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ABRAXANE FOR INJECTABLE is a brand name for Paclitaxel, supplied as a powder for suspension. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ABRAXANE® for Injectable Suspension (paclitaxel powder for injectable suspension) (nanoparticle, albumin-bound [nab®] paclitaxel) is indicated for: • the treatment of metastatic breast cancer. • the first-line treatment of metastatic adenocarcinoma of the pancreas, in combination with gemcitabine. ABRAXANE should be…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations No premedication to prevent hypersensitivity reactions is required prior to administration of ABRAXANE® for Injectable Suspension (paclitaxel powder for injectable suspension) (nanoparticle, albumin-bound [nab®] paclitaxel).
The primary elimination pathway for ABRAXANE is hepatic metabolism followed by biliary excretion. The exposure to paclitaxel may be higher in patients with hepatic impairment than in patients with normal hepatic function. 2 Recommended Dose and Dosage Adjustment).
As renal excretion is a minor elimination pathway for ABRAXANE, increased exposure to paclitaxel is not expected in patients with mild to moderate renal impairment. 2 Recommended Dose and Dosage Adjustment). Do not substitute for or with other paclitaxel formulations.
2 Recommended Dose and Dosage Adjustment Metastatic Breast Cancer The recommended regimen for ABRAXANE is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks. Dose levels of mg/m2 refer to mg of paclitaxel in ABRAXANE.
ABRAXANE® (paclitaxel) Page 6 of 47 Dose Adjustment for Treatment of Breast Cancer: Patients who experience severe neutropenia (neutrophil < 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, an 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.
Metastatic Pancreatic Cancer 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. The recommended dose of gemcitabine is 1000 mg/m2 as an intravenous infusion over 30-40 minutes beginning immediately after the completion of ABRAXANE administration on Days 1, 8 and 15 of each 28-day cycle.
Dose Adjustment for Treatment of Metastatic Pancreatic Cancer:
The recommended dose reductions for ABRAXANE and gemcitabine from the clinical trial are outlined in Tables 1 to 3 below. When a dose reduction was required, no dose re-escalation was permitted during the trial (with the exception of Day 15, see Table 2 below).
and 4 DOSAGE AND ADMINISTRATION). Hepatic/Biliary/Pancreatic In the randomized controlled trials, patients were excluded for elevated baseline serum bilirubin. ABRAXANE® (paclitaxel) Page 13 of 47 Exposure and toxicity of paclitaxel can increase with hepatic impairment.
Patients with hepatic impairment may be at increased risk of toxicity, particularly from myelosuppression; such patients should be closely monitored for development of profound myelosuppression. ABRAXANE is not recommended in patients that have total bilirubin > 5 x ULN or AST > 10 x ULN.
5 x ULN and AST < 10 x ULN). The starting dose should be reduced for patients with moderate or severe hepatic impairment (see 4 DOSAGE AND ADMINISTRATION). Immune Very rare occurrences of severe hypersensitivity reactions, including anaphylactic reactions with fatal outcome have been reported.
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be re-challenged with the drug. The use of ABRAXANE in patients exhibiting hypersensitivity to paclitaxel or human albumin has not been studied. Infection Sepsis was reported in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine.
Complications due to the underlying pancreatic cancer, especially biliary obstruction or presence of biliary stent, were identified as significant contributing factors. If a patient becomes febrile (regardless of neutrophil count), initiate treatment with broad spectrum antibiotics.
For febrile neutropenia, withhold ABRAXANE and gemcitabine until fever resolves and ANC ≥ 1500, then resume treatment at reduced dose levels (see 4 DOSAGE AND ADMINISTRATION). Injection Site Reactions Injection site reactions can occur with ABRAXANE.
Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Monitoring and Laboratory Tests 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.
Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX General Albumin (Human):
ABRAXANE® for Injectable Suspension (paclitaxel powder for injectable suspension) (nanoparticle, albumin-bound [nab®] paclitaxel) contains albumin (human), a derivative of human blood and is a nanoparticle albumin-bound (nab) form of paclitaxel.
Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote.
No cases of transmission of viral diseases or CJD have ever been identified for albumin. Carcinogenesis and Mutagenesis The carcinogenic potential of ABRAXANE has not been studied. Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice).
