Kit for the Preparation of Indium In 111 Pentetreotide

INDICATIONS AND USAGE Indium In 111 pentetreotide injection, after radiolabeling is an agent for the scintigraphic localization of primary and metastatic neuroendocrine tumors bearing somatostatin receptors.

DOSAGE AND ADMINISTRATION Before administration, a patient should be well hydrated. After administration, the patient must be encouraged to drink fluids liberally. Elimination of extra fluid intake will help reduce the radiation dose by flushing out unbound, labelled pentetreotide by glomerular filtration. It is also recommended that a mild laxative (e.g., bisacodyl or lactulose) be given to the patient starting the evening before the radioactive drug is administered, and continuing for 48 hours. Ample fluid uptake is necessary during this period as a support both to renal elimination and the bowel-cleansing process. In a patient with an insulinoma, bowel-cleansing should be undertaken only after consultation with an endocrinologist. The recommended intravenous dose for planar imaging is 111 MBq (3 mCi) of indium In 111 pentetreotide injection prepared from indium In 111 pentetreotide kit for kit Injection. The recommended intravenous dose for SPECT imaging is 222 MBq (6 mCi) of indium In 111 pentetreotide injection. The dose should be confirmed by a suitably calibrated radioactivity ionization chamber immediately before administration. As with all intravenously administered products, indium In 111 pentetreotide injection should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Preparations containing particulate matter or discoloration should not be administered. They should be disposed of in a safe manner, in compliance with applicable regulations. Aseptic techniques and effective shielding should be employed in withdrawing doses for administration to patients. Waterproof gloves should be worn during the administration procedure. Do not administer indium In 111 pentetreotide injection in TPN solutions or through the same intravenous line. Radiation Dosimetry The estimated radiation doses 2 to the average adult (70 kg) from intravenous administration of 111 MBq (3 mCi) and 222 MBq (6 mCi) are presented in Table 4 . These estimates were calculated by Oak Ridge Associated Universities using the data published by Krenning, et al. 3 Table 4: Estimated Absorbed Radiation Doses after Intravenous Administration of Indium In 111 Pentetreotide* to a 70 kg Patient PLANAR SPECT Organ mGy/111 MBq rads/3 mCi mGy/222 MBq rads/6 mCi Kidneys 54.16 5.42 108.32 10.83 Liver 12.15 1.22 24.31 2.43 Spleen 73.86 7.39 147.73 14.77 Uterus 6.34 0.63 12.67 1.27 Ovaries 4.89 0.49 9.79 0.98 Testes 2.90 0.29 5.80 0.58 Red Marrow 3.46 0.35 6.91 0.69 Urinary Bladder Wall 30.24 3.02 60.48 6.05 GI Tract Stomach Wall 5.67 0.57 11.34 1.13 Small Intestine 4.78 0.48 9.56 0.96 Upper Large Intestine 5.80 0.58 11.59 1.16 Lower Large Intestine 7.73 0.77 15.46 1.55 Adrenals 7.55 0.76 15.11 1.51 Thyroid 7.43 0.74 14.86 1.49 mSv/111 MBq * Assumes 4 .8 hour voiding interval and International Commission on Radiological Protection (ICRP) 30 model for the gastrointestinal tract calculations. rem/3 mCi mSv/222 MBq rem/6 mCi Effective Dose † Equivalent 13.03 1.30 26.06 2.61

CONTRAINDICATIONS None known.

WARNINGS DO NOT ADMINISTER IN TOTAL PARENTERAL NUTRITION (TPN) ADMIXTURES OR INJECT INTO TPN INTRAVENOUS ADMINISTRATION LINES; IN THESE SOLUTIONS, A COMPLEX GLYCOSYL OCTREOTIDE CONJUGATE MAY FORM. The sensitivity of scintigraphy with indium In 111 pentetreotide may be reduced in patients concurrently receiving therapeutic doses of octreotide acetate. Consideration should be given to temporarily suspending octreotide acetate therapy before the administration of indium In 111 pentetreotide injection and to monitoring the patient for any signs of withdrawal. Hypersensitivity reactions following administration of somatostatin receptor imaging agents predominantly consisted of cutaneous reactions such as rash and pruritus. Reactions reversed either spontaneously or with routine symptomatic management. Less frequently hypersensitivity reactions included angioedema or cases with features of anaphylaxis.

ADVERSE REACTIONS The following adverse effects were observed in clinical trials at a frequency of less than 1% of 538 patients: dizziness, fever, flush, headache, hypotension, changes in liver enzymes, joint pain, nausea, sweating, and weakness. These adverse effects were transient. Also in clinical trials, there was one reported case of bradycardia and one case of decreased hematocrit and hemoglobin. Pentetreotide is derived from octreotide which is used as a therapeutic agent to control symptoms from certain tumors. The usual dose for indium In 111 pentetreotide injection is approximately 5 to 20 times less than for octreotide and is subtherapeutic. The following adverse reactions have been associated with octreotide in 3% to 10% of patients: nausea, injection site pain, diarrhea, abdominal pain/discomfort, loose stools, and vomiting. Hypertension and hyper- and hypoglycemia have also been reported with the use of octreotide. The following adverse reactions have been identified during postapproval use of indium In 111 pentetreotide injection. 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 reactions, predominantly rash, pruritus, less frequently angioedema or features of anaphylaxis