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RENOCIS

Active substance(s): DIMERCAPTOSUCCINIC ACID

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
RENOCIS®
Kit for the preparation of technetium [99mTc] succimer injection.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

RENOCIS®, kit for the preparation of technetium [99mTc] succimer injection, consists
of 5 multidose vials, each containing the following sterile, pyrogen-free, freeze-dried
product under nitrogen :
Dimercaptosuccinic acid
Stannous chloride dihydrate
Inositol
:
50
Ascorbic acid :
0.7

:
:
mg
mg

1
0.36

mg
mg

The product contains no antimicrobial preservative.
The product is to be used after reconstitution by the addition of sterile, pyrogen-free,
isotonic sodium pertechnetate [99mTc], allowing the preparation of technetium [99mTc]
succimer injection (technetium [99mTc] dimercaptosuccinic acid, i.e. technetium
[99mTc] DMSA).
3.

PHARMACEUTICAL FORM

Powder for injection.
4.

CLINICAL PARTICULARS

4.1.

Therapeutic Indications

After reconstitution with sodium pertechnetate [99mTc] solution the agent may be used
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

In adults, the recommended activity is 30 to 120 MBq (0.8-3.2 mCi).

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).
Paediatric dose. The dose for children is adjusted according to body weight:
Paediatric dosage (MBq) =
Adult dosage (MBq) × 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
4.3.
Contra-Indications
None.
4.4.

Special Warnings and Special Precautions for Use

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 licences 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.
4.5. Interactions 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 ([99mTc] DMSA) i.e.,
ammonium chloride : may substantially reduce renal uptake and increase
hepatic uptake of technetium [99mTc] succimer ([99mTc] DMSA),
sodium bicarbonate : reduction of renal uptake of technetium [99mTc] succimer
([99mTc] DMSA),
mannitol : reduction of renal uptake of technetium [99mTc] succimer ([99mTc]
DMSA).
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 ([99mTc] DMSA) will be impaired in the affected kidney.
This is usually reversible after discontinuation of captopril.
4.6.

Pregnancy and Lactation

Women of childbearing potential : 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
should be considered.
Pregnancy : Radionuclide procedures carried out on pregnant women also involve
radiation doses to the foetus. Only imperative investigations should be carried out
during pregnancy, when the likely benefit exceeds the risk incurred by mother and
foetus.
Lactation : 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 radioactivity in breast milk. If the administration is considered necessary
the breast feeding should be interrupted for 12 hours and the expressed feeds
discarded. Breast feeding can be restarted when the level in the milk will not result in
a radiation dose to the child greater than 1 mSv.
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.
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.
Exposure to ionising radiation is linked with cancer induction and a potential for
development of hereditary defects. For diagnostic nuclear medicine investigations the
current evidence suggests that these adverse effects will occur with low frequency
because of the low radiation doses incurred.
For most diagnostic investigations using a nuclear medicine procedure the radiation
dose delivered (EDE) is less than 20 mSv. Higher doses may be justified in some
clinical circumstances.

4.9.

Overdose

In the event of the 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

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

After intravenous administration technetium [99mTc] succimer ([99mTc] DMSA) is
eliminated from blood with a triphasic pattern in patients with normal renal function.
The effective half-life of technetium [99mTc] succimer ([99mTc] DMSA) in blood is
around 1 hour. The technetium [99mTc] succimer ([99mTc] DMSA) 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.
5.3.

Pre-clinical 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 agent is not intended for regular or continuous administration.
Mutagenicity studies and long-term carcinogenicity studies have not been
carried out.

5.4.

Radiation dosimetry

[99mTc] technetium decays with the emission of gamma radiation with a mean energy
of 140 keV and a half-life of 6 hours, to [99mTc] technetium which, can be regarded as
quasi stable.
For technetium [99mTc] succimer ([99mTc] DMSA) the effective dose equivalent
resulting from an administered activity of 120 MBq (3.2 mCi) is typically 1.92 mSv
(per 70 kg individual).

According to ICRP (International Commission of Radiological Protection) the
radiation doses absorbed by the patients are the following :

Organ

ABSORBED DOSE PER UNIT OF ADMINISTERED ACTIVITY
(mGy/MBq)
Adult

15 years

10 years

5 years

1 year

Adrenals
Bladder wall
Bone surfaces
Breast
Gastrointestinal tract
Stomach wall
Small intestine
Upper large intestine wall
Lower large intestine wall

1.3E-02
1.9E-02
3.5E-03
1.8E-03

1.6E-02
2.4E-02
4.3E-03
1.8E-03

2.4E-02
3.5E-02
6.4E-03
2.8E-03

3.5E-02
5.1E-02
9.9E-03
4.5E-03

6.0E-02
9.4E-02
1.9E-02
8.4E-03

5.5E-03
5.2E-03
5.1E-03
3.2E-03

6.3E-03
6.4E-03
6.3E-03
4.2E-03

9.8E-03
1.0E-02
9.6E-03
6.7E-03

1.3E-02
1.5E-02
1.4E-02
1.0E-02

2.0E-02
2.5E-02
2.3E-02
1.8E-02

Kidneys
Liver
Lungs
Ovaries
Pancreas

1.7E-01
9.7E-03
2.5E-03
3.7E-03
9.0E-03

2.1E-01
1.2E-02
3.5E-03
4.6E-03
1.1E-02

2.9E-01
1.8E-02
5.2E-03
7.2E-03
1.6E-02

4.2E-01
2.5E-02
8.0E-03
1.1E-02
2.3E-02

7.3E-01
4.1E-02
1.4E-02
2.0E-02
3.7E-02

Red marrow
Spleen
Testes
Thyroid
Uterus

6.3E-03
1.3E-02
1.8E-03
1.1E-03
4.6E-03

7.5E-03
1.7E-02
2.4E-03
1.9E-03
5.5E-03

1.0E-02
2.6E-02
3.9E-03
3.1E-03
8.9E-03

1.4E-02
3.8E-02
6.2E-03
5.1E-03
1.3E-02

2.0E-02
6.1E-02
1.2E-02
9.2E-03
2.3E-02

Other tissue

3.0E-03

3.6E-03

5.2E-03

8.0E-03

1.4E-02

Effective
dose equivalent
(mSv/MBq)

1.6E-02

1.9E-02

2.7E-02

4.0E-02

6.9E-02

6.

PHARMACEUTICAL PARTICULARS

6.1

List of Excipients

Stannous chloride dihydrate
Inositol
Ascorbic acid
6.2.

Incompatibilities

None known.
6.3.

Shelf-Life

The expiry date for this kit is 12 months from the day of manufacture. The expiry date
is indicated on the outer packaging and on each vial.
The expiry date for the labelled product is 8 hours after labelling.
6.4.

Special Precautions for Storage

The kit must be stored at a temperature ranging between +2 °C and +8 °C.
The labelled product must be stored at a temperature ranging between +15 °C and +25
°C in accordance with national regulations for radioactive materials.
6.5.

Nature and Content of Container

15 mL, colourless, European Pharmacopoeia type I, drawn glass vials, closed with
rubber stoppers and aluminium capsules.
6.6
Instructions for Use, Handling and Disposal
-

Method of preparation

Usual precautions regarding sterility and radioprotection should be respected.
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 (100 mCi). 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.
The vial should never be opened and must be kept inside its lead shielding. The
solution should be removed aseptically through the stopper with a sterile lead
protected syringe.
-

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

x 100

Total radioactivity of the paper strip
Calculate the percentage of free [99mTc] technetium
% free [99mTc] technetium =
Radioactivity of the spot at Rf 1

x 100

Total radioactivity of the paper strip

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
%.

The administration of radiopharmaceuticals creates risks for other persons from
external radiation or contamination from spills of urine, vomiting, etc. Radiation
protection precautions in accordance with national regulations must therefore be
taken.
Radioactive waste must be disposed of in conformity with the relevant national and
international regulations.

7

MARKETING AUTHORISATION HOLDER

CIS bio international
B.P. 32
91192 Gif-sur-Yvette Cedex
FRANCE
Tel.: +33-(0)1.69.85.70.70
Fax: +33-(0)1.69.85.70.71
8.
MARKETING AUTHORISATION NUMBER
PL 11876/0008
9.

RENEWAL OF AUTHORISATION

16 July 2003

10

DATE OF REVISION OF THE TEXT

20/06/2006

11

DOSIMETRY (IF APPLICABLE)

12

INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS (IF APPLICABLE)

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Source: Medicines and Healthcare Products Regulatory Agency

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