Paclitaxel albumin bound parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Powder for suspension for infusion containing paclitaxel (as paclitaxel albumin).
Drugs List
Therapeutic Indications
Uses
Metastatic breast cancer where anthracycline therapy has failed
Metastatic pancreatic cancer in combination with gemcitabine
Non-small cell lung cancer(adj.)-if surgery/radiography not appropriate
Treatment of metastatic carcinoma of the breast where first-line therapy, including anthracycline therapy, has failed or is not appropriate.
First line treatment of metastatic adenocarcinoma of the pancreas in combination with gemcitabine.
First line treatment of non-small cell lung cancer (NSCLC) in patients unsuitable for curative surgery and/or radiation therapy, in combination with carboplatin.
Dosage
Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.
Patients with Hepatic Impairment
Breast Cancer and NSCLC
Bilirubin greater than 1.5 to equal to or below 5 x the Upper Limit of Normal (ULN) and AST equal to or below 10 x ULN: Reduce initial dose by 20%
Dose can be escalated to standard dosage if patient tolerates for 2 cycles.
Metastatic adenocarcinoma of the pancreas
Use not recommended.
Additional Dosage Information
Breast Cancer
Do not retreat with subsequent cycles of paclitaxel until neutrophils recover to greater than 1.5 x 10 to the power 9 / L and platelets recover to greater than 100 x 10 to the power 9 / L .
Severe neutropenia (neutrophil count less than 0.5 x 10 to the power of 9 / L for 7 days or longer) or severe sensory neuropathy
Reduce dose to 220 mg/square metre for subsequent courses.
Recurrence of severe neutropenia or severe sensory neuropathy
Reduce dose further to 180 mg/square metre.
If grade 3 sensory neuropathy occurs withhold treatment until resolution to grade 1-2 and subsequent doses of paclitaxel should be reduced.
Pancreatic Cancer
Dose reductions of paclitaxel albumin bound:
First dose reduction: 100 mg/ square metre.
Second dose reduction: 75 mg/ square metre.
Third dose reduction: Discontinue treatment.
Dose reductions of gemcitabine:
First dose reduction: 800 mg/ square metre.
Second dose reduction: 600 mg/ square metre.
Third dose reduction: Discontinue treatment.
Dose reductions if adverse reactions occur
Febrile neutropenia grade 3 or 4: withhold treatment until fever resolves and neutrophils recover to greater than 1.5 x 10 to the power 9 / L; resume treatment at next lower dose level.
Peripheral neuropathy grade 3 or 4: withhold treatment until improvement to grade 1; resume treatment at next lower dose level.
Cutaneous toxicity grade 2 or 3: reduce dose to next lower level; discontinue if problem persists.
Mucositis or diarrhoea grade 3: withhold treatment until improvement to grade 1; resume treatment at next lower dose level.
Dose reductions in neutropenia or thrombocytopenia
Prior to treating on day 1 of each cycle:
Absolute neutrophil count should be greater than 1.5 x 10 to the power 9/L.
Platelet count should be greater than 100 x 10 to the power 9/L.
Day 8 of cycle:
Absolute neutrophil count greater than or equal to 0.5 x 10 to the power 9/L and less than 1 x 10 to the power 9/L or platelet count greater than or equal to 50 x 10 to the power 9/L and less than 75 x 10 to the power 9/L: Reduce doses by 1 level.
Absolute neutrophil count less than 0.5 x 10 to the power 9/L or platelet count less than 50 x 10 to the power 9/L: Suspend treatment.
Day 15 with no prior dose reductions:
Absolute neutrophil count greater than or equal to 0.5 x 10 to the power 9/L and less than 1 x 10 to the power 9/L or platelet count greater than or equal to 50 x 10 to the power 9/L and less than 75 x 10 to the power 9/L: Reduce doses by 1 level from day 8 or treat with day 8 doses and follow with growth factors.
Absolute neutrophil count less than 0.5 x 10 to the power 9/L or platelet count less than 50 x 10 to the power 9/L: Suspend treatment.
Day 15 if day 8 doses were reduced:
Absolute neutrophil count greater than or equal to 1 x 10 to the power 9/L and platelet count greater than or equal to 75 x 10 to the power 9/L: Return to day 1 doses and follow with growth factors or treat with same dose as day 8.
