INDIUM (IN111) DTPA INJECTION - patient leaflet, side effects, dosage

1. is used for

This medicine is a radiopharmaceutical product for diagnostic use only.

Indium In111 DTPA is used through a scan to examine:

• the brain and spinal cord

• – obstruction in the flow of cerebrospinal fluid, which is the fluid that envelops the brain and spinal cord

• – differentiation between normal pressure associated with hydrocephalus and other forms of hydrocephalus

• leakage of cerebrospinal fluid from the nose or ears.

This medicine contains a radioactive substance which when injected, collects in certain organs such as, the brain.

The radioactive substance can be photographed from outside the body, using special cameras which take a scan. This scan shows the distribution of radioactivity within the organ and body. This also gives the doctor valuable information about the structure and function of that organ.

The use of Indium In111 DTPA does involve exposure to small amounts of radioactivity. Your doctor and the nuclear medicine doctor have considered that the clinical benefit that you will obtain from the procedure with the radiopharmaceutical outweighs the risk due to radiation.

What do you need to know before

• 2. Indium In111 DTPA is used

Indium In111 DTPA must not be used

If you are allergic to Indium In111 DTPA or to any of the other ingredients of this medicine (listed in section 6.)

if you have

• a tendency to bleed
• increased pressure in your head, which is not associated with hydrocephalus

Warnings and precautions

Take special care with Indium In111 DTPA

This medicine does involve treatment with radioactivity. Your doctor will only give you this medicine if the benefit outweighs the risk.

Indium In111 DTPA is given in one single dose by specialists, who will take responsibility for any necessary precautions.

Before administration of Indium In111 DTPA you should:

Your doctor will inform you if you need to take any special precautions -before using this medicine. Contact your doctor if you have any questions.

Other medicines and Indium In111 DTPA

Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other medicines.

There are no medicines known which influence or are influenced by Indium In111 DTPA.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your nuclear medicine doctor for advice before you are given this medicine.

You must inform the nuclear medicine doctor before the administration of Indium In111 DTPA if there is a possibility you might be pregnant, if you have missed your period or if you are breast-feeding.

When in doubt, it is important to consult your nuclear medicine doctor who will supervise the procedure.

• If you are pregnant

The nuclear medicine doctor will only administer this product during pregnancy if a benefit is expected which would outweigh the risks , as it could harm the unborn child.

• If you are breast-feeding

Tell your doctor if you are breast-feeding as he may delay treatment until breast-feeding is finished. He may also ask you to stop breastfeeding for 2 days and discard this milk, until the radioactivity is no longer in your body.

Driving and using machines

Indium In111 DTPA is unlikely to impair the ability to drive and operate machinery.

Indium In111 DTPA contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially “sodium-free”.

• 3. How Indium In111 DTPA is used

There are strict laws on the use, handling and disposal of radiopharmaceutical products. Indium In111 DTPA will only be used in specialised controlled areas. This product will only be handled and given to you by people who are trained and qualified to use it safely. These persons will take special care for the safe use of this product and will keep you informed of their actions.

The nuclear medicine doctor supervising the procedure will decide on the quantity of Indium In111 DTPA to be used in your case. It will be the smallest quantity necessary to get the desired information.

The usual dose is :

Approximate dose for adults is:

• 9 –20 MBq injected into the skull or spine

MBq is the unit used to measure radioactivity and defines the activity of a quantity of radioactive material.

Use in children and adolescents

Lower doses are used for children.

Administration of Indium In111 DTPA and conduct of the procedure

One injection is usually sufficient.

Duration of the procedure

The amount and duration of the scans usually depends on the type of procedure. Your Nuclear medicine doctor will inform you about the usual duration of the procedure.

After administration of Indium In111 DTPA, you should:

Drink and urinate as much as possible before and after treatment. This will prevent active substance gathering in the bladder. The Nuclear medicine doctor will inform you if you need to take any special precautions after receiving this medicine. Contact your Nuclear medicine doctor if you have any questions.

