Sipuleucel-T Suspension for Intravenous Infusion (Provenge)
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Sipuleucel-T Suspension for Intravenous Infusion (Provenge)

PROVENGE®
(sipuleucel-T) Suspension for Intravenous Infusion

DRUG DESCRIPTION

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. 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 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 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. 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 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 considered a marker of immune cell activation.

What are the possible side effects of sipuleucel-T (Provenge)?

Some people receiving a sipuleucel-T injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, tired, or nauseated, or if you have fever, chills, joint pain, severe headache, blurred vision, buzzing in your ears, anxiety, confusion, vomiting, chest pain, fast or uneven heartbeats, wheezing, chest tightness, or trouble breathing. These side effects may occur during the injection or within the first 24 hours after your infusion.

Get emergency medical help if you have any of these signs of an...

Read All Potential Side Effects and See Pictures of Provenge »

What are the precautions when taking sipuleucel-t suspension for intravenous infusion (Provenge)?

Before using sipuleucel-T, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems, lung problems, history of stroke.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Sipuleucel-T is not recommended for use by...

Read All Potential Precautions of Provenge »

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

DOSAGE AND ADMINISTRATION

For Autologous Use Only.

For Intravenous Use Only. Do Not Use a Cell Filter.

Do Not Initiate Infusion of Expired Product.

Dose and Schedule

Each dose of PROVENGE contains a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF [see DESCRIPTION].

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 if the course of treatment is to be continued. Patients should be advised of this possibility prior to initiating treatment.

Premedication

To minimize potential acute infusion reactions such as chills and/or fever, it is recommended that patients be premedicated orally with acetaminophen and an antihistamine such as diphenhydramine approximately 30 minutes prior to administration of PROVENGE [see WARNINGS AND PRECAUTIONS].

Handling Precautions for Control of Infectious Disease

PROVENGE is not routinely tested for transmissible infectious diseases. Therefore, patient leukapheresis material and PROVENGE may carry the risk of transmitting infectious diseases to health care professionals handling the product. Employ universal precautions in handling leukapheresis material or PROVENGE. [See Storage and Handling]

Storage

The PROVENGE infusion bag must remain within the insulated polyurethane container until the time of administration. Do not remove the insulated polyurethane container from the outer cardboard shipping box. [See Storage and Handling]

Confirm Product Release Before Infusion

Do not infuse PROVENGE until confirmation of product release has been received from Dendreon. Dendreon will send a Cell Product Disposition Form containing the patient identifiers, expiration date and time, and the disposition status (approved for infusion or rejected), to the infusion site. [See Storage and Handling]

Preparation for Infusion

See Storage and Handling for full handling instructions.

Confirm Patient Identity

PROVENGE is intended solely for autologous use. Confirm the proper product has been received according to the label on the outside of the insulated polyurethane container. Prior to PROVENGE infusion, match the patient's identity with the patient identifiers on the Cell Product Disposition Form and the PROVENGE infusion bag.

Inspect the Infusion Bag

Remove the infusion bag from the insulated polyurethane container and inspect the bag for signs of leakage. Do not administer if the bag leaks.

Contents of the bag will be slightly cloudy, with a cream-to-pink color. 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. Do not administer if the bag leaks during handling or if clumps remain in the bag.

Administration

Infusion must begin prior to the expiration date and time indicated on the Cell Product Disposition Form and Product Label. Do not initiate infusion of expired PROVENGE.

Administer PROVENGE via intravenous infusion over a period of approximately 60 minutes. Do not use a cell filter. PROVENGE is supplied in a sealed, patient-specific infusion bag; the entire volume of the bag should be infused.

Observe the patient for at least 30 minutes following each infusion.

Administration Modification for Infusion Reactions

Acute infusion reactions such as chills, fatigue, fever, nausea, and joint ache were frequently observed in studies of PROVENGE. To mitigate such reactions, premedication, consisting of acetaminophen and an antihistamine such as diphenhydramine, was administered in clinical studies prior to infusion.

