Pazenir

1 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 
 
 

1.  NAME OF THE MEDICINAL PRODUCT 
 
Pazenir 5 mg/ml powder for dispersion for infusion. 
 
 
2.  QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 100 mg of paclitaxel formulated as albumin bound 
nanoparticles.  
 
After reconstitution, each ml of dispersion contains 5 mg of paclitaxel formulated as albumin 
bound nanoparticles. 
 
 
For the full list of excipients, see section 6.1. 
 
 
3.  PHARMACEUTICAL FORM 
 
Powder for dispersion for infusion. 
 
The reconstituted dispersion 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 
 
Pazenir 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). 
 
Pazenir in combination with gemcitabine is indicated for the first-line treatment of adult patients with 
metastatic adenocarcinoma of the pancreas. 
 
Pazenir 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 
 
Pazenir 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 Pazenir is 260 mg/m2 administered intravenously over 30 minutes every 3 
weeks. 
 
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 Pazenir therapy should have the dose reduced to 220 mg/m2 for 



3 
 
 

subsequent courses. Following recurrence of severe neutropenia or severe sensory neuropathy, 
additional dose reduction should be made to 180 mg/m2. Pazenir 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 Pazenir 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 Pazenir 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 Pazenir 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) Pazenir 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 
ORTreat with same doses as Day 8 

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

Treat with Day 8 dose levels and follow 
with WBC Growth Factors 

OR 
Reduce doses 1 dose level from 

Day 8 doses 
 < 500 OR < 50,000 Withhold doses 



4 
 
 

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) Pazenir 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 

aSee Table 1 for dose level reductions 
 
Non-small cell lung cancer 
The recommended dose of Pazenir 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 
Pazenir administration. 
 
Dose adjustments during treatment of non-small cell lung cancer 
Pazenir 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 
Pazenir, patients must have an ANC ≥500 cells/mm3 and platelets >50,000 cells/mm3 or the dose is to 
be withheld 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. 
 



5 
 
 

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

e 
Dose of Pazenir  

(mg/m2)1 
Dose of 

carboplatin 
(AUC mg•min/mL

)1 
Nadir ANC <500/mm3 with 
neutropenic 
fever > 38°C 

O
R 

Delay of next cycle due to 
persistent neutropenia2 (Nadir 
ANC <1500/mm3) 

O
R 

Nadir ANC <500/mm3 for > 1 week 

Fir
st 

7
5 

4
.
5 

Second 5
0 

3
.
0 

Third Discontinue Treatment 

Nadir platelets <50,000/mm3 Fir
st 

7
5 

4
.
5 

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

Grade 4 cutaneous toxicity, diarrhoea, or 
mucositis 

Third Discontinue Treatment 
First Discontinue Treatment 

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



6 
 
 

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). 
 
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 Pazenir 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 Pazenir 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 human serum albumin-paclitaxel 
nanoparticles 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 human serum albumin-paclitaxel nanoparticles. However, a subsequent analysis in 981 
patients receiving human serum albumin-paclitaxel nanoparticles 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 human 
serum albumin-paclitaxel nanoparticles 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 human 
serum albumin-paclitaxel nanoparticles 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 human 
serum albumin-paclitaxel nanoparticles 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 human serum albumin-paclitaxel nanoparticles/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 human serum albumin-paclitaxel nanoparticles 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 
human serum albumin-paclitaxel nanoparticles in the paediatric population for the indication of 
metastatic breast cancer or pancreatic adenocarcinoma or non-small cell lung cancer. 
 
Method of administration 
Pazenir is for intravenous use. Reconstituted Pazenir dispersion should be administered 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 



7 
 
 

administration of the complete dose. 
 
For instructions on reconstitution of the medicinal product before administration, see section 6.6. 
 
4.3  Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 
6.1.  
Breast-feeding (see section 4.6). 
Patients who have baseline neutrophil counts <1500 cells/mm3. 
 
