Provenge

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
 

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▼ This medicinal product is subject to additional monitoring.  This will allow quick identification of 
new safety information.  Healthcare professionals are asked to report any suspected adverse reactions.  
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Provenge 50 x 106 CD54+ cells/250mL dispersion for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
2.1 General description 
 
Autologous peripheral blood mononuclear cells activated with PAP-GM-CSF (Sipuleucel-T). 
 
2.2 Qualitative and quantitative composition 
 
One bag contains autologous peripheral blood mononuclear cells activated with PAP-GM-CSF 
(prostatic acid phosphatase-granulocyte macrophage-colony stimulating factor), including a minimum 
of 50 x 106 autologous CD54+ cells. 
 
The cellular composition and the cell number per dose of Provenge will vary according to the 
patient’s leukapheresis.  In addition to antigen presenting cells (APCs), the final product thus contains 
T cells, B cells, natural killer (NK) cells, and other cells. 
 
Excipients with known effect 
This medicinal product contains approximately 800 mg of sodium and 45 mg of potassium per 
infusion. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Dispersion for infusion. 
The dispersion is slightly cloudy, with a cream-to-pink colour. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Provenge is indicated for treatment of asymptomatic or minimally symptomatic metastatic (non-
visceral) castrate resistant prostate cancer in male adults in whom chemotherapy is not yet clinically 
indicated. 
 
4.2 Posology and method of administration 
 
Provenge must be administered under the supervision of a physician experienced in the medical 
treatment of prostate cancer and in an environment where availability of resuscitation equipment must 
be ensured. 
 
Posology 
One dose of Provenge contains a minimum of 50 x 106 autologous CD54+ cells activated with 
PAP-GM-CSF, suspended in 250 mL of Lactated Ringer’s Injection, in a sealed, patient-specific 
polyolefin bag. 

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The recommended course of treatment is 3 doses at approximately 2-week intervals.  Each dose of 
Provenge is preceded by a standard leukapheresis procedure approximately 3 days prior to the 
scheduled infusion date.  Prior to the first leukapheresis procedure, a complete blood count (CBC) test 
should be performed and be within ranges acceptable for the local facility.  Additional CBC tests may 
be performed in accordance with local requirements. 
 
If, for any reason, the patient is unable to receive a scheduled infusion of Provenge, the patient will 
need to undergo an additional leukapheresis procedure if the course of treatment is to be continued.  
Patients should be advised of this possibility prior to initiating treatment.  In controlled clinical trials, 
25.4% of patients treated with Provenge required more than 3 leukapheresis procedures in order to 
receive 3 infusions.  In post-marketing experience of greater than 5,000 patients treated, this incidence 
is approximately 19% (see section 4.4).  In controlled clinical trials, the dosing interval range was 1 – 
15 weeks (see section 5.1). 
 
Premedication 
Acute infusion reactions such as chills, fatigue, fever, nausea, and joint ache were frequently observed 
in clinical studies.  To mitigate such reactions, premedication, consisting of paracetamol and an 
antihistamine was administered in clinical studies prior to infusion. 
 
To minimize potential acute infusion reactions such as chills and/or fever, it is recommended that 
patients be pre-medicated orally with paracetamol and an antihistamine approximately 30 minutes 
prior to administration of Provenge.  The doses of paracetamol and antihistamine given should be in 
accordance with local practice. 
 
In case of using premedication, the status of the patient and possible contraindications/interactions 
should be taken into account. 
 
Dose adjustments 
In the event of an acute infusion reaction, the infusion may be interrupted or slowed, depending on the 
severity of the reaction.  Appropriate medical therapy, which could include paracetamol, intravenous 
H1 and/or H2 blockers, and low dose intravenous pethidine, should be administered as needed. 
 
In controlled clinical trials, 23.8% of patients treated with Provenge required opioids (a single dose of 
pethidine) on the day of infusion for infusion reactions (see sections 4.4 and 4.8). 
 
If the infusion of Provenge must be interrupted, it should not be resumed if the infusion bag has been 
held at room temperature (25°C) for more than 3 hours (see section 6.3). 
 
Special populations 
 
Older people 
No dose adjustment is required in the elderly population. 
 
Patients with hepatic impairment 
Provenge has not been investigated in patients with hepatic impairment.  No specific dose 
recommendation can be provided in these patients. 
 
Patients with renal impairment and/or hyperkalaemia and/or on a controlled potassium diet 
Provenge has not been investigated in patients with renal impairment.  The potassium content per 
infusion should be taken into account if administered to patients with renal impairment and/or those 
on a controlled potassium diet.  Hyperkalaemia should be corrected prior to Provenge administration 
(see section 4.4). 
 
Paediatric population 

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There is no relevant use of Provenge in the paediatric population in children and adolescents less than 
18 years of age in the indication of asymptomatic or minimally symptomatic metastatic (non-visceral) 
castrate resistant prostate cancer in male adults in whom chemotherapy is not yet clinically indicated. 
 
Method of administration  
Provenge is solely intended for autologous use via intravenous infusion. 
 
Provenge should be infused intravenously over a period of approximately 60 minutes.  The entire 
volume of the bag should be infused.  A cell filter should not be used.  Vital signs should be taken at 
least 30 minutes prior to and 30 minutes following each infusion.  Patients should be observed for at 
least 30 minutes following each infusion.  For patients with cardiovascular disease or those at risk for 
cardiac ischaemia, physicians should consider observing patients for at least 60 minutes following 
each infusion with vital signs taken at 30 minutes and 60 minutes following the infusion. 
 
If the infusion of Provenge must be interrupted, it should not be resumed if the infusion bag has been 
held at room temperature (25°C) for more than 3 hours. 
 
Precautions to be taken before handling or administering the medicinal product 
Provenge is not tested for transmissible infectious diseases and hence may carry the risk of 
transmitting infectious diseases to healthcare professionals handling the product.  Appropriate 
precautions should be employed when handling Provenge (see section 4.4). 
 
It must be ensured that the APPROVED Final Product Disposition Notification form has been 
received from the marketing authorisation holder and the product has not expired (see section 6.6). 
 
Before infusion, it must be confirmed that the patient’s identity matches the essential unique patient 
information on the Provenge bag and on the Final Product Disposition Notification form. 
 
The bag should be removed from the insulated polyurethane container and inspected for leaks, 
external damage, foreign particulate matter, or clumps/clots. 
 
Contents of the bag will be slightly cloudy, with a cream to pink colour.  Gently mix and re-suspend 
the contents of the bag, inspecting for particles, clumps or clots.  Small clumps of cellular material 
should disperse with gentle manual mixing. 
 
Do not administer if the bag leaks during handling or if particles or clumps remain in the bag. 
 
For full instructions on the preparation and handling of Provenge, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
General 
Provenge is intended solely for autologous use and should under no circumstances be administered to 
other patients.  Prior to infusion, it must be confirmed that the patient’s identity matches the essential 
unique patient information on the Provenge bag and on the Final Product Disposition Notification 
form (see sections 4.2 and 6.6). 
 
Acute infusion reactions 
Acute infusion reactions have been observed in patients treated with Provenge.  Acute infusion 
reactions (reported within 1 day of infusion) included, but were not limited to, fever, chills, 
respiratory events (dyspnoea, hypoxia, and bronchospasm), nausea, vomiting, fatigue, hypertension, 
and tachycardia.  In the event of an acute infusion reaction, the infusion rate may be decreased, or the 

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infusion stopped, depending on the severity of the reaction.  Appropriate medical therapy should be 
administered as needed.  
 