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 should be administered as needed. In controlled clinical trials, symptoms of acute infusion reactions were treated with acetaminophen, intravenous HI and/or H2 blockers, and low dose intravenous meperidine.

If the infusion of PROVENGE must be interrupted, the infusion should not be resumed if the PROVENGE infusion bag will be held at room temperature for more than 3 hours. [See Storage and Handling]

HOW SUPPLIED

Dosage Forms and Strengths

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 in a sealed, patient-specific infusion bag.

PROVENGE IS INTENDED SOLELY FOR AUTOLOGOUS USE. 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, and supplied in an infusion bag labeled for the specific recipient. The identity of the patient must be matched with the patient identifiers on the infusion bag and the Cell Product Disposition Form prior to infusion. PROVENGE is not routinely tested for transmissible infectious diseases. Therefore, patient leukapheresis material and PROVENGE may carry the risk of transmitting infectious diseases to health care professionals handling the product. Accordingly, health care professionals should employ universal precautions when handling leukapheresis material or PROVENGE.

Handling Instructions

  1. PROVENGE is shipped directly to the infusing provider.
  2. PROVENGE will arrive 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.
  3. Upon receipt, the outer cardboard 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.
  4. Do not infuse PROVENGE until confirmation of product release has been received from Dendreon. Dendreon will send a Cell Product Disposition Form containing the patient identifiers, expiration date and time, and the disposition status (approved for infusion or rejected), to the infusion site.
  5. Infusion must begin prior to the expiration date and time indicated on the Cell Product Disposition Form and Product Label. Do not initiate infusion of expired PROVENGE. Once the PROVENGE infusion bag is removed from the insulated container, it should remain at room temperature for no more than 3 hours. PROVENGE should not be returned to the shipping container.
  6. Once the patient is prepared for infusion and the Cell Product Disposition Form has been received, remove the PROVENGE infusion bag from the insulated container and inspect the bag for signs of leakage. Contents of the bag will be slightly cloudy, with a cream-to-pink color. 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. Do not administer if the bag leaks or if clumps remain in the bag.
  7. Prior to PROVENGE infusion, match the patient's identity with the patient identifiers on the Cell Product Disposition Form and the PROVENGE infusion bag.

Dendreon Corporation 3005 First Avenue Seattle, Washington 98121

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

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 was non-activated autologous peripheral blood mononuclear cells.

Almost all (98.3%) patients in the PROVENGE group and 96.0% in the control group reported an adverse event. The most common adverse events, reported in patients in the PROVENGE group at a rate ≥ 15%, were chills, fatigue, fever, back pain, nausea, joint ache, and headache. 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 4.0% 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 24.0% 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], cerebrovascular events, 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 PROVENCE

