 500 cells/mm³ and platelet count of at least 50,000 cells/mm³ on Days 8 or 15 of the cycle
• Grade 3-4 peripheral neuropathy: Withhold dose; resume paclitaxel protein-bound and carboplatin at reduced doses when peripheral neuropathy improves to Grade 1 or completely resolves

Permanent dose reductions (NSCLC)

• Neutropenic fever (ANC less than 500/mm³ and a fever greater than 38°C) or next cycle delayed by more than 7 days for ANC less than 1500/mm³ or ANC less than 500/mm³ for more than 7 days or severe sensory neuropathy (grade 3 or 4):
• First occurrence: reduce dose to 75 mg/m² (and decrease carboplatin dose to 4.5 AUC mg/minute/mL)
• Second occurrence: reduce dose to 50 mg/m² (and decrease carboplatin dose to 3 AUC mg/minute/mL)
• Third occurrence: Discontinue treatment
• Platelets less than 50,000/mm³:
• First occurrence: reduce dose to 75 mg/m² (and decrease carboplatin dose to 4.5 AUC mg/minute/mL)
• Second occurrence: Discontinue treatment

Hepatic Impairment

Breast cancer

• Mild (AST less than 10 x ULN; bilirubin greater than ULN to 1.5 X ULN): No dose adjustment is required
• Moderate (AST less than 10 x ULN; bilirubin greater than 1.5 to up to 3 x ULN): Reduce starting dose to 200 mg/m²; may increase up to 260 mg/m² if the patient tolerates reduced dose for two cycles
• Severe: (AST less than 10 x ULN; bilirubin greater than 3 to up to 5 x ULN): Reduce starting dose to 200 mg/m²; may increase up to 260 mg/m² if the patient tolerates reduced dose for two cycles
• AST greater than 10 x ULN or bilirubin greater than 5 X ULN: Do not administer paclitaxel protein-bound

NSCLC

• Mild (AST less than 10 x ULN; bilirubin greater than ULN to 1.5 X ULN): No dose adjustment is required
• Moderate (AST less than 10 x ULN; bilirubin greater than 1.5 to up to 3 x ULN): Reduce starting dose to 80 mg/m²; may increase up to 100 mg/m² if the patient tolerates reduced dose for two cycles
• Severe: (AST less than 10 x ULN; bilirubin greater than 3 to up to 5 x ULN): Reduce starting dose to 80 mg/m²; may increase up to 100 mg/m² if the patient tolerates reduced dose for two cycles
• AST greater than 10 x ULN or bilirubin greater than 5 X ULN: Do not administer paclitaxel protein-bound

Pancreatic cancer

• Mild (AST less than 10 x ULN; bilirubin greater than ULN to 1.5 X ULN): No dose adjustment is required
• Moderate-to-severe (AST less than 10 x ULN; bilirubin greater than 1.5-5 x ULN): Not recommended
• AST greater than 10 x ULN or bilirubin greater than 5 X ULN: Do not administer paclitaxel protein-bound

Administration

• Use cytotoxic handling precautions
• Monitor for extravasation during infusion
• Premedication for hypersensitivity reaction is NOT required

Safety and efficacy not established in pediatric patients.

Side effects of Paclitaxel Protein Bound may include:

• Hair loss
• Low white blood cell count (neutropenia)
• Nerve damage
• Abnormal EKG
• Weakness/lethargy
• Muscle pain
• Joint pain
• AST increased
• Alkaline phosphatase increased
• Anemia
• Nausea
• Diarrhea
• Infections
• Vomiting
• Shortness of breath
• Edema
• Cough
• Inflammation of mucous membranes
• Bilirubin increased
• Hypotension, during infusion
• Hypersensitivity reactions
• Low platelets (thrombocytopenia)
• Febrile neutropenia
• Bleeding

Postmarketing side effects of paclitaxel protein-bound reported include:

