Quadramet
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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Quadramet 1.3 GBq/mL solution for injection. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of solution contains 1.3 GBq Samarium (153Sm) lexidronam pentasodium at the reference date 
(corresponding to 20 to 80 µg/ml of samarium per vial) 
 
Samarium specific activity is approximately 16 – 65 MBq/µg of samarium. 
 
Each vial contains 2-4 GBq at the reference date. 
 
Samarium-153 emits both medium-energy beta particles and an imageable gamma photon, and has a 
period of 46.3 hours (1.93 days). The primary radiation emissions of samarium-153 are shown in 
Table 1. 
 

TABLE 1 : SAMARIUM-153 PRINCIPAL RADIATION EMISSION DATA 

Radiation Energy (keV)* Abundance 

Beta 640 30% 

Beta 710 50% 

Beta 810 20% 

Gamma 103 29% 

* Maximum energies are listed for the beta emissions, the average beta particle energy is 
233 keV. 

 
Excipient with known effect: sodium 8.1 mg/mL. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
 
Clear, colourless to light amber solution with pH ranging between 7.0 and 8.5. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Quadramet is indicated for the relief of bone pain in patients with multiple painful osteoblastic skeletal 
metastases which take up technetium (99mTc)-labelled biphosphonates on bone scan. 
 
The presence of osteoblastic metastases which take up technetium (99mTc)-labelled biphosphonates 
should be confirmed prior to therapy. 
 



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4.2 Posology and method of administration 
 
Quadramet should only be administered by physicians experienced in the use of radiopharmaceuticals 
and after full oncological evaluation of the patient by qualified physicians. 
 
Posology 
The recommended dose of Quadramet is 37 MBq per kg body weight. 
 
Paediatric population 
Quadramet is not recommended for use in children below the age of 18 years due to a lack of data on 
safety and efficacy. 
 
Method of administration 
 
Quadramet is to be administered by slow intravenous route through an established intravenous line 
over a period of one minute. Quadramet should not be diluted before use. 
 
Patients who respond to Quadramet generally experience the onset of pain relief within 1 week after 
treatment. Relief of pain may persist for 4 weeks up to 4 months. Patients who experience a reduction 
in pain may be encouraged to decrease their use of opioid analgesics. 
 
Repeat administration of Quadramet should be based on an individual patient's response to prior 
treatment and on clinical symptoms. A minimum interval of 8 weeks should be respected, subject to 
recovery of adequate bone marrow function. 
 
The data on the safety of repeated dosing are limited and based on compassionate use of the product. 
 
For instructions on preparation of the medicinal product before administration, see section 12. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance (ethylenediaminetetramethylenephosphonate (EDTMP) 

or similar phosphonates) or to any of the excipients excipients listed in section 6.1. 
• in pregnant women (See section 4.6). 
• in patients having received chemotherapy or hemi-body external radiation therapy in a 

preceding period of 6 weeks. 
 
Quadramet is used only as a palliative agent and should not be used concurrently with myelotoxic 
chemotherapy as this may enhance myelotoxicity. 
 
It should not be used concurrently with other biphosphonates if an interference is shown on the 
technetium (99mTc)-labelled biphosphonate bone scans. 
 



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4.4 Special warnings and precautions for use 
 
In absence of clinical data, the injected activity should be adapted to the renal function. 
 
Use of Quadramet in patients with evidence of compromised bone marrow reserve from previous 
therapy or disease involvement is not recommended unless the potential benefit of the treatment 
outweighs its risks. 
 
Because of potential bone marrow suppression after administration, blood counts should be monitored 
weekly for at least 8 weeks, beginning 2 weeks after administration of Quadramet, or until recovery of 
adequate bone marrow function. 
 
The patient should be encouraged to ingest (or receive by intravenous administration) a minimum of 
500 ml of fluids prior to injection and should be encouraged to void as often as possible after injection 
to minimise radiation exposure to the bladder. 
 
The clearance of Quadramet being rapid, the precautions relating to the excreted urinary radioactivity 
need not be taken after 6-12 hours following administration. 
 
Special precautions, such as bladder catheterisation, should be taken during six hours following 
administration to incontinent patients to minimise the risk of radioactive contamination of clothing, 
bed linen, and the patient's environment. For the other patients the urine should be collected for at least 
six (6) hours. 
 
Bladder catheterisation should be undertaken in patients with urinary obstruction. 
 
Radiopharmaceuticals 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 the 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 Interaction with other medicinal products and other forms of interaction 
 
Because of the potential for additive effects on bone marrow, the treatment should not be given 
concurrently with chemotherapy or external beam radiation therapy. Quadramet may be given 
subsequent to either of these treatments after allowing for adequate marrow recovery. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Quadramet is contra-indicated (see 4.3) in pregnancy. The possibility of pregnancy must strictly be 
ruled out. Women of childbearing potential have to use effective contraception during the treatment 
and the whole period of follow-up. 
 
