4.2 Posology and method of administration

Adults and elderly population

The recommended activity for an adult weighing 70 kg is 100 to 400 MBq (this activity has to be adapted according to the body weight of the patient and the type of camera used and acquisition mode), administered by direct intravenous injection.

Renal and hepatic impairment

Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients.

Extensive dose-range and adjustment studies with this medicinal product in normal and special populations have not been performed.

The pharmacokinetics of fludeoxyglucose (18F) in renally impaired patients has not been characterised.

Paediatric population

The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. The activities to be administered to children and to adolescents may be calculated according to the recommendations of the European Association of Nuclear Medicine (EANM) paediatric dosage card; the activity administrated children and to adolescents may be calculated by multiplying a baseline activity (for calculation purposes) by the weight-dependent multiples given in the table below.

A[MBq]_Administered = Baseline Activity × Multiple

The baseline activity for 2D imaging is 25.9 MBq and for 3D imaging 14.0 MBq (recommended in children).

Method of administration

For intravenous injection.

For multidose use.

The activity of fludeoxyglucose (18F) has to be measured with activimeter immediately prior to injection.

The injection of fludeoxyglucose (18F) must be intravenous in order to avoid irradiation as a result of local extravasation, as well as imaging artefacts.

For instructions on dilution of the medicinal product before administration, see section 12.

For patient preparation, see section 4.4.

Image acquisition

The emission scans are usually started 45 to 60 minutes after the injection of fludeoxyglucose (18F). Provided a sufficient activity remains for adequate counting statistics, fludeoxyglucose (18F)-PET can also be performed up to two or three hours after administration, thus reducing background activity.

If required, repeated fludeoxyglucose (18F)-PET examinations can be reiterated within a short period of time.

4.3. Contraindications

Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to any of the components of the labelled radiopharmaceutical.

4.4. Special warnings and precautions for use

Potential for hypersensitivity or anaphylactic reactions

If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must be immediately available.

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.

Renal and hepatic impairment

Due to the major renal excretion of fludeoxyglucose (18F), in patients with reduced kidney function, careful consideration of the benefit risk ratio in these patients is required since an increased radiation exposure is possible. Activity should be adjusted if necessary.

Paediatric Population

For information on the use in paediatric population, see section 4.2 or 5.1.

Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).

Patient preparation

EFDEGE should be given to sufficiently hydrated patients fasting for a minimum of 4 hours, in order to obtain a maximum target activity, since glucose uptake in the cells is limited (“saturation kinetics”). The amount of liquid should not be limited (beverages containing glucose must be avoided). In order to obtain images of best quality and to reduce the radiation exposure of the bladder, patients should be encouraged to drink sufficient amounts and to empty their bladder prior to and after the PET examination.

Oncology and neurology and infectious diseases

In order to avoid hyperfixation of the tracer in muscle, it is advisable for patients to avoid all strenuous physical activity prior to the examination and to remain at rest between the injection and examination and during acquisition of images (patients should be comfortably lying down without reading or speaking). The cerebral glucose metabolism depends on the brain activity. Thus, neurological examinations should be performed after a relaxation period in a darkened room and with low background noise.

A blood glucose test should be performed prior to administration since hyperglycaemia may result in a reduced sensitivity of EFDEGE, especially when glycaemia is greater than 8 mmol/L. Similarly, PET with fludeoxyglucose (18F) should be avoided in subjects presenting uncontrolled diabetes.

Cardiology

Since glucose uptake in the myocardium is insulin-dependent, for a myocardial examination a glucose loading of 50 g approximately 1 hour prior to the administration of EFDEGE is recommended. Alternatively, especially for patients with diabetes mellitus, the blood sugar level can be adjusted by a combined infusion of insulin and glucose (insulin-glucose-clamp) if needed.

Interpretation of the FDG PET examination:

In the exploration of inflammatory bowel diseases, diagnostic performance of fludeoxyglucose (18F) has not been directly compared with that of scintigraphy using labelled white blood cells which may be indicated prior to fludeoxyglucose (18F) PET or after fludeoxyglucose (18F) PET when inconclusive.

Infectious and/or inflammatory diseases as well as regenerative processes after surgery can result in a significant uptake of fludeoxyglucose (18F) and therefore lead to false positive results, when search for infectious or inflammatory lesions is not the aim of the fludeoxyglucose (18F) PET. In cases where fludeoxyglucose (18F) accumulation can be caused by either cancer, infection or inflammation, additional diagnostic techniques for the determination of the causative pathologic alteration may be required to supplement the information obtained by PET with fludeoxyglucose (18F). In some settings e.g. staging of myeloma, both malignant and infectious foci are searched for and may be distinguished with a good accuracy on topographic criteria e.g. uptake at extramedullary sites and/or bone and joint lesions would be atypical for multiple myeloma lesions and identified cases associated with infection. There are currently no other criteria to distinguish infection and inflammation by means of fludeoxyglucose (18F) imaging.

Because of the high physiologic uptake of fludeoxyglucose (18F) within brain, heart and kidneys, PET/CT with fludeoxyglucose (18F) has not been evaluated for the detection of septic metastatic foci in these organs, when the patient has been referred due to bacteraemia or endocarditis. False positive or false negative PET with fludeoxyglucose (18F) results cannot be excluded after radiotherapy within the first 2-4 months. If the clinical indication is demanding an earlier diagnosis by PET with fludeoxyglucose (18F), the reason for earlier PET with fludeoxyglucose (18F) examination must be reasonably documented.

A delay of at least 4-6 weeks after the last administration of chemotherapy is optimal, in particular to avoid false negative results. If the clinical indication is demanding an earlier diagnosis by PET with fludeoxyglucose (18F), the reason for earlier PET with fludeoxyglucose (18F) examination must be reasonably documented. In case of chemotherapy regimen with cycles shorter than 4 weeks, the PET with fludeoxyglucose (18F) examination should be done just before re-starting a new cycle. In low-grade lymphoma, lower oesophagus cancer and suspicion of recurrent ovarian cancer, only positive predictive values have to be considered because of a limited sensitivity of PET with fludeoxyglucose (18F).

Fludeoxyglucose (18F) is not effective in detecting brain metastases.

The accuracy of fludeoxyglucose (18F) PET imaging is better using PET/CT than PET cameras alone.

When a hybrid PET-CT scanner is used with or without administration CT contrast media, some artefacts may occur on the attenuation-corrected PET images.

After the procedure

Close contact with infants and pregnant women should be restricted during the initial 12 hours following the injection.

Specific warnings

Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1 mmol (23 mg). This should be taken into account in patient on low sodium diet.

Precautions with respect to environmental hazard see section 6.6.

4.5. Interaction with other medicinal products and other forms of interaction

All medicinal products that modify blood glucose levels can affect the sensitivity of the examination (e.g. corticosteroids, valproate, carbamazepine, phenytoin, phenobarbital and catecholamines).

Under administration of colony-stimulating factors (CSFs) there is an increased uptake of fludeoxyglucose (18F) in the bone marrow and the spleen for several days. This must be taken into account for the interpretation of PET imaging. Separating CSF therapy from PET imaging by an interval of at least 5 days may diminish this interference.

The administration of glucose and insulin influences the influx of fludeoxyglucose (18F) into the cells. In the case of high blood glucose levels as well as low plasma insulin levels, the influx of fludeoxyglucose (18F) into organs and tumours is reduced.

No formal studies on the interaction between fludeoxyglucose (18F) and any contrast for computed tomography have been performed.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

Radionuclide procedures carried out on pregnant women also involve radiation doses to the fœtus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and foetus.

Breastfeeding

Before administering radiopharmaceuticals to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 12 hours and the expressed feeds discarded.

