EndolucinBeta

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EndolucinBeta 40 GBq/mL radiopharmaceutical precursor, solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 mL of solution contains 40 GBq Lutetium (177Lu) chloride on activity reference time (ART), 
corresponding to 10 micrograms of Lutetium (177Lu) (as chloride). 
The ART is 12:00 pm (noon) on the scheduled day of radiolabelling as indicated by the customer and 
can be within 0 to 7 days starting from the day of manufacture. 
 
Each 2 mL vial contains an activity ranging from 3 – 80 GBq, corresponding to 0.73 – 19 micrograms 
of Lutetium (177Lu), at ART. The volume is 0.075 – 2 mL. 
 
Each 10 mL vial contains an activity ranging from 8 – 150 GBq, corresponding to 1.9 –
 36 micrograms of Lutetium (177Lu), at ART. The volume is 0.2 – 3.75 mL. 
 
The theoretical specific activity is 4,110 GBq/mg of Lutetium (177Lu). The specific activity of the 
medicinal product at ART is indicated on the label and always greater than 3,000 GBq/mg. 
 
Non carrier added (n.c.a.) Lutetium (177Lu) chloride is produced by the irradiation of highly enriched 
(> 99 %) Ytterbium (176Yb) in neutron sources with a thermal neutron flux between 1013 and 
1016 cm−2 s−1. The following nuclear reaction is ongoing in the irradiation: 
 
176Yb(n, γ) 177Yb → 177Lu 
 
The produced Ytterbium (177Yb) with a half-life of 1.9 h decays to Lutetium (177Lu). In a 
chromatographic process, the accumulated Lutetium (177Lu) is separated chemically from the original 
target material. 
Lutetium (177Lu) emits both medium-energy beta particles and imageable gamma photons, and has a 
half-life of 6.647 days. The primary radiation emissions of Lutetium (177Lu) are shown in Table 1. 
 

Table 1: Lutetium (177Lu) principle radiation emission data 

Radiation Energy (keV)* Abundance (%) 

Beta (β−) 47.66 11.61 

Beta (β−) 111.69 9.0 

Beta (β−) 149.35 79.4 

Gamma 112.9498 6.17 

Gamma 208.3662 10.36 

* mean energies are listed for beta particles 

 
Lutetium (177Lu) decays by emission of beta radiation to stable Hafnium (177Hf). 
 
For the full list of excipients, see section 6.1. 
 
 



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3. PHARMACEUTICAL FORM 
 
Radiopharmaceutical precursor, solution. 
Clear colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
EndolucinBeta is a radiopharmaceutical precursor, and it is not intended for direct use in patients. It is 
to be used only for the radiolabelling of carrier molecules that have been specifically developed and 
authorised for radiolabelling with Lutetium (177Lu) chloride. 
 
4.2 Posology and method of administration 
 
EndolucinBeta is only to be used by specialists experienced with in vitro radiolabelling. 
 
Posology 
 
The quantity of EndolucinBeta required for radiolabelling and the quantity of 
Lutetium (177Lu)-labelled medicinal product that is subsequently administered will depend on the 
medicinal product radiolabelled and its intended use. Refer to the Summary of Product 
Characteristics/package leaflet of the particular medicinal product to be radiolabelled. 
 
Paediatric population 
 
For more information concerning paediatric use of Lutetium (177Lu)-labelled medicinal products refer 
to the Summary of Product Characteristics/package leaflet of the medicinal product to be 
radiolabelled. 
 
Method of administration 
 
EndolucinBeta is intended for in vitro radiolabelling of medicinal products which are subsequently 
administered by the approved route. 
 
EndolucinBeta should not be administered directly to the patient. 
 
For instructions on preparation of the medicinal product before administration, see section 12. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Established or suspected pregnancy or when pregnancy has not been excluded (see section 4.6) 
 
For information on contraindications to particular Lutetium (177Lu)-labelled medicinal products 
prepared by radiolabelling with EndolucinBeta, refer to the Summary of Product 
Characteristics/package leaflet of the particular medicinal product to be radiolabelled. 
 
4.4 Special warnings and precautions for use 
 
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 
therapeutic effect. 



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EndolucinBeta is not to be administered directly to the patient, but must be used for the radiolabelling 
of carrier molecules, such as monoclonal antibodies, peptides, vitamins or other substrates. 
 
Renal impairment and haematological disorders 
 
Careful consideration of the benefit risk ratio in these patients is required since an increased radiation 
exposure is possible. It is recommended to perform individual radiation dosimetry assessments of 
specific organs, which may not be the target organ of therapy. 
 
Myelodysplastic syndrome and acute myeloid leukaemia 
 
Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) have been observed after 
treatment with Lutetium (177 Lu) peptide receptor radionuclide therapy for neuroendocrine tumours 
(see section 4.8). This should be taken into account when considering the benefit/risk, especially in 
patients with possible risk factors like prior exposure to chemotherapeutic agents (such as alkylating 
agents). 

