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Sipuleucel-T: Drug information

Sipuleucel-T: Drug information
(For additional information see "Sipuleucel-T: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Provenge
Pharmacologic Category
  • Cellular Immunotherapy, Autologous
Dosing: Adult

Note: Premedicate with oral acetaminophen 650 mg and an antihistamine (eg, diphenhydramine 50 mg) ~30 minutes prior to infusion. For autologous use only. Do not infuse until confirmation of product release has been received from the manufacturing company.

Prostate cancer, metastatic

Prostate cancer, metastatic: IV: Each dose contains ≥50 million autologous CD54+ cells (obtained through leukapheresis) activated with PAP-GM-CSF; administer doses at ~2-week intervals for a total of 3 doses (Ref). If unable to receive a scheduled infusion, an additional leukapheresis procedure will be necessary prior to continuing a course of treatment.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Adjustment for Toxicity: Adult

Acute infusion reaction: Interrupt or slow infusion rate (depending on the severity of infusion reaction); may require acetaminophen, IV H1 and/or H2 antagonists, or low-dose meperidine to manage acute symptoms.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Initial infusion-related events usually present within the first 24 hours after administration.

>10%:

Central nervous system: Chills (53%; grades ≥3: 2%), fatigue (41%; grades ≥3: 1%), headache (18%; grades ≥3: <1%), dizziness (12%; grades ≥3: <1%), pain (12%)

Gastrointestinal: Nausea (22%; grades ≥3: <1%), vomiting (13% grades ≥3: <1%), constipation (12%; grades ≥3: <1%)

Hematologic: Anemia (13%)

Hypersensitivity: Severe infusion related reaction (71%; grade 3: 4%)

Neuromuscular & skeletal: Back pain (30%; grades ≥3: 3%), myalgia (12%; grades ≥3: <1%), weakness (11%; grades ≥3: 1%)

Miscellaneous: Fever (31%; grades ≥3: 1%), citrate toxicity (15%)

1% to 10%:

Cardiovascular: Hypertension (8% grades ≥3: <1%), hemorrhagic stroke (4%)

Dermatologic: Diaphoresis (5%; grades ≥3: <1%), skin rash (5%)

Gastrointestinal: Anorexia (7%), acute ischemic stroke (4%)

Genitourinary: Hematuria (8%)

Neuromuscular & skeletal: Musculoskeletal pain (9%; grades ≥3: <1%), muscle spasm (8%; grades ≥3: <1%), neck pain (6%), tremor (5%)

Renal: Hematuria (8%)

Respiratory: Flu-like symptoms (10%), dyspnea (9%; grades ≥3: 2%)

<1%, postmarketing, and/or case reports: Cerebrovascular accident, eosinophilia, hypotension, myasthenia gravis, myocardial infarction, myositis, paresthesia (grades ≥3), pulmonary embolism, rhabdomyolysis, sepsis, syncope, transient ischemic attacks, tumor flare, venous thrombosis

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Infusion reaction: Acute infusion reactions may occur within 1 day of infusion and are usually mild or moderate for most patients; the incidence of severe reaction may be higher with the second infusion, while the third infusion is associated with a decrease in the incidence of severe reactions. Premedication with oral acetaminophen and diphenhydramine is recommended. Depending on the severity of the infusion reaction, interrupt or slow infusion rate; in clinical trials, acetaminophen, IV H1 and/or H2 antagonists, and low-dose meperidine were used to manage acute symptoms. Symptoms of acute infusion reaction may include chills, rigor, fever, bronchospasm, dyspnea, hypoxia, hypertension, tachycardia, syncope, hypotension, joint or muscle aches, nausea, vomiting, dizziness, fatigue, headache, and weakness; fever and chills usually resolved within 2 days. Observe patient for at least 30 minutes after infusion. Closely monitor patients with cardiac or pulmonary conditions during infusion.

• Thromboembolic events: Deep venous thrombosis and pulmonary embolism occurred following sipuleucel-T infusion (postmarketing reports), usually in patients with multiple risk factors for thromboembolism. Use with caution in patients at risk for thromboembolic events.

• Vascular disorders: Cerebrovascular (hemorrhagic and ischemic stroke) and cardiovascular events (myocardial infarction) have occurred; transient ischemic attacks have been reported following infusion (postmarketing reports). Such events usually occurred in patients with multiple risk factors for cerebrovascular or cardiovascular incidents.

Concurrent drug therapy issues:

• Androgen deprivation therapy: In clinical trials evaluating sipuleucel-T, patients who had androgen deprivation therapy without prior bilateral orchiectomy were continued on gonadal suppression with a luteinizing hormone-releasing hormone agonist (Higano 2009; Kantoff 2010).

• Chemotherapy: Concurrent use with chemotherapy has not been studied.

• Immunosuppressive therapy: Concurrent use with immunosuppressives (eg, corticosteroids) has not been studied; may alter the efficacy and/or safety of sipuleucel-T. Carefully evaluate patients for appropriateness of reducing or discontinuing immunosuppressive agents prior to treatment.

Other warnings/precautions:

• Appropriate use: For autologous use only. Patient identity must be matched to the patient identifiers on the infusion bag and on the Final Product Disposition Notification (provided by manufacturer) prior to infusion. Confirmation of product release must be received from the manufacturer prior to infusion.

