Consumer medicine information

OctreoScan

Indium (111In) pentetreotide

BRAND INFORMATION

Brand name

OctreoScan

Active ingredient

Indium (111In) pentetreotide

Schedule

Unscheduled

What is in this leaflet

This leaflet answers some of the common questions about OctreoScan. It does not contain all of the available information about OctreoScan. It does not replace talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you or your child receiving OctreoScan against the benefits he or she expects it will have.

If you have any concerns about receiving this medicine, ask your doctor.

Keep this leaflet. You may need to read it again.

What is OctreoScan

OctreoScan is a kit that consists of two components, OctreoScan 10 mL Reaction Vial containing pentetreotide and 10 mL vial of Indium (¹¹¹In) Chloride Sterile Solution. These two components are combined on the day of intended use to form a single, sterile solution of the diagnostic agent Indium (¹¹¹In) Pentetreotide.

What OctreoScan is used for

OctreoScan is used to diagnose tumours containing somatostatin receptors. These tumours are commonly found in the pituitary gland, pancreas and gastrointestinal system

Your doctor may have prescribed OctreoScan for another purpose. Ask your doctor if you have any questions about why OctreoScan has been prescribed for you. If you have any concerns, you should discuss these with your doctor.

This medicine is only available with a doctor's prescription.

Before you are given OctreoScan

Before you are given OctreoScan your doctor will explain to you the procedure you are about to undergo, and the radioactive medicine you will be given. You must discuss any concerns you have with your doctor.

OctreoScan is not recommended for patients less than 18 years of age. If your doctor believes it is necessary to give OctreoScan to a patient under 18, he or she will discuss the benefits and risks with you.

You must tell your doctor if you have allergies to:

any other medicines
any other substances such as foods, preservatives or dyes

Tell your doctor if you are or plan to become pregnant. Like most medicines OctreoScan is not recommended for use during pregnancy. If there is a need to consider OctreoScan during your pregnancy, your doctor will discuss the benefits and risks of giving it to you.

Tell your doctor if you are breastfeeding or plan to breastfeed. Like most medicines OctreoScan is not recommended while you are breastfeeding. However if you are breastfeeding, formula feedings should be substituted for breastfeeding for 24 hours following the administration of OctreoScan. Breast milk produced within that time should be discarded.

Tell your doctor if you have any other medical conditions especially if you suffer from diabetes or kidney failure.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from pharmacy, supermarket or health food shop.

How OctreoScan is given

How much is given

Your doctor will decide how much you will be given. This depends on your condition and other factors, such as weight.

How it is given

OctreoScan is given as an injection into a vein. OctreoScan should only be given by a doctor or a nurse.

When you are given OctreoScan

Things you must do

Make sure you are well hydrated prior to the administration of OctreoScan.

Things you must not do

Do not take any other medicines unless advised by your doctor.

Things to be careful of

OctreoScan should not affect your ability to drive or operate machinery.

OctreoScan is eliminated from the body through the kidneys.

Side Effects

Tell your doctor as soon as possible if you do not feel well after being given OctreoScan.

All medicines have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some side effects.

Tell your doctor if you experience any of the following and they worry you

Feel faint (Vasovagal reaction)
Warmth and redness of skin (Flushing)
Itching
Hives

These side effects are usually mild. You may not experience any of them.

Product Description

What it looks like

OctreoScan is supplied as one pack containing two vials and a needle. The solution is prepared immediately prior to use and should be clear and colourless.

Ingredients

Active ingredients:

Vial A: Indium (¹¹¹In) chloride

Vial B: lyophilised pentetreotide

Final product: (¹¹¹In)-pentetreotide

Inactive Ingredients:

Vial A: Hydrochloric Acid, Water for Injection, Ferric Chloride Hexahydrate

Vial B: Sodium Citrate Dihydrate, Citric Acid Monohydrate, Inositol, Gentisic Acid

Sponsor

Landauer Radiopharmaceuticals Pty Ltd
Level 3/69 Phillip Street
Parramatta NSW 2150
Australia.

