Axumin

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

  



2 

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 
 
Axumin 1600 MBq/mL solution for injection 
Axumin 3200 MBq/mL solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Axumin 1600 MBq/mL solution for injection 
Each mL of solution contains 1600 MBq of fluciclovine (18F) at the date and time of calibration (ToC).  
 
The activity per vial ranges from 1600 MBq to 16000 MBq at the date and time of calibration (ToC).  
 
Axumin 3200 MBq/mL solution for injection 
Each mL of solution contains 3200 MBq of fluciclovine (18F) at the date and time of calibration (ToC).  
 
The activity per vial ranges from 3200 MBq to 32000 MBq at the date and time of calibration (ToC).  
 
Fluorine (18F) decays to stable oxygen (18O) with a half-life of 110 minutes by emitting a positronic 
radiation of maximum energy of 634 keV, followed by photonic annihilation radiations of 511 keV.  
 
Excipients with known effect  
Each mL of solution contains 7.7 mg of sodium.  
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection.  
Clear, colourless solution.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
This medicinal product is for diagnostic use only. 
 
Axumin is indicated for Positron Emission Tomography (PET) imaging to detect recurrence of 
prostate cancer in adult men with a suspected recurrence based on elevated blood prostate specific 
antigen (PSA) levels after primary curative treatment. 
 
For the limitations in the interpretation of a positive scan, see section 4.4 and 5.1. 
 
 
4.2 Posology and method of administration 
 
A PET scan with fluciclovine (18F) should be administered by appropriately qualified healthcare 
professionals. 
 



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Images should only be interpreted by readers trained in the interpretation of PET images with 
fluciclovine (18F). 
 
Posology 
Adults  
The recommended activity for an adult is 370 MBq fluciclovine (18F). 
 
Renal and hepatic impairment  
Axumin has not been studied in patients with renal or hepatic impairment. 
Careful consideration of the activity to be administered is required since an increased radiation 
exposure is possible in these patients. 
 
Elderly 
No dose adjustment required. 
 
Paediatric population 
There is no relevant use of fluciclovine (18F) in the paediatric population. 
 
Method of administration  
Axumin is for intravenous use.  
 
The activity of fluciclovine (18F) has to be measured with an activimeter immediately prior to 
injection. 
 
Axumin should be administered as a bolus intravenous injection. The recommended maximum volume 
of injection of undiluted Axumin is 5 mL. Axumin may be diluted with sodium chloride 9 mg/ml 
(0.9%) solution for injection by a factor of 8. The injection should be followed by an intravenous flush 
of sterile sodium chloride 9 mg/ml (0.9%) solution for injection to ensure full delivery of the dose. 
 
Axumin is for multidose use. 
 
For instructions on dilution of the medicinal product before administration, see section 12. 
 
For patient preparation, see section 4.4. 
 
Image acquisition 
The patient should be positioned supine with arms above the head. A CT scan should be obtained for 
attenuation correction and anatomic correlation. PET scanning should begin from 3-5 minutes (target 
4 minutes) after completion of the injection; an acquisition time of 3 minutes per bed position is 
recommended. Increasing the duration of acquisition over the pelvis may increase the sensitivity of 
detection of disease. It is recommended that image acquisition should start from mid-thigh and 
proceed to the base of the skull. Typical total scan time is between 20-30 minutes. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
 
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 
diagnostic information.  
 
The PSA value may affect the diagnostic performance of fluciclovine (18F) PET. (see section 5.1, 
Pharmacodynamic properties). 
 



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Renal impairment  
Careful consideration of the benefit/risk ratio in these patients is required since an increased radiation 
exposure is possible.  
 
Paediatric population 
For information on use in the paediatric population, see section 4.2. 
 
Patient preparation  
It should be recommended to the patient that they do not undertake any significant exercise for at least 
a day before the fluciclovine (18F) scan. 
 
Prior to administration of fluciclovine (18F), patients should not eat or drink for at least 4 hours (other 
than small amounts of water for taking medicinal products).   
In order to mitigate the quantity and intensity of early excretion into the bladder, which may mask or 
mimic local prostate cancer recurrence, patients should be informed that they may void at the latest 60 
minutes before injection of fluciclovine (18F), and should then refrain from voiding until after the scan 
has been completed. 
 
