Source: European Medicines Agency (EU) Revision Year: 2015 Publisher: Dendreon UK Limited, 41 Chalton Street, London, NW1 1JD, United Kingdom Tel: (0)20 7554 2222 Fax: (0)20 7554 2201 dendreonuk@dendreon.com
Provenge is indicated for treatment of asymptomatic or minimally symptomatic metastatic (nonvisceral) castrate resistant prostate cancer in male adults in whom chemotherapy is not yet clinically indicated.
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.
One dose of Provenge contains a minimum of 50 × 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.
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).
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.
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).
No dose adjustment is required in the elderly population.
Provenge has not been investigated in patients with hepatic impairment. No specific dose recommendation can be provided in these patients.
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).
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.
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.
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.
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 from the leukapheresis. There are no known instances of overdose from either a single infusion or a full course of therapy with Provenge.
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).
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.
250 mL dispersion in a bag (breathable polyolefin tri-laminate with 3 sample ports (2 spike ports and 1 port with sealed tubing)).
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).
Take care to ensure aseptic handling when preparing the infusion.
What to check prior to infusion:
Administration:
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.
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