Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
nab-PACLitaxel
nab-PACLitaxel
SYNONYM(S): nanoparticle albumin-bound paclitaxel; paclitaxel protein bound
COMMON TRADE NAME(S): Abraxane®
Nanoparticle albumin-bound (nab) paclitaxel is a form of paclitaxel which works as an antimicrotubule agent. Paclitaxel, the active ingredient in nab-paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This interferes with the normal dynamic reorganization of the microtubule network required for interphase and mitotic functions. It is hypothesized that nanoparticle albumin-bound paclitaxel facilitates the transport of paclitaxel across the endothelial cell via an albumin-receptor mediated pathway.
Following intravenous administration of nab-paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner, the initial rapid decline representing distribution to the peripheral compartment and the slower second phase representing drug elimination.
Extensive extravascular distribution and/or tissue binding. Drug exposure is dose-proportional over 80 to 300 mg/m2.
| PPB |
94% |
Hepatic metabolism (CYP2C8 forming major metabolite; minor metabolites via CYP3A4) account for the majority of elimination.
| Active metabolites |
yes |
| Inactive metabolites |
yes |
| Half-life |
13-27 hours |
| Feces |
Approximately 20% |
| Urine |
4% as unchanged drug, <1% as metabolites |
- Breast cancer
- Pancreatic cancer
Refer to the product monograph for a full list and details of approved indications.
Other Uses:
- Bladder/Urothelial cancer
- Melanoma
Emetogenic Potential:
Extravasation Potential: Irritant
The following adverse effects were reported in monotherapy trials for metastatic breast cancer. The incidence of many may be higher when used in combination with gemcitabine. Severe adverse events from other studies or post-marketing, may also be included.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Arterial thromboembolism (<1%) | E | |||
| Atrioventricular block (rare) | I E | ||||
| Bradycardia (<1%) | E | ||||
| Cardiotoxicity (<10%) (prior cardiac history or cardiotoxins) | D | ||||
| ECG changes (35%) | E | ||||
| Hypotension (5%) | I | ||||
| Venous thromboembolism (rare) | E | ||||
| Dermatological | Alopecia (90%) | E | |||
| Nail disorder (1%) | E | ||||
| Other - Scleroderma-like skin changes (rare) | E | ||||
| Photosensitivity (rare) | E | ||||
| Rash, pruritus (9%) (may be severe) | E | ||||
| Gastrointestinal | Anorexia (very common) | E | |||
| Constipation (very common) | E | ||||
| Dehydration (<10%) | E | ||||
| Diarrhea (27%) (may be severe) | E | ||||
| Esophagitis (rare) | E | ||||
| GI obstruction (<1%) | E | ||||
| GI perforation (<1%) | E | ||||
| Mucositis (7%) | E | ||||
| Nausea, vomiting (30%) | I | ||||
| General | Edema (10%) | E | |||
| Fatigue (47%) (8% severe) | E | ||||
| Hematological | Hemolytic uremic syndrome (rare) | E | |||
| Myelosuppression ± infection, bleeding (80%) (9% severe) | E | ||||
| Thrombotic thrombocytopenic purpura (TTP; rare) | E | ||||
| Hepatobiliary | ↑ LFTs (39%) (rarely severe) | E | |||
| Pancreatitis (<1%) | E | ||||
| Hypersensitivity | Hypersensitivity (4%) (rarely severe) | I | |||
| Injection site | Injection site reaction (1%) (including extravasation and radiation recall; rarely may be severe) | I E | |||
| Metabolic / Endocrine | Tumor lysis syndrome (rare) | E | |||
| Musculoskeletal | Musculoskeletal pain (44%) (8% severe) | E | |||
| Nervous System | Autonomic neuropathy (rare) | E D | |||
| Cognitive disturbance (rare) | E | ||||
| Cranial neuropathy (rare) | E | ||||
| Dizziness (rare) | E | ||||
| Mood changes (rare) | E | ||||
| Sensory neuropathy (71%) (10% severe ) | E D | ||||
| Ophthalmic | Conjunctivitis (rare) | E | |||
| Eye disorders (13%) (1% severe including keratitis and blurred vision) | E | ||||
| Optic neuritis (rare) | E | ||||
| Other - Cystoid macular edema (rare) | E | ||||
| Watering eyes (rare) | E | ||||
| Renal | Creatinine increased (11%) | E | |||
| Renal failure (<10%) (acute) | E | ||||
| Respiratory | Cough, dyspnea (12%) | E | |||
| Other - Lung Fibrosis (rare) | E D | ||||
| Pneumonitis (rare) | E D | ||||
| Pneumothorax (rare) | E D | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for nab-paclitaxel include alopecia, myelosuppression ± infection, bleeding, sensory neuropathy, fatigue, musculoskeletal pain, ↑ LFTs, ECG changes, nausea, vomiting, diarrhea and eye disorders.
