Bicisate Dihydrochloride

INDICATIONS NEUROLITE ® single photon emission computerized tomography (SPECT) is indicated as an adjunct to conventional CT or MRI imaging in the localization of stroke in patients in whom stroke has already been diagnosed. NEUROLITE ® is not indicated for assessment of functional viability of brain tissue. Also, NEUROLITE ® is not indicated for distinguishing between stroke and other brain lesions.

None known.

None known.

General USE WITH CAUTION IN PATIENTS WITH RENAL OR HEPATIC IMPAIRMENT. TECHNETIUM Tc-99m BICISATE IS ELIMINATED PRIMARILY BY RENAL EXCRETION. WHETHER TECHNETIUM Tc-99m BICISATE IS DIALYZABLE IS NOT KNOWN. DOSE ADJUSTMENTS IN PATIENTS WITH RENAL OR HEPATIC IMPAIRMENT HAVE NOT BEEN STUDIED. Patients should be encouraged to drink fluids and to void frequently during the 2-6 hours immediately after injection to minimize radiation dose to the bladder and other target organs. Contents of the vials are intended only for use in the preparation of Technetium Tc-99m Bicisate and are not to be administered directly to the patient without first undergoing the preparation procedure. The contents of each vial are sterile and non-pyrogenic. To maintain sterility, aseptic technique must be used during all operations in the manipulation and administration of NEUROLITE ® . Technetium Tc-99m Bicisate should be used within six hours of the time of preparation. As with any other radioactive material, appropriate shielding should be used to avoid unnecessary radiation exposure to the patient, occupational workers, and other people. Radiopharmaceuticals should be used only by physicians who are qualified by specific training in the safe use and handling of radionuclides. Carcinogenesis, Mutagenesis, Impairment of Fertility Studies have not been conducted to evaluate carcinogenic potential or effects on fertility. When tested in vitro, NEUROLITE ® prepared with decayed generator eluate induced unscheduled DNA synthesis in rat hepatocytes and caused an increased frequency of sister chromatid exchanges in CHO cells; but, it did not induce chromosome aberrations in human lymphocytes or cause gene mutations in the Ames test or in a CHO/HGPRT test. Unreacted bicisate dihydrochloride increased the apparent rate of gene mutation of the TA 97a strain of S. typhimurium in the Ames test; but, it did not demonstrate clastogenic activity in an in vivo micronucleus assay in mice. Pregnancy: Teratogenic Effects Animal reproduction studies have not been conducted with Technetium Tc-99m Bicisate. It is also not known whether Technetium Tc-99m Bicisate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Therefore, Technetium Tc-99m Bicisate should not be administered to a pregnant woman unless the potential benefit justifies the potential risk to the fetus. Nursing Mothers Technetium Tc-99m Pertechnetate can be excreted in human milk. Therefore, formula should be substituted for breast milk until the technetium has cleared from the body of the nursing woman. Pediatric Use Safety and effectiveness in the pediatric population has not been established. Geriatric Use Of 808 patients in clinical studies of NEUROLITE®, 421 patients were 65 or older and 190 were 75 or older. Based on the evaluation of the frequency of adverse events and review of vital signs and laboratory data, no overall differences in safety were observed between these subjects and younger subjects. Although reported clinical experience has not identified differences in response between elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out. NEUROLITE ® is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to assess renal function prior to administration.

In clinical trials, NEUROLITE ® has been administered to 1063 subjects (255 normals, 808 patients). Of these, 566 (53%) were men and 494 (47%) were women. The mean age was 58 years (range 17 to 92 years). In the 808 patients, who had experienced neurologic events, there were 11 (1.4%) deaths, none of which were clearly attributed toNEUROLITE ® . A total of 60 subjects experienced adverse reactions; the adverse reaction rates were comparable in the <65 year, and the >65 year age groups. The following adverse effects were observed in ≤ 1% of the subjects: headache, dizziness, seizure, agitation/anxiety, malaise/somnolence, parosmia, hallucinations, rash, nausea, syncope, cardiac failure, hypertension, angina, and apnea/cyanosis. In clinical trials of 197 patients, there were inconsistent changes in the serum calcium and phosphate levels. The cause of the changes has not been identified and their frequency and magnitude have not been clearly characterized. None of the changes required medical intervention.

Teratogenic Effects Animal reproduction studies have not been conducted with Technetium Tc-99m Bicisate. It is also not known whether Technetium Tc-99m Bicisate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Therefore, Technetium Tc-99m Bicisate should not be administered to a pregnant woman unless the potential benefit justifies the potential risk to the fetus.

Technetium Tc-99m Pertechnetate can be excreted in human milk. Therefore, formula should be substituted for breast milk until the technetium has cleared from the body of the nursing woman.

Safety and effectiveness in the pediatric population has not been established.

Of 808 patients in clinical studies of NEUROLITE®, 421 patients were 65 or older and 190 were 75 or older. Based on the evaluation of the frequency of adverse events and review of vital signs and laboratory data, no overall differences in safety were observed between these subjects and younger subjects. Although reported clinical experience has not identified differences in response between elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out. NEUROLITE ® is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to assess renal function prior to administration.