 
Myelosuppression 
 
Anaemia, thrombocytopenia, leucopenia, lymphopenia, and less commonly neutropenia may occur 
during radioligand therapy with Lutetium (177Lu). Most events are mild and transient. In some patients 
more than one cell line may be affected. A blood count should be taken at baseline and monitored 
regularly during treatment, in accordance with clinical guidance. 
 
Renal irradiation 
 
Radiolabelled somatostatin analogues are excreted by the kidney. Radiation nephropathy has been 
reported following peptide receptor radionuclide therapy for neuroendocrine tumours using other 
radioisotopes. Renal function should be assessed at baseline and during treatment and renal protection 
should be considered, in accordance with clinical guidance. 
 
Hepatotoxicity 
 
Cases of hepatotoxicity have been reported in the post-marketing setting and in the literature in 
patients with liver metastases undergoing treatment with Lutetium (177Lu) peptide receptor 
radionuclide therapy for neuroendocrine tumours. Liver function should be monitored regularly during 
treatment. Dose reduction may be necessary in affected patients. 
 
Hormone release syndromes 
 
There have been reports of carcinoid crisis and other syndromes associated with release of hormones 
from functional neuroendocrine tumours following Lutetium (177Lu) peptide receptor radionuclide 
therapy, which may be related to irradiation of tumour cells. Reported symptoms include flushing and 
diarrhoea associated with hypotension. Observation of patients by overnight hospitalisation should be 
considered in some cases (e.g. patients with poor pharmacologic control of symptoms). In case of 
hormonal crises, treatments may include: intravenous high dose somatostatin analogues, intravenous 
fluids, corticosteroids, and correction of electrolyte disturbances in patients with diarrhoea and/or 
vomiting. 
 
Tumour lysis syndrome 
 
Tumour lysis syndrome has been reported following Lutetium (177Lu) radioligand therapy. Patients 
with a history of renal insufficiency and high tumour burden may be at greater risk and should be 
treated with increased caution. Renal function as well as electrolyte balance should be assessed at 
baseline and during treatment. 
 



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Extravasation 
 
There have been reports of extravasation of Lutetium (177Lu) labelled ligands in the post-marketing 
setting. In case of extravasation, infusion of the medicinal product should be immediately ceased, and 
the nuclear medicine physician and the radiopharmacist should be promptly informed. Management 
should be in accordance with local protocols. 
 
Radiation protection 
 
Point-source approximation shows that the average dose rate experienced 20 hours after administration 
of a dose of 7.3 GBq EndolucinBeta labelled radiopharmaceutical (residual radioactivity 1.5 GBq) by 
a person at 1 meter distance from the patient’s body centre with an abdominal radius of 15 cm 
is 3.5 µSv/h. Doubling the distance to the patient to 2 meters reduces the dose rate by a factor of 4, 
to 0.9 µSv/h. The same dose in a patient with an abdominal radius of 25 cm yields a dose rate 
at 1 meter of 2.6 µSv/h. The generally accepted threshold for discharge of the treated patient from the 
hospital is 20 µSv/h. In most countries, the exposure limit for hospital staff is set the same as for the 
general public at 1 mSv/year. When taking the 3.5 µSv/h dose rate as an average, this would allow 
hospital staff to work approx. 300 hours/year in close vicinity of patients treated with EndolucinBeta 
labeled radiopharmaceuticals without wearing radiation protection. Of course, the nuclear medicine 
staff is expected to wear standard radiation protection. 
Any other person in close vicinity of the treated patient should be informed about possibilities to 
reduce his/her exposure due to radiation emitted from the patient. 
 
Specific warnings 
 
For information concerning special warnings and special precautions for use of Lutetium (177Lu)-
labelled medicinal products refer also to the Summary of Product Characteristics/package leaflet of the 
medicinal product to be radiolabelled. 
 
Further precautions with respect to relatives, carers and hospital staff are provided in section 6.6. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies of Lutetium (177Lu) chloride with other medicinal products have been 
performed. 
 
For information concerning interactions associated with the use of Lutetium (177Lu)-labelled medicinal 
products refer to the Summary of Product Characteristics/package leaflet of the medicinal product to 
be radiolabelled. 
 
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. Before the use of 177Lu-labelled 
medicinal products, pregnancy should be excluded using an adequate/validated test. 
 
Pregnancy 
 
The use of lutetium (177Lu)-labelled medicinal products is contraindicated during established or 
suspected pregnancy or when pregnancy has not been excluded due to the risk of ionizing radiation to 
the foetus (see section 4.3). 
 



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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 and the expressed feeds discarded. 
 
Fertility 
 
According to literature reports and taking a conservative approach (maximum patient dose of 10 GBq, 
average labeling yield and no additional measures), it may be considered that 177Lu-labelled medicinal 
products do not lead to reproductive toxicity including spermatogenetic damage in male testes or 
genetic damage in male testes or female ovaries. 
 
