ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactionshave been identified post-approval. Because these reactions are voluntarilyreported from population of uncertain size, it is not always possibleto reliably estimate their exact frequency or establish causal relationshipto Technetium Tc 99m pentetate exposure.Adverse reactions arepresented in decreasing order of reported frequency:Immune system disorders: allergic reaction,anaphylactic reaction, angioedema.Skin and subcutaneous tissue disorders:rash, itching, hives, erythema.Respiratory, thoracic and mediastinaldisorders: throat irritation, wheezing.Vascular disorders: hypotension, hypertension.Nervous system disorders: headache, fainting,dizziness.General disorders and administrationsite conditions: chills.Gastrointestinal disorders: nausea, vomiting.Cardiac disorders: cyanosis, tachycardia.. Immune system disorders: allergic reaction,anaphylactic reaction, angioedema.. Skin and subcutaneous tissue disorders:rash, itching, hives, erythema.. Respiratory, thoracic and mediastinaldisorders: throat irritation, wheezing.. Vascular disorders: hypotension, hypertension.. Nervous system disorders: headache, fainting,dizziness.. General disorders and administrationsite conditions: chills.. Gastrointestinal disorders: nausea, vomiting.. Cardiac disorders: cyanosis, tachycardia.. Most common adverse reactionsreported with Technetium Tc 99m pentetate injection include allergicreactions, rash, itching (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.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Intravenous AdministrationFollowing intravenousadministration for brain and renal imaging, Technetium Tc 99m pentetateis distributed in the vascular compartment. It is cleared by thekidneys, which results in the ability to image the kidney.Aerosolized Inhalation AdministrationFollowing inhalation of the aerosol, Technetium Tc 99m pentetatedeposits on the epithelium of ventilated alveoli.. 12.2 Pharmacodynamics. Brain ImagingTechnetium Tc 99m pentetate with intravenous administrationtends to accumulate in intra-cranial lesions with excessive neovascularityor an altered blood brain barrier. Technetium Tc 99m pentetate accumulationin the brain is prevented by an intact blood brain barrier. It doesnot accumulate in the choroid plexus.Renal ScintigraphyThe first few minutes after intravenous administration,Technetium Tc 99m pentetate is present in the vascular compartmentwithin the renal system.Lung VentilationImagingIn patients with normal lungs, thedeposition of Technetium Tc 99m pentetate is homogeneous throughoutthe lungs. In patients with airway disease, the deposition patternsbecome inhomogeneous with irregular deposition of Technetium Tc 99mpentetate in the airways and alveolar regions of the lung.. 12.3 Pharmacokinetics. After anintravenous administration, the pharmacokinetics of Technetium Tc99m pentetate were studied by monitoring radioactivity in serial venousblood samples for hours post-administration. The mean plasma clearancerate was 6.8 (L/h) and the mean plasma elimination half-life (t 1/2 )was 2.1 hours. The mean volume of distribution at steady state conditionscalculated with clearance and mean residence time was 17 L. Thisrelatively low volume of distribution after intravenous administrationsuggests that Technetium Tc 99m pentetate distributes to the extracellularfluid only. The rate of elimination of Technetium Tc 99m pentetatefrom the systemic circulation appears to be constant over an approximately20-fold intravenous dose range.AbsorptionFollowing inhalation Technetium Tc 99m pentetate wasabsorbed (Tmax <2 hours after inhalation)and distributed across the lung epithelium (bioavailability approximately70%) and into the systemic circulation.DistributionFollowing intravenous administration, TechnetiumTc 99m pentetate is distributed throughout the extracellular fluidspace and is cleared from the body by the kidney.The steady-state volumeof distribution (Vss) was 17 following an intravenous administration. Technetium Tc 99m pentetate distribution appears to be limited tothe extravascular compartment.A variable percentage of the TechnetiumTc 99m pentetate binds to the serum proteins; this ranges from 3.7%following single injection to approximately 10% if the materialis continuously infused. Although the chelate gives useful informationon the glomerular filtration rate, the variable percent which is proteinbound leads to measured renal clearance rate which is lower thanthat determined by inulin clearance.EliminationMetabolismTechnetium Tc99m pentetate is not metabolized.ExcretionAfter either intravenous administration or inhalation,excretion is by glomerular filtration. The mean fraction of intravenouslyadministered Technetium Tc 99m pentetate excreted in urine over 24hours was 102%.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Hypersensitivity to the activeingredient or to any component of the product [see Warningsand Precautions (5.1)]. Hypersensitivity to the activeingredient or any component of this product (4).

DESCRIPTION SECTION.

11 DESCRIPTION. 11.1 Chemical Characteristics. DRAXIMAGE(R) DTPAis kit for the preparation of Technetium Tc 99m pentetate injection,a radioactive diagnostic agent, for intravenous or inhalation use. Each multiple-dose 10 mL glass vial contains sterile, non-pyrogenic,non-radioactive lyophilized powder of 20 mg of pentetic acid, mgof p-aminobenzoic acid, 3.73 mg of calcium chloride dihydrate, andnot less than 0.25 mg stannous chloride dihydrate and not more than0.385 mg maximum tin expressed as stannous chloride dihydrate. Thelyophilized product is sealed under an atmosphere of nitrogen. Nobacteriostatic preservative is present. Its chemical name is:Technetate (1-)99mTc,[N,N-bis[2-[bis(carboxymethyl)amino]ethyl]-glycinato(5-)]-,sodium. The structure of the technetium labeled form is:The pH is adjusted with HCl and/or NaOHprior to lyophilization so that the pH range of the reconstitutedradiopharmaceutical is 6.5 to 7.5.. structure. 11.2 Physical Characteristics. Technetium Tc 99m decays by isomeric transitionwith physical half-life of hours. The principal photon that isuseful for detection and imaging studies is listed in Table 7.Table Principal Radiation Emission DataRadiationMean %per DisintegrationMean Energy(keV)Gamma-288.5140.5The air-kerma-rate (exposure-rate)constant for Technetium Tc 99m is 5.23 m2.pGy.(MBq)- 1.s- [0.795 cm2.R.(mCi)- 1.h- 1]. rangeof values for the relative radiation attenuation by the various thicknessesof lead is shown in Table 8. For example,the use of 3 mm thickness of lead will attenuate the radiation emittedby factor of about 1,000.Table Radiation Attenuation by Lead ShieldingShieldThickness (Pb) cmCoefficientof Attenuation0.250.5110-1 210-2 310-3 410-4 To correct for physicaldecay of this radionuclide, the fractions that remain at selectedintervals after the time of calibration are shown in Table 9.Table Physical Decay Chart of Technetium 99mTc, Half Life: HoursCalibration TimeHoursFractionRemainingHoursFractionRemaining0 1.00050.56210.89160.50120.79480.39830.708100.31640.631120.251.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. During preparation and handling, use water proof glovesand effective shielding, to minimize radiation exposure (2.1, 5.3).See the Full Prescribing Information for detailed informationregarding recommended Dosage and Image Acquisition Instructions (2.2) and Instructions for Drug Preparation(2.4).Do not administer more than one dose (2.2).. During preparation and handling, use water proof glovesand effective shielding, to minimize radiation exposure (2.1, 5.3).. See the Full Prescribing Information for detailed informationregarding recommended Dosage and Image Acquisition Instructions (2.2) and Instructions for Drug Preparation(2.4).. Do not administer more than one dose (2.2).. 2.1 Radiation Safety- Drug Handling. Tc 99m labeled DRAXIMAGE(R) DTPA injectionis radioactive drug and should be handled with appropriate safetymeasures to minimize radiation exposure to the patient and healthcareworker. During preparation and handling, use water proof gloves andeffective shielding, including syringe shields [see Warningsand Precautions (5.3)].. 2.2 Recommended Dosageand Image Acquisition Instructions. The recommended dose ranges for intravenousor inhalation administration of DRAXIMAGE(R) DTPA, after reconstitution, are presented in Table through Table 3.Do not administer more than one dose.Table Tc 99m Labeled DRAXIMAGE(R) DTPA Injection Intravenous Administration, AdultsIndicationRoute of AdministrationDoseImage AcquisitionBrain ImagingIntravenous Injection370 to 740 MBq(10 to 20 mCi)Immediate dynamic imaging. Obtain at least one blood-poolimage in same position as flow.Delayed images can be obtained1 hour later.Renal Visualization and Perfusion AssessmentIntravenous Injection370 to 740 MBq(10 to 20 mCi)Immediate dynamic imaging.Static imaging to 30 minutesafter injection.Renal Visualization with Estimation of Glomerular Filtration RateIntravenous Injection111 to 185 MBq(3 to mCi)Immediate dynamic imaging.Static imaging to 30 minutesafter injection.Estimation of Glomerular Filtration Rate (with no renal imaging)Intravenous Injection7.4 to 18.5 MBq(0.2 to 0.5 mCi)Blood sampling only is performed.Table Tc 99m Labeled DRAXIMAGE(R) DTPA Injection Intravenous Administration, Pediatric PatientsIndicationRoute of AdministrationDoseImage AcquisitionRenal Visualization and Perfusion AssessmentIntravenous Injection3.7 to 7.4 MBq/kg (0.1 to 0.2 mCi/kg) Minimum37 MBq (1 mCi) Maximum 185 MBq (5 mCi)Immediate dynamic imaging. Static imaging to 30 minutesafter injection.Estimation of Glomerular Filtration Rate (with no renal imaging)Intravenous Injection7.4 to 18.5 MBq (0.2 to 0.5 mCi)Blood sampling only is performed.Table Tc 99m Labeled DRAXIMAGE(R) DTPA Aerosol Inhalation Administration For lungimaging performed after perfusion imaging, target count rate shouldbe approximately three times that of perfusion count rate.IndicationRoute of AdministrationDoseImage AcquisitionLung Ventilation AdultsAerosol Inhalation925 to 1850 MBq (25 to 50 mCi) in the nebulizer to achieve lungdose of approximately 18.5 to 37 MBq (0.5 to 1.0 mCi)For lung imaging performed prior to perfusion imaging, the targetadministered dose to the lungs is achieved after to minutes ofinhalation or at an imaging count rate of 50,000 to 100,000 per minute.Lung VentilationPediatric PatientsAerosol Inhalation925 MBq (25 mCi) in the nebulizer to achieve lung dose of approximately18.5 MBq (0.5 mCi)For lung imaging performed prior to perfusion imaging, the targetadministered dose to the lungs is achieved at an imaging count rateof approximately 10,000 to 50,000 per minute.. The recommended dose ranges for intravenousor inhalation administration of DRAXIMAGE(R) DTPA, after reconstitution, are presented in Table through Table 3.. Do not administer more than one dose.. 2.3 Administration Instructions. Use aseptic technique for all drug preparation and handling.Visually inspect the Tc 99m labeled DRAXIMAGE(R) DTPA injection after reconstitution for particulatematter prior to administration. Do not use or administer if thereis evidence of foreign matter or the solution is not clear.Measure the patient dose by radioactivity calibrationsystem immediately prior to administration.IntravenousUseInstruct the patient to increase fluid intake and to voidfrequently for the next to hours after Tc 99m labeled DRAXIMAGE(R) DTPA administration by injection to minimize theradiation dose to the bladder.InhalationUseUse the selected nebulizer in accordancewith the manufacturers instructions.Instruct the patient to rinse their mouthand expectorate after Tc 99m labeled DRAXIMAGE(R) DTPA administration by inhalation to minimize the radiation doseto the mouth and esophagus.. Use aseptic technique for all drug preparation and handling.. Visually inspect the Tc 99m labeled DRAXIMAGE(R) DTPA injection after reconstitution for particulatematter prior to administration. Do not use or administer if thereis evidence of foreign matter or the solution is not clear.. Measure the patient dose by radioactivity calibrationsystem immediately prior to administration.. Instruct the patient to increase fluid intake and to voidfrequently for the next to hours after Tc 99m labeled DRAXIMAGE(R) DTPA administration by injection to minimize theradiation dose to the bladder.. Use the selected nebulizer in accordancewith the manufacturers instructions.. Instruct the patient to rinse their mouthand expectorate after Tc 99m labeled DRAXIMAGE(R) DTPA administration by inhalation to minimize the radiation doseto the mouth and esophagus.. 2.4 Instructions forDrug Preparation. The prepared solution can either be administeredvia intravenous injection or aerosolized by nebulizer for inhalationuse.Before reconstitution, inspect the integrityof the vial.Add to 10 mL [maximum amount 18.5 gigabecquerels(500 mCi)] of sodium pertechnetate Tc 99m injection USP to the reactionvial. The volume of pertechnetate added should be balanced by theremoval of the same volume of air. Cover the vial shield and invertto mix the contents.Assay the preparation in calibrator,record the radio assay information on the label with radiation warningsymbol, and affix it to the reaction vial.After reconstitution, store the solution at 25C (77F)in lead shield and discard after 12 hours; excursions permittedbetween 15 and 30C (59 and 86F).Allow the preparation to stand for 15 minutes before determiningthe radiochemical purity of Tc 99m labeled DRAXIMAGE(R) DTPA injection.After reconstitution, do not vent the vial.. The prepared solution can either be administeredvia intravenous injection or aerosolized by nebulizer for inhalationuse.. Before reconstitution, inspect the integrityof the vial.. Add to 10 mL [maximum amount 18.5 gigabecquerels(500 mCi)] of sodium pertechnetate Tc 99m injection USP to the reactionvial. The volume of pertechnetate added should be balanced by theremoval of the same volume of air. Cover the vial shield and invertto mix the contents.. Assay the preparation in calibrator,record the radio assay information on the label with radiation warningsymbol, and affix it to the reaction vial.. After reconstitution, store the solution at 25C (77F)in lead shield and discard after 12 hours; excursions permittedbetween 15 and 30C (59 and 86F).. Allow the preparation to stand for 15 minutes before determiningthe radiochemical purity of Tc 99m labeled DRAXIMAGE(R) DTPA injection.. After reconstitution, do not vent the vial.. 2.5 Determination ofRadiochemical Purity. Obtain the following:Two ITLC-SG (1 10 cm)0.9% Sodium Chloride Injection USP (fordetermination of reduced hydrolyzed technetium)Acetone (for determination of free pertechnetate)Two glass test tubes (18 mm 150 mm)with stoppersStep1:System A: Add mL of 0.9% Sodium Chloride Injection USP in an 18mm 150 mm test tube. Place the stopper and allow the atmospherein the tube to equilibrate for minute.System B: Repeat with Acetone in separate test tube.Step2:Mark each chromatographic strip witha pencil mark 1.5 cm (see Figure and Figure 2) from one endof the strip (mark as origin).Place one drop (approximately 0.01 -0.02 mL) of the Technetium Tc 99m pentetate injection at the origin.For System (saline), do not allow thestrip to dry.For System (acetone), dry the stripusing gentle stream of nitrogen gas.Step3:Place each strip with the origin endtowards the bottom of the previously equilibrated test tube to develop(the origin must be above the surface of the solvent).Place stopper in the test tube and keepupright.Step4:When the solvent front has reached thetop of the strip, remove the strip with forceps and allow it to dry.Step 5:System - Determination of reducedhydrolyzed technetium:In System (saline), reduced hydrolyzedtechnetium (99mTcO2) stays at the origin (Rf to 0.1), whilethe bound technetium and free pertechnetate (99mTcO4 -) migratesto the solvent front (Rf 0.85 to 1.0).Cut the dried strip cm from the origin.The short piece is marked as Part and the long piece is marked as Part II.Count the pieces in counter and determinethe percentage of reduced hydrolyzed technetium according to the followingformula:Figure System DiagramSystem - Determination of freepertechnetate:In System (acetone), the bound technetiumand reduced hydrolyzed technetium (99mTcO2) stay at the origin (Rf to0.1), while free pertechnetate (99mTcO4 -) migrates to the solventfront (Rf 0.85 to 1.0).Cut the dried strip cm from the solventfront end.The short piece is marked PartIII and the long piece is marked Part IV.Count the pieces in counter and determinethe percentage of free pertechnetate according to the following formula:Figure System DiagramStep6:Determine the radiochemical purity accordingto the following formula: Use Technetium Tc 99m pentetate injectiononly if the radiochemical purity is 90% or greater.. Two ITLC-SG (1 10 cm). 0.9% Sodium Chloride Injection USP (fordetermination of reduced hydrolyzed technetium). Acetone (for determination of free pertechnetate). Two glass test tubes (18 mm 150 mm)with stoppers. System A: Add mL of 0.9% Sodium Chloride Injection USP in an 18mm 150 mm test tube. Place the stopper and allow the atmospherein the tube to equilibrate for minute.. System B: Repeat with Acetone in separate test tube.. Mark each chromatographic strip witha pencil mark 1.5 cm (see Figure and Figure 2) from one endof the strip (mark as origin).. Place one drop (approximately 0.01 -0.02 mL) of the Technetium Tc 99m pentetate injection at the origin.. For System (saline), do not allow thestrip to dry.. For System (acetone), dry the stripusing gentle stream of nitrogen gas.. Place each strip with the origin endtowards the bottom of the previously equilibrated test tube to develop(the origin must be above the surface of the solvent).. Place stopper in the test tube and keepupright.. When the solvent front has reached thetop of the strip, remove the strip with forceps and allow it to dry.. In System (saline), reduced hydrolyzedtechnetium (99mTcO2) stays at the origin (Rf to 0.1), whilethe bound technetium and free pertechnetate (99mTcO4 -) migratesto the solvent front (Rf 0.85 to 1.0).. Cut the dried strip cm from the origin.. The short piece is marked as Part and the long piece is marked as Part II.. Count the pieces in counter and determinethe percentage of reduced hydrolyzed technetium according to the followingformula:. In System (acetone), the bound technetiumand reduced hydrolyzed technetium (99mTcO2) stay at the origin (Rf to0.1), while free pertechnetate (99mTcO4 -) migrates to the solventfront (Rf 0.85 to 1.0).. Cut the dried strip cm from the solventfront end.. The short piece is marked PartIII and the long piece is marked Part IV.. Count the pieces in counter and determinethe percentage of free pertechnetate according to the following formula:. Determine the radiochemical purity accordingto the following formula: Use Technetium Tc 99m pentetate injectiononly if the radiochemical purity is 90% or greater.. eq1. Figure1. eq2. figure2. step-6-formula. 2.6 Radiation Dosimetry. The estimated radiation absorbed dose tovarious organs from an intravenous injection of Tc 99m pentetate inpatients with normal and abnormal renal function is shown respectivelyin Table and Table5.Table Estimated Radiation Absorbed Dose for TechnetiumTc 99m Pentetate Injection in Patients With Normal Renal FunctionFollowing Intravenous InjectionAbsorbed Dose Per Unit Activity Administered (uGy/MBq)OrganAdult15 Years10 Years5 Years1 YearAdrenals1.41.82.74.07.2Bonesurfaces2.42.94.36.110Brain0.861.11.72.84.9Breast0.720.921.32.24.1Gallbladderwall1.52.13.85.06.1GastrointestinaltractEsophagus1.01.31.93.05.4Stomach wall1.31.72.84.06.8Small intestine wall2.53.14.97.010Colon wall3.13.96.08.111Upper large intestine wall2.12.84.36.59.2Lower large intestine wall4.35.48.21013Heartwall1.21.52.23.35.9Kidneys4.45.37.51118Liver1.21.62.53.86.4Lungs1.01.32.03.05.5Muscles1.62.03.04.36.8Ovaries4.25.37.71013Pancreas1.41.82.84.37.4Redmarrow1.51.82.73.75.7Skin0.871.01.72.64.4Spleen1.31.62.63.96.8Testes2.94.06.89.413Thymus1.01.31.93.05.4Thyroid1.01.32.13.36.0Urinarybladder wall6278110150170Uterus7.99.6151822Remainingorgans1.72.13.04.26.6Effective dose per unit activity(uSv/MBq)4.96.39.41216Table Estimated Radiation Absorbed Dose for TechnetiumTc 99m Pentetate Injection in Patients With Abnormal Renal FunctionFollowing Intravenous InjectionAbsorbed Dose Per Unit Activity Administered (uGy/MBq)OrganAdult15 Years10 Years5 Years1 YearAdrenals4.15.17.61121Bonesurfaces6.07.1111528Brain2.83.55.79.116Breast2.33.04.26.813Gallbladderwall4.25.79.21316GastrointestinaltractEsophagus3.34.26.29.617Stomach wall3.85.07.91119Small intestine wall4.55.68.51322Colon wall4.55.88.71322Upper large intestine wall4.35.68.11321Lower large intestine wall4.96.19.51323Heartwall3.74.77.01018Kidneys7.79.2131932Liver3.74.67.11119Lungs3.34.26.29.517Muscles3.24.06.19.117Ovaries5.06.29.21423Pancreas4.35.38.01221Redmarrow3.44.26.49.316Skin2.22.64.26.712Spleen3.84.77.31119Testes3.54.56.91018Thymus3.34.26.29.617Thyroid3.44.26.71119Urinarybladder wall2127395066Uterus6.17.4111625Remainingorgans3.34.16.39.717Effective dose per unit activity(uSv/MBq)4.65.88.71321The estimated radiationabsorbed dose to various organs from the inhalation of Tc 99m PentetateInjection is shown in Table 6.Table Estimated Radiation Absorbed Dose for TechnetiumTc 99m Pentetate Injection Administered by InhalationAbsorbed Dose Per Unit Activity Administered (uGy/MBq)OrganAdult15 Years10 Years5 Years1 YearAdrenals2.12.94.46.712Bonesurfaces1.92.43.55.39.8Breast1.91.93.34.87.8GastrointestinaltractStomach wall1.72.23.55.18.9Small intestine wall2.12.64.16.311Upper large intestine wall1.92.43.86.110Lower large intestine wall3.24.26.38.815Kidneys4.15.17.21119Liver1.92.53.75.59.7Lungs17263654100Ovaries3.34.16.18.915Pancreas2.12.64.06.111Redmarrow2.73.44.76.29.6Spleen1.92.43.65.69.9Testes2.13.15.27.915Thyroid0.991.72.74.47.8Urinarybladder wall475884120230Uterus5.97.2111627Othertissue1.82.23.24.98.6Effective dose per unit activity(uSv/MBq)5.98.0111731.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Kit forthe preparation of Technetium Tc 99m pentetate injection: multiple-dose10 mL glass vial contains non-radioactive (white) lyophilized powderwith 20 mg of pentetic acid, mg of p-aminobenzoic acid, 3.73 mgof calcium chloride dihydrate, and not less than 0.25 mg stannouschloride dihydrate and not more than 0.385 mg maximum tin expressedas stannous chloride dihydrate. The lyophilized product is sealedunder an atmosphere of nitrogen.Following reconstitution with the TechnetiumTc 99m eluate, the radioactive solution produced is clear solutionnot exceeding 9250 MBq/mL (250 mCi/mL) of Tc 99m.. Kit for the preparation of TechnetiumTc 99m pentetate injection: 10 mL multiple dose vials containingup to 9250 MBq mL (250 mCi mL) at time of preparation (reconstitution)(3).

GERIATRIC USE SECTION.

8.5 Geriatric Use. No formal studies ofTechnetium Tc 99m pentetate in the elderly were performed to determinewhether they respond differently from younger subjects. Other reportedclinical experience has not identified differences in responses betweenthe elderly and younger patients. In general, dose selection foran elderly patient should be cautious, usually starting at the lowend of the dosing range, reflecting the greater frequency of decreasedhepatic, renal, or cardiac function, and of concomitant disease orother drug therapy.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 How Supplied. DRAXIMAGE(R) DTPAis supplied as multiple dose kits consisting of 10 mL reaction vialscontaining white, lyophilized powder with 20 mg of pentetic acid,5 mg of p-aminobenzoic acid, 3.73 mg of calcium chloride dihydrate,and not less than 0.25 mg stannous chloride dihydrate and not morethan 0.385 mg tin expressed as stannous chloride dihydrate.The radionuclide is not partof the kit. Before reconstitution and radiolabeling with sodium pertechnetateTc 99m injection USP, the contents of the kit are not radioactive.The kits are supplied in thefollowing formats:Carton containing (five) kits NDC 65174.288.05Carton containing 30 (thirty) kits NDC65174.288.30. 16.2 Storage and Handling. Store the unreconstituted reactionvials at 25C (77F); excursions permitted between 15 and 30C (59and 86F). This radiopharmaceutical is approved foruse by persons under license by the Nuclear Regulatory Commissionor the relevant regulatory authority of an Agreement State.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. DRAXIMAGE(R) DTPA, after radiolabeling with Technetium Tc 99m, is indicated for. DRAXIMAGE(R) DTPA is kit for the preparation of Technetium Tc 99m pentetateinjection. Technetium Tc 99m pentetate is radioactive diagnosticagent indicated for:Brain imaging in adults (1.1).Renal visualization, assessment of renal perfusion, andestimation of glomerular filtration rate in adult and pediatric patients(1.2).Lung ventilation imaging and evaluation of pulmonary embolismwhen paired with perfusion imaging in adult and pediatric patients(1.3).. Brain imaging in adults (1.1).. Renal visualization, assessment of renal perfusion, andestimation of glomerular filtration rate in adult and pediatric patients(1.2).. Lung ventilation imaging and evaluation of pulmonary embolismwhen paired with perfusion imaging in adult and pediatric patients(1.3).. 1.1 BrainImaging. Brainimaging in adults by intravenous administration.. 1.2 RenalScintigraphy. Renal visualization, assessment of renal perfusion, and estimationof glomerular filtration rate in adult and pediatric patients by intravenousadministration.. 1.3 LungVentilation Imaging. Lung ventilation imaging and evaluationof pulmonary embolism when paired with perfusion imaging in adultand pediatric patients when administered by nebulizer for inhalation.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELINGINFORMATION. Administration InstructionsIntravenous UseAdvise patientsto hydrate after administration of Tc 99m labeled DRAXIMAGE(R) DTPA injection and to void frequently to minimizeradiation dose [see Dosage and Administration (2.3)].InhalationUseTo minimize the potential of mouth and esophagealactivity of Tc 99m labeled DRAXIMAGE(R) DTPA,advise the patient to rinse their mouth with water and spit it outprior to imaging [see Dosage and Administration (2.3)]. PregnancyAdvise pregnant women of the riskof fetal exposure to radiation if they undergo radionuclide procedure [see Use in Specific Populations (8.1)].

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Intravenous AdministrationFollowing intravenousadministration for brain and renal imaging, Technetium Tc 99m pentetateis distributed in the vascular compartment. It is cleared by thekidneys, which results in the ability to image the kidney.Aerosolized Inhalation AdministrationFollowing inhalation of the aerosol, Technetium Tc 99m pentetatedeposits on the epithelium of ventilated alveoli.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Radioactive Label. Radioactive Label.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. Technetium Tc 99m pentetate is indicatedfor lung ventilation and evaluation of pulmonary embolism when pairedwith perfusion imaging and for renal visualization, assessment ofrenal perfusion, and estimation of glomerular filtration rate in pediatricpatients ages birth to less than 17 years of age. Pediatric use issupported by evidence from controlled studies in adults and dosingand safety are based on clinical experience.The radiation risk of Technetium Tc 99mpentetate is greater in pediatric patients than adults [SeeWarnings and Precautions, (5.3)].

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Brain ImagingTechnetium Tc 99m pentetate with intravenous administrationtends to accumulate in intra-cranial lesions with excessive neovascularityor an altered blood brain barrier. Technetium Tc 99m pentetate accumulationin the brain is prevented by an intact blood brain barrier. It doesnot accumulate in the choroid plexus.Renal ScintigraphyThe first few minutes after intravenous administration,Technetium Tc 99m pentetate is present in the vascular compartmentwithin the renal system.Lung VentilationImagingIn patients with normal lungs, thedeposition of Technetium Tc 99m pentetate is homogeneous throughoutthe lungs. In patients with airway disease, the deposition patternsbecome inhomogeneous with irregular deposition of Technetium Tc 99mpentetate in the airways and alveolar regions of the lung.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. After anintravenous administration, the pharmacokinetics of Technetium Tc99m pentetate were studied by monitoring radioactivity in serial venousblood samples for hours post-administration. The mean plasma clearancerate was 6.8 (L/h) and the mean plasma elimination half-life (t 1/2 )was 2.1 hours. The mean volume of distribution at steady state conditionscalculated with clearance and mean residence time was 17 L. Thisrelatively low volume of distribution after intravenous administrationsuggests that Technetium Tc 99m pentetate distributes to the extracellularfluid only. The rate of elimination of Technetium Tc 99m pentetatefrom the systemic circulation appears to be constant over an approximately20-fold intravenous dose range.AbsorptionFollowing inhalation Technetium Tc 99m pentetate wasabsorbed (Tmax <2 hours after inhalation)and distributed across the lung epithelium (bioavailability approximately70%) and into the systemic circulation.DistributionFollowing intravenous administration, TechnetiumTc 99m pentetate is distributed throughout the extracellular fluidspace and is cleared from the body by the kidney.The steady-state volumeof distribution (Vss) was 17 following an intravenous administration. Technetium Tc 99m pentetate distribution appears to be limited tothe extravascular compartment.A variable percentage of the TechnetiumTc 99m pentetate binds to the serum proteins; this ranges from 3.7%following single injection to approximately 10% if the materialis continuously infused. Although the chelate gives useful informationon the glomerular filtration rate, the variable percent which is proteinbound leads to measured renal clearance rate which is lower thanthat determined by inulin clearance.EliminationMetabolismTechnetium Tc99m pentetate is not metabolized.ExcretionAfter either intravenous administration or inhalation,excretion is by glomerular filtration. The mean fraction of intravenouslyadministered Technetium Tc 99m pentetate excreted in urine over 24hours was 102%.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryLimited available data with TechnetiumTc 99m pentetate use in pregnant women are insufficient to informa drug associated risk for major birth defects and miscarriage. TechnetiumTc 99m pentetate is transferred across the placenta (see Data). No animal reproductivestudies have been conducted with Technetium Tc 99m pentetate. Allradiopharmaceuticals have the potential to cause fetal harm dependingon the fetal stage of development and the magnitude of the radiationdose. If considering Technetium Tc 99m pentetate administration toa pregnant woman, inform the patient about the potential for adversepregnancy outcomes based on the radiation dose from Technetium Tc99m pentetate and the gestational timing of exposure.The estimated backgroundrisk of major birth defects and miscarriage for the indicated populationis unknown. In the U.S., general population, the estimated backgroundrisk of major birth defects and miscarriage in clinically recognizedpregnancies are 2-4% and 15-20%, respectively.DataHuman DataLimited published literature describes Technetium Tc99m pentetate crossing the placental barrier. No adverse fetal effectsor radiation-related risks have been identified for diagnostic proceduresinvolving less than 50 mGy, which represents less than 10 mGy fetaldoses.

RECENT MAJOR CHANGES SECTION.

Indications and Usage, Lung Ventilation Imaging (1.3)12/2017Dosage and Administration, Lung Ventilation Imaging (2)12/2017.

SPL UNCLASSIFIED SECTION.

1.1 BrainImaging. Brainimaging in adults by intravenous administration.

STORAGE AND HANDLING SECTION.