4.4  Special warnings and precautions for use 
 
Pazenir 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 human serum albumin-
paclitaxel nanoparticles. Neutropenia is dose-dependent and a dose-limiting toxicity. Frequent 
monitoring of blood cell counts should be performed during Pazenir therapy. Patients should not be 
retreated with subsequent cycles of Pazenir 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 human serum albumin-paclitaxel nanoparticles, 
although development of severe symptoms is less common. The occurrence of Grade 1 or 2 sensory 
neuropathy does not generally require dose reduction. When Pazenir 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 Pazenir is recommended (see section 
4.2). For combination use of Pazenir and gemcitabine, if Grade 3 or higher peripheral neuropathy 
develops, withhold Pazenir; continue treatment with gemcitabine at the same dose. Resume Pazenir 
at reduced dose when peripheral neuropathy improves to Grade 0 or 1 (see section 4.2). For 
combination use of Pazenir 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 Pazenir and carboplatin (see section 4.2). 
 
Sepsis 
Sepsis was reported at a rate of 5% in patients with or without neutropenia who received Pazenir 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 Pazenir 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 human serum albumin-paclitaxel nanoparticles was 
used as monotherapy and in 4% of patients when Pazenir was used in combination with 
gemcitabine. Closely monitor all patients for signs and symptoms of pneumonitis. After ruling out 



8 
 
 

infectious etiology and upon making a diagnosis of pneumonitis, permanently discontinue 
treatment with Pazenir and gemcitabine and promptly initiate appropriate treatment and supportive 
measures (see section 4.2). 
 
Hepatic impairment 
Because the toxicity of paclitaxel can be increased with hepatic impairment, administration of Pazenir 
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. 
 
Pazenir is not recommended in patients that have total bilirubin > 5 x ULN or AST > 10 x ULN. In 
addition, Pazenir 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 human serum albumin-paclitaxel nanoparticles. Most of the individuals were 
previously exposed to cardiotoxic medicinal products such as anthracyclines, or had underlying 
cardiac history. Thus, patients receiving Pazenir should be vigilantly monitored by physicians for the 
occurrence of cardiac events. 
 
Central nervous system metastases 
The effectiveness and safety of human serum albumin-paclitaxel nanoparticles 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 Pazenir, 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 Pazenir and 
gemcitabine in comparison to gemcitabine monotherapy has been demonstrated. In the very elderly 
(≥75 years) who received Pazenir 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 Pazenir 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 Pazenir and gemcitabine (see section 5.1). 
 
Erlotinib should not be co-administered with Pazenir plus gemcitabine (see section 4.5). 
 
Excipients 
When reconstituted, Pazenir concentrate contains 4.2 mg of sodium per ml. To be taken into 
consideration by patients on a controlled sodium diet. 
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 
‘sodium-free’. 
 



9 
 
 

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 medicinal products 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 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 Pazenir and gemcitabine have not been evaluated in humans. 
 
A pharmacokinetic study was conducted with human serum albumin-paclitaxel nanoparticles and 
carboplatin in non-small cell lung cancer patients. There were no clinically relevant 
pharmacokinetic interactions between human serum albumin-paclitaxel nanoparticlesand 
carboplatin. 
 
Pazenir 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). Pazenir 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 breast-feeding 
 
Contraception in males and females 
Women of childbearing potential should use effective contraception during treatment and up to 1 
month after receiving treatment with Pazenir. Male patients treated with Pazenir 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 Pazenir. Pazenir 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, Pazenir is contraindicated during lactation.  Breast-feeding must be 
discontinued for the duration of therapy. 
 
Fertility 
Human serum albumin-paclitaxel nanoparticles 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 Pazenir. 
 



10 
 
 

4.7  Effects on ability to drive and use machines 
 
Paclitaxel has minor or moderate influence on the ability to drive and use machines. Paclitaxel 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. 
 
4.8  Undesirable effects 
 
Summary of the safety profile 
The most common clinically significant adverse reactions associated with the use of human serum 
albumin-paclitaxel nanoparticles have been neutropenia, peripheral neuropathy, arthralgia/myalgia 
and gastrointestinal disorders. 
 
The frequencies of adverse reactions associated with the administration of human serum albumin-
paclitaxel nanoparticles are listed in Table 6 (human serum albumin-paclitaxel nanoparticles as 
monotherapy) and Table 7 (human serum albumin-paclitaxel in combination with gemcitabine), and 
Table 9 (human serum albumin-paclitaxel nanoparticles in combination with carboplatin). 
 
Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 
to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Within each frequency grouping, 
adverse reactions are presented in order of decreasing seriousness. 
 