In controlled clinical trials, 23.8% of patients treated with Provenge required opioids (a single dose of 
pethidine) on the day of infusion for infusion reactions (see sections 4.2 and 4.8).   
 
Patients with cardiac or pulmonary conditions should be closely monitored (see section 4.8). 
 
Infection 
Patients with positive serology tests for human immunodeficiency virus [HIV] 1 and 2, human T cell 
lymphotropic virus [HTLV] 1, and hepatitis B and C were excluded from controlled clinical trials.  
No data are available for these patients. 
 
Provenge should be delayed in patients with active systemic infection until resolution.  Serious 
infections including sepsis have been observed in patients treated with Provenge.  Some serious 
infections and sepsis were related to the use of central venous catheters (CVCs).  To reduce the risk of 
catheter-related infections, CVCs should be considered only for patients with poor peripheral venous 
access.  These  patients should be closely monitored for signs and symptoms of infection. 
 
Embolic and thrombotic events 
Provenge should be used with caution in patients with a history of embolic and thrombotic disorders. 
 
Cerebrovascular disease 
In controlled clinical trials, cerebrovascular events (hemorrhagic and ischaemic strokes) were 
observed in 3.5% of patients in the Provenge group compared with 2.6% of patients in the control 
group.  The clinical significance is uncertain. 
 
Cardiovascular disorders 
In controlled clinical trials, myocardial infarctions were observed in 0.8% of patients in the Provenge 
group compared with 0.3% of patients in the control group.  The clinical significance is uncertain. 
 
Immunocompromised patients 
Provenge should be used with caution in immunocompromised patients in general including patients 
taking systemic immunosuppressive therapy, after careful consideration of the potential risk-benefit 
on an individiual basis.  No data are available for these patients.  
 
Microbiological testing 
Provenge is released for infusion based on the microbial and sterility results from several tests: 
microbial contamination determination by Gram stain, endotoxin content, and in-process sterility with 
a 2-day incubation to determine absence of microbial growth.  The final (7-day incubation) sterility 
test results will not be available at the time of infusion.  If the sterility results become positive for 
microbial contamination after Provenge has been approved for infusion, the marketing authorisation 
holder will notify the treating physician and may request additional information from the physician in 
order to determine the source of contamination.  The physician should monitor and/or treat the patient 
as appropriate. 
 
Handling precautions for control of infectious disease 
Provenge is prepared from human blood of the specific patient and is not  tested for transmissible 
infectious agents.  Patient leukapheresis material is tested for transmissible infectious agents in line 
with applicable member state requirements.  However, as Provenge is an autologous product, a 
positive test does not preclude the manufacture of the product.  Therefore, patient leukapheresis 
material and Provenge may carry the risk of transmitting infectious viruses (HIV 1 and 2, hepatitis B 
and C) to healthcare professionals handling the product.  Accordingly, healthcare professionals should 
employ appropriate precautions when handling leukapheresis material or Provenge. 
 
Additionally, there is the small possibility/risk of transmitting infectious viruses to a patient if he is 
not the intended recipient of the product.  Hence it is important that the procedures for handling and 

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administering the product are precisely followed (see section 6.6).  It is strongly recommended that 
upon completion of each Provenge infusion, the patient specific label on the infusion bag, which 
contains the patient name, product name, and chain of identity (COI) product lot number, is removed 
and adhered to the patient file in order to maintain a link between the patient and the lot of the 
product. 
 
Cases in which Provenge cannot be infused 
In some cases, the patient may be unable to receive a scheduled infusion of Provenge.  This may be 
due to release criteria not being met during manufacturing, the expiration time being exceeded, or the 
patient being unable to meet the scheduled infusion time.  In such cases, the patient may need to 
undergo an additional leukapheresis procedure if the treatment is to be continued.  It is recommended 
that the minimum interval between leukapheresis procedures should not be less than 2 weeks.  In 
controlled clinical trials, 25.4% of patients treated with Provenge required more than 3 leukapheresis 
procedures in order to receive 3  infusions.  In post-marketing experience of greater than 5,000 
patients treated, this incidence is approximately 19% (see section 4.2).   
 
Immunisations 
The risks and benefits of vaccinating patients during the course of treatment with Provenge have not 
been studied.  Therefore, vaccinations with live attenuated or inactivated vaccines whilst receiving 
Provenge should be carefully considered. 
 
Educational materials 
All physicians who intend to prescribe Provenge must review the educational materials and sign the 
training verification form.  Physicians must provide the educational materials to the patient as well as 
the package leaflet and the Patient Alert Card.    
 
Sodium and potassium content 
This medicinal product contains approximately 800 mg sodium per infusion.  To be taken into 
consideration by patients on a controlled sodium diet.  The product also contains approximately 45 
mg potassium per infusion.  To be taken into consideration by patients with reduced kidney function 
or patients on a controlled potassium diet. 
 
Patients with renal impairment and/or hyperkalaemia 
The content of sodium and potassium per infusion should be taken into account if administered in 
patients with cardiovascular diseases and/or renal impairment.  Hyperkalaemia should be corrected 
prior to Provenge administration (see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed with Provenge. 
 
Provenge is designed to stimulate the immune system.  Immunocompromised patients and patients 
taking systemic immunosuppressive therapy were excluded from controlled clinical trials.  Concurrent 
use of immunosuppressive agents (such as systemic corticosteroids) may alter its efficacy and/or 
safety.  Therefore, concurrent use of immunosuppressive agents (such as systemic corticosteroids) 
should be avoided during Provenge treatment.  Patients should be carefully evaluated to determine 
whether it is medically appropriate to discontinue immunosuppressive agents prior to treatment with 
Provenge (see section 4.4). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Provenge is not intended for use in women. 
 
Breast-feeding 
Provenge is not intended for use in women. 
 

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Fertility 
Effect on male fertility is not known. 
 
Conventional reproductive and development toxicity studies are not considered relevant given the 
nature and the intended clinical use of this autologous cell therapy product. 
 
4.7 Effects on ability to drive and use machines 
 
Provenge has moderate influence on the ability to drive and use machines, as it may cause fatigue, 
dizziness, syncope, chills, and headache.  Patients should be advised not to drive or use machines if 
they experience these symptoms following their infusion.  
 
4.8 Undesirable effects 
 
Summary of safety profile 
The safety evaluation of Provenge is based on data from 601 prostate cancer patients in four 
randomized, controlled clinical trials (3 studies in metastatic castrate resistant prostate cancer and 1 
study in androgen dependent prostate cancer) and post-marketing surveillance. 
 
Serious adverse reactions include acute infusion reactions, catheter sepsis, staphylococcal 
bacteraemia, myocardial infarction, and cerebrovascular events. 
 
The most commonly reported adverse reactions are chills, fatigue, pyrexia, nausea, arthralgia, 
headache, and vomiting. 
 
In the pivotal randomised controlled study (D9902B, IMPACT, see section 5.1) Provenge was 
discontinued in 1.5% of patients due to adverse reactions.  Some patients developed infection, 
including sepsis.  Infections due to contaminated product also occurred in some patients.  A small 
number of these patients discontinued treatment as a result.   
 
