 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CIS Sulfur ColloidDESCRIPTIONCIS-SULFUR COLLOID™ Kit for the Preparation of Technetium Tc 99m Sulfur Colloid Injection is a multidose reaction vial with a Solution A vial and a Solution B vial which contain the sterile non-pyrogenic, non-radioactive ingredients necessary to produce Technetium Tc 99m Sulfur Colloid Injection for diagnostic use by intravenous injection or oral administration. Each 10 mL multidose reaction vial contains, in lyophilized form 2.0 mg sodium thiosulfate anhydrous, 2.3 mg edetate disodium and 18.1 mg gelatin; a Solution A vial with 1.8 mL of 0.148 N hydrochloric acid solution and a Solution B vial with 1.8 mL aqueous solution of 24.6 mg/mL sodium biphosphate anhydrous and 7.9 mg/mL sodium hydroxide. When a solution of sterile and non-pyrogenic Sodium Pertechnetate Tc 99m Injection in isotonic saline is mixed with these components, following the instructions provided with the kit, Technetium Tc 99m Sulfur Colloid Injection is formed. The product so derived is intended for intravenous injection or oral administration. The precise structure of Technetium Tc 99m Sulfur Colloid Injection is not known at this time. Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours1. The principal photon that is useful for detection and imaging studies is listed in Table 1.
External radiation The specific gamma ray constant for Tc 99m is 0.78 R/millicurie-hr at 1 cm. The first half-value layer is 0.017 cm of lead (Pb). A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 2. For example, the use of a 0.25 cm thickness of Pb will attenuate the radiation emitted by a factor of about 1,000.
CLINICAL PHARMACOLOGYFollowing intravenous administration, Technetium Tc 99m Sulfur Colloid Injection is rapidly cleared by the reticuloendothelial system from the blood with a nominal clearance half-life of approximately 2 1/2 minutes. Uptake of the radioactive colloid by organs of the reticuloendothelial system is dependent upon both their relative blood flow rates and the functional capacity of the phagocytic cells. In the average patient 80 to 90% of the injected colloidal particles are phagocytized by the Kupffer cells of the liver, 5 to 10% by the spleen and the balance by the bone marrow. Following administration of Technetium Tc 99m Sulfur Colloid Injection by intraperitoneal injection, the radiopharmaceutical mixes with the peritoneal fluid. Clearance from the peritoneal cavity varies from insignificant, which may occur with complete shunt blockage, to very rapid clearance with subsequent transfer into the systemic circulation when the shunt is patent. Serial images should be obtained of both the shunt and liver (target organ). However, an adequate evaluation of the difference between total blockage of the shunt and partial blockage may not be feasible in all cases. INDICATIONSAND USAGETechnetium Tc 99m Sulfur Colloid Injection is used in adults and children as an agent for imaging areas of functioning reticuloendothelial cells in the liver, spleen and bone marrow. It is used orally in adults and children for esophageal transit studies, gastroesophageal reflux scintigraphy, and for the detection of pulmonary aspiration of gastric contents. Technetium Tc 99m Sulfur Colloid may be used in adults as an imaging agent to aid in the evaluation of peritoneo-venous (LaVeen) shunt patency. Geriatric Use Clinical studies of CIS-SULFUR COLLOIDTM did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. DOSAGE AND ADMINISTRATIONShielding should be utilized when preparing Technetium Tc 99m Sulfur Colloid Injection. Liver-Spleen Scanning and Bone Marrow Imaging In average ADULT (70 kg) patients: The suggested dose range used for liver/spleen images is 37 to 296 megabecquerels (1 to 8 millicuries) and for bone marrow images is 111 to 444 megabecquerels (3 to 12 millicuries) of Technetium Tc 99m Sulfur Colloid Injection. In PEDIATRIC patients: The suggested intravenous doses employed for various diagnostic indications are as follows: Liver/spleen imaging: The dose range is 0.56 to 2.78 megabecquerels (15 to 75 microcuries) per kilogram of body weight with a usual dose of 1.85 megabecquerels (50 microcuries) per kg body weight, except in newborns in whom the administered dose should be 7.4 to 18.5 megabecquerels (200 to 500 microcuries). A minimum dose of 7.4 megabecquerels (200 microcuries) should be employed for this procedure. Bone marrow imaging: The dose range is 1.11 to 5.55 megabecquerels (30 to 150 microcuries) per