Breast cancer (human serum albumin-paclitaxel nanoparticles administered as monotherapy) 
 
Tabulated list of adverse reactions 
Table 6 lists adverse reactions associated with the administration of human serum albumin-paclitaxel 
nanoparticles to patients from studies in which human serum albumin-paclitaxel nanoparticles has 
been administered as monotherapy at any dose in any indication (N = 789). 
 
Table 6: Adverse reactions reported with human serum albumin-paclitaxel 
nanoparticlesmonotherapy 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 



11 
 
 

 
Uncommon: Hypophosphataemia, fluid retention, hypoalbuminaemia, 
polydipsia, hyperglycaemia, hypocalcaemia, hypoglycaemia, 
hyponatraemia 

Psychiatric disorders 
Common: Insomnia, depression, anxiety 
 
Uncommon: Restlessness 

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 

Skin and subcutaneous 
tissue disorders 

Very common: Alopecia, rash 
 
Common: Nail disorder, pruritus, dry skin, erythema, nail 



12 
 
 

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. 
1The 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 human serum albumin-paclitaxel nanoparticles 
3 The frequency of pneumonitis is calculated based on pooled data in 1310 patients in clinical trials receiving 
human serum albumin-paclitaxel nanoparticlesmonotherapy for breast cancer and for other indications using 
MedDRA SMQ Interstitial lung disease. See section 4.4. 
 



13 
 
 

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 human serum albumin-paclitaxel 
nanoparticlesonce 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 human serum albumin-
paclitaxel nanoparticles. Febrile neutropenia occurred in four patients on human serum albumin-
paclitaxel nanoparticles. Anaemia (Hb < 10 g/dl) was observed in 46% of patients on human serum 
albumin-paclitaxel nanoparticles, 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 human serum albumin-paclitaxel nanoparticles. Peripheral neuropathy (mostly Grade 
1 or 2 sensory neuropathy) was observed in 68% of patients on human serum albumin-
paclitaxel nanoparticleswith 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 human serum albumin-paclitaxel 
nanoparticles. The majority of alopecia events occurred less than one month after initiation of 
human serum albumin-paclitaxel nanoparticles. 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 human serum albumin-paclitaxel nanoparticles and was 
severe in 6% of cases. Myalgia occurred in 24% of patients on human serum albumin-paclitaxel 
nanoparticles and was severe in 7% of cases. The symptoms were usually transient, typically occurred 
three days after human serum albumin-paclitaxel nanoparticles administration and resolved within a 
week. 
 
General disorders and administration site conditions 
Asthenia/Fatigue was reported in 40% of the patients. 
 
Pancreatic adenocarcinoma (Pazenir administered in combination with gemcitabine) 
 
Tabulated list of adverse reactions 
Adverse reactions were assessed in 421 patients treated with human serum albumin-paclitaxel 
nanoparticles 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 human serum albumin-paclitaxel nanoparticles in 
combination with gemcitabine. 
 



14 
 
 

Table 7: Adverse reactions reported with human serum albumin-paclitaxel nanoparticles 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 

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 



15 
 
 

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 human 
serum albumin-paclitaxel nanoparticles in combination with gemcitabine and for 4% of patients 
receiving gemcitabine monotherapy. 
 
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 human 
serum albumin-paclitaxel nanoparticlesin 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 human serum albumin-paclitaxel nanoparticlesin 
combination with gemcitabine or with gemcitabine. 
 
Table 8: Haematologic laboratory-detected abnormalities in pancreatic adenocarcinoma trial 
 Human serum albumin-

paclitaxel nanoparticles 
(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 human serum albumin-paclitaxel nanoparticles/gemcitabine-treated group 
b 388 patients assessed in gemcitabine-treated group 
c 404 patients assessed in human serum albumin-paclitaxel nanoparticles/gemcitabine-treated group 
 
Peripheral neuropathy 
For patients treated with human serum albumin-paclitaxel nanoparticlesin 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 human 
serum albumin-paclitaxel nanoparticlesat a reduced dose. No patients treated with human serum 
albumin-paclitaxel nanoparticlesin 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 human serum 
albumin-paclitaxel nanoparticlesin 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 Pazenir and gemcitabine until fever resolves and ANC ≥ 1500 
cells/mm3, then resume treatment at reduced dose levels (see section 4.2). 