16.2 Storage and Handling. Store the unreconstituted reactionvials at 25C (77F); excursions permitted between 15 and 30C (59and 86F). This radiopharmaceutical is approved foruse by persons under license by the Nuclear Regulatory Commissionor the relevant regulatory authority of an Agreement State.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryLimited available data with TechnetiumTc 99m pentetate use in pregnant women are insufficient to informa drug associated risk for major birth defects and miscarriage. TechnetiumTc 99m pentetate is transferred across the placenta (see Data). No animal reproductivestudies have been conducted with Technetium Tc 99m pentetate. Allradiopharmaceuticals have the potential to cause fetal harm dependingon the fetal stage of development and the magnitude of the radiationdose. If considering Technetium Tc 99m pentetate administration toa pregnant woman, inform the patient about the potential for adversepregnancy outcomes based on the radiation dose from Technetium Tc99m pentetate and the gestational timing of exposure.The estimated backgroundrisk of major birth defects and miscarriage for the indicated populationis unknown. In the U.S., general population, the estimated backgroundrisk of major birth defects and miscarriage in clinically recognizedpregnancies are 2-4% and 15-20%, respectively.DataHuman DataLimited published literature describes Technetium Tc99m pentetate crossing the placental barrier. No adverse fetal effectsor radiation-related risks have been identified for diagnostic proceduresinvolving less than 50 mGy, which represents less than 10 mGy fetaldoses.. 8.2 Lactation. Risk SummaryThere are limited data available in scientific literature on thepresence of Technetium Tc 99m pentetate in human milk. There areno data available on the effects of Technetium Tc 99m pentetate onthe breastfed infant or the effects on milk production. Based onthe United States Nuclear Regulatory Commission guidelines for breastfeeding interruption after exposure to radiopharmaceuticals, breastfeedinginterruption is not recommended for Technetium 99m pentetate at levelsless than 1000 MBq (30 mCi). The developmental and health benefitsof breastfeeding should be considered along with the mothers clinicalneed for Technetium Tc 99m pentetate, any potential adverse effectson the breastfed child from Technetium Tc 99m pentetate or from theunderlying maternal condition.. 8.4 Pediatric Use. Technetium Tc 99m pentetate is indicatedfor lung ventilation and evaluation of pulmonary embolism when pairedwith perfusion imaging and for renal visualization, assessment ofrenal perfusion, and estimation of glomerular filtration rate in pediatricpatients ages birth to less than 17 years of age. Pediatric use issupported by evidence from controlled studies in adults and dosingand safety are based on clinical experience.The radiation risk of Technetium Tc 99mpentetate is greater in pediatric patients than adults [SeeWarnings and Precautions, (5.3)]. 8.5 Geriatric Use. No formal studies ofTechnetium Tc 99m pentetate in the elderly were performed to determinewhether they respond differently from younger subjects. Other reportedclinical experience has not identified differences in responses betweenthe elderly and younger patients. In general, dose selection foran elderly patient should be cautious, usually starting at the lowend of the dosing range, reflecting the greater frequency of decreasedhepatic, renal, or cardiac function, and of concomitant disease orother drug therapy.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Hypersensitivity reactions: Hypersensitivity reactions,including anaphylaxis, have been reported during post-approval diagnosticuse of Technetium Tc 99m pentetate injection. Monitor all patientsfor hypersensitivity reactions (5.1).Image interpretation risks in lung ventilation studies: If proximal airway deposition is observed, consider additional diagnosticoptions (5.2).Radiation exposure risk: Technetium Tc 99m pentetate contributesto patients overall long-term radiation exposure (2.1, 2.3, 5.3).Bronchospasm in lung ventilation studies: Inhalation ofTechnetium Tc 99m pentetate solution may result in acute bronchoconstriction,especially in patients with heightened bronchoreactivity (5.4). Hypersensitivity reactions: Hypersensitivity reactions,including anaphylaxis, have been reported during post-approval diagnosticuse of Technetium Tc 99m pentetate injection. Monitor all patientsfor hypersensitivity reactions (5.1).. Image interpretation risks in lung ventilation studies: If proximal airway deposition is observed, consider additional diagnosticoptions (5.2).. Radiation exposure risk: Technetium Tc 99m pentetate contributesto patients overall long-term radiation exposure (2.1, 2.3, 5.3).. Bronchospasm in lung ventilation studies: Inhalation ofTechnetium Tc 99m pentetate solution may result in acute bronchoconstriction,especially in patients with heightened bronchoreactivity (5.4). 5.1 HypersensitivityReactions. Hypersensitivity reactions, including anaphylaxis, have been reportedduring post-approval diagnostic use of Technetium Tc 99m pentetateinjection. Monitor all patients for hypersensitivity reactions andhave access to cardiopulmonary resuscitation equipment and personnel.. 5.2 ImageInterpretation Risks in Lung Ventilation Studies. In patients with obstructivepulmonary disease there may be deposition of particles in the proximalairways influencing image quality and interfering with diagnosticinterpretation, therefore to ensure diagnostic quality, careful useof the nebulizer to assure optimal particle delivery is essential. If interfering particle deposition occurs, consider additional diagnosticoptions.. 5.3 RadiationExposure Risk. Technetium Tc 99m contributes to patients overall long-term cumulativeradiation exposure. Long-term cumulative radiation exposure is associatedwith an increased risk of cancer. Ensure safe handling and preparationprocedures to protect patients and health care workers from unintentionalradiation exposure. Use the lowest dose of Technetium Tc 99m pentetatenecessary for imaging. Encourage patients to drink fluids and voidas frequently as possible after intravenous administration [see Dosage and Administration (2.1, 2.3)].Radiation risks associated with the use ofTechnetium Tc 99m pentetate are greater in pediatric patients thanin adults due to greater radiosensitivity and longer life expectancy.. 5.4 Bronchospasmin Lung Ventilation Studies. As with other inhaled medications, inhalationof Technetium Tc 99m pentetate solution may result in acute bronchoconstriction,especially in patients with heightened bronchoreactivity, such aspatients with asthma or other lung or allergic disorders. Monitorall patients for bronchoconstriction.