All Grades n (%) PROVENCE
(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)
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 ache 118 (19.6) 11(1.8) 62 (20.5) 5(1.7)
Headache 109 (18.1) 4(0.7) 20 (6.6) 0 (0.0)
Citrate toxicity 89 (14.8) 0 (0.0) 43 (14.2) 0 (0.0)
Paresthesia 85 (14.1) 1 (0.2) 43 (14.2) 0 (0.0)
Vomiting 80 (13.3) 2 (0.3) 23 (7.6) 0 (0.0)
Anemia 75 (12.5) 11(1.8) 34(11.2) 7 (2.3)
Constipation 74 (12.3) 1 (0.2) 40 (13.2) 3 (1.0)
Pain 74 (12.3) 7(1.2) 20 (6.6) 3 (1.0)
Paresthesia oral 74 (12.3) 0 (0.0) 43 (14.2) 0 (0.0)
Pain in extremity 73 (12.1) 5 (0.8) 40 (13.2) 1 (0.3)
Dizziness 71 (11.8) 2 (0.3) 34(11.2) 0 (0.0)
Muscle ache 71 (11.8) 3 (0.5) 17 (5.6) 0 (0.0)
Asthenia 65 (10.8) 6(1.0) 20 (6.6) 2 (0.7)
Diarrhea 60 (10.0) 1 (0.2) 34(11.2) 3 (1.0)
Influenza-like illness 58 (9.7) 0 (0.0) 11(3.6) 0 (0.0)
Musculoskeletal pain 54 (9.0) 3 (0.5) 31 (10.2) 3 (1.0)
Dyspnea 52 (8.7) 11(1.8) 14 (4.6) 3(1.0)
Edema peripheral 50 (8.3) 1 (0.2) 31 (10.2) 1 (0.3)
Hot flush 49 (8.2) 2 (0.3) 29 (9.6) 1 (0.3)
Hematuria 46 (7.7) 6(1.0) 18(5.9) 3 (1.0)
Muscle spasms 46 (7.7) 2 (0.3) 17 (5.6) 0 (0.0)
Hypertension 45 (7.5) 3 (0.5) 14 (4.6) 0 (0.0)
Anorexia 39 (6.5) 1 (0.2) 33 (10.9) 3 (1.0)
Bone pain 38 (6.3) 4 (0.7) 22 (7.3) 3 (1.0)
Upper respiratory tract infection 38 (6.3) 0 (0.0) 18 (5.9) 0 (0.0)
Insomnia 37 (6.2) 0 (0.0) 22 (7.3) 1 (0.3)
Musculoskeletal chest pain 36 (6.0) 2 (0.3) 23 (7.6) 2 (0.7)
Cough 35 (5.8) 0 (0.0) 17 (5.6) 0 (0.0)
Neck pain 34 (5.7) 3 (0.5) 14 (4.6) 2 (0.7)
Weight decreased 34 (5.7) 2 (0.3) 24 (7.9) 1 (0.3)
Urinary tract infection 33 (5.5) 1 (0.2) 18 (5.9) 2 (0.7)
Rash 31 (5.2) 0 (0.0) 10 (3.3) 0 (0.0)
Sweating 30 (5.0) 1 (0.2) 3 (1.0) 0 (0.0)
Tremor 30 (5.0) 0 (0.0) 9 (3.0) 0 (0.0)
* Control was non-activated autologous peripheral blood mononuclear cells.

Cerebrovascular Events

In controlled clinical trials, cerebrovascular events, including hemorrhagic and ischemic strokes, were observed in 3.5% of patients in the PROVENGE group compared with 2.6% of patients in the control group.

Read the Provenge (sipuleucel-t suspension for intravenous infusion) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

No studies of drug interactions have been performed with PROVENGE.

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

PROVENGE is intended solely for autologous use.

Acute Infusion Reactions

Acute infusion reactions (reported within 1 day of infusion) included, but were not limited to, fever, chills, respiratory events (dyspnea, hypoxia, and bronchospasm), nausea, vomiting, fatigue, hypertension, and tachycardia. In controlled clinical trials, 71.2% of patients in the PROVENGE group developed an acute infusion reaction. The most common events ( ≥ 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, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. The incidence of severe events 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.

Closely monitor patients with cardiac or pulmonary conditions. In the event of an acute infusion reaction, the infusion rate may be decreased, or the infusion stopped, depending on the severity of the reaction. Appropriate medical therapy should be administered as needed. [See Administration Modification for Infusion Reactions and HOW SUPPLIED, Storage and Handling]

Handling Precautions for Control of Infectious Disease

PROVENGE is not routinely tested for transmissible infectious diseases. Therefore, patient leukapheresis material and PROVENGE may carry the risk of transmitting infectious diseases to health care professionals handling the product. Accordingly, health care professionals should employ universal precautions when handling leukapheresis material or PROVENGE. [See HOW SUPPLIED, Storage and Handling]

Concomitant Chemotherapy or Immunosuppressive Therapy

Use of either chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. PROVENGE is designed to stimulate the immune system, and concurrent use of immunosuppressive agents may alter the efficacy and/or safety of PROVENGE. Therefore, patients should be carefully evaluated to determine whether it is medically appropriate to reduce or discontinue immunosuppressive agents prior to treatment with PROVENGE.