Close contact with infants should be restricted during the initial 12 hours following injection.

Fertility

No studies on fertility have been performed.

4.7. Effects on ability to drive and use machines

Not relevant.

4.8. Undesirable effects

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 7.6 mSv when the maximal recommended activity of 400 MBq is administered these adverse reactions are expected to occur with a low probability.

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.

4.9. Overdose

In the event of administration of a radiation overdose with fludeoxyglucose (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 and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.

4.2 Posology and method of administration

Adults and elderly Population

In oncology, the recommended activity for an adult weighting 70 kg is 2 to 4 MBq/kg (this activity has to be adapted according to the body weight of the patient, the type of camera used PET(/CT), and acquisition mode), administered by direct slow intravenous injection over approximately one minute.

One half of this activity may be administered for neurological indications not requiring whole body images.

Renal / Hepatic impairment

Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients.

Paediatric Population

The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. The activities to be administered to children and adolescents may be calculated according to the recommendations of the European Association of Nuclear Medicine (EANM) paediatric dosage card; the activity administered to children and to adolescents may be calculated by multiplying a baseline activity (for calculation purposes) by the body-mass-dependent coefficients given in the table below.

A[MBq]_Administered = Baseline Activity × Coefficient

The Baseline Activity for 2D imaging is 25.9 MBq and for 3D imaging 14.0 MBq (recommended in children).

Method of Administration

For intravenous use : the fluoro-(18F)-L-dopa must be administered by slow intravenous injection, over approximately one minute.

For multidose use.

The activity of 6-fluoro-(18F)-L-dopa has to be measured with activimeter immediately prior to injection.

The injection of 6-fluoro-(18F)-L-dopa must be intravenous in order to avoid irradiation as a result of local extravasation, as well as imaging artefacts.

For instructions on extemporaneous preparation of the medicinal product before administration, see sections 6.6 and 12.

For patient preparation, see section 4.4.

Image acquisition

Neurology

• “dynamic” acquisition of PET images of the brain during 90 to 120 minutes right after injection,

• or one “static” PET acquisition starting 90 minutes after the injection.

Oncology

To detect foci in the liver, pancreas or brain area, early “static” images can be acquired starting 5 minutes after injection, or a “dynamic” acquisition starting right after the injection during 10 minutes.

• Brain tumours: “static” acquisition 10 to 30 minutes after injection.

• Whole-body: images are usually acquired 60 minutes after injection.

4.3 Contraindications

• Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to any of the components of the pH-adjusted radiopharmaceutical.

• Pregnancy (see section 4.6).

4.4 Special warnings and precautions for use

Potential for hypersensitivity or anaphylactic reactions

If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must be immediately available.

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.

Renal / hepatic 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 the use in paediatric population, see section 4.2.

Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).

Patient preparation

IASOdopa should be given to patients fasting for a minimum of 4 hours without limiting water intake.

In order to obtain images of best quality and to reduce the radiation exposure of the bladder, patients should be encouraged to drink sufficient amounts and to empty their bladder prior to and after the PET examination.

In neurological indications, it is recommended to suspend any antiparkinsonian treatment at least 12 hours before the PET examination.

The administration of 100 to 200 mg of carbidopa one to one and a half hours before the injection of 6-fluoro-(18F)-L-dopa is recognized for neurological indications but less frequent for oncological indications.

Interpretation of 6-fluoro-(18F)-L-dopa PET Images

Neurology

The interpretation of 6-fluoro-(18F)-L-dopa uptake values in the different parts of the brain requires the comparison to age and sex matched controls. Recent publications refer to data base of normal cases and voxel-based Statistical Parametric Mapping (SPM) and automated region of interest (ROI) analysis.

