Provenge
(sipuleucel-T)Dosage & Administration
For autologous use only.
For intravenous use only.
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Provenge Prescribing Information
PROVENGE ® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.
For autologous use only.
For intravenous use only.
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.
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 identity with the patient identifiers on the Final Product Disposition Notification form and the PROVENGE infusion bag.
- Infuse the entire volume of the PROVENGE infusion bag intravenously over approximately 60 minutes. Do not use a cell filter.
- Observe the patient for acute infusion reactions for at least 30 minutes following each infusion.
- If acute infusion reactions occur, such as chills, fatigue, fever, nausea, and joint ache, interrupt or slow the infusion and administer appropriate medical treatment as needed. In controlled clinical trials, symptoms of acute infusion reactions were treated with acetaminophen, intravenous H1 and/or H2 blockers, and low-dose intravenous meperidine.
- If the infusion is interrupted, keep the PROVENGE infusion bag at room temperature.
- Do not resume infusion if the PROVENGE infusion bag has been at room temperature for more than 3 hours.
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.
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.
None.
Acute Infusion Reactions
Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, hypertension, and tachycardia. Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, 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 reactions were mild or moderate. Fevers and chills generally resolved within 2 days (71.9% and 89%, respectively). 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 reactions were mild or moderate. Fevers and chills generally resolved within 2 days (71.9% and 89%, 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. 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, decrease the infusion rate or stop the infusion, depending on the severity of the reaction. Administer appropriate medical treatment as needed. [ ] Closely monitor patients with cardiac or pulmonary conditions. In the event of an acute infusion reaction, decrease the infusion rate or stop the infusion, depending on the severity of the reaction. Administer appropriate medical treatment as needed. [ See Dosage and Administration ( 2.2) ]
Thromboembolic Events
Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. PROVENGE should be used with caution in patients with risk factors for thromboembolic events. Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. PROVENGE should be used with caution in patients with risk factors for thromboembolic events.
Vascular Disorders
: In controlled clinical trials, cerebrovascular events (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. In the postmarketing setting, cerebrovascular events, including transient ischemic attacks, have been observed following infusion of Provenge. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. Cerebrovascular disease: In controlled clinical trials, cerebrovascular events (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. In the postmarketing setting, cerebrovascular events, including transient ischemic attacks, have been observed following infusion of Provenge. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.
: 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. In the postmarketing setting, myocardial infarctions have been observed following infusion of Provenge. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. 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. In the postmarketing setting, myocardial infarctions have been observed following infusion of Provenge. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.
Handling Precautions for Control of Infectious Disease
PROVENGE is not 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.
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 immune-suppressive agents may alter the efficacy and/or safety of PROVENGE. Therefore, evaluate patients carefully 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.