lantheus medical imaging, inc. - Medication Listings

Each 5 mL vial contains a sterile, non-pyrogenic, lyophilized mixture of: Tetrakis (2-methoxy isobutyl isonitrile) Copper (I) tetrafluoroborate - 1.0 mg Sodium Citrate Dihydrate - 2.6 mg L-Cysteine Hydrochloride Monohydrate - 1.0 mg Mannitol – 20 mg Stannous Chloride, Dihydrate, minimum (SnCl 2 ∙2H 2 O) - 0.025 mg Stannous Chloride, Dihydrate, (SnCl 2 ∙2H 2 O) - 0.075 mg Tin Chloride (stannous and stannic) Dihydrate, maximum (as SnCl 2 ∙2H 2 O) - 0.086 mg Prior to lyophilization the pH is 5.3 to 5.9. The contents of the vial are lyophilized and stored under nitrogen. This drug is administered by intravenous injection for diagnostic use after reconstitution with sterile, non-pyrogenic, oxidant-free Sodium Pertechnetate Tc99m Injection. The pH of the reconstituted product is 5.5 (5.0 - 6.0). No bacteriostatic preservative is present. The precise structure of the technetium complex is Tc99m[MIBI] 6 + where MIBI is 2-methoxy isobutyl isonitrile. 11.1 Physical Characteristics Technetium Tc99m decays by isomeric transition with a physical half-life of 6.02 hours Kocher, David, C., Radioactive Decay Data Tables, DOE/TIC-11026, 108(1981). . Photons that are useful for detection and imaging studies are listed below in Table 3.0. Table 3.0. Principal Radiation Emission Data Radiation Mean %/Disintegration Mean Energy (KeV) Gamma -2 89.07 140.5 11.2 External Radiation The specific gamma ray constant for Tc99m is 5.4 microcoulombs/Kg-MBq-hr (0.78R/mCi-hr) at 1 cm. The first half value layer is 0.017 cm of Pb. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 4.0. To facilitate control of the radiation exposure from Megabequerel (millicurie) amounts of this radionuclide, the use of a 0.25 cm thickness of Pb will attenuate the radiation emitted by a factor of 1,000. Table 4.0. 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 To correct for physical decay of this radionuclide, the fractions that remain at selected intervals after the time of calibration are shown in Table 5.0. Table 5.0 Physical Decay Chart; Tc99m Half-Life 6.02 Hours Hours Fraction Remaining Hours Fraction Remaining 0 Calibration Time 1.000 8 .398 1 .891 9 .355 2 .794 10 .316 3 .708 11 .282 4 .631 12 .251 5 .562 6 .501 7 .447

DEFINITY ( perflutren lipid microsphere ) injectable suspension is, after activation an ultrasound contrast agent for intravenous use. The perflutren lipid microspheres are composed of perflutren encapsulated in an outer lipid shell consisting of (R) – hexadecanoic acid, 1-[(phosphonoxy)methyl]-1,2-ethanediyl ester, monosodium salt (abbreviated DPPA); (R) - 4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxohexadecyl)oxy]-3,4,9-trioxa-4-phosphapentacosan-1-aminium, 4-oxide, inner salt (abbreviated DPPC); and (R)-∝-[6-hydroxy-6-oxido-9-[(1-oxohexadecyl)oxy]-5,7,11-trioxa-2-aza-6-phosphahexacos-1-yl]- ω-methoxypoly(ox-1,2-ethanediyl), monosodium salt; commonly called N-( m ethoxy p oly e thylene g lycol 5000 carbamoyl)-1,2- d i p almitoyl-sn-glycero-3- p hosphatidyl e thanolamine, monosodium salt (abbreviated MPEG5000 DPPE). Perflutren is chemically characterized as 1,1,1,2,2,3,3,3-octafluoropropane. It has a molecular weight of 188, empirical formula of C 3 F 8 and has the following structural formula: DPPA has a molecular weight of 670, empirical formula of C 35 H 68 O 8 PNa, and following structural formula: DPPC has a molecular weight of 734, empirical formula of C 40 H 80 NO 8 P, and following structural formula: MPEG5000 DPPE has an approximate molecular weight of 5750 represented by empirical formula C 265 H 527 NO 123 PNa, contains <100ppm Ca 2+ and Mg 2+ and the following structural formula: Prior to activation, perflutren is in the headspace of the vial with a concentration of 6.52 mg/mL which is confirmed by positive IR spectroscopic testing in every vial. The lipid blend is in the clear, colorless, hypertonic, sterile liquid. Each mL of the liquid contains 0.75 mg lipid blend (consisting of 0.045 mg DPPA, 0.401 mg DPPC, and 0.304 mg MPEG5000 DPPE) and the following inactive ingredients: 103.5 mg propylene glycol, 126.2 mg glycerin, 2.34 mg sodium phosphate monobasic monohydrate, 2.16 mg sodium phosphate dibasic heptahydrate, and 4.87 mg sodium chloride in water for injection. The pH is 6.2 to 6.8. DEFINITY does not contain bacterial preservative. After activation with the aid of the VIALMIX or VIALMIX RFID, each mL of the activated DEFINITY as homogenous milky white suspension contains a maximum of 1.2 × 10 10 perflutren lipid microspheres, and about 150 microL/mL (1.1 mg/mL) perflutren. The microsphere particle size parameters are listed in Table 2 below: Table 2 Microsphere Size Distribution Microsphere particle size parameters Mean diameter range 1.1 µm – 3.3 µm Percent less than 10 µm 98% Maximum diameter 20 µm Chemical Structure Chemical Structure Chemical Structure Chemical Structure

DEFINITY RT (perflutren lipid microsphere) injectable suspension is, after activation, an ultrasound contrast agent for intravenous use. The perflutren lipid microspheres are composed of perflutren encapsulated in an outer lipid shell consisting of (R) – hexadecanoic acid, 1-[(phosphonoxy)methyl]-1,2-ethanediyl ester, monosodium salt (abbreviated DPPA); (R) - 4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxohexadecyl)oxy]-3,4,9-trioxa-4-phosphapentacosan-1-aminium, 4-oxide, inner salt (abbreviated DPPC); and (R)- ∝-[6-hydroxy-6-oxido-9-[(1-oxohexadecyl)oxy]-5,7,11-trioxa-2-aza-6-phosphahexacos-1-yl]- ω-methoxypoly(ox-1,2-ethanediyl), monosodium salt; commonly called N-( m ethoxy p oly e thylene g lycol 5000 carbamoyl)-1,2- d i p almitoyl-sn-glycero-3- p hosphatidyl e thanolamine, monosodium salt (abbreviated MPEG5000 DPPE). Perflutren is chemically characterized as 1,1,1,2,2,3,3,3-octafluoropropane. It has a molecular weight of 188, empirical formula of C 3 F 8 and has the following structural formula: DPPA has a molecular weight of 670, empirical formula of C 35 H 68 O 8 PNa, and following structural formula: DPPC has a molecular weight of 734, empirical formula of C 40 H 80 NO 8 P, and following structural formula: MPEG5000 DPPE has an approximate molecular weight of 5750 represented by empirical formula C 265 H 527 NO 123 PNa, contains <100ppm Ca 2+ and Mg 2+ and the following structural formula: Prior to activation, perflutren is in the headspace of the vial with a concentration of 6.52 mg/mL which is confirmed by positive IR spectroscopic testing in every vial. The lipid blend is in the clear, colorless to translucent (hazy), viscous sterile solution. Each mL of the solution contains 3.75 mg lipid blend (consisting of 0.225 mg DPPA, 2.005 mg DPPC, and 1.520 mg MPEG5000 DPPE) and the following inactive ingredients: 517.5 mg propylene glycol, 631 mg glycerin, 0.370 mg anhydrous sodium acetate, and 0.030 mg glacial acetic acid. The pH is 5.2 to 6.4. DEFINITY RT does not contain bacterial preservative. After activation with the aid of VIALMIX RFID and dilution with 1.4 mL of preservative-free 0.9% Sodium Chloride, Injection, USP, each mL of the activated DEFINITY RT as homogeneous milky white suspension contains 0.045 mg DPPA, 0.401 mg DPPC, 0.304 mg MPEG5000 DPPE, 0.074 mg anhydrous sodium acetate, 0.006 mg glacial acetic acid, a maximum of 1.2 × 10 10 perflutren lipid microspheres, and about 80 microL/mL (0.65 mg/mL) perflutren. The microsphere particle size parameters are listed in Table 2 below: Table 2 Microsphere Size Distribution Microsphere particle size parameters Mean diameter range 1.1 µm – 3.3 µm Percent less than 10 µm 98% Maximum diameter 20 µm Chemical Structure Chemical Structure Chemical Structure Chemical Structure

Each 5 mL vial contains a sterile, non-pyrogenic, lyophilized mixture of: Tetrakis (2-methoxy isobutyl isonitrile) Copper (I) tetrafluoroborate - 1.0 mg Sodium Citrate Dihydrate - 2.6 mg L-Cysteine Hydrochloride Monohydrate - 1.0 mg Mannitol – 20 mg Stannous Chloride, Dihydrate, minimum (SnCl 2 ∙2H 2 O) - 0.025 mg Stannous Chloride, Dihydrate, (SnCl 2 ∙2H 2 O) - 0.075 mg Tin Chloride (stannous and stannic) Dihydrate, maximum (as SnCl 2 ∙2H 2 O) - 0.086 mg Prior to lyophilization the pH is 5.3 to 5.9. The contents of the vial are lyophilized and stored under nitrogen. This drug is administered by intravenous injection for diagnostic use after reconstitution with sterile, non-pyrogenic, oxidant-free Sodium Pertechnetate Tc99m Injection. The pH of the reconstituted product is 5.5 (5.0 - 6.0). No bacteriostatic preservative is present. The precise structure of the technetium complex is Tc99m[MIBI] 6 + where MIBI is 2-methoxy isobutyl isonitrile. 11.1 Physical Characteristics Technetium Tc99m decays by isomeric transition with a physical half-life of 6.02 hours Kocher, David, C., Radioactive Decay Data Tables, DOE/TIC-11026, 108(1981). . Photons that are useful for detection and imaging studies are listed below in Table 3.0. Table 3.0. Principal Radiation Emission Data Radiation Mean %/Disintegration Mean Energy (KeV) Gamma -2 89.07 140.5 11.2 External Radiation The specific gamma ray constant for Tc99m is 5.4 microcoulombs/Kg-MBq-hr (0.78R/mCi-hr) at 1 cm. The first half value layer is 0.017 cm of Pb. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 4.0. To facilitate control of the radiation exposure from Megabequerel (millicurie) amounts of this radionuclide, the use of a 0.25 cm thickness of Pb will attenuate the radiation emitted by a factor of 1,000. Table 4.0. 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 To correct for physical decay of this radionuclide, the fractions that remain at selected intervals after the time of calibration are shown in Table 5.0. Table 5.0 Physical Decay Chart; Tc99m Half-Life 6.02 Hours Hours Fraction Remaining Hours Fraction Remaining 0 Calibration Time 1.000 8 .398 1 .891 9 .355 2 .794 10 .316 3 .708 11 .282 4 .631 12 .251 5 .562 6 .501 7 .447

This kit formulation consists of two nonradioactive vials: Vial A contains bicisate dihydrochloride (N, N'-1,2-ethylenediylbis-L-cysteine diethyl ester dihydrochloride) and a reducing agent as a lyophilized solid and vial B contains a buffer solution. Both vials are sterile and non-pyrogenic. Vial A – Bicisate dihydrochloride (ECD•2HCl) 0.9 mg Edetate disodium, dihydrate 0.36 mg Mannitol 24 mg Stannous chloride, dihydrate, theoretical (SnCl 2 •2H 2 O) 72 µg Stannous chloride, dihydrate, minimum (SnCl 2 •2H 2 O) 12 µg Total Tin, (stannous and stannic), dihydrate (as SnCl 2 •2H 2 O) 83 µg The contents of vial A are lyophilized and stored under nitrogen. The pH of the solution before lyophilization is 2.7 ± 0.25. This vial is stored at 15-25°C. Protect from light. Vial B – Sodium phosphate dibasic heptahydrate 4.1 mg Sodium phosphate monobasic monohydrate 0.46 mg Water for Injection qs 1 mL The contents of vial B are stored under air. The pH of the solution is 7.6 ± 0.4. This vial is stored at 15-25°C. This drug is administered by intravenous injection for diagnostic use after reconstitution with sterile, non-pyrogenic, oxidant-free Sodium Pertechnetate Tc99m Injection. The precise structure of the Technetium complex is [ N , N '-ethylenedi- L -cysteinato(3-)]oxo[ 99m Tc] technetium (V), diethyl ester.

Sodium Pertechnetate Tc 99m Injection, as eluted according to the elution instructions with Lantheus Medical Imaging, Inc. TECHNELITE ® , Technetium Tc 99m Generator, is in 0.9% Sodium Chloride Injection, USP as a sterile, non-pyrogenic, diagnostic radiopharmaceutical suitable for intravenous injection and direct instillation. The pH is 4.5-7.5. The eluate should be clear, colorless, and free from visible foreign material. Each eluate of the TECHNELITE ® , Technetium Tc 99m Generator should not contain more than 0.0056MBq (0.15 microcuries) of Molybdenum Mo99 per 37MBq (1 millicurie) of Technetium Tc 99m per administered dose at the time of administration, and not more than 10 micrograms of aluminum per milliliter of the Technetium Tc 99m Generator eluate, both of which must be determined by the user before administration. Since the eluate does not contain an antimicrobial agent, it should not be used later than one (1) working day after the elution (12 hours). Lantheus Medical Imaging, Inc. TECHNELITE ® , Technetium Tc 99m Generator consists of a column containing uranium fission produced Molybdenum Mo99 adsorbed on alumina. The terminally sterilized and sealed column is enclosed in a lead shield; the shield and other components are sealed in a cylindrical plastic container with an attached handle. Built into the top surface are two recessed wells marked SALINE CHARGE and COLLECT. Needles protruding from these two wells accommodate supplied sterile eluant charge vials and sterile eluate collection vials. The eluting solvent consists of 0.9% Sodium Chloride Injection, USP, prepacked into septum-sealed vials, to make the solution isotonic. The eluate collection vial is evacuated, sterile and non-pyrogenic. A sterile 0.22 micrometer bacteriological filter is incorporated between the column outlet and the collection vials. During and subsequent to elution, the eluate collection vial should be kept in a radiation shield. The Generator is shipped with a silicone needle seal over the charge needle and a vented needle cover over the collect needle. A sterile collect needle seal is supplied for the customer to aseptically reseal the collect needle after each elution. Physical Characteristics Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours. 1 Photons that are useful for imaging studies are listed in Table 1. Table 1. Principal Radiation Emission Data - Technetium Tc 99m Radiation Mean %/Disintegration Mean Energy (keV) Gamma-2 89.07 140.5 External Radiation The specific gamma ray constant for Technetium Tc 99m is 5.4 microcoulombs/Kg-MBq-hr (0.795 R/mCi-hr) at 1cm. The first half-value thickness is 0.023cm of lead (Pb). To facilitate control of radiation exposure from millicurie amounts of Technetium Tc 99m, for example, the use of a 0.27 cm thick standard radiation elution lead shield will attenuate the radiation emitted by a factor of about 1000. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of lead is shown in Table 2. NOTE : Because the generator is well contained and essentially dry, there is little likelihood of contamination due to damage in transit. Table 2. Radiation Attenuation of Technetium Tc 99m by Lead Shielding Shield Thickness lead (Pb) cm Coefficient of Attenuation 0.023 0.5 0.09 10 -1 0.18 10 -2 0.27 10 -3 0.33 10 -4 Molybdenum Mo99 decays to Technetium Tc 99m with a Molybdenum Mo99 half-life of 66 hours. This means that only 78% of the activity remains after 24 hours; 60% remains after 48 hours, etc. (see Table 3). All units have a minimum of 38 mm, 1.5 inches (~ 6 half-value layers) of lead surrounding the activity. (See Table 3.) Table 3. Molybdenum Mo99 Decay Chart Half-Life 66.0 Hours Days Percent Remaining Days Percent Remaining 0 100 10 8 1 78 11 6 2 60 12 5 3 47 13 4 4 37 14 3 5 28 15 2 6 22 20 0.6 7 17 25 0.2 8 13 30 0.05 9 10 The physical decay characteristics of Molybdenum Mo99 are such that approximately 88% of the decaying Molybdenum Mo99 atoms form Technetium Tc 99m. Since the Molybdenum Mo99 is constantly decaying to fresh Technetium Tc 99m, it is possible to elute the generator at any time. However, the total amount of Technetium Tc 99m available will depend on the time interval from the previous elution, the quantity of Molydenum Mo99 remaining and the efficiency of the elution. Approximately 47% of maximum Technetium Tc 99m is reached after 6 hours and 95% after 23 hours. The elution vial shield has a wall thickness of 7.9 mm, 0.31 inches, and reduces transmitted Technetium Tc 99m radiation essentially to zero. To correct for physical decay of Tc 99m, the fractions that remain at selected intervals of time are shown in Table 4. Table 4. Physical Decay Chart: Technetium Tc 99m Half-Life 6 Hours *Calibration Time Hours Percent Remaining Hours Percent Remaining 0* 100.0 9 35 1 89 10 32 2 79 11 28 3 71 12 25 4 63 14 20 5 56 16 16 6 50 18 13 7 45 24 6 8 40

Xenon Xe 133 Gas is supplied in a mixture of xenon gas (5%) in carbon dioxide (95%). It is contained within septum sealed glass vials and is suitable for inhalation in the diagnostic evaluation of pulmonary function and imaging, as well as assessment of cerebral blood flow. Xenon Xe 133 Gas is reactor-produced as a by-product of Uranium U235 fission. Each vial contains the labeled amount of Xenon Xe 133 radioactivity at the time of calibration. The contents of the vial are in gaseous form, contain no preservatives, and are ready for use. Xenon Xe 133 is chemically and physiologically related to elemental Xenon, a non-radioactive monoatomic gas which is physiologically inert except for anesthetic properties at high doses. PHYSICAL CHARACTERISTICS Xenon Xe 133 decays by beta and gamma emissions with a half-life of 5.245 days. Kocher, David C., "Radioactive Decay Data Tables," DOE/TIC-11026, p. 138,1981. Significant radiations which are emitted by the nuclide are listed in Table 1. Table 1. Principal Radiation Emission Data from Xenon-133 Mean Mean % per Radiation Energy (KeV) Disintegration Beta-2 100.6 99.3 Ce-K-2 45.0 53.3 Ce-L-2 75.3 8.1 Ce-M-2 79.8 1.7 Gamma-2 81.0 36.5 K α2 X-ray 30.6 13.6 K α1 X-ray 31.0 25.3 K β X-ray 35.0 9.1 EXTERNAL RADIATION The specific gamma ray constant for Xenon Xe 133 is 3.6 microcoulombs/Kg-MBq-hr (0.51R/hr-mCi) at 1 cm. The first half value thickness of lead is 0.0035 cm. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from the interposition of various thicknesses of Pb is shown in Table 2. For example, the use of 0.20 cm of Pb will decrease the external radiation exposure by a factor of 1,000. Table 2. Radiation Attenuation by Lead Shielding cm of Pb Radiation Attenuation Factor 0.0035 0.5 0.037 10 -1 0.12 10 -2 0.20 10 -3 0.29 10 -4 To correct for physical decay of this radionuclide, the fractions that remain at selected time intervals after the time of calibration are shown in Table 3. Table 3. Xenon Xe 133 Physical Decay Chart (Half Life 5.245 days) Fraction Fraction Day Remaining Day Remaining 0 Calibration Day 1.000 8 .349 1 .877 9 .302 2 .768 10 .268 3 .674 11 .235 4 .591 12 .206 5 .518 13 .181 6 .452 14 .157 7 .398