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Drug Monographs
Treatment Regimens

Scientific Name:
NAB PACLITAXEL (NANOPARTICLE, ALBUMIN-BOUND)
Brand Name(s):
Abraxane®

Drug Monograph

Pharmacology

Mechanism of Action

Causes formation of stable microtubule bundles by promoting assembly and preventing depolymerization, interfering with the late G2 mitotic phase, and inhibiting cell replication; it may also supress cell proliferation and modulate immune response.

Pharmacokinetics

Similar to Paclitaxel
Distribution:
Vd indicates extensive extravascular distribution and/or tissue binding;
Vd  = 632 L/m2 Cmax = 18,741 ng/mL
AUC = 17,940 h*ng/mL
Metabolism:
uncertain, hepatic metabolism and biliary secretion probably account for the majority of elimination
metabolite(s): 6a-hydroxypaclitaxel, 3’-p-hydroxypaclitaxel
Excretion:
primarily as unchanged drug and unidentified metabolites in bile and feces
Urine: 4 % as unchanged drug
Cl = 15.2 L/hr/m2  t½ = 21 hours

Side Effects

IMMEDIATE ONSET (hours to days)
* hypersensitivity reaction (4%)- none severe- dyspnea, flushing, hypotension, chest pain, arrhythmia (monitoring and on-hand emergency medications required)
   decreased heart rate during infusion (<1%, bradycardia)
   low blood pressure during infusion (5%)
   injection site reactions- vein irritation (phlebitis, erythema, tenderness, discomfort)- rare
   nausea (30%), vomiting (18%), usually mild to moderate
EARLY ONSET  (days to weeks)
* neutropenia (89%- 9% grade 4), infections (24%), anemia (34%), thrombocytopenia (2%)
   asthenia (47%)
   diarrhea (27%)
   alopecia (90%) usually total)
   nerve problems (71% sensory neuropathy, 10% severe), peripheral motor neuropathy, cranial nerve palsies, vocal cord paresis
   muscle and joint pain (44%, myalgia/arthralgia, usually mild- 8% severe)
   dyspnea (12%), cough (7%)
   fluid retention/edema (10%)
   mouth sores (7%)
* heart problems (35% ECG changes, severe cardiovascular events 3%- chest pain, cardiac
arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism,
pulmonary emboli, hypertension)
* intestinal obstruction, intestinal perforation, pancreatitis, ischemic colitis- all rare
   liver problems- elevated liver function tests- (AST 39%, alkaline phosphatase 36%);  cholangitis
   acute renal failure, hemolytic uremic syndrome (HUS)
   pleural effusion, pulmonary edema, diffuse alveolar damage, diffuse pneumonitis- rare   ocular/visual disturbances (13%- 1% severe)- conjunctivitis, increased lacrimation, loss of vision, optic neuropathy, cystoid macular edema (CME)
   radiation recall reaction
   skin disorders- erythema, maculo-papular rash, pruritus, photosensitivity reaction
   Stevens-Johnson syndrome, toxic epidermal necrolysis- rare
DELAYED/LATE ONSET
* cerebrovascular attacks (strokes), transient ischemic attacks- rare
* cardiac ischemia/infarction- rare
* thrombosis/embolism- rare
* interstitial pneumonia, lung fibrosis, pulmonary embolism- all rare

Therapeutics

Approved Indications

• Metastatic breast cancer

Routes

IV infusion ( over 30 minutes).

Administration

• Infuse the dose over 30 minutes from the infusion bag through the sidearm of a free-flowing IV with NS; flush the tubing with NS after dose completed.  PVC equipment may be used.
• Do NOT use an in-line filter; do not dilute the infusion bag further or mix with any other diluents
• Take a baseline blood pressure measurement, if prior hypotension noted
• NO PREMEDICATION is needed

IV Compatibility

Normal saline ONLY.

Antiemetic Risk

INTERMEDIATE RISK (10-30% of patients)
• Use a  dexamethasone pre-chemotherapy and a dopamine receptor antagonist PRN post-chemotherapy

Contraindications

Use with caution in patients with known hypersensitivity to paclitaxel or any ingredients in Abraxane formulation.

Monitoring

Clinical Monitoring

RECOMMENDED CRITERIA
• Complete blood count including differential, platelets and hemoglobin (CBC) before each cycle of treatment
• Watch for symptoms of fever or infection
• Neurologic (Sensory)  and flu-like symptoms toxicity ratings at each visit
• Baseline blood pressure and pulse rate monitoring
 (Arthralgia, myalgia)
 
FLU-LIKE SYMPTOMS
0. None
1. Mild
2. Moderate
3. Severe
 
SENSORY
0. No change
1. Mild paraesthesia; no deep tendon reflex
2. Mild/moderate sensory loss; moderate paraesthesia
3. Sensory loss interferes with function
 Rated At Each Clinic Visit

SUGGESTED CRITERIA
• Baseline liver function tests (if liver failure suspected) [serum alkaline phosphatase, GGT, ALT, AST & Bilirubin levels (serum proteins may be added if indicated)]
• Periodic renal function tests [serum creatinine, electrolytes & BUN]
• Blood pressure and pulse rate monitoring during drug administration (& for the following hour)

Extravasation Hazard

IRRITANT (cellulitis, inflammation). Management- stop IV, aspirate, elevate limb, warm intermittent compresses. Follow Extravasation Guidelines.