Oncology

False positive results in inflammatory lesions seem to be very rare with 6-fluoro-(18F)-L-dopa PET. Nevertheless, the possibility of an inflammatory lesion should be kept in mind when an unexpected 6-fluoro-(18F)-L-dopa focus is detected. The physiologic biodistribution must be taken into account in the interpretation; in particular uptake in the basal ganglia, diffuse uptake in the pancreas, uptake in the gallbladder leading to subsequent activity in the gut, and uptake in the kidney leading to “hot spots” aspect in the ureters and a high activity in the bladder.

After the procedure

Close contact with infants and pregnant women should be restricted during the initial 12 hours following the injection.

Specific warnings

Depending on the time when you administer the injection prepared extemporaneously after pH adjustment, the content of sodium given to the patient may in some cases be greater than 1 mmol (23 mg). This should be taken into account in patient on low sodium diet.

Precautions with respect to environmental hazard : see section 6.6.

4.5 Interaction with other medicinal products and other forms of interaction

Carbidopa

Prior to 6-fluoro-(18F)-L-dopa administration, use of carbidopa may increase 6-fluoro-(18F)-L-dopa bioavailability to the brain by inhibiting peripheral decarboxylase activity and restricting peripheral 6-fluoro-(18F)-L-dopa metabolism with 3-O-methyl-6-fluoro-(18F)-L-dopa formation.

Haloperidol

Increased intracerebral dopamine turnover caused by haloperidol may result in increased accumulation of 6-fluoro-(18F)-L-dopa.

Monoamine oxidase (MAO) Inhibitors

Concurrent use with MAO inhibitors may result in increased accumulation of 6-fluoro-(18F)-L-dopa in the brain.

Reserpine

Reserpine-induced depletion of the contents of intraneuronal vesicles may prevent retention of 6-fluoro-(18F)-L-dopa in the brain.

Paediatric Population

Interaction studies have only been performed in adults.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

The use of 6-fluoro-(18F)-L-dopa is contraindicated in pregnant women due to preventive radiation protection of the foetus (see section 4.3).

Breastfeeding

Before administering radiopharmaceuticals to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 12 hours and the expressed feeds discarded.

Close contact with infants should be restricted during the initial 12 hours following the injection.

Fertility

No studies on fertility have been performed.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

No undesirable effects have been observed to date.

Pain at injection has been reported in rare cases which resolved within minutes without corrective measures.

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 7 mSv when the maximal recommended activity of 280 MBq is administered, these adverse reactions are expected to occur with a low probability.

Paediatric population

Not reported.

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.

4.9 Overdose

An overdose in the pharmacological sense is unlikely given with the doses used for diagnostic purposes.

In the event of administration of a radiation overdose with 6-fluoro-(18F)-L-dopa the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by forced diuresis and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.

4.2 Posology and method of administration

The recommended activity for an adult weighting 70kg is 200 to 500 MBq administered by direct intravenous injection. This activity has to be adapted according to the body weight of the patient and the type of PET or PET/CT camera used.

Renal impairment

Extensive dose-range and adjustment studies with this product in normal and special populations have not been performed. The pharmacokinetics of (¹⁸F) in renally impaired patients has not been characterised.

Paediatric population

No clinical data are available for patients aged less than 18 years concerning safety and diagnostic efficacy of the product. Therefore, the use in oncologic paediatrics is not recommended.

Method of administration

For patient preparation, see section 4.4.

The activity of fluorocholine (¹⁸F) chloride has to be measured with activimeter immediately prior to injection.

The injection of fluorocholine (¹⁸F) chloride must be intravenous in order to avoid irradiation as a result of local extravasation, as well as imaging artefacts. It should be administered by direct intravenous injection.

Image acquisition

For prostate cancer: dynamic PET acquisition over the pelvis including the prostate bed and the pelvic bones, during 8 min, starting 1 min after injection, or if not feasible one 2 min static acquisition starting 1 min post injection.

For all indications: “Static” whole-body PET acquisition started 10 to 20 min after injection. If there is doubt concerning lesions with a slow uptake (e.g. negative static images whereas serum PSA levels are increased), a second static acquisition may be performed after one hour.

4.3 Contraindications

• Hypersensitivity to the active substance, to any of the excipients or to any of the components of the labelled radiopharmaceutical.

• Pregnancy.

4.4 Special warnings and precautions for use

Pregnancy, see section 4.3 and 4.6

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.

Renal impairment

Careful consideration of the indication is required since an increased radiation exposure is possible in these patients.

Paediatric population

For information on the use in paediatric population, see section 4.2. or 5.1.

Patient preparation

IASOcholine should be given to patients fasting for a minimum of 4 hours.

In order to obtain images of best quality and to reduce the radiation exposure of the bladder, patients should be encouraged to drink sufficient amounts and to empty their bladder prior to and after the PET examination.

After the procedure

Close contact with infants and pregnant women should be restricted during the initial 12 hours following the injection.

Specific warnings

Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1 mmol. This should be taken into account in patients on low sodium diet.

Precautions with respect to environmental hazard see section 6.6.

The maximum volume to be administered to a patient should not exceed 10 mL.

4.5 Interaction with other medicinal products and other forms of interaction

In patients receiving anti-androgen therapy, the indication of IASOcholine PET must be particularly documented by rising serum PSA levels. Any recent change in therapy must lead to the revision of the IASOcholine PET indication taking into consideration the expected impact on patient management.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

The use of IASOcholine is contraindicated in pregnant women due to the radiation doses to the foetus (see section 4.3).

No data are available concerning the use of this product during pregnancy. No studies of reproductive function have been performed in animals.

Breastfeeding

Before administering radiopharmaceuticals to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for the initial 12 hours following injection and the expressed feeds discarded.

Close contact with infants should be restricted during this period.

4.7 Effects on ability to drive and use machines

Not relevant

4.8 Undesirable effects

No undesirable effects have been observed to date.

Since the administered substance quantity is very low, the major risk is caused by the radiation. Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 5.6 mSv when the maximal recommended activity of 280 MBq (4MBq/kg for a subject weighting 70kg) is administered these adverse events are expected to occur with a low probability.

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.

4.9 Overdose

An overdose in the pharmacological sense is unlikely given with the doses used for diagnostic purposes.

In the event of administration of a radiation overdose with fluorocholine (¹⁸F) chloride the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by forced diuresis and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.

4.2 Posology and method of administration

Posology

Adults

The recommended activity for an adult weighing 70 kg is 370 MBq (the activity will be adapted to the body mass, the type of camera used, PET/CT, and acquisition mode. The activity could vary from 100–400 MBq, administered by direct intravenous injection.

If required, sodium fluoride (¹⁸F) PET examinations can be repeated within a short period of time.

Special populations

Patients with renal impairment

In case of renal impairment, exposure to ionising radiation can be increased. This must be taken into account when calculating the activity to be administered.

Paediatric population

The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. The activities to be administered to children and adolescents may be calculated according to the recommendations of the EANM paediatric task group Dosage Card; the activity administered to children and to adolescents may be calculated by multiplying a baseline activity (for calculation purposes) by the body-mass-dependent coefficients given in the table below.

A[MBq]Administered = Baseline Activity × Coefficient

A minimum activity of 14 MBq is recommended in case of acquisition with 3D PET system and 26 MBq in the case of acquisition with 2D PET system. In children images acquisition in 3D mode should be preferred.

Method of administration

For intravenous use.

For multidose use.

Precautions to be taken before handling or administration of the medicinal product

For instructions on dilution of the medicinal product before administration, see section 12.

For patient preparation, see section 4.4.

The activity of sodium fluoride (¹⁸F) has to be measured with an activimeter immediately prior to injection.

The injection must be intravenous in order to avoid irradiation as a result of local extravasation, as well as imaging artefacts.

