Lumark

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Lumark 80 GBq/mL radiopharmaceutical precursor, solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each mL of solution contains 80 GBq lutetium (P177PLu) chloride at activity reference time (ART), 
corresponding to at most a maximum of 160 microgram of lutetium. The ART is defined as the end of 
production. 
 
Each vial contains a volume varying from 0.1 to 5 mL corresponding to an activity ranging from 8 to 
400 GBq (at ART). 
 
The minimal specific activity is 500 GBq/mg lutetium (P177PLu) at the ART.  
 
Lutetium (P177PLu) has a half-life of 6.647 days. Lutetium (P177PLu) is produced by neutron irradiation of 
enriched lutetium (P176PLu). Lutetium (P177PLu) decays by βP-P-emission to stable Hafnium (P177PHf), with the most 
abundant βP-P (79.3%) having a maximum energy of 0.497 MeV. Also low gamma energy is emitted, for 
instance at 113 keV (6.2%) and 208 keV (11%). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Radiopharmaceutical precursor, solution. 
Clear, colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Lumark is a radiopharmaceutical precursor. It is not intended for direct use in patients. It  must be used only 
for the radiolabelling of carrier molecules, which have been specifically developed and authorised for 
radiolabelling with this radionuclide. 
   
4.2 Posology and method of administration 
 
Lumark is only to be used by specialists experienced with in vitro radiolabelling. 
 
UPosology 
 
The quantity of Lumark required for radiolabelling and the quantity of the medicinal product to be 
radiolabelled with lutetium(P177PLu) that is subsequently administered will depend on the medicinal product to 
be radiolabelled and its intended use. Refer to the Summary of Product Characteristics/package leaflet of the 
particular medicinal product to be radiolabelled. 
 



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Paediatric population 
For more information concerning the paediatric use of lutetium (P177PLu)-labelled medicinal products refer to 
the Summary of Products Characteristics/package leaflet of the the particular medicinal product to be 
radiolabelled. 
 
UMethod of administration  
 
Lumark is intended for in vitro radiolabelling of medicinal products, which are subsequently administered by 
the approved route. 
Lumark should not be administered directly to the patient. 
Lumark is for single-use only. 
For instructions on extemporary 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 (P177PLu)-labelled medicinal products prepared 
by radiolabelling with Lumark, refer to the Summary of Product Characteristics/package leaflet of 
each particular medicinal product to be radiolabelled. 
 
4.4 Special warnings and precautions for use 
 
UIndividual 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. Lumark is 
not to be administered directly to the patient but must be used for the radiolabelling of carrier molecules, 
such as monoclonal antibodies, peptides or other substrates. 
 
UGeneral warnings 
 
Radiopharmaceuticals should be received, used and administered only by authorised persons in designated 
clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or 
appropriate licences of the competent official authorities.  
 
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. 
 
For information concerning special warnings and precautions for use of P177PLu-labelled medicinal products 
refer to the Summary of Product Characteristics/package leaflet of the medicinal product to be radiolabelled.  
 
URadiation protection 
 
Administration of a high activity (7.400 MBq) of the lutetium(P177PLu)-labelled medicinal product results in an 
average radiation dose rate at 1 m distance from the patient of 4-11 µSv/h after 24 hours. This is below the 
threshold considered acceptable for discharge from the clinic (20 µSv/h). For a person in the vicinity of the 
patient, assuming continuous exposure at 2 m and infinite biological half-life (no disposal by the patient after 
discharge from the hospital), this dose rate will result in an overall dose of approximately 0.6 mSv, which is 
approximately one half of the dose limit set for general public (1 mSv/year).  
 
Precautions with respect to relatives, carers and hospital staff are provided in section 6.6.  
 
URenal impairment and haematological disorders 
 



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Myelodysplastic syndrome and acute myeloid leukaemia 
Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) have been observed after treatment 
with lutetium (P177 PLu) 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 (P177PLu). 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 including glomerular filtration rate (GFR) should be assessed at baseline and during treatment and 
renal protection should be considered, in accordance with clinical guidance of the radiolabelled medicinal 
product. 
  