Product Safety 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 are not available at the time of infusion. If the sterility results become positive for microbial contamination after PROVENGE has been approved for infusion, Dendreon will notify the treating physician. Dendreon will attempt to identify the microorganism, perform antibiotic sensitivity testing on recovered microorganisms, and communicate the results to the treating physician. Dendreon may request additional information from the physician in order to determine the source of contamination.

Patient Counseling Information

Inform the patient or caregiver about the following:

  • The recommended course of therapy for PROVENGE is 3 complete doses. Each infusion of PROVENGE is preceded by a leukapheresis procedure approximately 3 days prior. It is important to maintain all scheduled appointments and arrive at each appointment on time because the leukapheresis and infusions must be appropriately spaced and the PROVENGE expiration time must not be exceeded.
  • If the patient is unable to receive an infusion of PROVENGE, the patient will need to undergo an additional leukapheresis procedure if the treatment is to be continued.
  • Counsel the patient on the importance of adhering to preparation instructions for the leukapheresis procedure, the possible side effects of leukapheresis, and post-procedure care.
  • If the patient does not have adequate peripheral venous access to accommodate the leukapheresis procedure and infusion of PROVENGE, inform the patient about the need for a central venous catheter. Counsel the patient on the importance of catheter care. Instruct the patient to tell their doctor if they are experiencing fevers or any swelling or redness around the catheter site, because these symptoms could be signs of an infected catheter.
  • Report signs and symptoms of acute infusion reactions such as fever, chills, fatigue, breathing problems, dizziness, high blood pressure, nausea, vomiting, headache, or muscle aches.
  • Report any symptoms suggestive of a cardiac arrhythmia.
  • Inform their doctor if they are taking immunosuppressive agents.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity or mutagenicity studies of PROVENGE in animals were conducted. No studies on the effects of PROVENGE on fertility have been conducted.

Use In Specific Populations

Geriatric

In controlled clinical trials, 72.9% of patients (438 of 601) in the PROVENGE group were ≥ 65 years of age. There were no apparent differences in the safety of PROVENGE between patients ≥ 65 years of age and younger patients.

In a survival analysis of the controlled clinical trials of PROVENGE in metastatic castrate resistant prostate cancer, 78.3% of randomized patients (382 of 488) were ≥ 65 years of age. The median survival of patients in the PROVENGE group ≥ 65 years of age was 23.4 months (95% confidence interval 22.0, 27.1), compared with 17.3 months in the control group (95% confidence interval: 13.5, 21.5).

Race

In controlled clinical trials, 90.6% of patients were Caucasian, 5.8% were African American, and 3.7% were "Other". Due to the low numbers of non-Caucasian patients in the trials, no conclusions can be made regarding the safety or efficacy of PROVENGE by race.

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.

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 collected from the leukapheresis. There are no known instances of overdosage from either a single infusion or a full course of therapy with PROVENGE.

CONTRAINDICATIONS

None.

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

PROVENGE is classified as an autologous cellular immunotherapy. While the precise mechanism of action is unknown, PROVENGE is designed to induce an immune response targeted against PAP, an antigen expressed in most prostate cancers. During ex vivo culture with PAP-GM-CSF, APCs take up and process the recombinant target antigen into small peptides that are then displayed on the APC surface.