• Hypersensitivity: Severe hypersensitivity reactions
• Cardiovascular: Congestive heart failure, left ventricular dysfunction, and atrioventricular block; most of the individuals were previously exposed to cardiotoxic drugs, such as anthracyclines, or had an underlying cardiac history
• Respiratory: Interstitial pneumonia, pulmonary embolism, lung fibrosis
• Neurologic: Cranial nerve palsies, vocal cord paresis, autonomic neuropathy resulting in paralytic ileus
• Vision Disorders: Persistent optic nerve damage; reduced visual acuity due to cystoid macular edema
• Hepatic: Hepatic necrosis and hepatic encephalopathy leading to death
• Gastrointestinal: Intestinal obstruction, intestinal perforation, pancreatitis, ischemic colitis, neutropenic enterocolitis (typhlitis)
• Injection Site Reaction: Extravasation, severe events such as phlebitis, cellulitis, induration, necrosis, and fibrosis (may be delayed by 7-10 ten days)
• Metabolic and nutritional disorders: Tumor lysis syndrome

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Paclitaxel protein-bound has no listed severe interactions with other drugs.
• Serious interactions of paclitaxel protein-bound include:
  • adenovirus types 4 and 7 live, oral
  • apalutamide
  • deferiprone
  • erdafitinib
  • idelalisib
  • influenza virus vaccine trivalent, adjuvanted
  • ivosidenib
  • lasmiditan
  • nefazodone
  • palifermin
  • quinidine
  • voxelotor
• Paclitaxel protein-bound has moderate interactions with at least 109 different drugs.
• Paclitaxel protein-bound has mild interactions with at least 69 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains Paclitaxel Protein Bound. Do not take Abraxane if you are allergic to paclitaxel protein-bound or any ingredients contained in this drug.
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Black Box Warnings

• Should not be administered if baseline neutrophil counts less than 1,500 cells/mm³; frequent monitoring of peripheral blood cell counts for all patients recommended to avoid bone marrow suppression
• An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of the drug in solution; do not substitute for or with other paclitaxel formulations

Contraindications

• Neutrophils less than 1500 cells/mm³
• Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, reported; do not re-challenge in patients who experience a severe hypersensitivity

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Paclitaxel Protein Bound?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Paclitaxel Protein Bound?"

Cautions

• Causes myelosuppression; monitor complete blood count (CBC) and withhold and/or reduce the dose as needed
• Sensory neuropathy occurs frequently and may require dose reduction or treatment interruption
• Sepsis occurred in 5% of patients with or without neutropenia; biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis
• Pneumonitis, including fatalities, occurred in 4% of patients
• Exposure and toxicity increased with hepatic impairment; particularly from myelosuppression; closely monitor for development of profound myelosuppression; monitor AST and bilirubin and adjust the dose if needed
• Contains albumin derived from human blood which has a theoretical risk of viral transmission
• Fetal harm may occur when administered to a pregnant woman; women of childbearing potential should avoid becoming pregnant
• Men should not father a child while taking paclitaxel
• CYP3A4 and CYP2C8 substrate; inducers or inhibitors of these isoenzymes may alter metabolism; if co-administered, monitor closely

Pregnancy and Lactation

• Based on its mechanism of action and findings in animals, paclitaxel protein-bound therapy can cause fetal harm when administered to a pregnant woman. There are no available human data to inform a 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 an mg/m² basis. Females of reproductive potential should be advised of the potential risk to a fetus. Females of reproductive potential should have a pregnancy test before starting treatment.
• Paclitaxel protein-bound therapy can cause fetal harm when administered to a pregnant woman. Females of reproductive potential are advised to use effective contraception and avoid becoming pregnant during treatment with paclitaxel protein-bound and for at least six months after the last dose. Based on findings in genetic toxicity and animal reproduction studies, males with female partners of reproductive potential are advised to use effective contraception and avoid fathering a child during treatment with paclitaxel protein-bound and for at least three months after the last dose.
• There are no data on the presence of paclitaxel protein-bound in human milk, or its effect on a breastfed child or milk production. In animal studies, paclitaxel and/or its metabolites were excreted into the milk of lactating rats. Because of the potential for serious adverse reactions in a breastfed child from therapy, women are advised not to breastfeed during treatment with paclitaxel protein-bound and for two weeks after the last dose.