If you have been given more Indium In111 DTPA than you should

It is unlikely that overdose will occur as this medicine is given under control by a doctor. However, if this happens you will receive appropriate treatment from your doctor.

Drinking as much as possible will help remove the radioactive substance more quickly.

Should you have any further question on the use of Indium In111 DTPA, please ask the nuclear medicine doctor who supervises the procedure.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

In the majority of cases the side effects are mild.

This radiopharmaceutical will deliver low amounts of ionising radiation associated with the least risk of cancer and hereditary abnormalities.

Frequency unknown , from the data available

• headache and symptoms associated with irritation from linings which cover the brain or spinal cord

Usually they improve within 48 hours.

• meningitis
• fever
• drooping of the eyelid or corner of the mouth
• ringing or buzzing in the ears

• 5. How Indium In111 DTPA is stored

You will not have to store this medicine. This medicine is stored under the responsibility of the specialist in appropriate premises. Storage of radiopharmace­uticals will be in accordance with national regulation on radioactive materials.

The following information is intended for the specialist only.

• – Keep this medicine out of the sight and reach of children

• – Do not use Indium In111 DTPA after the expiry date stated on the label.

• – Store below 25°C

Contents of the pack and other

• 6. information

What Indium In111 DTPA contains

• The active substances are Indium In111 pentetate and pentetic acid. One millilitre of Indium In111 DTPA contains 37 MBq.
• The other ingredients are: sodium chloride, disodium phosphate dodecahydrate, calcium chloride dihydrate, hydrochloric acid, sodium hydroxide, water for injections.

What Indium In111 DTPA looks like and contents of the pack

Indium In111 DTPA is packaged in a 10 ml type 1 glass vial closed with a bromobutyl rubber stopper and sealed with an aluminium crimp cap. It is supplied in one vial containing 0.5 or 1 ml.

Marketing Authorisation Holder and Manufacturer

• Marketing Authorisation Holder

Curium Netherlands B.V., Westerduinweg 3

1755 LE Petten, The Netherlands

PL 12288/0005

• Manufacturer

Curium Netherlands B.V., Westerduinweg 3

1755 LE Petten, The Netherlands

This leaflet was last revised in August 2020.

SUMMARY OF PRODUCT CHARACTERISTICS

• 1 NAME OF THE MEDICINAL PRODUCT

Indium (111In) DTPA Injection

(Curium Netherlands B.V catalogue number: DRN 4916)

• 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Composition per ml at activity reference time and date:

Indium (111In) pentetate 37 MBq

Pentetatic acid 0.1 mg

Summary of the physical characteristics of the radioactive isotope in the active substance: 111In.

Physical half-life 2.8 days.

Most important radiation emitted

Energy level Abundance (%)

171 keV 90.9%

245 keV 94 %

For the full list of excipients, see section 6.1.

• 3 PHARMACEUTICAL FORM Solution for injection.

• 4 CLINICAL PARTICULARS

  • 4.1 Therapeutic Indications

Diagnostic indications

Cisternoscinti­graphy:

• Detection of obstructions in cerebrospinal flow.
• Differentiation between normal pressure hydrocephalus and other forms of hydrocephalus.
• Detection of leaks of cerebrospinal fluid (rhinorrhoea or otorrhoea).

• 4.2 Posology and Method of Administration

Posology

Adults and elderly population: 9–20 MBq (250–500 pCi)

Paediatric population: 0.4–0.6 MBq/kg body weight (10–15 pCi/kg)

Method of administration

Indium (111In)-pentetate is administered by intrathecal injection (lumbar or suboccipital). 10–15 minutes after lumbar puncture a control scan should be performed at the puncture level to exclude extra-arachnoidal activity, which might cause false-negative results.

