Sipuleucel-T
FDA Drug Information • Also known as: Provenge
- Brand Names
- Provenge
- Drug Class
- Autologous Cellular Immunotherapy [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION
- Product Type
- CELLULAR THERAPY
Description
11 DESCRIPTION PROVENGE (sipuleucel-T) is an autologous cellular immunotherapy available as a suspension for intravenous infusion. PROVENGE consists of autologous peripheral blood mononuclear cells, including antigen presenting cells (APCs), that have been activated during a defined culture period with a recombinant human protein, PAP-GM-CSF, consisting of prostatic acid phosphatase (PAP), an antigen expressed in prostate cancer tissue, linked to granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune cell activator. Each dose of PROVENGE contains a minimum of 50 million autologous CD54 + cells activated with PAP-GM-CSF, suspended in 250 mL of Lactated Ringer's Injection, USP. The active components of PROVENGE are autologous APCs and PAP-GM-CSF. During culture, the recombinant antigen can bind to and be processed by APCs into smaller protein fragments. The recombinant antigen is designed to target APCs, and may help direct the immune response to PAP. Minimal residual levels of the intact PAP-GM-CSF are detectable in the final PROVENGE product. The patient's peripheral blood mononuclear cells are obtained via a standard leukapheresis procedure approximately 3 days prior to the infusion date. Due to the autologous nature of PROVENGE, it is important that the patient and physician adhere to the personalized leukapheresis and infusion schedules. The cellular composition of PROVENGE is dependent on the composition of cells obtained from the patient's leukapheresis. In addition to APCs, the final product contains T cells, B cells, natural killer (NK) cells, and other cells. The number of cells present and the cellular composition of each PROVENGE dose will vary. The potency of PROVENGE is in part determined by measuring the increased expression of the CD54 molecule, also known as ICAM-1, on the surface of APCs after culture with PAP-GM-CSF. CD54 is a cell surface molecule that plays a role in the immunologic interactions between APCs and T cells, and is...
What Is Sipuleucel-T Used For?
1 INDICATIONS AND USAGE PROVENGE ® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. For autologous use only. For intravenous use only. Administer 3 doses at approximately 2-week intervals. ( 2.1 ) Premedicate patients with oral acetaminophen and an antihistamine such as diphenhydramine. ( 2.2 ) Before infusion, confirm that the patient's identity matches the patient identifiers on the infusion bag. ( 2.2 ) Infuse PROVENGE intravenously over a period of approximately 60 minutes. Do Not Use a Cell Filter. ( 2.2 ) Interrupt or slow infusion for acute infusion reactions, depending on the severity of the reaction. ( 2.2 ) 2.1 Dose Each dose of PROVENGE contains a minimum of 50 million autologous CD54 + cells activated with PAP-GM-CSF [ see Description ( 11 ) ]. The recommended course of therapy for PROVENGE is 3 complete doses, given at approximately 2-week intervals. In controlled clinical trials, the median dosing interval between infusions was 2 weeks (range 1 to 15 weeks); the maximum dosing interval has not been established. 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 prior to continuing a course of treatment. Advise patients of this possibility prior to initiating treatment. 2.2 Administration Do not use PROVENGE until confirmation of product release is received from Dendreon. Dendreon will send the Final Product Disposition Notification form containing the patient identifiers, expiration date and time, and the disposition status (approved for infusion or rejected), to the infusion site. Infusion must begin prior to the expiration date and time indicated on the Final Product Disposition Notification form and Product Label. Do not use expired PROVENGE. Keep the sealed, patient-specific PROVENGE infusion bag within the insulated polyurethane container inside the outer cardboard shipping box until the time of administration. To minimize potential acute infusion reactions, premedicate the patients orally with acetaminophen and an antihistamine, such as diphenhydramine, approximately 30 minutes prior to administration of PROVENGE. Administration steps: Remove the infusion bag from the insulated polyurethane container and inspect the bag for signs of leakage or external damage. Contents of the bag will be clear to opaque, with a white to red color, including shades of off-white, cream, light yellow and orange. Remove the infusion bag from the insulated polyurethane container and inspect the bag for signs of leakage or external damage. Contents of the bag will be clear to opaque, with a white to red color, including shades of off-white, cream, light yellow and orange. Gently mix and resuspend the contents of the bag, inspecting for clumps and clots. Small clumps of cellular material should disperse with gentle manual mixing. Do not administer if the bag leaks during handling, is damaged, or if clumps remain in the bag. Match the patient's...