Abraxane

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Abraxane 5 mg/ml powder for suspension for infusion.  

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each vial contains 100 mg of paclitaxel formulated as albumin bound nanoparticles. 

Each vial contains 250 mg of paclitaxel formulated as albumin bound nanoparticles. 

 

After reconstitution, each ml of suspension contains 5 mg of paclitaxel formulated as albumin bound 

nanoparticles. 

 

Excipients with known effect 

Each ml of concentrate contains 0.183 mmol sodium, which is 4.2 mg of sodium. 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder for suspension for infusion. 

The reconstituted suspension has a pH of 6-7.5 and an osmolality of 300-360 mOsm/kg. 

The powder is white to yellow. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Abraxane monotherapy is indicated for the treatment of metastatic breast cancer in adult patients who 

have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing 

therapy is not indicated (see section 4.4). 

 

Abraxane in combination with gemcitabine is indicated for the first-line treatment of adult patients with 

metastatic adenocarcinoma of the pancreas. 

 

Abraxane in combination with carboplatin is indicated for the first-line treatment of non-small cell lung 

cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy. 

 

4.2 Posology and method of administration 

 

Abraxane should only be administered under the supervision of a qualified oncologist in units specialised 

in the administration of cytotoxic agents. It should not be substituted for or with other paclitaxel 

formulations. 

 

Posology 

 

Breast cancer 

The recommended dose of Abraxane is 260 mg/m2 administered intravenously over 30 minutes every 3 

weeks.  

 



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Dose adjustments during treatment of breast cancer 

Patients who experience severe neutropenia (neutrophil count < 500 cells/mm3 for a week or longer) or 

severe sensory neuropathy during Abraxane therapy should have the dose reduced to 220 mg/m2 for 

subsequent courses. Following recurrence of severe neutropenia or severe sensory neuropathy, additional 

dose reduction should be made to 180 mg/m2. Abraxane should not be administered until neutrophil 

counts recover to >1500 cells/mm3. For Grade 3 sensory neuropathy, withhold treatment until resolution 

to Grade 1 or 2, followed by a dose reduction for all subsequent courses. 

 

Pancreatic adenocarcinoma 

The recommended dose of Abraxane in combination with gemcitabine is 125 mg/m2 administered 

intravenously over 30 minutes on Days 1, 8 and 15 of each 28-day cycle. The concurrent recommended 

dose of gemcitabine is 1000 mg/m2 administered intravenously over 30 minutes immediately after the 

completion of Abraxane administration on Days 1, 8 and 15 of each 28-day cycle. 

 

Dose adjustments during treatment of pancreatic adenocarcinoma 

 

Table 1: Dose level reductions for patients with pancreatic adenocarcinoma 

Dose Level  Abraxane Dose (mg/m2) Gemcitabine Dose (mg/m2) 

Full dose 125 1000 

1st dose level reduction 100 800 

2nd dose level reduction 75 600 

If additional dose reduction 

required 
Discontinue treatment Discontinue treatment 

 

Table 2: Dose modifications for neutropenia and/or thrombocytopenia at the start of a cycle or 

within a cycle for patients with pancreatic adenocarcinoma 

Cycle 

Day 

ANC count 

(cells/mm3) 
 

Platelet count 

(cells/mm3) 

Abraxane 

 Dose   

Gemcitabine 

Dose  

Day 1 < 1500  OR < 100,000 Delay doses until recovery 

Day 8 ≥ 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 ≥ 500 but < 1000 OR ≥ 50,000 but < 75,000 

Treat with Day 8 dose level and 

follow with WBC Growth Factors  

OR 

 Reduce doses 1 dose level from 

Day 8 doses  

 < 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 levels and 

follow with WBC Growth Factors  

OR 

Treat with same doses as Day 8   

 ≥ 500 but < 1000 OR ≥ 50,000 but < 75,000 Treat with Day 8 dose levels and 



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follow with WBC Growth Factors  

OR  

Reduce doses 1 dose level from 

Day 8 doses  

 < 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 levels and 

follow with WBC Growth Factors  

OR 

Reduce doses 1 dose level from 

Day 1 doses  

 ≥ 500 but < 1000 OR ≥ 50,000 but < 75,000 

Reduce 1 dose level and follow 

with WBC Growth Factors  

OR 

Reduce doses 2 dose levels from 

Day 1 doses  

 < 500 OR < 50,000 Withhold doses 

Abbreviations: ANC=Absolute Neutrophil Count; WBC=white blood cell 

 

Table 3: Dose modifications for other adverse drug reactions in patients with pancreatic 

adenocarcinoma 

Adverse Drug Reaction 

(ADR) 
Abraxane Dose Gemcitabine Dose 

Febrile Neutropenia: 

Grade 3 or 4 

Withhold doses until fever resolves and ANC ≥ 1500; resume at next 

lower dose levela 

Peripheral Neuropathy: 

Grade 3 or 4 

Withhold dose until improves to 

≤ Grade 1;  

resume at next lower dose levela 

Treat with same dose 

Cutaneous Toxicity: 

Grade 2 or 3 

Reduce to next lower dose levela;  

discontinue treatment if ADR persists  

Gastrointestinal 

Toxicity: 

Grade 3 mucositis or 

diarrhoea 

Withhold doses until improves to ≤ Grade 1;  

resume at next lower dose levela 

a. See Table 1 for dose level reductions 
 

Non-small cell lung cancer: 

The recommended dose of Abraxane is 100 mg/m2 administered as an intravenous infusion over 30 

minutes on Days 1, 8 and 15 of each 21-day cycle.  The recommended dose of carboplatin is AUC = 6 

mg•min/mL on Day 1 only of each 21-day cycle, beginning immediately after the end of Abraxane 

administration.   

 

Dose adjustments during treatment of non-small cell lung cancer: 

Abraxane should not be administered on Day 1 of a cycle until absolute neutrophil count (ANC) is ≥1500 

cells/mm3 and platelet count is ≥100,000 cells/mm3. For each subsequent weekly dose of Abraxane, 

patients must have an ANC ≥500 cells/mm3 and platelets >50,000 cells/mm3 or the dose is to be withheld 



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until counts recover.  When counts recover, resume dosing the following week according to the criteria in 

Table 4. Reduce subsequent dose only if criteria in Table 4 are met.  

 

Table 4: Dose reductions for haematologic toxicities in patients with non-small cell lung cancer 
Haematologic Toxicity Occurrence Dose of Abraxane 

(mg/m2)1 

Dose of carboplatin 

(AUC mg•min/mL)1 

Nadir ANC <500/mm3 with neutropenic 

fever > 38°C 

OR 

Delay of next cycle due to persistent 

neutropenia2 (Nadir ANC <1500/mm3) 

OR 

Nadir ANC <500/mm3 for > 1 week 

First 75 4.5 

Second 50 3.0 

Third Discontinue Treatment 

Nadir platelets <50,000/mm3 
First 75 4.5 

Second Discontinue Treatment 
1On Day 1 of the 21-day cycle reduce the dose of Abraxane and carboplatin simultaneously. On Days 8 or 15 of the 21-day cycle reduce the dose 

of Abraxane; reduce the dose of carboplatin in the subsequent cycle. 
2Maximum of 7 days post scheduled Day 1 dose of next cycle.  

 

For Grade 2 or 3 cutaneous toxicity, Grade 3 diarrhoea, or Grade 3 mucositis, interrupt treatment until the 

toxicity improves to ≤ Grade 1, then restart treatment according to the guidelines in Table 5.  For ≥ Grade 

3 peripheral neuropathy, withhold treatment until resolution to ≤ Grade 1.  Treatment may be resumed at 

the next lower dose level in subsequent cycles according to the guidelines in Table 5.  For any other Grade 

3 or 4 non-haematologic toxicity, interrupt treatment until the toxicity improves to ≤ Grade 2, then restart 

treatment according to the guidelines in Table 5.  

 

Table 5: Dose reductions for non-haematologic toxicities in patients with non-small cell lung cancer 
Non-haematologic Toxicity Occurrence Dose of Abraxane 

(mg/m2)1 

Dose of carboplatin 

(AUC mg•min/mL)1 

Grade 2 or 3 cutaneous toxicity 

Grade 3 diarrhoea 

Grade 3 mucositis 

≥ Grade 3 peripheral neuropathy 

Any other Grade 3 or 4 non-

haematologic toxicity  

First 75 4.5 

Second 50 3.0 

Third Discontinue Treatment 

Grade 4 cutaneous toxicity, diarrhoea, or 

mucositis 

First Discontinue Treatment 

1On Day 1 of the 21-day cycle reduce the dose of Abraxane and carboplatin simultaneously. On Days 8 or 15 of the 21-day cycle reduce the dose 

of Abraxane; reduce the dose of carboplatin in the subsequent cycle. 

 

Special populations 

 

Hepatic impairment 

For patients with mild hepatic impairment (total bilirubin > 1 to ≤ 1.5 x ULN and aspartate 

aminotransferase [AST] ≤ 10 x ULN), no dose adjustments are required, regardless of indication. Treat 

with same doses as patients with normal hepatic function. 

 

For metastatic breast cancer patients and non-small cell lung cancer patients with moderate to severe 

hepatic impairment (total bilirubin > 1.5 to ≤ 5 x ULN and AST ≤ 10 x ULN), a 20% reduction in dose is 

recommended. The reduced dose may be escalated to the dose for patients with normal hepatic function if 

the patient is tolerating the treatment for at least two cycles (see sections 4.4 and 5.2). 

 

For patients with metastatic adenocarcinoma of the pancreas that have moderate to severe hepatic 

impairment, there are insufficient data to permit dosage recommendations (see sections 4.4 and 5.2). 



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For patients with total bilirubin > 5 x ULN or AST > 10 x ULN, there are insufficient data to permit 

dosage recommendations regardless of indication (see sections 4.4 and 5.2). 

 

Renal impairment 

Adjustment of the starting Abraxane dose is not required for patients with mild to moderate renal 

impairment (estimated creatinine clearance ≥30 to <90 ml/min). There are insufficient data available to 

recommend dose modifications of Abraxane in patients with severe renal impairment or end stage renal 

disease (estimated creatinine clearance <30 ml/min) (see section 5.2). 

 

Elderly 

No additional dosage reductions, other than those for all patients, are recommended for patients 65 years 

and older. 

 

Of the 229 patients in the randomized study who received Abraxane monotherapy for breast cancer, 13% 

were at least 65 years of age and < 2% were 75 years and older. No toxicities occurred notably more 

frequently among patients at least 65 years of age who received Abraxane. However, a subsequent 

analysis in 981 patients receiving Abraxane monotherapy for metastatic breast cancer, of which 15% were 

≥ 65 years old and 2% were ≥ 75 years old, showed a higher incidence of epistaxis, diarrhoea, 

dehydration, fatigue and peripheral oedema in patients ≥ 65 years. 

 

Of the 421 patients with pancreatic adenocarcinoma in the randomized study who received Abraxane in 

combination with gemcitabine, 41% were 65 years and older and 10% were 75 years and older. In patients 

aged 75 years and older who received Abraxane and gemcitabine, there was a higher incidence of serious 

adverse reactions and adverse reactions that led to treatment discontinuation (see section 4.4). Patients 

with pancreatic adenocarcinoma aged 75 years and older should be carefully assessed before treatment is 

considered (see section 4.4). 

 

Of the 514 patients with non-small cell lung cancer in the randomized study who received Abraxane in 

combination with carboplatin, 31% were 65 years or older and 3.5% were 75 years or older.  

Myelosuppression events, peripheral neuropathy events, and arthralgia were more frequent in patients 65 

years or older compared to patients younger than 65 years of age. There is limited experience of 

Abraxane/carboplatin use in patients 75 years or older. 

