Label: KIT FOR THE PREPARATION OF INDIUM IN 111 PENTETREOTIDE- indium in-111 pentetreotide kit

Indium In 111 pentetreotide is the kit for the preparation of indium In 111 pentetreotide injection, a radioactive diagnostic agent. It is a kit consisting of two components:

1). A 10-mL Pentetreotide 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.

Pentetreotide has the following structural formula:

Prior to 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 of 111 MBq/mL (3 mCi/mL) indium In 111 chloride in 0.02N 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.

Indium In 111 pentetreotide injection is prepared by combining the two kit components ( see INSTRUCTIONS FOR THE PREPARATION OF INDIUM In 111 PENTETREOTIDE INJECTION). Indium In 111 reacts with the diethylenetriaminetetraacetic acid portion of the pentetreotide molecule to form indium In 111 pentetreotide. The pH of the resultant indium In 111 pentetreotide injection is between 3.8 and 4.3. No bacteriostatic preservative is present.

The indium In 111 pentetreotide injection is suitable for intravenous administration as is, or it may be diluted to a maximum volume of 3 mL with 0.9% Sodium Chloride Injection, USP, immediately before intravenous administration. In either case, the radiolabeling yield of indium In 111 pentetreotide injection should be determined before administration to the patient. A method recommended for determining the labeling yield is presented at the end of this package insert (see RECOMMENDED METHOD FOR DETERMINATION OF RADIOLABELING YIELD OF INDIUM In 111 PENTETREOTIDE INJECTION).

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

None known.

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.

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

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 planarimaging 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 SPECTimaging 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.

The indium In 111 pentetreotide kit for injection (NDC 45567-0755-3) is supplied with the following components:

1.A 10-mL Pentetreotide 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 of 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 23 G x 1" needle used to transfer Indium In 111 Chloride Solution to the Pentetreotide Reaction Vial, (2) pressure sensitive label, and (3) a package insert.

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 Pentetreotide 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 Pentetreotide 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 Sterile Solution into the Pentetreotide Reaction Vial.

5.Gently swirl the Pentetreotide 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
   1 - 1-mL, with needle

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 Pentetreotide 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.

Assay

1.Assay the activity of Fraction 1 in a suitably calibrated ionization chamber. This fraction contains the hydrophilic impurities (e.g., unbound indium In-111).

2.Assay the activity of Fraction 2. This fraction contains the indium In 111 pentetreotide.

3.Assay the activity of the Sep-Pak cartridge. This component contains the remaining non-elutable impurities.

4.Dispose of all of the materials used in the preparation, the sample analysis, and the assay in a safe and approved manner.

Calculations

1.Percent indium In 111 pentetreotide =
      (Fraction 2 Activity / Total Activity) x 100%
Where Total Activity = Fraction 1 + Fraction 2 + activity remaining in Sep-Pak
Note: If this value is less than 90%, do not use the preparation. Discard it in a safe and approved manner.

2.Percent hydrophilic impurities =
      (Fraction 1 Activity / Total Activity) x 100%

3.Percent non-elutable impurities =
      (Activity remaining in Sep-Pak cartridge / Total Activity) x 100%

This radiopharmaceutical is licensed by the Illinois Emergency Management Agency for distribution to persons licensed pursuant to 32Ill. Adm. Code 330.260(a), (b) or (c) for radioactive material specified in 32Ill. Adm. Code 335.4010 or under equivalent licenses of the Nuclear Regulatory Commission or an Agreement State.

This reagent kit for the preparation of a radiopharmaceutical is approved for use by persons licensed pursuant to Section 120.547 Code of Massachusetts Regulation 105, or under equivalent license of the U.S. Nuclear Regulatory Commission of an Agreement State.

Sep-Pak TMis a trademark of Waters Technologies Corporation.

Distributed By:
GE Healthcare, Inc. (Medi-Physics, Inc. dba GE Healthcare)
Arlington Heights, IL 60004

For: Sun Pharmaceutical Industries, Inc.
Billerica, MA 01821

1-800-221-7554
(For International call 781-275-7120)

PL-000087

Rev 5.0
July 2024

Kit for the Preparation of Indium In 111 Pentetreotide

CAUTION
RADIOACTIVE MATERIALS

DIAGNOSTIC

For Intravenous use after drug preparation.
Use within six hours after preparation.
Rx only

NDC: 45567-0755-3

Pentetreotide Reaction Vial Pack

For Use with Indium In 111 Chloride Sterile Solution

Reaction Vial Contains:
10.0 μg Pentetreotide
2.0 mg Gentisic Acid
4.9 mg Sodium Citrate Anhydrous
0.37 mg Citric Aci Anhydrous
10.0 mg Inositol

Rx Only

Prior to lyophilization, sodium hydroxide or hydrochloric acid may be added for pH adjustment.

Pentetreotide Reaction Vial

Sterile, non-pyrogenic. For intravenous administration after drug preparation. See package insert for directions for use.
Vial Contains:
10.0 µg Pentetreotide
2.0 mg Gentisic Acid
4.9 mg Sodium Citrate, Anhydrous
0.37 mg Citric Acid, Anhydrous
10.0 mg Inositol
Prior to lyophilization, sodium hydroxide or hydrochloric acid may be added for pH adjustment. The pH of the reconstituted drug is between 3.8 and 4.3. Contents are sealed under nitrogen.

Manufactured by:
Sun Pharmaceutical Industries, Inc.
Billerica, MA 01821

Made in USA

Store Refrigerated at 2° to 8° C (36° t 46° F).
Protect from light.

Use only with Indium In 111 Chloride Sterile Solution

Rx only

GE Healthcare

Indium In 111 Chloride Solution

Sterile, non-pyrogenic solution, contains no bacteriostatic preservative.

Rx only

NOT FOR DIRECT ADMINISTRATION

GE Healthcare

Indium In 111 Chloride Solution

Sterile, non-pyrogenic solution, contains no bacteriostatic preservative.

Rx only

NOT FOR DIRECT ADMINISTRATION