Lutathera

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 
 

Lutathera 370 MBq/mL solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One mL of solution contains 370 MBq of lutetium (177Lu) oxodotreotide at the date and time of 

calibration. 

 

The total amount of radioactivity per single dose vial is 7,400 MBq at the date and time of infusion. 

Given the fixed volumetric activity of 370 MBq/mL at the date and time of calibration, the volume of 

the solution is adjusted between 20.5 mL and 25.0 mL in order to provide the required amount of 

radioactivity at the date and time of infusion. 

 

Lutetium (177Lu) has a half-life of 6.647 days. Lutetium (177Lu) decays by β- emission to stable 

Hafnium (177Hf) with the most abundant β- (79.3%) having a maximum energy of 0.497 MeV. The 

average beta energy is approximately 0.13 MeV. Low gamma energy is also emitted, for instance at 

113 keV (6.2%) and 208 keV (11%). 

 

Excipient with known effect 

Each mL of solution contains 0.14 mmol (3.2 mg) of sodium. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Solution for infusion. 

Clear, colourless to slightly yellow solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Lutathera is indicated for the treatment of unresectable or metastatic, progressive, well differentiated 

(G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours 

(GEP-NETs) in adults. 

 

4.2 Posology and method of administration 

 

Lutathera should be administered only by persons authorised to handle radiopharmaceuticals in 

designated clinical settings (see section 6.6) and after evaluation of the patient by a qualified 

physician. 

 

Before starting treatment with Lutathera, somatostatin receptor imaging (scintigraphy or positron 

emission tomography [PET]) must confirm the overexpression of these receptors in the tumour tissue 

with the tumour uptake at least as high as normal liver uptake. 

 



 

3 

Posology 

Adults 

The recommended treatment regimen of Lutathera in adults consists of 4 infusions of 7,400 MBq 

each. The recommended interval between each administration is 8 weeks. 

 

Information on dose modifications to manage severe or intolerable adverse drug reactions is given in 

the respective section below. 

 

For renal protection purpose, an amino acid solution must be administered intravenously during 

4 hours. The infusion of the amino acid solution should start 30 minutes prior to start of Lutathera 

infusion. 

 

Amino acid solution 

The amino acid solution can be prepared as a compounded product, in compliance with the hospital’s 

sterile medicinal product preparation good practices and according to the composition specified in 

Table 1. 

 

Table 1. Composition of the compounded amino acid solution 

 

Compound Amount 

L-Lysine HCl  25 g* 

L-Arginine HCl 25 g** 

Sodium chloride 9 mg/mL (0.9%) solution for injection, or 

water for injections 

1 L 

*equivalent to 20.0 g lysine 

** equivalent to 20.7 g arginine 

 

Alternatively, some commercially available amino acid solutions can be used if compliant with the 

specification described in Table 2. 

 

Table 2. Specification of commercially available amino acid solutions 

 

Characteristic Specification 

L-Lysine HCl content Between 18 and 25 g* 

L-Arginine HCl content Between 18 and 25 g** 

Volume 1 L to 2 L 

Osmolality < 1,200 mOsmol/kg 

*equivalent to 14.4-20 g lysine 

**equivalent to 14.9-20.7 g arginine 

 

An amino acid solution containing just lysine and arginine in the amounts specified in Table 1 is 

considered the medicinal product of choice, due to its lower total volume to be infused and lower 

osmolality. 

 

Treatment monitoring 

Before each administration and during the treatment, biological tests are required to re-assess the 

patient’s condition and adapt the therapeutic protocol if necessary (dose, infusion interval, number of 

infusions). 

The minimum laboratory tests needed before each infusion are: 

 Haematology (Haemoglobin [Hb], white blood cell count, platelet count) 

 Kidney function (serum creatinine and creatinine clearance) 

 Liver function (alanine aminotransferase [ALAT], aspartate aminotransferase [ASAT], albumin, 

bilirubin) 

 



 

4 

These tests should be performed at least once within 2 to 4 weeks prior to administration, and shortly 

before the administration. It is also recommended to perform these tests every 4 weeks for at least 

3 months after the last infusion of Lutathera and every 6 months thereafter, in order to be able to detect 

possible delayed adverse reactions (see section 4.8). Dosing may need to be modified based on the test 

results. 

 

Dose modification 

Management of severe or intolerable adverse drug reactions may require temporary dose interruption, 

extending dosing interval from 8 weeks up to 16 weeks, dose reduction, or discontinuation of 

treatment with Lutathera (see Table 3 and Figure 1). 

 

Table 3. Recommended dose modifications of Lutathera for Adverse Drug Reactions 

 

Adverse Drug 

Reaction 

Severity of Adverse Drug 

Reaction 

Dose Modification 

Thrombocytopenia 

Grade 2 (Platelets < 75 - 50 x 

109/L) 1 

Grade 3 (Platelets < 50 - 25 x 

109/L) 

Grade 4 (Platelets < 25 x 109/L) 

Withhold dose until complete or partial 

resolution (Grade 0 to 1). 

 

Resume Lutathera at 3,700 MBq (100 mCi) in 

patients with complete or partial resolution. If 

reduced dose does not result in Grade 2, 3 or 

4 thrombocytopenia, administer Lutathera at 

7,400 MBq (200 mCi) for next dose. 

 

Permanently discontinue Lutathera for 

Grade 2 or higher thrombocytopenia requiring 

a treatment delay of 16 weeks or longer. 

Recurrent Grade 2, 3 or 4 Permanently discontinue Lutathera. 

Anemia and 

neutropenia 

Grade 3 (Hb < 8.0 g/dL) 1; 

transfusion indicated 

 

Grade 4 (life threatening 

consequences) 

 

Grade 3 (Absolute Neutrophil 

Count (ANC) < 1.0 - 0.5 x 109/L) 

 

Grade 4 (ANC < 0.5 x 109/L) 

Withhold dose until complete or partial 

resolution (Grade 0, 1, or 2). 

 

Resume Lutathera at 3,700 MBq (100 mCi) in 

patients with complete or partial resolution. If 

reduced dose does not result in Grade 3 or 4 

anemia or neutropenia, administer Lutathera 

at 7,400 MBq (200 mCi) for next dose. 

 

Permanently discontinue Lutathera for 

Grade 3 or higher anemia or neutropenia 

requiring a treatment delay of 16 weeks or 

longer. 

Recurrent Grade 3 or 4 Permanently discontinue Lutathera. 

Renal toxicity1 

Defined as: 

• Creatinine clearance less than 

40 mL/min 1; calculate using 

Cockcroft Gault with actual body 

weight, or 

 

• 40% increase in baseline 

serum creatinine, or 

 

• 40% decrease in baseline 

creatinine clearance; calculate 

using Cockcroft Gault with 

actual body weight. 

Withhold dose until complete resolution or 

return to baseline. 

 

Resume Lutathera at 3,700 MBq (100 mCi) in 

patients with complete resolution or return to 

baseline. If reduced dose does not result in 

renal toxicity, administer Lutathera at 

7,400 MBq (200 mCi) for next dose. 

 

Permanently discontinue Lutathera for renal 

toxicity requiring a treatment delay of 

16 weeks or longer. 

Recurrent renal toxicity Permanently discontinue Lutathera. 



 

5 

Adverse Drug 

Reaction 

Severity of Adverse Drug 

Reaction 

Dose Modification 

Hepatotoxicity 

Defined as: 

• Bilirubinaemia greater than 

3 times the upper limit of normal 

(Grade 3 or 4)2, or 

• Hypoalbuminaemia2 less than 

30 g/L with a decreased 

prothrombin ratio less than 70% 

Withhold dose until complete resolution or 

return to baseline. 

 

Resume Lutathera at 3,700 MBq (100 mCi) in 

patients with complete resolution or return to 

baseline. If reduced Lutathera dose does not 

result in hepatotoxicity, administer Lutathera 

at 7,400 MBq (200 mCi) for next dose. 

 

Permanently discontinue Lutathera for 

hepatotoxicity; requiring a treatment delay of 

16 weeks or longer. 

Recurrent hepatotoxicity. Permanently discontinue Lutathera. 

Any other CTCAE* 

grade 3 or grade 4 

toxicity possibly 

related to Lutathera 

Grade 3 or 4 

Withhold dose until complete or partial 

resolution (Grade 0 to 2). 

 

Resume Lutathera at 3,700 MBq (100 mCi) in 

patients with complete or partial resolution. If 

reduced dose does not result in Grade 3 or 4 

toxicity, administer Lutathera at 7,400 MBq 

(200 mCi) for next dose. 

 

Permanently discontinue Lutathera for 

Grade 3 or higher toxicity requiring treatment 

delay of 16 weeks or longer. 

Recurrent Grade 3 or 4 Permanently discontinue Lutathera. 

1 The same thresholds are also applicable to baseline values at the time of treatment initiation (see 

section 4.4). 
2 If same thresholds are seen at baseline treatment initiation to be considered after benefit risk assessment 

(see section 4.4). 

* CTCAE: Common Terminology Criteria for Adverse Events, National Cancer Institute 

 

Figure 1. Scheme of instructions for dose modifications 

 

 
DMT: Dose modifying toxicity 

 

Other reasons to consider temporary dose interruption of Lutathera include occurrence of an 

intercurrent disease (e.g. urinary tract infection), which according to the physician could increase the 

risks associated to Lutathera administration, and which should be resolved or stabilized for treatment 

to resume; and major surgery, in which case treatment should be withheld for 12 weeks after the date 

of surgery. 

 



 

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Special populations 

Elderly 

No dosage adjustment is required in patients 65 years or above as clinical experience has not identified 

differences in responses between the elderly and younger patients. However, since increased risk of 

presenting haematotoxicity has been described in elderly patients (≥ 70 years old), a close follow up 

allowing for prompt dose adaptation (DMT) in this population is advisable. 

 

Renal impairment 

Careful consideration of the activity to be administered is required since an increased radiation 

exposure is possible in these patients. The pharmacokinetic profile and safety of lutetium (177Lu) 

oxodotreotide in patients with severe renal impairment or end-stage renal disease has not been studied. 

Treatment with Lutathera in patients with severe kidney failure with creatinine clearance < 30 mL/min 

is contraindicated (see section 4.3). Treatment with Lutathera in patients with creatinine clearance 

< 40 mL/min at baseline (using Cockcroft Gault) is not recommended. No dose adjustment is 

recommended for renally impaired patients with creatinine clearance ≥ 40 mL/min. However, as this 

medicinal product is known to be substantially excreted by the kidneys, renal function should be more 

frequently monitored during the treatment as these patients may be at a greater risk of toxicity. 

For additional details about the treatment of patient with renal impairment see Table 3 in section 4.2 

and section 4.4. 

 

Hepatic impairment 

No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Careful 

consideration of the activity to be administered to patients with hepatic impairment is required since 

an increased radiation exposure is possible in these patients. The pharmacokinetic profile of lutetium 

(177Lu) oxodotreotide in patients with severe hepatic impairment has not been studied (total bilirubin 

> 3 times upper limit of normal and any ASAT), therefore those patients should only be treated with 

Lutathera after careful benefit-risk assessment. 

For additional details about the treatment of patient with mild to moderate hepatic impairment, see 

Table 3 and section 4.4. 