 

Pharmacokinetic/pharmacodynamic modelling using data from 125 patients with advanced solid tumours 

indicates that patients ≥ 65 years of age may be more susceptible to development of neutropenia within the 

first treatment cycle. 

 

Paediatric population 

The safety and efficacy of Abraxane in children and adolescents aged 0 to less than 18 years has not been 

established. Currently available data are described in section s 4.8, 5.1 and 5.2 but no recommendation on 

a posology can be made. There is no relevant use of Abraxane in the paediatric population for the 

indication of metastatic breast cancer or pancreatic adenocarcinoma or non-small cell lung cancer. 

 

Method of administration 

Administer reconstituted Abraxane suspension intravenously using an infusion set incorporating a 15 µm 

filter. Following administration, it is recommended that the intravenous line be flushed with sodium 

chloride 9 mg/ml (0.9%) solution for injection to ensure administration of the complete dose. 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6.  

 



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4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

Lactation (see section 4.6). 

Patients who have baseline neutrophil counts <1500 cells/mm3. 

 

4.4 Special warnings and precautions for use 

 

Abraxane is an albumin-bound nanoparticle formulation of paclitaxel, which may have substantially 

different pharmacological properties compared to other formulations of paclitaxel (see sections 5.1 and 

5.2). It should not be substituted for or with other paclitaxel formulations. 

 

Hypersensitivity 

Rare occurrences of severe hypersensitivity reactions, including very rare events of anaphylactic reactions 

with fatal outcome, have been reported. If a hypersensitivity reaction occurs, the medicinal product should 

be discontinued immediately, symptomatic treatment should be initiated, and the patient should not be 

rechallenged with paclitaxel. 

 

Haematology 

Bone marrow suppression (primarily neutropenia) occurs frequently with Abraxane. Neutropenia is 

dose-dependent and a dose-limiting toxicity. Frequent monitoring of blood cell counts should be 

performed during Abraxane therapy. Patients should not be retreated with subsequent cycles of Abraxane 

until neutrophils recover to >1500 cells/mm3 and platelets recover to >100,000 cells/mm3 (see section 

4.2). 

 

Neuropathy 

Sensory neuropathy occurs frequently with Abraxane, although development of severe symptoms is less 

common. The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose reduction. 

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 is recommended (see section 4.2). For combination use of Abraxane and gemcitabine, if Grade 

3 or higher peripheral neuropathy develops, withhold Abraxane; continue treatment with gemcitabine at 

the same dose. Resume Abraxane at reduced dose when peripheral neuropathy improves to Grade 0 or 1 

(see section 4.2). For combination use of Abraxane and carboplatin, if Grade 3 or higher peripheral 

neuropathy develops, treatment should be withheld until improvement to Grade 0 or 1 followed by a dose 

reduction for all subsequent courses of Abraxane and carboplatin (see section 4.2). 

 

Sepsis 

Sepsis was reported at a rate of 5% in 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 cells/mm3, 

then resume treatment at reduced dose levels (see section 4.2). 

 

Pneumonitis 

Pneumonitis occurred in 1% of patients when Abraxane was used as monotherapy and in 4% of patients 

when Abraxane was used in combination with gemcitabine. Closely monitor all patients for signs and 

symptoms of pneumonitis. After ruling out infectious etiology and upon making a diagnosis of 

pneumonitis, permanently discontinue treatment with Abraxane and gemcitabine and promptly initiate 

appropriate treatment and supportive measures (see section 4.2). 

 



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Hepatic impairment 

Because the toxicity of paclitaxel can be increased with hepatic impairment, administration of Abraxane in 

patients with hepatic impairment should be performed with caution. 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. In 

addition, Abraxane is not recommended in patients with metastatic adenocarcinoma of the pancreas that 

have moderate to severe hepatic impairment (total bilirubin > 1.5 x ULN and AST ≤ 10 x ULN) (see 

section 5.2). 

 

Cardiotoxicity 

Rare reports of congestive heart failure and left ventricular dysfunction have been observed among 

individuals receiving Abraxane. Most of the individuals were previously exposed to cardiotoxic medicinal 

products such as anthracyclines or had underlying cardiac history. Thus, patients receiving Abraxane 

should be vigilantly monitored by physicians for the occurrence of cardiac events. 

 

CNS metastases 

The effectiveness and safety of Abraxane in patients with central nervous system (CNS) metastases has 

not been established. CNS metastases are generally not well controlled by systemic chemotherapy. 

 

Gastrointestinal symptoms 

If patients experience nausea, vomiting and diarrhoea following the administration of Abraxane, they may 

be treated with commonly used anti-emetics and constipating agents. 

 

Patients 75 years and older 

For patients of 75 years and older, no benefit for the combination treatment of Abraxane and gemcitabine 

in comparison to gemcitabine monotherapy has been demonstrated. In the very elderly (≥75 years) who 

received Abraxane and gemcitabine, there was a higher incidence of serious adverse reactions and adverse 

reactions that led to treatment discontinuation including haematologic toxicities, peripheral neuropathy, 

decreased appetite and dehydration. Patients with pancreatic adenocarcinoma aged 75 years and older 

should be carefully assessed for their ability to tolerate Abraxane in combination with gemcitabine with 

special consideration to performance status, co-morbidities and increased risk of infections (see section 

4.2 and 4.8). 

 

Other 

Although limited data is available, no clear benefit in terms of prolonged overall survival has been 

demonstrated in pancreatic adenocarcinoma patients with normal CA 19-9 levels prior to start of treatment 

with Abraxane and gemcitabine (see section 5.1). 

 

Erlotinib should not be co-administered with Abraxane plus gemcitabine (see section 4.5). 

 

Excipients 

When reconstituted, each ml of Abraxane concentrate contains 0.183 mmol sodium, which is 4.2 mg of 

sodium. To be taken into consideration by patients on a controlled sodium diet. 

 

4.5 Interactions with other medicinal products and other forms of interaction 

 

The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and 

CYP3A4 (see section 5.2). Therefore, in the absence of a PK drug-drug interaction study, caution should 

be exercised when administering paclitaxel concomitantly with medicines known to inhibit either 

CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, 

gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of 



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paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly 

with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, 

efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower 

paclitaxel exposures. 

 

Paclitaxel and gemcitabine do not share a common metabolic pathway. Paclitaxel clearance is primarily 

determined by CYP2C8 and CYP3A4 mediated metabolism followed by biliary excretion, while 

gemcitabine is inactivated by cytidine deaminase followed by urinary excretion. Pharmacokinetic 

interactions between Abraxane and gemcitabine have not been evaluated in humans. 

 

A pharmacokinetic study was conducted with Abraxane and carboplatin in non-small cell lung cancer 

patients. There were no clinically relevant pharmacokinetic interactions between Abraxane and 

carboplatin. 

 

Abraxane is indicated as monotherapy for breast cancer, in combination with gemcitabine for pancreatic 

adenocarcinoma, or in combination with carboplatin for non-small cell lung cancer (see section 4.1). 

Abraxane should not be used in combination with other anticancer agents.  

 

Paediatric population 

Interaction studies have only been performed in adults. 

 

4.6 Fertility, pregnancy and lactation  

 

Contraception in males and females 

Women of childbearing potential should use effective contraception during treatment and up to 1 month 

after receiving treatment with Abraxane. Male patients treated with Abraxane are advised to use effective 

contraception and to avoid fathering a child during and up to six months after treatment. 

 

Pregnancy 

There are very limited data on the use of paclitaxel in human pregnancy. Paclitaxel is suspected to cause 

serious birth defects when administered during pregnancy. Studies in animals have shown reproductive 

toxicity (see section 5.3). Women of childbearing potential should have a pregnancy test prior to starting 

treatment with Abraxane. Abraxane should not be used in pregnancy, and in women of childbearing 

potential not using effective contraception, unless the clinical condition of the mother requires treatment 

with paclitaxel. 

 

Breast-feeding 

Paclitaxel and/or its metabolites were excreted into the milk of lactating rats (see section 5.3). It is not 

known if paclitaxel is excreted in human milk. Because of potential serious adverse reactions in 

breast-feeding infants, Abraxane is contraindicated during lactation. Breast-feeding must be discontinued 

for the duration of therapy.  

 

Fertility 

Abraxane induced infertility in male rats (see section 5.3). Based on findings in animals, male and female 

fertility may be compromised. Male patients should seek advice on conservation of sperm prior to 

treatment because of the possibility of irreversible infertility due to therapy with Abraxane. 

 

4.7 Effects on ability to drive and use machines  

 

Abraxane has minor or moderate influence on the ability to drive and use machines. Abraxane may cause 

adverse reactions such as tiredness (very common) and dizziness (common) that may affect the ability to 

drive and use machinery. Patients should be advised not to drive and use machines if they feel tired or 

dizzy. 



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4.8 Undesirable effects  

 

Summary of the safety profile  

The most common clinically significant adverse reactions associated with the use of Abraxane have been 

neutropenia, peripheral neuropathy, arthralgia/myalgia and gastrointestinal disorders.  

 

The frequencies of adverse reactions associated with the administration of Abraxane are listed in Table 6 

(Abraxane as monotherapy) and Table 7 (Abraxane in combination with gemcitabine), and Table 9 

(Abraxane in combination with carboplatin). 

 

Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 

to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000). Within each frequency grouping, adverse 

reactions are presented in order of decreasing seriousness. 

 

Breast cancer (Abraxane administered as monotherapy) 

 

Tabulated list of adverse reactions 

Table 6 lists adverse reactions associated with the administration of Abraxane to patients from studies in 

which Abraxane has been administered as monotherapy at any dose in any indication (N = 789). 

 

Table 6: Adverse reactions reported with Abraxane monotherapy at any dose in clinical studies 

Infections and 

infestations 

Common: Infection, urinary tract infection, folliculitis, upper respiratory 

tract infection, candidiasis, sinusitis  

 

Uncommon: Oral candidiasis, nasopharyngitis, cellulitis, herpes simplex, 

viral infection, pneumonia, catheter-related infection, fungal infection, 

herpes zoster, injection site infection, sepsis2, neutropenic sepsis2 

Neoplasms benign, 

malignant and 

unspecified (including 

cysts and polyps) 

Uncommon: Metastatic pain, tumour necrosis 

Blood and lymphatic 

system disorders 

Very common: Neutropenia, anaemia, leukopenia, thrombocytopenia, 

lymphopenia, bone marrow suppression 

 

Common: Febrile neutropenia 

 

Rare: Pancytopenia 

Immune system 

disorders 

Uncommon1: Hypersensitivity 

 

Rare: Severe hypersensitivity 

Metabolism and 

nutrition disorders 

Very common: Anorexia 

 

Common: Dehydration, decreased appetite, hypokalaemia 

 

Uncommon: Hypophosphataemia, fluid retention, hypoalbuminaemia, 

polydipsia, hyperglycaemia, hypocalcaemia, hypoglycaemia, 

hyponatraemia 

Psychiatric disorders 

Common: Insomnia, depression, anxiety 

 

Uncommon: Restlessness 



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Nervous system 

disorders 

Very common: Peripheral neuropathy, neuropathy, hypoaesthesia, 

paraesthesia  

 

Common: Peripheral sensory neuropathy, headache, dysgeusia, dizziness, 

peripheral motor neuropathy, ataxia, sensory disturbance, somnolence 

 

Uncommon: Polyneuropathy, areflexia, dyskinesia, hyporeflexia, 

neuralgia, sensory loss, syncope, postural dizziness, neuropathic pain, 

tremor 

Eye disorders 

Common: Increased lacrimation, blurred vision, dry eye, 

keratoconjunctivitis sicca, madarosis 

 