UHepatotoxicity 
 
Cases of hepatotoxicity have been reported in the post-marketing setting and in the literature in patients with 
liver metastases undergoing treatment with P177PLu peptide receptor radionuclide therapy for neuroendocrine 
tumours. Liver function should be monitored regularly during treatment. Dose reduction may be necessary in 
affected patients.  
 
UHormone release syndromes 
 
There have been reports of carcinoid crisis and other syndromes associated with release of hormones from 
functional neuroendocrine tumours following P177PLu 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. 

UExtravasation 
 
There have been reports of extravasation of lutetium (P177PLu) 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. 

UTumour lysis syndrome 
Tumour lysis syndrome has been reported following Lutetium (P177PLu) 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. 

  
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies of lutetium (P177PLu) with other medicinal products have been performed. The possible 
use of chelating therapies could interfere with the use of lutetium(P177PLu)-labelled medicinal products. 
 



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For information concerning interactions associated with the use of lutetium (P177PLu)-labelled medicinal 
products refer to the Summary of Product Characteristics/package leaflet of the radiolabelled medicinal 
product. 
 
4.6 Fertility, pregnancy and lactation 
 
UWomen of childbearing potential  
 
When an administration of radiopharmaceutical 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 P177PLu -labelled medicinal products, 
pregnancy should be excluded using an adequate/validated test. 
 
UPregnancy 
 
The use of lutetium (P177PLu)-labelled medicinal products is contraindicated during established or suspected  
pregnancy or when pregnancy has not been excluded (see section 4.3). 
 
UBreast-feeding 
 
Before administering radiopharmaceuticals to a mother who is breast-feeding, consideration should be given 
to the possibility of delaying the administration of radionuclide until the mother has ceased breast-feeding, 
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, breast-feeding  should be interrupted and the 
expressed feeds discarded. 
 
UFertility 
 
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 P177PLu-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 P177PLu-labelled medicinal products 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 or use machines following treatment by lutetium (P177PLu)-labelled medicinal 
products is specified in the Summary of Product Characteristics/package leaflet of the particular medicinal 
product to be radiolabelled. 
 
4.8 Undesirable effects 
 
USummary of the safety profile 
 
Adverse reactions following the intravenous administration of lutetium (P177PLu)-labelled medicinal products 
prepared by radiolabelling with Lumark will be dependent on the specific medicinal product being used. 
Such information is supplied in the Summary of Product Characteristics/package leaflet of the medicinal 
product to be radiolabelled.  
For each patient, exposure to ionising radiation must be justifiable on the basis of likely clinical benefit. The 
activity administered must be such that the resulting radiation dose is as low as reasonably achievable 
bearing in mind the need to obtain the intended therapeutic result. 
 



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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.  
 
UTabulated list of adverse reactions 
 
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). 
 
Adverse drug reaction Frequency category 
Neoplasms benign, malignant and unspecified (including cysts and polyps) 
Refractory cytopenia with multilineage 
dysplasia (Myelodysplastic syndrome) (see 
section 4.4) 

Common 

Acute myeloid leukaemia (see section 4.4) Uncommon 
Blood and lymphatic system disorders 
Anaemia 

Very common Thrombocytopenia Leukopenia 
Lymphopenia 
Endocrine disorders 
Carcinoid crisis Not known 
Metabolism and nutrition disorders 
Tumour lysis syndrome Not known 
Gastrointestinal disorders 
Nausea Very common Vomiting 
Skin and subcutaneous tissue disorders 
Alopecia Very common 
 
UDescription of selected adverse reactions 
 
Dry mouth has been reported among patients with metastatic castration resistant prostate cancer receiving 
PSMA-targeted lutetium (P177PLu)-labelled radioligands and has been transient. 
 