Image acquisition

A first visualisation of the skull area should preferably be done

1 to 1.5 hrs after injection. Further imaging is done at 3, 6 and 24 hrs and sometimes 48 or 72 hours after administration, depending on the diagnostic information required.

In case of suboccipital injection scintigraphy should preferably be started as early as 15 minutes after injection. The time points given above, for obtaining the subsequent images, should be advanced by 1 or more hours.

In otorrhoea or rhinorrhoea leakage may be so minimal that it can not be seen on the scintigraphic images. Leakage through the nose or ear can be detected by introducing cotton wool plugs in the outer ear or in the nasal cavity, which are subsequently measured for radioactivity.

• 4.3 Contra-indications

• Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
• Haemorrhagic tendency.
• Increased intracranial pressure.

• 4.4 Special Warnings and Special Precautions for Use

Potential for hypersensitivity or anaphylactic reactions

If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must be immediately available.

Individual benefit/risk justification

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 result.

Paediatric population

For information on the use in the paediatric population, see section 4.2. Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11)

Patient preparation

The patient should be well hydrated before the start of the examination and urged to void as often as possible during the first hours after the examination in order to reduce radiation.

Interpretation of images

A control scan at the injection site for detecting extra-arachnoidal activity is recommended 10–15 minutes after lumbar puncture. In a high percentage of patient studies, extra-arachnoidal activity is seen due to failed lumbar puncture or to puncture leaks. This might lead to falsenegative results.

Specific warnings

This medicinal product contains less than 1 mmol sodium (23 mg) per milliliter solution for injection, i.e. it is essentially ‘sodium- free’.

• 4.5 Interactions with other Medicinal Products and other Forms of Interaction

No interaction studies have been performed.

• 4.6 Fertility, pregnancy and lactation

Women of childbearing potential / Contraception in males and females

When an administration of radiopharmace­uticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and foetus.

Breastfeeding

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 the administration is considered necessary, breast-feeding should be interrupted for two days and the expressed feeds discarded. Breast-feeding can be restarted when the level in the milk will not result in a radiation dose to a child greater than 1 mSv.

• 4.7 Effects on Ability to Drive and Use Machines

Administration of Indium(111In) Pentetate Injection itself has no influence on the ability to drive or to use machines.

• 4.8 Undesirable Effects

Performing a lumbar or occipital puncture may cause adverse reactions which are usually of a mild nature. The symptoms include headache and signs of meningeal irritation, which as a rule improve within 48 hours.

Aseptic meningitis and fever have been reported.

If, in the case of suboccipital administration, the radiopharmaceutical is deposited in the immediate vicinity of those places where cerebral nerves exit from the brainstem, the n. oculomotoris, the n. facialis and the n. vestibulocochlearis may be activated causing transitory effects like ptosis of the eyelid, tinnitus or drooping of a corner of the mouth.

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 2.8 mSv when the maximal recommended activity for adults of 20 MBq is administered these adverse reactions are expected to occur with a low probability. Higher doses may be justified in some clinical circumstances.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via Yellow Card Scheme

Website:

• 4.9 Overdose

The dose form of Indium(111In) Pentetate Injection contains so little material that overdosing with pharmacological effects is not probable. The danger of overdose to be expected are those relating to the inadvertent administration of excess of radioactivity. The radiation dose may be reduced by promoting diuresis and frequent voiding of urine.

• 5 PHARMACOLOGICAL PROPERTIES

• 5.1 Pharmacody­namic Properties

Pharmacotherapeutic group: Other central nervous system diagnostic radiopharmace­uticals, ATC code: V09A X01.

The pharmacology of pentetate has not been studied. However, pentetate is a complexing agent. Since sufficient Ca/Mg ions are included in the preparation to fill the complexing capacity of the fraction of pentetate that is not complexed with 111In, no pharmacodynamic effects are expected to occur.