Uncommon: Eye irritation, eye pain, abnormal vision, reduced visual 

acuity, conjunctivitis, visual disturbance, eye pruritus, keratitis 

 

Rare: Cystoid macular oedema2 

Ear and labyrinth 

disorders 

Common: Vertigo 

 

Uncommon: Ear pain, tinnitus 

Cardiac disorders 

Common: Tachycardia, arrhythmia, supraventricular tachycardia 

 

Rare: bradycardia, cardiac arrest, left ventricular dysfunction, congestive 

heart failure, atrioventricular block2 

Vascular disorders 

Common: Flushing, hot flushes, hypertension, lymphoedema 

 

Uncommon: Hypotension, peripheral coldness, orthostatic hypotension 

 

Rare: Thrombosis 

Respiratory, thoracic 

and mediastinal 

disorders 

Common: Interstitial pneumonitis3, dyspnoea, epistaxis, pharyngolaryngeal 

pain, cough, rhinitis, rhinorrhoea  

 

Uncommon: Productive cough, exertional dyspnoea, sinus congestion, 

decreased breath sounds, pleural effusion, allergic rhinitis, hoarseness, 

nasal congestion, nasal dryness, wheezing, pulmonary emboli, pulmonary 

thromboembolism 

Gastrointestinal 

disorders 

Very common: Nausea, diarrhoea, vomiting, constipation, stomatitis 

 

Common: Abdominal pain, abdominal distension, upper abdominal pain, 

dyspepsia, gastrooesophageal reflux disease, oral hypoaesthesia 

 

Uncommon: Dysphagia, flatulence, glossodynia, dry mouth, gingival pain, 

loose stools, oesophagitis, lower abdominal pain, mouth ulceration, oral 

pain, rectal haemorrhage 

Hepatobiliary disorders Uncommon: Hepatomegaly 



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Skin and subcutaneous 

tissue disorders 

Very common: Alopecia, rash 

 

Common: Nail disorder, pruritus, dry skin, erythema, nail 

pigmentation/discolouration, skin hyperpigmentation, onycholysis, nail 

changes 

 

Uncommon: Nail bed tenderness, urticaria, skin pain, photosensitivity 

reaction, pigmentation disorder, pruritic rash, skin disorder, hyperhidrosis, 

onychomadesis, erythematous rash, generalised rash, dermatitis, night 

sweats, maculo-papular rash, vitiligo, hypotrichosis, nail discomfort, 

generalized pruritus, macular rash, papular rash, skin lesion, swollen face 

 

Very rare: Stevens-Johnson syndrome2, toxic epidermal necrolysis2 

Musculoskeletal and 

connective tissue 

disorders 

Very common: Arthralgia, myalgia. 

 

Common: Pain in extremity, bone pain, back pain, muscle cramps, limb 

pain 

 

Uncommon: Chest wall pain, muscular weakness, neck pain, groin pain, 

muscle spasms, musculoskeletal pain, flank pain, limb discomfort, muscle 

weakness 

Renal and urinary 

disorders 

Uncommon: Dysuria, pollakiuria, haematuria, nocturia, polyuria, urinary 

incontinence 

Reproductive system 

and breast disorders 
Uncommon: Breast pain 

General disorders and 

administration site 

conditions 

Very common: Fatigue, asthenia, pyrexia 

 

Common: Peripheral oedema, mucosal inflammation, pain, rigors, oedema, 

weakness, decreased performance status, chest pain, influenza-like illness, 

malaise, lethargy, hyperpyrexia 

 

Uncommon: Chest discomfort, abnormal gait, swelling, injection site 

reaction 

 

Rare: Extravasation 

Investigations 

 

Common: Decreased weight, increased alanine aminotransferase, increased 

aspartate aminotransferase, decreased haematocrit, decreased red blood 

cell count, increased body temperature, increased 

gamma-glutamyltransferase, increased blood alkaline phosphatase 

 

Uncommon: Increased blood pressure, increased weight, increased blood 

lactate dehydrogenase, increased blood creatinine, increased blood 

glucose, increased blood phosphorus, decreased blood potassium, 

increased bilirubin 

Injury, poisoning and 

procedural 

complications 

Uncommon: Contusion 

 

Rare: Radiation recall phenomenon, radiation pneumonitis 
MedDRA = Medical Dictionary for Regulatory Activities.  
SMQ = Standardized MedDRA Query; SMQ is a grouping of several MedDRA preferred terms to capture a medical concept. 
1 The frequency of hypersensitivity reactions is calculated based on one definitely related case in a population of 789 patients. 
2 As reported in the post-marketing surveillance of Abraxane. 
3 The frequency of pneumonitis is calculated based on pooled data in 1310 patients in clinical trials receiving Abraxane monotherapy for breast 

cancer and for other indications using MedDRA SMQ Interstitial lung disease. See section 4.4.  

 



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Description of selected adverse reactions 

The following are the most common and clinically relevant adverse reactions related to 229 patients with 

metastatic breast cancer who were treated with 260 mg/m2 Abraxane once every three weeks in the pivotal 

phase III clinical study. 

  

Blood and lymphatic system disorders 

Neutropenia was the most notable important haematological toxicity (reported in 79% of patients), and 

was rapidly reversible and dose dependent; leukopenia was reported in 71% of patients. Grade 4 

neutropenia (< 500 cells/mm3) occurred in 9% of patients treated with Abraxane. Febrile neutropenia 

occurred in four patients on Abraxane. Anaemia (Hb < 10 g/dl) was observed in 46% of patients on 

Abraxane and was severe (Hb < 8 g/dl) in three cases. Lymphopenia was observed in 45% of the patients. 

 

Nervous system disorders 

In general, the frequency and severity of neurotoxicity was dose-dependent in patients receiving 

Abraxane. Peripheral neuropathy (mostly Grade 1 or 2 sensory neuropathy) was observed in 68% of 

patients on Abraxane with 10% being Grade 3, and no cases of Grade 4. 

 

Gastrointestinal disorders 

Nausea occurred in 29% of the patients and diarrhoea in 25% of the patients.  

 

Skin and subcutaneous tissue disorders 

Alopecia was observed in >80% of the patients treated with Abraxane. The majority of alopecia events 

occurred less than one month after initiation of Abraxane. Pronounced hair loss ≥50% is expected for the 

majority of patients who experience alopecia. 

 

Musculoskeletal and connective tissue disorders 

Arthralgia occurred in 32% of patients on Abraxane and was severe in 6% of cases. Myalgia occurred in 

24% of patients on Abraxane and was severe in 7% of cases. The symptoms were usually transient, 

typically occurred three days after Abraxane administration and resolved within a week.  

 

General disorders and administration site conditions 

Asthenia/Fatigue was reported in 40% of the patients. 

 

Pancreatic adenocarcinoma (Abraxane administered in combination with gemcitabine) 

 

Tabulated list of adverse reactions 

Adverse reactions were assessed in 421 patients treated with Abraxane in combination with gemcitabine 

and 402 gemcitabine monotherapy-treated patients receiving first-line systemic treatment for metastatic 

adenocarcinoma of the pancreas in a phase III randomized, controlled, open-label trial. Table 7 lists 

adverse reactions assessed in patients with pancreatic adenocarcinoma treated with Abraxane in 

combination with gemcitabine. 

 

Table 7: Adverse reactions reported with Abraxane in combination with gemcitabine (N =421) 

Infections and 

infestations 

Common: Sepsis, pneumonia, oral candidiasis 

 

Blood and lymphatic 

system disorders 

Very common: Neutropenia, anaemia, thrombocytopenia 

Common: Pancytopenia  

Uncommon: Thrombotic thrombocytopenic purpura 

 

Metabolism and 

nutrition disorders 

Very common: Dehydration, decreased appetite, hypokalaemia 

 



14 

Psychiatric disorders 
Very common: Insomnia, depression 

Common: Anxiety 

Nervous system 

disorders 

Very common: Peripheral neuropathy1, dysgeusia, headache, dizziness 

Uncommon: VIIth nerve paralysis 

 

Eye disorders 

Common: Lacrimation increased 

Uncommon: Cystoid macular oedema 

 

Cardiac disorders 
Common: Cardiac failure congestive, tachycardia  

 

Vascular disorders 
Common: Hypotension, hypertension  

 

Respiratory, thoracic 

and mediastinal 

disorders 

Very common: Dyspnoea, epistaxis, cough  

Common: Pneumonitis2, nasal congestion 

Uncommon: Dry throat, nasal dryness  

  

Gastrointestinal 

disorders 

Very common: Nausea, diarrhoea, vomiting, constipation, abdominal pain, 

abdominal pain upper 

Common: Stomatitis, intestinal obstruction, colitis, dry mouth 

 

Hepatobiliary disorders 
Common: Cholangitis  

 

Skin and subcutaneous 

tissue disorders 

Very common: Alopecia, rash 

Common: Pruritus, dry skin, nail disorder, flushing 

 

Musculoskeletal and 

connective tissue 

disorders 

Very common: Pain in extremity, arthralgia, myalgia 

Common: Muscular weakness, bone pain  

 

Renal and urinary 

disorders 

Common: Acute renal failure 

Uncommon: Haemolytic uraemic syndrome  

 

General disorders and 

administration site 

conditions 

Very common: Fatigue, oedema peripheral, pyrexia, asthenia, chills 

Common: Infusion site reaction 

 

Investigations 

 

Very common: Weight decreased, alanine aminotransferase increased 

Common: Aspartate aminotransferase increased, blood bilirubin increased, 

blood creatinine increased 

 
MedDRA = Medical Dictionary for Regulatory Activities; SMQ = Standardized MedDRA Query (a grouping of several MedDRA preferred terms 

to capture a medical concept). 

1 Peripheral neuropathy evaluated using the SMQ (broad scope).  
2 Pneumonitis is evaluated using the SMQ interstitial lung disease (broad scope) 

 

In this phase III randomized, controlled, open-label trial, adverse reactions resulting in death within 30 

days of the last dose of study drug were reported for 4% of patients receiving Abraxane in combination 

with gemcitabine and for 4% of patients receiving gemcitabine monotherapy.   



15 

 

Description of selected adverse reactions  

The following are the most common and important incidences of adverse reactions related to 421 patients 

with metastatic adenocarcinoma of the pancreas who were treated with 125 mg/m2 Abraxane in 

combination with gemcitabine at a dose of 1000 mg/m2 given on Days 1, 8 and 15 of each 28-day cycle in 

the phase III clinical study. 

 

Blood and lymphatic system disorders 

Table 8 provides the frequency and severity of haematologic laboratory-detected abnormalities for 

patients treated with Abraxane in combination with gemcitabine or with gemcitabine. 

 

Table 8: Haematologic laboratory-detected abnormalities in pancreatic adenocarcinoma trial 

 

Abraxane (125 mg/m2)/ 

Gemcitabine 
Gemcitabine 

Grades 1-4  

(%) 

Grade 3-4  

(%) 

Grades 1-4  

(%) 

Grade 3-4  

(%)   

Anaemiaa,b 97 13 96 12 

Neutropenia a,b 73 38 58 27 

Thrombocytopeniab,c 74 13 70 9 
a 405 patients assessed in Abraxane/gemcitabine-treated group 
b 388 patients assessed in gemcitabine-treated group  
c 404 patients assessed in Abraxane/gemcitabine-treated group   

 

Peripheral neuropathy 

For patients treated with Abraxane in combination with gemcitabine, the median time to first occurrence 

of Grade 3 peripheral neuropathy was 140 days. The median time to improvement by at least 1 grade was 

21 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 in combination with 

gemcitabine had Grade 4 peripheral neuropathy. 