Registration Number:

AUST R 55928

Date of Preparation:

August 2018.

Published by MIMS December 2018

BRAND INFORMATION

Brand name

OctreoScan

Active ingredient

Indium (111In) pentetreotide

Schedule

Unscheduled

1 Name of Medicine

Indium (¹¹¹In) chloride. (¹¹¹In) pentetreotide.

2 Qualitative and Quantitative Composition

OctreoScan is a composite pack containing two vials which cannot be used separately.

Vial A (DRN 4920/A).

1.1 mL solution contains at activity reference time, Indium (¹¹¹In) chloride 122 MBq.

Vial B (DRN 4920/B).

Contains pentetreotide 10 microgram.
After reconstitution and labelling the solution contains (¹¹¹In)-pentetreotide.
Physical characteristics of Indium (¹¹¹In) chloride is cyclotron produced and decays with a half-life of 2.83 days to stable cadmium.

Emission characteristics.

γ-rays 172 keV (90% abundance), g-rays 247 keV (94% abundance), X-rays 23-26 keV.

Radionuclidic purity.

¹¹¹In ≥ 99%, other γ-emitting nuclides ≤ 0.1%. ^114mIn: max. 500 Bq per 1 MBq of ¹¹¹In at activity reference time/date.

Half-life of ^114mIn.

49.51 days.
After reconstitution and labelling the pH of the aqueous solution is 3.8-4.3. The ready to use solution does not contain a preservative agent.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Vial A.

Radiopharmaceutical precursor.
Vial A is a glass vial with a teflon-coated rubber stopper and an aluminium crimp cap shielded with lead, containing a clear and colourless solution.

Vial B.

Powder for injection.
Vial B is a glass vial with grey rubber stopper and an aluminium crimp cap with orange flip off. It contains a white lyophilised powder.

4 Clinical Particulars

4.1 Therapeutic Indications

OctreoScan is indicated for the localisation of gastroentero-pancreatic (GEP) neuroendocrine tumours.

4.2 Dose and Method of Administration

The dose for planar scintigraphy is 110 MBq in one single intravenous injection. Careful administration is necessary to avoid paravasal deposition of activity.
For single photon emission tomography (SPECT) the dose depends on the available equipment. In general, an activity dose of 110 to 220 MBq in one single intravenous injection should be sufficient.
No special dosage regimen for elderly patients is required.
There is limited experience on administrations in paediatric patients, but the activity to be administered in a child should be a fraction of the adult activity calculated from the bodyweight according to Table 1.
Scintigraphy takes place approx. 4, 24 or 48 hours after administration. When activity in the abdomen is observed at 24 hours which cannot be interpreted with certainty as uptake in tumour or activity in bowel contents, scintigraphy should be repeated at 48 hours. In some cases, scintigraphy after 4 hours gives acceptable results. Physiologic uptake occurs in spleen, liver, kidneys and bladder. Thyroid, pituitary and intestines are visible in most patients.

Instructions for use and handling.

Radiopharmaceutical agents should only be used by qualified personnel with the appropriate government authorization for the use and manipulation of radionuclides.
This radiopharmaceutical may be received, used and administered only by authorised persons in designated clinical settings. Its receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licenses of the local competent official organisations.
Radiopharmaceuticals should be prepared by the user in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken, complying with the requirements of Good Manufacturing Practice for pharmaceuticals.

Instructions for labelling.

1. Add the contents of vial A (¹¹¹In-chloride) to vial B (lyophilised pentetreotide) to obtain the product Indium (¹¹¹In)-pentetreotide; only the Sterican (0.90 x 70) needle supplied with the shipped patient dose should be used to remove the indium chloride from its vial.
2. Observe an incubation period of 30 minutes following the reconstitution.
3. The preparation may be diluted with 2-3 mL of 0.9% sodium chloride solution if a larger volume is desired for easier handling in the syringe.
4. The solution must be clear and colourless, this can be checked behind a lead wall containing a lead glass window. If the solution does not comply it should be discarded.
5. Use a tiny sample of this (diluted or not) volume for the quality control, which is described in the following paragraph.
6. The solution is ready for use. The solution must be used within 6 hours.

Note.

For the reconstitution, do not use any other ¹¹¹In-chloride solution than the one supplied in the same container that holds the lyophilised pentetreotide.

Instructions for quality control.

Analysis of ¹¹¹In-bound peptides versus ¹¹¹In-bound non-peptide compounds may be done on silica gel impregnated glass fiber strips (ITLC SG by GELMAN, cat.nr.61885). Prepare a thoroughly dried strip, approx. 10 cm long and 2.5 cm wide by marking a starting line at 2 cm, with additional marks at 6 and 9 cm. Apply 5 to 10 microL of the reconstituted and labelled solution to the starting line and develop in freshly prepared sodium citrate solution 0.1 M, adjusted with HCl to pH 5. In approximately 2-3 min the front will have reached the 9 cm mark. Cut the strip at the 6 cm mark and measure the activity of both halves. Non-peptide bound ¹¹¹In moves with the front.

Requirement.

The lower end of the chromatogram should contain ≥ 98% of the applied activity.

Radiation dosimetry.

The following radiation dosimetry are calculated according to the MIRD system. The data are given in ICRP publication 106 in 2008. According to the biokinetic model described in ICRP 106 intravenously injected (¹¹¹In)-pentetreotide is assumed to be immediately taken up in liver, spleen, kidneys and thyroid, while the rest is assumed to be homogeneously distributed in the remainder of the body. The experimentally found retention data is best described by mono- or biexponential functions. The biokinetic data comes from patients with carcinoid tumours and endocrine tumours in the GI-tract. Uptake in tumour tissue present in any given organ may therefore be included in the published organ uptake values. The main route of excretion is via the kidneys and less than 2% is excreted in faeces. An observed excretion of 85% via urine after 24 h fits well with the model. The small excretion via the GI tract is not included in the model, since its contribution to the absorbed dose in normal circumstances is negligible. See Table 2 and Table 3.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed, see Section 6.1.
No specific contraindications have been identified.
For use during pregnancy and lactation see Section 4.6 Fertility, Pregnancy and Lactation.

4.4 Special Warnings and Precautions for Use

Administration of a laxative is necessary in patients not suffering from diarrhoea, to differentiate stationary activity accumulations in lesions in, or adjacent to, the intestinal tract from moving accumulations in the bowel contents.
In diabetic patients, receiving high doses of insulin, the administration of (¹¹¹In)-pentetreotide may cause paradoxical hypoglycaemia via a temporary inhibition of glucagon secretion.
Regarding patients on octreotide therapy it is recommended to withdraw this therapy temporarily to avoid a possible blockade of somatostatin receptors. This recommendation is given on empirical grounds; the absolute need for such measure has not been demonstrated. In some patients the withdrawal of therapy may not be tolerated and may cause rebound effects. This is notably the case in insulinoma patients, where the danger of sudden hypoglycaemia must be considered, and in patients suffering from the carcinoid syndrome.
If the clinician responsible for the patients therapeutic management considers withdrawal of octreotide therapy tolerable, a three day withdrawal period is recommended.
Positive scintigraphy with (¹¹¹In)-pentetreotide reflects the presence of an increased density of tissue somatostatin receptors rather than a malignant disease. Furthermore positive uptake is not specific for GEP and carcinoid-tumours. Positive scintigraphic results require evaluation of the possibility that another disease, characterised by high local somatostatin receptor concentrations, may be present. An increase in somatostatin receptor density can also occur in the following pathological conditions: tumours arising from tissue embryologically derived from the neural crest, (paragangliomas, medullary thyroid carcinomas, neuroblastomas, pheochromocytomas), tumours of the pituitary gland, endocrine neoplasms of the lungs (small-cell carcinoma), meningiomas, mamma-carcinomas, lympho-proliferative disease (Hodgkin's disease, non-Hodgkin lymphomas), and the possibility of uptake in areas of lymphocyte concentrations (subacute inflammations) must be considered.
For each patient, exposure to ionising radiation must be justifiable on the basis of likely benefit. The activity administered must be such that the resulting radiation dose is as low as reasonably achievable bearing in mind the need to obtain the intended diagnostic or therapeutic result.
The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spills of urine, vomiting, etc. Therefore, radiation protection precautions in accordance with national regulations must be taken.

