No information provided.
None known.
Rash with generalized erythema, facial edema and fever has been reported in less than 1% of patients. A transient increase in blood pressure was seen in 8% of patients.
Technetium Tc99m exametazime scintigraphy may be useful as an adjunct in the detection of altered regional cerebral perfusion in stroke.
Tc99m exametazime is indicated for leukocyte labeled scintigraphy as an adjunct in the localization of intra-abdominal infection and inflammatory bowel disease.
Studies in normal volunteers have shown that the technetium Tc99m complex of the RR,SS(d,l) diastereoisomer of exametazime is rapidly cleared from the blood after intravenous injection. Uptake in the brain reaches a maximum of 3.5-7.0% of the injected dose within one minute of injection. Up to 15% of the activity is eliminated from the brain by 2 minutes post injection, after which little activity is lost for the following 24 hours except by physical decay of technetium Tc99m. The activity not associated with the brain is widely distributed throughout the body, particularly in muscle and soft tissue. About 30% of the injected dose is found in the gastrointestinal tract immediately after injection and about 50% of this is excreted through the intestinal tract over 48 hours. Also, about 40% of the injected dose is excreted through the kidneys and urine over the 48 hours after injection.
No information provided.
PRECAUTIONSAs with any injected product, acute hypersensitivity or allergic reactions are possible. Limited reports have been received of hypersensitivity reactions following administration of Tc99m labeled leukocytes prepared using Tc99m exametazime. However, the materials used in leukocyte cell separation may cause hypersensitivity reactions. It is essential that cells are washed free of sedimentation agents before they are reinjected into the patient.
In case of side effects following administration of radiopharmaceuticals, users should ensure the availability of appropriate medical treatment at the time of administration of any radiopharmaceutical to the patient.
A thorough knowledge of the normal distribution of intravenously administered technetium Tc99m exametazime injection is essential in order to interpret pathologic studies accurately. Caution should be exercised in making the final diagnosis. Results can be affected by the presence of tumor, infarction, peritonitis, non-gastrointestinal or bony sites of inflammatory cell collections.
The contents of the Церетек vial are not radioactive. After the sodium pertechnetate Tc99m is added, the product is radioactive and adequate shielding of the final preparation must be maintained. The contents of the Церетек vial are intended only for use in preparation of technetium Tc99m exametazime injection and are NOT to be administered directly to the patient.
GeneralThe contents of the Церетек vial are sterile and pyrogen free. The vial contains no bacteriostatic preservative. It is essential that the user follow the directions carefully and adhere to strict aseptic procedures during preparation of the radiopharmaceutical.
Radiopharmaceuticals should be used only by or under the control of 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 governmental agency authorized to license the use of radionuclides.
To minimize radiation dose to the bladder, the patient should be encouraged to void when the examination is completed and as often thereafter as possible. Adequate hydration should be encouraged to permit frequent voiding.
Carcinogenesis, Mutagenesis, Impairment of FertilityLong term animal studies have not been performed to evaluate carcinogenic potential or whether exametazime affects fertility in males or females. When evaluated in the Ames test, exametazime increased the apparent rate of gene mutation in the TA100 strain of S. typhimurium. Exametazime did not cause chromosomal aberrations in vitro (Chinese Hamster Ovary cells) or in vivo (rat bone marrow).
Pregnancy Category C
Animal reproduction studies have not been conducted with Tc99m exametazime. It is also not known whether Tc99m exametazime can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity. Therefore, Tc99m exametazime should not be administered to a pregnant woman unless the potential benefit justifies the potential risk to the fetus.
Nursing MothersTechnetium Tc99m is excreted in human milk during lactation. It is not known whether exametazime is excreted in human milk. Therefore, formula feedings should be substituted for breast feeding for 60 hours.
Pediatric UseSafety and effectiveness in pediatric patients have not been established.
Geriatric UseClinical studies of Церетек™ 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.
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.
Tc99m labeled leukocytes for adjunctive localization of intra-abdominal infection or inflammation.
The normal adult (70 kg) dose is 0.259-0.925 GBq (7-25 mCi) as Tc99m labeled leukocytes by intravenous injection. Optimal planar imaging is between 2-4 hours.
Cerebral ScintigraphyThe recommended dose range for i.v. administration, of reconstituted sodium pertechnetate Tc99m exametazime in the average adult (70 kg) is 370-740 MBq (10-20 mCi).
Dynamic imaging may be performed between 0 to 10 minutes following injection. Static imaging may be performed from 15 minutes up to 6 hours after injection.
Instructions For Preparation And UseThe technetium Tc99m labeling reaction involved in preparing technetium Tc99m exametazime injection depends on maintaining tin in the divalent (reduced) state. Any oxidant present in the sodium pertechnetate Tc99m employed may adversely affect the quality of the preparation. Sodium pertechnetate Tc99m containing oxidants should not be used for the preparation of the labeled product. To meet the last requirement, a generator must be eluted within 24 hours prior to obtaining any elute for reconstitution with the Церетек kit.
Sodium Chloride Injection, USP must be used as the diluent. Do not use bacteriostatic sodium chloride as a diluent for sodium pertechnetate Tc99m injection because it will increase the oxidation products and adversely affect the biological distribution of Церетек.
The contents of the Церетек vial are sterile and pyrogen free. The vial contains no bacteriostatic preservative. It is essential that the user follow the directions carefully and adhere to strict aseptic procedures during preparation of the radiopharmaceutical.
Technetium Tc99m exametazime injection, like other radioactive drugs, must be handled with care and appropriate safety measures should be used to minimize radiation exposure to clinical personnel. Care should also be taken to minimize radiation exposure to the patient consistent with proper patient management.