 

Sepsis 

Sepsis was reported at a rate of 5% in patients with or without neutropenia who received Abraxane in 

combination with gemcitabine during the conduct of a trial in pancreatic adenocarcinoma. 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 cells/mm3, then resume treatment at reduced dose levels 

(see section 4.2). 

 

Pneumonitis 

Pneumonitis has been reported at a rate of 4% with the use of Abraxane in combination with gemcitabine. 

Of the 17 cases of pneumonitis reported in patients treated with Abraxane in combination with 

gemcitabine, 2 had a fatal outcome. Monitor patients closely for signs and symptoms of pneumonitis. 

After ruling out infectious etiology and upon making a diagnosis of pneumonitis, permanently discontinue 

treatment with Abraxane and gemcitabine and promptly initiate appropriate treatment and supportive 

measures (see section 4.2). 

 



16 

Non-small cell lung cancer (Abraxane administered in combination with carboplatin) 

 

Tabulated list of adverse reactions 

Table 9 lists adverse reactions associated with the administration of Abraxane in combination with 

carboplatin.  

 

Table 9: Adverse reactions reported with Abraxane in combination with carboplatin (N = 514) 

Infections and 

infestations 

Common: Pneumonia, bronchitis, upper respiratory tract infection, urinary 

tract infection 

 

Uncommon: Sepsis, oral candidiasis 

Blood and lymphatic 

system disorders1 

Very common: Neutropenia1, thrombocytopenia1, anaemia1, leukopenia1 

 

Common: Febrile neutropenia, lymphopenia 

 

Uncommon: Pancytopenia 

Immune system 

disorders 

Uncommon: Drug hypersensitivity, hypersensitivity 

Metabolism and 

nutrition disorders 

Very common: Decreased appetite 

 

Common: Dehydration 

Psychiatric disorders Common: Insomnia 

Nervous system 

disorders 

Very common: Peripheral neuropathy2 

 

Common: Dysgeusia, headache, dizziness 

Eye disorders Common: Vision blurred 

Vascular disorders Common: Hypotension, hypertension 

 

Uncommon: Flushing 

Respiratory thoracic and 

mediastinal disorders 

Very common: Dyspnoea 

 

Common: Haemoptysis, epistaxis, cough  

 

Uncommon: Pneumonitis3 

Gastrointestinal 

disorders 

Very common: Diarrhoea, vomiting, nausea, constipation  

 

Common: Stomatitis, dyspepsia, abdominal pain, dysphagia 

Hepatobiliary disorders Common: Hyperbilirubinaemia 

Skin and subcutaneous 

tissue disorders 

Very common: Rash, alopecia 

 

Common: Pruritus, nail disorder 

 

Uncommon: Skin exfoliation, dermatitis allergic, urticaria 

Musculoskeletal and 

connective tissue 

disorders 

Very common: Arthralgia, myalgia 

 

Common: Back pain, pain in extremity, musculoskeletal pain 



17 

General disorders and 

administration site 

conditions 

Very common: Fatigue, asthenia, oedema peripheral 

 

Common: Pyrexia, chest pain 

 

Uncommon: Mucosal inflammation, infusion site extravasation, infusion 

site inflammation, infusion site rash 

Investigations Common: Alanine aminotransferase increased, aspartate aminotransferase 

increased, blood alkaline phosphatase increased, weight decreased 

MedDRA = Medical Dictionary for Regulatory Activities: SMQ = Standardized MedDRA Query 
1 Based on laboratory assessments: maximal degree of myelosuppression (treated population) 
2 Peripheral neuropathy is evaluated using the SMQ neuropathy (broad scope) 
3 Pneumonitis is evaluated using the SMQ interstitial lung disease (broad scope) 

 

For non-small cell lung cancer patients treated with Abraxane and carboplatin, the median time to first 

occurrence of Grade 3 treatment related peripheral neuropathy was 121 days, and the median time to 

improvement from Grade 3 treatment related peripheral neuropathy to Grade 1 was 38 days.  No patients 

treated with Abraxane and carboplatin experienced Grade 4 peripheral neuropathy. 

 

Anemia and thrombocytopenia were more commonly reported in the Abraxane arm than in the Taxol arm 

(54% versus 28% and 45% versus 27% respectively).  

Patient-reported taxane toxicity was assessed using the 4 subscales of the Functional Assessment of 

Cancer Therapy (FACT)-Taxane questionnaire. Using repeated measure analysis, 3 of the 4 subscales 

(peripheral neuropathy, pain hands/feet, and hearing) favored Abraxane and carboplatin (p ≤ 0.002).  For 

the other subscale (oedema), there was no difference in the treatment arms. 

 

Post-marketing experience 

 

Cranial nerve palsies, vocal cord paresis, and rare reports of severe hypersensitivity reactions have been 

reported during post-marketing surveillance of Abraxane. 

 

There have been rare reports of reduced visual acuity due to cystoid macular oedema during treatment 

with Abraxane. Upon diagnosis of cystoid macular oedema, treatment with Abraxane should be 

discontinued. 

 

There have been reports of tumour lysis syndrome during treatment with Abraxane. 

 

Scleroderma of the skin has been reported. In some patients previously exposed to capecitabine, reports of 

palmar-plantar erythrodysaesthesiae have been reported as part of the continuing surveillance of 

Abraxane. Because these events have been reported voluntarily during clinical practice, true estimates of 

frequency cannot be made and a causal relationship to the events has not been established. 

 

Paediatric population 

The study consisted of 106 patients, 104 of whom were paediatric patients aged from 6 months to less than 

18 years (see section 5.1). Every patient experienced at least 1 adverse reaction. The most frequently 

reported adverse reactions were neutropenia, anaemia, leukopenia and pyrexia. Serious adverse reactions 

reported in more than 2 patients were pyrexia, back pain, peripheral oedema and vomiting. No new safety 

signals were identified in the limited number of paediatric patients treated with Abraxane and the safety 

profile was similar to that of the adult population. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are 

asked to report any suspected adverse reactions via the national reporting system listed in Appendix V. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


18 

 

4.9 Overdose 

 

There is no known antidote for paclitaxel overdose. In the event of an overdose, the patient should be 

closely monitored. Treatment should be directed at the major anticipated toxicities, which are bone 

marrow suppression, mucositis and peripheral neuropathy. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antineoplastic agents, plant alkaloids and other natural products, taxanes, 

ATC Code: L01CD01 

 

Mechanism of action  

Paclitaxel is an antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and 

stabilises microtubules by preventing depolymerisation. This stability results in the inhibition of the 

normal dynamic reorganisation of the microtubule network that is essential for vital interphase and mitotic 

cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules 

throughout the cell cycle and multiple asters of microtubules during mitosis.  

 

Abraxane contains human serum albumin-paclitaxel nanoparticles of approximately 130 nm in size, where 

the paclitaxel is present in a non-crystalline, amorphous state. Upon intravenous administration, the 

nanoparticles dissociate rapidly into soluble, albumin bound paclitaxel complexes of approximately 10 nm 

in size. Albumin is known to mediate endothelial caveolar transcytosis of plasma constituents, and in vitro 

studies demonstrated that the presence of albumin in Abraxane enhances transport of paclitaxel across 

endothelial cells. It is hypothesised that this enhanced transendothelial caveolar transport is mediated by 

the gp-60 albumin receptor, and that there is enhanced accumulation of paclitaxel in the area of tumour 

due to the albumin-binding protein Secreted Protein Acidic Rich in Cysteine (SPARC). 

 

Clinical efficacy and safety 

  

Breast cancer 

Data from 106 patients accrued in two single-arm open-label studies and from 454 patients treated in a 

randomised Phase III comparative study are available to support the use of Abraxane in metastatic breast 

cancer. This information is presented below. 

 

Single-arm open-label studies 

In one study, Abraxane was administered as a 30-minute infusion at a dose of 175 mg/m2 to 43 patients 

with metastatic breast cancer. The second trial utilised a dose of 300 mg/m2 as a 30-minute infusion in 63 

patients with metastatic breast cancer. Patients were treated without steroid pre-treatment or planned 

G-CSF support. Cycles were administered at 3-week intervals. The response rates in all patients were 

39.5% (95% CI: 24.9%-54.2%) and 47.6% (95% CI: 35.3%-60.0%), respectively. The median time to 

disease progression was 5.3 months (175 mg/m2; 95% CI: 4.6-6.2 months) and 6.1 months (300 mg/m2; 

95% CI: 4.2-9.8 months). 

 

Randomised comparative study 

This multi-centre trial was conducted in patients with metastatic breast cancer, who were treated every 3 

weeks with single-agent paclitaxel, either as solvent-based paclitaxel 175 mg/m2 given as a 3-hour 

infusion with premedication to prevent hypersensitivity (N = 225), or as Abraxane 260 mg/m2 given as a 

30 minute infusion without premedication (N = 229).  

 



19 

Sixty-four percent of patients had impaired performance status (ECOG 1 or 2) at study entry; 79% had 

visceral metastases; and 76% had > 3 sites of metastases. Fourteen percent of the patients had not received 

prior chemotherapy; 27% had received chemotherapy in the adjuvant setting only, 40% in the metastatic 

setting only, and 19% in both metastatic and adjuvant settings. Fifty-nine percent received study medicinal 

product as second or greater than second-line therapy. Seventy-seven percent of the patients had been 

previously exposed to anthracyclines. 

 

Results for overall response rate and time to disease progression, and progression-free survival and 

survival for patients receiving > 1st-line therapy, are shown below. 

 

Table 10: Results for overall response rate, median time to disease progression, and 

progression-free survival as assessed by the investigator  

Efficacy variable 
Abraxane 

(260 mg/m2) 

Solvent-based paclitaxel 

(175 mg/m2) 
p-value 

Response rate [95% CI] (%) 

> 1st-line therapy 26.5 [18.98, 34.05] (n = 132) 13.2 [7.54, 18.93] (n = 136) 0.006a 

*Median time to disease progression [95% CI] (weeks) 

> 1st-line therapy 20.9 [15.7, 25.9] (n = 131) 16.1 [15.0, 19.3] (n = 135) 0.011b 

*Median progression free survival [95% CI] (weeks) 

> 1st-line therapy 20.6 [15.6, 25.9] (n = 131) 16.1 [15.0, 18.3] (n = 135) 0.010b 

*Survival [95% CI] (weeks) 

> 1st-line therapy 56.4 [45.1, 76.9] (n = 131) 46.7 [39.0, 55.3] (n = 136) 0.020b 

*This data is based on Clinical Study Report: CA012-0 Addendum dated Final (23 March-2005) 

a Chi-squared test  
b Log-rank test 

 

Two hundred and twenty nine patients treated with Abraxane in the randomized, controlled clinical trial 

were evaluated for safety. Neurotoxicity to paclitaxel was evaluated through improvement by one grade 

for patients experiencing Grade 3 peripheral neuropathy at any time during therapy. The natural course of 

peripheral neuropathy to resolution to baseline due to cumulative toxicity of Abraxane after > 6 courses of 

treatment was not evaluated and remains unknown. 

 

Pancreatic adenocarcinoma 

A multicenter, multinational, randomized, open-label study was conducted in 861 patients to compare 

Abraxane/gemcitabine versus gemcitabine monotherapy as first-line treatment in patients with metastatic 

adenocarcinoma of the pancreas. Abraxane was administered to patients (N = 431) as an intravenous 



20 

infusion over 30-40 minutes at a dose of 125 mg/m2 followed by gemcitabine as an intravenous infusion 

over 30-40 minutes at a dose of 1000 mg/m2 given on Days 1, 8 and 15 of each 28-day cycle. In the 

comparator treatment arm, gemcitabine monotherapy was administered to patients (N = 430) in 

accordance with the recommended dose and regimen. Treatment was administered until disease 

progression or development of an unacceptable toxicity. Of the 431 patients with pancreatic 

adenocarcinoma who were randomized to receive Abraxane in combination with gemcitabine, the 

majority (93%) were white, 4% were black and 2% were Asian. 16% had a Karnofsky Performance Status 

of 100; 42% had a KPS of 90; 35% had a KPS of 80; 7% had a KPS of 70; and <1% of patients had a KPS 

of below 70. Patients with high cardiovascular risk, history of peripheral artery disease and/or of 

connective tissue disorders and/or interstitial lung disease were excluded from the study. 