Breast-feeding 
There are no available clinical data relating to the excretion of Quadramet in human milk. If therefore 
Quadramet administration is deemed necessary, formula feeding should be substituted for breast-
feeding and the expressed feeds discarded. 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 



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4.8 Undesirable effects 
 
Decreases in white blood cell and platelet counts and anaemia were observed in patients receiving 
Quadramet. 
In clinical trials white blood cell and platelet counts decreased to a nadir of approximately 40 % to 
50 % of baseline 3 to 5 weeks after a dose, and generally returned to pre-treatment levels by 8 weeks 
post treatment.  
 
The few patients who experienced Grade 3 or 4 hematopoietic toxicity usually either had a history of 
recent external beam radiation therapy or chemotherapy or had rapidly progressive disease with 
probable bone marrow involvement. 
 
Postmarketing reports of thrombocytopenia have included isolated reports of intracranial 
haemorrhage, and cases in which the outcome was fatal. 
 
A small number of patients have reported a transient increase in bone pain shortly after injection (flare 
reaction). This is usually mild and self-limiting and occurs within 72 hours of injection. Such reactions 
are usually responsive to analgesics. 
 
Adverse drug reactions such as nausea, vomiting, diarrhoea and sweating were reported. 
 
Hypersensitivity reactions including rare cases of anaphylactic reaction have been reported after 
Quadramet administration. 
 
A few patients experienced cord/root compressions, disseminated intravascular coagulation and 
cerebrovascular accidents. The occurrence of these events may be linked to the patients’ disease 
evolution. When there are spinal metastases at the cervico-dorsal level, an increased risk of spinal cord 
compression cannot be excluded. 
 
The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer and 
mutations. In all cases, it is necessary to ensure that the risks of the radiation are less than from the 
disease itself. 
 
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 the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
The product should only be administered by qualified personnel in authorised settings. The possibility 
of pharmacological overdose is therefore remote. 
 
The risks to be expected are associated with the inadvertent administration of excess radioactivity. 
Radiation dose to the body can be limited by promoting a diuresis and frequent voiding of urine. 
 
 



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5. PHARMACOLOGIC PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Various pain palliation radiopharmaceuticals. 
ATC Code: V10BX02 
 
Mechanism of action 
Quadramet has an affinity for skeletal tissue and concentrates in areas of bone turnover in intimate 
association with hydroxyapatite. 
 
Pharmacodynamic effects 
Studies in rats have demonstrated that Quadramet is cleared rapidly from the blood and localises to 
growing areas of bone matrix, specifically the layer of osteoid undergoing mineralisation. 
 
Clinical efficacy and safety 
In clinical studies employing planar imaging techniques, Quadramet accumulates with a lesion-to-
normal bone ratio of approximately 5 and a lesion-to-soft tissue ratio of approximately 6. Thus, areas 
of metastatic involvement can accumulate significantly greater amounts of Quadramet than 
surrounding normal bone. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Total skeletal uptake of Quadramet in studies of 453 patients with a variety of primary malignancies 
was 65.5 ± 15.5 % of the administered activity. A positive correlation was found between skeletal 
uptake and the number of metastatic sites. In contrast, skeletal uptake was inversely proportional to 
plasma radioactivity at 30 minutes. 
 
Elimination 
In patients, Quadramet is rapidly cleared from the blood. Thirty minutes after injection of the agent to 
22 patients, only 9.6 ± 2.8 % of the administered activity remained in plasma. At 4 and 24 hours, 
plasma radioactivity had decreased from 1.3 ± 0.7 % to 0.05 ± 0.03 %. 
 
Urinary excretion occurred predominantly during the first 4 hours (30.3 ± 13.5 %). At 12 hours, 
35.3 ± 13.6 % of the administered activity had been excreted into the urine. Less urinary excretion 
occurred in patients who had extensive bony metastases, regardless of the amount of 
radiopharmaceutical administered. 
 
Biotransformation 
Analysis of urine samples found the radioactivity to be present as the intact complex 
 



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5.3 Preclinical safety data 
 
The radiolysis products of Sm-EDTMP showed a renal toxicity in rats and dogs with a no effect level 
of 2.5 mg/kg. 
 
Repeated dose administration of samarium (153Sm)-EDTMP to dogs indicated a slightly longer time 
for depressed bone marrow and peripheral haematological parameters to recover when compared to 
recovery following only single dose administration. 
 
Radioactive Sm-EDTMP has not been tested for mutagenicity/carcinogenicity but due to the radiation 
dose resulting from therapeutic exposure it should be regarded as presenting a genotoxic/carcinogenic 
risk. 
 
Non-radioactive Sm-EDTMP showed no mutagenic potential in a battery of in vivo and in vitro tests. 
The same results were observed for Sm-EDTMP enriched with radiolysis degradants. 
 
In a carcinogenic potential study of EDTMP, osteosarcomas occurred in rats at high doses. In the 
absence of genotoxic properties, these effects can be assigned to the EDTMP chelatant properties 
leading to osseous metabolism disturbances. 
 
No studies have been performed to assess the effect of Quadramet on reproduction. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Total EDTMP (as EDTMP.H2O) 
Calcium-EDTMP sodium salt (as Ca) 
Total sodium (as Na) 
Water for Injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with the other 
medicinal products. 
 
6.3 Shelf-life 
 
1 day from the activity reference time stated on the label. 
 
Use within 6 hours of thawing. After thawing, do not freeze again. 
 
6.4 Special precautions for storage 
 
Quadramet is delivered frozen in dry ice. 
Store in a freezer at -10°C to -20°C in the original package. 
 
Storage procedures should be in accordance with local regulations for radioactive substances. 
 
6.5 Nature and contents of container 
 
15 ml colourless European Pharmacopoeia Type I drawn glass vial closed with Teflon-coated 
chlorobutyl/natural rubber stopper and aluminium flip-off overseal. 
 
Each vial contains 1.5 ml (2 GBq at calibration) to 3.1 ml (4 GBq at calibration) of solution for 
injection. 



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6.6 Special precautions for disposal and other handling 
 
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. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
(See section 12, for detailed instructions of product preparation) 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
CIS bio international 
Boîte Postale 32 
F-91192 GIF-SUR-YVETTE Cedex 
FRANCE 
 
 
8. MARKETING AUTHORISATION NUMBER  
 
EU/1/97/057/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION 
 
Date of first authorisation: 05 February 1998 
Date of latest renewal: 12 December 2007 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
 
11. DOSIMETRY 
 
The estimated absorbed radiation doses to an average adult patient from an intravenous injection of 
Quadramet are shown in Table 2. The dosimetry estimates were based on clinical biodistribution 
studies using methods developed for radiation dose calculations by the Medical Internal Radiation 
Dose (MIRD) Committee of the Society of Nuclear Medicine. 
 
Because Quadramet is excreted in the urine, radiation exposure was based on a urinary voiding 
interval of 4.8 hours. Radiation dose estimates for bone and marrow assume that radioactivity is 
deposited on bone surfaces, in accordance with autoradiograms of bone samples taken from patients 
who received Quadramet. 
 



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Radiation dose to specific organs, which may not be the target organ of therapy, may be influenced 
significantly by pathophysiological changes induced by the disease process. This should be taken into 
consideration when using the following information:  
 

TABLE 2 : RADIATION ABSORBED DOSES 

Organ Absorbed dose per injected activity (mGy/MBq) 

Adrenals 0.009 

Brain 0.011 

Chest 0.003 

Gallbladder 0.004 

Ascending colon wall 0.005 

Descending colon wall 0.010 

Small intestine 0.006 

Myocardial wall 0.005 

Kidneys 0.018 

Liver 0.005 

Lungs 0.008 

Muscle 0.007 

Ovaries 0.008 

Pancreas 0.005 

Red marrow 1.54 

Bone surfaces 6.76 

Skin 0.004 

Spleen 0.004 

Stomach 0.004 

Testes 0.005 

Thymus 0.004 

Thyroid 0.007 

Urinary bladder wall 0.973 

Uterus 0.011 

Effective dose  
(mSv/MBq) 

0.307 

 
For this product the effective dose resulting from an injected activity of 2 590 MBq is 796 mSv. 
 
For an administered activity of 2 590 MBq, the typical radiation dose to the target organ, skeletal 
metastases, is 86.5 Gy and the typical radiation doses to the critical organs are: normal bone surfaces 
17.5 Gy, red marrow 4.0 Gy, urinary bladder wall 2.5 Gy, kidneys 0.047 Gy and ovaries 0.021 Gy. 
 
 



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12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 
 
Allow the product to thaw at room temperature before administration. 
 
The solution for injection should be visually inspected before use. It should be clear without particles. 
The operator should be careful to protect the eyes while inspecting the solution for clarity. 
 
The activity should be measured by a dose calibrator immediately before administration. Verification 
of the dose to be administered and patient identification are necessary prior to administration of 
Quadramet. 
For radiation safety reasons, the patient should be treated in a facility with the appropriate agreement 
for the therapeutic use of radioactive non-sealed sources. He/she will be released when exposure rates 
comply with the limits prescribed by the regulations in force. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.



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ANNEX II 
 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE 

AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 



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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
CIS bio international 
Boîte Postale 32 
F-91192 Gif-sur-Yvette cedex 
France 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2) 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 
 
Pharmacovigilance system 
The MAH must ensure that the system of pharmacovigilance presented in Module 1.8.1. of the 
Marketing Authorisation, is in place and functioning before and whilst the medicinal product is 
on the market. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable 
 



 13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



 14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



 15 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
METALLIC BOX / LEADPOT 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Quadramet 1.3 GBq/mL solution for injection 
Samarium (153Sm) lexidronam pentasodium 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Samarium (153Sm) lexidronam pentasodium :  1.3 GBq/ml at reference date. 
(Corresponding to 20 to 80 µg/ml of samarium) 
 
 
3. LIST OF EXCIPIENTS 
 
Total EDTMP (as EDTMP.H2O) 
Calcium-EDTMP sodium salt (as Ca) 
Total sodium (as Na) 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in a single-dose vial. 
 
  ml 
 
  GBq/vial,   (12 h CET) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
For intravenous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
    
 
 
 



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8. EXPIRY DATE 
 
EXP: DD/MM/YYYY (12 h CET) 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a freezer at -10°C to -20°C in the original package 
 
Use within 6 hours of thawing 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CIS bio international, 
Boîte Postale 32, 
91192 GIF-SUR-YVETTE Cedex, 
FRANCE 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/97/057/001 
 
 
13. BATCH NUMBER 
 
Batch :   
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
<Justification for not including Braille accepted> 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL INTERMEDIATE PACKAGING 
UNITS 
 
GLASS VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Quadramet 1.3 GBq/mL solution for injection 
Samarium (153Sm) lexidronam pentasodium 
For intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
 
 
3. EXPIRY DATE 
 
EXP: DD/MM/YYYY (12 h CET) 
 
 
4. BATCH NUMBER 
 
Batch:   
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
  ml 
 
  GBq/vial,  (12 h CET) 
 
 
6. OTHER 
 

 
 
Manufacturer: CIS bio international. 



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B. PACKAGE LEAFLET 



 19 

 
Package leaflet: Information for the patient 

 
 

Quadramet 1.3 GBq/mL solution for injection 
Samarium (153Sm) lexidronam pentasodium. 

 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or your pharmacist. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet: 
 
1. What Quadramet is and what it is used for 
2. What you need to know before you take Quadramet 
3. How to take Quadramet 
4. Possible side effects 
5. How to store Quadramet 
6. Contents of the pack and other information 
 
 
1. What Quadramet is and what it is used for 
 
Quadramet is a medicinal product for therapeutic use only. 
 
This radiopharmaceutical is used for the treatment of bone pain due to your disease. 
 
Quadramet has a high affinity for skeletal tissue. Once injected it concentrates in bone lesions. 
Because Quadramet contains small amounts of a radioactive element, samarium-153, radiations are 
delivered locally to the bone lesions, allowing to develop the palliative action on bone pain. 
 
 
2. What you need to know before you take Quadramet 
 
Do not take Quadramet: 
• If you are allergic to ethylene diamine tetramethylene phosphonic acid (EDTMP) or similar 
phosphonate compounds or any of the other ingredients of this medicine (listed in section 6), 
• If you are pregnant, 
• If you have received chemotherapy or hemibody field external radiation therapy in a preceding 
period of 6 weeks. 
 



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Warnings and precautions 
Talk to your doctor before taking Quadramet. 
 
Your doctor will take blood samples weekly for at least 8 weeks to check your platelets, white and red 
blood cell counts which may slightly decrease due to the therapy. 
 
During 6 hours following the injection of Quadramet, your physician will encourage you to drink and 
void as often as possible. He will decide at which time you will be authorised to leave the nuclear 
medicine department. 
 
In the case of urine incontinence or urinary obstruction you will get a urine catheter for about 6 hours. 
For the other patients the urine should be collected for at least 6 hours. 
 
If your renal function is decreased, the amount of product will be adapted. 
 
Children and adolescents 
Quadramet is not recommended for use in children below 18 years of age. 
 
Other medicines  and Quadramet 
Tell your doctor if you are taking or have recently taken or might take any other medicines. 
 
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 doctor for advice before taking this medicine. 
 
Quadramet must not be administered to pregnant women. 
If Quadramet administration to a breastfeeding woman is deemed necessary, breastfeeding should be 
stopped. 
 
 
3. How to take Quadramet 
 
Your doctor will want to carry out a special scan before administering Quadramet to ascertain whether 
you are likely to benefit from Quadramet. 
 
Dosage 
One single dose of 37 megabecquerel (Becquerel is the unit in which radioactivity is measured) of 
Quadramet per kilogram of body weight is to be injected. 

If you have the impression that the effect of Quadramet is too strong or too weak, talk to your doctor 
or pharmacist. 

Method and route of administration 
Quadramet is to be administered by slow injection into a vein. 

Frequency of administration 
This medicinal product is not intended to be injected on a regular or continuous basis. The 
administration can however be repeated after 8 weeks following injection, subject to the evolution of 
your disease. 

Duration of treatment 
You will be authorised to leave the nuclear medicine department after a dosimetric follow-up 
(generally within 6 hours following Quadramet injection). 

If you take more Quadramet than you should 
Quadramet being supplied as a single-dose vial, an accidental overdose is unlikely to occur. 
Radiation dose to the body can be limited by increasing fluid intake and frequent voiding of urine. 

If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 



 21 

 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The undesirable effects due to Quadramet administration are linked with a decrease of red and white 
blood cells, and platelets. Cases of bleeding have been reported, some of which have been serious. 
 
This is the reason why your blood counts will be monitored strictly for a few weeks following 
Quadramet injection. 
 
You may exceptionally feel a slight increase in bone pain a few days after Quadramet injection. You 
should not be alarmed at this; in such case, your pain medicine will be slightly increased. This effect is 
moderate and brief and will disappear after some hours. 
 
Adverse drug reactions such as nausea, vomiting, diarrhoea and sweating were reported. 
 
Hypersensitivity reactions including rare cases of anaphylactic reaction have been reported after 
Quadramet administration. 
 
In rare cases, the following undesirable effects have been observed: neuralgia, coagulation disorders, 
cerebrovascular accidents. These effects were deemed to be related to the progression of the disease. 
 
If you experience back pain or sensory abnormalities, please inform your physician as soon as 
possible. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Quadramet 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use Quadramet after the expiry date which is stated on the label. 
Quadramet expires 1 day from the activity reference time stated on the label. 
 
Store at –10°C to –20°C in a freezer in its original packaging. 
 
Quadramet should be used within 6 hours of thawing. After thawing, do not freeze again. 
 
The product label includes the appropriate storage conditions and the expiry date for the batch of 
product. Hospital personnel will ensure that the product is stored correctly and not administered to you 
after the stated expiry date. 
 
Storage procedures should be in accordance with national regulations for radioactive materials. 
 
 



 22 

6. Contents of the pack and other information 
 
What Quadramet contains 
The active substance is samarium (153Sm) lexidronam pentasodium. 
Each ml of solution contains 1.3 GBq Samarium (153Sm) lexidronam pentasodium at the reference date 
(corresponding to 20-80 µg/ml of samarium per vial). 
 
The other ingredients are total EDTMP (as EDTMP.H2O), calcium-EDTMP sodium salt (as Ca), total 
sodium (as Na), water for injections. 
 
What Quadramet looks like and contents of the pack 
Quadramet is a solution for injection. 
 
This medicinal product is a clear, colourless to light amber solution which is packed in a 15 ml 
colourless European Pharmacopoeia Type I drawn glass vial closed with Teflon-coated 
chlorobutyl/natural rubber stopper and aluminium flip-off overseal. 
 
Each vial contains 1.5 ml (2 GBq at reference) to 3.1 ml (4 GBq at reference) of solution for injection. 
 
 
Marketing authorisation holder and manufacturer 
 
CIS bio international 
Boîte Postale 32 
F-91192 Gif-sur-Yvette cedex 
France 
 
 
The leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 
The following information is intended for medical or healthcare professionals only: 
The complete SmPC of Quadramet is provided as a separate document in the product package, with 
the objective to provide healthcare professionals with other additional scientific and practical 
information about the administration and use of this radiopharmaceutical. 
 
Please refer to the SmPC (SmPC should be included in the box) 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
{'Title': '1. what quadramet is and what it is used for', 'Section_Content': 'quadramet is a medicinal product for therapeutic use only. this radiopharmaceutical is used for the treatment of bone pain due to your disease. quadramet has a high affinity for skeletal tissue. once injected it concentrates in bone lesions. because quadramet contains small amounts of a radioactive element, samarium-153, radiations are delivered locally to the bone lesions, allowing to develop the palliative action on bone pain.', 'Entity_Recognition': [{'Text': 'quadramet', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 5, 'BeginOffset': 0, 'EndOffset': 9, 'Score': 0.3752496838569641, 'Text': 'quadramet', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'a medicinal product', 'Type': 'TREATMENT', 'BeginOffset': 13, 'EndOffset': 32}, {'Text': 'this radiopharmaceutical', 'Type': 'TREATMENT', 'BeginOffset': 59, 'EndOffset': 83}, {'Id': 7, 'BeginOffset': 113, 'EndOffset': 122, 'Score': 0.8331942558288574, 'Text': 'bone pain', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.8151988983154297}]}, {'Text': 'your disease', 'Type': 'PROBLEM', 'BeginOffset': 130, 'EndOffset': 142}, {'Id': 6, 'BeginOffset': 144, 'EndOffset': 153, 'Score': 0.3523973524570465, 'Text': 'quadramet', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 1, 'BeginOffset': 178, 'EndOffset': 193, 'Score': 0.7819820046424866, 'Text': 'skeletal tissue', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Text': 'bone lesions', 'Type': 'PROBLEM', 'BeginOffset': 228, 'EndOffset': 240}, {'Text': 'a radioactive element, samarium', 'Type': 'TREATMENT', 'BeginOffset': 286, 'EndOffset': 317}, {'Text': 'radiations', 'Type': 'TREATMENT', 'BeginOffset': 323, 'EndOffset': 333}, {'Text': 'the bone lesions', 'Type': 'PROBLEM', 'BeginOffset': 359, 'EndOffset': 375}, {'Text': 'the palliative action', 'Type': 'TREATMENT', 'BeginOffset': 397, 'EndOffset': 418}, {'Text': 'bone pain', 'Type': 'PROBLEM', 'BeginOffset': 422, 'EndOffset': 431}]}
{'Title': '2. what you need to know before you take quadramet', 'Section_Content': 'do not take quadramet: if you are allergic to ethylene diamine tetramethylene phosphonic acid (edtmp) or similar phosphonate compounds or any of the other ingredients of this medicine (listed in section 6), if you are pregnant, if you have received chemotherapy or hemibody field external radiation therapy in a preceding period of 6 weeks. warnings and precautions talk to your doctor before taking quadramet. your doctor will take blood samples weekly for at least 8 weeks to check your platelets, white and red blood cell counts which may slightly decrease due to the therapy. during 6 hours following the injection of quadramet, your physician will encourage you to drink and void as often as possible. he will decide at which time you will be authorised to leave the nuclear medicine department. in the case of urine incontinence or urinary obstruction you will get a urine catheter for about 6 hours. for the other patients the urine should be collected for at least 6 hours. if your renal function is decreased, the amount of product will be adapted. children and adolescents quadramet is not recommended for use in children below 18 years of age. other medicines and quadramet tell your doctor if you are taking or have recently taken or might take any other medicines. 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 doctor for advice before taking this medicine. quadramet must not be administered to pregnant women. if quadramet administration to a breastfeeding woman is deemed necessary, breastfeeding should be stopped.', 'Entity_Recognition': [{'Text': 'quadramet', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 12, 'EndOffset': 21, 'Score': 0.4190489947795868, 'Text': 'quadramet', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [{'Name': 'NEGATION', 'Score': 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'EndOffset': 306, 'Score': 0.9105479717254639, 'Text': 'external radiation therapy', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Type': 'TREATMENT_NAME', 'Traits': []}, {'Id': 25, 'BeginOffset': 332, 'EndOffset': 339, 'Score': 0.4051508605480194, 'Text': '6 weeks', 'Category': 'TIME_EXPRESSION', 'Type': 'TIME_TO_TREATMENT_NAME', 'Traits': [], 'Attributes': [{'Type': 'TREATMENT_NAME', 'Score': 0.9105479717254639, 'RelationshipScore': 0.6763016581535339, 'RelationshipType': 'OVERLAP', 'Id': 16, 'BeginOffset': 280, 'EndOffset': 306, 'Text': 'external radiation therapy', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Traits': []}]}, {'Id': 2, 'BeginOffset': 400, 'EndOffset': 409, 'Score': 0.5000635981559753, 'Text': 'quadramet', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 17, 'BeginOffset': 433, 'EndOffset': 446, 'Score': 0.7339543104171753, 'Text': 'blood samples', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Type': 'TEST_NAME', 'Traits': []}, {'Id': 26, 'BeginOffset': 467, 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'RelationshipType': 'OVERLAP', 'Id': 21, 'BeginOffset': 934, 'EndOffset': 939, 'Text': 'urine', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Traits': []}]}, {'Text': 'your renal function', 'Type': 'TEST', 'BeginOffset': 985, 'EndOffset': 1004}, {'Text': '18', 'Type': 'NUMBER', 'BeginOffset': 1138, 'EndOffset': 1140}, {'Text': 'other medicines', 'Type': 'TREATMENT', 'BeginOffset': 1155, 'EndOffset': 1170}, {'Id': 4, 'BeginOffset': 1175, 'EndOffset': 1184, 'Score': 0.4059242606163025, 'Text': 'quadramet', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'any other medicines', 'Type': 'TREATMENT', 'BeginOffset': 1257, 'EndOffset': 1276}, {'Id': 10, 'BeginOffset': 1278, 'EndOffset': 1287, 'Score': 0.9239488244056702, 'Text': 'pregnancy', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9118630886077881}]}, {'Id': 11, 'BeginOffset': 1319, 'EndOffset': 1327, 'Score': 0.9922269582748413, 'Text': 'pregnant', 'Category': 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{'Title': '3. how to take quadramet', 'Section_Content': 'your doctor will want to carry out a special scan before administering quadramet to ascertain whether you are likely to benefit from quadramet. dosage one single dose of 37 megabecquerel (becquerel is the unit in which radioactivity is measured) of quadramet per kilogram of body weight is to be injected. if you have the impression that the effect of quadramet is too strong or too weak, talk to your doctor or pharmacist. method and route of administration quadramet is to be administered by slow injection into a vein. frequency of administration this medicinal product is not intended to be injected on a regular or continuous basis. the administration can however be repeated after 8 weeks following injection, subject to the evolution of your disease. duration of treatment you will be authorised to leave the nuclear medicine department after a dosimetric follow-up (generally within 6 hours following quadramet injection). if you take more quadramet than you should quadramet being supplied as a single-dose vial, an accidental overdose is unlikely to occur. radiation dose to the body can be limited by increasing fluid intake and frequent voiding of urine. if you have any further questions on the use of this product, ask your doctor or pharmacist.', 'Entity_Recognition': [{'Text': 'quadramet', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'a special scan', 'Type': 'TEST', 'BeginOffset': 35, 'EndOffset': 49}, {'Id': 2, 'BeginOffset': 71, 'EndOffset': 80, 'Score': 0.30597811937332153, 'Text': 'quadramet', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 3, 'BeginOffset': 133, 'EndOffset': 142, 'Score': 0.4688590168952942, 'Text': 'quadramet', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.6781872510910034, 'RelationshipScore': 0.9646288156509399, 'RelationshipType': 'DOSAGE', 'Id': 4, 'BeginOffset': 151, 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{'Title': '4. possible side effects', 'Section_Content': 'like all medicines, this medicine can cause side effects, although not everybody gets them. the undesirable effects due to quadramet administration are linked with a decrease of red and white blood cells, and platelets. cases of bleeding have been reported, some of which have been serious. this is the reason why your blood counts will be monitored strictly for a few weeks following quadramet injection. you may exceptionally feel a slight increase in bone pain a few days after quadramet injection. you should not be alarmed at this; in such case, your pain medicine will be slightly increased. this effect is moderate and brief and will disappear after some hours. adverse drug reactions such as nausea, vomiting, diarrhoea and sweating were reported. hypersensitivity reactions including rare cases of anaphylactic reaction have been reported after quadramet administration. in rare cases, the following undesirable effects have been observed: neuralgia, coagulation disorders, cerebrovascular accidents. these effects were deemed to be related to the progression of the disease. if you experience back pain or sensory abnormalities, please inform your physician as soon as possible. reporting of side effects if you get any side effects, talk to your doctor or pharmacist. this includes any possible side effects not listed in this leaflet. you can also report side effects directly via the national reporting system listed in appendix v. by reporting side effects you can help provide more information on the safety of this medicine.', 'Entity_Recognition': [{'Text': 'quadramet', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 18}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 20, 'EndOffset': 33}, {'Id': 10, 'BeginOffset': 44, 'EndOffset': 56, 'Score': 0.9579789638519287, 'Text': 'side effects', 'Category': 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effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7074432969093323}]}, {'Id': 32, 'BeginOffset': 1433, 'EndOffset': 1444, 'Score': 0.3910084664821625, 'Text': 'appendix v.', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.6178454160690308}]}, {'Id': 33, 'BeginOffset': 1458, 'EndOffset': 1470, 'Score': 0.8602522015571594, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7422922849655151}]}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 1526, 'EndOffset': 1539}]}
{'Title': '5. how to store quadramet', 'Section_Content': 'keep this medicine out of the sight and reach of children. do not use quadramet after the expiry date which is stated on the label. quadramet expires 1 day from the activity reference time stated on the label. store at 10 to 20 in a freezer in its original packaging. quadramet should be used within 6 hours of thawing. after thawing, do not freeze again. the product label includes the appropriate storage conditions and the expiry date for the batch of product. hospital personnel will ensure that the product is stored correctly and not administered to you after the stated expiry date. storage procedures should be in accordance with national regulations for radioactive materials.', 'Entity_Recognition': [{'Text': 'quadramet', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 150, 'EndOffset': 151}, {'Text': '10', 'Type': 'NUMBER', 'BeginOffset': 219, 'EndOffset': 221}, {'Text': '20', 'Type': 'NUMBER', 'BeginOffset': 225, 'EndOffset': 227}, {'Text': 'its original packaging', 'Type': 'TREATMENT', 'BeginOffset': 244, 'EndOffset': 266}, {'Text': 'quadramet', 'Type': 'TREATMENT', 'BeginOffset': 268, 'EndOffset': 277}, {'Text': '6', 'Type': 'NUMBER', 'BeginOffset': 300, 'EndOffset': 301}, {'Text': 'storage procedures', 'Type': 'TREATMENT', 'BeginOffset': 590, 'EndOffset': 608}, {'Text': 'radioactive materials', 'Type': 'TREATMENT', 'BeginOffset': 663, 'EndOffset': 684}]}
{'Title': '6. contents of the pack and other information', 'Section_Content': 'what quadramet contains the active substance is samarium (153sm) lexidronam pentasodium. each ml of solution contains 1.3 gbq samarium (153sm) lexidronam pentasodium at the reference date (corresponding to 20-80 µg/ml of samarium per vial). the other ingredients are total edtmp (as edtmp.h2o), calcium-edtmp sodium salt (as ca), total sodium (as na), water for injections. what quadramet looks like and contents of the pack quadramet is a solution for injection. this medicinal product is a clear, colourless to light amber solution which is packed in a 15 ml colourless european pharmacopoeia type i drawn glass vial closed with teflon-coated chlorobutyl/natural rubber stopper and aluminium flip-off overseal. each vial contains 1.5 ml (2 gbq at reference) to 3.1 ml (4 gbq at reference) of solution for injection.', 'Entity_Recognition': [{'Text': 'quadramet', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 48, 'EndOffset': 56, 'Score': 0.5666614174842834, 'Text': 'samarium', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 1, 'BeginOffset': 65, 'EndOffset': 87, 'Score': 0.9773808717727661, 'Text': 'lexidronam pentasodium', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.473853200674057, 'RelationshipScore': 0.9999961853027344, 'RelationshipType': 'DOSAGE', 'Id': 2, 'BeginOffset': 89, 'EndOffset': 96, 'Text': 'each ml', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'FORM', 'Score': 0.953725278377533, 'RelationshipScore': 0.9997407793998718, 'RelationshipType': 'FORM', 'Id': 3, 'BeginOffset': 100, 'EndOffset': 108, 'Text': 'solution', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': '1.3', 'Type': 'NUMBER', 'BeginOffset': 118, 'EndOffset': 121}, {'Text': 'gbq samarium', 'Type': 'TREATMENT', 'BeginOffset': 122, 'EndOffset': 134}, {'Id': 6, 'BeginOffset': 143, 'EndOffset': 165, 'Score': 0.8585073947906494, 'Text': 'lexidronam pentasodium', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.8543615937232971, 'RelationshipScore': 0.999904990196228, 'RelationshipType': 'DOSAGE', 'Id': 7, 'BeginOffset': 206, 'EndOffset': 217, 'Text': '20-80 µg/ml', 'Category': 'MEDICATION', 'Traits': []}]}, {'Id': 8, 'BeginOffset': 221, 'EndOffset': 229, 'Score': 0.4327832758426666, 'Text': 'samarium', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.8543615937232971, 'RelationshipScore': 0.9984036087989807, 'RelationshipType': 'DOSAGE', 'Id': 7, 'BeginOffset': 206, 'EndOffset': 217, 'Text': '20-80 µg/ml', 'Category': 'MEDICATION', 'Traits': []}]}, {'Id': 9, 'BeginOffset': 295, 'EndOffset': 320, 'Score': 0.3184193968772888, 'Text': 'calcium-edtmp sodium salt', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'ca', 'Type': 'TEST', 'BeginOffset': 325, 'EndOffset': 327}, {'Text': 'total sodium', 'Type': 'TEST', 'BeginOffset': 330, 'EndOffset': 342}, {'Text': 'injections', 'Type': 'TREATMENT', 'BeginOffset': 362, 'EndOffset': 372}, {'Text': 'the pack quadramet', 'Type': 'TREATMENT', 'BeginOffset': 416, 'EndOffset': 434}, {'Text': 'a solution for injection', 'Type': 'TREATMENT', 'BeginOffset': 438, 'EndOffset': 462}, {'Text': 'light amber solution', 'Type': 'TREATMENT', 'BeginOffset': 513, 'EndOffset': 533}, {'Text': '15', 'Type': 'NUMBER', 'BeginOffset': 555, 'EndOffset': 557}, {'Text': 'teflon-coated chlorobutyl/natural rubber stopper', 'Type': 'TREATMENT', 'BeginOffset': 631, 'EndOffset': 679}, {'Text': 'aluminium flip', 'Type': 'TREATMENT', 'BeginOffset': 684, 'EndOffset': 698}, {'Text': 'overseal', 'Type': 'TREATMENT', 'BeginOffset': 703, 'EndOffset': 711}, {'Text': '1.5', 'Type': 'NUMBER', 'BeginOffset': 732, 'EndOffset': 735}, {'Text': '3.1', 'Type': 'NUMBER', 'BeginOffset': 763, 'EndOffset': 766}, {'Text': 'injection', 'Type': 'TREATMENT', 'BeginOffset': 807, 'EndOffset': 816}]}