Axumin

European Union - English - EMA (European Medicines Agency)

Active ingredient:
Fluciclovine (18F)
Available from:
Blue Earth Diagnostics Ireland Ltd
ATC code:
V09IX12
INN (International Name):
fluciclovine (18F)
Therapeutic group:
Diagnostic radiopharmaceuticals
Therapeutic area:
Prostatic Neoplasms, Radionuclide Imaging
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.
Product summary:
Revision: 12
Authorization status:
Authorised
Authorization number:
EMEA/H/C/004197
Authorization date:
2017-05-21
EMEA code:
EMEA/H/C/004197

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Read the complete document

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Axumin 1,600 MBq/mL solution for injection

Axumin 3,200 MBq/mL solution for injection

fluciclovine (

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

What Axumin is and what it is used for

What you need to know before Axumin is used

How Axumin is used

Possible side effects

How Axumin is stored

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 substance fluciclovine (

F) 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 (

F) 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").

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 (main component of cooking/table salt) in each dose. This

is equivalent to 2% of the recommended maximum daily dietary intake of sodium for an adult.

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

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.

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 (

Axumin 1,600 MBq/mL solution for injection

Each mL of solution contains 1,600 MBq fluciclovine (

F) at date and time of calibration

(ToC).

The activity per vial ranges from 1,600 MBq to 16,000 MBq at the date and time of calibration.

Axumin 3,200 MBq/mL solution for injection

Each mL of solution contains 3,200 MBq fluciclovine (

F) at date and time of calibration

(ToC).The activity per vial ranges from 3,200 MBq to 32,000 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.

Axumin 1,600 MBq/mL solution for injection

Each multidose vial contains 1

to 10 mL of solution, corresponding to 1,600

to 16,000 MBq at the date

and time of calibration (ToC).

Axumin 3,200 MBq/mL solution for injection

Each multidose vial contains 1

to 10 mL of solution, corresponding to 3,200

to 32,000 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

Advanced Accelerator Applications, 50100, La Almunia-Zaragoza, Spain

Advanced Accelerator Applications, 407014, Meldola (FC), Italy

Advanced Accelerator Applications, 92210 Saint Cloud, France

Synektik Pharma Sp. z o.o., 96-320 Mszczonów, Poland

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]

Read the complete document

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

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 1,600 MBq/mL solution for injection

Axumin 3,200 MBq/mL solution for injection

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Axumin 1,600 MBq/mL solution for injection

Each mL of solution contains 1,600

MBq of fluciclovine (

F) at the date and time of calibration

(ToC).

The activity per vial ranges from 1,600 MBq to 16,000 MBq at the date and time of calibration (ToC).

Axumin 3,200 MBq/mL solution for injection

Each mL of solution contains 3,200 MBq of fluciclovine (

F) at the date and time of calibration

(ToC).

The activity per vial ranges from 3,200 MBq to 32,000 MBq at the date and time of calibration (ToC).

Fluorine (

F) decays to stable oxygen (

O) 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 Axumin 1,600 MBq/mL and each mL Axumin 3,200 MBq/mL 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 (

F) should be administered by appropriately qualified healthcare

professionals.

Images should only be interpreted by readers trained in the interpretation of PET images with

fluciclovine (

Posology

Adults

The recommended activity for an adult is 370 MBq fluciclovine (

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 (

F) in the paediatric population.

Method of administration

Axumin is for intravenous use.

The activity of fluciclovine (

F) 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 (

F) PET. (see section 5.1,

Pharmacodynamic properties).

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 (

F) scan.

Prior to administration of fluciclovine (

F), 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 (

F), and should then refrain from voiding until after the scan

has been completed.

Interpretation of fluciclovine (

F) images and limitations of use

Fluciclovine (

F) images should be interpreted by appropriately trained personnel.

PET images with fluciclovine (

F) should be interpreted visually. Suspicion of cancer in sites typical

for prostate cancer recurrence is based on fluciclovine (

F) 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 (

F) uptake as an aid to

image interpretation has not been assessed.

Image interpretation errors can occur with PET with fluciclovine (

F) (see section 5.1).

Fluciclovine (

F) 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 (

F) 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 (

F) PET has been reported.

Diagnostic performance of fluciclovine (

F) 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.

Specific warnings

This medicinal product contains up to 39 mg sodium in each injected dose, equivalent to 2% of the

WHO recommended maximum daily intake of 2g sodium for an adult.

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 (

F) 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 studies.

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.

4.9

Overdose

In the event of administration of a radiation overdose with fluciclovine (

F) 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: Diagnostic radiopharmaceuticals, other diagnostic radiopharmaceuticals

for tumour detection, ATC code: V09IX12.

Mechanism of action

Fluciclovine (

F) 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 (

F) 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 (

F) 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 localised prostate cancer and with

negative bone scintigraphy. Patients with non-surgical therapy were treated at least 2 years before.

Fluciclovine (

F) 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 (

F) 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.

Table 1. Patient and region based diagnostic performance of fluciclovine

18

F PET vs histopathology

Patient based

Location

Prostate & prostate

Pelvic lymph

nodes

Extraprostatic

(pelvic and

distal

recurrence)

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 (

F) 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 (

F) 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

(

18

F) 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

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%]

An additional study BED002 conducted a blinded read of fluciclovine (

F) 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 (

F) 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 (

F) 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 (

F) 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 (

F) 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

F activity from the blood is such that about half

of the maximum

F 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 (

F) equates to the radioactive half-life of fluorine (

F), which

is approximately 110 minutes.

Renal/Hepatic impairment

The pharmacokinetics in patients with renal or hepatic impairment have not been characterised.

in vitro

studies, fluciclovine (

F) 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.

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 1,600 MBq/mL solution for injection

8 hours from the time of calibration (ToC)

Axumin 3,200 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 1,600 MBq/mL for 8 hours

and for Axumin 3,200 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 medicinal 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 1,600 MBq/mL solution for injection

One vial contains 1

to 10 mL of solution, corresponding to 1,600

to 16,000 MBq at calibration time.

Axumin 3,200 MBq/mL solution for injection

One vial contains 1

to 10 mL of solution, corresponding to 3,200

to 32,000 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.

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

Read the complete document

30 Churchill Place

Canary Wharf

London E14 5EU

United Kingdom

An agency of the European Union

Telephone

+44 (0)20 3660 6000

Facsimile

+44 (0)20 3660 5555

Send a question via our website

www.ema.europa.eu/contact

© European Medicines Agency, 2017. Reproduction is authorised provided the source is acknowledged.

EMA/240225/2017

EMEA/H/C/004197

EPAR summary for the public

Axumin

fluciclovine (

This is a summary of the European public assessment report (EPAR) for Axumin. It explains how the

Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is

not intended to provide practical advice on how to use Axumin.

For practical information about using Axumin, patients should read the package leaflet or contact their

doctor or pharmacist.

What is Axumin and what is it used for?

Axumin is a diagnostic medicine used with a body scan to check whether or not prostate cancer has

returned.

It is used specifically with the body scan known as positron-emission tomography (PET) in men whose

blood test for prostate-specific antigen (PSA) indicate that the cancer may have returned.

Axumin is a ‘radiopharmaceutical’: it contains the active substance fluciclovine (

F), which emits a

small amount of radiation.

How is Axumin used?

Axumin is available as a solution for injection, which is given as a single injection into a vein around 3

to 5 minutes before the patient is to undergo a PET scan.

Axumin can only be obtained with a prescription. The PET images must be read by nuclear medicine

physicians trained in interpreting PET scan images with Axumin. Patients should discuss the results of

their PET scan with their doctor. For further information, see the package leaflet.

Axumin

EMA/240225/2017

Page 2/3

How does Axumin work?

The active substance in Axumin, fluciclovine (

F), works by entering prostate cancer cells via

structures (LAT-1 and ASCT2) that are present in high numbers on the surface of these cells. Once

inside the cancer cells, it emits radiation which is detected on the PET scan, enabling doctors to see

where the cancer is located.

What benefits of Axumin have been shown in studies?

In a main study involving medical records from 115 men, PET scans with Axumin correctly detected

cancers in 99% of all patients whose cancer had in fact returned (as confirmed by tissue sampling).

When the scans from this study were looked at by another team of researchers, the scans were again

shown to be able to detect cancer in most patients who had it. (87% of patients with cancer had

positive scans.)

However, because some scans with Axumin were falsely positive (showing that cancer had returned

when tissue sampling was negative), a positive result on its own is not enough to make a diagnosis.

Depending on the person reading the scans, only 17 to 54% of patients whose tissue samples did not

show cancer had a negative scan result.

All men enrolled in this study had already shown some signs that the cancer might have returned, such

as increases in blood levels of PSA, a protein produced in the prostate glands. The accuracy of the

scans varied depending on the PSA levels.

What are the risks associated with Axumin?

The most common side effects with Axumin (seen in between 1 and 10 patients in 100) are taste

disturbances, altered sense of smell, and pain or rash at the site of injection. For the full list of side

effects and restrictions reported with Axumin, see the package leaflet.

Axumin delivers a very low amount of radiation which could pose a very low risk of cancer and

hereditary abnormalities.

Why is Axumin approved?

PET scans with Axumin are effective in detecting prostate cancer and can help exclude the presence of

the cancer. The side effects seen with the product are mild and rare, and there are no serious safety

risks. Furthermore, the risk from radiation is very low.

The Agency’s Committee for Medicinal Products for Human Use (CHMP) therefore concluded that

Axumin’s benefits are greater than its risks and recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of

Axumin?

The company that markets Axumin will ensure that all healthcare professional expected to use this

product have access to education material to reduce errors in interpreting PET scan images.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe

and effective use of Axumin have also been included in the summary of product characteristics and the

package leaflet.

Axumin

EMA/240225/2017

Page 3/3

Other information about Axumin

The European Commission granted a marketing authorisation valid throughout the European Union for

Axumin on 22 May 2017.

The full EPAR for Axumin can be found on the Agency’s website:

ema.europa.eu/Find medicine/Human

medicines/European public assessment reports. For more information about treatment with Axumin,

read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 05-2017.

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