 

Patients received a median treatment duration of 3.9 months in the Abraxane/gemcitabine arm and 2.8 

months in the gemcitabine arm. 32% of patients in the Abraxane/gemcitabine arm compared with 15% of 

patients in the gemcitabine arm received 6 or more months of treatment.  For the treated population, the 

median relative dose intensity for gemcitabine was 75% in the Abraxane/gemcitabine arm and 85% in the 

gemcitabine arm. The median relative dose intensity of Abraxane was 81%. A higher median cumulative 

dose of gemcitabine was delivered in the Abraxane/gemcitabine arm (11400 mg/m2) when compared with 

the gemcitabine arm (9000 mg/m2). 

 

The primary efficacy endpoint was overall survival (OS). The key secondary endpoints were progression-

free survival (PFS) and overall response rate (ORR), both assessed by independent, central, blinded 

radiological review using RECIST guidelines (Version 1.0).  

 

Table 11: Efficacy results from randomized study in patients with pancreatic adenocarcinoma 

(Intent-to-treat population) 

 

Abraxane(125 mg/m2)/gemcitabine 

(N=431) 

Gemcitabine 

(N=430) 

Overall Survival 

Number of deaths (%) 333 (77) 359 (83) 

Median Overall Survival, 

months (95% CI) 
8.5 (7.89, 9.53) 6.7 (6.01, 7.23) 

HRA+G/G (95% CI)a  0.72 (0.617, 0.835) 

P-valueb  <0.0001 

Survival Rate % (95% CI) at   

1 Year 35% (29.7, 39.5) 22% (18.1, 26.7) 

2 Year 9% (6.2, 13.1) 4% (2.3, 7.2) 

75th Percentile Overall 

Survival (months) 
14.8 11.4 

Progression-free Survival 

Death or progression, n (%) 277 (64) 265 (62) 

Median Progression-free 

Survival, months (95% CI) 
5.5 (4.47, 5.95) 3.7 (3.61, 4.04) 

HRA+G/G (95% CI)a 0.69 (0.581, 0.821) 

P-valueb  <0.0001 

Overall Response Rate 

Confirmed complete or partial 

overall response, n (%) 
99 (23) 31 (7) 

95% CI 19.1, 27.2 5.0, 10.1 

pA+G/pG (95% CI) 3.19 (2.178, 4.662) 

P-value (chi-square test) <0.0001 
CI = confidence interval, HRA+G/G = hazard ratio of Abraxane+gemcitabine/gemcitabine, pA+G/pG=response rate  ratio of 
Abraxane+gemcitabine/gemcitabine 
a stratified Cox proportional hazard model 



21 

b stratified log-rank test, stratified by geographic region (North America versus others), KPS (70 to 80 versus 90 to 100), and presence of liver 

metastasis (yes versus no). 

 
There was a statistically significant improvement in OS for patients treated with Abraxane/gemcitabine 

versus gemcitabine alone, with 1.8 months increase in median OS, 28% overall reduction in risk of death, 

59% improvement in 1-year survival, and 125% improvement in 2-year survival rates. 

 

Figure 1: Kaplan-Meier curve of overall survival (intent-to-treat population) 

 
 

Treatment effects on OS favoured the Abraxane/gemcitabine arm across the majority of pre-specified 

subgroups (including gender, KPS, geographic region, primary location of pancreatic cancer, stage at 

diagnosis, presence of liver metastases, presence of peritoneal carcinomatosis, prior Whipple procedure, 

presence of biliary stent at baseline, presence of pulmonary metastases, and number of metastatic sites). 

For patients ≥ 75 years of age in the Abraxane/gemcitabine and gemcitabine arms the survival Hazard 

Ratio (HR) was 1.08 (95% CI 0.653, 1. 797). For patients with normal baseline CA 19-9 levels the 

survival HR was 1.07 (95% CI 0.692, 1.661).  

 

There was a statistically significant improvement in PFS for patients treated with Abraxane/gemcitabine 

versus gemcitabine alone, with 1.8 months increase in median PFS.  

 

Non-small cell lung cancer 

A multicenter, randomized, open-label study was conducted in 1052 chemotherapy-naive patients with 

Stage IIIb/IV non-small cell lung cancer. The study compared Abraxane in combination with carboplatin 

versus solvent-based paclitaxel in combination with carboplatin as first-line treatment in patients with 

advanced non-small cell lung cancer. Over 99% of patients had an ECOG (Eastern Cooperative Oncology 

Group) performance status of 0 or 1. Patients with pre-existing neuropathy of Grade ≥ 2 or serious 

medical risk factors involving any of the major organ systems were excluded. Abraxane was administered 

to patients (N=521) as an intravenous infusion over 30 minutes at a dose of 100 mg/m2 on Days 1, 8 and 

15 of each 21-day cycle without any steroid premedication and without granulocyte colony stimulating 

(PT at  Risk) 

  
 

ABX/GEM 
 

:  
GEM : 

Time (months) 

 

ABRAXANE+Gemcitabine 
 Gemcitabine 
 

1.0 

0.9 

0.8 

0.7 

0.6 

0.5 

0.4 

0.3 

0.2 

0.1 

0.0 

Proportion 

of 
Survival 

P
ro

p
o

rt
io

n
 o

f 
S

u
rv

iv
al

 

 



22 

factor prophylaxis. Beginning immediately after the end of Abraxane administration, carboplatin at a dose 

of AUC = 6 mg•min/mL was administered intravenously on Day 1 only of each 21-day cycle.  Solvent-

based paclitaxel was administered to patients (N=531) at a dose of 200 mg/m2 as an intravenous infusion 

over 3 hours with standard premedication, immediately followed by carboplatin administered 

intravenously at AUC = 6 mg•min/mL. Each drug was administered on Day 1 of each 21-day cycle.  In 

both study arms treatment was administered until disease progression or development of an unacceptable 

toxicity. Patients received a median of 6 cycles of treatment in both study arms.  
 

The primary efficacy endpoint was overall response rate defined as the percentage of patients who 

achieved an objective confirmed complete response or partial response based on an independent, central, 

blinded radiological review using RECIST (Version 1.0).  Patients in the Abraxane/carboplatin arm had a 

significantly higher overall response rate compared with patients in the control arm: 33% versus 25%, 

p = 0.005 (Table 12). There was a significant difference in overall response rate in the 

Abraxane/carboplatin arm compared to the control arm in patients with non-small cell lung cancer of 

squamous histology (N=450, 41% vs. 24%, p<0.001), however this difference did not translate into a 

difference in PFS or OS. There was no difference in ORR between the treatment arms in patients with 

non-squamous histology (N=602, 26% vs 25%, p=0.808). 

 

Table 12: Overall response rate in randomized non-small cell lung cancer trial (intent-to-treat 

population)  

Efficacy Parameter 

Abraxane 

(100 mg/m2/week) 

+ carboplatin 

(N=521) 

Solvent-based paclitaxel 

(200 mg/m2 every 3 weeks) 

+ carboplatin 

(N=531) 

Overall Response Rate (independent review) 

Confirmed complete or partial overall response, n (%) 170 (33%) 132 (25%) 

95% CI (%) 28.6, 36.7 21.2, 28.5 

pA/pT (95.1% CI) 1.313 (1.082, 1.593) 

P-valuea 0.005 
CI = confidence interval; HRA/T = hazard ratio of Abraxane/carboplatin to solvent-based paclitaxel/carboplatin; pA/pT = response rate ratio of 
Abraxane/carboplatin to solvent-based paclitaxel/carboplatin. 
a P-value is based on a chi-square test. 

 

There was no statistically significant difference in progression-free survival (by blinded radiologist 

assessment) and overall survival between the two treatment arms. A non-inferiority analysis was 

conducted for PFS and OS, with a pre-specified non-inferiority margin of 15%. The non-inferiority 

criterion was met for both PFS and OS with the upper bound of the 95% confidence interval for the 

associated hazard ratios being less than 1.176 (Table 13). 

 



23 

Table 13: Non-inferiority analyses on progression-free survival and overall survival in randomized 

non-small cell lung cancer trial (intent-to-treat population) 

Efficacy Parameter  

Abraxane 

(100 mg/m2/week) 

+ carboplatin 

(N=521) 

Solvent-based paclitaxel 

(200 mg/m2 every 3 weeks) 

+ carboplatin 

(N=531) 

Progression-free Survivala (independent review) 

Death or progression, n (%) 429 (82%) 442 (83%) 

Median PFS (95% CI) (months) 6.8 (5.7, 7.7) 6.5 (5.7, 6.9) 

HRA/T (95% CI) 0.949 (0.830, 1.086) 

Overall Survival 

Number of deaths, n (%) 360 (69%) 384 (72%) 

Median OS (95% CI) (months) 12.1 (10.8, 12.9) 11.2 (10.3, 12.6) 

HRA/T (95.1% CI) 0.922 (0.797, 1.066) 
CI = confidence interval; HRA/T = hazard ratio of Abraxane/carboplatin to solvent-based paclitaxel/carboplatin; pA/pT = response rate ratio of 
Abraxane/carboplatin to solvent-based paclitaxel/carboplatin. 
a Per EMA methodological considerations for PFS endpoint, missing observations or initiation of subsequent new therapy were not used for 

censoring.  

 

Paediatric population 

Safety and effectiveness in paediatric patients have not been established (see section 4.2). 

 

Study ABI-007-PST-001, a Phase 1/2, multicenter, open-label, dose-finding study to assess the safety, 

tolerability and preliminary efficacy of weekly Abraxane in paediatric patients with recurrent or refractory 

solid tumours included a total of 106 patients aged ≥ 6 months to ≤ 24 years.  

 

The Phase 1 portion of the study included a total of 64 patients aged from 6 months to less than 18 years 

old and determined the maximum tolerated dose (MTD) to be 240 mg/m2, administered as an intravenous 

infusion over 30 minutes, on Days 1, 8, and 15 of each 28-day cycle.  

 

The Phase 2 portion enrolled a total of 42 patients using a Simon two-stage minimax design, aged from 6 

months to 24 years with recurrent or refractory Ewing’s sarcoma, neuroblastoma or rhabdomyosarcoma 

for the evaluation of antitumour activity assessed by the overall response rate (ORR). Of the 42 patients, 1 

patient was < 2, 27 were aged ≥ 2 to < 12, 12 were aged ≥12 to < 18 and 2 adult patients were aged ≥ 18 to 

24 years old. 

 

Patients were treated for a median of 2 cycles at the MTD. From the 41 patients eligible for efficacy 

evaluation in stage 1, 1 patient in the rhabdomyosarcoma group (N=14) had a confirmed partial response 

(PR) resulting in an ORR of 7.1% (95% CI:  0.2, 33.9). No confirmed complete response (CR) or PR was 

observed in either the Ewing’s sarcoma group (N=13) or the neuroblastoma group (N=14). None of the 

study arms continued into stage 2 because the protocol-defined requirement of ≥ 2 patients to have a 

confirmed response was not met.  

 

The median overall survival results, including the 1-year follow-up period were 32.1 weeks (95% CI: 

21.4, 72.9), 32.0 weeks (95% CI: 12, not established) and 19.6 weeks (95% CI: 4, 25.7) for the Ewing’s 

sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. 



