Ultra-Technekow V4

INDICATIONS AND USAGE The Ultra-Technekow™ V4 generator is a source of sodium pertechnetate Tc 99m for use in the preparation of FDA-approved diagnostic radiopharmaceuticals, as described in the labeling of these diagnostic radiopharmaceutical kits. Sodium Pertechnetate Tc 99m is used IN ADULTS as an agent for: Thyroid Imaging Salivary Gland Imaging Urinary Bladder Imaging (direct isotopic cystography) for detection of vesico-ureteral reflux Nasolacrimal Drainage System Imaging (dacryoscintigraphy) Sodium Pertechnetate Tc 99m is used IN PEDIATRIC PATIENTS as an agent for: Thyroid Imaging Urinary Bladder Imaging (direct isotopic cystography) for the detection of vesico-ureteral reflux

DOSAGE AND ADMINISTRATION Sodium Pertechnetate Tc 99m is administered by intravenous injection. When imaging the nasolacrimal drainage system, instill the Sodium Pertechnetate Tc 99m by the use of a device such as a micropipette or similar method which will ensure the accuracy of the dose. For imaging the urinary bladder and ureters (direct isotopic cystography), the Sodium Pertechnetate Tc 99m is administered by direct instillation aseptically into the bladder via a urethral catheter, following which the catheter is flushed with approximately 200 mL of sterile saline directly into the bladder. The suggested dose ranges employed for various diagnostic indications in the average ADULT PATIENT (70 kg) are as follows: Vesico-ureteral imaging: 18.5 to 37 MBq (0.5 to 1 mCi) Thyroid gland imaging: 37 to 370 MBq (1 to 10 mCi) Salivary gland imaging: 37 to 185 MBq (1 to 5 mCi) Nasolacrimal drainage system: Maximum dose of 3.7 MBq (100 µCi) The recommended dosages in PEDIATRIC PATIENTS are: Vesico-ureteral imaging: 18.5 to 37 MBq (0.5 to 1 mCi) Thyroid gland imaging: 2.22 to 2.96 MBq (60 to 80 µCi) per kg body weight The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. If the solution is discolored, discontinue use of the generator immediately. The solution to be administered as the patient dose should be clear, colorless, and contain no particulate matter. Radiation Dosimetry The estimated absorbed radiation doses to an average ADULT and PEDIATRIC patient from an intravenous injection of various doses of Sodium Pertechnetate Tc 99m distributed uniformly in the total body are shown in Tables 5 and 6. Table 5. Absorbed Radiation Doses from Intravenous Injection Organ Absorbed Radiation Dose (mGy) for a 1110 MBq (30mCi) dose Adrenals 4.1 Urinary Bladder Wall 20 Bone Surfaces 6.2 Brain 2.2 Breasts 2 Gallbladder Wall 8.3 Stomach Wall 29 Small Intestine 18 ULI Wall 63 LLI Wall 23 Heart Wall 3.5 Kidneys 6 Liver 4.7 Lungs 2.9 Muscle 3.6 Ovaries 11 Pancreas 6.3 Red Marrow 4.1 Skin 2 Spleen 4.8 Testes 3.1 Thymus 2.7 Thyroid 24 Uterus 9 Remaining Tissues 3.9 Effective Dose (mSv) 14 To obtain radiation absorbed dose in rads (30 mCi dose) from the above table, divide individual organ values by a factor of 10 (does not apply for effective dose). Table 6. Pediatric Absorbed Radiation Doses (mGy) from Intravenous Injection Age 15 years 10 years 5 years 1 year Administered activity in MBq (mCi) 1110 (30) 740 (20) 555 (15) 370 (10) Organ Adrenals 5.3 5.4 6.2 7.1 Urinary Bladder Wall 26 22 18 22 Bone Surfaces 7.6 7.5 8.1 10 Brain 2.8 3.1 3.7 4.5 Breasts 2.6 2.6 3.2 4.1 Gallbladder Wall 11 12 13 13 Stomach Wall 38 36 43 59 Small Intestine 22 23 26 30 ULI Wall 81 89 110 140 LLI Wall 31 33 40 48 Heart Wall 4.5 4.6 5.2 6.4 Kidneys 7.2 6.9 7.8 8.5 Liver 6 6.7 8 9.1 Lungs 3.8 3.8 4.4 5.3 Muscle 4.5 4.5 5 6 Ovaries 14 13 14 17 Pancreas 8.1 8.2 8.9 10 Red Marrow 5.1 5 5.2 6 Skin 2.5 2.6 3.2 3.8 Spleen 6 6 6.7 7.8 Testes 4.1 4.3 4.9 6 Thymus 3.6 3.5 4.2 5.3 Thyroid 40 41 67 81 Uterus 11 11 12 14 Remaining Tissues 4.8 4.8 5.4 6.4 Effective Dose (mSv) 19 19 23 29 To obtain radiation absorbed dose in rads (30 mCi dose) from the above table, divide individual organ values by a factor of 10 (does not apply for effective dose). The estimated absorbed radiation doses to an ADULT patient from the nasolacrimal imaging procedure using a maximum dose of 3.7 megabecquerels (100 microcuries) of Sodium Pertechnetate Tc 99m are shown in Table 7. Table 7. Absorbed Radiation Doses from Dacryoscintigraphy Tissue 3.7 MBq (100 µCi) Dose of Sodium Pertechnetate Tc 99m mGy rad Eye Lens: If lacrimal fluid turnover is 16%/min 0.140 0.014 If lacrimal fluid turnover is 100%/min 0.022 0.002 If drainage system is blocked 4.020 0.402 Total Body* 0.011 0.001 Ovaries* 0.030 0.003 Testes* 0.009 0.001 Thyroid* 0.130 0.013 *Assuming no blockage of draining system. In pediatric patients, an average 30 minute exposure to 37 MBq (1 mCi) of Tc-99m pertechnetate following instillation for direct cystography, will result in the following estimated radiation doses: Table 8. Absorbed Radiation Doses from Cystography (PEDIATRIC) Age Bladder wall dose, mGy (rad) Gonadal dose, mGy (rad) 1 year 3.6 (0.36) 0.15 (0.015) 5 years 2.0 (0.2) 0.095 (0.0095) 10 years 1.3 (0.13) 0.066 (0.0066) 15 years 0.92 (0.092) 0.046 (0.0046)

CONTRAINDICATIONS None.

WARNINGS Radiation risks associated with the use of Sodium Pertechnetate Tc 99m are greater in pediatric patients than in adults and, in general, the younger the patient the greater the risk owing to greater absorbed radiation doses and longer life expectancy. These greater risks should be taken firmly into account in all benefit risk assessments involving pediatric patients. Long-term cumulative radiation exposure may be associated with an increased risk of cancer. Only use generator eluant specified for use with the Ultra-Technekow ™ V4 Generator. Do not use any other generator eluant or saline from any other source.

ADVERSE REACTIONS Allergic reactions including anaphylaxis have been reported infrequently following the administration of Sodium Pertechnetate Tc 99m.

Pregnancy In animal reproductive studies, Sodium Pertechnetate Tc 99m (as free pertechnetate) has been shown to cross the placental barrier. It is not known whether Sodium Pertechnetate Tc 99m can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Sodium Pertechnetate Tc 99m should be given to pregnant women only if the expected benefits to be gained clearly outweigh the potential hazards. Ideally, examinations using radiopharmaceutical drug products - especially those elective in nature - of women of childbearing capability should be performed during the first ten days following the onset of menses.