16 
 
 

 
Pneumonitis 
Pneumonitis has been reported at a rate of 4% with the use of human serum albumin-paclitaxel 
nanoparticlesin combination with gemcitabine. Of the 17 cases of pneumonitis reported in patients 
treated with human serum albumin-paclitaxel nanoparticles 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 Pazenir and gemcitabine and promptly initiate appropriate treatment and supportive measures 
(see section 4.2). 
 
Non-small cell lung cancer (human serum albumin-paclitaxel nanoparticles administered in 
combination with carboplatin) 
 
Tabulated list of adverse reactions 
Table 9 lists adverse reactions associated with the administration of human serum albumin-
paclitaxel nanoparticles in combination with carboplatin. 
 
Table 9: Adverse reactions reported with human serum albumin-paclitaxel nanoparticles 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 



17 
 
 

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 
disordesrs 

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 

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 paclitaxel 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 human serum albumin-paclitaxel nanoparticles and carboplatin experienced 
Grade 4 peripheral neuropathy. 
 
Anemia and thrombocytopenia were more commonly reported in the human serum albumin-paclitaxel 
nanoparticles 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 human serum albumin-
paclitaxel nanoparticles 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 human serum albumin-paclitaxel 
nanoparticles. 
 
There have been rare reports of reduced visual acuity due to cystoid macular oedema during 
treatment with human serum albumin-paclitaxel nanoparticles. Upon diagnosis of cystoid macular 
oedema, treatment with Pazenir should be discontinued. 



18 
 
 

 
There have been reports of tumour lysis syndrome during treatment with human serum albumin-
paclitaxel nanoparticles. 
 
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 human serum albumin-paclitaxel nanoparticles. 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 human serum albumin-paclitaxel nanoparticles 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. 
 
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. 
 
Pazenir 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 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). 

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


19 
 
 

 
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 human serum 
albumin-paclitaxel nanoparticles in metastatic breast cancer. This information is presented below. 
 
Single-arm open-label studies 
In one study, human serum albumin-paclitaxel nanoparticles were 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 human serum albumin-
paclitaxel nanoparticles 260 mg/m2 given as a 30 minute infusion without premedication (N = 229). 
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 
human serum albumin-
paclitaxel nanoparticles 
(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) 



20 
 
 

> 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 human serum albumin-paclitaxel nanoparticles 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 human serum albumin-paclitaxel nanoparticles 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 
human serum albumin-paclitaxel nanoparticles/gemcitabine versus gemcitabine monotherapy as first-
line treatment in patients with metastatic adenocarcinoma of the pancreas. human serum albumin-
paclitaxel nanoparticles were administered to patients (N = 431) as an intravenous 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 human serum albumin-paclitaxel nanoparticles 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 human serum albumin-paclitaxel 
nanoparticles/gemcitabine arm and 2.8 months in the gemcitabine arm. 32% of patients in the human 
serum albumin-paclitaxel nanoparticles/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 human serum albumin-paclitaxel 
nanoparticles/gemcitabine arm and 85% in the gemcitabine arm. The median relative dose intensity of 
human serum albumin-paclitaxel nanoparticles was 81%. A higher median cumulative dose of 
gemcitabine was delivered in the human serum albumin-paclitaxel nanoparticles/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). 
 



21 
 
 

Table 11: Efficacy results from randomized study in patients with pancreatic adenocarcinoma 
(Intent-to-treat population) 
 Human serum albumin-paclitaxel 

nanoparticles 
(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% Cl)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%Cl)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% Cl) 3.19 (2.178, 4.662) 
P-value (chi-square 
test) 

<0.0001 

CI = confidence interval, HRA+G/G = hazard ratio of Paclitaxel human serum albumin-paclitaxel 
nanoparticles+gemcitabine/gemcitabine, pA+G/pG=response rate ratio of human serum albumin-paclitaxel 
nanoparticles+gemcitabine/gemcitabine 
a stratified Cox proportional hazard model 
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 human serum 
albumin-paclitaxel nanoparticles/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. 
 