• 5.2 Pharmacoki­netic Properties

Distribution/Organ uptake

After injection into the subarachnoidal space at lumbar level

Indium (111In)-pentetate moves upwards into the cervical subarachnoidal space and usually accumulates in the posterior fossa after

• 1 to 1.5 hours. 3 Hours after injection activity is observed in the Sylvian and interhemispheric fissures. After 6 hours the tracer has reached the convexity of the hemispheres. At this point it passes from the cerebrospinal fluid into the blood.

Elimination

Subsequently Indium (111In)-pentetate is quickly excreted by glomerular filtration. 24 hours after administration the highest activity can be found in the resorption sites along the superior sagittal sinus.

In the case of a pathological impairment of the cerebrospinal flow this characteristic distribution pattern disappears, which yields diagnostic information.

• 5.3 Pre-clinical Safety Data

Acute toxicity studies with Indium (111In)-pentetate have not been performed. Ytterbium-pentetate intrathecally administered in dogs (up to 300 mg) did not produce toxic effects. Studies of the toxicity after multiple administrations were not performed.

• 6 PHARMACEUTICAL PARTICULARS

• 6.1 List of Excipients

Sodium chloride

Disodium phosphate dodecahydrate

Calcium chloride dihydrate

Hydrochloric acid (for pH adjustment) Sodium hydroxide (for pH adjustment) Water for injections.

• 6.2 Incompati­bilities

No incompatibilities are known to exist, but to safeguard the sterility and the non-pyrogenicity of the injectate no attempts should be made to dilute the product prior to administration.

• 6.3 Shelf Life

The product expires 24 hours after activity reference date and time.

If multi-dose use is intended, each aliquot should be removed under aseptic conditions, and within one working day. Do not store above 25°C after first opening.

• 6.4 Special Precautions for Storage

Store below 25 °C in the original, unopened container.

For storage conditions after frist opening of the medicinal product, see section 6.3.

Storage should take place in accordance with national regulations for radioactive material.

• 6.5 Nature and Content of Container

10 ml glass vial (Type 1, Ph.Eur) closed with a butyl rubber stopper, sealed with an aluminium crimp cap.

Indium (In111) DTPA Injection is supplied in the following activity amounts at activity reference time:

18.5 MBq in 0.5 ml

37 MBq in 1.0 ml

6.6 instructions for use, handling and disposal

Radiopharmace­uticals should be received, used and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer and disposal is subject to the regulations and/or appropriate licences of the local competent official organisation.

Radiopharmace­uticals should be prepared in a manner which satisfies both radiation safety and pharmaceutical quality requirements.

Appropriate aseptic precautions should be taken.

If at any time in the preparation of this product the integrity of the vials is compromised they should not be used.

Administration procedures should be carried out in a way to minimise the risk of contamination of the medicinal product and irradiation of the operators. Adequate shielding is mandatory.

The administration of radiopharmace­uticals creates risks to other persons, from external radiation or contamination from spills or urine, vomiting, etc. Radiation protection precautions in accordance with national regulations must therefore be taken.

Instructions for waste disposal:

Any unused product or waste material should be disposed of in accordance with local requirements.

• 7 MARKETING AUTHORISATION HOLDER

Curium Netherlands B.V.

Westerduinweg 3

1755 LE Petten

Netherlands

• 8 MARKETING AUTHORISATION NUMBER(S)

PL 12288/0005

• 9 DATE OF FIRST AUTHORISATION, RENEWAL OF THE AUTHORISATION

06 August 2020

• 10 DATE OF (PARTIAL) REVISION OF THE TEXT

15 May 2019

• 11 DOSIMETRY

Data from ICRP publication 53 (Vol.18-No 1–4, 1987)

„Radiation dose to patients from radiopharmace­uticals“

The list includes only those organs which are also used in the calculation for the effective (whole body) dose equivalent. These are the seven standard organs and the additional five with the highest absorbed dose (marked with ).

Absorbed dose per unit activity administered (mGy/MBq)

Adult

• Brain 0.13

• * Kidneys 0.13