• Handling precautions: Apply universal precautions for product handling. Sipuleucel-T is not tested for transmissible infectious diseases; patient-specific leukapheresis collection and activated product may have a risk for infectious disease transmission.

• Sterility testing: Preliminary sterility testing is done based on a 2-day incubation period. Final (7-day incubation) testing is not available until after administration; health care providers will be notified if 7-day sterility tests are positive for microbial contamination.

• Treatment delays: If unable to receive a scheduled reinfusion, an additional leukapheresis procedure may be required; advise patients of this possibility before treatment initiation.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intravenous [preservative free]:

Provenge: (250 mL)

Generic Equivalent Available: US

No

Pricing: US

Suspension (Provenge Intravenous)

50000000CELLS (per mL): $300.49

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Prescribing and Access Restrictions

Patients may receive Sipuleucel-T at a participating site. Physicians must go through an inservice and register to prescribe the treatment; patients must also complete an enrollment form. Information on registration and enrollment is available at 1-877-336-3736 or at DendreonONCall.com.

Administration: Adult

IV: For autologous use only; the identity of the patient must be matched to the patient identifiers on the infusion bag and on the “Final Product Disposition Notification” prior to infusion. Do not infuse until confirmation of product release is received from the manufacturing company. Keep the sealed infusion bag in the insulated polyurethane container inside the shipping box until ready for administration. Prior to infusion, inspect bag for signs of leaks (do not administer if leaking) or damage. Gently mix to resuspend contents; inspect for clumps or clotting; small clumps should disperse with the gentle mixing; do not administer if clumps remain. Infusion must begin prior to the expiration date and time; do NOT infuse if expired.

For IV infusion only. Infuse over ~60 minutes; infuse the entire contents of the bag. Do NOT use a cell filter for infusion. Premedicate with oral acetaminophen and diphenhydramine ~30 minutes prior to infusion. If acute infusion reaction occurs, interrupt or slow infusion rate (depending on the severity of infusion reaction); may require acetaminophen, IV H1 and/or H2 antagonists, or low-dose meperidine to manage acute symptoms. If infusion is interrupted, keep infusion bag at room temperature; do not resume if bag is retained at room temperature for >3 hours. Observe patient for at least 30 minutes after infusion.

Use: Labeled Indications

Prostate cancer, metastatic: Treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

Medication Safety Issues
Other safety concerns:

For autologous use only; patient identity must be matched to the patient identifiers on the infusion bag and on the “Final Product Disposition Form” prior to infusion. Healthcare providers should apply universal precautions when handling both the initial leukapheresis product and the activated product.

Sound-alike/look-alike issues:

Sipuleucel-T may be confused with axicabtagene ciloleucel, betibeglogene autotemcel, brexucabtagene autoleucel, ciltacabtagene autoleucel, elivaldogene autotemcel, idecabtagene vicleucel, lisocabtagene maraleucel, tisagenlecleucel.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Corticosteroids (Systemic): May diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing immunosuppressants, such as systemic corticosteroids, prior to initiating sipuleucel-T therapy. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone given for 2 or more weeks are immunosuppressive. Risk D: Consider therapy modification

Immunosuppressants (Cytotoxic Chemotherapy): May diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Immunosuppressants (Miscellaneous Oncologic Agents): May diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Immunosuppressants (Therapeutic Immunosuppressant Agents): May diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Methotrexate: May diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of methotrexate prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Pregnancy Considerations

Animal reproduction studies have not been conducted. Not indicated for use in women.

Breastfeeding Considerations

Not indicated for use in women.

Monitoring Parameters

Monitor for infusion reaction during and for at least 30 minutes after infusion; monitor closely during infusion for patients with cardiovascular and pulmonary disease; monitor for thromboembolic and vascular events.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Sipuleucel-T is an autologous cellular immunotherapy that stimulates an immune response against an antigen (prostatic acid phosphatase [PAP]) expressed in most prostate cancer tissues. Peripheral blood is collected (~3 days prior to infusion) from the patient via leukapheresis, from which peripheral blood mononuclear cells (PBMCs) are isolated. Antigen presenting cell (APC) precursors, consisting of CD54-positive cells that include dendritic cells, are isolated from the PBMCs. The APCs are then activated (in vitro) with a recombinant human fusion protein, PAP-GM-CSF (also termed PA2024), composed of an antigen specific for prostate cancer, PAP linked to granulocyte-macrophage colony-stimulating factor and cultured for ~40 hours. The final product, sipuleucel-T, is reinfused into the patient, inducing T-cell immunity to tumors that express PAP.

  1. Higano CS, Schellhammer PF, Small EJ, et al. Integrated Data From 2 Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trials of Active Cellular Immunotherapy With Sipuleucel-T in Advanced Prostate Cancer. Cancer. 2009;115(16):3670-369. [PubMed 19536890]
  2. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  3. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. N Engl J Med. 2010;363(5):411-422. [PubMed 20818862]
  4. Provenge (sipuleucel-T) [prescribing information]. Seal Beach, CA: Dendreon Corporation; July 2017.
  5. Small EJ, Schellhammer PF, Higano CS, et al. Placebo-Controlled Phase III Trial of Immunologic Therapy With Sipuleucel-T (APC8015) in Patients With Metastatic, Asymptomatic Hormone Refractory Prostate Cancer. J Clin Oncol. 2006;24(19):3089-3094. [PubMed 16809734]
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