24 

 

The overall safety profile of Abraxane in paediatric patients was consistent with the known safety profile 

of Abraxane in adults (see section 4.8). Based on these results, it was concluded that Abraxane as 

monotherapy does not have meaningful clinical activity or survival benefit that warrants further 

development in the paediatric population. 

 

5.2 Pharmacokinetic properties 

 

The pharmacokinetics of total paclitaxel following 30- and 180-minute infusions of Abraxane at dose 

levels of 80 to 375 mg/m2 were determined in clinical studies. The paclitaxel exposure (AUC) increased 

linearly from 2653 to 16736 ng.hr/ml following dosing from 80 to 300 mg/m2. 

 

In a study in patients with advanced solid tumours, the pharmacokinetic characteristics of paclitaxel 

following Abraxane administered intravenously at 260 mg/m2 over 30 minutes were compared with those 

following 175 mg/m2 of the solvent-based paclitaxel injection administered over 3 hours. Based on 

non-compartmental PK analysis, the plasma clearance of paclitaxel with Abraxane was larger (43%) than 

that following a solvent-based paclitaxel injection and its volume of distribution was also higher (53%). 

There were no differences in terminal half-lives. 

In a repeat dose study with 12 patients receiving Abraxane administered intravenously at 260 mg/m2, 

intra-patient variability in AUC was 19% (range = 3.21%-37.70%). There was no evidence for 

accumulation of paclitaxel with multiple treatment courses. 

 

Distribution 

Following Abraxane administration to patients with solid tumours, paclitaxel is evenly distributed into 

blood cells and plasma and is highly bound to plasma proteins (94%). 

 

The protein binding of paclitaxel following Abraxane was evaluated by ultrafiltration in a within-patient 

comparison study. The fraction of free paclitaxel was significantly higher with Abraxane (6.2%) than with 

solvent-based paclitaxel (2.3%). This resulted in significantly higher exposure to unbound paclitaxel with 

Abraxane compared with solvent-based paclitaxel, even though the total exposure is comparable. This is 

possibly due to paclitaxel not being trapped in Cremophor EL micelles as with solvent-based paclitaxel. 

Based on the published literature, in vitro studies of binding to human serum proteins, (using paclitaxel at 

concentrations ranging from 0.1 to 50 µg/ml), indicate that the presence of cimetidine, ranitidine, 

dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel. 

 

Based on population pharmacokinetic analysis, the total volume of distribution is approximately 1741 L; 

the large volume of distribution indicates extensive extravascular distribution and/or tissue binding of 

paclitaxel. 

 

Biotransformation and elimination 

Based on the published literature, in vitro studies with human liver microsomes and tissue slices show that 

paclitaxel is metabolised primarily to 6-hydroxypaclitaxel; and to two minor metabolites, 

3’-p-hydroxypaclitaxel and 6-3’-p-dihydroxypaclitaxel. The formation of these hydroxylated metabolites 

is catalysed by CYP2C8, CYP3A4, and both CYP2C8 and CYP3A4 isoenzymes, respectively. 

 

In patients with metastatic breast cancer, after a 30-minute infusion of Abraxane at 260 mg/m2, the mean 

value for cumulative urinary excretion of unchanged active substance accounted for 4% of the total 

administered dose with less than 1% as the metabolites 6-hydroxypaclitaxel and 3’-p-hydroxypaclitaxel, 

indicating extensive non-renal clearance. Paclitaxel is principally eliminated by hepatic metabolism and 

biliary excretion. 

 

At the clinical dose range of 80 to 300 mg/m2, the mean plasma clearance of paclitaxel ranges from 13 to 

30 L/h/m2, and the mean terminal half-life ranges from 13 to 27 hours. 



25 

 

Hepatic impairment 

The effect of hepatic impairment on population pharmacokinetics of Abraxane was studied in patients 

with advanced solid tumours. This analysis included patients with normal hepatic function (n=130), and 

pre-existing mild (n=8), moderate (n=7), or severe (n=5) hepatic impairment (according to NCI Organ 

Dysfunction Working Group criteria). The results show that mild hepatic impairment (total bilirubin >1 to 

≤1.5 x ULN) has no clinically important effect on pharmacokinetics of paclitaxel. Patients with moderate 

(total bilirubin >1.5 to ≤3 x ULN) or severe (total bilirubin >3 to ≤5 x ULN) hepatic impairment have a 

22% to 26% decrease in the maximum elimination rate of paclitaxel and approximately 20% increase in 

mean paclitaxel AUC compared with patients with normal hepatic function. Hepatic impairment has no 

effect on mean paclitaxel Cmax. In addition, elimination of paclitaxel shows an inverse correlation with 

total bilirubin and a positive correlation with serum albumin. 

 

Pharmacokinetic/pharmacodynamic modeling indicates that there is no correlation between hepatic 

function (as indicated by the baseline albumin or total bilirubin level) and neutropenia after adjusting for 

Abraxane exposure. 

 

Pharmacokinetic data are not available for patients with total bilirubin >5 x ULN or for patients with 

metastatic adenocarcinoma of the pancreas (see section 4.2). 

 

Renal impairment 

Population pharmacokinetic analysis included patients with normal renal function (n=65), and pre-existing 

mild (n=61), moderate (n=23), or severe (n=l) renal impairment (according to draft FDA guidance criteria 

2010). Mild to moderate renal impairment (creatinine clearance ≥30 to <90 ml/min) has no clinically 

important effect on the maximum elimination rate and systemic exposure (AUC and Cmax) of paclitaxel. 

Pharmacokinetic data are insufficient for patients with severe renal impairment and not available for 

patients with end stage kidney disease. 

 

Elderly 

Population pharmacokinetic analysis for Abraxane included patients with ages ranging from 24 to 85 

years old and shows that age does not significantly influence the maximum elimination rate and systemic 

exposure (AUC and Cmax) of paclitaxel. 

 

Pharmacokinetic/pharmacodynamic modelling using data from 125 patients with advanced solid tumours 

indicates that patients ≥ 65 years of age may be more susceptible to development of neutropenia within the 

first treatment cycle, although the plasma paclitaxel exposure is not affected by age. 

 

Paediatric population  

The pharmacokinetics of paclitaxel following 30 minutes of intravenous administration at dose levels of 

120 mg/m2 to 270 mg/m2 were determined in 64 patients (2 to ≤ 18 years) in Phase 1 of a Phase 1/2 study 

in recurrent or refractory paediatric solid tumours. Following dosing increase from 120 to 270 mg/m2, the 

paclitaxel mean AUC(0-inf) and Cmax ranged from 8867 to 14361 ng*hr/ml and from 3488 to 8078 ng/ml, 

respectively. 

 

Dose normalized peak drug exposure values were comparable across the dose range studied; however, 

dose-normalized total drug exposure values were only comparable across 120 mg/m2 to 240 mg/m2; with 

lower dose-normalized AUC∞ at the 270 mg/m2 dose level. At the MTD of 240 mg/m2, the mean CL was 

19.1 L/h and the mean terminal half-life was 13.5 hours. 

 

In children and adolescent patients, exposure to paclitaxel increased with higher dosing and weekly drug 

exposures were higher than in adult patients. 

 

Other intrinsic factors 



26 

Population pharmacokinetic analyses for Abraxane indicate that gender, race (Asian vs. White), and type 

of solid tumours do not have a clinically important effect on systemic exposure (AUC and Cmax) of 

paclitaxel. Patients weighing 50 kg had paclitaxel AUC approximately 25% lower than those weighing 75 

kg. The clinical relevance of this finding is uncertain. 

 

5.3 Preclinical safety data 

 

The carcinogenic potential of paclitaxel has not been studied. However, based on the published literature, 

paclitaxel is a potentially carcinogenic and genotoxic agent at clinical doses, based upon its 

pharmacodynamic mechanism of action. Paclitaxel has been shown to be clastogenic in vitro 

(chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice). Paclitaxel has 

been shown to be genotoxic in vivo (micronucleus test in mice), but it did not induce mutagenicity in the 

Ames test or the Chinese hamster ovary/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) 

gene mutation assay. 

 

Paclitaxel at doses below the human therapeutic dose was associated with low fertility when administered 

prior and during mating in male and female rats and foetal toxicity in rats. Animal studies with Abraxane 

showed non-reversible, toxic effects on the male reproductive organs at clinically relevant exposure levels. 

 

Paclitaxel and/or its metabolites were excreted into the milk of lactating rats. Following intravenous 

administration of radiolabelled paclitaxel to rats on days 9 to 10 postpartum, concentrations of 

radioactivity in milk were higher than in plasma and declined in parallel with the plasma concentrations. 
 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Human albumin solution (containing sodium, sodium caprylate and N-acetyl DL tryptophanate). 

 

6.2 Incompatibilities 
 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

6.3 Shelf life 
 

Unopened vials 

3 years 

 

Stability of reconstituted suspension in the vial 

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C in the original 

carton, protected from light.  

 

Stability of the reconstituted suspension in the infusion bag 

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C followed by 4 hours 

at 25°C, protected from light. 

 

However, from a microbiological point of view, unless the method of reconstituting and filling of the 

infusion bags precludes the risks of microbial contamination, the product should be used immediately after 

reconstitution and filling of the infusion bags. 

 

If not used immediately, in-use storage times and conditions are the responsibility of the user. 



27 

 

The total combined storage time of reconstituted medicinal product in the vial and in the infusion bag 

when refrigerated and protected from light is 24 hours. This may be followed by storage in the infusion 

bag for 4 hours below 25°C. 

 

6.4 Special precautions for storage 
 

Unopened vials 

Keep the vial in the outer carton in order to protect from light. Neither freezing nor refrigeration adversely 

affects the stability of the product. This medicinal product does not require any special temperature 

storage conditions. 

 

Reconstituted suspension 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

50 ml vial (type 1 glass) with a stopper (butyl rubber), with an overseal (aluminium), containing 100 mg 

of paclitaxel formulated as albumin bound nanoparticles. 

 

100 ml vial (type 1 glass) with a stopper (butyl rubber), with an overseal (aluminium), containing 250 mg 

of paclitaxel formulated as albumin bound nanoparticles. 

 

Pack size of one vial. 

 

6.6 Special precautions for disposal and other handling 

 

Preparation and administration precautions 

Paclitaxel is a cytotoxic anticancer medicinal product and, as with other potentially toxic compounds, 

caution should be exercised in handling Abraxane. The use of gloves, goggles and protective clothing is 

recommended. If the suspension contacts the skin, the skin should be washed immediately and thoroughly 

with soap and water. If it contacts mucous membranes, the membranes should be flushed thoroughly with 

water. Abraxane should only be prepared and administered by personnel appropriately trained in the 

handling of cytotoxic agents. Pregnant staff should not handle Abraxane. 

 

Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible 

infiltration during administration of the medicinal product. Limiting the infusion of Abraxane to 30 

minutes, as directed, reduces the likelihood of infusion-related reactions. 

 

Reconstitution and administration of the product 

Abraxane is supplied as a sterile lyophilised powder for reconstitution before use. After reconstitution, 

each ml of suspension contains 5 mg of paclitaxel formulated as albumin bound nanoparticles. 

 

100 mg vial: Using a sterile syringe, 20 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion 

should slowly be injected into a vial of Abraxane over a minimum of 1 minute. 

 

250 mg vial: Using a sterile syringe, 50 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion 

should slowly be injected into a vial of Abraxane over a minimum of 1 minute. 

 

The solution should be directed onto the inside wall of the vial. The solution should not be injected 

directly onto the powder as this will result in foaming. 

