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RENOCIS

Active substance(s): DIMERCAPTOSUCCINIC ACID / DIMERCAPTOSUCCINIC ACID / DIMERCAPTOSUCCINIC ACID

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT

RENOCIS 1 mg kit for radiopharmaceutical preparation

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 1 mg of succimer (or dimercaptosuccinic acid, DMSA) .
The radionuclide is not part of the kit.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Kit for radiopharmaceutical preparation.
White pellet.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

This medicinal product is for diagnostic use only.
After radiolabelling with sodium pertechnetate (99mTc) solution, the solution of technetium
(99mTc) succimer is indicated for:
Static (planar or tomographic) renal imaging.
- morphological studies of renal cortex.
- individual kidney function.
- location of ectopic kidney.

4.2

Posology and method of administration

Posology
Adults
In adults, the recommended activity is 30 to 120 MBq
Paediatric population
The use in children and adolescents has to be considered carefully, based upon clinical needs
and assessing the risk/benefit ratio in this patient group. The activities to be administered to
children and to adolescents may be calculated according to body weight by using the
following formula:

Paediatric dosage (MBq) =Adult dosage (MBq) x Child weight (kg)
70
In some circumstances, dose adjustment according to surface area may be appropriate:

Paediatric dosage (MBq) = Adult dosage (MBq) x Child body surface (m²)
1.73
Method of administration
Multidose use.
This medicinal product should be reconstituted before administration to the patient.
Intravenous use.
For instructions on extemporaneous preparation of the medicinal product before
administration, see section 12.
For patient preparation, see section 4.4.
Image acquisition
The image acquisitions may be performed as soon as 1 to 3 hours post-injection. Where there
is renal impairment or obstruction, delayed views may be needed (6 to 24 hours respectively).

4.3

Contraindications

Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to any
of the components of the labelled radiopharmaceutical.

4.4

Special warnings and 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, the radiation exposure must be justifiable by the likely benefit. The activity
administered should in every case be as low as reasonably achievable to obtain the required
diagnostic information.
Paediatric population
For information on the use in paediatric population, see sections 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.
Precautions with respect to environmental hazard see section 6.6.

4.5

Interaction with other medicinal products and other forms of interaction

Some chemical compounds or medicaments may affect the function of tested organs and
influence the uptake of technetium (99mTc) succimer i.e:
- ammonium chloride: may substantially reduce renal uptake and increase hepatic uptake of
technetium (99mTc) succimer
- sodium bicarbonate: reduction of renal uptake of technetium (99mTc) succimer,
- mannitol: reduction of renal uptake of technetium (99mTc) succimer.
To avoid these influences, treatment with any of the above chemical products should be
interrupted where possible. Care should be taken to ensure the patient is adequately hydrated
before scanning.
- Captopril: In patients with unilateral renal artery stenosis, uptake of technetium (99mTc)
succimer will be impaired in the affected kidney. This is usually reversible after
discontinuation of captopril.

4.6

Fertility, pregnancy and lactation

Women of childbearing potential
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 dose 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.
Breast-feeding
Before administering radiopharmaceuticals to a mother who is breastfeeding consideration
should be given to the possibility of delaying the administration of radionuclide until the
mother has ceased breastfeeding, and to what is the most appropriate choice of
radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the
administration is considered necessary, breastfeeding should be interrupted for 12 hours and
the expressed feeds discarded.

4.7

Effects on ability to drive and use machines

Effects on ability to drive and use machines have not been described and are not expected.

4.8

Undesirable effects

Allergic reactions have been reported in the literature although to date these have been
inadequately described.
Exposure to ionising radiation is linked with cancer induction and a potential for development
of hereditary defects.

As the effective dose is 1.1 mSv when the maximal recommended activity of 120 MBq is
administered these adverse reactions are expected to occur with a low probability.

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: www.mhra.gov.uk/yellowcard.

4.9

Overdose

In the event of administration of a radiation overdose with technetium (99mTc) succimer
((99mTc) DMSA) the absorbed dose to the patient should be reduced where possible by
increasing the elimination of the radionuclide from the body by forced diuresis and frequent
bladder voiding.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Diagnostic Radiopharmaceuticals, ATC code: V09CA02
Pharmacodynamic effects
At the chemical concentrations and activities used for diagnostic procedures technetium
(99mTc) succimer ((99mTc) DMSA) does not appear to exert any pharmacodynamic effects.

5.2

Pharmacokinetic properties

Distribution
After intravenous administration technetium (99mTc) succimer is eliminated from blood with
a triphasic pattern in patients with normal renal function.
Organ uptake
The technetium (99mTc) succimer localizes in high concentrations in renal cortex. Maximal
localisation occurs within 3-6 hours after intravenous injection, with about 40-50 % of the
dose retained in the kidneys. Less than 3 % of the administered dose localizes in the liver.
However, this amount can be increased significantly and renal distribution decreased in
patients with impaired renal functions.
Half-life
The effective half-life of technetium (99mTc) succimer in blood is around 1 hour.

5.3

Preclinical safety data

Toxicity with repeated administration of 0.66 mg/kg/day succimer (DMSA) and 0.23
mg/kg/day SnCl2 over 14 days in rats was not observed. The dose usually administered to
humans is 0.14 mg/kg succimer (DMSA). This medicinal product is not intended for regular
or continuous administration.
Mutagenicity studies and long-term carcinogenicity studies have not been carried out.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Stannous chloride dihydrate
Inositol
Ascorbic acid

6.2

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those
mentioned in section 12.

6.3

Shelf life

1year.
The expiry date is indicated on the outer packaging and on each vial.
After radiolabelling: do not store above 25°C and use within 8 hours.

6.4

Special precautions for storage

Store the kit at 2°C – 8°C (in a refrigerator).
For storage conditions after labelling of the medicinal product, see section 6.3.
Storage of radiopharmaceuticals should be in accordance with national regulation on
radioactive materials.

6.5

Nature and contents of container

15 mL, colourless, European Pharmacopoeia type I, drawn glass vials, closed with rubber
stoppers and aluminium capsules.
Pack size: 5 multidose vials

6.6

Special precautions for disposal

General warnings
Radiopharmaceuticals should be received, used and administered only by authorised persons
in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to
the regulations and/or appropriate licences of the 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.
Contents of the vials are intended only for use in the preparation of technetium (99mTc)
succimer injection and are not to be administered directly to the patient without first
undergoing the preparative procedure.
For instructions on extemporaneous preparation of the medicinal product before
administration, see section 12.
If at any time in the preparation of this product the integrity of this vial is compromised it
should not be used.
Administration procedures should be carried out in a way to minimize risk of contamination
of the medicinal product and irradiation of the operators. Adequate shielding is mandatory.
The content of the kit before reconstitution is not radioactive. However, after sodium
pertechnetate (99mTc) , Ph. Eur.is added, adequate shielding of the final preparation must be
maintained.
The administration of radiopharmaceuticals creates risks for other persons from external
radiation or contamination from spill of urine, vomiting, etc. Radiation protection precautions
in accordance with national regulations must therefore be taken.
Any unused medicinal product or waste material should be disposed of in accordance with
local requirements

7

MARKETING AUTHORISATION HOLDER
CIS bio international
B.P. 32
91192 Gif-sur-Yvette Cedex
FRANCE

8

MARKETING AUTHORISATION NUMBER(S)
PL 11876/0008

9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of first authorisation: 13 March 1997
Date of latest renewal: 29 March 2011

10

DATE OF REVISION OF THE TEXT
26/11/2015

11

DOSIMETRY

Technetium (99mTc) is produced by means of a (99Mo/99mTc) generator and decays with
the emission of gamma radiation with a mean energy of 140 keV and a half-life of 6.02 hours
to technetium [99Tc] which, in view of its long half-life of 2.13 x 105 years, can be regarded
as quasi stable.
The data listed below are from ICRP (International Commission of Radiological Protection,
Publication 80) and are calculated according to the following assumptions:

Absorbed dose per unit activity administered (mGy/MBq)

Adult

15years

10years

5 years

1 year

Organ
Adrenals

0,012

0,016

0.024

0.035

0.060

Bladder

0.018

0,023

0.029

0.031

0.057

Bone surfaces

0.0050

0.0062

0.0092

0.014

0.026

Brain

0.0012

0.0015

0.0025

0.0040

0.0072

Breast

0.0013

0.0018

0.0028

0.0045

0.0084

Gall bladder

0.0083

0.010

0.014

0.022

0.031

GI-tract Stomach 0.0052

0.0063

0.010

0.014

0.020

SI

0.0050

0.0064

0.010

0.014

0.024

Colon

0.0043

0.0055

0.0082

0.012

0.020

(ULI

0.0050

0.0064

0.0095

0.014

0.023

(LLI

0.0033

0.0043

0.0065

0.0096

0.016

Heart

0.0030

0.0038

0.0058

0.0086

0.014

Kidneys

0.18

0,22

0.30

0.43

0.76

Liver

0.0095

0.012

0.018

0.025

0.041

Lungs

0.0025

0.0035

0.0052

0.0080

0.015

Muscles

0.0029

0.0036

0.0052

0.0077

0.014

Oesophagus

0.0017

0.0023

0.0034

0.0054

0.0094

Ovaries

0.0035

0.0047

0.0070

0.011

0.019

Pancreas

0.0090

0.011

0.016

0.023

0.037

Red marrow

0.0039

0.0047

0.0068

0.0090

0.014

Skin

0.0015

0.0018

0.0029

0.0045

0.0085

Spleen

0.013

0.017

0.026

0.038

0.061

Testes

0.0018

0.0024

0.0037

0.0053

0.010

Thymus

0.0017

0.0023

0.0034

0.0054

0.0094

Thyroid

0.0015

0.0019

0.0031

0.0052

0.0094

Uterus

0.00454

0.0056

0.0083

0.011

0.019

Remaining
organs

0.0029

0.0037

0.0052

0.0077

0.014

Effective dose
(mSv/MBq)

0.0088

0.011

0.015

0.021

0.037

The effective dose resulting from the administration of an activity of 120 MBq for an adult
weighing 70 kg is about 1.1 mSv.
For an administered activity of 120 MBq the typical radiation dose to the target organ
(kidneys) is 21.6 mGy and the typical radiation dose to the critical organ (bladder) is 2.2 mGy
respectively.

12

INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS

Usual precautions regarding sterility and radioprotection must be respected.
Withdrawals should be performed under aseptic conditions. The vial must not be opened and
must be kept inside the lead shielding. After disinfection of the stopper, the solution should be
withdrawn via the stopper using a single dose syringe fitted with suitable protective shielding
and a disposable sterile needle or using an authorised automated application system.
If the integrity of this vial is compromised, the product should not be used.
Method of preparation
Take a vial from the kit and put it in an appropriate lead shielding.
Using a hypodermic syringe, introduce through the rubber stopper 1 to 6 mL of sterile
pyrogen-free sodium pertechnetate (99mTc) injection corresponding to maximum 3.7 GBq.
Sodium pertechnetate (99mTc) injection should comply with European Pharmacopoeia
specifications. Do not use a breather needle as the contents are under nitrogen: after
introduction of the volume of sodium pertechnetate (99mTc) injection, without removing the
needle, withdraw an equivalent volume of nitrogen in order to avoid excess pressure in the
vial.
Shake for 5 to 10 minutes.
The obtained preparation is a clear and colourless solution, with a pH ranging between 2.3
and 3.5.
Before use, limpidity of the solution after preparation, pH, radioactivity and gamma spectrum
will be checked.
Quality control
The quality of labelling (radiochemical purity) could be checked according to the following
procedure.
Method
Ascending paper chromatography

Materials and reagents
1. Chromatographic paper
Whatman 1 strip of sufficient length and not less than 2.5 cm wide.
Trace two fine lines parallel to the ends of the strips, the one being called "deposit line" at
2.5 cm, the other one being called "solvent line" at 10 cm from the "deposit line".
2. Mobile phase
Methyl ethyl ketone
3. Glass tank

Glass tank of suitable size for the chromatographic paper used, ground at the top to take a
closely fitting lid. In the top of the tank is a device which suspends the chromatographic paper
and is capable of being lowered without opening the chamber.
4. Miscellaneous
Forceps, scissors, syringes, needles, appropriate counting assembly.

Procedure
1. Place into the glass tank a layer 2 cm deep of the mobile phase.
2. Apply a spot of the preparation to the "deposit line" of the paper strip using a syringe and
needle and dry in air.
3. Using forceps, insert the paper strip into the tank and close the lid. Lower the paper into the
mobile phase and allow the solvent to migrate to the "solvent line".
4. Remove the paper strip with forceps and dry in air.
5. Determine distribution of radioactivity with an appropriate detector.
Identify each radioactive spot by calculating the Rf. The Rf of technetium (99mTc) succimer is
0, and that of pertechnetate ion (free (99mTc) technetium) is 1.
Measure the radioactivity of each spot by integration of the peaks.
6. Calculations
Calculate the percentage of technetium (99mTc) succimer (radiochemical purity)

% technetium (99mTc) succimer = Radioactivity of the spot at Rf 0
Total radioactivity of the paper strip

× 100

Calculate the percentage of free (99mTc) technetium

% free (99mTc) technetium = Radioactivity of the spot at Rf 1
Total radioactivity of the paper strip

× 100

7. The percentage of technetium (99mTc) succimer (radiochemical purity) should be at least
95 % and the percentage of free (99mTc) technetium should not be greater than 2 %.
Any unused medicinal product or waste material should be disposed of in accordance with
local requirements.

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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