Alopecia, described as mild and temporary, has been observed among patients receiving lutetium (P177PLu) 
peptide receptor radionuclide therapy for neuroendocrine tumours. 
 
UReporting 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 30TUAppendix VU30T. 
 
4.9 Overdose 
 
The presence of free lutetium (P177PLu) chloride in the body after an inadvertent administration of Lumark will 
lead to increased bone marrow toxicity and haematopoetic stem cell damage. Therefore, in case of an 
inadvertent administration of Lumark, 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.  
 

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


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The following preparations must be available in medical institutions, which use Lumark for radiolabelling 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 (P177PLu) radiotoxicity by an exchange between 
the calcium ion in the complex and the lutetium (P177PLu) ion. Due to the capacity of the chelating 
ligands (DTPA, EDTA) of forming water soluble complexes, the complexes and bound lutetium(P177PLu) 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 damage to the blood marrow. 
 
The toxicity of the free lutetium (P177PLu) due to in vivo release from the labelled biomolecule in the body 
during therapy could be reduced by post-administration of chelating agents. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
  
Pharmacotherapeutic group: Not yet assigned, ATC code: Not yet assigned 
 
Lutetium (P177PLu) chloride is produced by irradiation of P176PLu with neutrons. It decays by emission of beta 
radiation of  maximal 498 keV  to P177PHf-Hafnium. P177PLu-lutetium has a half-life of 6.647 days. 
 
The pharmacodynamic properties of lutetium (P177PLu)-labelled medicinal products prepared by radiolabelling 
with Lumark, 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. 
 
Paediatric population  
 
The European Medicines Agency has waived the obligation to submit the results of the studies with Lumark 
in all subsets of the paediatric population on grounds that the specific medicinal product is likely to be 
ineffective or unsafe in part or all of the paediatric population and on grounds that the specific medicinal 
product does not represent a significant therapeutic benefit over existing treatments for the paediatric 
patients. This waiver does however not extend to any diagnostic or therapeutic uses of the medicinal 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 (P177PLu)-labelled medicinal products prepared by radiolabelling 
with Lumark, prior to administration, will be dependent on the nature of the medicinal product to be 
radiolabelled. 
 
Distribution 
 



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Pharmacokinetics of lutetium (P177PLu) was investigated in rats and mice. The distribution and mineral 
concentrations in the organs were investigated at low (9-10 mg/kg) and high (19-20 mg/kg) doses 
administered intravenously to rats. It appeared that more than 78% of the doses was distributed into liver, 
bone and spleen. For lutetium (P177PLu) the different dose levels did not result in significantly different uptake 
with 65% appearing in the liver, 5.3% in the spleen and 13% in the bones at one day after administration.  
With respect to the distribution pattern in blood it appeared that 2 h after administration 15% of the lutetium 
as being present in blood, had entered the blood cells with the remaining 85% still being present in the 
serum. 
 
A more detailed study of the biodistribution of lutetium (P177PLu) chloride in mice confirms the relatively high 
uptake in the liver, kidneys and bone marrow The results indicated that lutetium (P177PLu) chloride is 
accumulated in the bone marrow and emphasizes the importance of all lutetium (P177PLu) to be peptide-bound 
at injection, as well as the in-vivo stability of the radionuclide-chelate-complex during therapy. 
 
Pharmacokinetic data on Lumark related to free lutetium 
 
When the precursor is bound to a carrier molecule the content of radioactive free lutetium (P177PLu) is 
supposed to be less than the stated amounts depending on the carrier used. Relevant data is included in the 
Summary of Product Characteristics of the labelled medicinal products. 
 
5.3 Preclinical safety data 
 
The toxicological properties of lutetium (P177PLu)-labelled medicinal products prepared by radiolabelling with 
Lumark prior to administration, will be dependent on the nature of the medicinal product to be radiolabelled.  
 
No animal toxicity studies were conducted with Lumark.  
 