Paclitaxel injection was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay (see 16 NON-CLINICAL TOXICOLOGY). Cardiovascular AV block has been reported during treatment with paclitaxel as well as with the albumin-bound [nab] paclitaxel ABRAXANE.
08%). 5 Post-Market Adverse Reactions). ECG abnormalities were noted in 60% of patients treated with ABRAXANE in the metastatic breast cancer randomized trial. 2 Clinical Trial Adverse Reactions). ECG monitoring, particularly patients who are predisposed to cardiac risks from underlying malignancy, co-morbidities or concomitant use of chemotherapeutic drugs that may be cardiotoxic, should be considered during treatment with ABRAXANE.
Patients exhibiting signs and symptoms of AV block should be further monitored and appropriate medical therapy administered. Driving and Operating Machinery Adverse events such as fatigue, weakness and malaise may affect the ability to drive and use machines.
• ABRAXANE® is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing of ingredients, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
• ABRAXANE for Injectable Suspension (paclitaxel powder for injectable suspension) (nanoparticle, albumin-bound [nab®] paclitaxel) is contraindicated in patients who have baseline neutrophil counts of < 1,500 cells/mm3 on day 1 of each treatment cycle.
ABRAXANE® (paclitaxel) Page 5 of 47
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Due to dose-dependent and dose-limiting myelosuppression (primarily neutropenia) with ABRAXANE in combination with gemcitabine, more conservative dose modifications may be necessary based on clinical judgment and experience with chemotherapeutic drugs.
Note that the gemcitabine dose modifications used in the clinical trial differ from the recommendations in the GEMZAR product monograph.
Table 1:
Dose Level Reductions for Patients with Metastatic Pancreatic Cancer Dose Level ABRAXANE® Dose (mg/m2) Gemcitabine Dose (mg/m2) Full dose 125 1000a 1st dose level reduction 100 800a 2nd dose level reduction 75 600a If additional dose reduction required Discontinue treatment Discontinue treatmenta a.
dose modifications differ from the recommendations in the GEMZAR product monograph ABRAXANE® (paclitaxel) Page 7 of 47 Table 2: Dose Recommendation and Modifications for Neutropenia and/or Thrombocytopenia at the Start of a Cycle or Within a Cycle for Patients with Metastatic Pancreatic Cancer Cycle Day ANC count (cells/mm3) Platelet count (cells/mm3) ABRAXANE Dose Gemcitabine Dose Day 1 ≥ 1500 AND ≥ 100,000 Treat on time at current dose levels < 1500 OR < 100,000 Delay doses until recovery Day 8 ≥ 1000 AND ≥ 75,000 Treat on time at current dose levels ≥ 500 but < 1000 OR ≥ 50,000 but < 75,000 Reduce doses 1 dose level < 500 OR < 50,000 Withhold doses Day 15: IF Day 8 doses were given without modification: Day 15 ≥ 1000 AND ≥ 75,000 Treat on time at current dose levels ≥ 500 but < 1000 OR ≥ 50,000 but < 75,000 Treat at current dose level and follow with WBC Growth Factorsa, b < 500 OR < 50,000 Withhold doses Day 15: IF Day 8 doses were reduced: Day 15 ≥ 1000 AND ≥ 75,000 Return to the Day 1 dose level and follow with WBC Growth Factorsa, b ≥ 500 but < 1000 OR ≥ 50,000 but < 75,000 Treat with Day 8 dose level and follow with WBC Growth Factorsa, b < 500 OR < 50,000 Withhold doses Day 15: IF Day 8 doses were withheld: Day 15 ≥ 1000 AND ≥ 75,000 Return to Day 1 dose level and follow with WBC Growth Factorsa, b ≥ 500 but < 1000 OR ≥ 50,000 but < 75,000 Reduce 1 dose level and follow with WBC Growth Factorsa, b < 500 OR < 50,000 Withhold doses Abbreviations: ANC = Absolute Neutrophil Count; WBC GF = white blood cell growth factor.
a. In the clinical trials, G-CSF was optional if descent only affected platelets. b. If WBC Growth Factors are not available, a reduction in dose levels is recommended. Although this option was not included in the clinical trial protocol this approach is consistent with clinical practice.
