Abraxane (paclitaxel protein-bound particles)

Abraxane is a prescription medicine used to treat:

• advanced breast cancer in people who have already received certain other medicines for their cancer.
• advanced non-small cell lung cancer (NSCLC), in combination with carboplatin in people who cannot be treated with surgery or radiation.
• advanced pancreatic cancer, when used in combination with gemcitabine as the first medicine for advanced pancreatic cancer.

It is not known if Abraxane is safe or effective in children.

Abraxane may cause serious side effects, including:

• severe decreased blood cell counts. Abraxane can cause a severe decrease in neutrophils, a type of white blood cell which helps fight infections, and blood cells called platelets which help to clot blood. Your healthcare provider will check your blood cell count during your treatment with Abraxane.
• severe nerve problems (neuropathy). Tell your healthcare provider if you have numbness, tingling, pain, or weakness in your hands or feet.
• severe infection (sepsis). If you receive Abraxane in combination with gemcitabine, infections can be severe and lead to death. Tell your healthcare provider right away if you have a fever (temperature greater than 100.4° F) or develop signs of infection.
• lung or breathing problems. If you receive Abraxane in combination with gemcitabine, lung or breathing problems may be severe and can lead to death. Tell your healthcare provider right away if you suddenly get a dry cough that will not go away or shortness of breath.
• severe allergic reactions. Severe allergic reactions are medical emergencies that can happen in people who receive Abraxane and can lead to death. You may have an increased risk of having an allergic reaction to Abraxane if you are allergic to other taxane medicines. Your healthcare provider will monitor you closely for allergic reactions during your infusion of Abraxane. Tell your healthcare provider right away if you get any of these signs of a serious allergic reaction: trouble breathing, sudden swelling of your face, lips, tongue, throat, or trouble swallowing, hives (raised bumps), rash, or redness all over your body.

The most common side effects of Abraxane in people with breast cancer include:

• hair loss
• numbness, tingling, pain, or weakness in the hands or feet
• tiredness
• changes in your liver function tests
• nausea
• diarrhea
• infections
• decreased white blood cell count
• abnormal heartbeat
• joint and muscle pain
• low red blood cell count (anemia). Red blood cells carry oxygen to your body tissues. Tell your healthcare provider if you feel weak, tired, or short of breath.

The most common side effects of Abraxane in people with non-small cell lung cancer include:

• low red blood cell count (anemia)
• decreased platelet cell count
• numbness, tingling, pain, or weakness in the hands or feet
• tiredness
• decreased white blood cell count
• hair loss
• nausea

The most common side effects of Abraxane in people with pancreatic cancer include:

• decreased white blood cell count
• numbness, tingling, pain, or weakness in the hands or feet
• hair loss
• diarrhea
• vomiting
• rash
• tiredness
• nausea
• swelling in the hands or feet
• fever
• decreased appetite
• signs of dehydration including thirst, dry mouth, dark yellow urine, decreased urine, headache, or muscle cramps Tell your healthcare provider if you have vomiting, diarrhea, or signs of dehydration that does not go away. Abraxane may cause fertility problems in males and females, which may affect your ability to have a child.

Talk to your healthcare provider if this is a concern for you. These are not all of the possible side effects of Abraxane. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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.
• 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.

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/m² administered intravenously over 30 minutes every 3 weeks.

Recommended Dosage For Non-Small Cell Lung Cancer

• The recommended dose of Abraxane 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 Abraxane.

Recommended Dosage For Adenocarcinoma Of The Pancreas

• The recommended dose of Abraxane 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 Abraxane on Days 1, 8, and 15 of each 28-day cycle.

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

Dosage Modifications For Adverse Reactions

Metastatic Breast Cancer

• Patients who experience severe neutropenia (neutrophils less than 500 cells/mm³ for a week or longer) or severe sensory neuropathy during Abraxane therapy should have dosage reduced to 220 mg/m² for subsequent courses of Abraxane.
• For recurrence of severe neutropenia or severe sensory neuropathy, additional dose reduction should be made to 180 mg/m².
• 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.

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/mm³ and platelet count is at least 100,000 cells/mm³.
• In patients who develop severe neutropenia or thrombocytopenia withhold treatment until counts recover to an absolute neutrophil count of at least 1500 cells/mm³ and platelet count of at least 100,000 cells/mm³ on Day 1 or to an absolute neutrophil count of at least 500 cells/mm³ and platelet count of at least 50,000 cells/mm³ 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.

Table 2: Permanent Dose Reductions for Hematologic and Neurologic Adverse Reactions in NSCLC

Adenocarcinoma Of The Pancreas

Dose level reductions for patients with adenocarcinoma of the pancreas, as referenced in Tables 4 and 5, are provided in Table 3.

Table 3: Dose Level Reductions for Patients with Adenocarcinoma of the Pancreas

Recommended dose modifications for neutropenia and thrombocytopenia for patients with adenocarcinoma of the pancreas are provided in Table 4.

Table 4: Dose Recommendation and Modifications for Neutropenia and/or Thrombocytopenia at the Start of a Cycle orwithin a Cycle for Patients with Adenocarcinoma of the Pancreas

Recommended dose modifications for other adverse reactions in patients with adenocarcinoma of the pancreas are provided in Table 5.

Table 5: Dose Modifications for Other Adverse Reactions in Patients with Adenocarcinoma of the Pancreas

• 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.

• Based on its mechanism of action and findings in animals, Abraxane can cause fetal harm when administered to a pregnant woman.
• There are no available human data on Abraxane use in pregnant women to inform the drug-associated risk.
• 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.
• 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.