 



28 

Once the addition is complete, the vial should be allowed to stand for a minimum of 5 minutes to ensure 

proper wetting of the solid. Then, the vial should gently and slowly be swirled and/or inverted for at least 

2 minutes until complete resuspension of any powder occurs. The generation of foam must be avoided. If 

foaming or clumping occurs, the solution must stand for at least 15 minutes until foam subsides. 

 

The reconstituted suspension should be milky and homogenous without visible precipitates. Some settling 

of the reconstituted suspension may occur. If precipitates or settling are visible, the vial should be gently 

inverted again to ensure complete resuspension prior to use.  

 

Inspect the suspension in the vial for particulate matter. Do not administer the reconstituted suspension if 

particulate matter is observed in the vial. 

 

The exact total dosing volume of 5 mg/ml suspension required for the patient should be calculated and the 

appropriate amount of reconstituted Abraxane should be injected into an empty, sterile, PVC or non-PVC 

type intravenous bag. 

 

The use of medical devices containing silicone oil as a lubricant (i.e. syringes and IV bags) to reconstitute 

and administer Abraxane may result in the formation of proteinaceous strands. Administer Abraxane using 

an infusion set incorporating a 15 µm filter to avoid administration of these strands. Use of a 15 µm filter 

removes strands and does not change the physical or chemical properties of the reconstituted product.  

 

Use of filters with a pore size less than 15 µm may result in blockage of the filter. 

 

The use of specialized di(2-ethylhexyl)phthalate (DEHP)-free solution containers or administration sets is 

not necessary to prepare or administer Abraxane infusions.  

 

Following administration, it is recommended that the intravenous line be flushed with sodium chloride 9 

mg/ml (0.9%) solution for injection to ensure administration of the complete dose. 

 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V.  

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands 
 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/428/001 

EU/1/07/428/002 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 11 January 2008 

Date of latest renewal: 14 January 2013 

 

 



29 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

http://www.ema.europa.eu/


30 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D.  CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



31 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Celgene Distribution B.V.  

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic safety update reports (PSUR)  
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk management plan (RMP) 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and 

interventions detailed in the agreed RMP presented in Module 1.8.2. of the marketing authorisation and 

any agreed subsequent updates of the RMP.  

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency;  
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of an 

important (pharmacovigilance or risk minimisation) milestone being reached. 

 



32 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



33 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

Carton  

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Abraxane 5 mg/ml powder for suspension for infusion 

 

paclitaxel 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 100 mg of paclitaxel formulated as albumin bound nanoparticles.  

 

After reconstitution, each ml of suspension contains 5 mg of paclitaxel formulated as albumin bound 

nanoparticles. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Human albumin solution (containing sodium, sodium caprylate and N-acetyl DL 

tryptophanate). 

 

Contains sodium, see package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for suspension for infusion. 

 

1 vial 

 

100 mg/20 ml 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

Intravenous use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 



35 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Abraxane should not be substituted for or with other paclitaxel formulations. 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Unopened vials: Keep the vial in the outer carton in order to protect from light. 

 

Reconstituted suspension: It can be stored refrigerated at 2°C to 8°C for up to 24 hours in either the vial 

or an infusion bag, protected from light. The total combined storage time of reconstituted medicinal 

product in the vial and in the infusion bag when refrigerated and protected from light is 24 hours. This 

may be followed by storage in the infusion bag for 4 hours below 25°C. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V.  

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands 
 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/07/428/001 

 

 

13. BATCH NUMBER 

 

Lot  

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 



36 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 
 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 



37 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

Vial 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Abraxane 5 mg/ml powder for suspension for infusion 

 

paclitaxel  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 100 mg of paclitaxel formulated as albumin bound nanoparticles.  

 

After reconstitution, each ml of suspension contains 5 mg of paclitaxel. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Human albumin solution (containing sodium, sodium caprylate and N-acetyl DL 

tryptophanate). 

 

Contains sodium, see package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for suspension for infusion. 

 

1 vial 

 

100 mg/20 ml  

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 



38 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Unopened vials: Keep the vial in the outer carton in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V.  

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands 
 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/07/428/001 

 

 

13. BATCH NUMBER 

 

Lot  

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 



39 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

Carton 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Abraxane 5 mg/ml powder for suspension for infusion 

 

paclitaxel 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 250 mg of paclitaxel formulated as albumin bound nanoparticles.  

 

After reconstitution, each ml of suspension contains 5 mg of paclitaxel formulated as albumin bound 

nanoparticles. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Human albumin solution (containing sodium, sodium caprylate and N-acetyl DL 

tryptophanate). 

 

Contains sodium, see package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for suspension for infusion. 

 

1 vial 

 

250 mg/50 ml 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

Intravenous use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 



41 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Abraxane should not be substituted for or with other paclitaxel formulations. 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Unopened vials: Keep the vial in the outer carton in order to protect from light. 

 

Reconstituted suspension: It can be stored refrigerated at 2°C to 8°C for up to 24 hours in either the vial 

or an infusion bag, protected from light. The total combined storage time of reconstituted medicinal 

product in the vial and in the infusion bag when refrigerated and protected from light is 24 hours. This 

may be followed by storage in the infusion bag for 4 hours below 25°C. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V.  

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands 
 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/07/428/002 

 

 

13. BATCH NUMBER 

 

Lot  

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 



42 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 



43 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

Vial 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Abraxane 5 mg/ml powder for suspension for infusion 

 

paclitaxel  

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains 250 mg of paclitaxel formulated as albumin bound nanoparticles.  

 

After reconstitution, each ml of suspension contains 5 mg of paclitaxel. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Human albumin solution (containing sodium, sodium caprylate and N-acetyl DL 

tryptophanate). 

 

Contains sodium, see package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for suspension for infusion. 

 

1 vial 

 

250 mg/50 ml  

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 



44 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP  

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Unopened vials: Keep the vial in the outer carton in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V.  

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands 
 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/07/428/002 

 

 

13. BATCH NUMBER 

 

Lot  

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 



45 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 



46 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



47 

Package leaflet: Information for the user 

 

Abraxane 5 mg/ml powder for suspension for infusion 

 

paclitaxel 

 

Read all of this leaflet carefully before you start using this medicine because it contains important 

information for you. 

 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours.  

- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. See section 4. 

 

What is in this leaflet: 

1. What Abraxane is and what it is used for 
2. What you need to know before you are given Abraxane 
3. How to use Abraxane 
4. Possible side effects 
5. How to store Abraxane 
6. Contents of the pack and other information 
 

 

1. What Abraxane is and what it is used for  

 

What Abraxane is 

Abraxane contains, as its active substance, paclitaxel attached to the human protein albumin, in the form 

of tiny particles known as nanoparticles. Paclitaxel belongs to a group of medicines called “taxanes” used 

in cancer. 

• Paclitaxel is the part of the medicine that affects the cancer, it works by stopping cancer cells from 
dividing – this means that they die. 

• Albumin is the part of the medicine that helps paclitaxel dissolve in the blood and get across the 
walls of the blood vessels into the tumour. This means that other chemicals that can cause side 

effects that can be life threatening are not needed. Such side effects occur far less with Abraxane. 

 

What Abraxane is used for 

Abraxane is used to treat the following types of cancer: 

 

Breast Cancer 

• Breast cancer which has spread to other parts of the body (this is called “metastatic” breast cancer). 

• Abraxane is used in metastatic breast cancer when at least one other therapy has been tried but has 
not worked and you are unsuitable for treatments containing a group of medicines called 

“anthracyclines”. 

• People with metastatic breast cancer who received Abraxane where another therapy had failed, were 
more likely to experience a reduction in tumour size, and lived longer than people who took an 

alternative therapy. 

 

Pancreatic cancer 

• Abraxane is used together with a medicine called gemcitabine if you have metastatic cancer of the 
pancreas. People with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts 



48 

of the body) who received Abraxane with gemcitabine in a clinical trial lived longer than people 

who had only received gemcitabine. 

 

Lung Cancer 

• Abraxane is also used together with a medicine called carboplatin if you have the most common 
type of lung cancer, called “non-small cell lung cancer”. 

• Abraxane is used in non-small cell lung cancer where surgery or radiotherapy would not be suitable 
to treat the disease. 

 

2. What you need to know before you are given Abraxane 

 

Do not use Abraxane 

• if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of Abraxane (listed in 
section 6); 

• if you are breast-feeding; 

• if you have a low white blood cell count (baseline neutrophil counts <1500 cells/mm3 - your doctor 
will advise you on this). 

 

Warnings and precautions 

Talk to your doctor or nurse before using Abraxane 

• if you have poor kidney function; 

• if you have severe liver problems; 

• if you have heart problems. 
 

Talk to your doctor or nurse if you experience any of these conditions whilst being treated with Abraxane, 

your doctor may wish to stop treatment or reduce the dose: 

• if you experience any abnormal bruising, bleeding, or signs of infections such as a sore throat or a 
fever; 

• if you experience numbness, tingling, pricking sensations, sensitivity to touch, or muscle weakness; 

• if you experience breathing problems, like shortness of breath or dry cough. 
 

Children and adolescents 

Abraxane is only for adults and should not be taken by children and adolescents aged below 18 years. 

 

Other medicines and Abraxane 

Tell your doctor if you are taking or have recently taken any other medicines. This includes medicines 

obtained without a prescription, including herbal medicines. This is because Abraxane can affect the way 

some other medicines work. Also, some other medicines can affect the way Abraxane works. 

 

Take care and speak to your doctor when taking Abraxane at the same time as any of the following: 

• medicines for treating infections (i.e. antibiotics such erythromycin, rifampicin, etc.; ask your 
doctor, nurse or pharmacist if you are unsure whether the medicine you are taking is an antibiotic), 

and including medicines for treating fungal infections (e.g. ketoconazole) 

• medicines used to help you stabilize your mood also sometimes referred to as anti-depressants (e.g. 
fluoxetine)  

• medicines used to treat seizures (epilepsy) (e.g. carbamazepine, phenytoin) 

• medicines used to help you lower blood lipid levels (e.g. gemfibrozil) 

• medicine used for heartburn or stomach ulcers (e.g. cimetidine) 

• medicines used to treat HIV and AIDS (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, 
nevirapine) 

• a medicine called clopidogrel used to prevent blood clots. 
 



49 

Pregnancy breast-feeding and fertility 

Paclitaxel may cause serious birth defects and should therefore not be used if you are pregnant. Your 

doctor will arrange a pregnancy test before starting treatment with Abraxane. 

 

Women of childbearing age should use effective contraception during and up to 1 month after receiving 

treatment with Abraxane. 

 

Do not breast feed when taking Abraxane as it is not known if the active ingredient paclitaxel passes into 

the mother’s milk. 

 

Male patients are advised to use effective contraception and to avoid fathering a child during and up to six 

months after treatment and should seek advice on conservation of sperm prior to treatment because of the 

possibility of irreversible infertility due to therapy with Abraxane. 

 

Ask your doctor for advice before taking this medicine. 

 

Driving and using machines 

Some people may feel tired or dizzy after being given Abraxane. If this happens to you, do not drive or use 

any tools or machines. 

 

If you are given other medicines as part of your treatment, you should ask your doctor for advice on 

driving and using machines. 

 

Abraxane contains sodium 

Each ml of Abraxane contains approximately 4.2 mg of sodium. This should be taken into consideration if 

you are on a controlled sodium diet. 

 

 

3. How to use Abraxane 

 

Abraxane will be given to you by a doctor or nurse into a vein from an intravenous drip. The dose you 

receive is based on your body surface area and blood test results. The usual dose is for breast cancer is 

260 mg/m2 of body surface area given over a 30 minute period. The usual dose for advanced pancreatic 

cancer is 125 mg/m2 of body surface area given over a 30 minute period. The usual dose for non-small cell 

lung cancer is 100 mg/m2 of body surface area given over a 30 minute period. 