Further information concerning the use of Lutetium (177Lu)-labelled medicinal products concerning 
fertility is specified in the Summary of Product Characteristics of the medicinal product to be 
radiolabelled. 
 
4.7 Effects on ability to drive and use machines 
 
Effects on ability to drive and to use machines following treatment by Lutetium (177Lu)-labelled 
medicinal products will be specified in the Summary of Product Characteristics/package leaflet of the 
medicinal product to be radiolabelled. 
 
4.8 Undesirable effects 
 
Adverse reactions following the administration of a Lutetium (177Lu)-labelled medicinal product 
prepared by radiolabelling with EndolucinBeta will be dependent on the specific medicinal product 
being used. Such information will be supplied in the Summary of Product Characteristics/package 
leaflet of the medicinal product to be radiolabelled. 
 
Exposure to ionising radiation is linked with cancer induction and a potential for development of 
hereditary defects. 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. 
 
Adverse reactions are divided into groups according to the MedDRA convention frequencies: Very 
common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 
to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data). 
 
Blood and lymphatic system disorders: 
 
very common: Anaemia, thrombocytopenia, leukopenia and lymphopenia 
 
Endocrine disorders: 
 
not known: Carcinoid crisis 
 
Metabolism and nutrition disorders: 
 
not known: Tumour lysis syndrome 
 
Gastrointestinal disorders: 
 
very common: Nausea, vomiting 
 



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Neoplasms benign, malignant and unspecified (including cysts and polyps): 
 
common: Refractory cytopenia with multilineage dysplasia (Myelodysplastic syndrome) (see 
section 4.4) 
uncommon: Acute myeloid leukaemia (see section 4.4) 
 
Skin and subcutaneous tissue disorders: 
 
very common: Alopecia 
 
Description of selected adverse reactions 
 
Dry mouth has been reported among patients with metastatic castration resistant prostate cancer 
receiving PSMA-targeted Lutetium (177Lu)-labelled radioligands and has been transient. 
 
Skin and subcutaneous tissue disorders: Alopecia, described as mild and temporary, has been 
observed among patients receiving Lutetium (177Lu) peptide receptor radionuclide therapy for 
neuroendocrine tumours. 
 
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 presence of free Lutetium (177Lu) chloride in the body after an inadvertent administration of 
EndolucinBeta will lead to increased bone marrow toxicity and haematopoietic stem cell damage. 
Therefore, in case of an inadvertent administration of EndolucinBeta, the radiotoxicity for the patient 
must be reduced by immediate (i. e. within 1 hour) administration of preparations containing chelators 
like Ca-DTPA or Ca-EDTA in order to increase the elimination of the radionuclide from the body. 
 
The following preparations must be available in medical institutions, which use EndolucinBeta for 
labelling of carrier molecules for therapeutic purposes: 
- Ca-DTPA (Trisodium calcium diethylenetriaminepentaacetate) or 
- Ca-EDTA (Calcium disodium ethylenediaminetetraacetate) 
 
These chelating agents help with the elimination of Lutetium (177Lu) radiotoxicity by an exchange 
between the calcium ion in the complex and the Lutetium (177Lu) ion. Due to the capacity of the 
chelating ligands (DTPA, EDTA) of forming water soluble complexes, the complexes and bound 
Lutetium (177Lu) are rapidly eliminated by the kidneys. 
 
1 g of the chelating agents should be administered by slow intravenous injection over 3 – 4 minutes or 
by infusion (1 g in 100 – 250 mL of glucose, or sodium chloride 9 mg/mL (0.9 %) solution for 
injection). 
 
The chelating efficacy is greatest immediately or within one hour of exposure when the radionuclide is 
circulating in or available to tissue fluids and plasma. However, a post-exposure interval > 1 hour does 
not preclude the administration and effective action of chelator with reduced efficiency.Intravenous 
administration should not be protracted over more than 2 hours. 
 
In any case, the blood parameters of the patient have to be monitored and the appropriate actions 
immediately taken if there is evidence of radiotoxicity. 
 
The toxicity of free Lutetium (177Lu) due to in-vivo release from the labelled biomolecule in the body 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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during therapy could be reduced by post-administration of chelating agents. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other therapeutic radiopharmaceuticals, ATC code: V10X 
 
The pharmacodynamic properties of Lutetium (177Lu)-labelled medicinal products prepared by 
radiolabelling with EndolucinBeta, prior to administration, will be dependent on the nature of the 
medicinal product to be radiolabelled. Refer to the Summary of Product Characteristics/package 
leaflet of the particular medicinal product to be radiolabelled. 
 
Lutetium (177Lu) emits β-particles of moderate maximum energy (0.498 MeV) with a maximum tissue 
penetration of approximately 2 mm. Lutetium (177Lu) also emits low-energy γ-rays which allow 
scintigraphic, biodistribution and dosimetry studies with the same Lutetium (177Lu)-labelled medicinal 
products. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of the studies with 
EndolucinBeta in all subsets of the paediatric population on grounds that the specific medicinal 
product does not represent a significant therapeutic benefit over existing treatments for paediatric 
patients. This waiver does however not extend to any therapeutic uses of the product when linked to a 
carrier molecule (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetic properties of Lutetium (177Lu)-labelled medicinal products prepared by 
radiolabelling with EndolucinBeta, prior to administration, will be dependent on the nature of the 
medicinal product to be radiolabelled. 
 