Absolute neutrophil count greater than or equal to 0.5 x 10 to the power 9/L and less than 1 x 10 to the power 9/L or platelet count greater than or equal to 50 x 10 to the power 9/L and less than 75 x 10 to the power 9/L: Treat with day 8 dose and follow with growth factors or reduce dose by 1 dose level from day 8.
Absolute neutrophil count less than 0.5 x 10 to the power 9/L or platelet count less than 50 x 10 to the power 9/L: Suspend treatment.
Day 15 if day 8 doses were withheld:
Absolute neutrophil count greater than or equal to 1 x 10 to the power 9/L and platelet count greater than or equal to 75 x 10 to the power 9/L: Treat with day 1 doses and follow with growth factors or reduce dose by 1 level from day 1.
Absolute neutrophil count between 0.5 x 10 to the power 9/L and 1 x 10 to the power 9/L or platelet count between 50 x 10 to the power 9/L and 75 x 10 to the power 9/L: Reduce dose by 1 dose level from day 1 and follow with growth factors or reduce dose by 2 dose levels from day 1.
Absolute neutrophil count less than 0.5 x 10 to the power 9/L or platelet count less than 50 x 10 to the power 9/L: Suspend treatment.
Non-small cell lung cancer
Prior to treating on day 1 of each cycle:
Absolute neutrophil count should be greater than 1.5 x 10 to the power 9/L.
Platelet count should be greater than 100 x 10 to the power 9/L.
For each subsequent weekly dose:
Absolute neutrophil count should be greater than 0.5 x 10 to the power 9/L.
Platelet count should be greater than 50 x 10 to the power 9/L.
Dose reductions in neutropenia
First dose reduction: 75 mg/ square metre.
Second dose reduction: 50 mg/ square metre.
Third dose reduction: Discontinue treatment.
The dose should be reduced if any of the following events occur:
Absolute neutrophil count nadir less than 0.5 x 10 to the power 9/L and neutropenic fever greater than 38 degrees celsius.
Delay in next treatment cycle due to persistent neutropenia (absolute neutrophil count less than 1.5 x 10 to the power 9/L).
Absolute neutrophil count nadir less than 0.5 x 10 to the power 9/L for more than a week.
Dose reductions in thrombocytopenia
First dose reduction: 75 mg/metre square.
Second dose reduction: Discontinue treatment.
Reduce dose if platelet count is less than 50 x 10 to the power 9/L.
Dose reductions for non-haematological toxicities
First dose reduction: 75 mg/metre square.
Second dose reduction: 50 mg/metre square.
Third dose reduction: Discontinue treatment.
The dose should be reduced for any of the following toxicities:
Grade 2 cutaneous toxicity
Grade 3 diarrhoea
Grade 3 mucositis
Grade 3 or greater peripheral neuropathy
For any other grade 3 or 4 non-haematological toxicity, grade 4 cutaneous toxicity, diarrhoea or mucositis: Discontinue treatment at first occurrence.
Administration
For intravenous infusion after reconstitution.
Contraindications
Children under 18 years
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
Platelet count below 100 x 10 to the power of 9 / L at baseline
Breastfeeding
Hepatic enzymes above 10 times the upper limit of normal
Moderate hepatic impairment - if treating pancreatic cancer
Pregnancy
Serum bilirubin above 5 times upper limit of normal
Severe hepatic impairment
Precautions and Warnings
Concurrent radiotherapy
History of anthracycline therapy
Acute porphyria
Cardiac disorder
Central nervous system metastasis
End stage renal disease
Hepatic impairment
Patients over 75 years - if treating pancreatic cancer
Serum bilirubin between 1.5 and 5 times upper limit of normal
Severe renal impairment
Contains more than 1 mmol (23 mg) sodium per dose
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be initiated and supervised by a specialist
Different formulations are not bioequivalent
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Never rechallenge treatment after a hypersensitivity reaction
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor blood counts regularly
Monitor for hypersensitivity reactions during infusion
Monitor for signs and symptoms of pneumonitis
Monitor patients for signs of adverse cardiovascular effects
Reduce dose if neutrophil count < 500 cells/cubic mm for more than 7 days
Consider dose reduction for subsequent doses if severe diarrhoea occurs
Consider dose/ schedule adjustment if neuropathy occurs
Reduce dose if severe mucositis occurs
Consider suspending treatment for any grade 2 or worse toxicity
Discontinue if hypersensitivity reactions occur
Discontinue if treatment related pneumonitis is diagnosed
Interrupt treatment if febrile neutropenia occurs
Suspend treatment/reduce dose if grade 3/4 peripheral neuropathy occurs
BC & NSCLC: Reduce initial dose by 20% if bilirubin >1.5xULN & AST<10x ULN
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 1 month after treatment
Male: Contraception required during and for 6 months after treatment
Advise patients on the risk of neutropenia and the significance of fever
This albumin bound nanoparticle formulation of paclitaxel should not be substituted for or with other paclitaxel formulations.
