Sipuleucel-T

Pronunciation: SI-pu-LOO-sel tee
Class: Antineoplastic agent

Trade Names

Provenge
- Injection, suspension 50 million autologous CD54+ cells activated with prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony stimulating factor (GM-CSF) in 250 mL of lactated Ringer's injection

Pharmacology

Sipuleucel-T is an autologous cellular immunotherapy. While the precise mechanism of action is unknown, it 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, antigen-presenting cells (APCs) take up and process the recombinant target antigen into small peptides that are then displayed on the APC surface.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Special Populations

Renal Function Impairment

No data available.

Hepatic Function Impairment

No data available.

Race

No conclusions can be made regarding the safety or efficacy by race.

Indications and Usage

For the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

Contraindications

None well documented.

Dosage and Administration

Adults

IV 3 complete doses, given at approximately 2-week intervals. In the event of an acute infusion reaction, the infusion may be interrupted or slowed, depending on the severity of the reaction. If the infusion must be interrupted, the infusion should not be resumed if the infusion bag will be held at room temperature for more than 3 h.

General Advice

  • For autologous use only.
  • For IV use only. Administer via IV infusion over a period of approximately 60 min. Do not use a cell filter.
  • Sipuleucel-T is supplied in a sealed, patient-specific infusion bag; the entire volume of the bag should be infused.
  • If the patient is unable to receive a scheduled infusion, 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.
  • Observe the patient for at least 30 min following each infusion.
  • Premedicate patient with oral acetaminophen and an antihistamine, such as diphenhydramine, approximately 30 min prior to administration.
  • Sipuleucel-T is shipped directly to the infusing provider. Sipuleucel-T 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 until infusion. 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. The infusion bag must remain within the insulated polyurethane container until the time of administration.
  • Do not infuse until confirmation of product release has been received from the manufacturer. The manufacturer will send a Cell Product Disposition Form to the infusion site containing the patient identifiers, expiration date and time, and the disposition status (approved for infusion or rejected).
  • 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 sipuleucel-T. Once the infusion bag is removed from the insulated container, it should remain at room temperature for no more than 3 h. Sipuleucel-T should not be returned to the shipping container.
  • Once the patient is prepared for infusion and the Cell Product Disposition Form has been received, remove the sipuleucel-T 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 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 or if clumps remain in the bag.
  • Prior to infusion, match the patient's identity with the patient identifiers on the Cell Product Disposition Form and the sipuleucel-T infusion bag.

Storage/Stability

The infusion bag must remain in the unopened insulated container until the time of administration. Once the infusion bag is removed from the insulated container, it should remain at room temperature for no more than 3 h. If the infusion must be interrupted, do not resume the infusion if the infusion bag will be held at room temperature for more than 3 h.

Drug Interactions

Immunosuppressive agents

Because sipuleucel-T stimulates the immune system, concomitant use of immunosuppressive agents (eg, systemic corticosteroids) may alter the efficacy and/or safety of sipuleucel-T. Therefore, carefully evaluate the patient to determine whether it is medically appropriate to reduce or discontinue immunosuppressive agents prior to sipuleucel-T treatment.

Adverse Reactions

Cardiovascular

Hypertension (8%); cerebrovascular events, including hemorrhagic and ischemic strokes (4%).

CNS

Fatigue (41%); headache (18%); paresthesia (14%); dizziness, paresthesia oral (12%); asthenia (11%); insomnia (6%); tremor (5%).

Dermatologic

Rash, sweating (5%).

GI

Nausea (22%); vomiting (13%); constipation (12%); diarrhea (10%); anorexia (7%); weight decreased (6%).

Genitourinary

Hematuria (8%); UTI (6%).

Musculoskeletal

Back pain (30%); joint ache (20%); muscle ache, pain in extremity (12%); musculoskeletal pain (9%); muscle spasms (8%); bone pain, musculoskeletal chest pain, neck pain (6%).

Respiratory

Dyspnea (9%); cough, upper respiratory tract infection (6%).

Miscellaneous

Acute infusion reaction (71%); chills (53%); fever (31%); citrate toxicity (15%); anemia (13%); pain (12%); influenza-like illness (10%); hot flush, peripheral edema (8%).

Precautions

Monitor

Observe patient for at least 30 min following each infusion. Closely monitor patients with cardiac or pulmonary conditions. Monitoring for infectious sequelae in patients with central venous catheters is recommended.


Pregnancy

Category undetermined . Not indicated for use in women.

Lactation

Not indicated for use in women.

Children

Safety and efficacy not established.

Acute infusion reactions

Acute infusion reactions (reported within 1 day of infusion) included, but were not limited to, chills, fatigue, fever, hypertension, nausea, respiratory events (dyspnea, hypoxia, and bronchospasm), tachycardia, and vomiting. 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.

Handling

Patient leukapheresis material and sipuleucel-T may carry the risk of transmitting infectious diseases to health care providers handling the product. Employ universal precautions in handling leukapheresis material or sipuleucel-T.

Product safety testing

Sipuleucel-T is released for infusion based on the microbial and sterility results from several tests. 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 sipuleucel-T has been approved for infusion, the manufacturer will notify the treating health care provider. The manufacturer will attempt to identify the microorganism, perform antibiotic sensitivity testing on recovered microorganisms, and communicate the results to the treating health care provider. The manufacturer may request additional information from the health care provider in order to determine the source of contamination.

Overdosage

Symptoms

None reported.

Patient Information

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

Copyright © 2009 Wolters Kluwer Health.

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