Use in renal impairment.

In patients with significant renal failure administration of (¹¹¹In)-pentetreotide is not advisable because the reduced or absent function of the principal route of excretion will lead to delivery of an increased radiation dose (E.D.E. 1.9E-01 mSv/MBq). Administration should be considered only when the possible damage from radiation is outweighed by the potential diagnostic information. Interpretable scintigrams may be obtained after haemodialysis during which the high background activity can at least partially be removed. Prior to dialysis images are non-diagnostic because of activity in the circulation. After dialysis a higher than usual uptake in liver, spleen and intestinal tract, and a higher than usual activity in circulation, were observed.
(¹¹¹In)-pentetreotide not bound to receptors, and nonpeptide bound ¹¹¹In, are rapidly eliminated through the kidneys. To enhance the process of excretion, in order to reduce background noise and to reduce the radiation dose to kidneys and bladder, a liberal fluid intake (at least 2 litres) is required for 2 or 3 days following administration.

Use in the elderly.

No data available.

Paediatric use.

Because of the potential hazard of the ionizing radiation (¹¹¹In)-pentetreotide should not be used in children under 18 years of age, unless the value of the expected clinical information is considered to outweigh the possible damage from radiation.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No drug interactions have been reported to date.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
There is no experience with the use of OctreoScan in pregnant women. When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. Where uncertainty exists it is important that radiation exposure should be the minimum consistent with achieving the desired clinical information. Alternative techniques which do not involve ionising radiation have to be considered.
Radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus. The administration of the maximal diagnostic activity of 220 MBq to the patient results in an absorbed dose to the uterus of 8.6 mGy. In this dose range lethal effects and the induction of malformations, growth retardations and functional disorders are not to be expected; however the risk for the induction of cancer and hereditary defects may be increased. Therefore, OctreoScan should not be used during pregnancy unless clearly necessary.
It is not known whether (¹¹¹In)-pentetreotide is excreted into the breast milk. Before administering a radioactive medicinal product to a mother who is breast feeding consideration should be given as to whether the investigation could be reasonably delayed until the mother has ceased breast feeding and as to whether the most appropriate choice of radiopharmaceutical has been made, bearing in mind the secretion of activity in breast milk. If administration during lactation is considered necessary, breast feeding has to be discontinued and the expressed milk has to be discarded.

4.7 Effects on Ability to Drive and Use Machines

(¹¹¹In)-pentetreotide does not affect the ability to drive or to use machines.

4.8 Adverse Effects (Undesirable Effects)

Adverse effects attributable to the administration of OctreoScan are uncommon (> 1/1000, < 1/100). Specific effects have not been observed. The symptoms reported are suggestive of vasovagal reactions or of anaphylactoid drug effects.
The withdrawal of octreotide therapy as a preparatory step to scintigraphy might provoke severe adverse effects, generally of the nature of a return of the symptoms seen before this therapy was started.
Exposure to ionising radiation can lead to cancer or development of hereditary defects. As most diagnostic nuclear medicine investigations involve levels of radiation less than 20 mSv (effective dose), these adverse events can be expected with a low probability. However, with this product when performing SPECT this level might be exceeded. The EDE in a 70 kg individual with normal renal function is maximally 26 mSv. The higher dose may be justified under some clinical circumstances.
This product contains no excipients that have a recognised action or effect, or knowledge of which is important for safe and effective use of the product.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

The pharmaceutical form (monodose injection) makes inadvertent overdosing improbable. The renal elimination of (¹¹¹In)-pentetreotide, not bound to receptors, and of non-peptide bound ¹¹¹In can be enhanced by administration of fluids.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