Myelosuppression, primarily neutropenia, is a dose-dependent and dose-limiting toxicity. Neutropenia is usually rapidly reversible and may be more frequent in patients receiving a combination with gemcitabine for pancreatic cancer. Significant risk factors included complications of underlying pancreatic cancer, such as biliary obstruction or presence of a biliary stent. Febrile patients, even if not neutropenic, should receive broad spectrum antibiotics.
Hypotension during the 30-minute infusion occurred in 5% of patients; however, this was generally asymptomatic and required neither specific therapy nor treatment discontinuation.
ECG abnormalities were common; they did not usually result in symptoms, were not dose-limiting and required no intervention. AV block requiring pacing has been reported; patients should be monitored and managed appropriately.
Hypersensitivity reactions were observed in 4% of patients; severe occurrences have been reported rarely during post-marketing. Premedication is not generally necessary prior to nab-paclitaxel, although may be needed in patients with prior mild to moderate hypersensitivity reactions. Discontinue nab-paclitaxel permanently if patient experiences a severe hypersensitivity reaction (do not re-challenge).
Sensory neuropathy is dose-related and cumulative, may be dose-limiting or even require discontinuation of therapy (3% in breast cancer trial). Frequency and severity is also influenced by prior and/or concomitant therapy with neurotoxic agents. Median time to first occurrence of grade 3 peripheral neuropathy was 140 days and median time to improvement to grade 1 or less was 29 days.
Cystoid macular edema (CME) resulting in reduced visual acuity has been reported rarely. Most reports of CME have resolved following therapy discontinuation.
Refer to protocol by which patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Do not substitute for or with other paclitaxel formulations.
Nab-paclitaxel should only be administered if neutrophils ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L on day 1 of each treatment cycle.
In the pivotal trial for Metastatic Pancreatic Cancer where patients received nab-paclitaxel and gemcitabine:
-
Patients were provided with a supply of antibiotic prophylaxis (ciprofloxacin or amoxicillin/clavulanate), to be used at first occurrence of fever ≥ 38.5C. The use of long-term antibiotic prophylaxis for recurrences in patients who had experienced a first febrile episode will be at the discretion of the treating physician.
-
G-CSF may be given according to institutional guidelines (also refer to dose modifications).
Metastatic breast cancer:
Alternative schedules (e.g. 100mg/m2 to 150mg/m2 IV days 1, 8, 15; every 4 weeks) have been used in clinical trials, but these have not been approved by Health Canada.
Metastatic pancreatic cancer:
Intravenous: 125 mg/m² Days 1, 8, 15 of 28 day cycle (in combination with gemcitabine)
For information pertaining to gemcitabine dosing refer to GEMCNPAC(W).
Metastatic Breast Cancer
Do not retreat until recovery from toxicity and neutrophils ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L.
