Abraxane

Name: Abraxane

How is paclitaxel protein-bound given?

Paclitaxel protein-bound is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.

Paclitaxel protein-bound is usually given for breast cancer once every 3 weeks. For lung cancer or pancreatic cancer, this medicine is given in a 21-day or 28-day treatment cycle, and you may only need to receive the medicine during the first 1 to 2 weeks of each cycle. Follow your doctor's dosing instructions very carefully.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when this medicine is injected.

Paclitaxel protein-bound can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Uses For Abraxane

Paclitaxel protein-bound injection is used to treat metastatic breast cancer (cancer that has already spread) after other treatments have failed. It is used together with carboplatin, a cancer medicine, to treat advanced or metastatic non-small cell lung cancer in patients who cannot receive radiation therapy or have surgery. Paclitaxel protein-bound is used together with gemcitabine, a cancer medicine, to treat metastatic pancreas cancer.

Paclitaxel belongs to the group of medicines called antineoplastics (cancer medicines). It interferes with the growth of cancer cells, which are eventually destroyed by the body. Since the growth of normal body cells may also be affected by paclitaxel, other unwanted effects will also occur.

This medicine is to be given only by or under the direct supervision of a doctor.

Before Using Abraxane

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of paclitaxel protein-bound injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of paclitaxel protein-bound injection in the elderly. However, elderly patients are more likely to have unwanted effects which may require caution in patients receiving this medicine.

Pregnancy

Pregnancy Category Explanation
All Trimesters D Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Measles Virus Vaccine, Live
  • Mumps Virus Vaccine, Live
  • Rotavirus Vaccine, Live
  • Rubella Virus Vaccine, Live
  • Varicella Virus Vaccine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Adenovirus Vaccine
  • Bacillus of Calmette and Guerin Vaccine, Live
  • Cholera Vaccine, Live
  • Ethinyl Estradiol
  • Influenza Virus Vaccine, Live
  • Poliovirus Vaccine, Live
  • Smallpox Vaccine
  • Testosterone
  • Tretinoin
  • Typhoid Vaccine
  • Yellow Fever Vaccine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Infection—May decrease body's ability to fight infection.
  • Liver disease, moderate to severe—Should not be used to treat pancreas cancer in patients with this condition.
  • Neutropenia (low white blood cells) or
  • Sensory neuropathy (tingling, numbness of arms, hands, legs, or feet)—Use with caution. May make these conditions worse.

Adverse Reactions

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 (6.2)]. 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. 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%).

Clinical Trials Experience in Metastatic Breast Cancer

Table 6 shows the frequency of important adverse events 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: Frequencya of Important Treatment Emergent Adverse Events in the Randomized Metastatic Breast Cancer Study on an Every-3-Weeks Schedule
a Based on worst grade by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.
b Paclitaxel injection patients received premedication.
c Includes treatment-related events related to hypersensitivity (e.g., flushing, dyspnea, chest pain, hypotension) that began on a day of dosing.
d Severe events are defined as at least grade 3 toxicity.
Percent of Patients
Abraxane
260 mg/m2 over 30 min
(n=229)
Paclitaxel Injection
175 mg/m2 over 3 hb
(n=225)
Bone Marrow
 Neutropenia
   < 2.0 x 109/L 80 82
   < 0.5 x 109/L 9 22
 Thrombocytopenia
   < 100 x 109/L 2 3
   < 50 x 109/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 Reactionc
 All 4 12
 Severed 0 2
Cardiovascular
 Vital Sign Changes During Administration
   Bradycardia <1 <1
   Hypotension 5 5
 Severe Cardiovascular Eventsd 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 Symptomsd 10 2
Myalgia / Arthralgia
 Any Symptoms 44 49
 Severe Symptomsd 8 4
Asthenia
 Any Symptoms 47 39
 Severe Symptomsd 8 3
Fluid Retention/Edema
 Any Symptoms 10 8
 Severe Symptomsd 0 <1
Gastrointestinal
 Nausea
   Any Symptoms 30 22
   Severe Symptomsd 3 <1
 Vomiting
   Any Symptoms 18 10
   Severe Symptomsd 4 1
 Diarrhea
   Any Symptoms 27 15
   Severe Symptomsd <1 1
  Mucositis
   Any Symptoms 7 6
   Severe Symptomsd <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

Adverse Event Experiences by Body System

Hematologic Disorders
Neutropenia was dose dependent and reversible. Among patients with metastatic breast cancer in the randomized trial, neutrophil counts declined below 500 cells/mm3 (Grade 4) in 9% of the patients treated with a dose of 260 mg/m2 compared to 22% in patients receiving paclitaxel injection at a dose of 175 mg/m2. 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.

Hypersensitivity Reactions (HSRs)
Grade 1 or 2 HSRs occurred on the day of Abraxane administration and consisted of dyspnea (1%) and flushing, hypotension, chest pain, and arrhythmia (all <1%). The use of Abraxane in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied.

Cardiovascular
Hypotension, during the 30-minute infusion, occurred in 5% of patients. Bradycardia, during the 30-minute infusion, occurred in <1% of patients. These vital sign changes most often caused no symptoms and required neither specific therapy nor treatment discontinuation.

Severe cardiovascular events possibly related to single-agent Abraxane occurred in approximately 3% of patients. These events included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension. Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported.

Electrocardiogram (ECG) abnormalities were common among patients at baseline. ECG abnormalities on study did not usually result in symptoms, were not dose-limiting, and required no intervention. ECG abnormalities were noted in 60% of patients. Among patients with a normal ECG prior to study entry, 35% of all patients developed an abnormal tracing while on study. The most frequently reported ECG modifications were non-specific repolarization abnormalities, sinus bradycardia, and sinus tachycardia.

Respiratory
Dyspnea (12%), cough (7%), and pneumothorax (<1%) were reported after treatment with Abraxane.

Neurologic
The frequency and severity of sensory neuropathy increased with cumulative dose. Sensory neuropathy was the cause of Abraxane discontinuation in 7/229 (3%) patients. Twenty-four patients (10%) treated with Abraxane developed Grade 3 peripheral neuropathy; of these patients, 14 had documented improvement after a median of 22 days; 10 patients resumed treatment at a reduced dose of Abraxane and 2 discontinued due to peripheral neuropathy. Of the 10 patients without documented improvement, 4 discontinued the study due to peripheral neuropathy.

No Grade 4 sensory neuropathies were reported. Only one incident of motor neuropathy (Grade 2) was observed in either arm of the controlled trial.

Vision Disorders
Ocular/visual disturbances occurred in 13% of all patients (n=366) treated with Abraxane and 1% were severe. The severe cases (keratitis and blurred vision) were reported in patients who received higher doses than those recommended (300 or 375 mg/m2). These effects generally have been reversible.

Arthralgia/Myalgia
The symptoms were usually transient, occurred two or three days after Abraxane administration, and resolved within a few days.

Hepatic
Grade 3 or 4 elevations in GGT were reported for 14% of patients treated with Abraxane and 10% of patients treated with paclitaxel injection in the randomized trial.

Renal
Overall 11% of patients experienced creatinine elevation, 1% severe. No discontinuations, dose reductions, or dose delays were caused by renal toxicities.

Other Clinical Events
Nail changes (changes in pigmentation or discoloration of nail bed) have been reported. Edema occurred in 10% of patients; no patients had severe edema. Dehydration and pyrexia were also reported.

Clinical Trials Experience in Non-Small Cell Lung Cancer

Adverse reactions were assessed in 514 Abraxane/carboplatin-treated patients and 524 paclitaxel injection/carboplatin-treated patients receiving first-line systemic treatment for locally advanced (stage IIIB) or metastatic (IV) non-small cell lung cancer (NSCLC) in a multicenter, randomized, open-label trial. Abraxane was administered as an intravenous infusion over 30 minutes at a dose of 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as an intravenous infusion over 3 hours at a dose of 200 mg/m2, following premedication. In both treatment arms carboplatin at a dose of AUC = 6 mg•min/mL was administered intravenously on Day 1 of each 21-day cycle after completion of Abraxane/paclitaxel infusion.
The differences in paclitaxel dose and schedule between the two arms limit direct comparison of dose- and schedule-dependent adverse reactions. Among patients evaluable for adverse reactions, the median age was 60 years, 75% were men, 81% were White, 49% had adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG PS 1. Patients in both treatment arms received a median of 6 cycles of treatment.

The following common (≥ 10% incidence) adverse reactions were observed at a similar incidence in Abraxane plus carboplatin-treated and paclitaxel injection plus carboplatin-treated patients: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%, asthenia 16%, constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are for the Abraxane plus carboplatin treatment group).

Table 7 provides the frequency and severity of laboratory-detected abnormalities which occurred with a difference of ≥ 5% for all grades (1-4) or ≥ 2% for Grade 3-4 toxicity between Abraxane plus carboplatin-treated patients or paclitaxel injection plus carboplatin-treated patients.

Table 7: Selected Hematologic Laboratory-Detected Abnormalities With a Difference of ≥ 5% for grades (1-4) or ≥ 2% for Grade 3-4 Toxicity Between Treatment Groups
1 508 patients assessed in Abraxane/carboplatin-treated group
2 514 patients assessed in paclitaxel injection/carboplatin-treated group
3 513 patients assessed in paclitaxel injection/carboplatin-treated group
Abraxane (100 mg/m2 weekly)
plus carboplatin
Paclitaxel Injection (200 mg/m2 every 3 weeks)
plus carboplatin
Grades 1-4 (%) Grade 3-4 (%) Grades 1-4 (%) Grade 3-4 (%)
Anemia1,2 98 28 91 7
Neutropenia1,3 85 47 83 58
Thrombocytopenia1,3 68 18 55 9

Table 8 provides the frequency and severity of adverse reactions, which occurred with a difference of ≥ 5% for all grades (1-4) or ≥ 2% for Grade 3-4 between either treatment group for the 514 Abraxane plus carboplatin-treated patients compared with the 524 patients who received paclitaxel injection plus carboplatin.

Table 8: Selected Adverse Reactions with a Difference of ≥5% for All Grade Toxicity or ≥2% for Grade 3-4 Toxicity Between Treatment Groups
a Peripheral neuropathy is defined by the MedDRA Version 14.0 SMQ neuropathy (broad scope).
System Organ
Class
MedDRA v 12.1
Preferred Term
Abraxane (100 mg/m2 weekly)
+ carboplatin
(N=514)
Paclitaxel Injection (200 mg/m2
every 3 weeks) + carboplatin
(N=524)
Grade 1-4
Toxicity
(%)
Grade 3-4
Toxicity
(%)
Grades 1-4
Toxicity
(%)
Grade 3-4
Toxicity
(%)
Nervous system
disorders
Peripheral neuropathya 48 3 64 12
General disorders
and administration
site conditions
Edema peripheral 10 0 4 <1
Respiratory
thoracic and
mediastinal
disorders
Epistaxis 7 0 2 0
Musculoskeletal
and connective
tissue disorders
Arthralgia 13 <1 25 2
Myalgia 10 <1 19 2

For the Abraxane plus carboplatin treated group, 17/514 (3%) patients developed Grade 3 peripheral neuropathy and no patients developed Grade 4 peripheral neuropathy. Grade 3 neuropathy improved to Grade 1 or resolved in 10/17 patients (59%) following interruption or discontinuation of Abraxane.

Clinical Trials Experience in Adenocarcinoma of the Pancreas

Adverse reactions were assessed in 421 patients who received Abraxane plus gemcitabine and 402 patients who received gemcitabine for the first-line systemic treatment of metastatic adenocarcinoma of the pancreas in a multicenter, multinational, randomized, controlled, open-label trial. Patients received a median treatment duration of 3.9 months in the Abraxane/gemcitabine group and 2.8 months in the gemcitabine group. For the treated population, the median relative dose intensity for gemcitabine was 75% in the Abraxane/gemcitabine group and 85% in the gemcitabine group. The median relative dose intensity of Abraxane was 81%.

Table 9 provides the frequency and severity of laboratory-detected abnormalities which occurred at a higher incidence for Grades 1-4 (≥ 5%) or for Grade 3-4 (≥ 2%) toxicity in Abraxane plus gemcitabine-treated patients.

Table 9: Selected Hematologic Laboratory-Detected Abnormalities with a Higher Incidence (≥ 5% for Grades 1-4 or ≥ 2% for Grades 3-4 Events) in the Abraxane/Gemcitabine Arm
a 405 patients assessed in Abraxane/gemcitabine-treated group
b 388 patients assessed in gemcitabine-treated group
c 404 patients assessed in Abraxane/gemcitabine-treated group
d Neutrophil growth factors were administered to 26% of patients in the Abraxane/gemcitabine group.
Abraxane(125 mg/m2)/
Gemcitabined
Gemcitabine
Grades 1-4
(%)
Grade 3-4
(%)
Grades 1-4
(%)
Grade 3-4
(%)
Neutropeniaa,b 73 38 58 27
Thrombocytopeniab,c 74 13 70 9

Table 10 provides the frequency and severity of adverse reactions which occurred with a difference of ≥ 5% for all grades or ≥ 2% for Grade 3 or higher in the Abraxane plus gemcitabine-treated group compared to the gemcitabine group.

Table 10: Selected Adverse Reactions with a Higher Incidence (≥5% for All Grade Toxicity or ≥2% for Grade 3 or Higher Toxicity) in the Abraxane/Gemcitabine Arm
a Peripheral neuropathy is defined by the MedDRA Version 15.0 Standard MedDRA Query neuropathy (broad scope).
b Urinary tract infections includes the preferred terms of: urinary tract infection, cystitis, urosepsis, urinary tract infection bacterial, and urinary tract infection enterococcal.
System Organ Class Adverse Reaction Abraxane (125 mg/m2) and
gemcitabine (N=421)
Gemcitabine (N=402)
All Grades Grade 3 or
Higher
All Grades Grade 3 or
Higher
General disorders and
administration site conditions
Fatigue 248 (59%) 77 (18%) 183 (46%) 37 (9%)
Peripheral edema 194 (46%) 13 (3%) 122 (30%) 12 (3%)
Pyrexia 171 (41%) 12 (3%) 114 (28%) 4 (1%)
Asthenia 79 (19%) 29 (7%) 54 (13%) 17 (4%)
Mucositis 42 (10%) 6 (1%) 16 (4%) 1 (<1%)
Gastrointestinal disorders Nausea 228 (54%) 27 (6%) 192 (48%) 14 (3%)
Diarrhea 184 (44%) 26 (6%) 95 (24%) 6 (1%)
Vomiting 151 (36%) 25 (6%) 113 (28%) 15 (4%)
Skin and subcutaneous
tissue disorders
Alopecia 212 (50%) 6 (1%) 21 (5%) 0
Rash 128 (30%) 8 (2%) 45 (11%) 2 (<1%)
Nervous system disorders Peripheral neuropathya 227 (54%) 70 (17%) 51 (13%) 3 (1%)
Dysgeusia 68 (16%) 0 33 (8%) 0
Headache 60 (14%) 1 (<1%) 38 (9%) 1 (<1%)
Metabolism and nutrition
disorders
Decreased appetite 152 (36%) 23 (5%) 104 (26%) 8 (2%)
Dehydration 87 (21%) 31 (7%) 45 (11%) 10 (2%)
Hypokalemia 52 (12%) 18 (4%) 28 (7%) 6 (1%)
Respiratory, thoracic and
mediastinal disorders
Cough 72 (17%) 0 30 (7%) 0
Epistaxis 64 (15%) 1 (<1%) 14 (3%) 1 (<1%)
Infections and infestations Urinary tract infections b 47 (11%) 10 (2%) 20 (5%) 1 (<1%)
Musculoskeletal and
connective tissue disorders
Pain in extremity 48 (11%) 3 (1%) 24 (6%) 3 (1%)
Arthralgia 47 (11%) 3 (1%) 13 (3%) 1 (<1%)
Myalgia 44 (10%) 4 (1%) 15 (4%) 0
Psychiatric disorders Depression 51 (12%) 1 (<1%) 24 (6%) 0

Additional clinically relevant adverse reactions that were reported in < 10% of the patients with adenocarcinoma of the pancreas who received Abraxane/gemcitabine included:

Infections & infestations: oral candidiasis, pneumonia
Vascular disorders: hypertension
Cardiac disorders: tachycardia, congestive cardiac failure
Eye disorders: cystoid macular edema

Peripheral Neuropathy
Grade 3 peripheral neuropathy occurred in 17% of patients who received Abraxane/gemcitabine compared to 1% of patients who received gemcitabine only; no patients developed grade 4 peripheral neuropathy. The median time to first occurrence of Grade 3 peripheral neuropathy in the Abraxane arm was 140 days. Upon suspension of Abraxane dosing, the median time to improvement from Grade 3 peripheral neuropathy to ≤ Grade 1 was 29 days. Of Abraxane-treated patients with Grade 3 peripheral neuropathy, 44% resumed Abraxane at a reduced dose.

Sepsis
Sepsis occurred in 5% of patients who received Abraxane/gemcitabine compared to 2% of patients who received gemcitabine alone. Sepsis occurred both in patients with and without neutropenia. Risk factors for sepsis included biliary obstruction or presence of biliary stent.

Pneumonitis
Pneumonitis occurred in 4% of patients who received Abraxane/gemcitabine compared to 1% of patients who received gemcitabine alone. Two of 17 patients in the Abraxane arm with pneumonitis died.

Postmarketing Experience with Abraxane and other Paclitaxel Formulations

Unless otherwise noted, the following discussion refers to the adverse reactions that have been identified during post-approval use of Abraxane. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In some instances, severe events observed with paclitaxel injection may be expected to occur with Abraxane.

Hypersensitivity Reactions
Severe and sometimes fatal hypersensitivity reactions have been reported with Abraxane. The use of Abraxane in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied.

Cardiovascular
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with Abraxane. Most of the individuals were previously exposed to cardiotoxic drugs, such as anthracyclines, or had underlying cardiac history.

Respiratory
There have been reports of pneumonitis, interstitial pneumonia and pulmonary embolism in patients receiving Abraxane and reports of radiation pneumonitis in patients receiving concurrent radiotherapy. Reports of lung fibrosis have been received as part of the continuing surveillance of paclitaxel injection safety and may also be observed with Abraxane.

Neurologic
Cranial nerve palsies and vocal cord paresis have been reported, as well as autonomic neuropathy resulting in paralytic ileus.

Vision Disorders
Reports in the literature of abnormal visual evoked potentials in patients treated with paclitaxel injection suggest persistent optic nerve damage. These may also be observed with Abraxane.

Reduced visual acuity due to cystoid macular edema (CME) has been reported during treatment with Abraxane as well as with other taxanes. After cessation of treatment, CME improves and visual acuity may return to baseline.

Hepatic
Reports of hepatic necrosis and hepatic encephalopathy leading to death have been received as part of the continuing surveillance of paclitaxel injection safety and may occur following Abraxane treatment.

Gastrointestinal (GI)
There have been reports of intestinal obstruction, intestinal perforation, pancreatitis, and ischemic colitis following Abraxane treatment. There have been reports of neutropenic enterocolitis (typhlitis), despite the coadministration of G-CSF, occurring in patients treated with paclitaxel injection alone and in combination with other chemotherapeutic agents.

Injection Site Reaction
There have been reports of extravasation of Abraxane. Given the possibility of extravasation, it is advisable to monitor closely the Abraxane infusion site for possible infiltration during drug administration.

Severe events such as phlebitis, cellulitis, induration, necrosis, and fibrosis have been reported as part of the continuing surveillance of paclitaxel injection safety. In some cases the onset of the injection site reaction in paclitaxel injection patients either occurred during a prolonged infusion or was delayed by a week to ten days. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel injection at a different site, i.e., “recall”, has been reported.

Other Clinical Events
Skin reactions including generalized or maculopapular rash, erythema, and pruritus have been observed with Abraxane. There have been case reports of photosensitivity reactions, radiation recall phenomenon, and in some patients previously exposed to capecitabine, reports of palmar-plantar erythrodysesthesia. Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.

There have been reports of conjunctivitis, cellulitis, and increased lacrimation with paclitaxel injection.

Accidental Exposure

No reports of accidental exposure to Abraxane have been received. However, upon inhalation of paclitaxel, dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported. Following topical exposure, events have included tingling, burning, and redness.

Patient Counseling Information

See FDA-approved patient labeling

  • Abraxane injection may cause fetal harm. Advise patients to avoid becoming pregnant while receiving this drug. Women of childbearing potential should use effective contraceptives while receiving Abraxane [see Warnings and Precautions (5.8) and Use in Specific Populations (8.1)].
  • Advise men not to father a child while receiving Abraxane [see Warnings and Precautions (5.9)].
  • Patients must be informed of the risk of low blood cell counts and severe and life-threatening infections and instructed to contact their physician immediately for fever or evidence of infection. [see Warnings and Precautions (5.1), (5.3)].
  • Patients should be instructed to contact their physician for persistent vomiting, diarrhea, or signs of dehydration.
  • Patients must be informed that sensory neuropathy occurs frequently with Abraxane and patients should advise their physicians of numbness, tingling, pain or weakness involving the extremities [see Warnings and Precautions (5.2)].
  • Explain to patients that alopecia, fatigue/asthenia, and myalgia/arthralgia occur frequently with Abraxane
  • Instruct patients to contact their physician for signs of an allergic reaction, which could be severe and sometimes fatal. [see Warnings and Precautions (5.5)].
  • Instruct patients to contact their physician immediately for sudden onset of dry persistent cough, or shortness of breath [see Warnings and Precautions (5.4)].

Manufactured for:       Celgene Corporation
                                  Summit, NJ 07901

Abraxane® is a registered trademark of Abraxis BioScience, LLC.
©2005-2015 Abraxis BioScience, LLC.
All Rights Reserved.
Abraxis BioScience, LLC is a wholly owned subsidiary of Celgene Corporation.

U.S. Patent Numbers: See www.celgene.com.

ABRPI.009/PPI.009 07/15

Patient Information

Abraxane® (ah-BRAKS-ane)
(paclitaxel protein-bound particles for injectable suspension)
(albumin-bound)

Read this Patient Information before you start receiving Abraxane and before each infusion. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is Abraxane?

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, in combination with carboplatin in people who cannot be treated with surgery or radiation.
  • and 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.

Who should not receive Abraxane?

Do not receive Abraxane if:

  • your white blood cell count is below 1,500 cells/ mm3.
  • you have had a severe allergic reaction to Abraxane.

What should I tell my doctor before receiving Abraxane?
Before you receive Abraxane, tell your doctor if you:

  • have liver or kidney problems.
  • have any other medical conditions.
  • are a man planning to father a child. You should not father a child during your treatment with Abraxane. Abraxane can harm the unborn baby of your partner. Talk to your doctor if this is a concern to you.
  • are pregnant or plan to become pregnant. Abraxane can harm your unborn baby. You should not become pregnant while receiving Abraxane. Women who may become pregnant should use effective birth control (contraception). Talk to your doctor about the best way to prevent pregnancy while receiving Abraxane.
  • are breastfeeding or plan to breastfeed. It is not known if Abraxane passes into your breast milk. You and your doctor should decide if you will receive Abraxane or breastfeed.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list to show your doctor and pharmacist when you get a new medicine.

How will I receive Abraxane?

  • Your doctor will prescribe Abraxane in an amount that is right for you.
  • Premedication to prevent allergic reactions is generally not needed to receive Abraxane. Premedication may be needed if you have had an allergic reaction to Abraxane. In case of severe allergic reaction, Abraxane should not be used again.
  • Abraxane will be given to you by intravenous infusion into your vein.
  • Your doctor should do regular blood tests while you receive Abraxane.

What are the possible side effects of Abraxane?

Abraxane may cause serious side effects, including:

  • decreased blood cell counts. Abraxane can cause a severe decrease in neutrophils (a type of white blood cells important in fighting against bacterial infections) and platelets (important for clotting and to control bleeding). Your doctor will check your blood cell count during your treatment with Abraxane and after you have stopped your treatment.
  • numbness, tingling, pain, or weakness in your hands or feet (neuropathy).
  • severe infection (sepsis). If you receive Abraxane in combination with gemcitabine, infections can be severe and lead to death. Tell your doctor right away if you have a fever (temperature of 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 doctor right away if you have a sudden onset of persistent dry cough or shortness of breath.
  • allergic reactions. Allergic reactions to Abraxane may be severe and can lead to death.

The most common side effects of Abraxane include:

  • hair loss
  • numbness, tingling, pain, or weakness in the hands or feet
  • abnormal heart beat
  • tiredness
  • joint and muscle pain
  • changes in your liver function tests
  • rash
  • low red blood cell count (anemia). Red blood cells carry oxygen to your body tissues. Tell your doctor if you feel weak, tired or short of breath.
  • nausea and vomiting
  • infections. If you have a fever (temperature of greater than 100.4° F) or other signs of infection, tell your doctor right away.
  • Diarrhea
  • Loss of body fluid (dehydration)
  • Swelling in the hands or feet

These are not all the possible side effects of Abraxane. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Abraxane.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.

This Patient Information leaflet summarizes the important information about Abraxane. If you would like more information, talk to your doctor. You can ask your doctor or pharmacist for information about Abraxane that is written for health professionals.

For more information, call 1-888-423-5436.

What are the ingredients in Abraxane?

Active ingredient: paclitaxel (bound to human albumin).

Other ingredient: human albumin (containing sodium caprylate and sodium acetyltryptophanate)

This Patient Information has been approved by the U.S. Food and Drug Administration.


Revised: July 2015

Manufactured for:      Celgene Corporation
                                 Summit, NJ 07901

Abraxane® is a registered trademark of Abraxis BioScience, LLC.
©2005-2015 Abraxis BioScience, LLC.
All Rights Reserved.
Abraxis BioScience, LLC is a wholly owned subsidiary of Celgene Corporation.

U.S. Patent Numbers: See www.celgene.com.

ABRPPI.009 07/15

PRINCIPAL DISPLAY PANEL - 100 mg Vial

NDC 68817-134-50
103450

Abraxane®
for Injectable Suspension

(paclitaxel protein-bound particles for injectable suspension)
(albumin-bound)

100 mg per vial
Single Use Vial

Discard any unused portion.

For Intravenous Use Only
Rx only

Functional properties differ from other
paclitaxel products. DO NOT SUBSTITUTE.

PRINCIPAL DISPLAY PANEL - 100 mg Vial

NDC 68817-134-50
103450

Abraxane®
for Injectable Suspension

(paclitaxel protein-bound particles for injectable suspension)
(albumin-bound)

100 mg per vial
Single Use Vial

Discard any unused portion.

For Intravenous Use Only
Rx only

Functional properties differ from other
paclitaxel products. DO NOT SUBSTITUTE.

PRINCIPAL DISPLAY PANEL - 100 mg Vial Carton

NDC 68817-134-50
103450

Abraxane®
for Injectable Suspension

(paclitaxel protein-bound particles for injectable suspension)
(albumin-bound)

100 mg per vial
Single Use Vial

Discard any unused portion.

For Intravenous Use Only
Rx only

Functional properties differ from other
paclitaxel products. DO NOT SUBSTITUTE.

Abraxane 
paclitaxel injection, powder, lyophilized, for suspension
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68817-134
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
PACLITAXEL (PACLITAXEL) PACLITAXEL 100 mg  in 20 mL
Inactive Ingredients
Ingredient Name Strength
ALBUMIN HUMAN  
Packaging
# Item Code Package Description
1 NDC:68817-134-50 1 VIAL, SINGLE-USE in 1 CARTON
1 20 mL in 1 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021660 02/10/2005
Labeler - Abraxis BioScience, LLC (832108497)
Revised: 02/2016   Abraxis BioScience, LLC

Uses of Abraxane

Abraxane is a prescription medicine used to treat some forms of cancer including:

  • advanced breast cancer in people who have already received certain other medicines for their cancer.
  • advanced non-small cell lung cancer, 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.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Side Effects of Abraxane

The most common side effects of Abraxane include:

  • hair loss
  • numbness, tingling, pain, or weakness in the hands or feet
  • abnormal heart beat
  • tiredness
  • joint and muscle pain
  • changes in your liver function tests
  • rash
  • low red blood cell count (anemia). Red blood cells carry oxygen to your body tissues. Tell your doctor if you feel weak, tired or short of breath.
  • nausea and vomiting
  • infections. If you have a fever (temperature of greater than 100.4° F) or other signs of infection, tell your doctor right away.
  • Diarrhea
  • Loss of body fluid (dehydration)
  • Swelling in the hands or feet

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Abraxane Precautions

Serious side effects have been reported with Abraxane including the following:

  • decreased blood cell counts. This increases the risk that you will develop a serious infection. You should not receive Abraxane if you already have a low number of white blood cells. Your doctor will order laboratory tests before and during your treatment to check the number of white blood cells in your blood. Your doctor will delay or interrupt your treatment if the number of white blood cells is too low. Call your doctor immediately if you develop all or some of the following symptoms:
    • temperature greater than 100.4 °F (38 °C)
    • sore throat
    • cough
    • chills
    • difficult, frequent, or painful urination
  • numbness, tingling, pain, or weakness in your hands or feet (neuropathy)
  • severe infection (sepsis). If you receive Abraxane in combination with gemcitabine, infections can be severe and lead to death. Tell your doctor right away if you have a fever (temperature of 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 doctor right away if you have a sudden onset of persistent dry cough or shortness of breath.
  • allergic reactions. Allergic reactions to Abraxane may be severe and can lead to death.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to Abraxane injection.

Do not receive Abraxane if:

  • you are allergic to any of the ingredients in Abraxane. 
  • you have low white blood cell counts.

Abraxane and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Abraxane passes into your breast milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. You and your doctor should decide if you will receive Abraxane or breastfeed.

Abraxane FDA Warning

WARNING:

Abraxane should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.

Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in 2 to 4% of patients receiving Abraxane in clinical trials. Fatal reactions have occurred in patients despite premedication. All patients should be pretreated with corticosteroids, diphenhydramine, and H2 antagonists. Patients who experience severe hypersensitivity reactions to Abraxane should not be rechallenged with the drug.

Abraxane therapy should not be given to patients with solid tumors who have baseline neutrophil counts of less than 1500 cells/mm3 and should not be given to patients with AIDS-related Kaposi’s sarcoma if the baseline neutrophil count is less than 1000 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.

What is the most important information i should know about paclitaxel protein-bound (abraxane)?

Do not use paclitaxel protein-bound if you are pregnant. It could harm the unborn baby.

Use birth control to prevent pregnancy while you are receiving paclitaxel protein-bound, whether you are a man or a woman. Paclitaxel protein-bound use by either parent may cause birth defects.

You should not use paclitaxel protein-bound if you are allergic to it, or if you have a low white blood cell count.

Before you receive this medication, tell your doctor if you have kidney disease, liver disease, heart disease, or bone marrow suppression.

To make sure this medication is helping your condition and not causing harmful effects, your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Do not miss any follow-up visits to your doctor.

Call your doctor at once if you have a serious side effect such as fever, chills, flu symptoms, mouth sores, easy bruising or bleeding, pale skin, feeling light-headed or short of breath, swelling or rapid weight gain, chest pain, sudden cough, rapid heart rate, or trouble breathing.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Dose Adjustments

-Mild hepatic impairment (total bilirubin greater than 1 x ULN and less than or equal to 1.5 x ULN and aspartate aminotransferase [AST] less than or equal to 10 x ULN): No adjustment necessary, regardless of indication
-Moderate to severe hepatic impairment in patients with metastatic adenocarcinoma of the pancreas: Use is not recommended
-Patients with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN: Use is not recommended regardless of indication

DOSAGE ADJUSTMENT FOR HEPATIC IMPAIRMENT AT TREATMENT INITIATION:
BREAST CANCER:
-Moderate to Severe impairment (AST less than 10 x ULN and bilirubin greater than 1.5 to less than or equal to 5 x ULN): Reduce dose to 200 mg/m2; may increase up to 260 mg/m2 if the reduced dose is tolerated for 2 cycles

NON-SMALL CELL LUNG CANCER (NSCLC) REGIMEN:
- Moderate to Severe impairment (AST less than 10 x ULN and bilirubin greater than 1.5 to less than or equal to 5 x ULN): Reduce dose to 80 mg/m2; may increase up to 100 mg/m2 if the reduced dose is tolerated for 2 cycles

Dialysis

Data not available

How do I store and/or throw out Paclitaxel?

  • If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

For Healthcare Professionals

Applies to paclitaxel: intravenous solution

Cardiovascular

Very common (10% or more): Hypotension
Common (1% to 10%): Bradycardia
Uncommon (0.1% to 1%): Cardiomyopathy, asymptomatic ventricular tachycardia, tachycardia with bigeminy, atrioventricular block and syncope, myocardial infarction, hypertension, thrombosis, thrombophlebitis
Rare (0.01% to 0.1%): Cardiac failure
Very rare (less than 0.01%): Atrial fibrillation, supraventricular tachycardia, shock
Frequency not reported: Phlebitis[Ref]

Dermatologic

Very common (10% or more): Alopecia (90%), rash
Common (1% to 10%): Transient and mild nail and skin changes, discoloration of the nail bed
Rare (0.01% to 0.1%): Pruritus, rash, erythema
Very rare (less than 0.01%): Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), erythema multiforme, exfoliative dermatitis, urticaria, onycholysis (patients on therapy should wear sun protection on hands and feet), scleroderma-like reaction[Ref]

Gastrointestinal

Very common (10% or more): Nausea (52%), mucositis (31%), vomiting, diarrhea mucosal inflammation
Rare (less than 0.1%): Peritonitis, bowel obstruction, bowel perforation, ischemic colitis, pancreatitis
Very rare (less than 0.01%): Pseudomembranous colitis, mesenteric thrombosis, neutropenic colitis, esophagitis, constipation, ascites[Ref]

Hematologic

Very common (10% or more): Myelosuppression, neutropenia (90%), anemia, thrombocytopenia, leucopenia, bleeding
Rare (less than 0.1%): Febrile neutropenia[Ref]

Hepatic

Very common (10% or more): Elevated alkaline phosphatase (22%), elevated AST (SGOT) (19%)
Common (1% to 10%): Elevated bilirubin
Very rare (less than 0.01%): Hepatic necrosis, hepatic encephalopathy (both with reported cases of fatal outcome)[Ref]

Hypersensitivity

Very common (10% or more): Minor hypersensitivity reactions (mainly flushing and rash)
Uncommon (0.1% to 1%): Significant hypersensitivity reactions requiring therapy (e.g., hypotension, angioneurotic edema, respiratory distress, generalized urticaria, chills, back pain, chest pain, tachycardia, abdominal pain, pain in extremity, diaphoresis, hypertension)
Rare (less than 0.1%): Anaphylactic reactions
Very rare (less than 0.01%): Anaphylactic shock[Ref]

Immunologic

Very common (10% or more): Infections (mainly urinary tract and upper respiratory tract infections), with reported cases of fatal outcome
Uncommon (0.1% to 1%): Septic shock
Rare (less than 0.1%): Sepsis, pseudomembranous colitis[Ref]

Local

Common (1% to 10%): Injection site reactions (including localized edema, pain, erythema, induration, on occasion extravasation can result in cellulitis, skin fibrosis and skin necrosis)
Rare (less than 0.1%): Phlebitis[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia/myalgia (44%)
Frequency not reported: Systemic lupus erythematosus, scleroderma[Ref]

Metabolic

Common (1% to 10%): Severe elevation in aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)), severe elevation in alkaline phosphatase
Uncommon (0.1% to 1%): Severe elevation in bilirubin
Rare (0.01% to 0.1%): Dehydration, increased blood creatinine
Very rare (less than 0.01%): Anorexia
Frequency not reported: Tumor lysis syndrome[Ref]

Nervous system

Very common (10% or more): Neurotoxicity (mainly peripheral neuropathy)
Rare (0.01% to 0.1%): Motor neuropathy (with resultant minor distal weakness)
Very rare (less than 0.01%): Autonomic neuropathy (resulting in paralytic ileus and orthostatic hypotension), optic nerve disturbance, grand mal seizures, convulsions, encephalopathy, dizziness, headache, ataxia[Ref]

Ocular

Very rare (less than 0.01%): Optic nerve and/or visual disturbances (scintillating scotomata), particularly in patients who have received higher doses than recommended
Frequency not reported: Macular edema, photopsia, vitreous floaters[Ref]

Oncologic

Very rare (less than 0.01%): Acute myeloid leukemia, myelodysplastic syndrome[Ref]

Other

Rare (0.01% to 0.1%): Asthenia, pyrexia, edema, malaise
Very rare (less than 0.01%): Ototoxicity, hearing loss, tinnitus, vertigo[Ref]

Psychiatric

Very rare (less than 0.01%): Confusional state[Ref]

Respiratory

Rare (0.01% to 0.1%): Pneumonia, dyspnea, pleural effusion, interstitial pneumonia, lung fibrosis, pulmonary embolism, respiratory failure
Frequency not reported: Bronchospasm
Very rare (less than 0.01%): Cough[Ref]

Some side effects of paclitaxel may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Adult Dose for Ovarian Cancer

For previously untreated patients with cancer of the ovary:
175 mg/m2 IV over 3 hours every 3 weeks followed by cisplatin
OR
135 mg/m2 IV over 24 hours every 3 weeks followed by cisplatin

For patients previously treated for cancer of the ovary:
175 mg/m2 IV over 3 hours every 3 weeks
OR
135 mg/m2 IV over 3 hours every 3 weeks

Comment:
-All patients should be premedicated prior to receiving this drug to prevent severe hypersensitivity reactions. Consult the manufacturer product information or local protocol for premedication guidelines.

Uses: As subsequent therapy for the treatment of advanced carcinoma of the ovary; as first-line therapy in combination with cisplatin

Usual Adult Dose for Breast Cancer

After failure of initial chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy:
175 mg/m2 IV over 3 hours every 3 weeks

Comment:
-All patients should be premedicated prior to receiving this drug to prevent severe hypersensitivity reactions. Consult the manufacturer product information or local protocol for premedication guidelines.

Use: 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

Renal Dose Adjustments

Data not available

Other Comments

Administration advice:
-This drug should be administered using an in-line filter with a microporous membrane of less than or equal to 0.22 microns.

Storage requirements:
-Consult the manufacturer product information.

Reconstitution/preparation techniques:
-Consult the manufacturer product information.

IV compatibility:
-Consult the manufacturer product information.

General:
-All patients should be premedicated with corticosteroids, antihistamines and H2-receptor antagonists prior to receiving this drug to prevent severe hypersensitivity reactions. Consult the manufacturer product information or local protocol for premedication guidelines.

Monitoring:
-Because of the possibility of extravasation, it is advisable to monitor the infusion site for possible infiltration during administration.
-Dose adjustments based on hepatic function may be necessary.

Paclitaxel Identification

Substance Name

Paclitaxel

CAS Registry Number

33069-62-4

Drug Class

Antineoplastic Agents

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