CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Following intravenous administration for renal imaging, Technetium Tc 99m Mertiatide is rapidly cleared from the blood. It is cleared by the kidneys and excreted in the urine.. 12.2 Pharmacodynamics. Following intravenous injection of technetium Tc 99m mertiatide, the uptake, concentration, and excretion of the tracer by the kidney can be monitored to assess renal function.. 12.3 Pharmacokinetics. DistributionAfter an intravenous administration in healthy adult subjects, 89% of technetium Tc 99m mertiatide was plasma-protein bound. The protein binding is reversible.EliminationExcretionIn healthy subjects, the plasma clearance was approximately 0.3 liters/minute and the amount of technetium Tc 99m mertiatide excreted in the urine in hours was nearly 90% of the injected dose. Specific PopulationsPatients with Renal ImpairmentIn study performed in three patients with renal impairment (serum creatinine greater than 6.3 mg/dL), 78% of the tracer was plasma protein bound after intravenous injection. The mean plasma clearance of technetium Tc 99m mertiatide was 0.03 liters/minute and 21.3% was excreted in hours on average. In both healthy subjects and patients with renal impairment, the plasma concentration-time profile showed biexponential decline.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None.. None. (4).

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions associated with the use of Technetium Tc 99m Mertiatide Injection were identified in clinical studies or postmarketing reports. Because some of these reactions are voluntarily reported from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Cardiac disorders: tachycardia.Gastrointestinal disorders: nausea, vomiting.General disorders and administration site conditions: shaking chills, fever.Nervous system disorders: seizure.Respiratory, thoracic and mediastinal disorders: wheezing, dyspnea.Skin and subcutaneous tissue disorders: itching, rash.Vascular disorders: elevation in blood pressure.. Reported adverse reactions are: tachycardia, nausea, vomiting, shaking chills, fever, seizure, wheezing, dyspnea, itching, rash, and elevation in blood pressure. (6)To report SUSPECTED ADVERSE REACTIONS, contact Jubilant DraxImage Inc. at 1-888-633-5343 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. No long term animal studies have been performed to evaluate carcinogenic or mutagenic potential, or whether this drug affects fertility in males or females.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. No long term animal studies have been performed to evaluate carcinogenic or mutagenic potential, or whether this drug affects fertility in males or females.

OVERDOSAGE SECTION.

10 OVERDOSAGE. In the event of an overdose of technetium Tc 99m mertiatide, hydration and frequent micturition should be encouraged to minimize the absorbed radiation dose to patient. diuretic might also be considered. If possible, an estimate of the radiation effective dose given to the patient should be made.

DESCRIPTION SECTION.

11 DESCRIPTION. 11.1 Chemical Characteristics. Kit for the Preparation of Technetium Tc 99m Mertiatide Injection is sterile, multiple-dose kit for the preparation of technetium Tc 99m mertiatide injection, radioactive diagnostic agent for intravenous use.The active ingredient, betiatide, is N-[N-[N-[(benzoylthio) acetyl]glycyl]glycyl]-glycine and has molecular weight of 367.38 g/mol. After reconstitution with sodium pertechnetate Tc 99m injection, the radioactive agent technetium Tc 99m mertiatide (disodium[N-[N-[N- (mercaptoacetyl) glycyl]glycyl] glycinato (2-) N,N,N,S]oxotechnetate (2-)) is formed in situ.Each 10 mL vial contains mg betiatide, 20 mg lactose monohydrate, 40 mg sodium tartrate dihydrate, 0.07 mg (minimum) stannous chloride dihydrate and 0.2 mg (maximum) total tin expressed as stannous chloride dihydrate. Prior to lyophilization, hydrochloric acid is added for pH adjustment. The vial contents are sealed under argon.After radiolabeling with sodium pertechnetate Tc 99m injection, each vial contains up to 3,700 MBq (100 mCi) of technetium Tc 99m mertiatide in 0.9% sodium chloride injection in approximately 10 mL volume as sterile, clear, and colorless solution with pH between and 6.. betiatide-chem-stuct. tc-99m-mertiatide. 11.2 Physical Characteristics. Technetium Tc 99m decays by isomeric transition with physical half-life of 6.02 hours. The principal photon that is useful for detection and imaging is listed in Table 2.Table 2. Principal Radiation Emission Data Radiation Mean per Disintegration Energy (keV) Gamma-2 89.07 140.5To correct for physical decay of the radionuclide, the fractions that remain at selected time intervals after the time of calibration are shown in Table 3. Table 3. Physical Decay Chart: Technetium Tc 99m, Half-life 6.02 Hours Hours Fraction Remaining Hours Fraction Remaining 1.000 0.447 0.891 0.398 0.794 0.355 0.708 10 0.316 0.631 11 0.282 0.562 12 0.251 0.501 Calibration Time. 11.3 External Radiation. The specific gamma ray constant for technetium-99m is 0.78 R/mCi-hr at cm. The first half-value thickness of lead (Pb) for technetium-99m is 0.017 cm. The use of 0.25 cm of Pb, for example, will decrease the external radiation exposure by factor of about 1,000. Table displays the radiation attenuation by lead shielding. Table 4. Radiation Attenuation by Lead Shielding Shield Thickness (Pb) cm Coefficient of Attenuation 0.017 0.5 0.08 10-1 0.16 10-2 0.25 10-3 0.33 10-4.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Instruct patients to drink sufficient amount of water before administration and continue to drink and to void frequently following administration. (2.2)Recommended dose in adult patients:185 MBq to 370 MBq (5 mCi to 10 mCi) as an intravenous bolus injection. (2.3)Recommended dose in pediatric patients aged 30 days and older: 2.6 MBq/kg to 5.2 MBq/kg (0.07 mCi/kg to 0.14 mCi/kg) with minimum dose of 37 MBq (1 mCi) as an intravenous bolus injection. (2.3)See Full Prescribing Information for radiation safety, drug preparation, administration, and radiation dosimetry information. (2.1, 2.4, 2.5, 2.6, 2.7). Instruct patients to drink sufficient amount of water before administration and continue to drink and to void frequently following administration. (2.2). Recommended dose in adult patients:185 MBq to 370 MBq (5 mCi to 10 mCi) as an intravenous bolus injection. (2.3). Recommended dose in pediatric patients aged 30 days and older: 2.6 MBq/kg to 5.2 MBq/kg (0.07 mCi/kg to 0.14 mCi/kg) with minimum dose of 37 MBq (1 mCi) as an intravenous bolus injection. (2.3). See Full Prescribing Information for radiation safety, drug preparation, administration, and radiation dosimetry information. (2.1, 2.4, 2.5, 2.6, 2.7). 2.1 Radiation Safety Drug Handling. After radiolabeling, the kit produces Technetium Tc 99m Mertiatide Injection. Handle Technetium Tc 99m Mertiatide Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions (5.1)]. Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Technetium Tc 99m Mertiatide Injection.Radiopharmaceuticals should be used by or under the control of healthcare providers who are qualified by specific 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.. 2.2 Patient Preparation. Instruct patients to drink sufficient amount of water to ensure adequate hydration prior to administration of Technetium Tc 99m Mertiatide Injection and to continue to drink and void frequently following administration to reduce radiation exposure.. 2.3 Recommended Dosage. AdultThe recommended dose in adult patients is 185 MBq to 370 MBq (5 mCi to 10 mCi) as an intravenous bolus injection.PediatricThe recommended dose in pediatric patients aged 30 days and older is 2.6 MBq/kg to 5.2 MBq/kg (0.07 mCi/kg to 0.14 mCi/kg) of actual body weight with minimum dose of 37 MBq (1 mCi) as an intravenous bolus injection.. 2.4 Drug Preparation and Handling. Procedural PrecautionsContents of the vials are intended only for use in the preparation of Technetium Tc 99m Mertiatide Injection, and are NOT to be administered directly to the patient.Do not use Sodium Pertechnetate Tc 99m Injection USP more than hours after its elution from the generator.Use aseptic techniques for all transfers and vial stopper entries.Wear waterproof gloves during the procedure, particularly during the heating of the sample with boiling water.Use suitable shielding to reduce radiation exposure. Use one lead shield for incubation with water bath and another lead shield for dispensing as described in the Procedure for the Preparation of Technetium Tc 99m Mertiatide Injection section below. Make all transfers of sodium pertechnetate Tc 99m solution during the preparation procedure with an adequately shielded syringe.Procedure for the Preparation of Technetium Tc 99m Mertiatide InjectionPrepare rolling boil water bath containing lead incubation vial shield with openings cut in it to allow the water to circulate through the shield. Orient the openings of the lead incubation shield to prevent radiation leakage. Note: The vial should be in direct contact with the rolling boil water of the bath, and the level of the bath must be at least even with the level of the contents of the vial.Ensure the temperature of the water bath used for heating the reaction vial is at boiling temperature and the temperature of the lead incubation vial shield is equilibrated to the temperature of the water bath before proceeding with the preparation procedure below. Place the reaction vial in lead dispensing shield fitted with lid and with minimum wall thickness of 0.32 cm.Swab the rubber stopper of the reaction vial with an appropriate antiseptic wipe. Insert filter-containing venting needle (provided) through the vial stopper.Add mL to 10 mL of Sodium Pertechnetate Tc 99m Injection USP containing 740 MBq to 3,700 MBq (20 mCi to 100 mCi) into the vial using sterile syringe. If necessary, dilute the Sodium Pertechnetate Tc 99m Injection USP with 0.9% Sodium Chloride Injection USP to the desired concentration prior to addition to the vial.Immediately following the addition of Sodium Pertechnetate Tc 99m Injection USP to the reaction vial, withdraw the syringe plunger to volume of mL, thus removing mL of argon gas, which adds mL of filtered air to the vial to oxidize excess stannous ion and to prevent the formation of technetium-99m labeled impurities. Note:The sample vial must be placed in boiling water bath within minutes of the addition of Sodium Pertechnetate Tc 99m solution.Remove both needles from the vial.Invert the reaction vial several times to obtain complete mixing, prior to heating.Immediately transfer the reaction vial to the water bath. Place it inside the lead incubation shield which has been equilibrated to the temperature of the boiling water bath. The reaction vial should be in direct contact with the rolling boil water of the bath, and the level of the water must be at least even with the level of the contents of the vial. Incubate the reaction vial for 10 minutes.Remove the reaction vial from the boiling water bath and place it in the lead dispensing shield. Allow the contents of the vial to cool for approximately 15 minutes.Using proper shielding, visually inspect the vial contents. The solution should be clear and free of particulate matter. If not, do not use the preparation.Assay the reaction vial using suitable radioactivity calibration system. Record the date, time, total activity, volume, and concentration on the radioassay information label and affix the label to the lead dispensing shield.Test the radiochemical purity of the prepared Technetium Tc 99m Mertiatide Injection according to the recommended method [see Dosage and Administration (2.5) ]. If the radiochemical purity is less than 90%, do not use the product.Test the radiochemical impurities of the prepared Technetium Tc 99m Mertiatide Injection according to the recommended method [see Dosage and Administration (2.5) ]. If the sum of the hydrophilic impurities and non-elutable impurities is more than 10%, do not use the product.Use the Technetium Tc 99m Mertiatide Injection within hours of radiolabeling and store it at room temperature 15C to 30C (59F to 86F) until use.Handle and dispose unused radioactive material in accordance with applicable regulations.. Contents of the vials are intended only for use in the preparation of Technetium Tc 99m Mertiatide Injection, and are NOT to be administered directly to the patient.. Do not use Sodium Pertechnetate Tc 99m Injection USP more than hours after its elution from the generator.. Use aseptic techniques for all transfers and vial stopper entries.. Wear waterproof gloves during the procedure, particularly during the heating of the sample with boiling water.. Use suitable shielding to reduce radiation exposure. Use one lead shield for incubation with water bath and another lead shield for dispensing as described in the Procedure for the Preparation of Technetium Tc 99m Mertiatide Injection section below. Make all transfers of sodium pertechnetate Tc 99m solution during the preparation procedure with an adequately shielded syringe.. Prepare rolling boil water bath containing lead incubation vial shield with openings cut in it to allow the water to circulate through the shield. Orient the openings of the lead incubation shield to prevent radiation leakage. Note: The vial should be in direct contact with the rolling boil water of the bath, and the level of the bath must be at least even with the level of the contents of the vial.. Ensure the temperature of the water bath used for heating the reaction vial is at boiling temperature and the temperature of the lead incubation vial shield is equilibrated to the temperature of the water bath before proceeding with the preparation procedure below. Place the reaction vial in lead dispensing shield fitted with lid and with minimum wall thickness of 0.32 cm.. Swab the rubber stopper of the reaction vial with an appropriate antiseptic wipe. Insert filter-containing venting needle (provided) through the vial stopper.. Add mL to 10 mL of Sodium Pertechnetate Tc 99m Injection USP containing 740 MBq to 3,700 MBq (20 mCi to 100 mCi) into the vial using sterile syringe. If necessary, dilute the Sodium Pertechnetate Tc 99m Injection USP with 0.9% Sodium Chloride Injection USP to the desired concentration prior to addition to the vial.. Immediately following the addition of Sodium Pertechnetate Tc 99m Injection USP to the reaction vial, withdraw the syringe plunger to volume of mL, thus removing mL of argon gas, which adds mL of filtered air to the vial to oxidize excess stannous ion and to prevent the formation of technetium-99m labeled impurities. Note:The sample vial must be placed in boiling water bath within minutes of the addition of Sodium Pertechnetate Tc 99m solution.. Remove both needles from the vial.. Invert the reaction vial several times to obtain complete mixing, prior to heating.. Immediately transfer the reaction vial to the water bath. Place it inside the lead incubation shield which has been equilibrated to the temperature of the boiling water bath. The reaction vial should be in direct contact with the rolling boil water of the bath, and the level of the water must be at least even with the level of the contents of the vial. Incubate the reaction vial for 10 minutes.. Remove the reaction vial from the boiling water bath and place it in the lead dispensing shield. Allow the contents of the vial to cool for approximately 15 minutes.. Using proper shielding, visually inspect the vial contents. The solution should be clear and free of particulate matter. If not, do not use the preparation.. Assay the reaction vial using suitable radioactivity calibration system. Record the date, time, total activity, volume, and concentration on the radioassay information label and affix the label to the lead dispensing shield.. Test the radiochemical purity of the prepared Technetium Tc 99m Mertiatide Injection according to the recommended method [see Dosage and Administration (2.5) ]. If the radiochemical purity is less than 90%, do not use the product.. Test the radiochemical impurities of the prepared Technetium Tc 99m Mertiatide Injection according to the recommended method [see Dosage and Administration (2.5) ]. If the sum of the hydrophilic impurities and non-elutable impurities is more than 10%, do not use the product.. Use the Technetium Tc 99m Mertiatide Injection within hours of radiolabeling and store it at room temperature 15C to 30C (59F to 86F) until use.. Handle and dispose unused radioactive material in accordance with applicable regulations.. 2.5 Determination of Radiochemical Purity of Technetium Tc 99m Mertiatide Injection. Required MaterialsWaters Sep-Pak(TM) C18 Cartridges, Part 51910200 proof ethanol0.9% Sodium Chloride Injection, USP0.001N hydrochloric acid (May be prepared by diluting mL of 0.1N hydrochloric acid to 100 mL with Water for Injection, USP, or by other dilution of more concentrated hydrochloric acid. For example, 0.1 mL of 36% (~11.6N) hydrochloric acid diluted to total volume of 1,150 mL)1:1 ethanol: 0.9% Sodium Chloride Injection, USP (Prepared by mixing equal volumes of 200 proof ethanol and 0.9% Sodium Chloride Injection, USP)10 mL disposable syringe, no needle required1 mL disposable syringe, with needleDisposable culture tubes or vials, minimum 15 mL capacityIon chamber for measurement of radioactive samplesPreparation of Sep-Pak CartridgeUsing 10 mL syringe, push 10 mL of 200 proof ethanol through the Sep-Pak cartridge. Discard the eluate.Flush the cartridge with 10 mL of the 0.001N hydrochloric acid. Discard the eluate.Drain the cartridge by pushing mL of air through the cartridge with the syringe. Discard the eluate.Sample AnalysisApply 0.1 mL of the Technetium Tc 99m Mertiatide Injection preparation to the head of the cartridge through the longer end of the cartridge using 1 mL syringe with needle. Note: The cartridge and all solutions eluted from it will be radioactive after this step, therefore, use lead dispensing shield to minimize radiation exposure.With disposable 10 mL syringe, slowly push 10 mL of 0.001N hydrochloric acid through the cartridge. Collect this fraction in first culture tube or vial for counting.Elute the cartridge with 10 mL of the 1:1 ethanol: 0.9% Sodium Chloride Injection USP solution. Ensure that this solution is pushed through the cartridge slowly so that the elution occurs in drop-wise manner. Collect this 10 mL fraction in second culture tube or vial for counting.Place the Sep-Pak cartridge in third culture tube or vial for counting.CountingAssay the activity of the first fraction (in 0.001N hydrochloric acid) in an ion chamber. This fraction contains the hydrophilic impurities (free pertechnetate, technetium tartrate, etc.) and fraction of reduced-hydrolyzed technetium.Assay the activity of the second fraction (in 1:1 ethanol: 0.9% Sodium Chloride Injection, USP). This fraction contains Technetium Tc 99m Mertiatide.Assay the activity of the Sep-Pak cartridge in the third culture tube or vial. This component contains the remaining reduced-hydrolyzed technetium and non-elutable impurities.Calculations1. Percent Technetium Tc 99m Mertiatide Activity of 2nd (1:1 ethanol: 0.9% Sodium Chloride Injection) fraction 100% Total activity of all fractionsNote: Not less than 90% of the activity must be Technetium Tc 99m Mertiatide.2. Percent hydrophilic impurities Activity of 1st (0.001N hydrochloric acid) fraction 100% Total activity of all fractions3. Percent non-elutable impurities Activity remaining on Sep-Pak cartridge 100% Total activity of all fractionsNote: Total impurities must not be more than 10%.. Waters Sep-Pak(TM) C18 Cartridges, Part 51910. 200 proof ethanol. 0.9% Sodium Chloride Injection, USP. 0.001N hydrochloric acid (May be prepared by diluting mL of 0.1N hydrochloric acid to 100 mL with Water for Injection, USP, or by other dilution of more concentrated hydrochloric acid. For example, 0.1 mL of 36% (~11.6N) hydrochloric acid diluted to total volume of 1,150 mL). 1:1 ethanol: 0.9% Sodium Chloride Injection, USP (Prepared by mixing equal volumes of 200 proof ethanol and 0.9% Sodium Chloride Injection, USP). 10 mL disposable syringe, no needle required. mL disposable syringe, with needle. Disposable culture tubes or vials, minimum 15 mL capacity. Ion chamber for measurement of radioactive samples. Using 10 mL syringe, push 10 mL of 200 proof ethanol through the Sep-Pak cartridge. Discard the eluate.. Flush the cartridge with 10 mL of the 0.001N hydrochloric acid. Discard the eluate.. Drain the cartridge by pushing mL of air through the cartridge with the syringe. Discard the eluate.. Apply 0.1 mL of the Technetium Tc 99m Mertiatide Injection preparation to the head of the cartridge through the longer end of the cartridge using 1 mL syringe with needle. Note: The cartridge and all solutions eluted from it will be radioactive after this step, therefore, use lead dispensing shield to minimize radiation exposure.. With disposable 10 mL syringe, slowly push 10 mL of 0.001N hydrochloric acid through the cartridge. Collect this fraction in first culture tube or vial for counting.. Elute the cartridge with 10 mL of the 1:1 ethanol: 0.9% Sodium Chloride Injection USP solution. Ensure that this solution is pushed through the cartridge slowly so that the elution occurs in drop-wise manner. Collect this 10 mL fraction in second culture tube or vial for counting.. Place the Sep-Pak cartridge in third culture tube or vial for counting.. Assay the activity of the first fraction (in 0.001N hydrochloric acid) in an ion chamber. This fraction contains the hydrophilic impurities (free pertechnetate, technetium tartrate, etc.) and fraction of reduced-hydrolyzed technetium.. Assay the activity of the second fraction (in 1:1 ethanol: 0.9% Sodium Chloride Injection, USP). This fraction contains Technetium Tc 99m Mertiatide.. Assay the activity of the Sep-Pak cartridge in the third culture tube or vial. This component contains the remaining reduced-hydrolyzed technetium and non-elutable impurities.. 2.6 Administration Instructions. Measure the patient dose using suitable radioactivity calibration system immediately prior to administration.Visually inspect the prepared Technetium Tc 99m Mertiatide Injection behind lead glass shield for particulate matter and discoloration prior to administration. Only use solutions that are clear without visible particles.Use aseptic procedures and shielded syringe to withdraw doses for administration to patients. Wear waterproof gloves during the administration procedure.. Measure the patient dose using suitable radioactivity calibration system immediately prior to administration.. Visually inspect the prepared Technetium Tc 99m Mertiatide Injection behind lead glass shield for particulate matter and discoloration prior to administration. Only use solutions that are clear without visible particles.. Use aseptic procedures and shielded syringe to withdraw doses for administration to patients. Wear waterproof gloves during the administration procedure.. 2.7 Radiation Dosimetry. The estimated radiation doses per injected activity of Technetium Tc 99m Mertiatide Injection by an intravenous administration are presented in Table 1.Table 1. Estimated Radiation Equivalent Dose for Intravenously Administered Technetium Tc 99m MertiatideRadiation Equivalent Dose per Unit Activity Administered (mSv/MBq) OrganAdult 15 Years 10 Years Years Year DaysGallbladder Wall 0.0044 0.0053 0.007 0.011 0.034 0.073 Lower Large Intestine Wall 0.0088 0.011 0.01 0.016 0.022 0.047 Small Intestine 0.0044 0.0055 0.0059 0.0085 0.0075 0.014 Upper Large Intestine Wall 0.0051 0.0066 0.0086 0.013 0.013 0.026 Kidneys 0.0039 0.0047 0.0064 0.0093 0.015 0.038 Liver 0.00098 0.0013 0.0018 0.0028 0.0042 0.0087 Ovaries 0.007 0.009 0.0065 0.0094 0.0085 0.016 Red Marrow 0.0013 0.0017 0.0015 0.002 0.0022 0.0044 Testes 0.0044 0.0064 0.005 0.0077 0.0073 0.014 Urinary Bladder Wall 0.13 0.16 0.1 0.15 0.13 0.31 Total Body 0.0018 0.0022 0.0017 0.0026 0.003 0.0045Calculated by Oak Ridge Associated Universities, based upon the pediatric phantom series of Christy and Eckerman of Oak Ridge National Laboratories. The adult radiation absorbed doses were calculated based on data from 10 healthy subjects using the Medical Internal Radiation Dose Committee (MIRD) schema. Technetium Tc 99m Mertiatide Injection is not approved for pediatric patients younger than 30 days old [see Indications and Usage (1)].

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Kit for the Preparation of Technetium Tc 99m Mertiatide Injection contains mg betiatide supplied as white lyophilized powder packaged in 10 mL glass multiple-dose vials. Radiolabeling with sodium pertechnetate Tc 99m injection provides clear, colorless solution containing up to 3,700 MBq (100 mCi) technetium Tc 99m mertiatide in approximately 10 mL volume at calibration time... Kit for the Preparation of Technetium Tc 99m Mertiatide Injection: mg betiatide as lyophilized powder in 10 ml glass multiple-dose vial. Upon radiolabeling with technetium-99m, it contains up to 3,700 MBq (100 mCi) technetium Tc 99m mertiatide in approximately 10 mL volume at calibration time.

GERIATRIC USE SECTION.

8.5 Geriatric Use. No formal studies of Technetium Tc 99m Mertiatide Injection in subjects aged 65 and over were performed to determine whether they respond differently than younger adult subjects.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. How SuppliedKit for the Preparation of Technetium Tc 99m Mertiatide Injection containing mg betiatide, is supplied as white lyophilized powder packaged in sterile, multiple-dose 10 mL vial as carton of vials (NDC 65174-261-05). The carton also contains:- venting needles with filter.- radioassay information labels for the radiolabeled product.The radionuclide is not part of Kit for the Preparation of Technetium Tc 99m Mertiatide Injection.Storage and HandlingBefore radiolabeling, store at controlled room temperature 20C to 25C (68F to 77F) [see USP Controlled Room Temperature] and protect from light.After radiolabeling with sodium pertechnetate Tc 99m injection, store vial upright in shielding to protect from radiation at room temperature 15C to 30C (59F to 86F). Use within hours of radiolabeling.Dispose of unused Technetium Tc 99m Mertiatide Injection in compliance with the regulations of the government agency authorized to license the use of this radionuclide.This preparation is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Kit for the Preparation of Technetium Tc 99m Mertiatide Injection, after radiolabeling with technetium-99m, is indicated for use in the diagnosis of congenital and acquired renal abnormalities, renal failure, urinary tract obstruction, and calculi in adults and pediatric patients aged 30 days and older. The product is diagnostic aid in providing renal function, split function, renal angiograms, and renogram curves for whole kidney and renal cortex.. Kit for the Preparation of Technetium Tc 99m Mertiatide Injection, after radiolabeling with technetium-99m, is radioactive diagnostic agent indicated for use in the diagnosis of congenital and acquired renal abnormalities, renal failure, urinary tract obstruction, and calculi in adults and pediatric patients aged 30 days and older. The product is diagnostic aid in providing renal function, split function, renal angiograms, and renogram curves for whole kidney and renal cortex. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Adequate HydrationAdvise patients to drink sufficient amount of water to ensure adequate hydration before administration of Technetium Tc 99m Mertiatide Injection and to continue to drink and void frequently following administration to minimize radiation dose [see Dosage and Administration (2.2) and Warning and Precautions (5.1)]. Pregnancy: Advise pregnant women of the risk of fetal exposure to radiation doses if they undergo radionuclide procedure [see Use in Specific Populations (8.1)].Lactation:Advise lactating woman to temporarily discontinue breastfeeding and to pump and discard breast milk for at least 24 hours after Technetium Tc 99m Mertiatide Injection administration to minimize radiation exposure to breastfed infant [see Use in Specific Populations (8.2)].Manufactured for:Jubilant DraxImage Inc., dba Jubilant Radiopharma(TM)16 751 TransCanada HighwayKirkland, Quebec H9H 4J4 Canada1-888-633-5343 www.jubilantradiopharma.com Art Rev.: 3.0Sep-Pak(TM) is trademark of Waters Technologies Corporation.Jubilant Radiopharma(TM) is trademark used under license by Jubilant DraxImage Inc.. jbl-logo.

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere are no data on the presence of technetium Tc 99m mertiatide in breast milk, however, published case reports describe the presence of technetium Tc 99m in breast milk. There are no data on the effects of technetium Tc 99m mertiatide on the breastfed infant or the effects on milk production. Based on clinical guidelines, exposure of technetium Tc 99m mertiatide to breastfed infant may be minimized by advising lactating woman to temporarily discontinue breastfeeding and to pump and discard breast milk for minimum of 24 hours after administration of Technetium Tc 99m Mertiatide Injection. The developmental and health benefits of breastfeeding should be considered along with mothers clinical need for Technetium Tc 99m Mertiatide Injection and any potential adverse effects on the breastfed child from technetium Tc 99m mertiatide or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Following intravenous administration for renal imaging, Technetium Tc 99m Mertiatide is rapidly cleared from the blood. It is cleared by the kidneys and excreted in the urine.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL 5 VIAL BOX. NDC 65174-261-05Kit for the Preparation of Technetium Tc 99m Mertiatide1 mg Betiatide per VialRx onlyFor intravenous use only after radiolabeling withSodium Pertechnetate Tc 99m Injection, USPDIAGNOSTIC For Renal ImagingManufactured for:Jubilant DraxImage Inc., dba Jubilant Radiopharma(TM)Kirkland, Quebec H9H 4J4 Canada1-888-633-5343, www.jubilantradiopharma.comCONTENTS:Five (5) sterile, non-pyrogenic multiple-dose vials of Kit for the preparation of technetium Tc 99m mertiatide, radioassay information labels, venting needles (filter containing) and prescribing information.Each 10 mL multiple dose vial contains: mg betiatide, 20 mg lactose monohydrate, 40 mg tartrate dihydrate, 0.07 (minimum) stannous chloride dihydrate, and 0.2 mg (maximum) total tin as stannous chloride dihydrate. Hydrochloric acid is added for pH adjustment, prior to lyophilization.The pH of the reconstituted drug is between and 6.The contents are sealed under argon.Rx only Recommended Dosage: See Prescrbing Information.Storage: Before radiolabeling, store at 20 to 25 (68 to 77 F) and protect from light.After radiolabeling, store upright inappropriate shielding to protect from radiation at 15C to 30C (59F to 86F). Use within hours of radiolabeling. Preservative-free.. outer-carton-label.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. Kit for the Preparation of Technetium Tc 99m Mertiatide Injection, after radiolabeling with technetium-99m, is indicated for use in the diagnosis of congenital and acquired renal abnormalities, renal failure, urinary tract obstruction, and calculi in pediatric patients aged 30 days and older.The safety and effectiveness of Kit for the Preparation of Technetium Tc 99m Mertiatide Injection have not been established in pediatric patients younger than 30 days old.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Following intravenous injection of technetium Tc 99m mertiatide, the uptake, concentration, and excretion of the tracer by the kidney can be monitored to assess renal function.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. DistributionAfter an intravenous administration in healthy adult subjects, 89% of technetium Tc 99m mertiatide was plasma-protein bound. The protein binding is reversible.EliminationExcretionIn healthy subjects, the plasma clearance was approximately 0.3 liters/minute and the amount of technetium Tc 99m mertiatide excreted in the urine in hours was nearly 90% of the injected dose. Specific PopulationsPatients with Renal ImpairmentIn study performed in three patients with renal impairment (serum creatinine greater than 6.3 mg/dL), 78% of the tracer was plasma protein bound after intravenous injection. The mean plasma clearance of technetium Tc 99m mertiatide was 0.03 liters/minute and 21.3% was excreted in hours on average. In both healthy subjects and patients with renal impairment, the plasma concentration-time profile showed biexponential decline.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryThere are no data with technetium Tc 99m mertiatide use in pregnant women to determine drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No animal reproductive studies have been conducted with technetium Tc 99m mertiatide. Although all radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose, the radiation exposure to the fetus from technetium Tc 99m mertiatide is expected to be low (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defects, 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 are 2% to 4% and 15% to 20%, respectively.DataHuman DataNo adverse fetal effects of radiation risks have been identified for diagnostic procedures involving less than 50 mGy, which represents less than 10 mGy fetal doses.

SPL UNCLASSIFIED SECTION.

2.1 Radiation Safety Drug Handling. After radiolabeling, the kit produces Technetium Tc 99m Mertiatide Injection. Handle Technetium Tc 99m Mertiatide Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions (5.1)]. Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Technetium Tc 99m Mertiatide Injection.Radiopharmaceuticals should be used by or under the control of healthcare providers who are qualified by specific 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.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Lactation: Temporarily discontinue breastfeeding. lactating woman should pump and discard breast milk for at least 24 hours after Technetium Tc99m Mertiatide administration. (8.2). 8.1 Pregnancy. Risk SummaryThere are no data with technetium Tc 99m mertiatide use in pregnant women to determine drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No animal reproductive studies have been conducted with technetium Tc 99m mertiatide. Although all radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose, the radiation exposure to the fetus from technetium Tc 99m mertiatide is expected to be low (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defects, 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 are 2% to 4% and 15% to 20%, respectively.DataHuman DataNo adverse fetal effects of radiation risks have been identified for diagnostic procedures involving less than 50 mGy, which represents less than 10 mGy fetal doses.. 8.2 Lactation. Risk SummaryThere are no data on the presence of technetium Tc 99m mertiatide in breast milk, however, published case reports describe the presence of technetium Tc 99m in breast milk. There are no data on the effects of technetium Tc 99m mertiatide on the breastfed infant or the effects on milk production. Based on clinical guidelines, exposure of technetium Tc 99m mertiatide to breastfed infant may be minimized by advising lactating woman to temporarily discontinue breastfeeding and to pump and discard breast milk for minimum of 24 hours after administration of Technetium Tc 99m Mertiatide Injection. The developmental and health benefits of breastfeeding should be considered along with mothers clinical need for Technetium Tc 99m Mertiatide Injection and any potential adverse effects on the breastfed child from technetium Tc 99m mertiatide or from the underlying maternal condition.. 8.4 Pediatric Use. Kit for the Preparation of Technetium Tc 99m Mertiatide Injection, after radiolabeling with technetium-99m, is indicated for use in the diagnosis of congenital and acquired renal abnormalities, renal failure, urinary tract obstruction, and calculi in pediatric patients aged 30 days and older.The safety and effectiveness of Kit for the Preparation of Technetium Tc 99m Mertiatide Injection have not been established in pediatric patients younger than 30 days old.. 8.5 Geriatric Use. No formal studies of Technetium Tc 99m Mertiatide Injection in subjects aged 65 and over were performed to determine whether they respond differently than younger adult subjects.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Radiation risks: Ensure safe handling to minimize radiation exposure to patients and healthcare providers. (5.1). 5.1 Radiation Risks. Technetium Tc 99m Mertiatide Injection contributes to patients overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe handling to minimize radiation exposure to the patient and healthcare providers. Advise patients to hydrate before and after administration and to void frequently after administration see Dosage and Administration (2.2) ].