WARNINGS
Patient management should not be based on Indium In 111 ProstaScint® (Capromab Pendetide) scan results without appropriate confirmatory studies since in the pivotal trials, there was a high rate of false positive and false negative image interpretations (See PRECAUTIONS).
Indium In 111 ProstaScint® images should be interpreted only by physicians who have had specific training in Indium In 111 ProstaScint® image interpretation (see PRECAUTIONS, Imaging Precautions).
Allergic reactions, including anaphylaxis, can occur in patients who receive murine antibodies. Although serious reactions of this type have not been observed in clinical trials after Indium In 111 ProstaScint® administration, medications for the treatment of hypersensitivity reactions should be available during administration of this agent.
Indium In 111 ProstaScint® may induce human anti-mouse antibodies which may interfere with some immunoassays, including those used to assay PSA and digoxin (see PRECAUTIONS, Drug/Laboratory Test Interactions).
PRECAUTIONS
General
There were high rates of false positive and false negative image interpretations in the pivotal trials (see Clinical Studies). False positive scan interpretations may result in: (1) inappropriate surgical intervention to confirm scan results; (2) inappropriate denial of curative therapy if results are not confirmed; or (3) inadequate surgical staging if only areas of uptake are sampled. Surgical sampling should not be limited to the areas of positive uptake, unless histologic examination of these areas is diagnostic. Due to the potential for false negative scan interpretations, negative images should not be used in lieu of histologic confirmation. Proper patient preparation is mandatory to obtain optimal images for interpretation (see Imaging Precautions, below).
Bone scans are more sensitive than ProstaScint® (Capromab Pendetide) for the detection of metastases to bone, and Indium In 111 ProstaScint® should not replace bone scan for the evaluation of skeletal metastases
Imaging Precautions
Radiopharmaceuticals should be used only by physicians and other professionals who are qualified by training and experience in the safe use and handling of radionuclides. Indium In 111 ProstaScint® images should be interpreted only by physicians who have had specific training in the interpretation of Indium In 111 ProstaScint® images.
There may be Indium In 111 ProstaScint® clearance and imaging localization observed in the bowel, blood pool, kidneys, and urinary bladder. When obtaining all 72-120 hour planar and Single-Photon Emission Computed Tomography (SPECT) images, the bladder should be catheterized and irrigated. The administration of a cathartic is required the evening before imaging the patient, and a cleansing enema should be administered within an hour prior to each 72-120 hour imaging session.
The contents of the kit are not radioactive. However, after the Indium In 111 chloride is added, appropriate shielding of Indium In 111 ProstaScint® (Capromab Pendetide) must be maintained. Care should be taken to minimize radiation exposure to patients and medical personnel, consistent with proper hospital and patient management procedures.
Each ProstaScint® kit is a unit of use package. The contents of the kit are to be used only to prepare Indium In 111 ProstaScint®; unlabeled ProstaScint® should NOT be administered directly to the patient. After radiolabeling with Indium In 111, the entire Indium In 111 ProstaScint® dose must be administered to the patient for whom it was prescribed. Reducing the dose of Indium In 111, unlabeled ProstaScint®, or Indium In 111 ProstaScint® may adversely impact imaging results and is not recommended.
The components of the kit are sterile and pyrogen-free and contain no preservative. Indium In 111 ProstaScint® should be used within 8 hours after radiolabeling. It is essential to follow the directions for preparation carefully and to adhere to strict aseptic procedures during preparation of the radiolabeled product.
Information for Patients
Murine monoclonal antibodies (MAbs) are foreign proteins, and their administration can induce HAMA. While limited data exist concerning the clinical significance of HAMA, the presence of HAMA may interfere with murine-antibody based immunoassays, or could compromise the efficacy of diagnostic or therapeutic murine antibody-based agents and increase the risk of adverse reactions. For these reasons, patients should be informed that the use of this product could adversely affect the future ability to diagnose recurrence of their tumor, the ability to perform certain other laboratory tests, or to use other murine-based products. Patients should be advised to discuss prior use of murine-antibody based products with their physicians (see Heterologous Protein Administration, below).
Heterologous Protein Administration
Indium In 111 ProstaScint® (Capromab Pendetide) has been shown to induce HAMA to murine IgG infrequently and with low peak levels after single administration. HAMA levels were detected (at >8 ng/mL) by RIA after single infusion in 8% (20/239) of patients, while 1% of patients had levels greater than 100 ng/mL. In addition, serum HAMA levels were detected by RIA after repeat infusion in 19% (5/27) of the patients.
While limited data exist concerning the clinical significance of HAMA, detectable serum levels can alter the clearance and tissue biodistribution of MAbs. The development of persistently elevated serum HAMA levels could compromise the efficacy of diagnostic or therapeutic murine antibody-based agents. In repeat administration trials, 93% (65/70) of the evaluable repeat infusions were associated with normal tissue distribution of the MAb conjugate. Pre-infusion serum HAMA levels were generally not predictive of altered distribution.
When considering the administration of Indium In 111 ProstaScint® to patients who have previously received other murine antibody-based products, physicians should be aware of the potential for assay interference and increased clearance and altered biodistribution, which may interfere with the quality or sensitivity of the imaging study. Prior to administration of murine antibodies, including Indium In 111 ProstaScint®(Capromab Pendetide), the physician should review the patient history to determine whether the patient has previously received such products.
Drug Interactions
The effect of surgical and/or medical androgen ablation on the imaging performance of Indium In 111 ProstaScint® has not been studied. Preliminary data suggest hormone ablation may increase PSMA expression, with concurrent decrease in tumor expression of PSA.3 The use of ProstaScint® in this patient population cannot be recommended at this time.
Drug/Laboratory Test Interactions
The presence of HAMA in serum as a result of ProstaScint® may interfere with some antibody-based immunoassays (such as PSA and digoxin). When present, this interference generally results in falsely high values. When following PSA levels, assay methods resistant to HAMA interference should be utilized. PSA assays which were found to be resistant to HAMA interference were Hybritech Tandem-R and Abbott IMX.
When patients have received Indium In 111 ProstaScint®, the clinical laboratory should be notified to take appropriate measures to avoid interference by HAMA with clinical laboratory testing procedures. These methods include the use of non-murine-based immunoassays, HAMA removal by adsorption, or sample pre-treatment to block HAMA activity.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic or mutagenic potential of Indium In 111 ProstaScint® or to evaluate its effect on fertility.
Pregnancy
ProstaScint® is not indicated for use in women.
Nursing Mothers and/or Lactating Women
ProstaScint® is not indicated for use in women.
Pediatric Use
The safety and effectiveness of Indium In 111 ProstaScint® in pediatric patients have not been established. ProstaScint® is not indicated for use in children.
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