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reactions reported in clinical trials (≥ 15% of patients receiving PROVENGE) were chills, fatigue, fever, back pain, nausea, joint ache, and headache. The most common adverse reactions (incidence ≥ 15%) are chills, fatigue, fever, back pain, nausea, joint ache, and headache. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Dendreon Pharmaceuticals LLC at 1-877-336-3736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety evaluation of PROVENGE is based on 601 prostate cancer patients in the PROVENGE group who underwent at least 1 leukapheresis procedure in four randomized, controlled clinical trials. The control group (n = 303) received non-activated autologous peripheral blood mononuclear cells. Patients received 3 infusions of PROVENGE or control every other week over a period of 4 weeks. Almost all (98.3%) patients in the PROVENGE group and 96% in the control group reported an adverse event. In 67.4% of patients in the PROVENGE group, these adverse events were mild or moderate in severity. Severe (Grade 3) and life-threatening (Grade 4) adverse events were reported in 23.6% and 4% of patients in the PROVENGE group compared with 25.1% and 3.3% of patients in the control group. Fatal (Grade 5) adverse events were reported in 3.3% of patients in the PROVENGE group compared with 3.6% of patients in the control group. The most common (≥ 2%) Grade 3-5 adverse events reported in the PROVENGE group were back pain and chills. Serious adverse events were reported in 24% of patients in the PROVENGE group and 25.1% of patients in the control group. Serious adverse events in the PROVENGE group included acute infusion reactions [ see Warnings and Precautions ( 5.1 ) ], cerebrovascular events [ see Warnings and Precautions ( 5.3 ) ], and single case reports of eosinophilia, rhabdomyolysis, myasthenia gravis, myositis, and tumor flare. PROVENGE was discontinued in 1.5% of patients in Study 1 due to adverse events. Some patients who required central venous catheters for treatment with PROVENGE developed infections, including sepsis. A small number of these patients discontinued treatment as a result. Monitoring for infectious sequelae in patients with central venous catheters is recommended. Each dose of PROVENGE requires a standard leukapheresis procedure approximately 3 days prior to the infusion. Adverse events that were reported ≤ 1 day following a leukapheresis procedure in ≥ 5% of patients in controlled clinical trials included citrate toxicity (14.2%), oral paresthesia (12.6%), paresthesia (11.4%), and fatigue (8.3%). Table 1 provides the frequency and severity of adverse events reported in ≥ 5% of patients in the PROVENGE group of randomized, controlled trials of men with prostate cancer. The population included 485 patients with metastatic castrate-resistant prostate cancer and 116 patients with non-metastatic androgen-dependent prostate cancer who were scheduled to receive 3 infusions of PROVENGE at approximately 2-week intervals. The population was age 40 to 91 years (median 70 years), and 90.6% of patients were Caucasian. Table 1 Incidence of Adverse Events Occurring in ≥ 5% of Patients Randomized to PROVENGE PROVENGE (N = 601) Control * (N = 303) All Grades n (%) Grade 3-5 n (%) All Grades n (%) Grade 3-5 n (%) Any Adverse Event 591 (98.3) 186 (30.9) 291 (96.0) 97 (32.0) * Control group received non-activated autologous peripheral blood mononuclear cells. Chills 319 (53.1) 13 (2.2) 33 (10.9) 0 (0.0) Fatigue 247 (41.1) 6 (1.0) 105 (34.7) 4 (1.3) Fever 188 (31.3) 6 (1.0) 29 (9.6) 3 (1.0) Back pain 178 (29.6) 18 (3.0) 87 (28.7) 9 (3.0) Nausea 129 (21.5) 3 (0.5) 45 (14.9) 0 (0.0) Joint...
Drug Interactions
7 DRUG INTERACTIONS
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Overdosage
10 OVERDOSAGE 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 collected from the leukapheresis. There are no known instances of overdosage from either a single infusion or a full course of therapy with PROVENGE.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING PROVENGE is a 250 mL suspension containing a minimum of 50 million autologous CD54 + cells activated with PAP-GM-CSF in Lactated Ringer's Injection, USP. It is supplied in a sealed infusion bag, labeled for the specific recipient. NDC 30237-8900-6: One bag individually packed in a carton. PROVENGE is shipped directly to the infusing provider in a cardboard shipping box with a special insulated polyurethane container inside. The insulated container and gel packs within the container are designed to maintain the appropriate transportation and storage temperature of PROVENGE until infusion. Upon receipt, open the outer cardboard shipping box to verify the product and patient-specific labels located on the top of the insulated container. Do not remove the insulated container from the shipping box, or open the lid of the insulated container, until the patient is ready for infusion.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.