Table 1:
|
Worst Toxicity / Counts (x109/L) in previous cycle
|
Nab-paclitaxel Dose (mg/m2) Every 3 Weeks
|
||
|
First occurrence
|
Second occurrence
|
Third Occurrence
|
|
|
ANC < 0.5 ≥ 7 days or
Febrile neutropenia or Grade 4 platelets or bleeding |
*220 mg/m2
|
*180 mg/m2
|
Discontinue
|
| Grade 3 or 4 sensory neuropathy or other grade 3 related organ toxicity | *220 mg/m2 OR consider discontinuing for Grade 4 neurotoxicity | *180 mg/m2 OR consider discontinuing for Grade 4 neurotoxicity | Discontinue |
| Other grade 4 related organ toxicity; severe hypersensitivity, or any cystoid macular edema | Discontinue | ||
| Pneumonitis | Hold and investigate; discontinue if confirmed | n/a | |
| *Do not retreat until ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and other toxicity ≤ grade 2. | |||
Metastatic Pancreatic Cancer
Table 2: Dose levels
| Dose Level | Nab-paclitaxel Dose (mg/m2) |
| Full dose | 125 |
| -1 | 100 |
| -2 | 75 |
| Further reduction required | Discontinue |
Start Day 1 when ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and other toxicities ≤ grade 2 or as stated below. Do not escalate reduced doses (with the exception of Day 15; see Table 4).
Table 3: Dose modifications at the start of cycle or during cycle
|
Worst Toxicity
|
Nab-paclitaxel Dose
|
|
Grade 3 or 4 febrile neutropenia
|
Hold until afebrile and ANC ≥ 1.5 x 109/L, then ↓1 dose level*
|
|
Grade 2 or 3 cutaneous toxicity
|
↓1 dose level; discontinue if persists
|
|
Grade 3 or 4 sensory neuropathy
|
Hold until ≤ grade 1*; restart at 1 dose level ↓ OR consider discontinuing for grade 4 |
|
Other grade 3 toxicity, including mucositis, diarrhea (except nausea/vomiting/alopecia)
|
Hold until ≤ grade 1*; restart at 1 dose level ↓ |
|
Other grade 4 toxicity or severe hypersensitivity, or any cystoid macular edema
|
Discontinue
|
|
Pneumonitis
|
Hold and investigate; discontinue if confirmed.
|
*In the clinical trial (Hoff et al), if treatment was delayed for ≥ 21 days (including neutropenia despite uninterrupted G-CSF treatment), treatment was discontinued.
Table 4: Hematologic dose modifications within cycle
Omitted doses during the cycle will not be made up. Note day 15 dose modifications depend on day 8 dosing.
|
Day 8 counts x 109/L
|
Day 8 Nab-paclitaxel Dose
|
Day 15 counts x 109/L
|
Day 15 Nab-paclitaxel
Doses
|
|
ANC ≥ 1 and platelets ≥ 75
|
Day 1 dose
|
If Day 8 dose unchanged from Day 1:
|
|
|
ANC ≥ 1 and platelets ≥ 75
|
Day 1 dose
|
||
|
ANC 0.5-0.99 or platelets 50-74
|
Day 1 dose, add G-CSF1, 2
|
||
|
ANC < 0.5 or platelets < 50
|
Omit, add G-CSF2
|
||
|
ANC 0.5- 0.99 or platelets 50-74
|
↓ 1 Dose Level
|
If Day 8 dose was REDUCED:
|
|
|
ANC ≥ 1 and platelets ≥ 75
|
Day 1 dose, add G-CSF1, 2
|
||
|
ANC 0.5-0.99 or platelets 50-74
|
Day 8 dose, add G-CSF1, 2
|
||
|
ANC < 0.5 or platelets < 50
|
Omit, add G-CSF2
|
||
|
ANC < 0.5 or platelets < 50
|
Omit for Day 8
|
If Day 8 dose was OMITTED:
|
|
|
ANC ≥ 1 and platelets ≥ 75
|
Day 1 dose , add G-CSF1, 2
|
||
|
ANC 0.5-0.99 or platelets 50-74
|
↓ 1 Dose Level, add G-CSF1, 2
|
||
|
ANC < 0.5 or platelets < 50
|
Omit, add G-CSF2
|
||
1If G-CSF is not available, suggest reducing an additional dose level. G-CSF was optional for isolated thrombocytopenia.