Significant Interactions

None known, but likely similar to regular Paclitaxel. Cytochrome P450 Substrate.

Product Information

Commercial Product Description

50 mL Vials with 100mg Paclitaxel (Nanoparticle, Albumin-Bound) powder.

Pharmaceutical Considerations

Injection:
Reconstitute each vial with 20 mL Normal Saline by slowly injecting the diluent down the side of each vial over 1 minute for each vial.  Be careful not to inject the diluent directly onto the lyophilized cake, to avoid foaming.  Allow vials to sit for 5 minutes, for wetting of the drug powder.  When the powder is fully wetted, gently swirl and/or invert each vial for at least 2 minutes until dissolution is complete.  Avoid generation of foam- if foaming or clumping occurs, let solution stand for at least 15 minutes until foam subsides.  Inspect final product for particulate matter or idiscoloration.  The final product should be milky and homogenous.
WIthdraw the volume of drug needed to fill the prescribed dose at 5 mg/mL.  Inject the full dose into an empty,sterile PVC infusion bag.  PVC equipment and tubing may be used, but do not attach an in-line filter.  The drug is administered without further dilution.
The vials of dissolved product or the filled bags should be used as soon as possible, but may be stored for up to 8 hours at room temperature or refrigeration.  Protect from bright light, but the product does not need protection from normal ambient room light.  Use precautions for handling cytotoxic antineoplastic products.

Product:
Abraxane is similar to Paclitaxel in most characteristics, except that the final product is formulated as nanoparticles which are bound to serum albumin.  This formulation is hypothesized to facilitate transport of paclitaxel across endothelial cells and to result in higher intra-tumour concentrations.  The formulation also eliminates the need for Cremophor as a solubilizing agent, and the hypersensitivity reactions associated with the Cremophor.  Thus, the drug may be given without premedications to prevent hypersensitivity and may be administered over a short time period.  Most other adverse effects are the same as regular Paclitaxel.

Handling Risk Level

Pregnancy DKNOWN HAZARDOUS DRUG
FDA Pregnancy Risk Factor D

  • This drug must be handled using precuations outlined in CCNS Policies for Occupational Safety and Administering Cancer Chemotherapy

Note

HANDLING RISK LEVEL:

HAZARD RISK LEVEL 2
FDA Pregnancy Risk Factor D
• This drug must be handled using precautions outlined in CCNS Policies for Preparing Cancer Chemotherapy and Administering Cancer Chemotherapy
• Go to "Additional Information" tab (above) for links to CCNS Policies

GUIDELINES:

NCDF Coverage Criteria:  Treatment of Advanced Breast Cancer
As a single agent treatment option in a q 3 week schedule (as a first, second, or third line therapy) for patients with metastatic breast cancer (MBC) who have an ECOG performance status of 0 to 2 and choose to receive systemic chemotherapy.  Nab-paclitaxel in the adjuvant setting is currently not recommended.

Pancreatic Cancer:
NAB-Paclitaxel in combination with gemcitabine in patients with locally advanced unresectable or metastatic adenomacarcinoma of the pancreas, and with an ECOG performance status of 0 – 2. (Pending availability of funding).  September 23, 2014

Visit the Pan-Canadian Oncology Drug Review website (www.pcodr.ca) for the guidelines on NAB-paclitaxel for pancreatic cancer.
• Go to "Additional Information" tab (above) for links to pCODR Reviews


Availability & Funding

Administrative Information (Nova Scotia)

• CCNS Provincial Formulary Status- Intermediate Level • Go to "Additional Information" tab (above) for links to Provincial Formulary of Cancer Drugs • Pharmacare Formulary Status- Non-Formulary • NOTE: It is recommended to limit ordering of this medication to standard preprinted order forms, for patient safety.

New Cancer Drug Fund Status (Nova Scotia)

New Cancer Drug Fund (NCDF) funding approved for: Treatment of Advanced Breast Cancer- As a single agent treatment option in a q 3 week schedule (as a first, second, or third line therapy) for patients with metastatic breast cancer (MBC) who have an ECOG performance status of 0 to 2 and choose to receive systemic chemotherapy. Nab-paclitaxel in the adjuvant setting is currently not recommended.



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