 
 
 
 
 
 



22 
 
 

Pr
op

or
tio

n 
of

 S
ur

vi
va

l 

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

Time (months) 
 
Treatment effects on OS favoured the human serum albumin-paclitaxel nanoparticles/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 
human serum albumin-paclitaxel nanoparticles/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 human serum 
albumin-paclitaxel nanoparticles/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 human serum albumin-paclitaxel 
nanoparticles 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. Human serum albumin-paclitaxel nanoparticles were 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 
factor prophylaxis. Beginning immediately after the end of human serum albumin-paclitaxel 
nanoparticles 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 medicinal product was administered on Day 1 of each 21-day cycle. In both study 

(PT at Risk) 
 
ABX/GEM: 
          GEM: 

 [Teva invented name]+Gemcitabine 
 Gemcitabine 

 



23 
 
 

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 human serum 
albumin-paclitaxel nanoparticles/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 human serum albumin-paclitaxel 
nanoparticles/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 

Human serum 
albumin-paclitaxel 

nanoparticles 
(100mg/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 reponse, n 
(%) 

170 (33%) 132 (25%) 

95% Cl (%) 28.6, 36.7 21.2, 28.5 
PA/pT (95.1% Cl) 1.313 (1.082, 1.593) 
P-valuea 0.005 

CI = confidence interval; HRA/T = hazard ratio of Human serum albumin-paclitaxel nanoparticles/carboplatin to solvent-
based paclitaxel/carboplatin; pA/pT = response rate ratio of Human serum albumin-paclitaxel nanoparticles/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). 
 
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 

Human serum 
albumin-paclitaxel 

nanoparticles 
(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) 



24 
 
 

CI = confidence interval; HRA/T = hazard ratio of Human serum albumin-paclitaxel nanoparticles/carboplatin to solvent-
based paclitaxel/carboplatin; pA/pT = response rate ratio of Human serum albumin-paclitaxel nanoparticles/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 human serum albumin-paclitaxel nanoparticles 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. 
 
The overall safety profile of human serum albumin-paclitaxel nanoparticles in paediatric patients 
was consistent with the known safety profile of human serum albumin-paclitaxel nanoparticles in 
adults (see section 4.8). Based on these results, it was concluded that human serum albumin-
paclitaxel nanoparticles 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 human serum 
albumin-paclitaxel nanoparticles 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 human serum albumin-paclitaxel nanoparticles 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 human serum albumin-paclitaxel nanoparticles 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. 
 



25 
 
 

In a repeat dose study with 12 patients receiving human serum albumin-paclitaxel nanoparticles 
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 human serum albumin-paclitaxel nanoparticles 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 human serum albumin-paclitaxel nanoparticles was 
evaluated by ultrafiltration in a within-patient comparison study. The fraction of free paclitaxel was 
significantly higher with human serum albumin-paclitaxel nanoparticles (6.2%) than with solvent-
based paclitaxel (2.3%). This resulted in significantly higher exposure to unbound paclitaxel with 
human serum albumin-paclitaxel nanoparticles 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 6α-hydroxypaclitaxel; and to two minor metabolites, 3’-p-
hydroxypaclitaxel and 6α-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 human serum albumin-
paclitaxel nanoparticles 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 
6α-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. 
 
Hepatic impairment 
The effect of hepatic impairment on population pharmacokinetics of human serum albumin-paclitaxel 
nanoparticles 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 human serum albumin-paclitaxel nanoparticles exposure. 



26 
 
 

 
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 human serum albumin-paclitaxel nanoparticles 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 
Population pharmacokinetic analyses for human serum albumin-paclitaxel nanoparticles 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 



27 
 
 

administered prior and during mating in male and female rats and foetal toxicity in rats. Animal 
studies with human serum albumin-paclitaxel nanoparticles 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 
 
Albumin (human) 
Sodium caprylate 
N-acetyl-DL-tryptophan 
Sodium chloride 
Hydrochloric acid 
Sodium hydroxide  
 
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 
2 years 
 
Stability of reconstituted dispersion in the vial 
Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8 °C when the vial is 
in the original carton, and protected from bright light. Alternative light-protection may be used in the 
clean room. From a microbiological point of view, unless the method of 
opening/reconstituting/dilution precludes the risks of microbial contamination, the product should be 
filled into an infusion bag immediately. If not used immediately, in-use storage times and conditions 
are the responsibility of the user. 
 