Image acquisition

The emission scans are usually started 60 minutes after the injection of sodium fluoride (¹⁸F). Provided a sufficient activity remains for adequate counting statistics, sodium fluoride (¹⁸F)-PET scans can also be performed up to two or three hours after administration, thus reducing background activity. Voiding immediately prior to imaging is recommended in order to reduce the activity in the pelvis.

4.3. Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Pregnancy (see section 4.6).

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.

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 the use in paediatric population, see section 4.2.

Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).

Patient preparation

The patient should be well hydrated before the start of the examination and urged to void as often as possible during the first hours after the study in order to reduce radiation.

Interpretation of sodium fluoride (¹⁸F)-PET images

Sodium fluoride (¹⁸F) has a higher sensitivity for the detection of bone lesions than other “bone-seeking” tracers (^99mTc-labelled phosphate and phosphonic acid derivatives). Since sodium fluoride (¹⁸F) does not show secondary cancerous processes directly, but notifies cancer effects (osteogenic activity following osseous lesions), sodium fluoride (¹⁸F) is less effective for the detection of early stages of bone metastases, like bone marrow metastases without substantial bone damage.

Hardware fusion of the functional sodium fluoride (¹⁸F) PET images with morphologic images e.g. PET-CT can lead to an increased sensitivity and specificity in bone diagnostics.

As there is no significant difference in uptake by malignant or benign lesions, the differentiation between bone metastases and non-malignant bone lesions benefits from the analysis of PET and CT image fusion, better obtained from hybrid PET-CT imaging, or if not available from supplemental diagnostic procedures (MRI, CT).

After the procedure

Close contact with infants and pregnant women should be restricted during the initial 12 hours following the injection.

Specific warnings

Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1 mmol (23 mg). This should be taken into account in patient on low sodium diet.

Precautions with respect to environmental hazard are in section 6.6.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

The use of sodium fluoride (¹⁸F) is contraindicated in pregnant women due to the radiation exposure to the foetus (see section 4.3).

Breastfeeding

Before administering radiopharmaceuticals to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 12 hours and the expressed feeds discarded.

Close contact with infants should be restricted during the initial 12 hours following injection.

Fertility

No studies on fertility have been performed.

4.7. Effects on ability to drive and use machines

Not relevant.

4.8. Undesirable effects

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 6.8 mSv when the maximal recommended activity of 400 MBq is administered for an adult of 70 kg, these adverse reactions are expected to occur with a low probability.

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.

4.9. Overdose

In the event of administration of a radiation overdose with sodium fluoride (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 and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.

4.2 Posology and method of administration

Posology

Adults and elderly

The recommended activity for an adult weighing 70 kg is 180 to 250 MBq (the activity will be adapted to the body mass, the type of camera used, PET/CT, and acquisition mode), administered by direct intravenous injection.

Special populations

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.

Paediatric population

The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. The activities to be administered to children and adolescents may be calculated according to the recommendations of the European Association of Nuclear Medicine (EANM) for paediatric task group Dosage Card, by multiplying a baseline activity (for calculation purposes) by the weight-dependent multiples given in the table below.

When 3D TEP acquisition mode is available, which is highly recommended :

A(MBq)_Administered = 14 × Multiple (see table below), minimum activity = 14 MBq.

When only 2D TEP acquisition mode is available : A(MBq)_Administered = 25.9 × Multiple (see table below), minimum activity = 26 MBq.

Method of administration

For intravenous use.

For multidose use.

The activity of IASOglio has to be measured with an activimeter immediately prior to injection.

Precautions to be taken before handling or administration of the medicinal product

For instructions on the dilution of the medicinal product before administration, see section 12.

For patient preparation, see section 4.4.

The injection of IASOglio must be intravenous in order to avoid irradiation as a result of local extravasation, as well as imaging artefacts.

Image acquisition

• Dynamic acquisition of PET images of the brain during 40 minutes starting immediately after injection.

• Or one static PET acquisition starting 20 to 40 minutes after injection.

4.3. Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Pregnancy (see section 4.6)

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.

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 the use in paediatric population, see sections 4.2.

Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).

Patient preparation

IASOglio should be administered to patients fasting for a minimum of 4 hours.

In order to obtain images of best quality and to reduce the radiation exposure of the bladder, patients should be encouraged to drink sufficient amounts and to empty their bladder prior to and after the PET examination.

After the procedure

Close contact with infants and pregnant women should be restricted during the first 12 hours following the injection.

Specific warnings

Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1 mmol (23 mg). This should be taken into account in patients on low sodium diet.

This medicinal product contains maximum 10% ethanol, i.e. up to 0.8 g per maximum volume of 10 mL. This amount will produce a blood alcohol concentration of 0.02 g/L (2 mg/100 mL) for an adult weighing 70 kg. This is equivalent to 20 mL beer or 8 mL wine per maximum dose. This should be taken into account in patients suffering from alcoholism, breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.

Precautions with respect to environmental hazard are in section 6.6.

The maximum volume to be administered to a patient should not exceed 10 mL.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

The use of IASOglio is contraindicated in pregnant women due to the radiation exposure to the foetus (see section 4.3).

Breastfeeding

Before administering radiopharmaceuticals to a mother who is breastfeeding, consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 12 hours and the expressed feeds discarded.

Close contact with infants should be restricted during this period.

Fertility

No studies on fertility have been performed.

4.7. Effects on ability to drive and use machines

Not relevant.

4.8. Undesirable effects

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 4 mSv when the maximal recommended activity of 250 MBq is administered these adverse reactions are expected to occur with a low probability.

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 reaction via the national reporting system ().

4.9. Overdose

In the event of administration of a radiation overdose with IASOglio the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by forced diuresis and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.

4.2 Posology and method of administration

Posology

Adults and elderly

The recommended activity for an adult weighing 70 kg is 100 to 200 MBq (the activity will be adapted to the body mass, the type of camera used, PET or PET/CT, and acquisition mode), administered by direct intravenous injection.

Patients with renal impairment

Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients.

Paediatric Population

There is limited clinical data on the safety and efficacy of this product in the under 18 year old patient. The use in children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. The activities to be administered to children and adolescents may be calculated according to the recommendations of the European Association of Nuclear Medicine (EANM) for paediatric task group Dosage Card; the activity administered to children and to adolescents may be calculated by multiplying a recommended activity for an adult (for calculation purposes) by the multiples given in the table below.

A(MBq)Administered = Recommended Activity for an adult × Multiple

Method of Administration

For intravenous use.

The injection of Sogacin/TOCscan must be intravenous in order to avoid irradiation as a result of local extravasation, as well as imaging artefacts. The injection site should be selected remote from the pathological areas to be examined in priority, usually in the forearm.

For multidose use.

Precautions to be taken before handling or administration of the medicinal product

For patient preparation, see section 4.4.

The activity of Sogacin/TOCscan has to be measured with an activimeter immediately prior to injection.

Image acquisition

Image acquisition starts between 45 and 60 minutes after injection.

If required, repeated gallium (68Ga) edotreotide PET examinations can be reiterated within a short period of time.

4.3. Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Pregnancy (see section 4.6)

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 in order to obtain the required diagnostic information.

Diagnostic efficacy of gallium (68Ga) edotrotide has not been demonstrated in the pretherapeutic dosimetry evaluation prior to peptide receptor radionuclide therapy targeting somatostatin receptors.

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 the use in paediatric population, see section 4.2.

Patient preparation

Administration of Sogacin/TOCscan does not require that the patient be fasting.

In order to obtain images of best quality and to reduce the radiation exposure of the bladder, patients should be encouraged to drink sufficient amounts and to empty their bladder prior to and after the PET examination.

Interpretation of Sogacin/TOCscan Images

PET images with Sogacin/TOCscan reflect the density of somatostatin receptors.

The image interpretation must take into account the normal biodistribution of the radiopharmaceutical.

Sogacin/TOCscan is constantly taken-up by the normal pituitary gland, thyroid gland, liver, spleen, kidneys and adrenals. Sogacin/TOCscan may also be variably taken-up by the normal posterior part of the head of the pancreas (uncinate process).

Some pathological conditions (like subacute inflammation, breast cancer, lymphoma) can also show a variable uptake of Sogacin/TOCscan.

Inversely, tumours which do not bear somatostatin receptors will not be visualised with Sogacin/TOCscan.

In case of Cushing syndrome, a long-term exposure to endogenous hypercortisolism may down regulate somatostatin receptor expression and negatively influence the results of somatostatin receptor imaging with gallium (68Ga) edotreotide. In patients with Cushing syndrome, the normalisation of hypercortisolism should be considered before performing PET with gallium (68Ga) edotreotide.

An increased uptake of gallium (68Ga) edotreotide is not specific for GEP-NET. Positive results require evaluating the possibility that another disease, characterised by high local somatostatin receptor concentrations, may be present. For example, an increase in somatostatin receptor density can also occur in the following pathological conditions: subacute inflammations (areas of lymphocyte concentrations), thyroid diseases (e.g. autonomous thyroid nodule and Hashimoto’s thyroiditis), tumours of the pituitary gland, neoplasms of the lungs (small-cell carcinoma), meningiomas, mammary carcinomas, lympho-proliferative disease (e.g. Hodgkin’s and non-Hodgkin lymphomas) and tumours arising from tissue embryologically derived from the neural crest (e.g. paragangliomas, medullary thyroid carcinomas, neuroblastomas, pheochromocytomas).

In patients after splenectomy, splenosis should also be considered as a source of false positive results of imaging with gallium (68Ga) edotreotide.

Concomitant use of somatostatin analogues

It is preferable to perform imaging with gallium (68Ga) edotreotide the day(s) before the next administration of a somatostatin analogue. See section 4.5.

After the procedure

Close contact with infants and pregnant women should be restricted during the initial 8 hours following the injection.

Specific warnings

Depending on the time when you administer the injection, the content of sodium given to the patient may in some cases be greater than 1 mmol (23 mg). This should be taken into account in patients on low sodium diet.

This medicinal product contains 7.4% ethanol, i.e. up to 0.6 g per maximum volume of 10 mL. This amount will produce a blood alcohol concentration of 0.015 g/L (1.5 mg/100 mL) for an adult weighing 70 kg. This is equivalent to 15 mL of beer or 6 mL of wine per maximum dose. This should be taken into account in patients suffering from alcoholism, breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.

Precautions with respect to environmental hazard are in section 6.6.

The maximum volume to be administered to a patient should not exceed 10 mL.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Somatostatin analogues seem not to compete with Sogacin/TOCscan for binding to somatostatin receptors in target cells.

However it is recommended to avoid concurrent treatment with somatostatin analogues with a long half-life for a few days before PET/CT with Sogacin/TOCscan. Somatostatin analogues with a short half-life may be used up to 24 hours before PET/CT with Sogacin/TOCscan.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.

Pregnancy

The use of Sogacin/TOCscan is contraindicated in pregnant women due to the radiation exposure to the foetus (see section 4.3).

Breastfeeding

Before administering radiopharmaceuticals to a mother who is breastfeeding, consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 8 hours and the expressed feeds discarded.

Close contact with infants should be restricted during this period.

Fertility

No studies on fertility have been performed.

4.7. Effects on ability to drive and use machines

Not relevant.

4.8. Undesirable effects

Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 4.4 mSv in men and 5 mSv in women when the maximal recommended activity of 200 MBq is administered these adverse reactions are expected to occur with a low probability.

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 reaction via the national reporting system ().

4.9. Overdose

In the event of administration of a radiation overdose with Sogacin/TOCscan the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by forced diuresis and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.