Tabulated list of adverse reactions 
The following list of adverse reactions is based on experience from clinical trials and on post-
marketing experience and are displayed by system organ class and frequency of occurrence: 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), and not known (cannot be estimated from the available data).  
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
 

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Table 1 Adverse reactions from clinical studies and post-marketing reports 
 
System organ class Frequency Adverse reactions 
Infections and infestations Common Bacteraemia 

Uncommon Catheter sepsis 
Catheter related infection 
Catheter site infection 
Sepsis 

Blood and lymphatic system 
disorders 

Very common Anaemia* 
Common Thrombocytopenia* 
Uncommon Eosinophilia 

Nervous system disorders Very common Dizziness 
Paraesthesia* 
Paraesthesia oral* 
Headache 

Common Cerebrovascular accident 
Transient ischaemic attack 
Tremor 
Hypoaesthesia 
Spinal cord compression 
Syncope 

 Uncommon Cerebral infarction 
Cardiac disorders Common Atrial fibrillation 

Uncommon Myocardial infarction 
Myocardial ischaemia 

Vascular disorders Common Hypertension 
Hypotension 

Respiratory, thoracic, and 
mediastinal disorders 

Common Hypoxia 
Wheezing 
Dyspnoea 

Uncommon Bronchospasm 
Gastrointestinal disorders 
 

Very common 
 

Vomiting 
Nausea 

Common Abdominal pain 
Skin and subcutaneous tissue 
disorders 

Common Rash 
Hyperhidrosis 
Pruritus 
Urticaria 

Musculoskeletal and 
connective tissue disorders 

Very common Arthralgia 
Myalgia 

Common Muscle spasms* 
Renal and urinary disorders Common Haematuria 
General disorders and 
administration site conditions 
 
 
 

Very common Chills 
Fatigue 
Pyrexia 
Pain 
Asthenia 

Common Influenza-like illness 
Chest discomfort 

Uncommon Infusion site reaction 
Injury, poisoning and 
procedural complications 

Very common Citrate toxicity* 

* Primarily associated with the leukapheresis procedure 
 
 

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Description of selected adverse reactions  
 
Acute infusion reactions 
In controlled clinical trials, 71.2% of patients in the Provenge group developed an acute infusion 
reaction.  The most common reactions (≥ 20%) were chills, fever, and fatigue.  In 95.1% of patients 
reporting acute infusion reactions, the events were mild or moderate.  Fevers and chills generally 
resolved within 2 days (71.9% and 89.0%, respectively). 
 
In controlled clinical trials, severe (Grade 3) acute infusion reactions were reported in 3.5% of 
patients in the Provenge group.  Reactions included chills, fever, fatigue, asthenia, dyspnoea, hypoxia, 
bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting.  The incidence 
of severe reactions was greater following the second infusion (2.1% vs. 0.8% following the first 
infusion), and decreased to 1.3% following the third infusion.  Some (1.2%) patients in the Provenge 
group were hospitalized within 1 day of infusion for management of acute infusion reactions.  No 
Grade 4 or 5 acute infusion reactions were reported in patients in the Provenge group. 
 
In controlled clinical trials, 23.8% of patients in the Provenge group required opioids (a single dose of 
pethidine) on the day of infusion for infusion reactions compared with 2.4% of patients in control 
group (see sections 4.2 and 4.4).  
 
In the post-marketing setting, serious acute infusion reactions involving hypotension and syncope 
have been reported.  Some have resulted in hospitalization.  
 
Patients should be informed of the possibility of late onset reactions and instructed to contact their 
physician if symptoms of dyspnoea, bronchospasm, dizziness, rash, or pyrexia occur. 
 
Infection 
In controlled clinical trials, infection occurred in 27.5% of subjects in the Provenge group and 27.7% 
of subjects in the control group.  Serious infections occurred in 4.7% of subjects in the Provenge 
group and 4.0% of subjects in the control group.  The most frequently occurring serious infections in 
the Provenge group were catheter sepsis (0.7%), staphylococcal bacteraemia (0.7%), sepsis (0.7%), 
staphylococcal sepsis (0.5%), and pneumonia (0.5%).  
 
Reports of serious infection have been received in post-marketing surveillance including device-
related infection, device-related sepsis, pneumonia, sepsis, bacteraemia, and urinary tract infection. 
 
Adverse reactions associated with leukapheresis 
Each dose of Provenge requires a standard leukapheresis procedure approximately 3 days prior to the 
infusion.  Citrate is generally the preferred anticoagulant used during leukapheresis and can result in 
hypocalcaemia.  Adverse reactions that were reported most commonly ≤ 1 day following a 
leukapheresis procedure in controlled clinical trials included citrate toxicity (14.6%), oral paraesthesia 
(12.0%), and paraesthesia (11.1%).  Additional adverse reactions that were seen commonly ≤ 1 day 
following a leukapheresis procedure in controlled clinical trials included fatigue (5.5%), muscle 
spasm (4.0%), chills (3.0%), dizziness (2.8%), and anaemia (2.8%).  Additionally, there have been 
reports of thrombocytopenia received in spontaneous post-marketing reporting that have been 
temporally associated with leukapheresis. 
 
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 
 
Each Provenge infusion comprises the maximum number of cells that can be manufactured from a 
single leukapheresis procedure.  The number of cells in Provenge does not exceed the number of cells 

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from the leukapheresis.  There are no known instances of overdose from either a single infusion or a 
full course of therapy with Provenge. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, other immunostimulants, ATC code: L03AX17. 
 
Mechanism of action 
Provenge is an autologous cellular immunotherapy designed to induce an immune response targeted 
against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers.  Peripheral 
blood mononuclear cells collected from the patients are cultured with PAP-GM-CSF, a fusion protein 
consisting of PAP linked to granulocyte-macrophage colony-stimulating factor (GM-CSF) an immune 
cell activator.  During ex vivo culture with PAP-GM-CSF, activated APCs (antigen presenting cells) 
take up and process the recombinant target antigen into peptides that are then presented to T cells.  
Product characterization shows that PAP and PAP-GM-CSF fusion protein-specific T cells are 
generated during treatment and are detected in the peripheral blood of patients after treatment with 
Provenge. 
 
Pharmacodynamic effects 
As part of lot release, each product is assessed for activation of antigen presenting cells (APCs) by 
virtue of increased surface CD54 expression after culture with PAP-GM-CSF.  CD54 is an adhesion 
and costimulatory molecule essential in the formation of the immunological synapse between an APC 
and a T cell.  The degree of CD54 upregulation correlates with overall survival in the randomised 
controlled clinical trials carried out with Provenge in metastatic castrate resistant prostate cancer.  In 
clinical study D9902B (IMPACT), 237 out of the 512 patients randomized were evaluated for the 
development of humoral or cellular immune responses (T cell proliferation and gamma-interferon 
(γIFN) ELISPOT) to the target antigens at baseline, and at Weeks 6, 14, and 26.  Antibody (IgM and 
IgG) responses against both PAP-GM-CSF and the PAP antigens were observed in the Provenge 
group through the follow up period.  T cell proliferative and γIFN ELISPOT responses to PAP and 
PAP-GM-CSF were observed in cells collected from peripheral blood of patients through the 
follow-up period in the Provenge treatment group but not in controls.  There was a correlation 
between cellular or antibody responses to PAP or PAP-GM-CSF in the Provenge group and improved 
survival.  Neutralising antibody responses to GM-CSF were transient. 
 
Clinical efficacy and safety 
The efficacy and safety of Provenge in patients with asymptomatic or minimally symptomatic 
metastatic castrate resistant prostate cancer were studied in three similar Phase III, randomised, 
double-blind, controlled, multicentre trials: D9902B (IMPACT), D9901, and D9902A.  The patients 
enrolled in these trials had failed surgical or medical castration (e.g. luteinising hormone-releasing 
hormone [LHRH] agonist or gonadotropin-releasing hormone [GnRh] antagonist) therapies and had 
metastatic disease in the soft tissue and/or bone.  Patients did not require opioid analgesics for pain 
management and the majority had not received prior chemotherapy. 
 
Following randomization, patients from both treatment groups underwent a series of 3 leukapheresis 
procedures (at approximately 2 week intervals, range 1 to 15 weeks).  Each leukapheresis was 
followed approximately 3 days later by infusion of Provenge or control.  The control was non-
activated autologous peripheral blood mononuclear cells.  Following disease progression, patients 
were treated at the physician’s discretion with other anti-cancer interventions.  Patients in the control 
group could enrol in an open-label protocol and receive an investigational autologous cellular therapy 
manufactured from cells cryopreserved at the time the control product was prepared. 
 
IMPACT study 
The IMPACT study was a randomised, double-blind, controlled, multicentre trial in patients with 
asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer.  Eligible 

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patients had metastatic disease in the soft tissue and/or bone with current or historical evidence of 
disease progression concomitant with surgical or medical castration, as evidenced by progression of 
serum prostate specific antigen (PSA) and/or bone or soft tissue disease, and an Eastern Cooperative 
Oncology Group (ECOG) performance status of 0 or 1.  Exclusion criteria included visceral (liver, 
lung, or brain) metastases, malignant pleural effusions or malignant ascites, pathologic long bone 
fractures, imminent pathologic long-bone fractures (cortical erosion on radiography >50%), spinal 
cord compression, moderate to severe prostate cancer-related pain and use of narcotics for cancer-
related pain, and treatment with chemotherapy at least 3 months prior to randomisation.  The primary 
endpoint was overall survival.  Secondary endpoints included time to objective disease progression, 
time to clinical progression, and PSA doubling time (PSADT). 
 
A total of 512 patients were randomised in a 2:1 ratio to receive Provenge (n=341) or control (n=171).  
The median age was 71, 90% of the patients were Caucasian, and all had a life expectancy of at least 
6 months.  Thirty-five percent of patients had undergone radical prostatectomy, 54% had received 
local radiotherapy, and 82% had received combined androgen blockade.  All patients had baseline 
testosterone levels < 50 ng/mL.  Forty-eight percent of patients were receiving bisphosphonates and 
18% had received prior chemotherapy, including docetaxel.  Eighty-two percent of patients had an 
ECOG performance status of 0; 75% had a Gleason sum ≤ 7; 44% had bone and soft tissue disease; 
48% had bone-only disease; 7% had soft tissue-only disease; and 43% had greater than ten bony 
metastases. 
 
A statistically significant improvement in overall survival was seen in patients treated with Provenge, 
with a 22.5% reduction in the risk of death compared with control (see Table 2 and Figure 1).  Of the 
control arm patients, 64% crossed over to receive an investigational autologous cellular 
immunotherapy manufactured from cells cryopreserved at the time the control was manufactured; 
patients were not randomised to subsequent autologous cellular immunotherapy.   

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Figure 1 Kaplan-Meier overall survival curve, IMPACT study 

 
 
 
A retrospective subgroup analysis has suggested a greater Provenge treatment effect in patients with a 
baseline PSA < 22.1 ng/mL [HR= 0.521 (95% CI:  0.309, 0.879)].  Intermediate results were observed 
in patients with baseline PSA > 22.1 to 50.1 ng/mL [HR=0.685 (95% CI:  0.431, 1.088)] and patients 
with baseline PSA > 50.1 to 134.1 ng/mL [HR=0.819 (95% CI:  0.532, 1.262)].  A smaller treatment 
effect was observed in those with baseline PSA > 134.1 ng/mL [HR=0.853 (95% CI:  0.554, 1.315)].   
 
Analyses of time to objective disease progression, time to clinical progression, or PSA doubling time 
(PSADT) did not meet statistical significance. 
 
Supportive studies 
Study D9901 was a randomised, double-blind, controlled, multicentre trial in patients with metastatic 
castrate resistant prostate cancer and no cancer-related pain.  The primary endpoint was time to 
disease progression, which did not reach statistical significance.  Overall survival was not a study 
endpoint but a pre-specified analysis.  Patients treated with Provenge had a statistically significant 
survival advantage compared with control. 
 
A third study, D9902A, similar in design to study D9901, was terminated prior to completion of 
planned accrual based on the time to disease progression results in study D9901.  The primary 
endpoint was time to disease progression and the secondary endpoint was overall survival.  Neither 
endpoint met statistical significance. 
 
Summary of study results 
Table 2 presents overall survival results observed in IMPACT, study D9901, and study D9902A. 
 

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Table 2 Summary of overall survival (all patients as randomized) 
 
 IMPACT D9901 D9902A 
 Provenge 

(N=341) 
Control 
(N=171) 

Provenge 
(N=82) 

Control 
(N=45) 

Provenge 
(N=65) 

Control 
(N=33) 

Overall survival       
 Median, months 
 (95% CI) 

25.8 
(22.8, 27.7) 

21.7 
(17.7, 23.8) 

25.9 
(20.0, 32.4) 

21.4 
(12.3, 25.8) 

19.0 
(13.6, 31.9) 

15.7 
(12.8, 25.4) 

 Hazard ratio 
 (95% CI) 0.775

a (0.614, 0.979) 0.586b (0.388, 0.884) 0.786b (0.484, 1.278) 

 p-value 0.032a  0.010c  0.331 c   
 36-month 
 survival (%) 

32% 23% 34% 11% 32% 21% 

a Hazard ratio and p-value based on the Cox Model adjusted for PSA (ln) and LDH (ln) and stratified by 
bisphosphonate use, number of bone metastases, and primary Gleason grade. 

b Hazard ratio based on the unadjusted Cox Model. 
c  p-value based on a log-rank test. 
Abbreviations:  CI = confidence interval. 
 
Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Provenge in all subsets of the paediatric population in the treatment of prostate cancer (see section 4.2 
for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Provenge is an autologous cellular therapy.  The nature of Provenge is such that conventional studies 
on pharmacokinetics, absorption, distribution, metabolism, and elimination are not applicable. 
 
5.3 Preclinical safety data 
 
Conventional toxicology, carcinogenicity, mutagenicity, and reproductive toxicity studies have not 
been performed. 
 
 
6. QUALITY PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Sodium lactate 
Potassium chloride 
Calcium chloride 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other 
medicinal products. 
 
6.3 Shelf life 
 
In the insulated container 
18 hours. 
 
After removal from the insulated container 
The medicinal product should be used immediately.  If not used immediately, in-use storage times and 
conditions should not exceed 3 hours at room temperature (25°C). 

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6.4 Special precautions for storage 
 
Store the bag in the insulated container to maintain the correct storage temperature (2°C–8°C) until 
infusion.   
Do not refrigerate or freeze the container.   
 