kilogram of body weight. A minimum dose of 22.2 megabecquerels (600 microcuries) is suggested for this procedure. (See Table 5) Gastroesophageal and Pulmonary Aspiration In average ADULT (70 kg) patients: The suggested oral dose range is 5.55-11.1 megabecquerels (150-300 microcuries) for gastroesophageal studies. The suggested oral dose range for pulmonary aspiration studies is 11.1-18.5 megabecquerels (300-500 microcuries). In PEDIATRIC patients: The suggested oral dose range in infants and children is 3.7-11.1 megabecquerels (100-300 microcuries) for gastroesophageal and pulmonary aspiration studies. The drug should be incorporated into a milk feeding when administered orally. Equally good results may be obtained by intubating the stomach and directly instilling the material into the stomach, followed by a dextrose or milk meal. This latter method avoids the introduction of radiation into the esophagus: thus, any tracer appearing there must be due to reflux. The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Peritoneo-Venous (LeVeen) Shunt Patency Evaluation The suggested intraperitoneal dosage range used in the average patient (70 kg) for peritoneo-venous (LeVeen) shunt patency evaluation is 37 to 111 megabecquerels (1 to 3 millicuries). Adequate measures should be taken to assure uniform mixing with peritoneal fluid. Serial images of both the shunt and target organ should be obtained and correlated with other clinical findings. Alternately, the drug may be administered by percutaneous transtubal injection. The suggested percutaneous transtubal (efferent limb) dosage range for the average patient (70 kg) is 12 to 37 megabecquerels (0.3 to 1.0 millicurie) in a volume not to exceed 0.5 mL. Transperitoneal absorption of Sulfur Colloid may occur, but it occurs slowly. Therefore, the most definitive scintigraphic evaluation of shunt patency will be obtained if there is visualization of both the shunt itself and the liver and/or spleen within the first three hours post intraperitoneal injection. Radiation Dosimetry The estimated absorbed radiation doses2 to an average ADULT patient (70 kg) from an intravenous injection of a maximum dose of 296 megabecquerels (8 millicuries) of Technetium Tc 99m Sulfur Colloid Injection are shown in Table 4.
Pediatric radiation doses In PEDIATRIC patients, the radiation absorbed doses, using the maximum recommended doses for liver/spleen imaging [2.78 megabecquerels (75 microcuries) per kilogram of body weight] and for bone marrow imaging [5.55 megabecquerels (150 microcuries) per kilogram of body weight], except in the newborn where the doses used for calculating the radiation absorbed dose estimates are 18.5 megabecquerels (500 microcuries) for liver/spleen imaging and 22.2 megabecquerels (600 microcuries) for bone marrow imaging, are shown in Table 5.
Assumptions
Assumptions Calculations for the absorbed radiation dose are based upon an effective half-time of 3 hours for the open shunt and 6.02 hours for the closed shunt and an even distribution of the radiopharmaceutical in the peritoneal cavity with no biological clearance. HOW SUPPLIED The CIS-SULFUR COLLOID™ is supplied as a 5-kit package. Five complete kits are included in each package. All components are sterile and non-pyrogenic. Each 10mL multidose reaction vial contains, in lyophilized form, 2.0 mg sodium thiosulfate anhydrous, 2.3 mg edetate disodium and 18.1 mg gelatin; each Solution A vial contains 1.8 mL 0.148 N hydrochloric acid solution and each Solution B vial contains 1.8 mL aqueous solution of 24.6 mg/mL sodium biphosphate anhydrous and 7.9 mg/mL sodium hydroxide. Included in each 5-kit package are one package insert and 10 radiation labels. Store the kit as packaged at 15-30°C. Directions for Use Technetium Tc 99m Sulfur Colloid Injection is prepared from CIS-Sulfur Colloid™ by the following aseptic procedure:
NDC # 45567-0030-1 This reagent kit for the preperation of a radiopharmaceutical is approved for use by persons licensed pursuant to Section 120.533, Code of Massachusetts Regulation 105, or under equivalent license of the U.S. Nuclear Regulatory Commission or an Agreement State. CIS-SULFUR COLLOID™ Kit for Preparation of Technetium Tc99m Sulfur Colloid Injection Diagnostic -For Intravenous and Oral Use Revised on 09 Dec 2002 SIDE EFFECTSThe following adverse reactions have been reported associated with the use of Technetium Tc 99m Sulfur Colloid Injection: cardiopulmonary arrest, seizures, anaphylactic shock, hypotension, dyspnea, abdominal pain, fever, chills, bronchospasm, nausea, vomiting, perspiration, redness, urticaria, numbness, dizziness and burning at the injection site. Several deaths and cases of lung and soft tissue uptake other than RES have been reported in association with the use of Technetium Tc 99m Sulfur Colloid Injection (see WARNINGS). The size and physical-chemical properties of the sulfur colloid particles formed from the components of the kit may determine the biodistribution of the colloid and its uptake by the RE system. Diseases affecting the RE system may also alter the expected uptake pattern. DRUG INTERACTIONSNo information available. WARNINGSAlthough rare, deaths have occurred following intravenously administered gelatin stabilized Technetium Tc 99m Sulfur Colloid Injection. Advanced cardiopulmonary life support systems should be readily available where and when the drug is administered. PRECAUTIONSGeneral The contents of the two Solution vials, the Solution A vial containing the appropriate acidic solution and the Solution B vial containing the appropriate buffer solution, are intended only for use in the preparation of the Technetium Tc 99m Sulfur Colloid Injection and are NOT to be directly administered to the patient. Sodium Pertechnetate Tc 99m Injection containing oxidants should not be used to reconstitute this kit. The contents of the kit are not radioactive. However, after the Sodium Pertechnetate Tc 99m Injection is added, adequate shielding of the final preparation must be maintained. The contents of the kit are sterile and non-pyrogenic. It is essential to follow the directions carefully and to adhere strictly to aseptic procedures during preparation. This preparation contains no bacteriostatic preservative. The stability of the colloidal preparation may be decreased in the presence of polyvalent cations, thus resulting in the agglomeration of the individual colloidal particles. These larger particles are likely to be trapped by the pulmonary capillary bed following intravenous injection. Sodium Pertechnetate Tc 99m Injection containing more than 10 micrograms per milliliter of aluminum ion should not be used to formulate the Technetium Tc 99m Sulfur Colloid Injection. Technetium Tc 99m Sulfur Colloid Injection is physically unstable, and the particles will settle with time. Failure to agitate the vial adequately before use may result in non-uniform distribution of radioactivity. Because of the increasing probability of agglomeration with aging, it is recommended that a vial of the prepared finished drug should not be used more than six hours from the time of formulation. The components of CIS-Sulfur Colloid™ are supplied sterile and non-pyrogenic. Aseptic procedures normally employed in making additions and withdrawals for sterile, non-pyrogenic containers should be used during addition of the pertechnetate solution and the withdrawal of doses for patient administration. No special handling is required for the non-radioactive drug product. Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides. As in the use of any other radioactive material, care should be taken to minimize radiation exposure to patient and clinical personnel, consistent with proper patient management. Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to evaluate carcinogenic potential or whether Technetium Tc 99m Sulfur Colloid Injection affects fertility in males or females. Mutagenesis studies have not been conducted. Pregnancy Category C Animal reproduction and teratogenicity studies have not been conducted with Technetium Tc 99m Sulfur Colloid Injection. It is also not known whether Technetium Tc 99m Sulfur Colloid Injection can cause fetal harm when administered to a pregnant woman, or can affect reproductive capacity. There have been no studies in pregnant women. Technetium Tc 99m Sulfur Colloid Injection should be given to a pregnant woman only if clearly needed. Ideally, examinations using radiopharmaceuticals, especially those elective in nature, of a woman of childbearing capability, should be performed during the first few (approximately 10) days following the onset of menses. Nursing Mothers Technetium Tc 99m is excreted in human milk during lactation. Therefore, formula feeding should be substituted for breast feeding. Geriatric Use Clinical studies of Sulfur Colloid did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. This drug 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 monitor renal function.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||