 

How often will you receive Abraxane? 

For treatment of metastatic breast cancer, Abraxane is usually given once every three weeks (on day 1 of a 

21-day cycle). 

 

For treatment of advanced pancreatic cancer, Abraxane is given on days 1, 8 and 15 of each 28-day 

treatment cycle with gemcitabine being given immediately after the Abraxane.  

 

For treatment of non-small cell lung cancer Abraxane is given once every week (i.e. on days 1, 8 and 15 of 

a 21-day cycle), with carboplatin being given once every three weeks (i.e. only on day 1 of each 21-day 

cycle), immediately after the Abraxane dose has been given. 

 

If you have any further questions on the use of this medicine, ask your doctor or nurse. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everyone gets them. 



50 

 

The very common side effects may affect more than 1 in 10 people: 

• Loss of hair (the majority of cases of hair loss happened less than one month after starting 
Abraxane. When it happens, hair loss is pronounced (over 50%) in the majority of patients) 

• Rash 

• Abnormal decrease in the number of types of white blood cells (neutrophils, lymphocytes or 
leukocytes) in the blood  

• Deficiency of red blood cells  

• Reduction in the number of platelets in the blood  

• Effect on peripheral nerves (pain, numbness, tingling or loss of feeling)  

• Pain in a joint or joints  

• Pain in the muscles  

• Nausea, diarrhoea, constipation, sore mouth, loss of appetite  

• Vomiting  

• Weakness and tiredness, fever  

• Dehydration, taste disturbance, weight loss  

• Low levels of potassium in the blood 

• Depression, sleep problems 

• Headache 

• Chills  

• Difficulty in breathing  

• Dizziness  

• Swelling of mucosal and soft tissues  

• Increased liver function tests 

• Pain in extremities 

• Cough 

• Abdominal pain 

• Nose bleeds  
 

The common side effects may affect up to 1 in 10 people:  

• Itching, dry skin, nail disorder 

• Infection, fever with decrease in the number of a type of white blood cell (neutrophils) in the blood, 
flushing, thrush, severe infection in your blood which may be caused by reduced white blood cells 

• Reduction in all blood cell counts 

• Chest or throat pain 

• Indigestion, abdominal discomfort 

• Stuffy nose 

• Pain in back, bone pain 

• Diminished muscular coordination or difficulty in reading, increased or decreased tears, loss of 
eyelashes 

• Changes in heart rate or rhythm, heart failure 

• Decreased or increased blood pressure 

• Redness or swelling at the site where the needle entered the body 

• Anxiety 

• Infection in the lungs 

• Infection in the urinary tract 

• Obstruction in the gut, inflammation of the large bowel, inflammation of the bile duct 

• Acute kidney failure 

• Increased bilirubin in the blood 

• Coughing up blood 



51 

• Dry mouth, difficulty in swallowing 

• Muscle weakness 

• Blurred vision 
 

The uncommon side effects may affect up to 1 in 100 people: 

• Increased weight, increased lactate dehydrogenase in the blood, decreased kidney function, 
increased blood sugar, increased phosphorus in the blood 

• Decreased or lack of reflexes, involuntary movements, pain along a nerve, fainting, dizziness when 
standing up, shaking, facial nerve paralysis 

• Irritated eyes, painful eyes, red eyes, itchy eyes, double vision, reduced vision, or seeing flashing 
lights, blurred vision due to swelling of the retina (cystoid macular oedema) 

• Ear pain, ringing in your ears 

• Coughing with phlegm, shortness of breath when walking or climbing stairs, runny nose, or dry 
nose, decreased breath sounds, water on the lung, loss of voice, blood clot in the lung, dry throat 

• Gas, stomach cramps, painful or sore gums, rectal bleeding 

• Painful urination, frequent urination, blood in the urine, inability to hold your urine 

• Fingernail pain, fingernail discomfort, loss of fingernails, hives, skin pain, red skin from sunlight, 
skin discolouration, increased sweating, night sweats, white areas on the skin, sores, swollen face 

• Decreased phosphorus in the blood, fluid retention, low albumin in the blood, increased thirst, 
decreased calcium in the blood, decreased sugar in the blood, decreased sodium in the blood 

• Pain and swelling in the nose, skin infections, infection due to catheter line 

• Bruising 

• Pain at site of tumour, death of the tumour 

• Decreased blood pressure when standing up, coldness in your hands and feet 

• Difficulty walking, swelling 

• Allergic reaction 

• Decreased liver function, increased size of liver 

• Pain in the breast 

• Restlessness 

• Small bleedings in your skin due to blood clots 

• A condition involving destruction of red blood cells and acute kidney failure 

 
The rare side effects may affect up to 1 in 1,000 people: 

• Skin reaction to another agent or lung inflammation following radiation 

• Blood clot 

• Very slow pulse, heart attack 

• Leaking of drug outside the vein 

• A disorder of the electrical conduction system of the heart (atrioventricular block) 
 

The very rare side effects may affect up to 1 in 10,000 people: 

• Severe inflammation/eruption of the skin and mucous membranes (Stevens-Johnson syndrome, 
toxic epidermal necrolysis) 

 
Not known side effects (frequency cannot be estimated from the available data): 

• Hardening/thickening of the skin (scleroderma).  
 
Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in 

this leaflet. You can also report side effects directly via the national reporting system listed in Appendix 

V. By reporting side effects you can help provide more information on the safety of this medicine. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


52 

 

5. How to store Abraxane 
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the carton and the vial after EXP. The 

expiry date refers to the last day of that month. 

 

Unopened vials: Keep the vial in the outer carton in order to protect from light. 

 

After first reconstitution the suspension should be used immediately. If not used immediately, the 

suspension may be stored in a refrigerator (2°C-8°C) for up to 24 hours in the vial when kept in the outer 

carton in order to protect it from light. 

 

The reconstituted suspension in the intravenous drip may be stored in a refrigerator (2°C-8°C) for up to 24 

hours protected from light. 

 

The total combined storage time of reconstituted medicinal product in the vial and in the infusion bag 

when refrigerated and protected from light is 24 hours. This may be followed by storage in the infusion 

bag for 4 hours below 25°C. 

 

Your doctor or pharmacist is responsible for disposing of any unused Abraxane correctly. 

 

 

6. Contents of the pack and further information 

 

What Abraxane contains 

The active substance is paclitaxel. 

Each vial contains 100 mg or 250 mg of paclitaxel formulated as albumin bound nanoparticles. 

After reconstitution, each ml of suspension contains 5 mg of paclitaxel formulated as albumin bound 

nanoparticles. 

The other ingredient is human albumin (containing sodium, sodium caprylate and N-acetyl DL 

tryptophanate). 

 

What Abraxane looks like and contents of the pack 

Abraxane is a white to yellow powder for suspension for infusion. Abraxane is available in glass vials 

containing 100 mg or 250 mg of paclitaxel formulated as albumin bound nanoparticles. 

 

Each pack contains 1 vial. 

 

Marketing Authorisation Holder  

 

Celgene Europe B.V.  

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands 

 

Manufacturer 

 

Celgene Distribution B.V.  

Winthontlaan 6 N 

3526 KV Utrecht  

Netherlands  



53 

 

For any information about this medicine, please contact the Marketing Authorisation Holder. 

 

This leaflet was last revised in  

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

 

------------------------------------------------------------------------------------------------------------------------- 

 

Medical or healthcare professionals 

 

The following information is intended for medical or healthcare professionals only: 

 

Instructions for use, handling and disposal 

 

Preparation and administration precautions 

Paclitaxel is a cytotoxic anticancer medicinal product and, as with other potentially toxic compounds, 

caution should be exercised in handling Abraxane. Gloves, goggles and protective clothing should be 

used. If Abraxane suspension contacts the skin, the skin should be washed immediately and thoroughly 

with soap and water. If Abraxane contacts mucous membranes, the membranes should be flushed 

thoroughly with water. Abraxane should only be prepared and administered by personnel appropriately 

trained in the handling of cytotoxic agents. Pregnant staff should not handle Abraxane. 

 

Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible 

infiltration during administration of the medicinal product. Limiting the infusion of Abraxane to 30 

minutes, as directed, reduces the likelihood of infusion-related reactions. 

 

Reconstitution of the product and administration 

Abraxane should be administered under the supervision of a qualified oncologist in units specialised in the 

administration of cytotoxic agents. 

 

Abraxane is supplied as a sterile lyophilised powder for reconstitution before use. After reconstitution, 

each ml of suspension contains 5 mg of paclitaxel formulated as albumin bound nanoparticles. 

Reconstituted Abraxane suspension is administered intravenously using an infusion set incorporating a 

15 µm filter. 

 

Reconstitution of 100 mg: 

Using a sterile syringe, 20 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion should slowly be 

injected into the 100 mg vial of Abraxane over a minimum of 1 minute.  

 

Reconstitution of 250 mg: 

Using a sterile syringe, 50 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion should slowly be 

injected into the 250 mg vial of Abraxane over a minimum of 1 minute.  

 

The solution should be directed onto the inside wall of the vial. The solution should not be injected 

directly onto the powder as this will result in foaming. 

 

Once the addition is complete, the vial should be allowed to stand for a minimum of 5 minutes to ensure 

proper wetting of the solid. Then, the vial should gently and slowly be swirled and/or inverted for at least 

2 minutes until complete resuspension of any powder occurs. The generation of foam should be avoided. 

If foaming or clumping occurs, the suspension should stand for at least 15 minutes until foam subsides. 

 



54 

The reconstituted suspension should be milky and homogenous without visible precipitates. Some settling 

of the reconstituted suspension may occur. If precipitates or settling are visible, the vial should be gently 

inverted again to ensure complete resuspension prior to use. 

 

Inspect the suspension in the vial for particulate matter. Do not administer the reconstituted suspension if 

particulate matter is observed in the vial. 

 

The exact total dosing volume of 5 mg/ml suspension required for the patient should be calculated and the 

appropriate amount of reconstituted Abraxane should be injected into an empty, sterile, PVC or non-PVC 

type intravenous bag 

 

The use of medical devices containing silicone oil as a lubricant (i.e. syringes and IV bags) to reconstitute 

and administer Abraxane may result in the formation of proteinaceous strands. Administer Abraxane using 

an infusion set incorporating a 15 µm filter to avoid administration of these strands. Use of a 15 µm filter 

removes strands and does not change the physical or chemical properties of the reconstituted product.  

 

Use of filters with a pore size less than 15 µm may result in blockage of the filter. 

 

The use of specialized DEHP-free solution containers or administration sets is not necessary to prepare or 

administer Abraxane infusions.  

 

Following administration, it is recommended that the intravenous line be flushed with sodium chloride 9 

mg/ml (0.9%) solution for injection to ensure administration of the complete dose. 

 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

Stability 

Unopened vials of Abraxane are stable until the date indicated on the package when the vial is kept in the 

outer carton in order to protect from light. Neither freezing nor refrigeration adversely affects the stability 

of the product. This medicinal product does not require any special temperature storage conditions.  

 

Stability of the reconstituted suspension in the vial 

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C in the original 

carton, protected from light. 

 

Stability of the reconstituted suspension in the infusion bag 

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C followed by 4 hours 

at 25°C, protected from light.  

 

However, from a microbiological point of view, unless the method of reconstituting and filling of the 

infusion bags precludes the risks of microbial contamination, the product should be used immediately 

after reconstitution and filling of the infusion bags. 

 

If not used immediately, in-use storage times and conditions are the responsibility of the user. 

 

The total combined storage time of reconstituted medicinal product in the vial and in the infusion bag 

when refrigerated and protected from light is 24 hours. This may be followed by storage in the infusion 

bag for 4 hours below 25°C. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET