OCTREOSCAN: Package Insert and Label Information (Page 2 of 3)

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Indium In 111 Pentetreotide Injection is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

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 Octreoscan. 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.

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 an Octreoscan kit. 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, Octreoscan 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 Octreoscan 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

* Assumes 4.8 hour voiding interval and International Commission on Radiological Protection (ICRP) 30 model for the gastrointestinal tract calculations. † Estimated according to ICRP Publication 53.
	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	rem/3 mCi	mSv/222 MBq	rem/6 mCi
Effective Dose †Equivalent	13.03	1.30	26.06	2.61

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2

Values listed include a correction for a maximum of 0.1% indium In-114m radiocontaminant at calibration.

3

E.P. Krenning, W.H. Bakker, P.P.M. Kooij, W.A.P. Breeman, H.Y. Oei, M. de Jong, J.C. Reubi, T.J. Visser, C. Bruns, D.J. Kwekkeboom, A.E.M. Reijs, P.M. van Hagen, J.W. Koper, and S.W.J. Lamberts, “Somatostatin Receptor Scintigraphy with Indium-111-DTPA-D-Phe-1-Octreotide in Man: Metabolism, Dosimetry and Comparison with Iodine-123-Try-3-Octreotide,” The Journal of Nuclear Medicine, Vol. 33, No. 5, May 1992, pp. 652-658.

HOW SUPPLIED

The Octreoscan kit (NDC 69945-050-40) is supplied with the following components:

1. A 10-mL Octreoscan Reaction Vial which contains a lyophilized mixture of:

   (i) 10 mcg pentetreotide [N-(diethylenetriamine-N,N,N’,N”-tetraacetic acid-N”-acetyl)-D-phenylalanyl-L-hemicystyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-L-hemicystyl-L-threoninol cyclic (2→7) disulfide], (also known as octreotide DTPA),
   (ii) 2 mg gentisic acid [2, 5-dihydroxybenzoic acid],
   (iii) 4.9 mg trisodium citrate, anhydrous,
   (iv) 0.37 mg citric acid, anhydrous, and
   (v) 10 mg inositol.
   Before lyophilization, sodium hydroxide or hydrochloric acid may have been added for pH adjustment. The vial contents are sterile and nonpyrogenic. No bacteriostatic preservative is present.

2. A 10-mL vial of Indium In 111 Chloride Solution, which contains 1.1 mL or 111 MBq/mL (3 mCi/mL) Indium In 111 chloride in 0.02 N HCl at time of calibration. The vial also contains ferric chloride at a concentration of 3.5 mcg/mL (ferric ion, 1.2 mcg/mL). The vial contents are sterile and nonpyrogenic. No bacteriostatic preservative is present.

In addition, the kit also contains the following items: (1) a 25 G x 5/8” needle (B-D, Monoject) used to transfer Indium In 111 Chloride Solution to the Octreoscan Reaction Vial, (2) pressure sensitive label, and (3) a package insert.

Storage

The Octreoscan kit should be stored refrigerated at 2° to 8°C (36° to 46°F).

After reconstitution, store at controlled room temperature 20° to 25°C (68° to 77°F). Indium In 111 Pentetreotide Injection must be used within 6 hours of preparation.

INSTRUCTIONS FOR THE PREPARATION OF INDIUM In 111 PENTETREOTIDE INJECTION

Note: Read complete directions thoroughly before starting preparation.

Procedure Precautions and Notes

1. All transfers and penetrations of the vial stoppers by a needle must use aseptic technique.
2. Wear waterproof gloves during the entire procedure and while withdrawing the patient-dose from the Octreoscan Reaction Vial.
3. Transfer Indium In 111 Chloride Solution with an adequately shielded, sterile syringe using the transfer needle in the kit.
4. Adequate shielding should be maintained at all times until the preparation is administered to the patient, disposed of in an approved manner, or allowed to decay to safe levels of radioactivity. A shielded, sterile syringe should be used for withdrawing and injecting the preparation.
5. Do not inject into TPN administration bags or their intravenous lines.

Procedure for the Preparation of Indium In 111 Pentetreotide Injection

1. Place the Octreoscan Reaction Vial in a lead dispensing shield (of minimum wall thickness 1/4 inch) fitted with a lid.
2. Swab the rubber stopper of the reaction vial with an appropriate antiseptic and allow the vial to dry.
3. Aseptically remove the contents of the Indium In 111 Chloride Solution vial using the needle provided and a shielded, sterile syringe.
4. Inject the Indium In 111 Chloride Solution into the Octreoscan Reaction Vial.
5. Gently swirl the Octreoscan Reaction Vial until the lyophilized pellet is completely dissolved.
6. Incubate the Indium In 111 Pentetreotide Injection at or below 25°C (77°F) for a minimum of 30 minutes. Note: A 30 minute incubation time is required. Shorter incubation periods may result in inadequate radiolabeling.
7. Using proper shielding, visually inspect the vial contents. The solution should be clear, colorless, and free of particulate matter. If not, the solution should not be used. It should be disposed in a safe and approved manner.
8. Assay the Indium In 111 Pentetreotide Injection using a suitably calibrated ionization chamber. Record the date, time, total activity, and patient identifier (e.g., patient name and number) on the radioassay information label and affix the label to the lead dispensing shield.
9. The radiolabeling yield of the reconstituted solution should be checked before administration to the patient, according to the instructions given below. If the radiochemical purity is less than 90%, the product should not be used.
10. Store the reaction vial containing the Indium In 111 Pentetreotide Injection at controlled room temperature 20° to 25°C (68° to 77°F) until use. The Indium In 111 Pentetreotide Injection must be used within 6 hours of preparation.
11. If desired, the preparation can be diluted to a maximum volume of 3 mL with 0.9% Sodium Chloride Injection, USP immediately prior to injection. The sample should be drawn up into a shielded, sterile syringe and administered to the patient.

RECOMMENDED METHOD FOR DETERMINATION OF RADIOLABELING YIELD OF INDIUM In 111 PENTETREOTIDE INJECTION

Required Materials

1. Waters Sep-Pak™ C18 Cartridge, Part No. 51910
2. Methanol, 15 mL (Caution: toxic and flammable. Exercise due caution.)
3. Distilled water, 20 mL
4. Disposable syringes:

   2 — 10-mL, no needle required

   2 — 5-mL, no needle required

5. Three disposable culture tubes or vials, minimum 10-mL capacity
6. Ion chamber

Preparation of the Sep-Pak Cartridge

1. Rinse the Sep-Pak cartridge with 10 mL methanol as follows: fill a 10-mL syringe with 10 mL methanol, attach the syringe to the longer end of the Sep-Pak cartridge, and push the methanol through the cartridge. Discard the eluate in a safe and approved manner.
2. Similarly, rinse the cartridge with 10 mL water. Ensure that the cartridge is kept wet and that there is no air bubble present. If an air bubble is present, rinse the cartridge with additional 5 mL of water. Discard the eluate.

Sample Analysis

1. Using a 1-mL syringe with needle, withdraw 0.05 to 0.1 mL Indium In 111 Pentetreotide Injection from the Octreoscan Reaction Vial. Apply the preparation to the Sep-Pak cartridge through the longer end of the cartridge. Make sure that the sample is migrating onto the column of the cartridge. Note: After this step, the cartridge and all solutions eluted from it will be radioactive.
2. With a disposable 5-mL syringe, slowly (in dropwise manner) push 5 mL water through the longer end of the cartridge, collecting the eluate in a counting vial or tube. Label this eluate as “Fraction 1.”
3. Similarly, elute the cartridge with 5 mL methanol. Be sure that this solution is pushed slowly through the longer end of the cartridge so that the elution occurs in a dropwise manner. Collect this fraction in a second culture tube or vial for counting. Label it as “Fraction 2.” Push two 5-mL portions of air through the longer end of the cartridge and collect the eluate with Fraction 2.
4. Place the Sep-Pak cartridge in a third culture tube or vial for assay.