Distribution after inadvertent intravenous administration of Lutetium (177Lu) chloride 
 
In the male and female rat, following intravenous administration, Lutetium (177Lu) chloride is rapidly 
cleared from the blood: at 5 min post injection, only 1.52 % of the injected activity (%ID) is found in 
blood (corresponding to 0.08 %ID/g) and no activity above background levels remains 1 hour post 
dose. Lutetium (177Lu) chloride distributes mainly to the liver, spleen and bone. After one hour, the 
amount in the liver is 9.56 % of the injected activity per gram (%ID/g) and in the spleen 5.26 %ID/g. 
In bone, the content increases from 0.01 %ID/g at 5 min to 0.23 %ID/g after 12 hours. For the 
next 28 days, further uptake of 177Lu can be observed in the bone, which is compensated in part by 
radioactive decay. Taking into account the radioactive half-life of 177Lu of 6.647 days, the 
radioactivity remaining in the bone after 28 days is only about 0.06 %ID/g. 
Faecal and urinary elimination is slow. As a result of both excretion and radioactive decay, the total 
radioactivity remaining in the body after 28 days is about 1.8 % of the injected dose. 
 
5.3 Preclinical safety data 
 
The toxicological properties of Lutetium (177Lu)-labelled medicinal products prepared by 
radiolabelling with EndolucinBeta prior to administration, will be dependent on the nature of the 
medicinal product to be radiolabelled. 
 
The toxicity of non-radioactive Lutetium chloride has been studied in different mammalian species 
and using different administration routes. The intraperitoneal LD50 in mice was found to be 
approximately 315 mg/kg. In cats, no pharmacological effects on respiration and cardiovascular 
function were observed up to a cumulative intravenous dose of 10 mg/kg. A high dose of 10 GBq of 



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177Lu-chloride contains 2.4 µg Lutetium, corresponding to a human dose of 0.034 µg/kg. This dose is 
approximately 7 orders of magnitude lower than the intraperitoneal LD50 in mice and more than 
5 orders of magnitude lower than the NOEL observed in cats. Therefore, Lutetium metal-ion toxicity 
of EndolucinBeta (177Lu)-labelled medicinal products can be excluded. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Hydrochloric acid solution 
 
6.2 Incompatibilities 
 
Radiolabelling of medicinal products, such as monoclonal antibodies, peptides, vitamins or other 
substrates, with Lutetium (177Lu) chloride is very sensitive to the presence of trace metal impurities. 
 
It is important that all glassware, syringe needles etc., used for the preparation of the radiolabelled 
medicinal product are thoroughly cleaned to ensure freedom from such trace metal impurities. Only 
syringe needles (for example, non-metallic) with proven resistance to dilute acid should be used to 
minimise trace metal impurity levels. 
 
In the absence of compatibility studies, this medicinal product must not be mixed with medicinal 
products other than the medicinal products to be radiolabelled. 
 
6.3 Shelf life 
 
Up to 9 days from the date of manufacture. 
 
From a microbiological point of view, unless the method of withdrawal from the vial or any insertion 
into the vial preclude the risk of microbial contamination, the product should be used immediately. 
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the 
user. 
 
6.4 Special precautions for storage 
 
Store in the original package in order to avoid unnecessary radiation exposure. 
 
Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive 
materials. 
 
This medicinal product does not require any special temperature storage conditions. 
 
6.5 Nature and contents of container 
 
Colourless type I glass 2 mL or 10 mL vial with a V-shaped and flat bottom, respectively, with a 
bromobutyl stopper, closed with an aluminium seal. 
 
The vials are placed into a lead container for protective shielding and packed in a metallic can and an 
outer carton. 
 
Pack size: 1 vial 
 
6.6 Special precautions for disposal and other handling 
 
EndolucinBeta is not intended for direct use in patients. 
 



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General warning 
 
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. 
 
For instructions on extemporary preparation of the medicinal product before administration, see 
section 12. 
 
If at any time in the preparation of this product the integrity of this container is compromised it should 
not be used. 
 
Administration procedures should be carried out in a way to minimise risk of contamination of the 
medicinal product and irradiation of the operators. Adequate shielding is mandatory. 
 
The surface dose rates and the accumulated dose depend on many factors. Measurements on the 
location and during work are critical and should be practiced for more precise and instructive 
determination of overall radiation dose to the staff. Healthcare personnel are advised to limit the time 
of close contact with patients injected with Lutetium (177Lu)-labelled radiopharmaceuticals. The use of 
television monitor systems to monitor the patients is recommended. Given the long half-life of 
Lutetium (177Lu), it is specially recommended to avoid internal contamination. For this reason it is 
mandatory to use protective high quality (latex/nitrile) gloves in any direct contact with the 
radiopharmaceutical (vial/syringe) and with the patient. For minimising radiation exposure resulting 
from repeated exposition there is no recommendation except the strict observance of the above ones. 
 
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 must be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
ITM Medical Isotopes GmbH 
Lichtenbergstrasse 1 
D-85748 Garching 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
2 mL vial:  EU/1/16/1105/001 
10 mL vial: EU/1/16/1105/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 6 July 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 



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11. DOSIMETRY 
 
The radiation dose received by various organs following intravenous administration of a 
Lutetium (177Lu)-labelled medicinal product is dependent on the specific molecule being radiolabelled. 
 
Information on radiation dosimetry of each different medicinal product following administration of the 
radiolabelled preparation is available in the Summary of Product Characteristics/package leaflet of the 
particular medicinal product to be radiolabelled. 
 
The dosimetry table below is presented in order to evaluate the contribution of non-conjugated 
Lutetium (177Lu) to the radiation dose following the administration of a Lutetium (177Lu)-labelled 
medicinal product or resulting from an accidental intravenous injection of EndolucinBeta. 
 
The dosimetry estimates were based on a rat biodistribution study performed according to MIRD 
pamphlet no.16, and the calculations were performed using the OLINDA 1.1 software package. Time 
points for measurements were 5 minutes, 1 hour, 12 hours, 2 days, 7 days and 28 days. 
 
Table 2: Estimated organ absorbed radiation doses and effective doses (mSv/MBq) after 

inadvertent intravenous administration of 177LuCl3 for various human age classes, 
based on data collected in rats (n = 24) 

 
 
 
 
Organ 

Absorbed dose per unit radioactivity administered (mSv/MBq) 

Adult 
(73.7 kg) 

15 years old 
(56.8 kg) 

10 years old 
(33.2 kg) 

5 years old 
(19.8 kg) 

1 year old 
(9.7 kg) 

Adrenals 0.2130 0.3070 0.4450 6.0400 0.9120 
Brain 0.0056 0.0068 0.0089 1.3500 0.0197 
Breasts 0.0107 0.0134 0.0239 0.0377 0.0697 
Gallbladder Wall 0.1090 0.1240 0.1610 0.2530 0.4500 
LLI Wall 0.0104 0.0097 0.0167 0.0292 0.0522 
Small Intestine 0.1090 0.0244 0.0434 0.0731 0.1260 
Stomach Wall 0.0556 0.0381 0.0648 0.1040 0.1860 
ULI Wall 0.0297 0.0334 0.0609 0.1050 0.1830 
Heart Wall 0.0415 0.0535 0.0805 0.1190 0.2090 
Kidneys 0.3720 0.4490 0.6460 0.956 1.7200 
Liver 5.5600 7.5600 11.900 17.900 35.700 
Lungs 0.0574 0.0808 0.1140 0.1720 0.3230 
Muscle 0.0143 0.0180 0.0260 0.0386 0.0697 
Ovaries 0.0106 0.0129 0.0224 0.0379 0.0709 
Pancreas 0.0663 0.0818 0.1250 0.1900 0.3050 
Red Marrow 0.5910 0.6670 1.2300 2.6200 6.6000 
Osteogenic Cells 2.1500 2.8100 4.5900 7.8000 18.800 
Skin 0.0073 0.0091 0.0140 0.0217 0.0412 
Spleen 5.7300 8.5000 13.500 21.600 40.700 
Testes 0.0022 0.0029 0.0049 0.0088 0.0188 
Thymus 0.0102 0.0128 0.0179 0.0276 0.0469 
Thyroid 0.0058 0.0075 0.0113 0.0206 0.0377 
Urinary Bladder Wall 0.0043 0.0056 0.0116 0.0247 0.0435 
Uterus 0.0085 0.0102 0.0184 0.0331 0.0635 
Rest of Body 0.2330 0.2990 0.5060 0.8380 1.6900 
      



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Effective Dose 
(mSv/MBq) 

 
0.534 

 
0.721 

 
1.160 

 
1.88 

 
3.88 

 
The effective dose to a 73.7 kg adult resulting from an inadvertently injected intravenous activity of 
1 GBq would be 534 mSv. 
 
 
12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 
 
Before use, packaging and radioactivity should be checked. Activity may be measured using an 
ionisation chamber. 
 
Lutetium (177Lu) is a beta(-)/gamma emitter. Activity measurements using an ionization chamber are 
very sensitive to geometric factors and therefore should be performed only under geometric conditions 
which have been appropriately validated. 
 
Usual precautions regarding sterility and radioactivity should be respected. 
 
Withdrawals should be performed under aseptic conditions. The vials must not be opened before 
disinfecting 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. 
 
The complexing agent and other reagents should be added to the vial with Lutetium (177Lu) chloride. 
Free Lutetium (177Lu) is taken up and accumulates in the bones. This could potentially result in 
osteosarcomas. It is recommended to add a binding agent such as DTPA prior to intravenous 
administration of Lutetium (177Lu)-labelled conjugates in order to form a complex with free 
Lutetium (177Lu), if present, leading to a rapid renal clearance of Lutetium (177Lu). 
 
Adequate quality control of the radiochemical purity of ready to use radiopharmaceuticals gained after 
radiolabelling with EndolucinBeta should be assured. Limits for radiochemical impurities should be 
set recognising the radiotoxicological potential of Lutetium (177Lu). Free non-bound Lutetium (177Lu) 
should be consequently minimised. 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER 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 RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
ITM Medical Isotopes GmbH 
Lichtenbergstrasse 1 
Garching b. Muenchen 
Bayern, 85748 
Germany 
 
 
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 
 
• Periodic safety update reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



17 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
METALLIC CAN AND OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EndolucinBeta 40 GBq/mL radiopharmaceutical precursor, solution 
Lutetium (177Lu) chloride 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 mL of solution contains 40 GBq of Lutetium (177Lu) chloride at activity reference time (ART). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipient: Hydrochloric acid solution 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Radiopharmaceutical precursor, solution. 
 
VOLUME: …mL  
ACTIVITY: …GBq/vial at ART ART: {DD/MM/YYYY 12:00 CET } 
Specific 
activity: 

…GBq/mg at ART  

 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For administration after in vitro radiolabelling. 
 
 
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 
 

 
 
 
8. EXPIRY DATE 
 
EXP: {DD/MM/YYYY, hh:00 CET} 
 
 



18 

9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to avoid unnecessary radiation exposure. 
 
Storage should be in accordance with local regulations for radioactive substances. 
 
 
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 must be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ITM Medical Isotopes GmbH 
D-85748 Garching/Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
2 mL vial: EU/1/16/1105/001 
10 mL vial: EU/1/16/1105/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
 



19 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
LEAD POT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
EndolucinBeta 40 GBq/mL radiopharmaceutical precursor, solution 
Lutetium (177Lu) chloride 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 mL of solution contains 40 GBq of Lutetium (177Lu) chloride at activity reference time (ART). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipient: Hydrochloric acid solution 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Radiopharmaceutical precursor, solution. 
 
VOLUME: …mL  
ACTIVITY: …GBq/vial at ART ART: {DD/MM/YYYY 12:00 CET } 
Specific activity: …GBq/mg at ART  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For administration after in vitro radiolabelling. 
 
 
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 
 

 
 
 
8. EXPIRY DATE 
 
EXP: {DD/MM/YYYY, hh:00 CET} 
 
 
9. SPECIAL STORAGE CONDITIONS 



20 

 
Store in the original package in order to avoid unnecessary radiation exposure. 
 
Storage should be in accordance with local regulations for radioactive substances. 
 
 
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 must be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ITM Medical Isotopes GmbH 
D-85748 Garching/Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
2 mL vial: EU/1/16/1105/001 
10 mL vial: EU/1/16/1105/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
 



21 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL (2 mL, 10 mL) 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
EndolucinBeta 40 GBq/mL 
 
Lutetium (177Lu) chloride 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP:{DD/MM/YYYY, hh:00 CET} 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
VOLUME: …mL  
ACTIVITY: …GBq/vial ART: {DD/MM/YYYY 12:00 CET} 
 
 
6. OTHER 
 

 
 
ITM Medical Isotopes GmbH 
D-85748 Garching 
Germany 
 



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



23 

Package leaflet: Information for the patient 
 

EndolucinBeta 40 GBq/mL radiopharmaceutical precursor, solution 
Lutetium (177Lu) chloride 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you are given the medicine combined with EndolucinBeta 
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 nuclear medicine doctor who will supervise the 

procedure. 
- If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What EndolucinBeta is and what it is used for 
2. What you need to know before the medicine radiolabelled with EndolucinBeta is used 
3. How the medicine radiolabelled with EndolucinBeta is used 
4. Possible side effects 
5. How EndolucinBeta is stored 
6. Contents of the pack and other information 
 
 
1. What EndolucinBeta is and what it is used for 
 
EndolucinBeta is not a medicine and it is not intended to be used on its own. It has to be used in 
combination with other medicines (carrier medicines). 
 
EndolucinBeta is a type of product called a radiopharmaceutical precursor. It contains the active 
substance Lutetium (177Lu) chloride which gives off beta-radiation, allowing a localised radiation 
effect. This radiation is used to treat certain diseases. 
 
EndolucinBeta has to be combined with a carrier medicine in a process called radiolabelling before 
administration. The carrier medicine then takes the EndolucinBeta to the disease site in the body. 
 
These carrier medicines have been specially developed for use with Lutetium (177Lu) chloride and may 
be substances that have been designed to recognise a particular type of cell in the body. 
 
The use of a medicine radiolabelled with EndolucinBeta does involve exposure to 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. 
 
Please refer to the package leaflet of the medicine that is to be radiolabelled with EndolucinBeta. 
 
 
2. What you need to know before the medicine radiolabelled with EndolucinBeta is used 
 
The medicine radiolabelled with EndolucinBeta must not be used 
- if you are allergic to Lutetium (177Lu) chloride or any of the other ingredients of this medicine 

(listed in section 6). 
- if you are pregnant or believe you may be pregnant. 
 
Please refer to the package leaflet of the medicine that is to be radiolabelled with EndolucinBeta for 



24 

additional information. 
 
Warnings and precautions 
EndolucinBeta is not to be administered directly to patients. 
Take special care with the medicine that is radiolabelled with EndolucinBeta: 
- if you have renal impairment or bone marrow disease. 
 
Treatment with Lutetium (177Lu) radioligand therapy may lead to the following side effects 
- a reduced number of red blood cells (anaemia) 
- a reduced number of platelets in the blood (thrombocytopenia) which are important to stop 

bleeding 
- a reduced number of white blood cells (leukopenia, lymphopenia or neutropenia) which are 

important for protecting the body against infection 
 
Most of these events are mild and only temporary. Because Lutetium (177Lu) can sometimes affect 
your blood cells, your doctor will do blood tests before you start and at regular intervals during 
treatment. 
 
During peptide-receptor radionuclide therapy for neuroendocrine tumours, radiolabelled somatostatin 
analogues are excreted by the kidneys. Your doctor will therefore take a blood test to measure your 
kidney function before you start and during treatment. 
 
Treatment with Lutetium (177Lu) may cause disturbances of liver function. Your doctor will take a 
blood test to monitor your liver function during treatment.  
 
After neuroendocrine tumours are treated with Lutetium (177Lu), patients may experience symptoms 
associated with release of hormones from the tumour cells, known as a carcinoid crisis. Tell your 
doctor if you feel faint or dizzy or experience flushing or diarrhoea following your treatment. 
 
Treatment with Lutetium (177Lu) may cause tumour lysis syndrome, due to the rapid breakdown of 
tumour cells. This may result in abnormal blood test results, irregular heartbeat, kidney failure or 
seizures within a week of treatment. Your doctor will perform blood tests to monitor you for this 
syndrome. Tell your doctor if you have muscle cramping, muscle weakness, confusion, or shortness of 
breath. 
 
Please refer to the package leaflet of the medicine that is to be radiolabelled with EndolucinBeta for 
additional warnings and precautions. 
 
Children and adolescents 
EndolucinBeta is not to be used directly in childrens and adolescent patients under 18 years old. 
 
Other medicines and medicines radiolabelled with EndolucinBeta 
Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other 
medicines since they may interfere with the procedure. 
It is not known whether Lutetium (177Lu) chloride may interact with other medicines as specific 
studies have not been carried out. 
 
Pregnancy and breast-feeding 
You must inform the nuclear medicine doctor before the administration of medicines radiolabelled 
with EndolucinBeta 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 
Medicines radiolabelled with EndolucinBeta must not be administered if you are pregnant. 



25 

 
If you are breast-feeding 
You will be asked to stop breast-feeding. 
Please ask your nuclear medicine doctor when you can resume breast-feeding. 
 
Driving and using machines 
There could be effects on your ability to drive and to use machines due to the medicine used in 
combination with EndolucinBeta. Please read the package leaflet of that medicine carefully. 
 
 
3. How the medicine radiolabelled with EndolucinBeta is used 
 
There are strict laws on the use, handling and disposal of radiopharmaceutical products. Medicines 
radiolabelled with EndolucinBeta will only be used in special 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 a medicine 
radiolabelled with EndolucinBeta to be used in your case. It will be the smallest quantity necessary to 
achieve the appropriate outcome, depending on the medicine you take with EndolucinBeta and what it 
is used for. 
 
Administration of the medicine radiolabelled with EndolucinBeta and conduct of the procedure 
EndolucinBeta must be used only in combination with another medicine (carrier medicine) which has 
been specifically developed and authorised for being combined with Lutetium (177Lu) chloride. The 
administration will depend on the type of the carrier medicine. Please read the package leaflet of that 
medicine. 
 
Duration of the procedure 
Your nuclear medicine doctor will inform you about the usual duration of the procedure. 
 
After administration of the medicine radiolabelled with EndolucinBeta, you should 
The nuclear medicine doctor will inform you if you need to take any special precautions after 
receiving the medicine radiolabelled with EndolucinBeta. Contact your nuclear medicine doctor if you 
have any questions. 
 
If you have been given more medicine radiolabelled with EndolucinBeta than you should 
Since the medicine radiolabelled with EndolucinBeta is handled by a nuclear medicine doctor under 
strictly controlled conditions, there is only a very small chance of possible overdose. However, in the 
case of an overdose or an inadvertent intravenous injection of the unlabelled product, you will receive 
appropriate treatment that will remove the radionuclide from the body. 
 
Should you have any further questions on the use of the medicine radiolabelled with EndolucinBeta, 
ask your nuclear medicine doctor who supervises the procedure. 
 
 
4. Possible side effects 
 
Like all medicines, the medicine radiolabelled with EndolucinBeta can cause side effects, although not 
everybody gets them. 
 
Dry mouth has been reported among patients with prostate cancer receiving treatment with 
Lutetium (177Lu) and has been temporary. 
 
Very common side effects (may affect more than 1 in 10 people): 
 
- Reduction in blood cell counts (platelets, red or white blood cells) 



26 

- Nausea 
- Vomiting 
 
Side effects reported among patients treated for neuroendocrine tumors: 
 
Very common (may affect more than 1 in 10 people): 
 
- Mild temporary hair loss 
 
Common (may affect up to 1 in 10 people): 
 
- Bone marrow cancer (myelodysplastic syndrome) 
 
Uncommon (may affect up to 1 in 100 people): 
 
- Bone marrow cancer (acute myeloid leukaemia) 
 
Not known (frequency cannot be estimated from the available data): 
 
- Carcinoid crisis 
- Tumour lysis syndrome (rapid breakdown of tumour cells) 
 
Bone marrow cancer (myelodysplastic syndrome and acute myeloid leukaemia) has been reported in 
patients several years after treatment with Lutetium (177Lu) peptide receptor radionuclide therapy for 
neuroendocrine tumours.  
 
After the medicine radiolablelled with EndolucinBeta is administered, it will deliver certain amounts 
of ionising radiation (radioactivity) which can induce a certain risk of cancer and development of 
hereditary defects. In all cases, the risk of the radiation is outweighed by the potential benefit of 
receiving the radiolabelled medicine. 
 
For more information, refer to the package leaflet of the particular medicinal product to be 
radiolabelled. 
 
Reporting of side effects 
If you get any side effects, talk to your nuclear medicine doctor. 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 EndolucinBeta 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. 
 
EndolucinBeta must not be used after the expiry date and time which is stated on the label after EXP. 
EndolucinBeta will be stored in the original package that provides protection from radiation. 
 
 
6. Contents of the pack and other information 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


27 

What EndolucinBeta contains 
- The active substance is Lutetium (177Lu) chloride. 

1 mL sterile solution contains 40 GBq Lutetium (177Lu) chloride on the activity reference time 
(corresponding to 10 micrograms of Lutetium (177Lu) as Lutetium (177Lu) chloride). 
(GBq: GigaBecquerel is the unit in which radioactivity is measured). 

- The other ingredient is hydrochloric acid solution. 
 
What EndolucinBeta looks like and contents of the pack 
EndolucinBeta is a radiopharmaceutical precursor, solution. It is presented as a clear and colourless 
solution in a colourless type I glass 2 mL or 10 mL vial with a V-shaped and flat bottom, respectively, 
with a bromobutyl stopper, closed with an aluminium seal. 
Each pack contains 1 vial placed into a lead container for protective shielding and packed in a metallic 
can and an outer carton. 
 
The volume of one vial ranges from 0.075 – 3.75 mL solution (corresponding to 3 – 150 GBq at 
activity reference time). The volume depends on the quantity of medicine combined with 
EndolucinBeta required for administration by the nuclear medicine doctor. 
 
Marketing Authorisation Holder and Manufacturer 
 
ITM Medical Isotopes GmbH 
Lichtenbergstrasse 1 
D-85748 Garching 
Germany 
Tel: + 49-89-289 139-08 
info@itm.ag 
 
This leaflet was last revised in {month YYYY} 
 
Other sources of information 
 
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 healthcare professionals only: 
 
The complete SmPC of EndolucinBeta 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. 
 

http://www.ema.europa.eu/


28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 

 



29 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for Lutetium (177Lu) chloride, the 
scientific conclusions of the CHMP are as follows:  
 
Five cases of tumour lysis syndrome (TLS) were identified in the scientific literature in association 
with Lu-177 based radioligand therapy (RLT). The cases occurred in close temporal proximity to the 
RLT, alternative aetiologies were excluded and most cases either met or were close to meeting formal 
criteria of TLS definition. All cases recovered with treatment. 
 
The lower bound of the 95 % confidence interval of the reporting odds ratio for tumour lysis syndrome 
in EudraVigilance in association with Lu-177 is increased at 34.50, with 3 cases. These are duplicates 
of those identified in the literature.  
 
The PRAC is of the view that although the number of identified cases is limited, the exposure to date 
is relatively low, and the association with tumour lysis syndrome is biologically plausible. The PRAC 
therefore recommends that the Product Information should be updated accordingly. 
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
 
On the basis of the scientific conclusions for Lutetium (177Lu) chloride the CHMP is of the opinion 
that the benefit-risk balance of the medicinal product(s) containing Lutetium (177Lu) chloride is 
unchanged subject to the proposed changes to the product information. 
 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied.