Myoview

Overdose

No information provided.

Contraindications

None.

Undesirable effects

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Hypersensitivity Reactions

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of MYOVIEW cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions were evaluated in clinical studies (using an exercise/rest protocol) of 764 adults (511 men and 253 women) with a mean age of 58.7 years (range 29-94 years). The subjects received a mean dose of 285 MBq (7.7 mCi) on the first injection and 829 MBq (22.4 mCi) on the second injection of MYOVIEW.

After MYOVIEW injection, angina occurred in 4 subjects, ventricular tachycardia in 1 subject, and respiratory arrest in 1 subject.

The following reactions were noted in less than 1% of subjects:

Cardiovascular: angina, hypertension, torsades de pointes.

Gastrointestinal: vomiting, abdominal discomfort.

Hypersensitivity: cutaneous allergy, hypotension, dyspnea.

Special Senses: metallic taste, burning of the mouth, smell alteration.

In four studies, 438 adults (232 men and 205 women: gender was not recorded for one subject) with a mean age of 65 years (range 27-97 years) received a single pharmacologic stress agent. The subjects received a mean dose of 7 - 8 mCi on the rest/first injection and 22 - 34 mCi on the stress/second injection. Among the 438 subjects, 319 subjects (73%) experienced an adverse reaction. Reactions occurring in ≥ 1% of the subjects included angina (39%), flushing (36%), dyspnea (28%), headache (14%), abdominal pain (11%), dizziness (7%), palpitations (2%), nausea (2%), hypotension (1%) and pain (1%). Events occurring in < 1% include cough, arrhythmia, bronchospasm, ECG abnormalities, hypertension, vomiting and asthenia.

The following adverse reactions have been identified during post approval use of MYOVIEW. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most common adverse reactions reported included: rash, urticaria, abnormal vision, hypersensitivity reactions, and fever.

Therapeutic indications

Myocardial perfusion imaging under rest and/or exercise or pharmacologic stress conditions to delineate regions of reversible myocardial ischemia or infarcted myocardium in patients with known or suspected coronary artery disease.

MYOVIEW is indicated for assessment of left ventricular function (left ventricular ejection fraction and wall motion) in patients with known or suspected heart disease.

Pharmacodynamic properties

The relationship between Tc99m tetrofosmin plasma concentrations and successful imaging has not been explored in clinical trials.

Pharmacokinetic properties

Uptake in the myocardium is dependent on coronary flow and reaches a maximum of 1.2% of the injected dose (i.d.) at 5 minutes and 1% of the i.d. at 2 hours, respectively. Background activities in the blood, liver and lung were less than 5% of the administered activity in whole blood at 10 minutes post-injection, less than 4.5% i.d., after 60 minutes, and less than 2% i.d. after 30 minutes.

Approximately 66% of the injected activity is excreted within 48 hours post-injection, with approximately 40% excreted in the urine and 26% in the feces.

Date of revision of the text

Name of the medicinal product

Fertility, pregnancy and lactation

There are no data with technetium Tc 99m tetrafosmin use in pregnant women to inform any drug associated risks. Animal reproduction studies with technetium Tc 99m tetrofosmin have not been conducted. However, all radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. If considering technetium Tc 99m tetrafosmin administration to a pregnant woman advise the pregnant woman of risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Qualitative and quantitative composition

Kit for the preparation of technetium Tc 99m tetrofosmin injection: 10 mL multiple-dose, clear, glass vial with a white sterile, non-pyrogenic, lyophilized powder of 0.23 mg tetrofosmin, 0.03 mg stannous chloride dihydrate, 0.32 disodium sulphosalicylate, 1 mg sodium D-gluconate and 1.8 mg sodium hydrogen carbonate.

Following reconstitution with the Tc99m eluate, MYOVIEW is a clear solution not exceeding 1110 MBq/mL (30mCi/mL) of Tc99m.

Five (5) multiple-dose kits, each containing a 10 mL glass vial with a sterile, non-pyrogenic, lyophilized powder containing 0.23 mg tetrofosmin, 0.03 mg stannous chloride dihydrate, 0.32 mg disodium sulphosalicylate, 1 mg sodium D-gluconate, 1.8 mg sodium hydrogen carbonate.

NDC 17156-024-05

The radionuclide is not part of the kit. Before reconstitution and radiolabeling with Tc 99m, the contents of the kit are not radioactive.

Store the kit at 2°-8°C (36°-46°F). Protect the kit from light.