Interpretation of fluciclovine (18F) images and limitations of use 
Fluciclovine (18F) images should be interpreted by appropriately trained personnel.  
 
PET images with fluciclovine (18F) should be interpreted visually. Suspicion of cancer in sites typical 
for prostate cancer recurrence is based on fluciclovine (18F) uptake in comparison with tissue 
background. For small lesions (<1 cm diameter) focal uptake greater than blood pool should be 
considered suspicious for cancer. For larger lesions, uptake equal to or greater than bone marrow is 
considered suspicious for cancer. 
 
The impact of quantitative/semiquantitative measurement of fluciclovine (18F) uptake as an aid to 
image interpretation has not been assessed. 
 
Image interpretation errors can occur with PET with fluciclovine (18F) (see section 5.1).   
 
Fluciclovine (18F) uptake is not specific for prostate cancer and may occur with other types of cancer, 
prostatitis and benign prostatic hyperplasia. False-positive cases have been also described in 
association with an inflammatory response after cryotherapy and radiation artefacts in patients 
previously treated with radiotherapy. Clinical correlation, which may include histopathological 
evaluation of the suspected recurrence site, should be considered where appropriate. 
 
The use of either intravenous iodinated CT contrast or oral contrast media is not required to interpret 
fluciclovine (18F) PET images. 
 
The detection of prostate cancer recurrence in prostate/prostate bed, regional lymph nodes, bone, soft 
tissue and non-regional lymph nodes by fluciclovine (18F) PET has been reported.  
 
Diagnostic performance of fluciclovine (18F) to detect recurrences has not been investigated in patients 
with a suspected recurrence based on elevated blood PSA levels after primary radical treatment with a 
recent positive whole-body bone scintigraphy. 
 
After the procedure  
The patient should be encouraged to drink sufficient amounts and void as often as possible during the 
first hours after the scan in order to reduce radiation exposure of the bladder. 
 
Close contact with infants and pregnant women should be restricted during the initial 12 hours 
following the injection.  
 



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Specific warnings  
This medicinal product contains up to 39 mg sodium per dose. To be taken into consideration by 
patients on a controlled sodium diet.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed.  
 
The impact of anti-mitotic agents and colony stimulating factors on uptake of fluciclovine in patients 
with prostate cancer has not been studied. 
 
4.6 Fertility, pregnancy and lactation 
 
Fluciclovine (18F) is not indicated for use in women. 
 
Fertility 
No studies on fertility have been performed. 
 
4.7 Effects on ability to drive and use machines 
 
Axumin has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Exposure to ionising radiation is linked with cancer induction and a potential for development of 
hereditary defects. As the effective dose is 8.2 mSv when the maximal recommended activity of 
370 MBq is administered these adverse reactions are expected to occur with a low probability.  
 
Tabulated list of adverse reactions 
Adverse reactions were reported commonly (≥ 1/100 to < 1/10) during clinical trials.  
They are listed below by MedDRA body system organ class.  
 

MedDRA system organ class Adverse reactions 
 

Nervous system disorders Dysgeusia  
 

Respiratory thoracic and 
mediastinal disorders 

Parosmia 

General disorders and 
administration site conditions 

Injection site reactions  
 

 
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. 
 

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


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4.9 Overdose 
 
In the event of administration of a radiation overdose with fluciclovine (18F) the absorbed dose to the 
patient should be reduced where possible by increasing the elimination of the radionuclide from the 
body by forced diuresis, frequent micturition and defecation. It might be helpful to estimate the 
effective dose that was applied. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other diagnostic radiopharmaceuticals for tumour detection, ATC code: 
V09IX12. 
 
Mechanism of action 
Fluciclovine (18F) is a synthetic amino acid which is transported across mammalian cell membranes by 
amino acid transporters such as LAT-1 and ASCT2. The activities of LAT-1 and ASCT2 are known to 
be upregulated in prostate cancer, providing a mechanism for the enhanced accumulation of 
fluciclovine (18F) in prostate cancer.  
 
A quantitative correlation between fluciclovine uptake and enhanced fluciclovine influx into cells was 
not assessed in vivo in healthy volunteers or prostate cancer patients. 
 