Patients should not be retreated with subsequent cycles of paclitaxel until neutrophils recover to greater than 1.5 x 10 to the power 9 / L and platelets recover to greater than 100 x 10 to power 9 / L.
In the event of grade 3 sensory neuropathy, treatment should be withheld until resolution to grade 1 or 2, followed by dose reduction for subsequent courses. Grade 1 or 2 sensory neuropathy does not generally require dose reduction.
Congestive heart failure and left ventricular dysfunction have been reported during paclitaxel therapy. Patients who have previously received anthracyclines or have a history of cardiac disease should be treated with caution. Should significant abnormalities develop during treatment, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy.
Consider pseudomembranous colitis in patients presenting with severe or persistent diarrhoea during or shortly after paclitaxel treatment. This has been observed with a different formulation of paclitaxel.
Pregnancy and Lactation
Pregnancy
Paclitaxel is contraindicated during pregnancy.
The manufacturer states that paclitaxel should not be used during pregnancy unless the clinical condition of the mother requires treatment with paclitaxel. The use of paclitaxel is limited in human pregnancy. Paclitaxel has been shown to be clastogenic with in vitro and in vivo tests (Briggs et al., 2015) and animal studies have shown reproductive toxicity and it is suspected to cause serious birth defects when administered during pregnancy. The effect of concurrent therapies must also be considered.
Lactation
Paclitaxel is contraindicated during breastfeeding.
The manufacturer states that the use of paclitaxel during breastfeeding is contraindicated due to the potential serious adverse reactions in breastfeeding infants. However, animal studies have shown that paclitaxel and/or its metabolites were excreted in animal milk. It is unknown if paclitaxel is excreted in human breast milk. The effect of concurrent therapies must also be considered.
Side Effects
Alopecia
Anaemia
Anorexia
Anxiety
Areflexia
Arrhythmias
Arthralgia
Asthenia
Ataxia
Blood pressure changes
Blood sugar changes
Cardiac arrest
Cellulitis
Congestive cardiac failure
Conjunctivitis
Cough
Cranial nerve palsy
Cystoid macular oedema
Decrease in haematocrit
Decreased appetite
Dehydration
Depression
Dizziness
Dysgeusia
Dyskinesia
Dysphagia
Dyspnoea
Dysuria
Epistaxis
Erythema
Extravasation
Eye disorder
Fatigue
Febrile neutropenia
Flushing
Gait abnormality
Gastro-intestinal symptoms
Haematuria
Headache
Hepatomegaly
Hyperhidrosis
Hyperpigmentation of skin
Hypersensitivity reactions
Hypoalbuminaemia
Hypocalcaemia
Hypokalaemia
Hyponatraemia
Hypophosphataemia
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Infections
Insomnia
Interstitial pneumonitis
Keratitis
Leukopenia
Local reaction at injection site
Lymphoedema
Lymphopenia
Musculoskeletal disturbances
Myalgia
Myelosuppression
Nail disorders
Neuralgia
Neuropathy
Neutropenia
Oedema
Pain
Pancytopenia
Peripheral coldness
Photosensitivity
Pleural effusion
Polydipsia
Pruritus
Pulmonary embolism
Pyrexia
Radiation recall dermatitis
Rectal haemorrhage
Restlessness
Rhinitis
Rigors
Sensory disturbances
Sepsis
Serum bilirubin increased
Serum creatinine increased
Skin disorder
Somnolence
Stevens-Johnson syndrome
Stomatitis
Syncope
Thrombocytopenia
Thrombosis
Tinnitus
Toxic epidermal necrolysis
Tremor
Tumour lysis syndrome
Tumour necrosis
Urinary incontinence
Ventricular dysfunction
Vertigo
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: May 2021
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 12 May 2021.
Summary of Product Characteristics: Abraxane 5mg/ml. Celgene Europe Ltd. Revised October 2020.
Summary of Product Characteristics: Pazenir 5mg/ml powder for dispersion for infusion. Teva UK Ltd. Revised April 2021.
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