Abraxane (paclitaxel protein-bound particles)

Abraxane is a prescription medicine used to treat:

• advancedbreast cancerin people who have already received certain other medicines for theircancer.
• advancednon-small cell lung cancer(NSCLC), in combination with carboplatin in people who cannot be treated with surgery orradiation.
• advancedpancreatic cancer, when used in combination with gemcitabine as the first medicine for advancedpancreatic cancer.

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

Abraxane可能导致严重的副作用,inc .luding:

• 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, orweaknessin your hands orfeet.
• 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 afever(temperature greater than 100.4° F) or develop signs of infection.
• lung orbreathingproblems.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 drycoughthat will not go away orshortness of breath.
• severeallergicreactions.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 anallergic reactionto 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(raisedbumps),rash, or redness all over your body.

The most common side effects of Abraxane in people withbreast cancerinclude:

• hair loss
• numbness, tingling,pain, or weakness in the hands or feet
• tiredness
• changes in yourliver functiontests
• nausea
• diarrhea
• infections
• decreased white blood cell count
• abnormal heartbeat
• joint andmuscle pain
• low red blood cell count(anemia).Red blood cellscarry 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 cancerinclude:

• 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 withpancreatic cancerinclude:

• 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 ofdehydrationincludingthirst,dry mouth, dark yellow urine, decreased urine,头疼, ormuscle crampsTell your healthcare provider if you havevomiting,diarrhea, or signs ofdehydrationthat does not go away. Abraxane may causefertilityproblems 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 combinationchemotherapyfor metastaticbreast canceror relapse within 6 months ofadjuvant 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

	AST水平		Bilirubin Levels	Abraxane Dosea
				MBC	NSCLCc	Adenocarcinoma of Pancreasc
Moderate	<10xULN	AND	> 1.5 to ≤ 3 x ULN	200 mg/m²b	80 mg/m²b	not recommended
Severe	<10x ULN	AND	> 3 to ≤ 5 x ULN	200 mg/m²b	80 mg/m²b	not recommended
	>10x ULN	OR	> 5 x ULN	not recommended	not recommended	not recommended
AST = Aspartate Aminotransferase; MBC = Metastatic Breast Cancer; NSCLC = Non-Small Cell Lung Cancer; ULN = Upper limit of normal. aDosage recommendations are for the first course of therapy. The need for further dose adjustments in subsequent courses should be based on individual tolerance. bA dose increase to 260 mg/m² for patients with metastatic breast cancer or 100 mg/m² for patients with non-small cell lung cancer in subsequent courses should be considered if the patient tolerates the reduced dose for two cycles. cPatients with bilirubin levels above the upper limit of normal were excluded from clinical trials for pancreatic or lung cancer.

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

• 不管理Abraxane周期单元的第一天吗ilabsolute neutrophil count(ANC) is at least 1500 cells/mm³ andplatelet countis at least 100,000 cells/mm³.
• In patients who develop severe neutropenia orthrombocytopenia拒绝治疗,直到abso计数恢复lute 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 3-4peripheral 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

Adverse Reaction	Occurrence	Weekly Abraxane Dose (mg/m²)	Every 3-Week Carboplatin Dose (AUC mg•min/mL)
Neutropenic Fever (ANC less than 500/mm³ with fever >38°C) OR	First	75	4.5
Delay of next cycle by more than 7 days for ANC less than 1500/mm³ OR	Second	50	3
ANC less than 500/mm³ for more than 7 days	Third	Discontinue Treatment
Platelet count less than 50,000/mm³	First	75	4.5
	Second	Discontinue Treatment
Severe sensory Neuropathy - Grade 3 or 4	First	75	4.5
	Second	50	3
	Third	Discontinue Treatment

Adenocarcinoma Of The Pancreas

Dose level reductions for patients withadenocarcinomaof 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

Dose Level	Abraxane (mg/m²)	Gemcitabine (mg/m²)
Full dose	125	1000
1st dose reduction	100	800
2nd dose reduction	75	600
If additional dose reduction required	Discontinue	Discontinue

Recommended dose modifications for neutropenia andthrombocytopeniafor 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

Cycle Day	ANC (cells/mm³)		Platelet count (cells/mm³)	Abraxane / Gemcitabine
Day 1	< 1500	OR	< 100,000	Delay doses until recovery
Day 8	500 to < 1000	OR	50,000 to < 75,000	Reduce 1 dose level
	< 500	OR	< 50,000	Withhold doses
Day 15: If Day 8 doses were reduced or given without modification:
	500 to < 1000	OR	50,000 to < 75,000	Reduce 1 dose level from Day 8
	< 500	OR	< 50,000	Withhold doses
Day 15: If Day 8 doses were withheld:
	≥ 1000	OR	≥ 75,000	Reduce 1 dose level from Day 1
	500 to < 1000	OR	50,000 to < 75,000	Reduce 2 dose levels from Day 1
	< 500	OR	< 50,000	Withhold doses
ANC = Absolute Neutrophil Count

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

Adverse Reaction	Abraxane	Gemcitabine
Febrile Neutropenia: Grade 3 or 4	Withhold until fever resolves and ANC ≥ 1500; resume at next lower dose level
Peripheral Neuropathy: Grade 3 or 4	Withhold until improves to ≤ Grade 1; resume at next lower dose level	No dose reduction
Cutaneous Toxicity: Grade 2 or 3	Reduce to next lower dose level; discontinue treatment if toxicity persists
Gastrointestinal Toxicity: Grade 3 mucositis or diarrhea	Withhold until improves to ≤ Grade 1; resume at next lower dose level

• 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 causefetal harmwhen administered to apregnantwoman.
• 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 inhuman milk, or its effect on thebreastfedchild 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.