2G-CSF was optional in clinical trials for isolated thrombocytopenia.
Patients with hepatic impairment may be at increased risk of myelosuppression and should be closely monitored.
Nab-paclitaxel is not recommended in patients with metastatic pancreatic cancer who have moderate to severe hepatic impairment.
|
Bilirubin |
|
AST |
Nab-paclitaxel* (% previous dose - suggested) |
|
>1 to ≤ 1.5 x ULN |
and |
≤ 10 x ULN |
100% |
|
>1.5 to ≤ 5 x ULN |
and |
≤ 10 x ULN |
↓ to 80% for metastatic breast cancer**; Discontinue for metastatic pancreatic cancer (has not been studied). |
|
> 5 x ULN |
or |
> 10 x ULN |
Discontinue (has not been studied). |
*Based on clinical judgment. Patients with elevated baseline bilirubin were excluded from clinical trials. Less conservative adjustments can be considered if hepatic changes are secondary to metastases rather than hepatic cirrhosis or hepatitis.
**Reduced dose may be escalated to 100% if treatment is tolerated for at least 2 cycles at the reduced dose.
|
Creatinine Clearance (mL/min) |
Nab-paclitaxel* (% previous dose - suggested) |
|
≥ 30 to < 90 |
100% |
|
< 30 |
Discontinue (has not been studied). |
*Based on clinical judgment. Patients with elevated baseline creatinine were excluded from clinical trials.
No dose adjustment is required. Patients aged 65 years or older may have higher incidence of neutropenia in cycle 1. Patients aged 65 and older who received nab-paclitaxel monotherapy for metastatic breast cancer had a higher incidence of epistaxis, diarrhea, dehydration, fatigue and peripheral edema.
Patients 75 years and older who received nab-paclitaxel in combination with gemcitabine for pancreatic cancer had a higher incidence of serious adverse reactions and no demonstrated survival benefit.
Safety and effectiveness in children have not been determined.
- Refer to the product monograph for full instructions on reconstitution.
- The reconstituted suspension should be milky and homogenous without visible particulates.
- Avoid shaking drug suspension in order to minimize foaming.
- No further dilution is required after reconstitution. Transfer reconstituted drug to an empty, sterile IV PVC or non-PVC infusion bag.
- Infuse intravenously over 30 minutes (breast cancer) or over 30 to 40 minutes (pancreatic cancer). Slower infusion rates may increase the likelihood of infusion-related reactions.
- When administered as part of a combination chemotherapy regimen with gemcitabine, nab-paclitaxel should be given first, followed immediately by gemcitabine.
- DEHP-free containers or administration sets may be used but are not required.
- Do not admix with other drugs.
- Use of syringes and IV bags containing silicone oil as lubricant may cause formation of proteinaceous strands. If strands are observed by visual inspection of IV bag, administer reconstituted suspension through filter of at least 15 µm pore size. If this is not possible, discard the product.
- Store unopened vial at 20-25⁰C in its original carton; protect from light.
- Patients who have a hypersensitivity to this drug or any of its components (such as albumin) in the formulation or container
- Patients with baseline ANC of < 1.5 x 109/L on day 1 of each treatment cycle
- Do not administer nab-paclitaxel to patients with platelets < 100 x 109/L.
- The use of nab-paclitaxel in patients exhibiting hypersensitivity to paclitaxel or human albumin has not been studied.
- Patients with elevated baseline bilirubin or elevated baseline creatinine were excluded from clinical trials.
- The use of albumin-containing solutions is associated with a remote risk of viral transmission, including CJD.
- Radiation recall and pneumonitis have been reported in patients with concurrent radiotherapy.
- Nab-paclitaxel is not recommended for use in patients with a history of interstitial lung disease, multiple allergies, progressive dyspnea or unproductive cough (cases of serious pneumonitis were reported in those treated with combination nab-paclitaxel and gemcitabine).