Pharmacodynamic effects 
At the chemical concentrations used for diagnostic examinations, fluciclovine (18F) does not appear to 
have any pharmacodynamic activity.   
 
Clinical efficacy and safety 
 
The pivotal efficacy data derives from 115 patients recruited into the BED-001 study at Emory 
University.  Patients were adult and elderly men presenting with suspected recurrence, based on 
elevated blood PSA levels after primary curative treatment of localized prostate cancer and with 
negative bone scintigraphy. Patients with non-surgical therapy were treated at least 2 years before. 
Fluciclovine (18F) PET-CT was restricted to the abdomino-pelvic region. 
 
Histopathology standard of truth data was available for 99 of the 115 subjects. Histological assessment  
of extraprostatic sites (either regional lymph nodes or distant sites) was only conducted for sites with 
positive image findings. 

The diagnostic performance of fluciclovine (18F) PET-CT for the detection of recurrence overall (at any 
location), and in 3 different locations (prostate/bed, pelvic lymph nodes, and distant metastases) is 
shown in Table 1. Distant metastases involved distal lymph nodes, soft tissue and bone. 



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Table 1. Patient and region based diagnostic performance of fluciclovine 18F PET vs histopathology  
 
  

Patient based 
Location  

Prostate & prostate 
bed  

Pelvic lymph 
nodes 

Extraprostatic 
(pelvic and 

distal 
recurrence) 

N 105 97 24 29 
True positive n (%) 73 (69.5) 57 (58.8) 23 (95.8) 27 (93.1) 
False positive n (%) 19 (18.1) 27 (27.8) 1 (4.2) 2 (6.9) 
True negative n (%) 12 (11.4) 12 (12.4) 0 (0.0) 0 (0.0) 
False negative n (%) 1 (1.0) 1(1.0) 0 (0.0) 0 (0.0) 

Sensitivity 
[95% CI] 

98.6% (73/74) 
[92.7 - 100%] 

98.3% (57/58) 
[90.8 - 100%] 

100% (23/23) 
[85.2 - 100%] 

100% (27/27) 
[87.2 - 100%] 

Specificity 
[95% CI] 

38.7% (12/31) 
[21.8 - 57.8%] 

30.8% (12/39) 
[17.0 - 47.6%] 

  

Positive likelihood ratio 
[95% CI] 

1.61 
[1.22 - 2.13] 

1.42 
[1.15 - 1.75] 

  

Negative likelihood ratio 
[95% CI] 

0.03 
[0 - 0.26] 

0.06 
[0.01 - 0.41] 

  

 
Using the findings of other relevant imaging modalities and clinical follow-up as reference standard in 
the recruited population, patient-based sensitivity and specificity of fluciclovine (18F) PET-CT for 
detection of prostate/prostate bed recurrences were 94.7% (89/94) (95%CI: 88.0-98.3%) and 54.8% 
(17/31) (95%CI:36-72.7%), respectively.  For detection of extraprostatic recurrences (regional lymph 
node and/or distal metastases) sensitivity was 84.2% (32/38) (95%CI: 68.7-94%) and specificity was 
89.7% (78/87) (95%CI: 81.3-95.2%), respectively. 
 
The Patient-based diagnostic performance of fluciclovine (18F) PET-CT by blood PSA level is shown 
in Table 2. 
 
Table 2. Effect of blood PSA level on the patient-based diagnostic performance of fluciclovine 
(18F) PET-CT at BED-001 Emory 
 

PSA (ng/mL) 
 ≤1.05 >1.05 - ≤3.98 >3.98 - ≤8.90 >8.90 

No. subjects in 
analysis 

16 31 25 27 

True positive (%) 3 (18.8) 23 (74.2) 20 (80) 23 (85.2) 
False positive (%) 4 (25)  5 (16.1)   4 (16)  4 (14.8) 
True negative (%) 8 (50) 3 (9.7) 1 (4)  

False negative (%) 1 (6.3) 0 (0) 0 (0)  

Sensitivity 75% (3/4) 100% (23/23) 100% (20/20) 100% (23/23) 
[95% CI] [19.4 - 99.4%] [85.2 - 100%] [83.2 – 100%] [85.2 – 100%] 
Specificity 66.7% (8/12) 37.5% (3/8) 20% (1/5)  

[95% CI] [34.9 - 90.1%] [8.5 - 75.5%] [0.5 - 71.6%]  

 
 
 
 



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An additional study BED002 conducted a blinded read of fluciclovine (18F) PET-CT images from the 
Emory subset data in BED-001 study by 3 readers. Blinded reads were compared with the 
histopathological standard of truth. The patient-based sensitivity of fluciclovine (18F) was higher than 
88.6% for all three readers while specificity ranged from 17.2-53.6%. 

Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Axumin in one or more subsets of the paediatric population in diagnosis of amino acid metabolism in 
solid tumours (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Distribution 
Fluciclovine (18F) distributes immediately following administration to the liver (14% of administered 
activity), pancreas (3%), lung (7%), red bone marrow (12%) and heart wall (4%).  
Fluciclovine is not incorporated into proteins. Fluciclovine is not metabolised in vivo. 
 
Organ uptake 
Fluciclovine (18F) accumulates in prostate cancer and other types of cancer but also in normal tissues 
and some other prostate pathologies (such as benign prostatic hyperplasia, chronic prostatitis, high 
grade prostatic intraepithelial hyperplasia). In addition, fluciclovine uptake may be increased by an 
inflammatory reaction to recent radiotherapy or cryotherapy. 
 
Fluciclovine (18F) is preferentially taken up into prostate cancer cells compared with surrounding 
normal tissues.  Uptake by tumours is rapid, with the highest tumour-to-normal tissue contrast between 
4 and 10 minutes after injection and continuing for around 30 minutes, with a 61% reduction in mean 
tumour uptake at 90 minutes after injection. 
 
Washout of activity from most organs and tissues (with the exception of the pancreas) is slow. 
Activity in the brain is low. With increasing time post injection, distributed uptake is apparent and is 
mostly associated with skeletal muscle. Washout of 18F activity from the blood is such that about half 
of the maximum 18F concentration in blood is reached by about 1 hour after administration. 
 
Elimination 
The major route of elimination is via the renal pathway. Urinary excretion is slow, reaching 
approximately 3% of administered radioactivity within 4 hours and 5% within 24 hours. 
 
Half-life  
The effective half-life of fluciclovine (18F) equates to the radioactive half-life of fluorine (18F), which 
is approximately 110 minutes.  
 
Renal/Hepatic impairment 
The pharmacokinetics in patients with renal or hepatic impairment have not been characterised. 
 
In in vitro studies, fluciclovine (18F) was not taken up by common drug transporters indicating a 
negligible potential for drug interactions. 
 
5.3 Preclinical safety data 
 
Toxicological studies with rats and dogs have demonstrated that with a single intravenous injection no 
deaths were observed. Toxicity with repeated administration of up to 1000 mcg/kg/day over 14 days in 
rats and dogs was not observed. This medicinal product is not intended for regular or continuous 
administration. Long-term carcinogenicity studies have not been carried out.  
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity and genotoxicity. 
 



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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium citrate 
Concentrated hydrochloric acid 
Sodium hydroxide 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
sections 6.6 and 12. 
 
6.3 Shelf life 
 
Axumin 1600 MBq/mL solution for injection 
8 hours from the time of calibration (ToC) 
 
Axumin 3200 MBq/mL solution for injection 
10 hours from the time of calibration (ToC) 
 
In use 
Chemical and physical in-use stability has been demonstrated for Axumin 1600 MBq/mL for 8 hours 
and for Axumin 3200 MBq/mL for 10 hours. 
 
From a microbiological point of view, unless the method of opening/ dose withdrawal/dilution 
precludes the risk of microbiological contamination, the product should be used immediately. 
If not used immediately, in-use storage times and conditions are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive 
materials. 
 
6.5 Nature and contents of container  
 
Axumin is supplied in a 10 mL or 15 mL type 1 glass vial sealed with a fluoro-coated chlorobutyl, 
chlorobutyl or bromobutyl rubber closure and aluminium overseal.  
 
Axumin 1600 MBq/mL solution for injection 
One vial contains 1 to 10 mL of solution, corresponding to 1600 to 16000 MBq at calibration time.  
 
Axumin 3200 MBq/mL solution for injection 
One vial contains 1 to 10 mL of solution, corresponding to 3200 to 32000 MBq at calibration time.  
 
Not all pack sizes may be marketed. 
 
As a result of the manufacturing process some vials are distributed with punctured rubber stoppers. 
 
6.6 Special precautions for disposal and other handling 
 
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.  
 



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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 dilution of the medicinal product before administration, see section 12. 
 
If at any time in the preparation of this medicinal product the integrity of the vial 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 administration of radiopharmaceuticals creates risks for other persons from external radiation or 
contamination from spill of urine, vomiting etc. Radiation protection precautions in accordance with 
national regulations must therefore be taken.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Blue Earth Diagnostics Ireland Ltd 
6th Floor, 2 Grand Canal Square 
Dublin 2 
Ιreland  
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1186/001 
EU/1/17/1186/002 
EU/1/17/1186/003 
EU/1/17/1186/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 22 May 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
11. DOSIMETRY 
 
The estimated absorbed radiation doses for adult patients following intravenous injection of 
fluciclovine (18F) are shown in Table 3. Values were calculated from human biodistribution data using 
OLINDA/EXM (Organ Level Internal Dose Assessment/Exponential Modeling) software. 
 



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Table 3: Estimated radiation absorbed doses for adults receiving Axumin 
 

Organ/Tissue Mean absorbed dose per 
unit administered activity 

(µGy/MBq) 
Adrenal glands  16 
Brain  9 
Breasts  14 
Gallbladder wall  17 
Lower large intestine wall  12 
Small intestine wall  13 
Stomach wall  14 
Upper large intestine wall  13 
Heart wall  52 
Kidneys  14 
Liver 33 
Lungs  34 
Muscle  11 
Ovaries  13 
Pancreas  102 
Red bone marrow  25 
Osteogenic cells  23 
Skin  8 
Spleen  24 
Testes  17 
Thymus gland  12 
Thyroid  10 
Urinary bladder wall  25 
Uterus 45 
Total body 13 
Effective dose  22 (µSv/MBq) 

 
The adult effective dose resulting from the administration of the recommended activity of 370 MBq of 
fluciclovine (18F) is 8.2 mSv. For an administered activity of 370 MBq the typical radiation doses to 
the critical organs, pancreas, the cardiac wall and uterine wall are 37.8 mGy, 19.1 mGy and 16.5 mGy, 
respectively. 
 
 
12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 
 
Method of preparation 
The medicinal product may be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection by 
up to a factor of 8. 
 
Withdrawals should be performed under aseptic conditions. The vial 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 medicinal product should not be used. 
 
Axumin should only be used when the injection volume is greater than 0.5 mL (approximately 2 hours 
after time of calibration for Axumin 1600 MBq/mL and 4 hours after time of calibration for Axumin 
3200 MBq/mL). 
 



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If the injection volume is between 0.5 and 1 mL, only syringes of an appropriate size (1 mL) should be 
used. 
 
Quality control  
The solution should be inspected visually prior to use. Only clear solutions, free of visible particles 
should be used.  
 
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. MANUFACTURERS 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. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 

Norsk medisinsk syklotronsenter AS 
Rikshospitalet 
Sognsvannsveien 20 
OSLO 
NO-0372 
Norway 
 
Seibersdorf Labor GmbH 
Grundstück Nr. 482/2 EZ 98 KG 
2444 Seibersdorf 
AUSTRIA 
  
Advanced Accelerator Applications (AAA), Marseille 
Bâtiment CERIMED 
27 Boulevard Jean Moulin 
13005 Marseille, 
FRANCE 
 
Nucleis SA 
Allée du 6 Août, 8 
Bâtiment 30 
Liège 4000 
Belgium 
 
GE Healthcare Ltd 
The Grove Centre 
White Lion Road 
Amersham 
HP7 9LL 
UK 
 
Advanced Accelerator Applications Ibérica S.L. 
Polígono Industrial La Cuesta-Sector 3. Parcelas 1 y 2 
La Almunia de Doña Godina  
50100 Zaragoza 
Spain 
 
Advanced Accelerator Applications (Italy) s.r.l. 
Via Piero Maroncelli 40 
47014 
Meldola (FC) 
Italy 
 
Advanced Accelerator Applications 
3 rue Charles Lauer 
92210 Saint Cloud 
France 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
  
 



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B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to 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.  

 
• Additional risk minimisation measures  
Prior to launch of Axumin in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational programme with the National Competent 
Authority.  
The MAH shall ensure that in each Member State where Axumin is marketed, all Healthcare 
professionals who are expected to use Axumin have access to self-training educational material in 
order to reduce the risk of PET imaging interpretation errors. 
 
The Healthcare professionals self-training material shall contain the following key elements:  
 

o Physiological distribution of fluciclovine 
o Image interpretation guidelines 
o Examples of incidental findings on PET-CT with fluciclovine 
o Examples of positive and negative findings on PET-CT with fluciclovine 
o Demonstration cases with image interpretation provided by an expert 

 
 
 
  



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
SHIELD LABEL: 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Axumin 1600 MBq/mL solution for injection 
fluciclovine (18F) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL of solution for injection contains 1600 MBq of fluciclovine (18F) at date and time of 
calibration (ToC). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium citrate, concentrated hydrochloric acid, sodium hydroxide, and water for 
injections. For sodium, see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 vial  
Volume: {xx.x} mL  
Activity: {YYYY} MBq in {xx.x} mL at {hh:mm}{Time Zone} {DD/MM/YYYY} 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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

 
 
 

radioactive 
 
 
8. EXPIRY DATE 
 
Exp{hh:mm}{Time Zone}{DD/MM/YYYY} 



19 

9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused material should be disposed of in accordance with local requirements.  
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Blue Earth Diagnostics Ireland Ltd, 6th Floor, 2 Grand Canal Square, Dublin 2, Ιreland  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1186/001 
EU/1/17/1186/003 
 
 
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 
 
Not applicable.  
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
 



20 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
SHIELD LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Axumin 3200 MBq/mL solution for injection 
fluciclovine (18F) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL of solution for injection contains 3200 MBq of fluciclovine (18F) at date and time of 
calibration (ToC). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sodium citrate, concentrated hydrochloric acid, sodium hydroxide, and water for 
injections. For sodium, see leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 vial  
Volume: {xx.x} mL  
Activity: {YYYY} MBq in {xx.x}mL at {hh:mm}{Time Zone} {DD/MM/YYYY} 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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

 
 
 

radioactive 
 
 
8. EXPIRY DATE 
 
Exp{hh:mm}{Time Zone}{DD/MM/YYYY} 
 



21 

9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused material should be disposed of in accordance with local requirements.  
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Blue Earth Diagnostics Ireland Ltd, 6th Floor, 2 Grand Canal Square, Dublin 2, Ιreland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1186/002 
EU/1/17/1186/004 
 
 
 
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 
 
Not applicable.  
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
 
  



22 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Axumin 1600 MBq/mL solution for injection 
fluciclovine (18F) 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
Exp: ToC + 8h  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
Activity: {YYYY} MBq 
Volume: {xx.x] mL 
 
 
6. OTHER 
 

  
 
Seibersdorf Labor GmbH,  2444 Seibersdorf, Austria 
 
Norsk medisinsk syklotronsenter AS,  0372 Oslo, Norway 
 
Advanced Accelerator Applications, 13005 Marseille, France 
 
Nucleis SA, 4000 Liège, Belgium 
 
GE Healthcare Ltd,  Amersham HP7 9LL, UK 
 
Advanced Accelerator Applications, 50100, La Almunia-Zaragoza, Spain 
Advanced Accelerator Applications, 407014, Meldola (FC), Italy 
 
Advanced Accelerator Applications, 92210 Saint Cloud, France 



23 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Axumin 3200 MBq/mL solution for injection 
fluciclovine (18F) 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
Exp: ToC + 10h  
 
 
4. BATCH NUMBER 
 
Lot  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
Activity: {YYYY} MBq 
Volume: {xx.x] mL 
 
 
6. OTHER 
 

  
 
Seibersdorf Labor GmbH,  2444 Seibersdorf, Austria 
 
Norsk medisinsk syklotronsenter AS,  0372 Oslo, Norway 
 
Advanced Accelerator Applications, 13005 Marseille, France 
 
Nucleis SA, 4000 Liège, Belgium 
 
GE Healthcare Ltd, Amersham HP7 9LL, UK 
 
Advanced Accelerator Applications, 50100, La Almunia-Zaragoza, Spain 
 
Advanced Accelerator Applications, 407014, Meldola (FC), Italy 
 
Advanced Accelerator Applications, 92210 Saint Cloud, France 
 
  



