ABRAXANE(r)
CLASSIFICATION: antimicrotubule agent,1 cytotoxic
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
This is a paclitaxel formulation that contains albumin (human) and is nanoparticle albumin-bound.1 See Paclitaxel Monograph for detailed mechanism of action.
| Distribution | cross blood brain barrier? | no information found |
| volume of distribution | 632 L/m 2 | |
| plasma protein binding | no information found | |
| Metabolism | hepatic via CYP2C8 and CYP3A4 | |
| active metabolite(s) | 6a-hydroxypaclitaxel (major); 3 -p-hydroxypaclitaxel and 6a, 3 -p-dihydroxypaclitaxel (minor) | |
| inactive metabolite(s) | no information found | |
| Excretion | extensive non-renal clearance | |
| urine | unchanged drug (4%) | |
| feces | (20%) | |
| terminal half life | 27.4 h | |
| clearance | 15.2 L/h/m 2 | |
Adapted from standard reference1 unless specified otherwise.
Primary uses: Other uses:
*Breast cancer, metastatic
*Health Canada approved indication
Do not administer if neutrophil counts are <1,500 cells/mm3 at baseline (equivalent to 1.5 x 109 cells/L). Do not substitute with or for other paclitaxel formulations. Theoretical risk of viral disease transmission, due to human albumin component, is extremely remote. Premedication to prevent hypersensitivity reactions is not required prior to administration. Contains no alcohol.
Carcinogenicity: 1
not studied
Mutagenicity: Paclitaxel nab is not mutagenic in Ames test and mammalian in vitro mutation test.1 It is clastogenic in mammalian in vitro and in vivo chromosome tests.
Fertility: 1
testicular atrophy/degeneration in male rats, and reduced fertility in untreated female mates
Pregnancy: FDA Pregnancy Category D.2 There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life- threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Breastfeeding 1
is not recommended due to the potential secretion into breast milk.
The table includes adverse events that presented during drug treatment but may not necessarily have a causal relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they were reported in more than 1% of patients in the product monograph. When placebo-controlled trials are available, adverse events are included if the incidence is >5% higher in the treatment group.
| ORGAN SITE | SIDE EFFECT |
| allergy/immunology | hypersensitivity reaction (1-4%) |
| blood/bone marrow/ febrile neutropenia | anemia (20%) |
| febrile neutropenia (2%) | |
| neutropenia (80%), may be severe | |
| leucopenia (72%) | |
| thrombocytopenia (2%) | |
| cardiovascular (arrhythmia) | abnormal ECG (all patients 60%, patients with abnormal baseline 35%) |
| cardiovascular (general) | hypotension(5%); during infusion, often asymptomatic |
| severe cardiovascular events (3%), including chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension | |
| constitutional symptoms | asthenia (47%, severe 8%) |
| dermatology/skin | extravasation hazard: irritant |
| alopecia (90%) | |
| injection site reaction (1%) | |
| nail changes (1%) | |
| skin changes, transient including rash (9%), flushing 2%, pruritus 6% | |
| gastrointestinal | emetogenic potential: low 3 |
| anorexia | |
| constipation | |
| dehydration | |
| diarrhea (27%) | |
| mucositis (7%) | |
| nausea (30%) | |
| vomiting (18%) | |
| hemorrhage | bleeding (2%) |
| infection | fever (14%) |
| infections (24%); most frequently oral candidiasis, respiratory tract infection, pneumonia | |
| ORGAN SITE | SIDE EFFECT |
| metabolic/laboratory | alkaline phosphatase elevations (36%) |
| ALT elevations (36%) | |
| AST elevations (39%) | |
| bilirubin elevations (7%) | |
| GGT elevations (50%, severe 14%) | |
| musculoskeletal | arthralgia/myalgia (44%, severe 8%) |
| asthenia (47%) | |
| neurology | sensory neuropathy (71%, severe 10%) |
| ocular/visual | ocular/visual disturbances (13%) |
| pulmonary | see severe cardiovascular events in cardiovascular (general) |
| cough (7%) | |
| dyspnea (12%) | |
| fluid retention/edema (10%) | |
| renal/genitourinary | creatinine elevation (11%, severe <1%) |
Adapted from standard reference1 unless specified otherwise.
Nab-paclitaxel 1
is metabolized by CYP2C8 and CYP3A4; caution should be exercised when administering with drugs which are CYP 2C8 or CYP3A4 inducers or inhibitors.
Injection: Abraxis Oncology supplies the drug as a single use vial containing 100 mg of paclitaxel and approximately 900 mg of human albumin.1 Store vials in original containers at 20-25deg C. Protect from bright light.
For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation and Stability Chart in Appendix.
For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation and Stability Chart in Appendix.
.
Additional information1: do NOT inject NS diluent directly onto powder or excessive foaming will occur allowing reconstituted solution to stand will enable wetting of powder if foaming or clumping occurs, stand solution for a minimum of 15 minutes until foam subsides reconstituted solution should be milky and homogenous without visible particles If visible particulates present, gently invert vial for complete resuspension prior to use latex-free stopper neither freezing nor refrigeration adversely affects the stability of the product
Compatibility: 1
Do not mix any other drugs.
| BCCA administration guideline noted in bold , italics | |
| Subcutaneous | no information found |
| Intramuscular | no information found |
| Direct intravenous | no information found |
| Intermittent infusion | over 30 min 1 |
| Continuous infusion | no information found |
| Intraperitoneal | no information found |
| Intrapleural | no information found |
| Intrathecal | no information found |
| Intra-arterial | no information found |
| Intravesical | no information found |
non-PVC bag and tubing are NOT needed
do NOT filter
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Guidelines for dosing also include consideration of absolute neutrophil count (ANC). Dosage may be reduced, delayed or discontinued in patients with bone marrow depression due to cytotoxic/radiation therapy or with other toxicities.
Adults: Cycle Length: BCCA usual dose noted in bold, italics Intravenous: 3 weeks1: 260 mg/m2 IV for one dose on day 1 Dose reductions:
220 mg/m2 for neutrophils <500 cells/mm3 (equivalent to
0.5 x 109 cells/L) for a week or longer, or severe sensory neuropathy 180 mg/m2 for severe neutropenia or severe sensory neuropathy hold for grade 3 sensory neuropathy, until resolution to grade 1 or 2, followed by a dose reduction for all subsequent doses
Concurrent radiation:
no information found
Dosage in myelosuppression:
modify according to protocol by which patient is being treated; if no guidelines
available, refer to Appendix 6 "Dosage Modification for Myelosuppression" Dosage in renal failure: not studied1; in the randomized controlled trial, patients were excluded for baseline serum creatinine >2 mg/dL1 (equivalent to 177 mmol/L) Dosage in hepatic failure: not studied1; in the randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL1
Dosage in dialysis:
no information found
Abraxis Oncology. ABRAXANE(r) product monograph. Richmond Hill, Ontario; 26 June 2006.
Karen Law, B. Pharm. Personal communication. Product Director, Abraxis Oncology, A Division of Abraxis Bioscience, Inc; 6 September 2007.
BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in Adults. Vancouver, British Columbia: BC Cancer Agency; 1 November 2005.