- Caution is recommended prior to driving or operating machinery if fatigue, weakness or dizziness are present.
Other Drug Properties:
-
Carcinogenicity:
Unknown
-
Clastogenicity:
Yes
-
Fetotoxicity:
Yes
-
Mutagenicity:
No
-
Teratogenicity:
Probable
-
Embryotoxicity:
Yes
Nab-paclitaxel is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 6 months after the last dose.
-
Excretion into breast milk:
Documented in animals
Breastfeeding is not recommended during treatment and for 2 weeks after the last dose.
-
Fertility effects:
Probable
No drug interaction studies have been conducted with nab-paclitaxel, but are likely to be similar to those reported for paclitaxel, which is metabolized by CYP2C8 and CYP3A4 (refer to the paclitaxel drug monograph). Pharmacokinetic interactions between nab-paclitaxel and gemcitabine have not been evaluated in vivo. The drugs have different metabolic pathways.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Radiation | Radiation pneumonitis | ↑ pulmonary effects | Avoid/Caution |
| CYP2C8 substrates (e.g. paclitaxel, repaglinide, rosiglitazone) | May ↑/↓ effects of substrates or paclitaxel | Altered metabolism of CYP2C8 substrates or paclitaxel | Caution |
| CYP2C8 Inducers (e.g. rifampin) | May ↓ paclitaxel levels and effects | ↑ metabolism of paclitaxel | Caution |
| CYP 2C8 inhibitors (i.e. gemfibrozil, montelukast) | May ↑ paclitaxel levels and effects | ↓ metabolism of paclitaxel | Caution |
| CYP 3A4 substrates (i.e., verapamil, etoposide, dexamethasone, vincristine) | May ↑/↓ effects of substrates or paclitaxel | Altered metabolism of CYP3A4 substrates or paclitaxel | Caution |
| CYP3A4 inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc) | May ↓ paclitaxel levels and effects | ↑ metabolism of paclitaxel | Caution |
| CYP3A4 inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit) | May ↑ paclitaxel levels and effects | ↓ metabolism of paclitaxel | Caution |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
Liver function tests |
Baseline, before each cycle and as clinically indicated |
CBC |
Baseline and before each dose |
Renal function tests |
Baseline and as clinically indicated |
ECG monitoring especially in patients who have cardiac risk factors |
Baseline and as clinically indicated |
Clinical toxicity assessment of fatigue, neuropathy, infection and bleeding, hypersensitivity, musculoskeletal, GI, ophthalmic, thromboembolism, local reactions and pneumonitis |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
New Drug Funding Program (NDFP Website )
- Nab-Paclitaxel - Metastatic Breast Cancer
- Gemcitabine and Nab-Paclitaxel - Advanced Pancreatic Cancer
Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. U.S. Food and Drug Administration. Accessed May 29, 2013. Available from:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/
DrugInteractionsLabeling/ucm093664.htm
Gradishar WJ, Krasnojon D, Cheporov S, et al. Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival. Clin Breast Cancer 2012;12(5):313-21.
Gradishar WJ, Krasnojon D, Cheporov S, et al. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol 2009; 27: 3611-9.
Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil–based paclitaxel in women with breast cancer. J Clin Oncol 2005; 23: 7794-803.
P450 Drug Interaction Table. Indiana University School of Medicine, January 12, 2009. Available from: http://medicine.iupui.edu/clinpharm/ddis/table.aspx
Prescribing information: Abraxane® (paclitaxel protein-bound). Abraxis BioScience (US), September 2009 and August 2020.
Product Monograph: Abraxane® (nab-paclitaxel). Celgene Inc., May 2018 and Aug 2023.
Robinson DM, Keating GM. Albumin-bound paclitaxel in metastatic breast cancer. Drugs 2006; 66(7): 941-8.
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369(18):1691-703.
November 2023 Modified Indications and Pregnancy/lactation sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.