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



25 

Package leaflet: Information for the patient 
 

Axumin 1600 MBq/mL solution for injection 
Axumin 3200 MBq/mL solution for injection 

fluciclovine (18F) 
 

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 this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your 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 Axumin is and what it is used for  
2. What you need to know before Axumin is used 
3. How Axumin is used 
4. Possible side effects  
5. How Axumin is stored 
6. Contents of the pack and other information 
 
 
1. What Axumin is and what it is used for 
 
This medicine is a radiopharmaceutical product for diagnostic use only. 
 
Axumin contains the active ingredient fluciclovine (18F) and is given so that doctors can perform a 
special type of scan called a PET scan. If you have previously had treatment for prostate cancer and 
information from other tests (e.g. prostate specific antigen, PSA) indicates that the cancer may have 
returned, an Axumin PET scan can help your doctor find the locations where the cancer has come 
back.  
 
You should discuss the results of the test with the doctor that requested the scan. 
 
The use of Axumin does involve exposure to small amounts of radioactivity. Your doctor and the 
nuclear medicine doctor have considered that the benefit of this procedure with the 
radiopharmaceutical outweighs the risk of being exposed to radiation.  
 
 
2. What you need to know before Axumin is used 
 
Axumin must not be used: 
- if you are allergic to fluciclovine (18F) or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions  
Talk to your nuclear medicine doctor before you are given Axumin if you: 
- have kidney problems 
- are on a low sodium diet (see section "Axumin contains sodium"). 
 



26 

Before administration of Axumin you: 
- should avoid exercise for at least a day before the Axumin scan. 
- should not eat or drink for at least 4 hours before the scan (you can take your usual medicines 

with small amounts of water).   
- may urinate at the latest 60 minutes before the Axumin injection and you should avoid urination 

until after the scan has been completed. 
 
Children and adolescents 
Talk to your nuclear medicine doctor if you are under 18 years old. Axumin is not intended for use in 
children and adolescents aged under 18 years. 
 
Other medicines and Axumin  
Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other 
medicines since they may interfere with the interpretation of the images. 
 
Pregnancy and breast-feeding 
This medicine is not indicated for use in women. 
 
Driving and using machines  
It is considered unlikely that Axumin will affect your ability to drive or to use machines. 
 
Axumin contains sodium 
This medicine contains up to 39 mg sodium per dose. This should be taken into consideration if you 
are on a controlled sodium diet. 
 
 
3. How Axumin is used 
 
There are strict laws on the use, handling and disposal of radiopharmaceutical products.  
Axumin will only be used in specially controlled areas. This medicine 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 medicine and will keep you informed of their actions.  
 
The nuclear medicine doctor supervising the procedure will decide on the quantity of Axumin to be 
used in your case. It will be the smallest quantity necessary to get the desired information.  The 
quantity to be administered usually recommended for an adult is 370 MBq (megabecquerel, the unit 
used to express radioactivity). 
 
Administration of Axumin and conduct of the procedure  
Axumin is administered intravenously as an injection into your vein followed by a flush of sodium 
chloride solution to ensure that you receive the full dose.  
 
One injection is usually sufficient to conduct the test that your doctor needs. 
 
Duration of the procedure  
Your nuclear medicine doctor will inform you about the usual duration of the procedure. The scan will 
usually start approximately 5 minutes after the Axumin injection is given. 
 
After administration of Axumin you should:  
- avoid any close contact with young children and pregnant women for the 12 hours following the 

injection 
- urinate frequently in order to eliminate the product from your body. 
 
The nuclear medicine doctor will inform you if you need to take any other special precautions after 
receiving this medicine. Contact your nuclear medicine doctor if you have any questions.  
 



27 

If you have been given more Axumin than you should 
An overdose is unlikely because you will only receive a single dose of Axumin precisely controlled by 
the nuclear medicine doctor supervising the procedure. However, in the case of an overdose, you will 
receive the appropriate treatment. In particular, the nuclear medicine doctor in charge of the procedure 
may provide ways to increase the passing of urine and stools in order to facilitate the removal of 
radioactivity from your body. 
 
