新型的放射活性的诊断性注射剂Axumin([F-18] Fluciclovine)用于检测前列腺癌复发,日前获美国FDA批准
Injection: supplied as a clear, colorless solution in a 30 mL multiple-dose vial containing 335 to 8200 MBq/mL (9 to 221 mCi/mL) fluciclovine F 18 at calibration time and date. 4 CONTRAINDICATIONS None 5 WARNINGS AND PRECAUTIONS 5.1 Risk for Image Misinterpretation Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out the presence of recurrent prostate cancer and a positive image does not confirm the presence of recurrent prostate cancer. The performance of Axumin seems to be affected by PSA levels [See Clinical Studies (14)]. Fluciclovine F 18 uptake is not specific for prostate cancer and may occur with other types of cancer and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation of the suspected recurrence site, is recommended. 5.2 Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available. 5.3 Radiation Risks Axumin use contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe handling to minimize radiation exposure to the patient and health care providers [see Dosage and Administration (2.1)]. 6 ADVERSE REACTIONS 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 clinical trial database for Axumin includes data from 877 subjects including 797 males diagnosed with prostate cancer. Most patients received a single administration of Axumin, a small number of subjects (n = 50) received up to five administrations of the drug. The mean administered activity was 370 MBq (range, 163 to 485 MBq). Adverse reactions were reported in ≤1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Axumin is not indicated for use in females and there is no information on the risk of adverse development outcomes in pregnant women or animals with the use of fluciclovine F 18. 8.2 Lactation Risk Summary Axumin is not indicated for use in females and there is no information of the presence of fluciclovine F 18 in human milk. 8.4 Pediatric Use Safety and effectiveness have not been established in pediatric patients. 8.5 Geriatric Use Of the total number of patients in clinical studies of Axumin, the average age was 66 years with a range of 21 to 90 years. No overall differences in safety or effectiveness were observed between older subjects and younger subjects. 10 OVERDOSAGE In case of overdose of Axumin, encourage patients to maintain hydration and to void frequently to minimize radiation exposure. 11 DESCRIPTION 11.1 Chemical Characteristics Axumin contains the fluorine 18 (F 18) labeled synthetic amino acid analog fluciclovine. Fluciclovine F 18 is a radioactive diagnostic agent used with PET imaging. Chemically, fluciclovine F 18 is (1r, 3r)-1-amino-3[18F]fluorocyclobutane-1-carboxylic acid. The molecular weight is 132.1 and the structural formula is:
The point source air-kerma coefficient for F 18 is 3.75 × 10-17 Gy m2/(Bq s). The first half-value thickness of lead (Pb) for F 18 gamma rays is approximately 6 mm. The relative reduction of radiation emitted by F 18 that results from various thicknesses of lead shielding is shown in Table 4. The use of 8 cm of Pb will decrease the radiation transmission (i.e., exposure) by a factor of about 10,000. Table 3: Radiation Attenuation of 511 keV Gamma Rays by Lead Shielding
12.1 Mechanism of action Fluciclovine F 18 is a synthetic amino acid transported across mammalian cell membranes by amino acid transporters, such as LAT-1 and ASCT2, which are upregulated in prostate cancer cells. Fluciclovine F 18 is taken up to a greater extent in prostate cancer cells compared with surrounding normal tissues. 12.2 Pharmacodynamics Following intravenous administration, the tumor-to-normal tissue contrast is highest between 4 and 10 minutes after injection, with a 61% reduction in mean tumor uptake at 90 minutes after injection. 12.3 Pharmacokinetics Distribution Following intravenous administration, fluciclovine F 18 distributes to the liver (14% of administered activity), pancreas (3%), lung (7%), red bone marrow (12%) and myocardium (4%). With increasing time, fluciclovine F 18 distributes to skeletal muscle. Excretion Across the first four hours post-injection, 3% of administered radioactivity was excreted in the urine. Across the first 24 hours post-injection, 5% of administered radioactivity was excreted in the urine. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No long term studies in animals have been performed to evaluate the carcinogenic potential of fluciclovine. Mutagenesis Fluciclovine was not mutagenic in vitro in reverse mutation assay in bacterial cells and in chromosome aberration test in cultured mammalian cells, and was negative in an in vivo clastogenicity assay in rats after intravenous injection of doses up to 43 mcg/kg. However, fluciclovine F 18 has the potential to be mutagenic because of the F 18 radioisotope. Impairment of Fertility No studies in animals have been performed to evaluate potential impairment of fertility in males or females. 14 CLINICAL STUDIES The safety and efficacy of Axumin were evaluated in two studies (Study 1 and Study 2) in men with suspected recurrence of prostate cancer based on rising PSA levels following radical prostatectomy and/or radiotherapy. Study 1 evaluated 105 Axumin scans in comparison to histopathology obtained by biopsy of the prostate bed and biopsies of lesions suspicious by imaging. PET/CT imaging generally included the abdomen and pelvic regions. The Axumin images were originally read by on-site readers. The images were subsequently read by three blinded independent readers. Table 4 shows the performance of Axumin in the detection of recurrence in each patient scan and, specifically, within the prostatic bed and extra-prostatic regions, respectively. The results of the independent read were generally consistent with one another and confirmed the results of the on-site reads. Table 4: Performance of Axumin in Patients with Biochemically Suspected Recurrent Prostate Cancer, at the Patient Level and at the Prostate Bed and Extraprostatic Region Levels
Study 2 evaluated the concordance between 96 Axumin and C11 choline scans in patients with median PSA value of 1.44 ng/mL (interquartile range = 0.78 to 2.8 ng/mL). The C 11 choline scans were read by on-site readers. The Axumin scans were read by the same three blinded independent readers used for Study 1. The agreement values between the Axumin and C11 choline reads were 61%, 67% and 77%, respectively. 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Axumin is supplied as a clear, colorless injection in a 30 mL multiple-dose glass vial containing approximately 26 mL solution of 335-8200 MBq/mL (9-221 mCi/mL) fluciclovine F 18 at calibration time and date. 30 mL sterile multiple-dose vial: NDC 69932-001-30 16.2 Storage and Handling Store Axumin at controlled room temperature (USP) 20°C to 25°C (68°F to 77°F). Axumin does not contain a preservative. Store Axumin within the original container in radiation shielding. This preparation is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State. 17 PATIENT COUNSELING INFORMATION Instruct patients to avoid significant exercise for at least a day before the PET scan. Instruct patients not to eat or drink for at least 4 hours before the PET scan (other than small amounts of water for taking medications). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=389a502e-a7d5-43dd-b6bf-f022ff23f3b9 |
Axumin(Fluciclovine F 18 Intravenous Injection)简介:
新型的放射活性的诊断性注射剂Axumin([F-18] Fluciclovine)用于检测前列腺癌复发,日前获美国FDA批准2016年5月27日,美国FDA批准Blue Earth Diagnostics 的Axumin,一种新型放射性注射性诊断剂,用于 ... 责任编辑:admin
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