In Study 1, 237 out of the 512 patients randomized were evaluated for the development of humoral and T cell immune responses (proliferative and gamma-interferon (γIFN) ELISPOT) to the target antigens at Baseline, and at Weeks 6, 14, and 26. Antibody (IgM and IgG) responses against PAP-GM-CSF and PAP antigen alone were observed through the follow-up period in the PROVENGE group. Neutralizing antibody responses to GM-CSF were transient. T cell proliferative and γIFN ELISPOT responses to PAP-GM-CSF fusion protein were observed in cells collected from peripheral blood of patients through the follow-up period in the PROVENGE treatment group but not in controls. In some patients a response to PAP antigen alone was observed. No conclusions could be made regarding the clinical significance of the observed immune responses.

Clinical Studies

The effect of PROVENGE on patients with metastatic castrate resistant (hormone refractory) prostate cancer was studied in three similar randomized, double-blind, placebo-controlled, multicenter trials. Following randomization, patients from both treatment groups underwent a series of 3 leukapheresis procedures (at approximately Weeks 0, 2, and 4). Each leukapheresis was followed approximately 3 days later by infusion of PROVENGE or control. The control was autologous peripheral blood mononuclear cells that had not been activated [see DESCRIPTION]. Following disease progression, patients were treated at the physician's discretion with other anti-cancer interventions.

Study 1

Study 1 was a randomized, double-blind, placebo-controlled, multicenter trial in patients with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Eligible patients had metastatic disease in the soft tissue and/or bone with evidence of progression either at these sites or by serial Prostate Specific Antigen (PSA) measurements. Exclusion criteria included visceral (liver, lung, or brain) metastases, moderate to severe prostate cancer-related pain, and use of narcotics for cancer-related pain.

A total of 512 patients were randomized in a 2:1 ratio to receive PROVENGE (n=341) or control (n=171). The median age was 71, and 90% of the patients were Caucasian. 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; 58% had primary Gleason scores of four or more; 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.

Supportive Studies

Study 2 was a randomized, double-blind, placebo-controlled, multicenter trial in patients with metastatic castrate resistant prostate cancer and no cancer-related pain. The primary endpoint was time to disease progression; analysis of the primary endpoint did not reach statistical significance. All patients were to be followed for survival; however, the survival analysis was not pre-specified. A third study, similar in design to Study 2, was terminated prior to completion of planned accrual.

Summary of Study Results

Figure 1 and Table 2 present overall survival results observed in two randomized, Phase 3 studies of PROVENGE in men with metastatic castrate resistant prostate cancer. The survival findings were consistent across multiple subgroups. Analyses of time to disease progression did not meet statistical significance in any Phase 3 study of PROVENGE.

Figure 1: Kaplan-Meier Overall Survival Curve for Study 1

Kaplan-Meier Overall Survival Curve for Study 1 - Illustration

Table 2: Summary of Overall Survival (All Patients as Randomized)

  Study 1 Study 2
PROVENGE
(N=341)
Control
(N=171)
PROVENGE
(N=82)
Control
(N=45)
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)
  Hazard Ratio (95% CI) 0.775a (0.614, 0.979) 0.586b (0.388, 0.884)
  p-value 0.032a 0.010c
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 (not pre-specified).
c p-value based on a log-rank test (not pre-specified).
Abbreviations: CI = confidence interval.

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

PROVENGE®
(sipuleucel-T)

This leaflet is designed to help you understand treatment with PROVENGE (pronounced PROH-venj). The more you understand your treatment, the better you will be able to participate in your care. This leaflet does not take the place of talking with your doctor or healthcare professional about your medical condition or your treatment. If you have any questions, speak with your doctor.

What is PROVENGE?

PROVENGE is a prescription medicine that is used to treat certain patients with advanced prostate cancer. PROVENGE is made from your own immune cells.

What should I tell my doctor before getting PROVENGE?

Tell your doctor about all your medical problems, including:

Tell your doctor about all the medicines you take, including prescription and nonprescription drugs, vitamins, and dietary supplements.

How will I get PROVENGE?