Should you have any further question on the use of Axumin, please ask your nuclear medicine doctor 
who supervises the procedure. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. In clinical 
studies side effects were reported by less than 1 in 100 patients given the medicine. 
 
The following side effects of Axumin are common (may affect up to 1 in 100 people).  
- Pain or rash at the site of injection, altered taste in the mouth, altered sense of smell. 
 
This radiopharmaceutical will deliver low amounts of ionising radiation associated with the least risk 
of cancer and hereditary abnormalities.  
 
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 Axumin 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.  
 
Axumin must not be used after the expiry date which is stated on the shield label after Exp. 
 
 
6. Contents of the pack and other information 
 
What Axumin contains  
- The active substance is fluciclovine (18F).  

Axumin 1600 MBq/mL solution for injection  
Each mL of solution contains 1600 MBq fluciclovine (18F) at date and time of calibration (ToC).  
The activity per vial ranges from 1600 MBq to 16000 MBq at the date and time of calibration. 
Axumin 3200 MBq/mL solution for injection  
Each mL of solution contains 3200 MBq fluciclovine (18F) at date and time of calibration 
(ToC).The activity per vial ranges from 3200 MBq to 32000 MBq at the date and time of 
calibration. 

- The other ingredients are sodium citrate, concentrated hydrochloric acid, sodium hydroxide, 
water for injections (see section 2 "Axumin contains sodium") 

 
What Axumin looks like and contents of the pack 
Axumin is a clear, colourless solution stored in a glass vial. 

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


28 

Axumin 1600 MBq/mL solution for injection 
Each multidose vial contains 1 to 10 mL of solution, corresponding to 1600 to 16000 MBq at the date 
and time of calibration (ToC). 
 
Axumin 3200 MBq/mL solution for injection 
Each multidose vial contains 1 to 10 mL of solution, corresponding to 3200 to 32000 MBq at the date 
and time of calibration (ToC).  
Pack size: 1 vial. 
 
Marketing Authorisation Holder and Manufacturer 
Marketing Authorisation Holder  
Blue Earth Diagnostics Ireland Ltd, 6th Floor, 2 Grand Canal Square, Dublin 2, Ιreland 
 
Manufacturer 
Seibersdorf Labor GmbH, 2444 Seibersdorf, Austria. 
 
Norsk medisinsk syklotronsenter AS, 0372 Oslo, Norway. 
 
Advanced Accelerator Applications, 13005 Marseille, France 
 
Nucleis SA, 4000 Liège, Belgium 
 
GE Healthcare Ltd, Amersham HP7 9LL, UK 
 
Advanced Accelerator Applications, 50100, La Almunia-Zaragoza, Spain 
 
Advanced Accelerator Applications, 407014, Meldola (FC), Italy 
 
Advanced Accelerator Applications, 92210 Saint Cloud, France 
 
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.  
 
This leaflet is available in all EU/EEA languages on the European Medicines Agency website. 
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 
The complete SmPC of Axumin is provided as a separate document in the package of the medicinal 
product, with the objective to provide healthcare professionals with other additional scientific and 
practical information about the administration and use of this radiopharmaceutical. 
Please refer to the SmPC [SmPC should be included in the box] 

  

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


29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 

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

 
 
 
 
 

 



30 

Scientific conclusions 

Taking into account the PRAC Assessment Report on the PSUR(s) for fluciclovine (18F), the 
scientific conclusions of the CHMP are as follows:  

Based on literature, relatively higher than expected degree of fluciclovine (18F) urinary excretion was 
noticed in clinical practice compared to that reported in the research studies using the standard 
PET/CT protocol including instruction to the patient to void before radiotracer injection. High 
bladder fluciclovine activity may have significant impact on the evaluation of local prostate cancer 
recurrence, as it may mask areas of local prostate cancer recurrence. Therefore, in view of the 
available data, the PRAC concluded that a recommendation concerning voiding instructions prior to 
administration of fluciclovine (18F) was considered necessary. The product information of products 
containing fluciclovine (18F) should be amended 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 fluciclovine (18F) the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing fluciclovine (18F) 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. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS 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
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)