The toxicity of lutetium (P177PLu) chloride has been studied in different mammals and using different 
administration routes. Intraperitoneal administration resulted in generalised peritonitis with adhesion and 
accumulation of some ascetic fluid. By intraperitoneal route, the LD50 is approximately 300 mg/kg in mice 
and rats. By intravenous route, the LD50 in rats and mice ranges between 30 and 60 mg/kg. Intravenously 
administrated doses resulted in varying effects on the blood pressure and a decreased heart rate. 
Electrocardiograms showed no irregularities in cardiac rhythm or conduction. Effects of the respiration were 
slight and variable. No gross differentiating changes were found of the tissues demonstrating no evidence of 
acute damage resulting from the experiment. The studies suggest that the intravenous toxicity of the ionic 
compounds of the rare earth elements would decrease with atomic weight resulting in lutetium (P177PLu) being 
the least toxic of the series.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Hydrochloric acid 
Water for injections 
 
6.2 Incompatibilities 
 
Radiolabelling of carrier molecules, such as monoclonal antibodies, peptides or other substrates, with 
lutetium (P177PLu) 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. 
 



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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 
 
8 days from the date of ART (= end of production). 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from radiation. 
Storage of radiopharmaceuticals should be in accordance with national regulations for radioactive materials. 
 
6.5 Nature and contents of container   
 
The radiopharmaceutical precursor solution is packaged in a colourless type I glass vial of 10 mL, closed 
with a bromobutylrubber stopper and aluminium overseal. 
Each vial contains a volume varying from 0.1 to 5 mL corresponding to an activity ranging from 8 to 
400 GBq at the ART. 
 
The vials are placed in a lead container for protective shielding and packed in a plastic jar. 
Each pack contains one vial in a lead container. 
 
6.6 Special precautions for disposal and other handling 
 
Lumark is not intended for direct use in patients. 
 
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 instruction on extemporary preparation of the medicinal product before administration, see section 12.  
 
If at any time in the preparation of this medicinal 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 (P177PLu)-radiopharmaceuticals. The use of television monitor systems to monitor the 
patients is recommended. Given the long half-life of lutetium (P177PLu) 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 exposure, there is no specific 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. 
 
Lumark is for single use only. 



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Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
I.D.B. Holland B.V. 
Weverstraat 17  
5111 PV Baarle-Nassau 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1013/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 June 2015 
Date of latest renewal:  
 
10. DATE OF REVISION OF THE TEXT 
 
 
11. DOSIMETRY 
 
The radiation dose received by the various organs following administration of a lutetium (P177PLu)-labelled 
medicinal product will be dependent on the specific molecule being radiolabelled.  
 
Information on radiation dosimetry of each different medicinal product following administration of the 
radiolabelled preparation will be 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(P177PLu) to the radiation dose following the administration of lutetium (P177PLu)-labelled medicinal 
product or resulting from an accidental intravenous injection of Lumark. 
 
The dosimetry estimates are based on biodistribution data provided by ICRP-30, showing bone, liver and 
kidneys as the significant target organs for the biodistribution of lutetium.   
 
Table 1. Absorbed dose per unit activity administered for various tissues  

 ICRP-30 data 

Target organ Dose / Injected activity (mGy/MBq) 
Adrenals             0.018 
Brain                0.017 
Breasts              0.005 
Gallbladder wall     0.012 
LLI wall             0.868 
Small intestine      0.069 
Stomach wall         0.038 



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ULI wall             0.327 
Heart wall           0.009 
Kidneys              0.210 
Liver                0.220 
Lungs                0.010 
Muscle               0.012 
Ovaries              0.015 
Pancreas             0.012 
Red marrow           1.090 
Osteogenic cells     7.530 
Skin                 0.007 
Spleen               0.008 
Testes               0.006 
Thymus               0.007 
Thyroid              0.011 
Urinary bladder wall 0.240 
Uterus               0.011 

Total body           0.185 

  

Effective dose (mSv/MBq)  0.35 
 
 
12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 
 
Before use, packaging and radioactivity should be checked. Activity may be measured using an ionisation 
chamber. Lutetium (P177PLu) 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.  
 
