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.
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 Provenge is and what it is used for
What you need to know before you are given Provenge
How Provenge is given to you
Possible side effects of Provenge
How to store Provenge
Medicinal product no longer authorised
Contents of the pack and other information
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.
If you are allergic (hypersensitive) to the active substances or any of the ingredients of this medicine
(listed in section 6).
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
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.
Medicinal product no longer authorised
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.
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.
Provenge is for use in adult men only. It should not be given to children or adolescents under the age
of 18 years.
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
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.
Provenge is for use in men only. The effects of Provenge on male fertility are not known at this time.
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.
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.
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.
Medicinal product no longer authorised
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).
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.
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.
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.
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).
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.
Medicinal product no longer authorised
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.
Like all medicines, Provenge can cause side effects, although not everybody gets them. The most severe side effects are described below:
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.
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.
numbness and/or weakness affecting one side of the body as any of these may be signs of a stroke.
breath as any of these may be signs of a heart attack.
Other side effects with Provenge include:
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
flu-like illness
abdominal pain
Medicinal product no longer authorised
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
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)
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.
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.
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.
Medicinal product no longer authorised
The other ingredients are: sodium chloride, sodium lactate, potassium chloride, and calcium chloride.
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.
Dendreon UK Limited 41 Chalton Street London, NW1 1JD United Kingdom
Tel: (0)20 7554 2222
Fax: (0)20 7554 2201
Manufacturer
PharmaCell Oxfordlaan 70
NL-6229 EV, Maastricht The Netherlands
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:
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.
One bag containins autologous peripheral blood mononuclear cells activated with PAP-GM-CSF, including a minimum of 50 x 106 autologous CD54+ cells.
Medicinal product no longer authorised
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.
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.
Medicinal product no longer authorised
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.
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).
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).
Any unused product or waste material should be disposed of in accordance with local requirements.