Abraxane

Name: Abraxane

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Abraxane (paclitaxel (protein bound)), please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Abraxane. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Abraxane.

Review Date: October 4, 2017

Dosage Forms and Strengths

For injectable suspension: lyophilized powder containing 100 mg of paclitaxel formulated as albumin-bound particles in single-use vial for reconstitution.

Contraindications

  • Abraxane should not be used in patients who have baseline neutrophil counts of < 1,500 cells/mm3.
  • Patients who experience a severe hypersensitivity reaction to Abraxane should not be rechallenged with the drug.

Overdosage

There is no known antidote for Abraxane overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, sensory neurotoxicity, and mucositis.

Abraxane Overview

Abraxane is a prescription medication used to treat cancer, including breast, and lung, pancreatic cancer. Abraxane belongs to a group of drugs called antimicrotubule agents or taxanes. It works by stopping the growth and spread of cancer cells.

This medication comes in an injectable form to be given directly into a vein (IV) by a healthcare provider.

Common side effects of Abraxane include low blood cell count, hair loss, and joint or muscle pain.

Inform MD

Before receiving Abraxane, tell your healthcare provider about all your medical conditions, including if you:

  • are allergic to Abraxane or any of its ingredients
  • 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 healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Abraxane Usage

  • 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 should i discuss with my healthcare provider before receiving paclitaxel protein-bound (abraxane)?

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

To make sure you can safely receive paclitaxel protein-bound, tell your doctor if you have any of these other conditions:

  • kidney disease;
  • liver disease;
  • heart disease, heart rhythm disorder; or
  • bone marrow suppression.

FDA pregnancy category D. Do not use paclitaxel protein-bound if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

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.

It is not known whether paclitaxel protein-bound passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are receiving paclitaxel protein-bound.

Side effects

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 Clinical Trials Experience in Metastatic Breast Cancer below].

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 Clinical Trials Experience in Non-Small Cell Lung Cancer below]. 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], 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

  Percent of Patients
ABRAXANE260 mg/m² over 30 min
(n=229)
Paclitaxel Injection175 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
Severea 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
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.

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 carboplatintreated 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

  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
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

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

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
a Peripheral neuropathy is defined by the MedDRA Version 14.0 SMQ neuropathy (broad scope).

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

  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
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.

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

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
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.

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.

Read the entire FDA prescribing information for Abraxane (Albumin-bound Paclitaxel for Injectable Suspension)

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What is Abraxane?

Abraxane (paclitaxel) is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Abraxane is used in the treatment of breast cancer, lung cancer, and pancreatic cancer.

Abraxane is sometimes given with other cancer medicines.

Renal Dose Adjustments

-Mild to moderate renal impairment (CrCl greater than or equal to 30 mL/min to less than 90 mL/min): No adjustment recommended
-Severe renal impairment (CrCl 15 to less than 30 mL/min) and end stage renal disease (ESRD) (CrCl less than 15 mL/min): Data not available

Liver 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 recommended, regardless of indication
-Moderate to severe hepatic impairment in patients with metastatic adenocarcinoma of the pancreas: Not recommended
-Patients with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN: Not recommended regardless of indication

DOSAGE ADJUSTMENT FOR HEPATIC IMPAIRMENT AT TREATMENT INITIATION:
BREAST CANCER:
-Mild impairment (AST less than 10 x ULN and bilirubin greater than 1 to less than or equal to 1.5 x ULN): No adjustment necessary
-Moderate impairment (AST less than 10 x ULN and bilirubin greater than 1 to less than or equal to 3 x ULN): Reduce dose to 200 mg/m2; may increase up to 260 mg/m2 if the reduced dose is tolerated for 2 cycles
-Severe impairment: AST greater than 10 x ULN and bilirubin greater than 3 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
-Severe impairment: AST less than 10 x ULN and bilirubin greater than 5 x ULN: Use is not recommended
NON-SMALL CELL LUNG CANCER (NSCLC) REGIMEN:
-Mild impairment (AST less than 10 x ULN and bilirubin greater than 1 to less than or equal to 1.5 x ULN): No adjustment necessary
-Moderate impairment (AST less than 10 x ULN and bilirubin greater than 1 to less than or equal to 3 x ULN): Reduce dose to 80 mg/m2; may increase up to 100 mg/m2 if the reduced dose is tolerated for 2 cycles
-Severe impairment: AST greater than 10 x ULN and bilirubin greater than 3 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
-Severe impairment: AST less than 10 x ULN and bilirubin greater than 5 x ULN: Use is not recommended
PANCREATIC ADENOCARCINOMA:
-Mild impairment (AST less than 10 x ULN and bilirubin greater than 1 to less than or equal to 1.5 x ULN): No adjustment necessary
-Moderate impairment (AST less than 10 x ULN and bilirubin greater than 1 to less than or equal to 3 x ULN): Use is not recommended
-Severe impairment: AST greater than 10 x ULN and bilirubin greater than 3 to less than or equal to 5 x ULN: Use is not recommended
-Severe impairment: AST less than 10 x ULN and bilirubin greater than 5 x ULN: Use is not recommended

Precautions

US BOXED WARNINGS:
-NEUTROPENIA: Do not administer this drug 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.
-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.