Since PROVENGE is made from your own immune cells, your cells will be collected approximately 3 days before each scheduled infusion of PROVENGE. You will need to go to a cell collection center for this collection. The collection is called "leukapheresis" (pronounced loo-kuh-fuh-REE-sis). Your collected cells are sent to a special manufacturing center where they are mixed with a protein to make them ready for your infusion.

You will get PROVENGE in 3 intravenous infusions (put into your veins), about 2 weeks apart. Each infusion takes about 60 minutes. Following each infusion, you will be monitored for at least 30 minutes.

Your doctor will give you a schedule for your cell collection and infusion appointments. It is very important that you arrive on time for your appointments. If you miss an appointment and cannot be infused, your PROVENGE dose will not be usable. Your doctor will work with you to schedule a new appointment at the cell collection center. You may also get a new infusion appointment.

What are the possible or reasonably likely side effects of PROVENGE?

The most common side effects of PROVENGE include:

  • chills
  • fatigue
  • fever
  • back pain
  • nausea
  • joint ache
  • headache

PROVENGE infusion can cause serious reactions. Tell your doctor right away if you have breathing problems, chest pains, racing heart or irregular heartbeats, dizziness, nausea, or vomiting after getting PROVENGE because any of these may be signs of heart or lung problems.

Tell your doctor right away if you get a fever over 100°F, or redness or pain at the infusion or collection sites, because any of these may be signs of infection.

Tell your doctor about any side effect that concerns you or does not go away.

These are not all the possible side effects of PROVENGE treatment. For more information, talk with your doctor.

What are the ingredients in PROVENGE?

The active components of PROVENGE are your own immune cells mixed with the other active component, a protein designed to produce an immune response to prostate cancer. The product is suspended in an infusion solution called Lactated Ringer's Injection, USP, an inactive ingredient.

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

PROVENGE®
(sipuleucel-T)

This leaflet is designed to help you understand treatment with PROVENGE (pronounced PROH-venj). The more you understand your treatment, the better you will be able to participate in your care. This leaflet does not take the place of talking with your doctor or healthcare professional about your medical condition or your treatment. If you have any questions, speak with your doctor.

What is PROVENGE?

PROVENGE is a prescription medicine that is used to treat certain patients with advanced prostate cancer. PROVENGE is made from your own immune cells.

What should I tell my doctor before getting PROVENGE?

Tell your doctor about all your medical problems, including:

Tell your doctor about all the medicines you take, including prescription and nonprescription drugs, vitamins, and dietary supplements.

How will I get PROVENGE?

Since PROVENGE is made from your own immune cells, your cells will be collected approximately 3 days before each scheduled infusion of PROVENGE. You will need to go to a cell collection center for this collection. The collection is called "leukapheresis" (pronounced loo-kuh-fuh-REE-sis). Your collected cells are sent to a special manufacturing center where they are mixed with a protein to make them ready for your infusion.

You will get PROVENGE in 3 intravenous infusions (put into your veins), about 2 weeks apart. Each infusion takes about 60 minutes. Following each infusion, you will be monitored for at least 30 minutes.

Your doctor will give you a schedule for your cell collection and infusion appointments. It is very important that you arrive on time for your appointments. If you miss an appointment and cannot be infused, your PROVENGE dose will not be usable. Your doctor will work with you to schedule a new appointment at the cell collection center. You may also get a new infusion appointment.

What are the possible or reasonably likely side effects of PROVENGE?

The most common side effects of PROVENGE include:

  • chills
  • fatigue
  • fever
  • back pain
  • nausea
  • joint ache
  • headache

PROVENGE infusion can cause serious reactions. Tell your doctor right away if you have breathing problems, chest pains, racing heart or irregular heartbeats, dizziness, nausea, or vomiting after getting PROVENGE because any of these may be signs of heart or lung problems.

Tell your doctor right away if you get a fever over 100°F, or redness or pain at the infusion or collection sites, because any of these may be signs of infection.

Tell your doctor about any side effect that concerns you or does not go away.