ABRAXANE® (paclitaxel) Page 8 of 47 Table 3:
Dose Modifications for Other Adverse Drug Reactions in Patients with Metastatic Pancreatic Cancer Adverse Drug Reaction ABRAXANE Dose Gemcitabine Dose Febrile Neutropenia: Grade 3 or 4 Withhold doses until fever resolves and ANC ≥ 1500; resume at reduced dose levels.
5 x ULN and aspartate aminotransferase [AST] ≤ 10 x ULN), no dose adjustments are required regardless of indication. Treat […]
Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level > 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3 (see 4 DOSAGE AND ADMINISTRATION). Neurologic Sensory neuropathy occurs frequently with ABRAXANE.
The occurrence of grade 1 or 2 sensory neuropathy does not generally require dose modification. When ABRAXANE is used as monotherapy, if grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE (see 4 DOSAGE AND ADMINISTRATION).
For combination use of ABRAXANE and gemcitabine, if grade 3 or higher peripheral neuropathy develops, withhold ABRAXANE treatment until resolution to ≤ Grade 1 and resume at a reduced dose for all subsequent courses of ABRAXANE. The median time to first occurrence of Grade 3 peripheral neuropathy was 140 days, and the median time to improvement from Grade 3 peripheral neuropathy to Grade 0 or 1 was 29 days.
Of the patients with treatment interrupted due to peripheral neuropathy, 44% (31/70 patients) were able to resume ABRAXANE at a reduced dose. No patients treated with ABRAXANE/gemcitabine had Grade 4 peripheral neuropathy (see 4 DOSAGE AND ADMINISTRATION).
ABRAXANE® (paclitaxel) Page 14 of 47 Ophthalmologic There have been reports of reduced visual acuity due to cystoid macular edema (CME) during treatment with ABRAXANE as well as with other taxanes. 5 Post-Market Adverse Reactions). Patients with visual impairment during ABRAXANE treatment should seek a prompt and complete ophthalmologic examination.
ABRAXANE should be discontinued if a CME diagnosis is confirmed. Renal The use of ABRAXANE has not been adequately studied in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance <30 mL/min).
In the randomized controlled trials, patients were excluded for elevated baseline serum creatinine.
Reproductive Health:
Female and Male Potential Men should be advised to use effective contraception and to avoid fathering a child while receiving treatment with ABRAXANE and up to six months after treatment. Advise females of reproductive potential to use effective contraception during treatment with ABRAXANE and for at least six months after the last dose.
• Fertility Animal studies with ABRAXANE showed irreversible, toxic effects on the male reproductive organs including testicular atrophy/degeneration and decreased germinal epithelial cells at clinically relevant exposure levels. ABRAXANE induced infertility in male rats.
Administration of paclitaxel prior to and during mating produced impairment of fertility in male and female rats. Based on these findings in animals, ABRAXANE may impair fertility in females and males of reproductive potential. As ABRAXANE may decrease male fertility, preservation of sperm may be considered for the purpose of later fatherhood (see 16 NON-CLINICAL TOXICOLOGY).
• Teratogenic Risk Based on its mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman and male with reproductive potential (see 16 NON-CLINICAL TOXICOLOGY). Respiratory Pneumonitis, including some cases that were fatal, has been reported in 4% of patients treated with ABRAXANE in combination with gemcitabine.
Of the 17 pneumonitis ADRs in the ABRAXANE/gemcitabine arm, 2 had a fatal outcome. Due to cases of pneumonitis seen in the clinical trial, patients with a history of interstitial lung disease, multiple allergies or progressive dyspnea and […]
Hematologic Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3/4 neutropenia occurred in 34% of patients with metastatic breast cancer and in 38% of patients with pancreatic cancer.
ABRAXANE therapy should not be administered to patients with baseline neutrophil counts of less than 1,500 cells/mm3 and baseline platelet counts of less than 100,000 cells/mm3 on day 1 of each treatment cycle. In order to monitor the occurrence of myelotoxicity, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE.
Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level > 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3 (see