Get your patient on Octreoscan - Indium In -111 Pentetreotide (Indium In -111 Pentetreotide)

Octreoscan, after radiolabeling, is an agent for the scintigraphic localization of primary and metastatic neuroendocrine tumors bearing somatostatin receptors.

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.

None known.

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.

Octreoscan ^™ is a 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 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.

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 or 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 radiolabeling yield is presented at the end of this package insert (see RECOMMENDED METHOD FOR DETERMINATION OF RADIOLABELING YIELD OF INDIUM In 111 PENTETREOTIDE INJECTION ).

Octreoscan was studied in nine unblinded clinical studies in a total of 365 patients. Of these patients, 174 were male and 191 were female. Their mean age was 54.0 years (range 1.8 to 86 years). One patient was under the age of 2 and 2 patients were between the ages of 2 and 12; 223 patients (61.1%) were between 18 and 60 years; and 136 patients (37.3%) were older than 60 years. A racial distribution is not available.

Eligible patients had a demonstrated or high clinical suspicion of a neuroendocrine tumor. The most common tumors were carcinoids (132 of 309 evaluable patients). Scintigraphic results were compared to results of conventional localization procedures (CT, ultrasound, MRI, angiography, surgery and/or biopsy). The mean dose of radioactivity administered was 173.4 MBq (4.7 mCi).

Octreoscan results were consistent with the final diagnosis (success) in 267 of 309 evaluable patients (86.4%). Compared with carcinoids and gastrinomas, lower success rates were noted for localization of insulinomas, neuroblastomas, pituitary adenomas and medullary thyroid carcinomas. Octreoscan success was observed in 27 of 32 patients (84.4%) with clinically nonfunctioning neuroendocrine tumors (i.e., no symptom of a clinical syndrome mediated by abnormally elevated hormones).

Octreoscan localized previously unidentified tumors in 57/204 patients. In 55/195 patients, indium In 111 pentetreotide uptake occurred in lesions not thought to have somatostatin receptors. In a small subgroup of 39 patients who had tissue confirmation, the sensitivity rate for Octreoscan scintigraphy was 85.7%; for CT/MRI the rate was 68%. The specificity rate for Octreoscan scintigraphy was 50%, the rate for CT/MRI was 12%. Larger studies are needed to confirm these comparisons. Overall, including all tumor types with or without the presence of somatostatin receptors, there were 3/508 false positives and 104/508 false negatives.

Of the 309 patients, 87 had received octreotide for therapeutic purposes within 72 hours of Octreoscan administration. These patients had an overall 95% success rate. The effect of different dose levels of octreotide on success rates has not been evaluated.

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.