These are not all the possible side effects of PROVENGE treatment. For more information, talk with your doctor.

What are the ingredients in PROVENGE?

The active components of PROVENGE are your own immune cells mixed with the other active component, a protein designed to produce an immune response to prostate cancer. The product is suspended in an infusion solution called Lactated Ringer's Injection, USP, an inactive ingredient.

Last reviewed on RxList: 7/18/2011
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Provenge Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

SIPULEUCEL-T - INJECTION

(SI-pu-LOO-sel-tee)

COMMON BRAND NAME(S): Provenge

USES: This medication is used to treat advanced prostate cancer. Sipuleucel-T is a type of vaccine created from your own immune system cells that works by causing your immune system to attack prostate cancer cells. This requires that you have a procedure to remove some of your white blood cells, which are used to prepare sipuleucel-T. Talk to your doctor about the risks and benefits of this treatment.

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start using sipuleucel-T and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

This medication is created specifically for you from your own blood and should not be given to another patient. Three days before your dose you will have a procedure in which your own white blood cells are removed and then used to create sipuleucel-T.

Sipuleucel-T is given as a slow infusion into a vein by a health care professional, roughly every 2 weeks for a total of 3 doses, as directed by your doctor.

Your doctor may prescribe premedications (such as acetaminophen, antihistamines) to lessen infusion reactions (see also Side Effects section). These medications are usually given 30 minutes before your dose of sipuleucel-T.

To get the most benefit from this medication, do not miss any doses. To help you remember, mark the days on the calendar when you need to receive the medication.

Disclaimer

Provenge Consumer (continued)

SIDE EFFECTS: Headache, sweating, muscle aches, or back pain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Symptoms of an infusion reaction that may occur during sipuleucel-T treatment include chills, tiredness, fever, nausea, vomiting, shortness of breath, fast/irregular heartbeat, and joint pain. Tell your health care professional right away if you have any of these symptoms during or after receiving your treatment. Your doctor will have you monitored closely and may slow the infusion or temporarily stop your treatment if a severe reaction occurs.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: weakness on one side of the body, confusion, slurred speech.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Provenge (sipuleucel-t suspension for intravenous infusion) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before using sipuleucel-T, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart problems, lung problems, history of stroke.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Sipuleucel-T is not recommended for use by women.

Disclaimer

Provenge Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

It is very important to be on time to each of your appointments. This product has a short expiration period and must be used before it expires, or additional procedures will be needed to collect your white blood cells to prepare more sipuleucel-T.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor immediately to establish a new dosing schedule.

STORAGE: Not applicable. This medication is given in a hospital or clinic and will not be stored at home.

Information last revised December 2010. Copyright(c) 2010 First Databank, Inc.

Provenge Patient Information Including Side Effects

Brand Names: Provenge

Generic Name: sipuleucel-T (Pronunciation: SI pu LOO sel tee)

What is sipuleucel-T (Provenge)?

Sipuleucel-T contains a protein that stimulates the body's immune system to help it respond against certain cancer cells.

Sipuleucel-T is used to treat advanced prostate cancer in men.

Sipuleucel-T is mixed with certain immune cells drawn from your own blood, and the mixture is later injected into your body. This type of treatment is called autologous (ah-TAL-oh-gus) immunotherapy.

Sipuleucel-T is usually given after surgery or other medications have been tried without successful treatment.

Sipuleucel-T may also be used for other purposes not listed in this medication guide.

What are the possible side effects of sipuleucel-T (Provenge)?

Some people receiving a sipuleucel-T injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, tired, or nauseated, or if you have fever, chills, joint pain, severe headache, blurred vision, buzzing in your ears, anxiety, confusion, vomiting, chest pain, fast or uneven heartbeats, wheezing, chest tightness, or trouble breathing. These side effects may occur during the injection or within the first 24 hours after your infusion.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any other serious side effect, such as:

  • fever;
  • redness, swelling, oozing, or other signs of infection where the IV needle was placed; or
  • signs of infection around the veins your cells were collected from.

Less serious side effects may include:

  • back pain;
  • mild nausea;
  • headache; or
  • mild body aches.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Provenge (sipuleucel-t suspension for intravenous infusion) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about sipuleucel-T (Provenge)?

Before you are treated with sipuleucel-T, tell your doctor about all of your medical conditions, especially heart disease, asthma, COPD or other breathing problems, or if you have ever had a stroke.

Sipuleucel-T is used in a treatment called autologous (ah-TAL-oh-gus) immunotherapy. Sipuleucel-T is mixed with certain immune cells drawn from your own blood, and this mixture is injected into your body.

Your doctor will determine your schedule for cell collection and sipuleucel-T injection. Follow your doctor's instructions very carefully. The timing of cell collection in relation to sipuleucel-T infusion is extremely important. If you miss an infusion appointment your prepared infusion cannot be used in the future.

Some people receiving a sipuleucel-T injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, tired, or nauseated, or if you have fever, chills, joint pain, severe headache, blurred vision, buzzing in your ears, anxiety, confusion, vomiting, chest pain, fast or uneven heartbeats, wheezing, chest tightness, or trouble breathing. These side effects may occur during the injection or within the first 24 hours after your infusion.

Side Effects Centers

Provenge Patient Information including How Should I Take

What should I discuss with my health care provider before receiving sipuleucel-T (Provenge)?

Before you are treated with sipuleucel-T, tell your doctor about all of your medical conditions.

If you have any of these conditions, you may need a sipuleucel-T dose adjustment or special tests:

  • heart disease;
  • asthma, chronic obstructive pulmonary disease (COPD), or other breathing problems; or
  • if you have ever had a stroke.

How is sipuleucel-T given (Provenge)?

Approximately 3 days before you receive this medication, your immune cells will be collected with a procedure called leukapheresis (LOO-ka-fe-REE-sis).

During the leukapheresis procedure, your immune cells will be collected through a small tube (catheter) placed into a vein in each of your arms. If the veins in your arms cannot be used, the catheter will be placed into a vein in your neck or upper chest.

The cell-collection catheter is connected to a machine that draws out your blood and separates your immune cells from other parts of the blood.

The cell collection process can take up to 4 hours to complete.

The collected immune cells are then mixed with sipuleucel-T, which contains a special protein that helps activate your body's immune cells. When injected back into your, these activated immune cells may be able to "recognize" and attack certain prostate cancer cells.

Your prepared sipuleucel-T solution will be injected into a vein through an IV. You will receive this injection in a clinic or hospital setting approximately 3 days after your cell collection procedure. Sipuleucel-T must be given slowly, and the IV infusion can take about 60 minutes to complete.

Your doctor will determine your schedule for cell collection and sipuleucel-T injection. Follow your doctor's instructions very carefully. The timing of cell collection in relation to sipuleucel-T infusion is extremely important. If you miss an infusion appointment your prepared infusion cannot be used in the future.

Sipuleucel-T is usually given in 3 doses spaced 2 weeks apart. Follow your doctor's instructions.

You will be given oral medications before your IV infusion to help prevent certain side effects.

Side Effects Centers

Provenge Patient Information including If I Miss a Dose

What happens if I miss a dose (Provenge)?

Call your doctor for instructions if you miss any appointment in your cell collection or sipuleucel-T infusion schedule.

What happens if I overdose (Provenge)?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid while receiving sipuleucel-T (Provenge)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

What other drugs will affect sipuleucel-T (Provenge)?

Tell your doctor if you use any drugs that weaken your immune system, such as:

  • other cancer medicines;
  • steroids (prednisone and others); or
  • medicines to prevent rejection of a transplanted organ.

This list is not complete and other drugs may interact with sipuleucel-T. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about sipuleucel-T.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.02. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

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