Care should be taken when handling blood specimens to be labeled using this radiopharmaceutical. Even if the subject has been tested, no method can offer complete assurance that Hepatitis B Virus, Human Immuno-deficiency Virus (HIV) or other infectious agents are absent. All human blood samples should be considered potentially infectious. Precautions for handling are as those for handling radioactive materials.
Procedure for the preparation of Tc99m Exametazime InjectionNote: Sterile technique must be used throughout. The user should wear waterproof gloves during the handling and administration procedure.
Note: Sterile technique must be used throughout. The user should wear waterproof gloves during the handling and administration procedure.
Radiochemical purity determination must be performed before administration to the patient. Three potential radiochemical impurities may be present in the prepared injection of the lipophilic technetium Tc99m exametazime complex.
These are a secondary technetium Tc99m exametazime complex, free pertechnetate, and reduced-hydrolyzed-technetium Tc99m. A combination of 3 chromatographic systems is necessary for the complete definition of the radiochemical composition of the injection.
The following protocol has been designed to enable analysis of the radiochemical purity of Церетек (99mTc-exametazime). It should be started within 2 minutes of reconstitution. The entire procedure takes approximately 15 minutes.
Equipment and EluentsSA ITLC strips 20 cm x 2.0 cm
Whatman No. 1 strips 6 cm x 0.7 cm
MEK (methyl ethyl ketone [butanone]) (99.9 + % HPLC Grade)
0.9% aqueous sodium chloride (non-bacteriostatic)
50% aqueous acetonitrile (99.9 + % HPLC Grade)
Dilute with non-bacteriostatic Water for Injection
Glass test tubes (12 x 75 mm)
Glass measuring cylinders (100 mL) with covers
1 mL syringes with 25 gauge needles
% bottom of saline strip – % bottom of MEK strip
(= % lipophilic exametazime complex)
% top of saline strip (= % pertechnetate)
% bottom of Whatman No. 1 paper strip (= % reduced-hydrolyzed-Tc)
A radiochemical purity of > 80% may be expected provided the measurement has been carried out within 4 hours of reconstitution for stabilized Церетек and 30 minutes for Церетек used for WBC labeling.
Interpretation of ChromatogramSystem 1 (SA ITLC: MEK [butanone])
Secondary Tc exametazime complex and reduced-hydrolyzed-Tc remain at the origin.
Lipophilic Tc exametazime complex and pertechnetate migrate at Rf 0.8-1.0.
System 2 (SA ITLC: 0.9% sodium chloride) Lipophilic-Tc exametazime complex, secondary Tc exametazime complex and reducedhydrolyzed-Tc remain at the origin. Pertechnetate migrates at Rf 0.8-1.0.
System 3 (Whatman No. 1: 50% aqueous acetonitrile) Reduced-hydrolyzed-Tc remains at the origin. Lipophilic Tc exametazime complex, secondary Tc exametazime complex and pertechnetate migrate at Rf 0.8-1.0.
Radiation DosimetryBased on human data, the absorbed radiation doses to an average human adult (70 kg) from an intravenous injection of this product are estimated below. The values are listed as μGy/MBq, rads/mCi with urination every 2 hours. Bladder wall dose is 19 μGy/MBq, 0.07 rads/mCi with 4 hour urination and 89 μGy/MBq, 0.33 rads/mCi with no urination.
Table 4: Estimated Absorbed Radiation Dose* for Cerebral Scintigraphy
Target Organ | Absorbed radiation dose Tc99m exametazime injection | |||
μGy/MBq | rads/mCi | mGy/740 MBq | rads/20 mCi | |
Lachrymal Glands | 69.4 | 0.258 | 51.36 | 5.16 |
Gallbladder Wall | 51 | 0.19 | 37.74 | 3.8 |
Kidney | 35 | 0.13 | 25.9 | 2.6 |
Thyroid | 27 | 0.1 | 19.98 | 2 |
Upper Large Intestine Wall | 21 | 0.079 | 15.54 | 1.58 |
Liver | 15 | 0.054 | 11.1 | 1.08 |
Small Intestine Wall | 12 | 0.044 | 8.88 | 0.88 |
Lower Large Intestine Wall | 15 | 0.054 | 11.1 | 1.08 |
Urinary Bladder Wall | 13 | 0.047 | 9.62 | 0.94 |
Brain | 6.9 | 0.026 | 5.11 | 0.52 |
Ovaries | 6.3 | 0.023 | 4.66 | 0.46 |
Testes | 1.8 | 0.007 | 1.33 | 0.14 |
Whole Body | 3.6 | 0.013 | 2.66 | 0.26 |
Red Marrow | 3.4 | 0.013 | 2.52 | 0.26 |
Bone Surfaces | 4.8 | 0.018 | 3.55 | 0.36 |
Eyes | 6.9 | 0.026 | 5.11 | 0.52 |
* Data supplied by Oak Ridge Associated Universities, Radiopharmaceutical Internal Dose Information Center. |
Table 5: In vivo Localization of Tc99m Labeled Leukocytes
The estimated absorbed radiation doses to various organs following the intravenous administration of Tc99m labeled leukocytes given by ICRP 53** are as follows (bladder voiding every 3.5 hours)
Target Organ | Absorbed Radiation Dose | |
(mGy per 200 MBq) | rads/25 mCi | |
Spleen | 30 | 13.89 |
Red Marrow | 4.4 | 2.04 |
Liver | 4 | 1.85 |
Pancreas | 2.8 | 1.3 |
Ovaries | 0.84 | 0.39 |
Testes | 0.34 | 0.16 |
Uterus | 0.76 | 0.35 |
Effective Dose Equivalent (EDE) 3.4 mSv/200 MBq. ** International Commission on Radiological Protection, “Radiation Dose to Patients from Radiopharmaceuticals”, ICRP 53, 1988. |