This reagent kit is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State; store and dispose of technetium Tc 99m tetrofosmin in accordance with these regulations.

Manufactured by: GE Healthcare AS, Oslo, Norway, Patent No. 5,045,302 (r). Distributed by: GE Healthcare, Medi-Physics, Inc., Arlington Heights, IL 60004. Revised: Apr 2017

Special warnings and precautions for use

Included as part of the PRECAUTIONS section.

Patients evaluated with exercise or pharmacologic stress may experience serious adverse reactions such as myocardial infarction, arrhythmia, hypotension, bronchoconstriction, and cerebrovascular reactions such as headache, paraesthesias, convulsions, somnolence and cerebrovascular accident, including hemorrhage. Perform stress testing in the setting where cardiac resuscitation equipment and trained staff are readily available. When pharmacologic stress is selected as an alternative to exercise, perform the procedure in accordance with the pharmacologic stress agent's prescribing information.

Technetium Tc99m contributes to a patient's overall long-term cumulative radiation exposure. Longterm cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling and preparation reconstitution procedures to protect patients and health care workers from unintentional radiation exposure. Encourage adequate hydration; instruct patients to void when the examination is completed and as often thereafter as possible.

Hypersensitivity reactions including anaphylaxis, dyspnea, bronchospasm, throat tightness, coughing, tachycardia, chest pain, hypotension, abdominal pain, and cutaneous reactions (rash, urticaria, pruritus, erythema, and swelling or angioedema) have been observed after the administration of MYOVIEW. Always have cardiopulmonary resuscitation equipment and personnel available and monitor all patients for hypersensitivity reactions.

Studies have not been conducted to evaluate carcinogenic potential or effects on fertility. Tetrofosmin sulphosalicylate was not mutagenic in vitro in the Ames test, mouse lymphoma, or human lymphocyte tests, nor was it clastogenic in vivo in the mouse micronucleus test.

There are no data with technetium Tc 99m tetrafosmin use in pregnant women to inform any drug associated risks. Animal reproduction studies with technetium Tc 99m tetrofosmin have not been conducted. However, all radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. If considering technetium Tc 99m tetrafosmin administration to a pregnant woman advise the pregnant woman of risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Technetium Tc99m tetrofosmin is present in human milk in small amounts ( < 1% of maternal dose). There are no data available regarding the effects of technetium Tc 99m tetrofosmin on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for MYOVIEW and any potential adverse effects on the breastfed child from MYOVIEW or from the underlying maternal condition.

To decrease radiation exposure to the breastfed infant, advise a lactating woman to pump and discard breast milk for 60 hours (10 half lives) after technetium Tc 99m tetrofosmin administration.

Safety and effectiveness in pediatric patients have not been established.

Of 2300 subjects in clinical studies of MYOVIEW, 1053 (46%) were 65 or older and 270 (12%) were 75 or older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Dosage (Posology) and method of administration

Technetium Tc99m tetrofosmin is a radioactive drug and should be handled with appropriate safety measures to minimize radiation exposure during administration.

1. The technetium Tc99m labeling reaction involved in the preparation of MYOVIEW Injection depends on maintaining tin in the divalent (reduced) state. Any oxidant present in the sodium pertechnetate Tc99m used may adversely affect the quality of the preparation. Sodium pertechnetate Tc99m containing oxidants should not be used for the preparation of the labeled product.
2. Elute the technetium generator with sodium chloride injection, USP.
3. Insert a venting needle (standard 18-26 gauge needle, not provided) through the rubber septum of the shielded vial containing the lyophilized powder.
4. Inject no more than 8.8 GBq (240 mCi) of technetium Tc99m generator eluate into the shielded vial.
5. Use sodium chloride injection, USP as a diluent. Inject 4-8 mL to achieve a radioactive concentration no greater than 1.1 GBq/mL (30 mCi/mL) in the vial.
6. Before removing the syringe from the vial, withdraw 2 mL of gas from above the solution.
7. Remove the venting needle.
8. Mix gently for 10 seconds to ensure complete dissolution of the powder.
9. Incubate at room temperature for 15 minutes.
10. Assay the total activity using a suitably calibrated instrument; complete the user radiation label and attach it to the vial.
11. Measure the pH of the prepared injection and verify it is between 7.5-9.0
12. Store the reconstituted MYOVIEW vial at 2°-25°C (36°-77°F) and use reconstituted injection within 12 hours of preparation.

Obtain the following materials:

1. Varian SA TLC strip (2 cm x 20 cm), do not heat activate
2. Ascending chromatography tank and cover
3. Mixture of acetone and dichloromethane (65:35% v/v), prepare freshly
4. Syringe (1 mL) with needle (22-25 gauge)
5. Suitable counting equipment

Perform the following:

1. Pour the 65:35% v/v acetone:dichloromethane mixture into the chromatography tank to a depth of 1 cm and cover the tank to allow the solvent vapor to equilibrate.
2. Mark a Varian SA TLC strip with a pencil line at 3 cm from the bottom and, using an ink marker pen, at 15 cm from the pencil line. The pencil line indicates the origin where the sample is to be applied and movement of color from the ink line will indicate the position of the solvent front when upward elution should be stopped.
3. Mark cutting positions at 3.75 cm and 12 cm above the origin [retention value (Rf) 0.25 and 0.8 respectively] in pencil.
4. Using a 1 mL syringe and needle, apply a 10 microliter sample of the prepared injection at the origin of the strip. Do not allow the spot to dry. Place the strip in the chromatography tank immediately and replace the cover. Ensure that the strip is not adhering to the walls of the tank. Note: A 10 microliter sample will produce a spot with a diameter of approximately 10 mm. Different sample volumes have been shown to give unreliable radiochemical purity values.
5. When the solvent reaches the ink line, remove the strip from the tank and allow it to dry.
6. Cut the strip into 3 pieces at the marked cutting positions and measure the activity on each using suitable counting equipment. Ensure similar counting geometry for each piece and minimize equipment dead time losses. Note: Free Tc99m pertechnetate runs to the top piece of the strip. MYOVIEW runs to the center piece of the strip. Reduced hydrolyzed Tc99m and any hydrophilic complex impurities remain at the origin in the bottom piece of the strip.
7. Calculate the radiochemical purity from:

% Tc99m tetrofosmin =	Activity of Center Piece (B)	X 100
	Total Activity of Three Pieces (A+B+C)

8. Do not use material if the radiochemical purity is less than 90%.

• Imaging may begin 15 minutes after injection.
• The recommended imaging duration of the scan may vary depending on dose, imaging acquisition, and reconstruction parameters.

Radiation absorbed dose per unit activity of the agent injected intravenously in an adult of average weight (74 kg) is estimated in Table 1 for exercise and resting conditions. The values listed correspond to a 3.5-hour voiding period for excretion from the urinary bladder.

Table 1 : Estimated Radiation Absorbed Dose (Technetium Tc99m Tetrofosmin Injection)

Interaction with other medicinal products and other forms of interaction

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Hypersensitivity Reactions

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of MYOVIEW cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions were evaluated in clinical studies (using an exercise/rest protocol) of 764 adults (511 men and 253 women) with a mean age of 58.7 years (range 29-94 years). The subjects received a mean dose of 285 MBq (7.7 mCi) on the first injection and 829 MBq (22.4 mCi) on the second injection of MYOVIEW.

After MYOVIEW injection, angina occurred in 4 subjects, ventricular tachycardia in 1 subject, and respiratory arrest in 1 subject.

The following reactions were noted in less than 1% of subjects:

Cardiovascular: angina, hypertension, torsades de pointes.

Gastrointestinal: vomiting, abdominal discomfort.

Hypersensitivity: cutaneous allergy, hypotension, dyspnea.

Special Senses: metallic taste, burning of the mouth, smell alteration.

In four studies, 438 adults (232 men and 205 women: gender was not recorded for one subject) with a mean age of 65 years (range 27-97 years) received a single pharmacologic stress agent. The subjects received a mean dose of 7 - 8 mCi on the rest/first injection and 22 - 34 mCi on the stress/second injection. Among the 438 subjects, 319 subjects (73%) experienced an adverse reaction. Reactions occurring in ≥ 1% of the subjects included angina (39%), flushing (36%), dyspnea (28%), headache (14%), abdominal pain (11%), dizziness (7%), palpitations (2%), nausea (2%), hypotension (1%) and pain (1%). Events occurring in < 1% include cough, arrhythmia, bronchospasm, ECG abnormalities, hypertension, vomiting and asthenia.

The following adverse reactions have been identified during post approval use of MYOVIEW. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most common adverse reactions reported included: rash, urticaria, abnormal vision, hypersensitivity reactions, and fever.

No information provided.