Abraxane (paclitaxel) for Breast Cancer: Side Effects & Warnings

What is Abraxane, and how does it work?

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.

What are the side effects of Abraxane?

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.

WARNING

NEUTROPENIA

Do not administer
Abraxane therapy to patients who have baseline neutrophil
counts of less than 1,500 cells/mm³. In order to monitor the occurrence of bone
marrow suppression, primarily neutropenia, which may be severe and result in
infection, it is recommended that frequent peripheral blood cell counts be
performed on all patients receiving Abraxane.

Note: An albumin form of paclitaxel may substantially affect a drug's functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS.

What is the dosage for Abraxane?

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

AST LevelsBilirubin Levels
Abraxane Dose^aMBCNSCLC ^cAdenocarcinoma of Pancreas^cModerate<10xULNAND> 1.5 to ≤ 3 x ULN200 mg/m² ^b80 mg/m² ^bnot recommendedSevere<10x ULNAND> 3 to ≤ 5 x ULN200 mg/m² ^b80 mg/m² ^bnot recommended>10x ULNOR> 5 x ULNnot recommendednot recommendednot recommendedAST = 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/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.
^c Patients 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

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

Adverse ReactionOccurrenceWeekly
Abraxane Dose (mg/m²)Every 3-Week Carboplatin Dose (AUC mg•min/mL)Neutropenic Fever (ANC less than 500/mm³ with fever >38°C) ORFirst754.5Delay of next cycle by more than 7 days for ANC less than 1500/mm³ ORSecond503ANC less than 500/mm³ for more than 7 daysThirdDiscontinue TreatmentPlatelet count less than 50,000/mm³First754.5SecondDiscontinue TreatmentSevere sensory Neuropathy – Grade 3 or 4First754.5Second503ThirdDiscontinue Treatment

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

Dose Level
Abraxane (mg/m²)Gemcitabine (mg/m²)Full dose12510001st dose reduction1008002nd dose reduction75600If additional dose reduction requiredDiscontinueDiscontinue

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

Cycle DayANC (cells/mm³)Platelet count (cells/mm³)
Abraxane / GemcitabineDay 1< 1500OR< 100,000Delay doses until recoveryDay 8500 to < 1000OR50,000 to < 75,000Reduce 1 dose level< 500OR< 50,000Withhold dosesDay 15: If Day 8 doses were reduced or given without modification:500 to < 1000OR50,000 to < 75,000Reduce 1 dose level from Day 8< 500OR< 50,000Withhold dosesDay 15: If Day 8 doses were withheld:≥ 1000OR≥ 75,000Reduce 1 dose level from Day 1500 to < 1000OR50,000 to < 75,000Reduce 2 dose levels from Day 1< 500OR< 50,000Withhold dosesANC = 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
AbraxaneGemcitabineFebrile Neutropenia: Grade 3 or 4Withhold until fever resolves and ANC ≥ 1500; resume at next lower dose levelPeripheral Neuropathy: Grade 3 or 4Withhold until improves to ≤ Grade 1; resume at next lower dose levelNo dose reductionCutaneous Toxicity: Grade 2 or 3Reduce to next lower dose level; discontinue treatment if toxicity persistsGastrointestinal Toxicity: Grade 3 mucositis or diarrheaWithhold until improves to ≤ Grade 1; resume at next lower dose level

QUESTION

A lump in the breast is almost always cancer.
See Answer

What drugs interact with Abraxane?

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.

Is Abraxane safe to use while pregnant or breastfeeding?

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.