6.5 Nature and contents of container and special equipment for use, administration or 
implantation 
 
250 mL dispersion in a bag (breathable polyolefin tri-laminate with 3 sample ports (2 spike ports and 
1 port with sealed tubing)). 
 
6.6 Special precautions for disposal and other handling 
 
Provenge is intended solely for autologous use.  The identity of the patient must be matched with the 
essential unique patient information on the infusion bag and the Final Product Disposition 
Notification form prior to infusion.   
 
Provenge is not  tested for transmissible infectious agents.  Patient leukapheresis material is tested for 
transmissible infectious agents in line with applicable member state requirements.  However, as it is 
an autologous product, a positive test does not preclude the manufacture of the product.  Therefore 
patient leukapheresis material and Provenge may carry the risk of transmitting infectious diseases to 
healthcare professionals handling the product.  Accordingly, healthcare professionals should employ 
appropriate precautions when handling leukapheresis material or Provenge (see section 4.4). 
 
Handling instructions 
 
Before handling or administering Provenge 

•  Provenge is shipped directly to the medical facility where the infusion will be administered.  
The infusion bag is placed inside an insulated polyurethane container and packed in a 
shipping box.  The insulated container and the gel packs within are designed to maintain the 
appropriate transportation and storage temperature of Provenge until infusion.  Do not 
irradiate. 

•  The outer shipping box should be opened to verify the product and patient-specific labels 
located on the top of the insulated container.  Do not remove this insulated container from 
the shipping box, or open the lid of the insulated container, until the patient is ready for 
infusion. 

 
Preparing the infusion 
Take care to ensure aseptic handling when preparing the infusion.  
 

What to check prior to infusion 
•  It must be ensured that the Final Product Disposition Notification form containing the 

patient identifiers, expiration date and time, and the disposition status (approved for infusion 
or rejected), has been received from the marketing authorisation holder. 

•  It must be ensured that the patient’s identity matches the essential unique patient 
information on the Provenge bag and on the Final Product Disposition form. 

•  Once the patient is prepared for infusion and the APPROVED Final Product Disposition 
Notification form has been received, the Provenge bag should be removed from the 
insulated container and inspected for leaks, external damage, foreign particulate matter, or 
clumps/clots. 

•  Contents of the bag will be slightly cloudy, with a cream to pink colour.  Gently mix and 
re-suspend the contents of the bag, inspecting for clumps and clots.  Small clumps of 
cellular material should disperse with gentle manual mixing. 

•  If the Provenge bag leaks, is damaged, or if particles or clumps remain in the bag after 
gentle manual mixing, the product must not be used. 

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Administration 

•  Infusion must begin prior to the expiration date and time indicated on the Final Product 
Disposition Notification form and bag label.  Do not initiate infusion of expired Provenge. 

•  Only one of the 2 spike ports should be used and should not be opened prior to 
administration in order to avoid contamination. 

•  Provenge is infused over a period of approximately 60 minutes through a large bore needle 
appropriate for transfusion of red blood cells.  This peripheral delivery system is commonly 
used in clinical practice for the transfusion of blood components.  Do not use a cell filter 
for infusion.  The entire volume of the infusion bag should be used. 

•  If the infusion of Provenge must be interrupted, it should not be resumed if the infusion bag 
has been held at room temperature (25°C) for more than 3 hours.   

 
After the infusion 

•  Upon completion of the infusion, the patient specific label on the infusion bag should be 
removed and adhered to the patient file. 

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

 
 
7. MARKETING AUTHORISATION HOLDER 
 
Dendreon UK Limited 
41 Chalton Street 
London, NW1 1JD 
United Kingdom 
 
Tel:  (0)20 7554 2222 
Fax:  (0)20 7554 2201 
dendreonuk@dendreon.com 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/867/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
 
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. 

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


16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE  

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
 
 
 

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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance  
 
PharmaCell 
Oxfordlaan 70 
NL-6229 EV, Maastricht 
The Netherlands 
 
Name and address of the manufacturer responsible for batch release 
 
PharmaCell 
Oxfordlaan 70 
NL-6229 EV, Maastricht 
The Netherlands 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within six months following authorisation. Subsequently, the marketing authorisation holder shall 
submit periodic safety update reports for this product in accordance with the requirements set out in 
the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and 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 MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.  
 
An updated RMP should be submitted:  

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

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 
 
 

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• Additional risk minimisation measures  
 
Prior to launch of Provenge in each Member State, the Marketing Authorisation Holder (MAH) shall 
agree the content and format of the educational materials with the National Competent Authority.  
The MAH shall also agree with the National Competent Authority any requirements for prior audit of 
apheresis centres and training courses for healthcare professionals in the use of Provenge. 
 
The MAH shall ensure that all healthcare professionals who are expected to prescribe or use Provenge 
are provided with the following items: 
 

1. Summary of Product Characteristics (SmPC) 
2. Educational material for Healthcare professionals 
3. Provenge treatment checklists  
4. Apheresis catheter care sheets  
5. Educational materials for patients 
6. Patient Alert card to record the scheduled leukapheresis and infusion dates 

 
The educational material for healthcare professionals will include the following key elements: 
 

•  Training completion form as agreed with the national competent authority  
•  Selection of patients for treatment with Provenge 
•  Specific handling and administration requirements for Provenge 
•  Chain of identity requirements 
•  The need to provide patients with the educational material and explain the use of the patient 

alert card 
•  The existence of the EU Registry of patients treated for metastatic castrate resistant prostate 

cancer and how to enter patients in it. 
 

Educational material for patients and/or carers to explain: 
 

•  The leukapheresis process 
•  The Provenge treatment process 

 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due dates 
To establish and keep an observational EU-based 
registry of men with mCRPC to evaluate overall 
survival, the risk of ischemic stroke or myocardial 
infarction following treatment with Provenge and 
other identified and potential risks (observational 
study P13-1) 

Submission of study protocol with first 
PSUR 
Interim data submitted in each PSUR 
Final study report by 31 December 2018 

To provide data from the observational US-based 
registry (PROCEED, Study P10-3) 

Interim data submitted in each PSUR 
Final study report by 30 September 2016 

To submit the results from study P-11, a randomised, 
double-blind trial evaluating Provenge versus placebo 
in patients with non-metastatic prostate cancer who 
experience PSA elevation following radical 
prostatectomy 

Final study report by 31 December 2020 

To conduct study P12-1 to evaluate characteristics 
predictive of a positive imaging study for distant 
metastases in patients with castrate-resistant prostate 
cancer. The study should provide a summary of 
baseline patient characteristics including PSA and 

Submission of study protocol within 1 month 
of authorisation 
Update on study outcome annually 
Final study report by 31 December 2019 

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PSA doubling time, the number of patients who 
develop metastatic disease, subsequent therapies 
received after diagnosis of metastatic disease, and 
efficacy parameters following subsequent therapies, 
including PSA progression, PSA progression-free 
survival, time to next line therapy, and overall 
survival.  

 
 
 

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20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 

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A. LABELLING 
 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INSULATED POLYURETHANE CONTAINER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
PROVENGE 50 x 106 CD54+ cells/250 mL dispersion for infusion. 
 
Autologous peripheral blood mononuclear cells activated with PAP-GM-CSF (Sipuleucel-T). 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One bag contains autologous peripheral blood mononuclear cells activated with PAP-GM-SF 
(prostatic acid phosphatase-granulocyte macrophage-colony stimulating factor), including a minimum 
of 50 x 106 autologous CD54+ cells. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride 
Sodium lactate 
Potassium chloride 
Calcium chloride. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Dispersion for infusion. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Gently mix and re-suspend the contents of the bag. 
Read the package leaflet before use. 
For intravenous infusion 
 
 
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 
 
For autologous use only. 

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Do not remove the top insulated lid and do not open the insulated box until both of the following have 
occurred: 

• The disposition form verifying the product has been APPROVED has been provided 
• The patient has arrived at the site and is ready for infusion 

Do not initiate infusion if expired, after 3 hours at room temperature (25°C), or if particles/clumps are 
visible despite gentle manual mixing  
 
 
8. EXPIRY DATE 
 
Exp. Date {DD month YYYY}, Exp. Time {hh:mm}, Time Zone 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store the bag in the insulated container to maintain the correct storage temperature (2°C–8°C) until 
infusion. 
Do not refrigerate or freeze the container. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Dispose of in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Dendreon UK Ltd. 
41 Chalton Street 
London, NW1 1JD 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/867/001 
 
 
13. BATCH NUMBER, DONATION AND PRODUCT CODES 
 
Lot /COI {lot number/chain of identity} 
First Name, Middle Initial, Last Name {patient name} 
DOB {patient date of birth} 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 

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16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
 
 
 

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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
INFUSION BAG 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
PROVENGE 50 x 106 CD54+ cells/250 mL dispersion for infusion. 
 
Autologous peripheral blood mononuclear cells activated with PAP-GM-CSF (Sipuleucel-T). 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One bag contains autologous peripheral blood mononuclear cells activated with PAP-GM-CSF 
(prostatic acid phosphatase-granulocyte macrophage-colony stimulating factor), including a minimum 
of 50 x 106 autologous CD54+ cells 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride 
Sodium lactate 
Potassium chloride 
Calcium chloride. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Dispersion for infusion. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Gently mix and re-suspend the contents of the bag. 
Read the package leaflet before use. 
For intravenous infusion. 
 
 
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 
 
For autologous use only. 
Do not initiate infusion if expired, after 3 hours at room temperature (25°C), or if particles/clumps are 
visible despite gentle manual mixing. 
 
 
8. EXPIRY DATE 

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Exp. Date {DD month YYYY}, Exp. Time {hh:mm}, Time Zone 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store the bag in the insulated container to maintain the correct storage temperature (2°C–8°C) until 
infusion. 
Do not refrigerate or freeze the container. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Dispose of in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Dendreon UK Ltd. 
41 Chalton Street 
London, NW1 1JD 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER, DONATION AND PRODUCT CODES 
 
Lot/COI {lot number/chain of identity} 
First Name, Middle Initial, Last Name {patient name} 
DOB {patient date of birth} 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 

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B. PACKAGE LEAFLET 
 
 

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Package leaflet: Information for the patient 
 

Provenge 50 x 106 CD54+ cells/250 mL dispersion for infusion 
 

Autologous peripheral blood mononuclear cells activated with PAP-GM-CSF (Sipuleucel-T) 
 
▼ This medicine is subject to additional monitoring.  This will allow quick identification of new 
safety information.  You can help by reporting any side effects you may get.  See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you are given 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. 
- 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 Provenge is and what it is used for  
2. What you need to know before you are given Provenge 
3. How Provenge is given to you 
4. Possible side effects of Provenge 
5. How to store Provenge 
6. Contents of the pack and other information 
 
 
1. What Provenge is and what it is used for 
 
Provenge is used to control your prostate cancer.  It consists of immune cells (part of your body’s 
natural defense system) taken from your own blood (also called autologous immune cells).  These 
immune cells are then mixed with an antigen (a protein, which is able to stimulate your immune 
system) at a specific manufacturing facility.  When given as a drip (infusion) into your vein, Provenge 
works by teaching your immune cells to recognise and attack prostate cancer cells.  
 
Provenge is used as treatment for prostate cancer that has spread outside of the prostate but not to the 
liver, lung or brain, and no longer responds to medicines that lower the levels of the male hormone 
testosterone in patients who are not considered appropriate for treatment with chemotherapy.   
 
 
2. What you need to know before you are given Provenge  
 
Do not use Provenge 
If you are allergic (hypersensitive) to the active substances or any of the ingredients of this medicine 
(listed in section 6). 
 
Warnings and precautions 
Tell your doctor if you have any of the conditions listed below as you will have to be closely 
monitored during and after your infusion: 

•  An infection which affects your whole body (e.g., sepsis, seen as high temperature, 
increased heart rate or breathing) 

•  A history of stroke 
•  A heart condition including blocked blood vessels which could lead to a heart attack 
•  You are immunocompromised (your immune system’s ability to fight infections is reduced) 

or taking any immunosuppressant medicines (such as those used to treat or prevent organ 

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rejection and certain medicines used to treat rheumatoid arthritis, multiple sclerosis, Crohn’s 
disease, and ulcerative colitis) 

•  You are on a controlled sodium/potassium diet or you have reduced kidney function. 
 
Your doctor may decide that Provenge is not suitable for you due to one or more of these conditions. 
 
On the first day of the infusion, Provenge may cause infusion-related reactions such as: 

•  high temperature, chills, breathing difficulties 
•  feeling or being sick (nausea and vomiting) 
•  tiredness 
•  increased heart rate, high blood pressure, low blood pressure, fainting. 

 
To reduce these reactions your doctor may suggest that you take paracetamol and an antihistamine 
medicine about 30 minutes before your treatment with Provenge. 
 
If you have severe reactions during the infusion your doctor may either slow down the infusion or 
stop it.  You may also be given other medicines if needed.  Tell the doctor or nurse if you do not feel 
well during the infusion. 
 
Provenge is manufactured specifically for you using your own blood and must not be used in anyone 
else. 
 
Provenge undergoes several tests before use to show that it is sterile.  As it has to be given to you 
shortly after it has been manufactured, the final sterility results may not always be available before 
you are given your infusion of Provenge.  If the final results show that your medicine was not sterile, 
your doctor will be notified and you will be monitored closely for any signs of infection and will be 
treated accordingly. 
 
When Provenge cannot be given 
In some cases, you may be unable to receive a scheduled infusion of Provenge.  This may be due to a 
number of reasons, for example, if there is: 

•  a problem at the time your blood cells are taken for the manufacturing of Provenge. 
•  not enough of the right type of cells to manufacture the medicine. 
•  contamination of the product. 
•  a delay in Provenge reaching the clinic where you will be given your treatment. 
•  damage to the product when it arrives at the clinic; for example, the bag containing the 

product has leaked, or the cells have formed clumps that cannot be dispersed. 
 

In such cases, if your doctor decides that the course of treatment should be continued, he or she will 
arrange for another collection of your blood cells (leukapheresis) and the manufacturing process will 
be repeated (see information on leukapheresis in section 3).  In clinical studies, about one quarter of 
the patients required more than 3 leukapheresis procedures in order to receive 3 infusions of 
Provenge. 
 
Children and adolescents 
Provenge is for use in adult men only.  It should not be given to children or adolescents under the age 
of 18 years. 
 
Other medicines and Provenge 
Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines.  
This includes medicines obtained without a prescription and herbal medicines. 
 
Provenge is designed to stimulate your immune system, and therefore it may not be appropriate to be 
treated with Provenge if you are currently taking other treatments that could affect the ability of your 
immune system to respond to Provenge e.g., immunosuppressant medicines such as those used to treat 

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or prevent organ rejection and certain medicines used to treat rheumatoid arthritis, multiple sclerosis, 
Crohn’s disease, and ulcerative colitis.  
 
If you need a vaccination whilst receiving Provenge, you should first discuss this with your doctor.  
 
Pregnancy, breast-feeding and fertility 
Provenge is for use in men only.  The effects of Provenge on male fertility are not known at this time. 
 
Driving and using machines 
You may feel tired, faint, or dizzy or have a headache or chills after receiving your Provenge infusion.  
If this happens, do not drive or use any tools or machines until you feel better. 
 
Provenge contains sodium and potassium 
This medicine contains: 

•  approximately 800 mg sodium per infusion.  To be taken into consideration by patients with 
heart conditions or those on a controlled sodium diet. 

•  approximately 45 mg potassium per infusion.  To be taken into consideration by patients 
with reduced kidney function or on a controlled potassium diet. 

 
 
3. How Provenge is given to you 
 
Provenge can only be administered by a doctor or nurse who has been trained in using this medicine.  
Practical information for handling and administration of Provenge for the doctor or nurse can be 
found at the end of this leaflet. 
 
As Provenge is made from your own blood cells, your cells will be collected approximately 3 days 
before each scheduled infusion.  This procedure will take 3 to 4 hours (see section “Steps before 
Provenge treatment” below).  Your blood will be tested before it is collected (see section “Tests” 
below). 
 
Steps before Provenge treatment 

1. The first step in your Provenge treatment is to collect your blood cells in order to 
manufacture your personal infusion of Provenge.  This involves a procedure called 
leukapheresis, which consists of extracting white blood cells from your blood, usually from 
the veins in your arms.  A machine is used to take blood from one arm, extract the white 
blood cells and return the rest of the blood to you, usually in the other arm.  This procedure 
usually takes 3-4 hours.  You will have to have this procedure on at least 3 occasions 
approximately 3 days before each of your 3 Provenge infusion treatments. 

2. The second step is to send your collected cells to a special manufacturing centre where they 
are mixed with an antigen to make them ready for your infusion. 

 
Tests 
Before, or on the day, your blood cells are collected, a blood sample will be taken from you for a 
complete blood count (CBC) test.  This test will determine whether you have enough blood cells to 
allow the leukapheresis procedure to be safely carried out.  In addition, your blood will be tested for 
specific viruses (for example HIV-1, HIV-2, hepatitis B and hepatitis C).  This testing is a legal 
requirement and is to ensure that your blood cells can be safely handled by the healthcare 
professionals involved in your treatment.  You may need to have further CBC tests during your 
treatment in line with local or country-wide practices.  If you need more information on the testing of 
your blood please ask your doctor or nurse. 
 
How Provenge is given and duration of treatment 
Your doctor may suggest you take paracetamol and an antihistamine medicine about 30 minutes 
before your infusion to reduce the possible reactions to Provenge. 
 
Your Provenge treatment will be given by a drip (infusion) into one of your veins (intravenous use). 

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You will receive a total of 3 infusions of Provenge at approximately 2 week intervals. 
 
The first infusion of Provenge will be given approximately 3 days after the cell collection and will last 
approximately 1 hour (see also section 2 “Warnings and precautions”).  You will be monitored before 
and during the infusion.  If your infusion of Provenge has to be interrupted for any reason, your doctor 
will not be able to restart the infusion if the medicine has been at room temperature for more than 3 
hours. 
 
Once the infusion is complete you will be observed and monitored for at least 30–60 minutes, after 
which, you may go home. 
 
Your treatment will involve at least 6 visits to the cell collection site and/or clinic.  You may need one 
or more additional visits in order to have your blood tested before your leukapheresis procedure 
(depending on the usual pratice in the clinic where you are having your treatment), or your blood may 
be tested during your leukapheresis visits: 
Visit 1 – Blood cell collection (leukapheresis)  
Visit 2 – Provenge infusion 
Visit 3 – Blood cell collection (leukapheresis) 
Visit 4 – Provenge infusion 
Visit 5 – Blood cell collection (leukapheresis)  
Visit 6 – Provenge infusion 
 
Your doctor will give you a schedule for your cell collection and infusion appointments.  This will be 
added to your Patient Alert Card that you should bring to each appointment. 
 
Missed treatment 
It is very important that you arrive on time for your appointments.  If you miss an appointment and 
you cannot be given your Provenge infusion, it will no longer be usable.  Your doctor will work with 
you to schedule new appointments for cell collection and infusion. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects of Provenge 
 
Like all medicines, Provenge can cause side effects, although not everybody gets them. 
 
The most severe side effects are described below:  
 
Infusion-related side effects 
During or within 24 hours of the infusion, you may develop very common symptoms such as chills, 
fever, tiredness, feeling weak, headache, feeling sick (nausea), being sick (vomiting), muscle ache, 
and dizziness,.  Common symptoms include a fainting episode, bluish discoloration of the skin, lips 
and/or nail beds due to low levels of oxygen in the blood, wheezing, high or low blood pressure and 
difficulty breathing. 
 
Tell your doctor or nurse if you develop any of these symptoms, as the infusion may need to be 
slowed down or stopped.  You may also be given other medicines if needed. 
 
If you experience any of the following side effects several days after the infusion, contact a doctor 
immediately: 

•  shortness of breath, wheezing, dizziness, rash, or fever. 
 

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Infection 
Tell your doctor after your Provenge treament if you get any symptoms of an infection, for example, a 
fever or high temperature above 38°C, chills, a fast heartbeat, fast breathing, dizziness on standing up, 
confusion or feeling/being sick. 
 
Stroke 
Contact a doctor immediately if you experience sudden vision loss in one eye, difficulty speaking, 
numbness and/or weakness affecting one side of the body as any of these may be signs of a stroke. 
 
Heart attack 
Contact a doctor immediately if you experience chest pain, pain in the left arm and/or shortness of 
breath as any of these may be signs of a heart attack. 
 
Other side effects with Provenge include: 
 
Very common side effects (may affect more than 1 in 10 patients): 

-  pain 
-  joint ache or pain (arthralgia) 
-  tingling, numbness or abnormal sensation (paraesthesia) around lips, in mouth, or in the 

arms and/or legs during the leukapheresis procedure 
-  muscle spasms, chest pain, and low blood pressure during the leukapheresis procedure 

(caused by a medicine (citrate) used to prevent blood clotting). 
-  anaemia (decrease in number of red blood cells) due tothe leukapheresis procedure 

 
Common side effects (may affect up to 1 in 10 patients): 

-  flu-like illness 
-  abdominal pain 
-  tremor 
-  rash, including raised itchy rash (urticaria), or itching 
-  excessive sweating 
-  bacteria in the blood (bacteraemia) 
-  reduced sense of touch or sensation (hypoaesthesia) 
-  collapse of one of the bones in the spine (spinal cord compression) 
-  irregular or rapid heart rate 
-  stroke 
-  temporary symptoms of a stroke 
-  blood in the urine 
-  chest discomfort 
-  decrease of platelets in the blood due to the leukapheresis procedure 
 

Uncommon side effects (may affect up to 1 in 100 patients 
-  severe infection in the blood(sepsis) 
-  severe infection in the blood from a contaminated catheter (catheter sepsis) 
-  infection from a contaminated catheter (catheter-related infection) 
-  skin infection of the area where the infusion drip was inserted 
-  heart attack 
-  symptoms of a heart attack 
-  increase in a type of white blood cells called eosinophils 
-  infusion site reaction (a reaction of the skin area where the infusion drip was inserted) 
 

Reporting 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 any 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. 
 
 

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5. How to store Provenge 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiration date and time, which is stated on the insulated container 
and the infusion bag. 
 
Store the bag in the insulated container to maintain the correct storage temperature (2°C–8°C) until 
infusion.   
Do not refrigerate or freeze the container. 
 
After removal from the insulated container, the medicinal product should be used immediately.  If not 
used immediately, in-use storage times and conditions should not exceed 3 hours at room temperature 
(25°C). 
 
Do not throw away any medicines via wastewater.  Since this medicine will be given by a qualified 
doctor or nurse, they are responsible for the correct disposal of the product.  These measures will help 
to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Provenge contains  
The active substance is autologous peripheral blood mononuclear cells activated with PAP-GM-CSF 
(prostatic acid phosphatase-granulocyte macrophage-colony stimulating factor), including a minimum 
of 50 x 106 autologous CD54+ cells. 
The other ingredients are: sodium chloride, sodium lactate, potassium chloride, and calcium 
chloride. 
 
What Provenge looks like and contents of the pack 
Provenge is a slightly cloudy dispersion of cream-to-pink colour and is supplied in a plastic bag with 
3 sample ports. 
 
Each Provenge bag contains one individual infusion treatment and the container will only be opened 
when you are ready to receive your treatment.  Your doctor or nurse will confirm that your details 
(name and date of birth) correspond to the details provided with the Provenge container. 
 
Marketing Authorisation Holder  
 
Dendreon UK Limited 
41 Chalton Street 
London, NW1 1JD 
United Kingdom 
Tel:  (0)20 7554 2222 
Fax:  (0)20 7554 2201 
dendreonuk@dendreon.com 
 
Manufacturer 
 
PharmaCell 
Oxfordlaan 70  
NL-6229 EV, Maastricht 
The Netherlands 
 
This leaflet was last revised in  
 
 

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Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
This leaflet is available in all EU/EEA languages on the European Medicines Agency website.  
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for medical or healthcare professionals only: 
 
Practical information for medical or healthcare professionals on handling and administration of 
Provenge dispersion for infusion 
 
Provenge must be administered under the supervision of a physician experienced in the medical 
treatment of prostate cancer and in an environment where availability of resuscitation equipment must 
be ensured.   
 
It is important that you read the entire content of this procedure prior to administering Provenge. 
 
Dose and course of treatment 
One bag containins autologous peripheral blood mononuclear cells activated with PAP-GM-CSF, 
including a minimum of 50 x 106 autologous CD54+ cells. 
 
The recommended course of treatment is 3 doses at approximately 2 week intervals.  Each dose of 
Provenge is preceded by a standard leukepheresis procedure approximately 3 days prior to the 
scheduled infusion date.  Prior to the first leukapheresis proceedure, a complete blood count (CBC) 
test should be performed.  Additional CBC tests may be performed in accordance with local 
requirements. 
 
Handling instructions 
 
Before handling or administering Provenge 

•  Provenge is shipped directly to the medical facility where the infusion will be administered.  
The infusion bag is placed inside an insulated polyurethane container and packed in a 
shipping box.  The insulated container and the gel packs within are designed to maintain the 
appropriate transportation and storage temperature of Provenge until infusion.  Do not 
irradiate. 

•  The outer shipping box should be opened to verify the product and patient-specific labels 
located on the top of the insulated container.  Do not remove this insulated container from 
the shipping box, or open the lid of the insulated container, until the patient is ready for 
infusion. 

•  Provenge is prepared from human blood of the specific patient and is not tested for 
transmissible infectious agents.  Patient leukapheresis material is tested for transmissible 
infectious agents in line with applicable local requirements.  However, as Provenge is an 
autologous product, a positive test does not preclude the manufacture of the product.  
Therefore, Provenge may carry the risk of transmitting infectious viruses (HIV 1 and 2, 
hepatitis B and C) to health care professionals handling the product.  Accordingly, 
healthcare professionals should employ appropriate precautions when handling the 
leukapheresis material or Provenge. 
 

Preparing the infusion 
•  Take care to ensure aseptic handling when preparing the infusion. 

 

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What to check prior to infusion 
•  It must be ensured that the Final Product Disposition Notification form containing the 

patient identifiers, expiration date and time, and the disposition status (approved for infusion 
or rejected), has been received from the market authorisation holder. 

•  It must be ensured that the patient’s identity matches the essential unique patient 
information on the Provenge bag and the Final Product Disposition Notification form. 

•  Once the patient is prepared for infusion and the APPROVED Final Product Disposition 
Notification form has been received, the Provenge bag should be removed from the 
insulated container and inspected for leaks, external damage, foreign particulate matter, or 
clumps/clots. 

•  Contents of the bag will be slightly cloudy, with a cream to pink colour.  Gently mix and re-
suspend the contents of the bag, inspecting for clumps and clots.  Small clumps of cellular 
material should disperse with gentle manual mixing. 

•  If the Provenge bag leaks, is damaged, or if particles or clumps remain in the bag after 
gentle manual mixing, the product must not be used. 

 
Administration 

•  Infusion must begin prior to the expiration date and time indicated on the Final Product 
Disposition Notification form and bag label.  Do not initiate infusion of expired Provenge.  

•  Only one of the 2 spike ports should be used and should not be opened prior to 
administration in order to avoid contamination. 

•  Provenge is infused over a period of approximately 60 minutes through a large bore needle 
appropriate for transfusion of red blood cells.  This peripheral delivery system is commonly 
used in clinical practice for the transfusion of blood components.  Do not use a cell filter 
for infusion.  The entire volume of the infusion bag should be used. 

•  If the infusion of Provenge must be interrupted, it should not be resumed if the infusion bag 
has been held at room temperature (25°C) for more than 3 hours. 

 
After the infusion 

•  Upon completion of the infusion, the patient specific label on the infusion bag should be 
removed and adhered to the patient file. 

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

 
IMPORTANT - Do not infuse Provenge if 
• You have not received the Final Product Disposition Notification form. 
• The Final Product Disposition Notification form is marked REJECTED. 
• The expiration date and time have passed. 
• The essential unique patient information on the infusion bag does not match that of the 

scheduled patient. 
• The product integrity has been breached in any way (the infusion bag is damaged, leaks, or 

particles/clumps remain in the bag after gentle manual mixing). 
 
Shelf life and special precautions for storage 
Provenge has a shelf life of 18 hours in the insulated container that is shipped to the medical facility 
where the infusion will be administered.  Store the bag in the insulated container to maintain the 
correct storage temperature (2°C–8°C) until infusion.  Do not refrigerate or freeze the container. 
 
After removal from the insulated container, Provenge should be used immediately.  If not used 
immediately, in use storage times and conditions should not exceed 3 hours at room temperature 
(25°C). 
 
Disposal 
Any unused product or waste material should be disposed of in accordance with local requirements. 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET