Iodinated I-131 Albumin

INDICATIONS AND USAGE MEGATOPE is indicated in adults for use in determinations of total blood and plasma volumes.

DOSAGE AND ADMINISTRATION Premedication Administer 10 drops of Strong Iodine Solution, USP (e.g., Lugol’s Solution) three times daily, beginning at least 24 hours before administration of MEGATOPE and continue for 1 week or 2 weeks thereafter to minimize the uptake of iodine-131. Recommended Dosage The recommended dose of MEGATOPE for total blood or plasma volume determination in adult patients is from 0.185 MBq to 1.85 MBq (5 microCi to 50 microCi) administered intravenously. When a procedure such as a blood volume is to be repeated, do not exceed 7.4 MBq (200 microCi) in any 1 week. Administration Instructions • Measure the patient dose using a suitable dose calibrator immediately prior to administration. • Use a shielded syringe for withdrawing and injecting MEGATOPE. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. MEGATOPE is a colorless to very pale yellow solution. Do not use MEGATOPE if excessive coloration is present. • The expiration date given on the MEGATOPE vial label pertains to the stability of MEGATOPE and not to the radioactivity level. Blood Volume Determination Preparation of Reference Solution 1. Remove the amount from the vial to be used in the procedure identical in volume to the dose to be administered to the patient. 2. Prepare a reference solution using 0.9% Sodium Chloride Injection, USP as a diluent. The recommended dilution is 1:4,000 [Dilution Factor (DF) = 4,000]. 3. Determine the radioactivity concentration (net cpm/mL) of the reference solution. 4. Assay the reference solution and the blood samples (Step 3 of Administration of Dose ) using the same geometric configuration. Administration of Dose 1. Inject the dose into a large vein in patient’s arm. Measure the residual radioactivity in the syringe and needle. 2. Do not reuse the syringe. Dispose the syringe in accordance with the US Nuclear Regulatory Commission or Agreement State regulations pertaining to the disposal of radioactive waste. 3. At 5 minutes and 15 minutes after injecting the dose, withdraw blood samples from the patient’s other arm with a sterile heparinized syringe. Calculation of Blood Volume 1. Take a known aliquot from each blood sample and determine radioactivity concentration in net cpm/mL. 2. Plot the 5-minute and 15- minute sample counts (net cpm/mL) on semilog graph paper using the average count value of each sample and determine the radioactivity concentration at injection time (zero time) by drawing a straight line through the 15-minute and 5-minute points to zero time. The x ordinate of the graph is the sample withdrawal time and the logarithmic y ordinate is radioactivity concentration in net cpm/mL. 3. Calculate patient’s blood volume (in mL) using the following formula: Net cpm/mL reference solution x DF* = blood volume (in mL) Net cpm/mL patient's blood sample *DF: Dilution factor of reference solution Sample Blood Volume Calculations Volume of blood sample aliquot = 1 mL Volume of reference solution aliquot = 1 mL Net counts at zero time = 48,100 Net counts obtained from reference solution aliquot = 52,430 Using the formula above gives 52,430 x 4,000 = 4,360 mL 48,100 Serial Blood Volume Determinations • Use a low dose of MEGATOPE to permit repetitions as often as required by clinical circumstances. • In each determination after the first dose, correct the background radioactivity remaining in the blood from former determinations by subtracting the radioactivity concentration of a blood sample obtained before the injection of MEGATOPE (i.e., background blood sample) from the radioactivity concentration of a post-injection blood sample. Background Blood Sample 1. Prior to injecting MEGATOPE, withdraw background blood sample from large vein in patient’s arm with a sterile heparinized syringe. 2. Leaving needle in patient’s vein, detach syringe containing blood sample. 3. Attach syringe containing the dose of MEGATOPE to the indwelling needle and administer (see instructions under Blood Volume Determination, Administration of Dose ). 4. Determine radioactivity concentration in net cpm/mL of aliquots taken from background and post-injection blood samples, and from the reference solution. Calculation of Blood Volume Subtract the radioactivity concentration (net cpm/mL) per aliquot of the background blood sample from the radioactivity concentration per aliquot of the blood sample obtained after the injection of MEGATOPE. The formula for calculating each blood volume determination after the first one thus becomes: Net cpm/mL reference solution x DF* = blood volume (in mL) Net cpm/mL Net cpm/mL postinjection minus background blood sample blood sample *DF: Dilution Factor of reference solution Plasma Volume Determination The procedure is essentially the same as that for blood volume determination, except that the blood sample drawn from the patient is centrifuged, the red blood cells are removed, and net cpm /mL of the plasma is determined. The formula for calculation of plasma volume, therefore, is: Net cpm/mL reference solution x DF* = plasma volume (in mL) Net cpm/mL patient's plasma sample *DF: Dilution factor of reference solution Radiation Dosimetry The estimated absorbed radiation doses to an adult patient from an intravenous injection of 1.85 MBq (50 microCi) of MEGATOPE are shown in Table 4. Method of Calculation: Hine GJ, Johnston RE: Absorbed Doses from Radionuclides, J. Nucl Med 11:468-469,1970. MegaT-4

ADVERSE REACTIONS The following adverse reactions have been identified with the use of radioiodinated albumin products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Hypersensitivity