Stability of the reconstituted dispersion in the infusion bag 
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C, 
protected from light followed by 4 hours at 15°C-25°C. From a microbiological point of view, 
unless the method of opening/reconstituting/dilution precludes the risks of microbial 
contamination, the product should be used immediately. If not used immediately, in-use 
storage times and conditions are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Unopened vials 
This medicinal product does not require any special temperature storage conditions. Keep the 
container in the outer carton in order to protect from light. Neither freezing nor refrigeration adversely 
affects the stability of the product.  
 
Reconstituted dispersion 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 



28 
 
 

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. 
 
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 Pazenir. The use of gloves, goggles and protective clothing is 
recommended. If the dispersion 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. Pazenir should only be prepared and administered by personnel appropriately 
trained in the handling of cytotoxic agents. Pregnant staff should not handle Pazenir. 
 
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 
Pazenir to 30 minutes, as directed, reduces the likelihood of infusion-related reactions. 
 
Reconstitution and administration of the product 
Pazenir is supplied as a sterile lyophilised powder for reconstitution before use. After 
reconstitution, each ml of dispersion contains 5 mg of paclitaxel formulated as albumin bound 
nanoparticles. 
 
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 Pazenir 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 redispersion 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 dispersion should be milky and homogenous without visible precipitates. Some 
settling of the reconstituted dispersion may occur. If precipitates or settling are visible, the vial 
should be gently inverted again to ensure complete redispersion prior to use. Inspect the dispersion 
in the vial for particulate matter. Do not administer the reconstituted dispersion if particulate matter 
is observed in the vial. 
 
The exact total dosing volume of 5 mg/ml dispersion required for the patient should be calculated and 
the appropriate amount of reconstituted Pazenir 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 Pazenir may result in the formation of proteinaceous strands. Administer 
Pazenir 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. 
 



29 
 
 

The use of specialized di(2-ethylhexyl)phthalate (DEHP)-free solution containers or administration 
sets is not necessary to prepare or administer Pazenir 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 
 
ratiopharm GmbH 
Graf-Arco-Straße 3 
89079 Ulm 
Germany 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1317/001 
 
 
9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
06 May 2019 
 
 
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(S) 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(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) responsible for batch release 

Merckle GmbH 
Ludwig-Merckle-Strasse 3 
89143 Blaubeuren 
Germany 
 
Pharmachemie B.V. 
Swensweg 5 
2031 GA Haarlem 
Netherlands 
 
Teva Nederland B.V. (additional entity) 
Swensweg 5 
2031GA Haarlem 
NETHERLANDS 
 
Teva Pharma B.V. 
Swensweg 5 
GA-2031 Haarlem 
Netherlands 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 

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 (PSURs) 
 

The requirements for submission of periodic safety update reports 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 



32 
 
 

authorisation and any agreeed  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. 

 
  



33 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



34 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  



35 
 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
CARTON 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Pazenir 5 mg/ml powder for dispersion 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 dispersion 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 dispersion for infusion. 
 
1 vial 
 
100 mg/20 ml 
 
 
5.  METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use. 
 
Read the package leaflet before 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. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Do not substitute for or with other paclitaxel formulations. 
 
 



36 
 
 

8.  EXPIRY DATE 
 
EXP: 
 
 
9.  SPECIAL STORAGE CONDITIONS 
 
Keep the container in the outer carton until use in order to protect from light. 
 
 
For storage conditions after reconstitution, see package leaflet. 
 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements 
 
 
11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ratiopharm GmbH 
Graf-Arco-Straße 3 
89079 Ulm 
Germany 
 
12.  MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1317/001 
 
 
13.  BATCH NUMBER 
 
Batch: 
 
 
14.  GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15.  INSTRUCTIONS ON USE 
 
 
16.  INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
17.  UNIQUE IDENTIFIER – 2D BARCODE 
  
2D bar code carrying the unique identifier 



37 
 
 

18.  UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN  



38 
 
 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  
VIAL 
 
1.  NAME OF THE MEDICINAL PRODUCT 
 
Pazenir 5 mg/ml powder for dispersion 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 dispersion 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 dispersion for infusion. 
 
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. 
 
 
7.  OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Do not substitute for or with other paclitaxel formulations. 
 
8.  EXPIRY DATE 
 
EXP 
 
 



39 
 
 

9.  SPECIAL STORAGE CONDITIONS 
 
Unopened vials: Keep the container in the outer carton until use 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 medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11.  NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ratiopharm GmbH 
Graf-Arco-Straße 3 
89079 Ulm 
Germany 
 
12.  MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1317/001 
 
 
13.  BATCH NUMBER 
 
Batch: 
 
 
14.  GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15.  INSTRUCTIONS ON USE 
 
 
16.  INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted.  
 
 
17.  UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18.  UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 

  



40 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 
 
 
 
 
 
 

 
 
 

 



41 
 
 

Package leaflet: Information for the user 
 

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

 
What Pazenir is used for 
Pazenir 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). 
• Pazenir 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 paclitaxel attached to the human protein 
albumin 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 
• Pazenir 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 of the body) who received paclitaxel attached to the human protein albumin with 



42 
 
 

gemcitabine in a clinical trial lived longer than people who had only received gemcitabine. 
 
Lung cancer 
• Pazenir 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”. 
• Pazenir 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 use Pazenir 
 
Do not use Pazenir 
• if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of Pazenir (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 Pazenir 
• 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 
Pazenir, 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 
This medicine is only for adults and should not be taken by children and adolescents aged below 18 
years. 
 
Other medicines and Pazenir  
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 Pazenir can 
affect the way some other medicines work. Also, some other medicines can affect the way Pazenir 
works. 
 
Take care and speak to your doctor when taking Pazenir at the same time as any of the following: 
 
• medicines for treating infections (i.e. antibiotics such as 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) 



43 
 
 

• a medicine called clopidogrel used to prevent blood clots 
 
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 Pazenir. 
 
If you are a woman of childbearing age, you should use effective contraception during and up to 1 
month after receiving treatment with Pazenir. 
 
Do not breast-feed when taking Pazenir as it is not known if the active ingredient paclitaxel passes into 
the mother’s milk. 
 
If you are a male patient, you are advised not to father a child during and up to six months after 
treatment and you should seek advice on conservation of sperm prior to treatment because of the 
possibility of irreversible infertility due to therapy with Pazenir. 
 
Ask your doctor for advice before taking this medicine. 
 
Driving and using machines 
Some people may feel tired or dizzy after being given Pazenir. 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. 
 
Pazenir contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 
‘sodium-free’. 
 
 
3.  How to use Pazenir 
 
Pazenir 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 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 Pazenir? 
For treatment of metastatic breast cancer, Pazenir is usually given once every three weeks (on day 1 of 
a 21 day cycle). 
 
For treatment of advanced pancreatic cancer, Pazenir is given on days 1, 8 and 15 of each 28-
day treatment cycle with gemcitabine being given immediately after the Pazenir. 
 
For treatment of non-small cell lung cancer Pazenir 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 Pazenir 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. 



44 
 
 

 
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 

paclitaxel. 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 
• Dry mouth, difficulty in swallowing 
• Muscle weakness 



45 
 
 

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


46 
 
 

5.  How to store Pazenir  
 
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 container in the outer carton until use in order to protect from light. 
 
After first reconstitution the dispersion should be used immediately. If not used immediately, the 
dispersion 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 dispersion in the intravenous drip may be stored for up to 24 hours at 2°C-8°C, 
protected from light followed by 4 hours at 15°C-25°C. 
 
Your doctor or pharmacist is responsible for disposing of any unused Pazenir correctly. 
 
 
6.  Contents of the pack and other information 
 
What Pazenir contains 
The active substance is paclitaxel. 
Each vial contains 100 mg of paclitaxel formulated as albumin bound nanoparticles. 
After reconstitution, each ml of dispersion 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), see section 2 “Pazenir contains sodium”. 
 
What Pazenir looks like and contents of the pack 
Pazenir is a white to yellow powder for dispersion for infusion. Pazenir is available in glass vials 
containing 100 mg of paclitaxel formulated as albumin bound nanoparticles. 
 
Each pack contains 1 vial. 
 
Marketing Authorisation Holder ratiopharm GmbH 
Graf-Arco-Straße 3 
89079 Ulm 
Germany 
 
ManufacturerMerckle GmbH 
Ludwig-Merckle-Straße 3 
89143 Blaubeuren 
Germany 
 
Pharmachemie B.V. 
Swensweg 5 
Haarlem 
2031 GA 
The Netherlands 
 
Teva Pharma B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 



47 
 
 

 
Teva Nederland B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./A.G. 
Tel/Tél: +32 3 820 73 73  

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 

 
България  
Actavis EAD 
Tel: +359 2 489 95 85 

 
Luxembourg/Luxemburg  
Teva Pharma Belgium N.V./S.A./A.G.,  
Tél: +32 3 820 73 73 

 
Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  

 
Magyarország  
Teva Gyógyszergyár Zrt. 
Tel.: +36 1 288 6400 

 
Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  

 
Malta  
Teva Pharmaceuticals Ireland, L-Irlanda 
Τel: +353 (0)1912 7700 

 
Deutschland 
ratiopharm GmbH 
Tel: +49 731 402 02 

 
Nederland  
Teva Nederland B.V. 
Tel: +31 (0) 800 0228400 

 
Eesti 
UAB Sicor Biotech Eesti filiaal 
Tel: +372 661 0801 

 
Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 

 
Ελλάδα 
Specifar ΑΒΕΕ 
Τηλ: +30 211 880 5000 

 
Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1 970070 

 
España 
Teva Pharma, S.L.U. 
Tél: +34 91 387 32 80   

 
Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 

 
France 
Teva Santé 
Tél: +33 1 55 91 78 00 

 
Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 214 767 550 

 
Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 

 
România 
Teva Pharmaceuticals S.R.L 
Tel: +40 21 230 65 24 

 
Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 (0)1912 7700 

 
Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 



48 
 
 

 
Ísland 
Actavis Pharmaceutical Iceland ehf. 
Sími: + 354 550 3300 

 
Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 

 
Italia 
Teva Italia S.r.l. 
Tel: +39 0289 17981 

 
Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Κύπρος 
Specifar ΑΒΕΕ, Ελλάδα 
Τηλ: +30 211 880 5000 

 
Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 

 
Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 67 323 666 

 
United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 

 
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 Pazenir. Gloves, goggles and protective 
clothing should be used. If Pazenir dispersion contacts the skin, the skin should be washed 
immediately and thoroughly with soap and water. If Pazenir contacts mucous membranes, the 
membranes should be flushed thoroughly with water. Pazenir should only be prepared and 
administered by personnel appropriately trained in the handling of cytotoxic agents. Pregnant staff 
should not handle Pazenir. 
 
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 
Pazenir to 30 minutes, as directed, reduces the likelihood of infusion-related reactions. 
 
Reconstitution of the product and administration 
Pazenir should be administered under the supervision of a qualified oncologist in units specialised in 
the administration of cytotoxic agents. 
 
Pazenir is supplied as a sterile lyophilised powder for reconstitution before use. After 
reconstitution, each ml of dispersion contains 5 mg of paclitaxel formulated as albumin bound 
nanoparticles. Reconstituted Pazenir dispersion 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 Pazenir over a minimum of 1 minute. 

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


49 
 
 

 
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 redispersion of any powder occurs. The generation of foam 
should be avoided. If foaming or clumping occurs, the dispersion should stand for at least 15 minutes 
until foam subsides. 
 
The reconstituted dispersion should be milky and homogenous without visible precipitates. Some 
settling of the reconstituted dispersion may occur. If precipitates or settling are visible, the vial should 
be gently inverted again to ensure complete redispersion prior to use. 
 
Inspect the dispersion in the vial for particulate matter. Do not administer the reconstituted 
dispersion if particulate matter is observed in the vial. 
 
The exact total dosing volume of 5 mg/ml dispersion required for the patient should be calculated and 
the appropriate amount of reconstituted Pazenir 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 Pazenir may result in the formation of proteinaceous strands. Administer 
Pazenir 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 Pazenir 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 Pazenir 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 dispersion in the vial 
After first reconstitution, the dispersion should be filled into an infusion bag immediately. However, 
chemical and physical in use stability has been demonstrated for 24 hours at 2°C-8°C in the original 
carton, and protected from bright light. 
 
Stability of the reconstituted dispersion in the infusion bag 
After reconstitution, the reconstituted dispersion in the infusion bag should be used 
immediately. However chemical and physical in use stability has been demonstrated for 24 
hours at 2°C-8°C, protected from light followed by 4 hours at 15°C-25°C. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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