Lumark isfor single use only 
 
Usual precautions regarding sterility and radioactivity should be respected. 
 
The vial should never be opened and must be kept inside its lead shielding. The medicinal product should be 
aseptically withdrawn through the stopper using sterilised single use needle and syringe after disinfection of 
the stopper. 
 
Appropriate aseptic precautions should be taken, in order to maintain the sterility of Lumark and to maintain 
sterility throughout the labelling procedures.  
 
The complexing agent and other reagents should be added to the vial with lutetium (P177PLu)-chloride. 
Free lutetium (P177PLu) 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 (P177PLu)-labelled conjugates in order to form a complex with free lutetium (P177PLu), if present, 
leading to a rapid renal clearance of lutetium (P177PLu). 
 
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/


12 

 
   



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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(s) responsible for batch release 
 
I.D.B. Holland B.V. 
Weverstraat 17 
5111 PV Baarle-Nassau 
NETHERLANDS 
 

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 (PSURs) 
 

The requirements for submission of PSURs 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. 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT 

• Risk management plan (RMP) 
The marketing authorisation holder (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.  

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 

 
 
 
 
 
 
 
 
 
 



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



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A. LABELLING 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PLASTIC JAR and LEAD CONTAINER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lumark 80 GBq/mL radiopharmaceutical precursor, solution 
lutetium (P177PLu) chloride 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL of solution contains 80 GBq lutetium (P177PLu) chloride at activity reference time (ART), 
corresponding to at most a maximum of 160 microgram of Lutetium. The ART is defined as the end of 
production. 
 
 
3. LIST OF EXCIPIENTS 
 
Hydrochloric acid 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Radiopharmaceutical precursor, solution. 
1 vial  
 
Volume: {Z} mL 
Activity (at ART): {Y} GBq  
Activity Reference Time (ART): {DD/MM/YYYY} {hh:mm} CET 
Specific activity (at ART): {YY} GBq/mg 
Lu mass: 
Client code: 
Destination: 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For administration after in vitro radiolabelling. Read the package leaflet before use. 
For single-use only. 
 
 
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 
 
Expiry date: {DD/MM/YYYY} hh:mm CET 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from radiation. 
Storage must 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 product or waste material should be disposed of in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
I.D.B. Holland B.V. 
Weverstraat 17  
5111 PV Baarle-Nassau 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1013/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
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 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 



19 

Not applicable 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
Not applicable 



20 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Lumark 80 GBq/mL radiopharmaceutical precursor, solution 
lutetium (P177PLu) chloride 
 
 
2. METHOD OF ADMINISTRATION 
 
For administration after in vitro radiolabelling. 
 
 
3. EXPIRY DATE 
 
EXP {DD/MM/YYYY}  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
Client code:  
 
 
6. OTHER 
 
 

 
 

 
 
 

http://www.google.nl/url?sa=i&rct=j&q=radioactiviteit&source=images&cd=&cad=rja&docid=x0pnEZs5B8Q9pM&tbnid=gjHaw7Gw8h8aXM:&ved=0CAUQjRw&url=http://wetenschap.infonu.nl/natuurkunde/17982-radioactiviteit-natuurkundig-verschijnsel.html&ei=7DjlUaDvLcGj0QWw8oCYAQ&bvm=bv.48705608,d.d2k&psig=AFQjCNH0wHslz31YiPmapQZQEvXMZjxhow&ust=1374063069004379�


21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



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Package leaflet: Information for the patient 
 

Lumark 80 GBq/mL radiopharmaceutical precursor solution 
Lutetium (P177PLu) chloride 

 
Read all of this leaflet carefully before you are given the medicine combined with Lumark 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 Lumark is and what it is used for  
2. What you need to know before the medicine radiolabelled with Lumark is used  
3. How to use the medicine radiolabelled with Lumark  
4. Possible side effects  
5. How to store Lumark   
6. Contents of the pack and other information 
 
 
1. What Lumark is and what it is used for 
 
Lumark is not a medicine and it is not intended to be used on its own.  
 
Lumark is a so-called radiopharmaceutical precursor. It contains the active substance 
lutetium (P177PLu) chloride.  
 
Lumark is used for radiolabelling medicines, a technique in which medicines are tagged (radiolabelled) with 
a radioactive form of the element lutetium, known as lutetium (P177PLu). These medicines can then be used in 
medical procedures to carry radioactivity to where it is needed in the body such as sites of tumour cells. 
 
Lumark is only used to radiolabel medicines that have been specifically developed for use with the active 
substance lutetium (P177PLu) chloride. 
 
The use of lutetium (P177PLu)-labelled medicines does involve exposure to small amounts of radioactivity. 
Your doctor and the nuclear medicine doctor have considered that the clinical benefit that you will obtain 
from the procedure with the radiopharmaceutical outweighs the risk due to radiation.  
 
Please refer to the package leaflet of the medicine that is to be radiolabelled with Lumark. 
 
 
2. What you need to know before the medicine radiolabelled with Lumark is used 
 
The medicine radiolabelled with Lumark must not be used: 
- if you are allergic to lutetium or any of the other ingredients of this medicine (listed in section 6). 
- if you are pregnant or believe you may be pregnant 
 
Warnings and precautions  
Treatment with medicine radiolabelled with lutetium (P177PLu) 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 

 



23 

Most of these events are mild and only temporary. Because lutetium (P177PLu) 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 (P177PLu) may cause disturbances of liver function. Your doctor will take a blood test 
to monitor your liver function during treatment.  

Lumark-labelled medicines may be administered directly into your vein through a tube known as a cannula. 
There have been reports of leakage of the fluid into the surrounding tissue (extravasation). Tell your doctor if 
you experience any swelling or pain in your arm. 

After neuroendocrine tumours are treated with lutetium (P177PLu), patients may experience symptoms 
associated with release of hormones from the tumour cells, known as carcinoid crisis. Tell your doctor if you 
feel faint or dizzy or experience flushing or diarrhoea following your treatment. 
 
Treatment with Lutetium (P177PLu) 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. 

 
Before administration of Lumark you should  
Drink plenty of water before being given the radiolabelled medicine in order to urinate as often as possible 
during the first few hours after the procedure. 
 
Children and adolescents 
Please refer to the package leaflet of the medicine that is to be radiolabelled with Lumark. 
 
Other medicines and medicines radiolabelled with Lumark 
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 (P177PLu) chloride may interact with other medicines as specific studies have 
not been carried out. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 
nuclear  medicine doctor for advice before you are given medicines radiolabelled with Lumark. 
 
You must inform the nuclear medicine doctor before the administration of medicines radiolabelled with 
Lumark 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.  
 
If you are pregnant  
Medicines radiolabelled with Lumark must not be administered if you are pregnant.  
 
If you are breast-feeding  
You will be asked to stop breast-feeding if you are treated with medicines radiolabelled with Lumark.  
Please ask your nuclear medicine doctor when you can resume breast-feeding. 
 
Driving and using machines 
The medicines used in combination with Lumark could affect your ability to drive and to use machines. 
Please read the package leaflet of that medicine carefully. 



24 

 
 
3. How to use the medicine radiolabelled with Lumark  
 
There are strict laws on the use, handling and disposal of radiopharmaceutical products. Medicines 
radiolabelled with Lumark 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 people 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 medicine radiolabelled 
with Lumark to be used in your case. It will be the smallest quantity necessary to achieve the appropriate 
outcome, depending on the co-administered medicine and its intended use.  
 
Administration of the medicine radiolabelled with Lumark and conduct of the procedure  
Lumark must be used only in combination with another medicine which has been specifically developed and 
authorised for being combined with Lumark. It will only be administered as a combination. 
 
Duration of the procedure  
Your nuclear medicine doctor will inform you about the usual duration of the procedure after the 
administration of the medicine radiolabelled with Lumark.  
 
After administration of the medicine radiolabelled with Lumark has been performed  
The nuclear medicine doctor will inform you if you need to take any special precautions after receiving the 
medicine radiolabelled with Lumark. Contact your nuclear medicine doctor if you have any questions. 
 
If you have been given more medicine radiolabelled with Lumark than you should  
Since the medicine radiolabelled with Lumark is handled by a nuclear medicine doctor under strictly 
controlled conditions, there is only a very small chance of possible overdose. However, in case of an 
overdose, you will receive the appropriate treatment.  
 
Should you have any further question on the use of Lumark, please ask the nuclear medicine doctor who 
supervises the procedure. 
 
 
4. Possible side effects 
 
Like all medicines, the medicine radiolabelled with Lumark can cause side effects, although not everybody 
gets them.  
 
Dry mouth has been reported among patients with prostate cancer receiving treatment with Lutetium (P177PLu) 
and has been temporary. 
 
Very common (may affect more than 1 in 10 people) 
 

• Reduction in blood cell counts (platelets, red or white blood cells) 
• Nausea 
• Vomiting 
• 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) 
 



25 

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 (P177PLu) peptide receptor radionuclide therapy for neuroendocrine 
tumours.  

After the medicine radiolabelled with Lumark is administered, it will deliver certain amounts of ionising 
radiation (radioactivity) which carries a small 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 medicine to be radiolabelled. 
 
If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side effects not 
listed in this leaflet. 
 
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 Lumark is stored 
 
You will not have to store this radiopharmaceutical. Storing Lumark is the responsibility of the specialist 
and will be done in appropriate premises. Storage of radiopharmaceuticals will be in accordance with 
national regulation on radioactive materials.  
 
The following information is intended for the specialist only. 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date and time which are stated on the label after EXP.  
 
Store in the original package to protect from radiation. 
 
 
6. Contents of the pack and other information 
 
What Lumark contains  

- The active substance is lutetium (P177PLu) chloride. Each mL of solution contains 80 GBq 
lutetium (P177PLu) chloride at activity reference time (ART), corresponding to a maximum of 
160 microgram of lutetium. The ART is defined as the end of production. (GBq: GigaBecquerel is the 
unit in which radioactivity is measured). 

- The other ingredients are hydrochloric acid and water for injections.  
 
What Lumark looks like and contents of the pack 
Lumark is presented as a sterile, clear, and colourless solution in a colourless type I glass vial of 10 mL, 
closed with a bromobutylrubber stopper and aluminium overseal. 
 
Each vial contains a volume varying from 0.1 to 5 mL corresponding to an activity ranging from 8 to 
400 GBq (at ART). The volume depends on the quantity of medicines combined with Lumark required for 
administration by the nuclear medicine doctor. 
 

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


26 

Each pack contains 1 glass vial in a lead cannister placed in a plastic jar. 
 
Marketing Authorisation Holder and Manufacturer 
I.D.B. Holland B.V. 
Weverstraat 17  
5111 PV Baarle-Nassau 
The Netherlands 
Tel:  +31(0)13 5079 558 
Fax: +31(0)13 5079 912 
Email: quality@idb-radiopharmacy.com 
 
This leaflet was last revised in 
 
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 Summary of Product Characteristics (SmPC) of Lumark is provided as a separate document in 
the pack of the medicinal product, with the objective to provide healthcare professionals with other 
additional scientific and practical information about the use of this product.  
 
Please refer to the SmPC. 

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

	SUMMARY OF PRODUCT CHARACTERISTICS
	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
	A. LABELLING
	B. PACKAGE LEAFLET