This drug is not recommended for use in children.

Consult WARNINGS section for additional precautions.

For the Consumer

Applies to paclitaxel: intravenous solution

Along with its needed effects, paclitaxel may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking paclitaxel:

More common
  • Black or tarry stools
  • blurred vision
  • burning, numbness, tingling, or painful sensations
  • confusion
  • cough or hoarseness with fever or chills
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • feeling of warmth
  • fever or chills
  • lower back or side pain
  • painful or difficult urination
  • pale skin
  • redness of the face, neck, arms, and occasionally, upper chest
  • shortness of breath
  • skin rash or itching
  • sore throat
  • sweating
  • troubled breathing with exertion
  • ulcers, sores, or white spots in the mouth
  • unsteadiness or awkwardness
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • weakness in the arms, hands, legs, or feet
Less common
  • Blood in the urine or stools
  • difficult or labored breathing
  • pinpoint red spots on the skin
  • shortness of breath (severe)
  • slow heartbeat
  • tightness in the chest
  • wheezing
Incidence not known
  • Anxiety
  • blue lips, fingernails, or skin
  • difficult or troubled breathing
  • fainting
  • fast heartbeat
  • irregular, fast or slow, or shallow breathing
  • sudden shortness of breath

Some side effects of paclitaxel may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
  • cracked lips
  • diarrhea
  • difficulty with swallowing
  • hair loss
  • nausea or vomiting
  • numbness, burning, or tingling in the hands or feet
  • pain in the joints or muscles, especially in the arms or legs
  • thinning of the hair

Paclitaxel Levels and Effects while Breastfeeding

Summary of Use during Lactation

Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy.[1] Based on limited data, paclitaxel appears to be excreted into milk in relatively large amounts. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence, but the duration abstinence is not clear. In one case, paclitaxel was detectable in milk for at least a week, but not at 13 days after a dose of 30 mg per square meter. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[2] Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.

Drug Levels

Maternal Levels. A woman with a history of treatment for thyroid cancer and recurrence during pregnancy was treated postpartum with paclitaxel and carboplatin. Her intravenous paclitaxel dose was 56.1 mg (30 mg per square meter) weekly for 6 weeks. Whole milk samples were obtained at 4, 28, 172, and 316 hours after the sixth dose. The highest milk paclitaxel level was 1.17 mg/L in the 28-hour sample and paclitaxel was undetectable (<80 mcg/L) in the 316 hour sample. Metabolites were not measured. The authors calculated an average milk paclitaxel level over the 316 hour collection period of 0.78 mg/L, resulting in an estimated total weight-adjusted infant daily dose of 16.7% of the maternal weekly dose.[3] Note that the above estimate of the infant daily dose is expressed as percentage of the maternal weekly dose, and that authors used a level of zero as the trough milk level, rather than a milk level taken before the sixth dose (which would equal approximately the 172-hour level of 0.97 mg/L), resulting in an underestimate of the AUC and infant dose.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 9 women who received a taxane-containing regimen, 7 had breastfeeding difficulties.[4]

References

1. Pistilli B, Bellettini G, Giovannetti E et al. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: How should we counsel cancer patients about breastfeeding? Cancer Treat Rev. 2013;39:207-11. PMID: 23199900

2. Urbaniak C, McMillan A, Angelini M et al. Effect of chemotherapy on the microbiota and metabolome of human milk, a case report. Microbiome. 2014;2:24. PMID: 25061513

3. Griffin SJ, Milla M, Baker TE et al. Transfer of carboplatin and paclitaxel into breast milk. J Hum Lact. 2012;28:457-9. PMID: 23087196

4. Stopenski S, Aslam A, Zhang X et al. After chemotherapy treatment for maternal cancer during pregnancy, is breastfeeding possible? Breastfeed Med. 2017;12:91-7. PMID: 28170295

Administrative Information

LactMed Record Number

1013

Last Revision Date

20170808

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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