OctreoScan attaches to somatostatin receptors in tissues where, as consequence of disease, the cell-surfaces contain these receptors in a more than physiologic density. In individual patients, where the disease did not lead to an increased receptor density, scintigraphy will not be successful.
In carcinoids and GEP-tumours the prevalence of increased receptor density in the tumour-tissue in general is rather high.
Only limited studies of pharmacodynamic effects have been performed.
The in vitro biological activity is approximately 30% of the biological activity of natural somatostatin. The in vivo biological activity, measured in rats, is less than that of equal amounts of octreotide. Intravenous administration of 20 microgram of pentetreotide resulted in some patients in a measurable but very limited decrease of serum gastrin and serum glucagon levels of less than 24 hours duration.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Excretion.

Approximately 80% (resp. 90%) of intravenously administered radiolabelled pentetreotide is eliminated through the urinary system in 24 (resp. 48) hours. ¹¹¹In-pentetreotide is taken up by the following organs: liver (approx. 2% at 24 hours) and spleen (approx. 2.5% at 24 hours). Uptake in thyroid and pituitary occurs but not reproducibly. The uptake in kidneys is partly a reflection of ongoing elimination through the urine and partly due to delayed excretion by the kidney. The elimination via the gallbladder and subsequently the faeces is approx. 2% of the administered activity dose in patients with normal intestinal function.
Up to 6 hours post-administration radioactivity in urine is predominantly intact ¹¹¹In-pentetreotide. Thereafter, increasing amounts of nonpeptide-bound activity are excreted.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

Preclinical safety testing did not yield remarkable findings. No testing has been done on carcinogenic potential nor of the influence of pentetreotide on fertility or on embryotoxicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Vial A.

Hydrochloric acid, water for injections, ferric chloride hexahydrate.

Vial B.

Sodium citrate dihydrate, citric acid monohydrate, inositol, gentisic acid.

6.2 Incompatibilities

Major incompatibilities: not known.
After reconstitution and labelling OctreoScan may be diluted with 0.9% sodium chloride solution. Do not mix the injectate with any other solution in order to avoid possible incompatibilities.

6.3 Shelf Life

Vial A and by consequence vial B of OctreoScan expire 24 hours after the activity reference time/date of the ¹¹¹In activity reference time/date and expiry time/date are both stated on the label on the shielding (sealed container) and appear in the documents that accompany each shipment.
After reconstitution and labelling the solution must be used within 6 hours.

6.4 Special Precautions for Storage

The vials A and B are to be stored below 25°C. Storage should take place in accordance with national regulations for radioactive materials. Store the reconstituted solution below 25°C during the prescribed shelf life.

6.5 Nature and Contents of Container

Both 10 mL vials comply with the requirements for glass Type I, Ph. Eur.

Vial A.

Containing Indium (¹¹¹In) chloride is closed with a polytetrafluoroethylene-coated bromobutylrubber stopper.

Vial B.

Containing pentetreotide is closed with a bromobutyl rubber stopper.
Both vials are sealed with an aluminium crimp cap.
OctreoScan is supplied as one pack containing two vials that cannot be used separately, one of which has a lead shielding.
Both vials are packed in a closed, folded tin. Enclosed in the tin is a Sterican Luer Lock 0.90 x 70 mm/20 G x 2 4/5 needle to be used for the labeling procedure.

6.6 Special Precautions for Disposal

Unused ¹¹¹In activity or unused OctreoScan should be allowed to decay until the activity has dropped to such a low level that, according to local regulations, it is no longer considered radioactive. Then it may be disposed of as harmless waste. Unused vials with lyophilized pentetreotide may be disposed of as harmless waste.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Pentetreotide has the following structural formula:

Indium In 111 Pentetreotide has the following structural formula:

Molecular Formula: C₆₅H₉₅N₁₆O₁₂S₂.

CAS number.

Vial A: 10025-82-8.
Vial B: 138661-02-6.

7 Medicine Schedule (Poisons Standard)

Unscheduled- not considered by the committee.

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OctreoScan

Indium (111In) pentetreotide

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