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Technetium TC99mtilmanocept(Lymphoseek kit)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Kit for the Preparation of Technetium Tc 99m Sestamibi Injection safely and effectively. See full prescribing information for Kit for the Preparation of Technetium Tc 99m Sestamibi Injection.
Kit for the Preparation of Technetium Tc 99m Sestamibi Injection Kit for Intravenous use
Initial U.S. Approval: 1990
INDICATIONS AND USAGE
Technetium Tc 99m Sestamibi, is a myocardial perfusion agent indicated for:
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detecting coronary artery disease by localizing myocardial ischemia (reversible defects) and infarction (non-reversible defects) (1)
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eva luating myocardial function and developing information for use in patient management decisions (1)
DOSAGE AND ADMINISTRATION
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For Myocardial Imaging: The suggested dose range for I.V. administration of Technetium Tc 99m Sestamibi in a single dose to be employed in the average patient (70 Kg) is 370-1110 MBq (10-30 mCi) (2).
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For Breast Imaging: The recommended dose range for I.V. administration of Technetium Tc 99m Sestamibi is a single dose of 740-1110 MBq (20-30 mCi) (2).
DOSAGE FORMS AND STRENGTHS
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Kit for the Preparation of Technetium Tc 99m Sestamibi Injection is supplied as a 10 mL vial in a kit of five (5) (NDC # 0019-9092-20) or a carton of thirty (30) (NDC # 0019-9092-40), sterile and non-pyrogenic (3).
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Prior to lyophilization the pH is between 5.6–5.7. The contents of the vial are lyophilized and stored under nitrogen. Protect from light prior to reconstitution. Store at 15°–25°C (59°–77°F) before and after reconstitution (3).
CONTRAINDICATIONS
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Pharmacologic induction of cardiovascular stress may be associated with serious adverse events such as myocardial infarction, arrhythmia, hypotension, bronchoconstriction and cerebrovascular events (5.1).
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Technetium Tc 99m Sestamibi has been rarely associated with acute severe allergic and anaphylactic events of angioedema and generalized urticaria. In some patients the allergic symptoms developed on the second injection during Technetium Tc 99m Sestamibi imaging (5.1).
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Caution should be exercised and emergency equipment should be available when administering Technetium Tc 99m Sestamibi (5.1).
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Before administering Technetium Tc 99m Sestamibi patients should be asked about the possibility of allergic reactions to either drug (5.1).
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The contents of the vial are intended only for use in the preparation of Technetium Tc 99m Sestamibi and are not to be administered directly to the patient without first undergoing the preparative procedure (5.2).
ADVERSE REACTIONS
The following adverse reactions have been reported in > 0.5% of patients: signs and symptoms consistent with seizure occurring shortly after administration of the agent; transient arthritis; angioedema, arrhythmia, dizziness, syncope, abdominal pain, vomiting, and severe hypersensitivity characterized by dyspnea, hypotension, bradycardia, asthenia, and vomiting within two hours after a second injection of Technetium Tc 99m Sestamibi. A few cases of flushing, edema, injection site inflammation, dry mouth, fever, pruritis, rash, urticaria and fatigue have also been attributed to administration of the agent (6).
To report SUSPECTED ADVERSE REACTIONS, contact Mallinckrodt Inc. at 1-800-778-7898 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
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Specific drug-drug interactions have not been studied (7).
USE IN SPECIFIC POPULATIONS
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In one study of 46 subjects who received Technetium Tc 99m Sestamibi, the radioactivity in both children and adolescents exhibited blood PK profiles similar to those previously reported in adults (8.4).
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 8/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
Myocardial Imaging: Technetium Tc 99m Sestamibi Injection is a myocardial perfusion agent that is indicated for detecting coronary artery disease by localizing myocardial ischemia (reversible defects) and infarction (non-reversible defects), in eva luating myocardial function and developing information for use in patient management decisions. Technetium Tc 99m Sestamibi eva luation of myocardial ischemia can be accomplished with rest and cardiovascular stress techniques (e.g., exercise or pharmacologic stress in accordance with the pharmacologic stress agent's labeling).
It is usually not possible to determine the age of a myocardial infarction or to differentiate a recent myocardial infarction from ischemia.
Breast Imaging: Technetium Tc 99m Sestamibi is indicated for planar imaging as a second line diagnostic drug after mammography to assist in the eva luation of breast lesions in patients with an abnormal mammogram or a palpable breast mass.
Technetium Tc 99m Sestamibi is not indicated for breast cancer screening, to confirm the presence or absence of malignancy, and it is not an alternative to biopsy.
2 DOSAGE AND ADMINISTRATION
For Myocardial Imaging: The suggested dose range for I.V. administration of Technetium Tc 99m Sestamibi in a single dose to be employed in the average patient (70 Kg) is 370–1110 MBq (10–30 mCi).
For Breast Imaging: The recommended dose range for I.V. administration of Technetium Tc 99m Sestamibi is a single dose of 740–1110 MBq (20–30 mCi).
2.1 Image Acquisition
Breast Imaging: It is recommended that images are obtained with a table overlay to separate breast tissue from the myocardium and liver, and to exclude potential activity that may be present in the opposite breast. For lateral images, position the patient prone with the isolateral arm comfortably above the head, shoulders flat against the table, head turned to the side and relaxed, with the breast imaged pendent through an overlay cutout. The breast should not be compressed on the overlay. For anterior images, position the patient supine with both arms behind the head. For either lateral or anterior images, shield the chest and abdominal organs, or remove them from the field of view.
For complete study, sets of images should be obtained five minutes after the injection, and in the following sequence:
Beginning five minutes after the injection of Technetium Tc 99m Sestamibi:
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ten-minute lateral image of breast with abnormality
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ten-minute lateral image of contralateral breast
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ten-minute anterior image of both breasts
2.2 Radiation Dosimetry
The radiation doses to organs and tissues of an average patient (70 Kg) per 1110 MBq (30 mCi) of Technetium Tc 99m Sestamibi injected intravenously are shown in Table 1.
2.3 Instructions for Preparation
Preparation of the Technetium Tc 99m Sestamibi from the Kit for the Preparation of Technetium Tc 99m Sestamibi is done by the following aseptic procedure:
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Prior to adding the Sodium Pertechnetate Tc 99m Injection to the vial, inspect the vial carefully for the presence of damage, particularly cracks, and do not use the vial if found.
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Waterproof gloves should be worn during the preparation procedure. Remove the plastic disc from the vial and swab the top of the vial closure with alcohol to sanitize the surface.
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Place the vial in a suitable radiation shield with a fitted radiation cap.
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With a sterile shielded syringe, aseptically obtain additive-free, sterile, non-pyrogenic Sodium Pertechnetate Tc 99m Injection [925–5550 MBq, (25–150 mCi)] in approximately 1 to 3 mL.
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Aseptically add the Sodium Pertechnetate Tc 99m Injection to the vial in the lead shield. Without withdrawing the needle, remove an equal volume of headspace to maintain atmospheric pressure within the vial.
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Shake vigorously, about 5 to 10 quick upward-downward motions.
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Remove the vial from the lead shield and place upright in an appropriately shielded and contained boiling water bath, such that the vial is suspended above the bottom of the bath, and boil for 10 minutes. Timing for 10 minutes is begun as soon as the water begins to boil again. Do not allow the boiling water to come in contact with the aluminum crimp.
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Remove the vial from the water bath, place in the lead shield and allow to cool for fifteen minutes.
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Using proper shielding, the vial contents should be visually inspected. Use only if the solution is clear and free of particulate matter and discoloration.
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Assay the reaction vial using a suitable radioactivity calibration system. Record the Technetium Tc 99m concentration, total volume, assay time and date, expiration time and lot number on the radioassay information label and affix the label to the shield.
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Store the reaction vial containing the Technetium Tc 99m Sestamibi at 15° to 25°C (59° to 77°F) until use; at such time the product should be aseptically withdrawn. Technetium Tc 99m Sestamibi should be used within six hours of preparation. The vial contains no preservative.
Note: Adherence to the above product reconstitution instructions is recommended.
Mallinckrodt Inc.'s Kit for the Preparation of Technetium Tc 99m Sestamibi Injection is not to be used with the Recon-o-Stat™ thermal cycler due to the smaller vial size requirements of this heating device.
The potential for cracking and significant contamination exists whenever vials containing radioactive material are heated.
Product should be used within 6 hours after preparation.
Final product with radiochemical purity of at least 90% was used in the clinical trials that established safety and effectiveness. The radiochemical purity was determined by the following method.
2.4 Determination of Radiochemical Purity in Technetium Tc 99m Sestamibi
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Obtain a Baker-Flex Aluminum Oxide coated, plastic TLC plate, #1 B-F, pre-cut to 2.5 cm x 7.5 cm.
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Dry the plate or plates at 100°C for 1 hour and store in a desiccator. Remove pre-dried plate from the desiccator just prior to use.
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Apply 1 drop of ethanol* using a 1 mL syringe with a 22–26 gauge needle, 1.5 cm from the bottom of the plate. THE SPOT SHOULD NOT BE ALLOWED TO DRY.
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Add 2 drops of Technetium Tc 99m Sestamibi solution, side by side on top of the ethanol* spot. Return the plate to a desiccator and allow the sample spot to dry (typically 15 minutes).
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The TLC tank is prepared by pouring ethanol* to a depth of 3–4 mm. Cover the tank and let it equilibrate for ~10 minutes.
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Develop the plate in the covered TLC tank in ethanol* for a distance of 5 cm from the point of application.
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Cut the TLC plate 4 cm from the bottom and measure the Tc 99m activity in each piece by appropriate radiation detector.
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Calculate the % Tc 99m Sestamibi as:
*The ethanol used in this procedure should be 95% or greater. Absolute ethanol (99%) should remain at ≥95% ethanol content for one week after opening if stored tightly capped, in a cool dry place.
3 DOSAGE FORMS AND STRENGTHS
Kit for the Preparation of Technetium Tc 99m Sestamibi Injection is supplied as a 10 mL vial in a kit of five (5) (NDC # 0019-9092-20) or a carton of thirty (30) (NDC # 0019-9092-40), sterile and non-pyrogenic.
Prior to lyophilization the pH is between 5.6–5.7. The contents of the vial are lyophilized and stored under nitrogen. Protect from light prior to reconstitution. Technetium Tc 99m Sestamibi contains no preservatives.
Store at 15°–25°C (59°–77°F) before and after reconstitution.
Included in each five (5) vial kit is one (1) package insert and five (5) radioassay information labels. Included in each thirty (30) vial carton is one (1) package insert and thirty (30) radioassay information labels.
This reagent kit is approved by the U.S. Nuclear Regulatory Commission for distribution to persons licensed to use by-product material identified in §35.200 to 10 CFR Part 35, to persons who have a similar authorization issued by an Agreement State, and, outside the United States, to persons authorized by the appropriate authority.
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Warnings
In studying patients in whom cardiac disease is known or suspected, care should be taken to assure continuous monitoring and treatment in accordance with safe, accepted clinical procedure. Infrequently, death has occurred 4 to 24 hours after Tc 99m Sestamibi use and is usually associated with exercise stress testing [see Warnings and Precautions (5.2)].
Pharmacologic induction of cardiovascular stress may be associated with serious adverse events such as myocardial infarction, arrhythmia, hypotension, bronchoconstriction and cerebrovascular events. Caution should be used when pharmacologic stress is selected as an alternative to exercise; it should be used when indicated and in accordance with the pharmacologic stress agent's labeling.
Technetium Tc 99m Sestamibi has been rarely associated with acute severe allergic and anaphylactic events of angioedema and generalized urticaria. In some patients the allergic symptoms developed on the second injection during Tc 99m Sestamibi imaging. Patients who receive Technetium Tc 99m Sestamibi for either myocardial or breast imaging are receiving the same drug. Caution should be exercised and emergency equipment should be available when administering Technetium Tc 99m Sestamibi. Also, before administering Technetium Tc 99m Sestamibi Injection, patients should be asked about the possibility of allergic reactions to the drug.
5.2 General Precautions
The contents of the vial are intended only for use in the preparation of Technetium Tc 99m Sestamibi and are not to be administered directly to the patient without first undergoing the preparative procedure.
Radioactive drugs must be handled with care and appropriate safety measures should be used to minimize radiation exposure to clinical personnel. Also, care should be taken to minimize radiation exposure to the patients consistent with proper patient management.
Contents of the kit before preparation are not radioactive. However, after the Sodium Pertechnetate Tc 99m Injection is added, adequate shielding of the final preparation must be maintained. The components of the kit are sterile and non-pyrogenic. It is essential to follow directions carefully and to adhere to strict aseptic procedures during preparation.
Technetium Tc 99m labeling reactions depend on maintaining the stannous ion in the reduced state. Hence, Sodium Pertechnetate Tc 99m Injection containing oxidants should not be used.
Technetium Tc 99m Sestamibi should not be used more than six hours after preparation.
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.
Stress testing should be performed only under the supervision of a qualified physician and in a laboratory equipped with appropriate resuscitation and support apparatus.
The most frequent exercise stress test endpoints sufficient to stop the test reported during controlled studies (two-thirds were cardiac patients) were:
Fatigue 35%
Dyspnea 17%
Chest Pain 16%
ST-depression 7%
Arrhythmia 1%
6 ADVERSE REACTIONS
Adverse events were eva luated in 3741 adults who were eva luated in clinical studies. Of these patients, 3068 (77% men, 22% women, and 0.7% of the patients' genders were not recorded) were in cardiac clinical trials and 673 (100% women) in breast imaging trials. Cases of angina, chest pain, and death have occurred [see Warnings and Precautions (5)]. Adverse events reported at a rate of 0.5% or greater after receiving Technetium Tc 99m Sestamibi administration are shown in the following table:
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