 

Paediatric population 

There is no relevant use of Lutathera in the paediatric population in the indication of treatment of 

GEP-NETs (excluding neuroblastoma, neuroganglioblastoma, phaeochromocytoma). 

 

Method of administration 

Lutathera is for intravenous use. It is a ready to use radiopharmaceutical medicinal product for single 

use only. 

 

Lutathera must be administered by slow intravenous infusion over approximately 30 minutes, 

concomitantly with amino acid solution administered by contralateral intravenous infusion. This 

medicinal product must not be injected as a bolus. 

Premedication with antiemetics should be injected at least 30 minutes prior to the start of amino acid 

solution infusion to reach the full antiemetic efficacy of the selected product, according to the 

respective product information. 
 

The recommended infusion method for administration of Lutathera is the gravity method, described in 

more detail in this section. Treating physicians may use other methods deemed appropriate and safe, 

including the use of infusion pumps, particularly when dose reduction is required. During the 

administration the recommended radiation safety precaution measures should be undertaken regardless 

of the infusion method (see section 6.6). 

 

Lutathera should be infused directly from its original container. The vial must not be opened or the 

solution transferred to another container. During the administration only disposable materials should 

be used. 

The medicinal product should be infused through an intravenous catheter placed in the vein 

exclusively for its infusion. 

 



 

7 

Requirements 

Storage of the vial 

 Either in a container made of polymethyl methacrylate (PMMA), a transparent radioprotection 

container that allows a direct visual inspection of the vial, 

 Or in the lead container in which Lutathera is delivered. 

 

Room and equipment preparation: 

 Administration room: 

 The floor and the furniture should be covered with tissue paper to avoid any accidental 

contamination 

 

 Medicinal products to be administered: 

 One vial of Lutathera 

 One bag of sodium chloride 9 mg/mL (0.9%) solution for injection (500 mL) 

 Amino acid solution bag(s) 

 Antiemetics 

 

 Care supplies and equipment: 

 Two infusion poles 

 One Long needle (recommended 90 – 100 mm, 18 gauge) 

 One Short needle (recommended 25 mm, 20 gauge) 

 Two gravity intravenous infusion sets with a clamp to regulate or stop the flow (one for 

Lutathera, one for amino acid solution administration) 

 Two peripheral intravenous plastic catheters 

 One sterile tubing line with a clamp to regulate or stop the flow 

 A pair of tongs (for Lutathera vial handling) 

 Calibrated radioactivity measurement system and Geiger counter to monitor the 

radioactivity of Lutathera 

 

  



 

8 

Lutathera vial tubing connections procedure (see Figure 2): 

 The tubing line should be pre-filled with sodium chloride 9 mg/mL (0.9%) solution for injection 

and then connected with a venous catheter previously inserted to the patient’s arm. 

 The infusion set should be connected to the bag of sodium chloride 9 mg/mL (0.9%) solution 

for injection and pre-filled by opening the clamp. 

 The short needle should be inserted into the Lutathera vial, so that it does not touch the 

radiopharmaceutical solution. This will equilibrate pressure thus reducing any risk of leakage. 

 The short needle should be then connected to the pre-filled infusion set. 

 The long needle should be connected to the pre-filled tubing line and then inserted into the 

Lutathera vial, so that it touches the bottom of the vial. This will allow for the complete 

extraction of the radiopharmaceutical solution. 

 The flow of the radiopharmaceutical solution should be regulated with the clamps. 

 

Figure 2. Gravity infusion method - tubing connection scheme 

 

  
 

  



 

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Administration procedure (gravity method) 

During the infusion, the flow of sodium chloride 9 mg/mL (0.9%) solution for injection increases the 

pressure in the Lutathera vial, facilitating the flow of Lutathera into the catheter inserted in the 

patient’s peripheral vein. 

Careful monitoring of the vital signs during the infusion is recommended. 

 

1. Two intravenous plastic catheters should be inserted into patient’s peripheral veins, one on each 

arm. 

2. The catheters should be connected to the infusion sets (one for Lutathera, one for amino acid 

solution). 

3. Antiemetic premedication should be administered at least 30 minutes prior to the start of amino 

acid solution infusion (see section 4.2). 

4. Administration of the amino acid solution should be initiated 30 minutes before Lutathera 

infusion, with an infusion rate of 250 to 500 mL/h (depending on volume). Amino acid solution 

should be administered over 4 hour time span. In case of severe nausea or vomiting during 

amino acid solution infusion, an antiemetic of a different pharmacological class can be 

administered. 

5. Radioactivity in the Lutathera vial should be measured immediately before infusion using a 

calibrated radioactivity measurement system. 

6. Lutathera infusion should start 30 minutes after the beginning of the amino acid solution 

infusion, with the infusion rate of approximately 400 mL/h (this infusion rate is the reference 

rate; the infusion should start at a lower rate of < 100mL/h for the first 5 to 10 minutes and 

should then be increased depending on the patient’s venous status). Lutathera should be 

administered over 30 ± 10 minute time span. Constant intra-vial pressure should be maintained 

during the entire infusion. 

7. Lutathera administration should be initiated by opening first the tubing line connected to the 

patient’s peripheral vein, and then, by opening the infusion set connected to the bag of sodium 

chloride 9 mg/mL (0.9%) solution for injection. The pole height should be adjusted in order to 

compensate any increase or reduction of pressure inside the vial. Moving the patient’s arm 

position should be avoided if possible (extreme flexion or extension which could lead to vein 

compression). 

8. The flow of Lutathera from the vial to the patient should be monitored during the entire 

infusion. Soon after the start of the infusion, the radioactivity emission over the patient’s thorax 

should be measured using Geiger counter to verify the presence of Lutathera in the bloodstream. 

Subsequent checks of the radioactivity emission should be performed approximately every 

5 minutes at the level of the patient’s thorax and vial. During the infusion, the radioactivity 

emission from the patient’s thorax should steadily increase while the one from the Lutathera 

vial should decrease. 

9. To ensure complete administration, the Lutathera vial should be kept under even pressure. The 

level of solution in the vial should remain constant during the entire infusion. 

Visual controls of the solution levels should be repeated during the administration by direct 

visual control (when PMMA container is used) or using a pair of tongs to handle the vial when 

the lead shipping container is used. 

10. The infusion should be stopped once the radioactivity emission from the vial becomes stable for 

several minutes (or during two consecutive measurements). This is the only parameter to 

determine the procedure completion. The volume of sodium chloride 9 mg/mL (0.9%) solution 

for injection necessary to complete the infusion may vary. 

11. Total activity administered is equal to the activity in the vial before infusion minus the activity 

remaining in the vial after the infusion. The measurements should be performed using a 

calibrated system. 

 



 

10 

The following table summarises the required procedures during a treatment course with Lutathera 

using the gravity method: 

 

Table 4. Administration procedure of antiemetic, amino acid solution and Lutathera 

 

Administered agents Start time 

(min) 

Infusion rate 

(mL/h) 

Duration 

Antiemetic at least 

30 minutes prior 

to amino acid 

solution 

as per prescribing 

information 

as per 

prescribing 

information 

Amino acid solution, either 

extemporaneously compounded 

(1 L) or commercial (1 L to 2 L) 

0 
250 – 500 depending 

on volume 
4 hours 

Lutathera with sodium chloride 

9 mg/mL (0.9%) solution for 

injection 

30 Up to 400 30 ± 10 minutes 

 

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

For patient preparation, see section 4.4. 

For recommendations in case of extravasation, see section 4.4. 

 

4.3 Contraindications 
 

 Hypersensitivity to the active substance, to any of the excipients listed in section 6.1. 

 Established or suspected pregnancy or when pregnancy has not been excluded (see section 4.6). 

 Kidney failure with creatinine clearance < 30 mL/min 

 

4.4 Special warnings and precautions for use 

 

Individual benefit/risk justification 

For each patient, the radiation exposure must be justifiable by the likely benefit. The activity 

administered should in every case be as low as reasonably achievable to obtain the required 

therapeutic effect. 

Given the mechanism of action and the tolerance profile of Lutathera, it is not recommended to start 

treatment with Lutathera in patients with somatostatin receptor negative or mixed visceral lesions 

according to somatostatin receptor imaging. 

 

Myelosuppression 

Because of the potential for undesirable effects, blood counts must be monitored at baseline and 

during treatment and until resolution of any eventual toxicity (see section 4.2). Patients with impaired 

haematological function and patients who have received prior chemotherapy or external beam 

radiotherapy (involving more than 25% of the bone marrow) may be at higher risk of haematological 

toxicity during Lutathera treatment. Treatment initiation is not recommended in patients with severely 

impaired haematological function at baseline (e.g. Hb < 4.9 mmol/L or 8 g/dL, platelets < 75 g/L or 

75 x 103/mm3, or leukocytes < 2 g/L or 2000/mm3) (except lymphopenia). 

 

Myelodisplastic syndrome and acute leukaemia 

Late-onset myelodisplastic syndrome (MDS) and acute leukaemia (AL) have been observed after 

treatment with Lutathera (see section 4.8), occurring approximately 28 months (9 – 41) for MDS and 

55 months (32 - 125) for AL after the end of treatment. Etiology of this therapy related secondary 

myeloid neoplasms (t-MNs) is unclear. Factors such as age > 70 years, impaired renal function, 

baseline cytopenias, prior number of therapies, prior exposure to chemotherapeutic agents (specifically 

alkylating agents), and prior radiotherapy are suggested as potential risks and/or predictive factors for 

MDS/AL. 



 

11 

 

Renal toxicity 

Because lutetium (177Lu) oxodotreotide is almost exclusively eliminated through the renal system, it is 

mandatory to concomitantly administer an amino acid solution containing the amino acids L-lysine 

and L-arginine. The amino acids solution will help to decrease reabsorption of lutetium (177Lu) 

oxodotreotide through the proximal tubules, resulting in a significant reduction in the kidney radiation 

dose (see section 4.2). When the recommended concomitant amino acids infusion is delivered over a 

4 hour time span, a mean reduction in kidney radiation exposure of about 47% has been reported. 

It is not recommended to decrease the amount of amino acid solution in case of Lutathera dose 

adaptation. 

Patients should be encouraged to empty their bladder as frequently as possible during the 

administration of amino acids and the hours after administration. 

Renal function as determined by serum creatinine and calculated creatinine clearance must be assessed 

at baseline, during and at least for the first year after treatment (see section 4.2). 

Patients with renal impairment at baseline, or with renal or urinary tract morphological abnormalities 

may be at greater risk of toxicity. Treatment with Lutathera in patients with creatinine clearance 

< 40 mL/min (using Cockcroft Gault) at baseline is not recommended. More frequent monitoring of 

renal function is recommended in renally impaired patients with creatinine clearance > 40 mL/min 

(see section 4.2). 

For patients with creatinine clearance < 50 mL/min, an increased risk for transient hyperkalemia due 

to the amino acid solution should also be taken into consideration (see Warning and precaution 

regarding the co-administered renal protective amino acid solution). 

 

Hepatic toxicity 

Since many patients referred for Lutathera therapy have hepatic metastasis, it may be common to 

observe patients with altered baseline liver function. Patients with hepatic metastasis or pre-existing 

advanced hepatic impairment may be at increased risk of hepatotoxicity due to radiation exposure. 

Therefore, it is recommended to monitor ALAT, ASAT, bilirubin and albumin serum during treatment 

(see section 4.2). 

Patients with baseline liver impairment with either total bilirubinemia > 3 times the upper limit of 

normal or albuminemia < 30 g/L and prothrombin ratio decreased < 70%, should only be treated with 

Lutathera after careful benefit-risk assessment (see section 4.2). 

 

Nausea and vomiting 

To avoid treatment-related nausea and vomiting, an intravenous bolus of an antiemetic medicinal 

product should be injected at least 30 minutes prior to the start of amino acid solution infusion to reach 

the full antiemetic efficacy (see section 4.2). 

 

Concomitant use of somatostatin analogues 

Somatostatin and its analogues competitively bind to somatostatin receptors and may interfere with the 

efficacy of Lutathera (see section 4.5). 

 

Neuroendocrine hormonal crises 

Crises due to excessive release of hormones or bioactive substances may occur following treatment 

with Lutathera, therefore observation of patients by overnight hospitalisation should be considered in 

some cases (e.g. patients with poor pharmacologic control of symptoms). In case of hormonal crises, 

recommended treatments are: intravenous high dose somatostatin analogues, intravenous fluids, 

corticosteroids, and correction of electrolyte disturbances in patients with diarrhoea and/or vomiting. 

 

Tumour lysis syndrome 

Tumour lysis syndrome has been reported following therapy with medicines containing lutetium 

(177Lu). Patients with a history of renal insufficiency and high tumour burden may be at greater risk 

and should be treated with increased caution. Renal function as well as electrolyte balance should be 

assessed at baseline and during treatment. 

 



 

12 

Radioprotection rules 

Lutathera should always be infused through an intravenous catheter placed exclusively for its infusion. 

The adequate position of the catheter should be checked before and during infusion. 

 

The patient treated with Lutathera should be kept away from others during the administration and up 

to reaching the radiation emission limits stipulated by applicable laws, usually within the 4-5 hours 

following medicinal product administration. The nuclear medicine physician should determine when 

the patient can leave the controlled area of the hospital, i.e. when the radiation exposure to third parties 

does not exceed regulatory thresholds. 

 

The patient should be encouraged to urinate as much as possible after Lutathera administration. 

Patients should be instructed to drink substantial quantities of water (1 glass every hour) on the day of 

infusion and the day after to facilitate elimination. The patient should also be encouraged to defecate 

every day and to use laxative if needed. Urine and faeces should be disposed according to the national 

regulations. 

 

As long as the patient’s skin is not contaminated, such as from the leakage of the infusion system or 

because of urinary incontinence, radioactivity contamination is not expected on the skin and in the 

vomited mass. However, it is recommended that when conducting standard care or exams with 

medical devices or other instruments which contact the skin (e.g. electrocardiogram (ECG)), basic 

protection measures should be observed such as wearing gloves, installing the material/electrode 

before the start of radiopharmaceutical infusion, changing the material/electrode after measurement, 

and eventually monitoring the radioactivity of equipment after use. 

 

Before the patient is released, the nuclear physician should explain the necessary radioprotection rules 

of interacting with family members and third parties, and the general precautions the patient must 

follow during daily activities after treatment (as given in next paragraph and the package leaflet) to 

minimize radiation exposure to others. 

Close contact (less than 1 meter) with other people should be limited for 7 days following an 

administration of Lutathera. For children and/or pregnant women, close contact (less than 1 meter) 

should be limited to less than 15 minutes per day for 7 days. Patients should sleep in a separate 

bedroom from other people for 7 days following an administration of Lutathera. Patients should sleep 

in separate bedrooms from children and/or pregnant women for 15 days. 

 

Recommended measures in case of extravasation 

Disposable waterproof gloves should be worn. The infusion of the medicinal product must be 

immediately ceased and the administration device (catheter, etc.) removed. The nuclear medicine 

physician and the radiopharmacist should be informed. 

All the administration device materials should be kept in order to measure the residual radioactivity 

and the activity actually administered and eventually the absorbed dose should be determined. The 

extravasation area should be delimited with an indelible pen and a picture should be taken if possible. 

It is also recommended to record the time of extravasation and the estimated volume extravasated. 

To continue Lutathera infusion, it is mandatory to use a new catheter possibly placing it in a 

contralateral venous access. 

 

No additional medicinal product can be administered to the same side where the extravasation 

occurred. 

In order to accelerate medicinal product dispersion and to prevent its stagnation in tissue, it is 

recommended to increase blood flow by elevating the affected arm. Depending on the case, aspiration 

of extravasation fluid, sodium chloride 9 mg/mL (0.9%) solution for injection flush injection, or 

applying warm compresses or a heating pad to the infusion site to accelerate vasodilation should be 

considered. 

 



 

13 

Symptoms, especially inflammation and/or pain, should be treated. Depending on the situation, the 

nuclear medicine physician should inform the patient about the risks linked to extravasation injury, 

and give advice about potential treatment and necessary follow-up requirements. The extravasation 

area must be monitored until the patient is discharged from the hospital. Depending upon its 

seriousness, this event should be declared as an adverse reaction. 

 

Patients with urinary incontinence 

During the first 2 days following administration of this medicinal product, special precautions should 

be taken with patients with urinary incontinence to avoid spread of radioactive contamination. This 

includes the handling of any materials possibly contaminated with urine. 

 

Patients with brain metastases 

There is no efficacy data in patients with known brain metastases therefore individual benefit-risk 

must be assessed in these patients. 

 

Secondary malignant neoplasms 

Exposure to ionising radiation is linked with cancer induction and a potential for development of 

hereditary defects. The radiation dose resulting from therapeutic exposure may result in higher 

incidence of cancer and mutations. In all cases it is necessary to ensure that the risks of the radiation 

exposure are less than from the disease itself. 

 

Other patients with risk factors 

A patient presenting with any of the conditions below is more prone to develop adverse reactions. 

Therefore, it is recommended to monitor those patients more frequently during the treatment. Please 

see Table 3 in case of dose modifying toxicity. 

 Bone metastasis; 

 Previous oncologic radiometabolic therapies with 131Icompounds or any other therapy using 

unshielded radioactive sources; 

 History of other malignant tumours unless the patient is considered to be in remission for at 

least 5 years. 

 

Specific warnings 

This medicinal product contains up to 3.5 mmol (81.1 mg) sodium per dose, equivalent to 4% of the 

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

 

Precautions with respect to environmental hazard see section 6.6. 

 

Specific warnings and precautions regarding the co-administered renal protective amino acid solution 

 

Hyperkalemia 

A transient increase in serum potassium levels may occur in patients receiving arginine and lysine, 

usually returning to normal levels within 24 hours from the start of the amino acid infusion. 

Serum potassium levels must be tested before each treatment with amino acid solutions. In case of 

hyperkalemia, patient’s history of hyperkalemia and concomitant medication should be checked. 

Hyperkalemia must be corrected accordingly before starting the infusion. 

In case of pre-existing clinically significant hyperkalemia, a second monitoring prior to amino acid 

infusion must confirm that hyperkalemia has been successfully corrected. The patient should be 

monitored closely for signs and symptoms of hyperkalemia, e.g. dyspnea, weakness, numbness, chest 

pain and cardiac manifestations (conduction abnormalities and cardiac arrhythmias). An 

electrocardiogram (ECG) should be performed prior to discharging the patient. 

Vital signs should be monitored during the infusion regardless of baseline serum potassium levels. 

Patients should be instructed to drink substantial quantities of water (at least 1 glass every hour) on the 

day of infusion to remain hydrated and facilitate excretion of excess serum potassium. 

In case hyperkalemia symptoms develop during amino acid infusion, appropriate corrective measures 

must be taken. In case of severe symptomatic hyperkalemia, discontinuation of amino acid solution 

infusion should be considered, taking into consideration the risk-benefit of renal protection versus 

acute hyperkalemia. 



 

14 

 

Heart failure 

Due to potential for clinical complications related to volume overload, care should be taken with use 

of arginine and lysine in patients with severe heart failure defined as class III or class IV in the NYHA 

classification (New York Heart Association). Patients with severe heart failure defined as class III or 

class IV in the NYHA classification should only be treated after careful benefit-risk assessment, taking 

into consideration volume and osmolality of the amino acid solution. 

 

Metabolic acidosis 

Metabolic acidosis has been observed with complex amino-acid solutions administered as part of total 

parenteral nutrition (TPN) protocols. Shifts in acid-base balance alter the balance of extracellular-

intracellular potassium and the development of acidosis may be associated with rapid increases in 

plasma potassium. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Somatostatin and its analogues competitively bind to somatostatin receptors and may interfere with the 

efficacy of Lutathera. Therefore, administration of long acting somatostatin analogues should be 

avoided within 30 days prior to the administration of this medicinal product. If necessary, patients may 

be treated with short acting somatostatin analogues until at least 24 hours preceding Lutathera 

administration. 

 

There is some evidence that corticosteroids can induce down-regulation of SST2 receptors. Therefore, 

as a matter of cautiousness, repeated administration of high-doses of glucocorticosteroids should be 

avoided during Lutathera treatment. Patients with a history of chronic use of glucocorticosteroids 

should be carefully evaluated for sufficient somatostatin receptor expression. It is not known if there is 

of interaction between glucocorticosteroids used intermittently for the prevention of nausea and 

vomiting during Lutathera administration. Therefore, glucocorticosteroids should be avoided as 

preventive anti-emetic treatment. In the case where the treatments previously provided for nausea and 

vomiting are insufficient, a single dose of corticosteroids can be used, as long as it is not given before 

initiating or within one hour after the end of Lutathera infusion. 

 

The absence of inhibition or significant induction of the human CYP450 enzymes, the absence of 

specific interaction with P-glycoprotein (efflux transporter) as well as OAT1, OAT3, OCT1, OCT2, 

OATP1B1, OATP1B3 and BCRP transporters in pre-clinical studies suggest that Lutathera has a low 

probability of causing significant other drug-drug interactions. 

 

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 any doubt about her potential pregnancy (if the 

woman has missed a period, if the period is very irregular, etc.), alternative techniques not using 

ionising radiation (if there are any) should be offered to the patient. Before the use of Lutathera, 

pregnancy should be excluded using an adequate/validated test. 

 

Contraception in males and females 

Lutathera can cause fetal harm when administered to a pregnant woman. During treatment with 

Lutathera and for a minimum of the following 6 months after the end of the treatment, appropriate 

measures must be taken to avoid pregnancy; this applies to patients of both genders. 

 

  



 

15 

Pregnancy 

No studies on animal reproductive function have been conducted with lutetium (177Lu) oxodotreotide. 

Radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus. The 

use of Lutathera is contraindicated during established or suspected pregnancy or when pregnancy has 

not been excluded due to the risk associated with the ionizing radiation (see section 4.3). Pregnant 

women should be advised of the risk to a foetus. 

 

Breast-feeding 

It is unknown whether lutetium (177Lu) oxodotreotide is excreted in breast milk. A risk to the suckling 

child associated with ionising radiation cannot be excluded. Breast-feeding should be avoided during 

treatment with this medicinal product. If treatment with Lutathera during breast-feeding is necessary, 

the child must be weaned. 

 

Fertility 

No animal studies have been performed to determine the effects of lutetium (177Lu) oxodotreotide on 

the fertility of either gender. Ionizing radiations of lutetium (177Lu) oxodotreotide may potentially have 

temporary toxic effects on female and male gonads. Genetic consultation is recommended if the 

patient wishes to have children after treatment. Cryopreservation of sperm or eggs can be discussed as 

an option to patients before the treatment. 

 

4.7 Effects on ability to drive and use machines 
 

Lutathera has no or negligible influence on the ability to drive and use machines. Nevertheless, the 

general condition of the patient and the possible adverse reactions to treatment must be taken into 

account before driving or using machines. 

 

4.8 Undesirable effects 

 

Summary of safety profile 

The overall safety profile of Lutathera is based on pooled data from patients from clinical trials 

(NETTER-1 phase III and Erasmus phase I/II Dutch patients) and from compassionate use programs. 

 

The most common adverse reactions in patients receiving Lutathera treatment were nausea and 

vomiting which occurred at the beginning of the infusion in 58.9% and 45.5% of patients, 

respectively. The causality of nausea / vomiting is confounded by the emetic effect of the concomitant 

amino acids infusion administered for renal protection. 

 

Due to the bone marrow toxicity of Lutathera, the most expected adverse reactions were related to 

haematological toxicity: thrombocytopenia (25%), lymphopenia (22.3%), anaemia (13.4%), 

pancytopenia (10.2%). 

 

Other very common adverse reactions reported include fatigue (27.7%) and decreased appetite 

(13.4%). 

 

Tabulated list of adverse reactions 

The adverse reactions are listed in Table 5 according to the frequency and the MedDRA System Organ 

Class (SOC). The frequencies are categorized as follows: very common (≥1/10), common (≥1/100 to 

<1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not 

known (cannot be estimated from the available data). 

 



 

16 

Table 5. Frequency of adverse reactions reported from clinical trials and from post-marketing 

surveillance 

 
MedDRA System Organ 

Class (SOC) 

Very common Common Uncommon 

Infections and infestations   Conjunctivitis 

Respiratory tract infection 

Cystitis 

Pneumonia 

Herpes zoster 

Ophthalmic herpes zoster 

Influenza 

Staphylococcal infections 

Streptococcal bacteraemia 

Neoplasms benign, 

malignant and unspecified 

(including cysts and 

polyps) 

 Refractory cytopenia with 

multilineage dysplasia 

(Myelodysplastic 

syndrome) 

Acute myeloid leukaemia 

Acute leukaemia 

Chronic myelomonocytic 

leukaemia 

Blood and lymphatic 

system disorders  

Thrombocytopenia2 

Lymphopenia3 

Anaemia4 

Pancytopenia 

Leukopenia5 

Neutropenia6 

Refractory cytopenia with 

unilineage dysplasia 

Nephrogenic anaemia 

Bone marrow failure 

Thrombocytopenic purpura 

Immune system disorders   Hypersensitivity 

Endocrine disorders  Secondary hypothyroidism Hypothyroidism 

Diabetes mellitus 

Carcinoid crisis 

Hyperparathyroidism 

Metabolism and nutrition 

disorders 

Decreased appetite Hyperglycaemia 

Dehydration 

Hypomagnesaemia 

Hyponatremia 

Hypoglycaemia 

Hypernatremia 

Hypophosphatemia 

Tumor lysis syndrome 

Hypercalcaemia 

Hypocalcaemia 

Hypoalbuminaemia 

Metabolic acidosis 

Psychiatric disorders  Sleep disorders Anxiety 

Hallucination 

Disorientation 

Nervous system disorders  Dizziness 

Dysgeusia 

Headache10 

Lethargy 

Syncope 

Formication 

Hepatic encephalopathy 

Paraesthesia 

Parosmia 

Somnolence 

Spinal cord compression 

Eye disorders   Eye disorders 

Ear and labyrinth 

disorders 

  Vertigo 

Cardiac disorders  Electrocardiogram QT 

prolonged 

Atrial fibrillation 

Palpitations 

Myocardial infarction 

Angina pectoris 

Cardiogenic shock 

Vascular disorders  Hypertension7 

Flushing 

Hot flush 

Hypotension 

Vasodilatation 

Peripheral coldness 

Pallor 

Orthostatic hypotension 

Phlebitis 

Respiratory, thoracic and 

mediastinal disorders 

 Dyspnoea Oropharyngeal pain 

Pleural effusion 

Sputum increased 

Choking sensation 



 

17 

MedDRA System Organ 

Class (SOC) 

Very common Common Uncommon 

Gastrointestinal disorders Nausea 

Vomiting 

Abdominal distension  

Diarrhoea 

Abdominal pain 

Constipation 

Abdominal pain upper 

Dyspepsia 

Gastritis 

Dry mouth 

Flatulence 

Ascities 

Gastrointestinal pain 

Stomatitis 

Haematochezia 

Abdominal discomfort 

Intestinal obstruction 

Colitis 

Pancreatitis acute 

Rectal haemorrhage 

Melaena 

Abdominal pain lower 

Haematemesis 

Haemorrhagic ascites 

Ileus 

Hepatobiliary disorders  Hyperbilirubinaemia9 Pancreatic enzymes decreased 

Hepatocellular injury 

Cholestasis 

Hepatic congestion 

Hepatic failure 

Skin and subcutaneous 

tissue disorders 

 Alopecia Rash 

Dry skin 

Swelling face 

Hyperhidrosis 

Pruritus generalized 

Musculoskeletal and 

connective tissue disorders 

 Musculoskeletal pain8 

Muscle spasms 

 

Renal and urinary 

disorders 

 Acute kidney injury 

Haematuria 

Renal failure 

Proteinuria 

Leukocyturia 

Urinary incontinence 

Glomerular filtration rate decreased 

Renal disorder 

Acute prerenal failure 

Renal impairment 

General disorders and 

administration site 

conditions 

Fatigue1 Injection site reaction11 

Oedema peripheral 

Administration site pain 

Chills 

Influenza like illness 

Injection site mass 

Chest discomfort 

Chest pain 

Pyrexia 

Malaise 

Pain 

Deaths 

Feeling abnormal 

Investigations  Blood creatinine increased 

GGT* increased 

ALAT** increased 

ASAT*** increased 

Blood ALP**** increased 

Blood potassium decreased 

Blood urea increased 

Glycosylated haemoglobin 

increased 

Haematocrit decreased 

Protein urine 

Weight decreased 

Blood creatine phosphokinase 

increased 

Blood lactate dehydrogenase 

increased 

Blood catecholamines 

c-reactive protein increased 

Injury, poisoning and 

procedural complications 

  Clavicle fracture 



 

18 

MedDRA System Organ 

Class (SOC) 

Very common Common Uncommon 

Surgical and medical 

procedures 

 Transfusion Abdominal cavity drainage 

Dialysis 

Gastrointestinal tube insertion 

Stent placement 

Abscess drainage 

Bone marrow harvest 

Polypectomy 

Social circumstances   Physical disability 
1 Includes Asthenia and Fatigue 
2 Includes Thrombocytopenia and Platelet count decreased 
3 Includes Lymphopenia and Lymphocyte count decreased 
4 Includes Anaemia and Haemoglobin decreased 
5 Includes Leukopenia and White blood cell count decreased 
6 Includes Neutropenia and Neutrophil count decreased 
7 Includes Hypertension and Hypertensive crisis 
8 Includes Arthralgia, Pain in extremity, Back pain, Bone pain, Flank pain, Musculoskeletal chest pain and Neck 

pain 
9 Includes Blood bilirubin increased and Hyperbilirubinaemia 
10 Includes Headache and migraine  
11 Includes injection site reaction, injection site hypersensibility, injection site induration, injection site swelling 

* Gamma-glutamyltransferase 

**Alanine amino transferase 

*** Aspartate amino transferase 

**** Alkaline phosphatase 

 

Description of selected adverse reactions 

Bone marrow toxicity 

Bone marrow toxicity (myelo-/hematotoxicity) manifested with reversible / transient reductions in 

blood counts affecting all lineages (cytopenias in all combinations, i.e., pancytopenia, bicytopenias, 

isolated monocytopenias – anemia, neutropenia, lymphocytopenia, and thrombocytopenia). In spite of 

an observed significant selective B-cell depletion, no increase in the rate of infectious complications 

occurs after PRRT. Cases of irreversible hematological pathologies, i.e., premalignant and malignant 

blood neoplasms (i.e., myelodysplastic syndrome and acute myeloid leukemia, respectively) have been 

reported following Lutathera treatment. 

 

Nephrotoxicity 

Lutetium (177Lu) oxodotreotide is excreted by the kidney. 

The long-term trend of progressive glomerular filtration function deterioration demonstrated in the 

clinical studies confirms that Lutathera-related nephropathy is a chronic kidney disease that develops 

progressively over months or years after exposure. An individual benefit-risk assessment is 

recommended prior to treatment with Lutathera in patients with mild and moderate renal impairment, 

for additional details see section 4.2 (Table 3) and section 4.4. The use of Lutathera is contraindicated 

in patients with severe kidney failure (see section 4.3). 

 

Hormonal crises 

Hormonal crises related to bioactive substances release (probably due to lysis of the neuroendocrine 

tumour cells) have rarely been observed and resolved after appropriate medical treatment (section 4.4). 

 

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


 

19 

4.9 Overdose 
 

Overdose is unlikely with Lutathera as this medicinal product is supplied as a “single dose” and “ready 

to use” product containing a predefined amount of radioactivity. In the case of overdose, an increase in 

the frequency of the adverse reactions related to radiotoxicity is expected. 

 

In the event of administration of a radiation overdose with Lutathera, the absorbed dose to the patient 

should be reduced where possible by increasing the elimination of the radionuclide from the body by 

frequent micturition or by forced diuresis and frequent bladder voiding during the first 48 hours after 

infusion. It is helpful to estimate the effective dose that was applied. 

 

The following checking should be carried out every week, for the next 10 weeks: 

 Hematologic monitoring: white blood cells, platelets, and haemoglobin 

 Blood chemistry monitoring: serum creatinine and glycaemia. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Other therapeutic radiopharmaceuticals, ATC code: V10XX04 

 

Mechanism of action 

Lutetium (177Lu) oxodotreotide has a high affinity for subtype 2 somatostatin receptors (sst2). It binds 

to malignant cells which overexpress sst2 receptors. 

Lutetium-177 (177Lu) is a β- emitting radionuclide with a maximum penetration range in tissue of 

2.2 mm (mean penetration range of 0.67 mm), which is sufficient to kill targeted tumour cells with a 

limited effect on neighbouring normal cells. 

 

Pharmacodynamic effects 

At the concentration used (about 10 μg/mL in total, for both free and radiolabeled forms), the peptide 

oxodotreotide does not exert any clinically relevant pharmacodynamic effect. 

 

Clinical efficacy and safety 

NETTER-1 phase III study was a multicentre stratified, open labelled, randomized, 

comparator-controlled, parallel-group study comparing treatment with Lutathera (4 doses of 

7,400 MBq every 8 weeks) co-administered with amino acid solution plus best supportive care (BSC; 

octreotide long acting release [LAR] 30 mg every 4 weeks for symptoms control, replaced by short 

acting octreotide in the 4 weeks interval before Lutathera administration) to high dose octreotide LAR 

(60 mg every 4 weeks) in patients with inoperable, progressive, somatostatin receptor positive, midgut 

carcinoid tumours. The primary endpoint for the study was progression-free survival (PFS) evaluated 

by response evaluation criteria in solid tumours (RECIST 1.1), based on independent radiology 

assessment. Secondary endpoints included objective response rate (ORR), overall survival (OS), time 

to tumour progression (TTP), safety and tolerability of the medicinal product and quality of life (QoL). 

Two hundred twenty-nine (229) patients have been randomized to receive either Lutathera (n=116) or 

high dose 60 mg octreotide LAR (n=113). Demographics as well as patients and disease 

characteristics were well balanced between groups with a median age of 64 years and 82.1% 

Caucasian in the general population. 

 

At the time of final per-protocol PFS statistical analysis (cut–off date 24 July 2015), the number of 

centrally confirmed disease progressions or deaths was 21 events in the Lutathera arm and 70 events in 

the octreotide LAR arm (Table 6). PFS differed significantly (p<0.0001) between the treatment 

groups. The median PFS for Lutathera was not reached at the time of analysis whereas the one of 

octreotide LAR was 8.5 months. The hazard ratio for Lutathera was 0.18 (95% CI: 0.11 - 0.29), 

indicating 82% reduction in the risk for a patient to progress or die under Lutathera compared to 

octreotide LAR. 

 



 

20 

Table 6. PFS observed in the NETTER-1 phase III study in patients with progressive midgut 

carcinoid tumour – cut–off date 24 July 2015 (full analyses set (FAS), N=229) 

 

 Treatment 

 Lutathera Octreotide LAR 

N 116 113 

Patients with events 21 70 

Censored patients 95 43 

Median months (95%-CI) Not reached 8.5 (5.8 ; 9.1) 

p-value of Log-rank test <0.0001 

Hazard ratio (95%-CI) 0.177 (0.108 ; 0.289) 
N: number of patients, CI: confidence interval. 

 

The PFS Kaplan-Meier graph for the full analysis set (FAS) at the cut–off date 24 July 2015 is 

depicted in Figure 3. 

 

Figure 3. PFS Kaplan Meier curves of patients with progressive midgut carcinoid tumour - cut–

off date 24 July 2015 (NETTER-1 phase III study; FAS, N=229) 

 

 
 

At the cut-off date for post-hoc statistical analysis (30 June 2016), the number of centrally confirmed 

disease progressions or deaths was 30 events in the Lutathera arm and 78 events in the octreotide LAR 

arm (Table 7). PFS differed significantly (p<0.0001) between the treatment groups. The median PFS 

for Lutathera was 28.4 months whereas the one of octreotide LAR was 8.5 months. The hazard ratio 

for Lutathera was 0.21 (95% CI: 0.14 - 0.33), indicating 79% reduction in the risk for a patient to 

progress or die under Lutathera compared to octreotide LAR. 

 

Table 7. PFS observed in the NETTER-1 phase III study in patients with progressive midgut 

carcinoid tumour - cut-off date 30 June 2016 (full analyses set (FAS), N=231) 

 

 Treatment 

 Lutathera Octreotide LAR 

N 117 114 

Patients with events 30 78 

Censored patients 87 36 

Median months (95%-CI) 28.4 (28.4; NE) 8.5 (5.8; 11.0) 

p-value of Log-rank test <0.0001 

Hazard ratio (95%-CI) 0.214 (0.139 ; 0.331) 
N: number of patients, CI: confidence interval. 

 



 

21 

The PFS Kaplan-Meier graph for the full analysis set (FAS) at the cut-off date 30 June 2016 is 

depicted in Figure 4. 

 

Figure 4. PFS Kaplan Meier curves of patients with progressive midgut carcinoid tumour - cut-off 

date 30 June 2016 (NETTER-1 phase III study; FAS, N=231) 

 

 
 

With respect to overall survival OS, at the time of interim analysis (24 July 2015), there were 

17 deaths in the Lutathera arm and 31 in octreotide LAR 60 mg arm and the hazard ratio was 0.459 in 

favour of Lutathera, but did not reach the level of significance for interim analysis (HR 99.9915% CI: 

0.140, 1.506). OS median was 27.4 months in octreotide LAR arm and was not reached in Lutathera 

arm. An update conducted about one year after (30 June 2016) showed similar trend with 28 deaths in 

the Lutathera arm and 43 in octreotide LAR 60 mg arm, an HR of 0.536, and a median OS of 

27.4 months in octreotide LAR arm and still not reached in Lutathera arm. The final OS analysis is 

foreseen after 158 cumulative deaths. 

 

Health Related Quality of Life (HRQOL) was assessed using the European Organisation for Research 

and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) (generic instrument) and 

its neuroendocrine tumour module (EORTC QLQ-GI.NET-21). 

The results indicate an improvement in the overall global health-related quality of life up to week 84, 

for patients on Lutathera treatment as compared to patients on Octreotide LAR. 
 

Erasmus phase I/II study was a monocentric single arm open-label study to evaluate the efficacy of 

Lutathera (7,400 MBq administered for 4 times every 8 weeks) co-administered with amino acid 

solution in patients with somatostatin receptor positive tumours. The mean age of patients enrolled in 

the study was 60 years. Most patients were Dutch (811) with the remaining (403) residents of various 

European and non-European countries. The main analysis has been conducted on 811 Dutch patients 

with different somatostatin receptor positive tumour types. The ORR (including complete response 

(CR) and partial response (PR) according to RECIST criteria) and duration of response (DoR) for the 

FAS Dutch population with gastroenteropancreatic (GEP) and bronchial NETs (360 patients) as well 

as per tumour type are presented in Table 8. 

 



 

22 

Table 8. Best response, ORR and DoR observed in the Erasmus phase I/II study in Dutch patients 

with GEP and bronchial NETs – (FAS, N=360) 

 

  N CR PR SD ORR DoR (months) 

Tumour 

type 
 n % n % N % n % 95%CI Median 95%CI 

All* 360 11 3% 151 42% 183 51% 162 45% 40% 50% 16.3 12.2 17.8 

Bronchial 19 0 0% 7 37% 11 58% 7 37% 16% 62% 23.9 1.7 30.0 

Pancreatic 133 7 5% 74 56% 47 35% 81 61% 52% 69% 16.3 12.1 21.8 

Foregut** 12 1 8% 6 50% 4 33% 7 58% 28% 85% 22.3 0.0 38.0 

Midgut 183 3 2% 58 32% 115 63% 61 33% 27% 41% 15.3 10.5 17.7 

Hindgut 13 0 0% 6 46% 6 46% 6 46% 19% 75% 17.8 6.2 29.9 
CR = Complete response; PR = Partial response; SD = Stable disease; ORR = Objective response (CR+PR); DoR = Duration of response 

* Includes Foregut, Midgut and Hindgut; **Foregut NETs other than bronchial and pancreatic 

 

The overall median PFS and OS for the FAS Dutch population with GEP and bronchial NETs 

(360 patients) as well as per tumour type are presented in Table 9. 

 

Table 9. PFS and OS observed in the Erasmus phase I/II study in Dutch patients with GEP and 

bronchial NET – (FAS, N=360) 

 

  
PFS 

Time (months) 
OS 

Time (months) 

Median 95%CI Median 95%CI 

All* 360 28.5 24.8 31.4 61.2 54.8 67.4 

Bronchial 19 18.4 10.4 25.5 50.6 31.3 85.4 

Pancreatic 133 30.3 24.3 36.3 66.4 57.2 80.9 

Foregut** 12 43.9 10.9   21.3  

Midgut 183 28.5 23.9 33.3 54.9 47.5 63.2 

Hindgut 13 29.4 18.9 35.0    
PFS = Progression free survival; OS = Overall survival 

* Includes Foregut, Midgut and Hindgut; **Foregut NETs other than bronchial and pancreatic 

 

In the Erasmus phase I/II study 188 patients (52%) received and 172 (48%) did not receive 

concomitant octreotide LAR during Lutathera treatment. No statistically significant difference in PFS 

was observed between the subgroup of patients who did not receive octreotide LAR (25.4 months 

[95% CI 22.8-30.6]) versus the subgroup who did receive concomitant treatment with octreotide LAR 

(30.9 months [95% CI 25.6-34.8]) (p= 0.747). 

 

Paediatric population 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Lutathera in all subsets of the paediatric population in the treatment of GEP-NETs (excluding 

neuroblastoma, neuroganglioblastoma, phaeochromocytoma). See section 4.2. 

 

  



 

23 

5.2 Pharmacokinetic properties 

 

Absorption 

The medicinal product is administered intravenously and is immediately and completely bioavailable. 

 

Organ uptake 

At 4 hours after administration, the distribution pattern of lutetium (177Lu) oxodotreotide shows a rapid 

uptake in kidneys, tumour lesions, liver and spleen, and in some patients in the pituitary gland and in 

the thyroid. The co-administration of amino acid solution decreases the kidney uptake, enhancing the 

elimination of radioactivity (see section 4.4). Biodistribution studies show that lutetium (177Lu) 

oxodotreotide is rapidly cleared from the blood. 

An analysis performed with human plasma to determine the extent of plasma protein binding of 

non-radioactive compound (lutetium (175Lu) oxodotreotide) showed that about 50% of the compound 

is bound to plasmatic proteins. 

Transchelation of lutetium from lutetium (175Lu) oxodotreotide into serum proteins has not been 

observed. 

 

Biotransformation 

There is evidence, from the analysis of urine samples of 20 patients included in the NETTER-1 phase 

III Dosimetry, pharmacokinetic and ECG substudy, that lutetium (177Lu) oxodotreotide is poorly 

metabolized and is excreted mainly as intact compound by renal route. 

The high performance liquid chromatography (HPLC) analyses performed on urine samples collected 

up to 48 hours post infusion showed lutetium (177Lu) oxodotreotide radiochemical purity close to 

100% in most of the analysed samples (with lowest radiochemical purity value being greater than 

92%), indicating that the compound is eliminated in urine mainly as intact compound. 

This evidence confirms what has been previously observed in the Erasmus phase I/II study, in which 

HPLC analysis of a urine specimen collected 1 hour post administration of lutetium (177Lu) 

oxodotreotide from one patient receiving 1.85 MBq of lutetium (177Lu) oxodotreotide indicated that 

the main portion (91%) was excreted unchanged. 

These finding are supported by in vitro metabolism data in human hepatocytes, in which no metabolic 

degradation of lutetium (175Lu) oxodotreotide was observed. 

 

Elimination 

Based on the data collected during the Erasmus phase I/II and NETTER-1 phase III studies, lutetium 

(177Lu) oxodotreotide is primarily eliminated by renal excretion: about 60% of the medicinal product is 

eliminated in the urine within 24 hours, and about 65% within 48 hours following the administration. 

 

Elderly: 

The pharmacokinetics profile in elderly patients (≥ 75 years) has not been established. No data are 

available. 

 

5.3 Preclinical safety data 
 

Toxicological studies with rats have demonstrated that a single intravenous injection of up to 

4,550 MBq/kg was well tolerated and no deaths were observed. When testing the cold compound 

(non-radioactive lutetium (175Lu) oxodotreotide) as a single intravenous injection in rats and dogs at 

doses up to 20,000 µg/kg (rats) and 3,200 µg/kg (dogs), the compound was well tolerated in both 

species and no deaths were observed. Toxicity with four repeated administrations, once every 2 weeks, 

of 1,250 µg/kg of the cold compound in rats and 80 µg/kg in dogs was not observed. This medicinal 

product is not intended for regular or continuous administration. 

Mutagenicity studies und long-term carcinogenicity studies have not been carried out. 

Non-clinical data on the cold compound (non-radioactive lutetium (175Lu) oxodotreotide) reveal no 

special hazard for humans based on conventional studies of safety pharmacology, repeated dose 

toxicity, genotoxicity. 

 

 



 

24 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Acetic acid 

Sodium acetate  

Gentisic acid 

Ascorbic acid 

Pentetic acid 

Sodium chloride 

Sodium hydroxide 

Water for injections 

 

6.2 Incompatibilities 
 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 4.2. 

 

6.3 Shelf life 
 

72 hours from the date and time of calibration. 

 

6.4 Special precautions for storage 

 

Store below 25°C. 

Store in the original package to protect from ionizing radiation (lead shielding). 

Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive 

materials. 

 

6.5 Nature and contents of container 

 

Clear colourless Type I glass vial, closed with a bromobutyl rubber stopper and aluminium seal. 

Each vial contains a volume varying from 20.5 to 25.0 mL of solution corresponding to an activity of 

7,400 MBq at date and time of infusion. 

The vial is enclosed within a lead container for protective shielding. 

 

6.6 Special precautions for disposal and other handling 
 

For single use only. 

 

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 instruction on preparation of the medicinal product before administration, see section 12. 

 

If at any time in the preparation of this medicinal product the integrity of this container and 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. 

It is necessary to wear waterproof gloves and suitable aseptic techniques when handling the medicinal 

product. 



 

25 

 

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. 

 

The surface dose rates and the accumulated dose depend on many factors. Measurements on the 

location and during work are critical and should be practiced for more precise and instructive 

determination of overall radiation dose to the staff. Healthcare personnel are advised to limit the time 

of close contact with patients injected with Lutathera. The use of television monitor systems to 

monitor the patients is recommended. Given the half-life of 177Lu it is specially recommended to avoid 

internal contamination. It is necessary to use protective high quality (latex/nitrile) gloves to avoid 

direct contact with the radiopharmaceutical (vial/syringe). For minimising radiation exposure, always 

use the principles of time, distance and shielding (reducing the manipulation of the vial and using the 

material already supplied par the manufacturer). 

 

This preparation is likely to result in a relatively high radiation dose to most patients. The 

administration of 7,400 MBq may result in significant environmental hazard. 

This may be of concern to the immediate family of those individuals undergoing treatment or the 

general public depending on the level of activity administered, hence radioprotection rules should be 

followed (section 4.4). Suitable precautions in accordance with national regulations should be taken 

concerning the activity eliminated by the patients in order to avoid any contaminations. 

 

Any unused medicinal product or waste material should be disposed according to local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Advanced Accelerator Applications 

20 rue Diesel 

01630 Saint Genis Pouilly 

France 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1226/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 26 September 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

11. DOSIMETRY 

 

The following conclusions on treatment with Lutathera were determined from radiation dosimetry 

evaluations performed in clinical studies: 

 The critical organ is the bone marrow, however, with the recommended Lutathera cumulative 

dose of 29,600 MBq (4 administrations of 7,400 MBq), no correlation between hematologic 

toxicity and the total radioactivity administered or bone marrow absorbed dose has been 

observed either in Erasmus phase I/II or in NETTER-1 phase III study. 

 Kidney is not a critical organ if a co-infusion of an appropriate amino acids solution is 

performed. 

 



 

26 

Overall, the results of the dosimetric analysis performed in the NETTER-1 phase III dosimetry 

substudy and in the Erasmus phase I/II study are in agreement and indicate that Lutathera dose 

regimen (4 administrations of 7,400 MBq) is safe. 

 

Table 10. Absorbed dose estimates for lutetium (177Lu) oxodotreotide from NETTER-1 phase III 

study (Olinda output) 

 

Organ 
Organ absorbed dose (mGy/MBq) 

(n = 20) 

 Mean  SD 

Adrenals 0.04 0.02 

Brain 0.03 0.02 

Breasts 0.03 0.01 

Gallbladder Wall 0.04 0.02 

Lower Large Intestine Wall 0.03 0.02 

Small Intestine 0.03 0.02 

Stomach Wall 0.03 0.02 

Upper Large Intestine Wall 0.03 0.02 

Heart Wall 0.03 0.02 

Kidneys 0.65 0.29 

Liver 0.49 0.62 

Lungs 0.03 0.01 

Muscle 0.03 0.02 

Ovaries** 0.03 0.01 

Pancreas 0.04 0.02 

Red Marrow 0.03 0.03 

Osteogenic Cells 0.15 0.27 

Skin 0.03 0.01 

Spleen 0.85 0.80 

Testes* 0.03 0.02 

Thymus 0.03 0.02 

Thyroid 0.03 0.02 

Urinary Bladder Wall 0.45 0.18 

Uterus** 0.03 0.01 

Total Body 0.05 0.03 

*n=11 (male patients only) 

**n=9 (female patients only) 

 

Radiation dose to specific organs, which may not be the target organ of therapy, can be influenced 

significantly by pathophysiological changes induced by the disease process. This should be taken into 

consideration when using the following information. 

 

 

  



 

27 

12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 

 

Quality controls 

The solution should be visually inspected for damage and contamination before use, and only clear 

solutions free of visible particles should be used. The visual inspection of the solution should be 

performed under a shielded screen for radioprotection purposes. The vial must not be opened. 

 

If at any time in the preparation of this medicinal product the integrity of this vial is compromised, it 

should not be used. 

 

The amount of radioactivity in the vial must be measured prior to infusion using a suitable 

radioactivity calibration system in order to confirm that the actual amount of radioactivity to be 

administered is equal to the planned amount at the infusion time. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements (see section 6.6). 

 

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/


 

28 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 



 

29 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturers responsible for batch release 

 

Advanced Accelerator Applications Ibérica, S.L.U. 

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 40/42 

47014 

Meldola (FC) 

Italy 

 

Advanced Accelerator Applications (Italy) S.r.l 

Via Ribes 5 

10010 

Colleretto Giacosa (TO) 

Italy 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic safety update reports (PSURs) 

 

The requirements for submission of PSURs for this medicinal product are set out in the list of 

Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 

and any subsequent updates published on the European medicines web-portal. 

 

The marketing authorisation holder (MAH) shall submit the first PSUR 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 marketing authorisation holder (MAH) shall perform the required pharmacovigilance 

activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 

marketing authorisation and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



 

30 

 

 Additional risk minimisation measures 
 

Prior to launch of Lutathera in each Member State the marketing authorisation holder (MAH) 

must agree about the content and format of the educational programme, including 

communication media, distribution modalities, and any other aspects of the programme, with 

the National Competent Authority. 

 

The educational programme is aimed at increasing patients’ awareness on the risk of 

radiotoxicity by occupational exposure and inadvertent exposure to peptide receptor 

radionuclide therapy, and at providing information concerning the necessary precautions to take 

to limit unnecessary exposure to themselves and the people around them. 

 

The MAH shall ensure that in each Member State where Lutathera is marketed, all 

patients/carers who are expected to be administered Lutathera have access to/are provided with 

a patient educational material containing: 

 The package leaflet 

 Patient guide 

 

The patient guide shall contain the following key elements: 

 Brief introduction to the treatment and the administration procedure 

 Information on the precautions the patient should take before, during and after the 

administration procedure, at the hospital and at home, to limit unnecessary exposure to 

radiations of themselves and their entourage. 

 Information that PPRT can cause serious side effects during or after treatment and that any side 

effect should be reported to the physician. 

  



 

31 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



 

32 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



 

33 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

LEAD SHIELDING CONTAINER  

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Lutathera 370 MBq/mL solution for infusion 

Lutetium (177Lu) oxodotreotide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One mL contains 370 MBq of lutetium (177Lu) oxodotreotide at calibration time. 

Volumetric activity at calibration time: 370 MBq/mL - {DD/MM/YYYY hh:mm UTC} 

 

 

3. LIST OF EXCIPIENTS 

 

Acetic acid, sodium acetate, gentisic acid, ascorbic acid, pentetic acid, sodium chloride 9 mg/mL 

injection, sodium hydroxide, water for injections. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for infusion 

Vial No.: {X}         

Volume: {Y} mL 

Activity at infusion time: {Z} MBq - {DD/MM/YYYY hh:mm UTC} 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Single-dose vial. 

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 

 

 
 

 



 

34 

8. EXPIRY DATE 

 

EXP: {DD MM YYYY hh:mm UTC} 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25°C. 

Store in the original package to protect from ionizing radiation (lead shielding). 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Advanced Accelerator Applications 

20 rue Diesel, 

01630 Saint Genis Pouilly 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1226/001 

 

 

13. BATCH NUMBER 

 

Batch: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

Not applicable. 

 

 



 

35 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

Not applicable. 

  



 

36 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Lutathera 370 MBq/mL solution for infusion 

Lutetium (177Lu) oxodotreotide 

Intravenous use 

 

 

2. METHOD OF ADMINISTRATION 

 

Single-dose vial. 

 

 

3. EXPIRY DATE 

 

EXP: {DD MM YYYY hh:mm UTC} 

 

 

4. BATCH NUMBER 

 

Batch: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

Vial No.: {X} 

Volume: {Y} mL 

Volumetric activity at calibration time: 370 MBq/mL - {DD/MM/YYYY hh:mm UTC} 

Activity at infusion time: {Z} MBq - {DD/MM/YYYY hh:mm UTC} 

 

 

6. OTHER 

 

 
 

Manufacturer 

Advanced Accelerator Applications Ibérica, S.L.U. 

Polígono Industrial la Cuesta – Sector 3 

Parcelas 1 y 2 La Almunia de Doña Godina 

50100 Zaragoza 

Spain 

 



 

37 

Advanced Accelerator Applications (Italy) S.r.l 

Via Piero Maroncelli 40/42 

47014 

Meldola (FC) 

Italy 

 

Advanced Accelerator Applications (Italy) S.r.l 

Via Ribes 5 

10010 

Colleretto Giacosa (TO) 

Italy 

  



 

38 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

39 

Package leaflet: Information for the user 
 

Lutathera 370 MBq/mL solution for infusion 

Lutetium (177Lu) oxodotreotide 

 

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 Lutathera is and what it is used for 

2. What you need to know before Lutathera is used 

3. How Lutathera is used 

4. Possible side effects 

5. How Lutathera is stored 

6. Contents of the pack and other information 

 

 

1. What Lutathera is and what it is used for 

 

Lutathera is a radiopharmaceutical medicine used for the treatment of certain tumours 

(gastroenteropancreatic neuroendocrine tumours), which cannot be completely removed from your 

body by surgery, have spread in your body (metastatic) and does not respond more to your current 

treatment. The tumour needs to have somatostatin receptors on the surface of its cells in order for the 

medicine to be effective. Lutathera binds with these receptors and emits radioactivity directly into the 

tumour cells, causing their death. 

 

The use of Lutathera does involve exposure to amounts of radioactivity. Your doctor and the nuclear 

medicine doctor have considered that the clinical benefit that you will obtain from the procedure with 

the radiopharmaceutical outweighs the risk due to radiation. 

 

In addition to administration of Lutathera, an infusion with amino acids will be given to you in order 

to protect your kidneys as well as medicines (antiemetics) to avoid nausea and vomiting that may be 

caused by amino acid infusion. 

 

 

2. What you need to know before Lutathera is used  
 

Lutathera must not be used 

- if you are allergic to lutetium (177Lu) oxodotreotide or any of the other ingredients of this 

medicine (listed in section 6) 

- if you are pregnant or think you may be pregnant or it is not confirmed if you are pregnant 

- if your kidneys are seriously impaired 

 

Warnings and precautions 

Talk to your doctor before you are given Lutathera as it may cause: 

- secondary blood cancer (myelodisplastic syndrome or acute leukaemia) which can rarely occur 

several years after you have completed Lutathera treatment. 



 

40 

 

If any of these apply to you, tell your doctor or pharmacist or healthcare provider before receiving 

Lutathera, as well as during treatment with Lutathera: 

- If you had or have weakness, fatigue, shortness of breath, poor concentration, frequent 

infections, fever, easily bleeding or difficulty to stop bleeding (signs and symptoms of 

myelossupression). Tell your doctor if you had other type of cancer within the last 5 years, bone 

metastasis, previous anti-cancer treatment (chemotherapy) or radiation therapy. 

- If you had or have swollen feet and ankle, too much urine or not enough urine, itching or 

trouble catching your breath (signs and symptoms of chronic kidney disease). 

- If you had or have any itchy yellow skin or if the whites of your eye turn yellow, nausea or 

vomiting, fatigue, loss of appetite, pain in the upper right side of your stomach area (abdomen), 

dark or brown urine, or you bleed or bruise more easily than normal (signs and symptoms of 

liver disease). 

- If you have breathlessness, weakness, numbness, chest pain, palpitations or abnormal heart 

rhythm (signs and symptoms of high potassium levels in blood (hyperkalemia)). 

- If you have breathlessness, difficulty breathing when lying down or swelling of the feet or legs 

(signs and symptoms of heart failure). 

- If your kidney or urinary tract is not correctly developed. 

- If you are suffering from urinary incontinence. 

 

Treatment with Lutathera (lutetium (177Lu) oxodotreotide) may cause tumour lysis syndrome, due to 

the rapid breakdown of tumour cells. This may result in abnormal blood test results, irregular 

heartbeat, kidney failure or seizures within a week of treatment. Your doctor will perform blood tests 

to monitor you for this syndrome. Tell your doctor if you have muscle cramping, muscle weakness, 

confusion, or shortness of breath. 

 

Unless your doctor has considered that the clinical benefit of  the treatment overcomes the possible 

risks, you will not be given this medicine: 

- if you have received a previous external radiation therapy on more than 25% of your bone 

marrow 

- if you heart is seriously impaired 

- if you have seriously affected blood cell counts 

- if your liver is seriously impaired 

- if it appears that your tumour does not have sufficient somatostatin receptors 

 

Children and adolescents 

The safety and efficacy of this medicine has not yet been established in children and adolescents under 

18 years of age. Talk to your nuclear medicine doctor if you are under 18 years old. 

 

Other medicines and Lutathera 
Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other 

medicines including somatostatin analogues, glucocorticoids (also called corticosteroids), since they 

may interfere with your treatment. If you are taking somatostatin analogues you might be asked to stop 

and/or adapt your treatment for a short period of time. 

 

Pregnancy, breast-feeding and fertility 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your nuclear medicine doctor for advice before you are given this medicine. 

 

Lutathera is contraindicated in pregnant women, as ionizing radiation is dangerous for the foetus. 

Breast-feeding should be avoided during treatment with this medicinal product. If treatment with 

Lutathera during breast-feeding is necessary, the child must be weaned. 

You must inform the nuclear medicine doctor before the administration of Lutathera if there is a 

possibility you might be pregnant or if you have missed your period or if you are breast-feeding. 

When in doubt, it is important to consult your nuclear medicine doctor who will supervise the 

procedure. 

 



 

41 

During treatment with Lutathera and for a minimum of the following 6 months after the end of the 

treatment, appropriate measures must be taken to avoid pregnancy; this applies to patients of both 

genders. 

 

Fertility 

Ionizing radiations of the medicine may potentially decrease your fertility. Genetic consultation is 

recommended if you wish to have children after treatment. Cryopreservation of sperm or eggs may be 

offered to you before the treatment. 

 

Driving and using machines 
It is considered unlikely that Lutathera will affect your ability to drive or to use machines; however, 

your general condition and the possible adverse reactions to treatment must be taken into account to 

assess this ability before driving or using machines. 

 

Lutathera contains sodium 

This medicine contains up to 81.1 mg sodium (main component of cooking/table salt) in each vial. 

This is equivalent to 4% of the recommended maximum daily dietary intake of sodium for an adult. 

 

 

3. How Lutathera is used 
 

There are strict laws on the use, handling and disposal of radiopharmaceutical products. Lutathera will 

only be used in special 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 recommended dose is 7,400 MBq (megabecquerel, the unit used to express radioactivity) in a 

single infusion, which is given at 4 times once every 8 weeks. 

 

Administration of Lutathera and conduct of the procedure 
Lutathera is administered directly into a vein. 

 

Due to the radiation emitted by this medicine, during the administration procedure, you should be 

isolated from other patients who are not receiving the same treatment. The doctor will inform you 

when you can leave the controlled area or the hospital. 

 

In addition to administration of Lutathera, an infusion with amino acids will be given to you in order 

to protect your kidneys. This might induce nausea and vomiting; you will also receive an injection 

before the start of the treatment to reduce these symptoms. 

 

Duration of the procedure 
Your nuclear medicine doctor will inform you about the usual duration of the procedure. 

The medicine infusion takes 30 ±10 minutes; but the complete administration procedure will take 

approximately 5 hours. This treatment is given in 4 treatment cycles which are separated by 8 to 

16 weeks. Your doctor will regularly monitor your condition to check that the treatment is having the 

desired effect. 

 

Treatment monitoring 
Treatment with Lutathera can have an impact on blood cells, liver and kidneys (see section 4). In 

consequence, your doctor will ask you to have regular blood tests in order to check your eligibility for 

this treatment and to detect any side effects as early as possible. Based on the results, your doctor may 

decide to delay or stop your treatment with this medicine if necessary. 

 

  



 

42 

After administration of Lutathera 

You will be requested to drink a sufficient amount of water (1 glass every hour) necessary to urinate 

every hour on the day of infusion and the day after, and try to defecate every day, in order to eliminate 

the medicine from your body. 

Because this medicine is radioactive, you will have to follow the instructions described below to 

minimize radiation exposure to others. 

Considering current knowledge and experience in this field and the physical and pharmaceutical 

properties of the medicine, it is estimated that the health risks to your family members and the general 

public are low. However, you must adhere to the following rules to maximize the safety of other 

persons. These rules are the result of many years of experience in the use of radioactivity in medicine, 

and they include recommendations issued by international organizations. 

 

General rule 

You should limit close contact with people who live with you by keeping a distance of at least one 

meter for 7 days after you receive Lutathera. 

 

Use of toilets 

Toilets must be used in a seated position, even for men. It is absolutely necessary to use toilet paper 

each time. It is also important to wash your hands to avoid contaminating the door handles. It is 

strongly recommended to move your bowels every day and use a laxative if necessary. Furthermore, 

drink frequently and try to urinate every hour on the day you received treatment and on the day after. 

Follow your doctor’s advice on how much fluid to drink. 

 

Contact with children and/or pregnant women 

After your receive Lutathera, it is strongly recommended that you limit close contact (less than 

1 meter) with children and/or pregnant women to less than 15 minutes per day for 7 days. 

 

Contact with spouse and people in the family circle 

You should sleep in a separate bedroom from other people for 7 days after you receive Lutathera. You 

should sleep in separate bedrooms from children and/or pregnant women for 15 days after you receive 

Lutathera. 

 

Breast-feeding 

Breast-feeding must be stopped. If treatment with Lutathera during breast-feeding is necessary, the 

child must be weaned. 

 

Pregnancy 

Ionizing radiation is dangerous for the foetus, therefore pregnancy is contraindicated. Men and women 

of child-bearing potential must refrain from procreation by using effective contraceptive methods 

during the treatment and for 6 months after. 

 

People who need extra assistance 

People who are confined to the bed or have reduced mobility will preferably receive assistance by a 

care provider. It is recommended that when providing assistance in the bathroom, the care provider 

wears disposable gloves for 7 days after administration. In the case of the use of special medical 

equipment such as catheters, colostomy bags bedpan, water nozzle, or anything that could be 

contaminated by your body fluids these must be emptied immediately in the toilet and then cleaned. If 

anyone helps you clean up vomit, blood, urine, or stool they should wear plastic gloves; the gloves 

should then be disposed of in a specific trash plastic bag (according to the recommendation stated in 

section "Trash recommendations" below). 

 

  



 

43 

Dishes and bathroom accessories 

Take special precautions during the 7 days after treatment: 

- Flush all wipes and/or toilet paper down the toilet immediately after use, 

- Always wash your hands well after using the toilet, 

- Take a shower every day, 

- Flush any tissues or any other items that contain anything from your body, such as blood, urine 

and faeces down the toilet. Items that cannot be flushed down the toilet, such as menstrual pads 

and bandages, must be placed in specific trash plastic bags (according to the recommendation 

stated in section "Trash recommendations" below). 

- Wash your underwear, pyjamas, sheets and any clothes that contain sweat, blood or urine 

separately from the laundry of other members of your household, using a standard washing 

cycle. You do not need to use bleach and do not need extra rinses. 

 

Trash recommendations 

Keep the specific plastic trash bags separated from the other trash; keep the bags away from children 

and animals. 

 

A member of the hospital staff will tell you how and when to get rid of these trash bags. You might be 

asked to bring the bag back to your treatment facility, or, after 70 days, the bag may be removed as the 

other household waste. 

 

Hospitalisation and Emergency Care 

If for any reason you require emergency medical assistance or unplanned hospitalisation occurs during 

the 3 months after your treatment, you should inform the medical providers about the nature, the date 

and the dose of your radioactive treatment. To facilitate that, carry your discharge letter with you at all 

times. 

 

Travel 

Keep the discharge letter with you whenever you are travelling for at least 3 months after treatment. 

 

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 Lutathera than you should 
An overdose is unlikely because you will only receive a single dose of Lutathera precisely controlled 

by the nuclear medicine doctor supervising the administration procedure. However, in the case of an 

overdose, you will receive the appropriate treatment. 

Should you have any further question on the use of this medicine, please ask the 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. 

Lutathera side effects are mainly linked to radioactivity. 

The most common side effect seen in patients being treated with Lutathera is the impact on the bone 

marrow. This can lead to the decrease of the different types of blood cells, most importantly, red blood 

cells (responsible for transporting the oxygen from the lungs to the different organs), platelets (a 

special cell which helps the blood to clot), and other blood cells such as white blood cells (helps to 

fight infection). This happens in many patients and is frequently temporary. However, in rare cases the 

decrease in blood cells may be long standing and/or permanent. 

As a consequence, a decrease in the various blood cell types may put you at risk for bleeding, fatigue, 

shortness of breath, and infection. If this does occur to you, your doctor may decide to delay or stop 

the treatment administration. 

 



 

44 

Some side effects could be serious 

If you experience any serious side effects, tell your doctor immediately. 

 

Very common: may affect more than 1 in 10 people 

 Spontaneous bleeding or bruising (possible signs of low level of blood platelets) 

(thrombocytopenia) 

 Fever, sore throat or mouth ulcers due to infections (possible signs of low level of white blood 

cells) (lymphopenia) 

 Tiredness, fatigue, pale skin (possible signs of low level of red blood cells) (anaemia) 

 Pale skin, weakness, spontaneous bleeding or bruising and frequent infections with signs such 

as fever, chills, sore throat or mouth ulcers (possible signs of low level of blood cells) 

(pancytopenia) 

 

Common: may affect up to 1 in every 10 people 

 Bone marrow cancer resulting in poorly formed blood cells or ones that do not work properly, 

with signs and symptoms of anaemia (myelodysplastic syndrome) 

 Fever, sore throat or mouth ulcers due to infections (possible signs of low level of white blood 

cells) (leukopenia and neutropenia) 

 Weight gain, tiredness, hair loss, muscle weakness, feeling cold (possible signs of underactive 

thyroid gland)  (secondary hypothyroidism) 

 Thirst, low urine output, weight loss, dry flushed skin, irritability (possible signs of dehydration) 

 Transient, self-limited loss of consciousness followed by spontaneous recovery (syncope) 

 Irregular heart-beat (change in the electrical activity of the heart) 

 Dizziness, light-headedness (possible signs of low blood pressure) 

 Severely decreased urine output (possible signs of kidney disorders) (renal failure and acute 

kidney injury) 

 

Uncommon: may affect up to 1 in every 100 people 

 Sore throat, runny nose, difficult or painful breathing and fever (possible signs of a respiratory 

tract infection) 

 Cough, difficult or painful breathing, wheezing, pain in chest when breathing, fever (possible 

symptoms of upper respiratory tract infection) (pneumonia) 

 Rash of small fluid-filled blisters, appearing on reddened skin, signs of viral infection that can 

be potentially severe (herpes zoster) 

 Viral infection of the eyes (ophthalmic herpes zoster) 

 Staphylococcal infections 

 Streptococcal bacteraemia 

 Persistent fatigue, frequent or severe infections, easy bleeding, weight loss (possible symptoms 

of bone marrow cancer) (acute myeloid leukaemia, acute leukaemia and chronic 

myelomonocytic leukaemia) 

 Bone marrow cancer resulting in poorly formed blood cells or ones that do not work properly, 

with signs and symptoms of anaemia (refractory cytopenia with unilineage dysplasia) 

 Nephrogenic anaemia 

 Bone pain or fractures, fatigue, increased infections, changes in urination frequency, confusion, 

thirst, nausea or vomiting, weight loss (possible symptoms of bone marrow failure) 

 Bleeding and/or bruising underneath the skin (possible signs of low level of blood platelets) 

(thrombocytopenic purpura) 

 Rash, itching, hives, breathlessness or difficult breathing, wheezing or coughing, light-

headedness, dizziness, changes in levels of consciousness, hypotension, with or without mild 

generalized itching, skin reddening, facial/throat swelling, blue discoloration of the lips, tongue 

or skin (signs of severe allergic reaction) (hypersensitivity) 

 Excessive thirst, high urine output, increased appetite with weight loss, tiredness (signs of high 

level of sugar in blood) (diabetes mellitus) 



 

45 

 Facial flushing, redness, and a sudden rush of warmth in the face that is sometimes confused 

with the hot flashes of menopause, diarrhoea, a fast heartbeat, wheezing, a sudden drop in blood 

pressure (possible signs of carcinoid crisis) 

 Nausea, sweating, weakness, dizziness, trembling, headache (sign of low level of sugar in the 

blood) 

 Rapid and shallow breathing, confusion, fatigue, headache, sleepiness, lack of appetite, 

jaundice, increased heart rate, possible signs of metabolic acidosis that occurs when the body 

produces excessive quantities of acid or when the kidneys are not removing enough acid from 

the body (metabolic acidosis) 

 Seeing, feeling or hearing things that are not there (hallucination) 

 Altered level of consciousness as a result of liver failure (possible signs of hepatic 

encephalopathy) 

 Pressure on the spinal cord nerves which can be caused by a tumour or other lesion (spinal cord 

compression) 

 Irregular heartbeat (atrial fibrillation) 

 Sudden and crushing chest pain, tiredness, irregular heart-beat (possible symptoms of heart 

attack) (myocardial infarction) 

 Crushing chest pain (possible symptoms of problem in the heart) (angina pectoris) 

 Collapse caused by a heart problem, during which you may become breathless, pale, experience 

cold sweat and dry mouth (cardiogenic shock) 

 Dizziness, fainting on standing up, fall in blood pressure upon standing (orthostatic 

hypotension) 

 Swelling and reddening of a vein (sign of phlebitis) 

 Chest pain, cough, hiccups, rapid breathing (signs of fluid collection between the layers of 

tissue that line the lungs and chest cavity) (pleural effusion) 

 Swelling of the abdomen due to accumulation of fluid (ascites) 

 Constipation, swollen abdomen, abdominal pain (intestinal obstruction) 

 Diarrhoea, abdominal pain, fever (possible signs of inflammation of the colon) 

 Vomiting, belching, abdominal pain upper and lower, with or without nausea and vomiting 

(possible signs of inflammation of the pancreas) (acute pancreatitis) 

 Blood vomiting (haematemesis) 

 Acute pain and swelling of the abdomen due to accumulation of fluid (haemorrhagic ascites) 

 Abdominal pain, general feeling of being unwell (ileus) 

 Decreased blood levels of pancreatic enzymes 

 Yellow skin and eyes, nausea, loss of appetite, dark urine (signs of liver disorder) 

(hepatocellular injury) 

 Yellow eyes or skin (cholestasis) (signs of liver disorder) 

 Liver injury or congestion 

 Liver failure 

 Acute pre-renal failure 

 Death 

 Clavicle fracture 

 

  



 

46 

Other possible side effects 

Other side effects include the following listed below. If these side effects become severe, please tell 

your doctor, pharmacist or healthcare provider. 

 

Very common: may affect more than 1 in 10 people 

 Loss of appetite 

 Nausea 

 Vomiting 

 Tiredness (fatigue) 

 

Common: may affect up to 1 in every 10 people 

 Excessive thirst, high urine output, increase appetite with weight loss (signs of high level of 

sugar in the blood) 

 Sleep disturbance 

 Dizziness 

 Disturbed sense of taste (dysgeusia) 

 Headache 

 Feeling of having little energy, fatigue, (lethargy) 

 Headache, dizziness (sign of high blood pressure) 

 Flushing and hot flushes 

 Short of breath, labored breathing (dyspnoea) 

 Swelling, feeling of fullness in the abdomen 

 Diarrhoea 

 Stomach pain 

 Constipation 

 Upper stomach pain 

 Indigestion, pain or an uncomfortable feeling in the upper middle part of your stomach 

(dyspepsia) 

 Stomach pain, nausea (gastritis) 

 Yellow skin and eyes, possible symptoms of high amounts of bile pigment (bilirubin) in the 

blood 

 Hair loss (alopecia) 

 Pain in muscles, bones or joints 

 Muscle spasm 

 Blood in urine 

 Abnormal results of urine test (presence of serum proteins) 

 Skin reaction such as redness or swelling and pain at the site of injection 

 Swollen hands, ankles or feet (oedema peripheral) 

 Pain in the site of injection 

 Chills 

 Tiredness, chills, sore throat, joint or muscles aching 

 

Uncommon: may affect up to 1 in every 100 people 

 Discharge from the eye with itching, redness and swelling (signs of conjunctivitis) 

 Painful and frequent urination (possible symptoms of bladder inflammation) (cystitis) 

 Flu-like symptoms (Influenza) 

 Weight gain, tiredness, hair loss, muscle weakness, feeling cold (signs of underactive thyroid 

gland) (hypothyroidism) 

 Bone and joint pain, excessive urination, abdominal pain, weakness, tiredness (signs of 

overactive parathyroid gland) (hyperparathyroidism) 

 Nausea, shortness of breath, irregular heart-beat, clouding of urine, tiredness and/or joint 

discomfort associated with abnormal laboratory values - high potassium, uric acid, and 

phosphorous levels and low calcium levels in the blood (signs of dying tumour cells) 

 Excessive emotional distress, troubled (anxiety) 

 Disorientation 



 

47 

 A sensation like insects crawling over the skin (formication) 

 Sensation of pins and needles (pricking, burning, tingling or numbing sensation) (paraesthesia) 

 A distorted sense of smell (parosmia) 

 Drowsiness (somnolence) 

 Eye disorders 

 Dizziness, with spinning sensation (vertigo) 

 Rapid or irregular heartbeat or tremor (palpitations) 

 Redness and/or facial flushing due to widening of blood vessels (vasodilation) 

 Coldness of hands and feet 

 Pale skin (pallor) 

 Sore throat (oropharyngeal pain) 

 Increased sputum 

 Choking sensation 

 Dry mouth 

 Flatulence 

 Gastrointestinal pain 

 Mouth sores with gum inflammation (stomatitis) 

 Passage of fresh blood through the anus usually in or with stool (haematochezia) 

 Abdominal discomfort 

 Bloody stools (rectal haemorrhage) 

 Black stools (melaena) 

 Lower abdominal pain 

 Rash 

 Dry skin 

 Swelling face 

 Excessive sweating (hyperhidrosis) 

 Generalized itching (pruritus generalised) 

 Abnormal results of urine test (presence of leukocytes) 

 Involuntary leakage of urine (urinary incontinence) 

 Test result that indicates kidney disorders (glomerular filtration rate decreased) 

 Kidney disorder 

 Renal impairment 

 Injection site mass 

 Tiredness, chest discomfort, light headedness pain, palpitations (possible signs of heart 

disorder) 

 Chest pain 

 Fever 

 Generally feeling unwell (malaise) 

 Pain 

 Feeling abnormal 

 Loss of weight 

 Physical disability 

 

  



 

48 

During Lutathera treatment, you may also have side effects of abnormal blood test results, 

which can give your doctor information on the functioning of some parts of your body 

 

Common: may affect up to 1 in every 10 people 

 High level of the following enzymes: 

 Gamma glutamyl transferase, alanine amino transferase, aspartate amino transferase, blood 

alkaline phosphate 

 High level of blood creatinine 

 Low levels of magnesium and sodium in the blood 

 

Uncommon: may affect up to 1 in every 100 people 

 High level of the following enzymes: 

 High level of creatine phosphokinase in the blood that may indicate muscle damage, such as of 

the heart 
 High level of lactate dehydrogenase in the blood that gives information about the health of 

certain organs 

 Low levels of potassium, phosphate, calcium and albumin in the blood 

 High levels of sodium, calcium, urea, glycosylated hemoglobin, catecholamines and c-reactive 

protein in the blood 

 Haematocrit decreased  

 Presence of protein in urine 

 

During Lutathera treatment, you may also have surgical/medical procedures 

 

Common 

 Blood transfusion 

 

Uncommon 

 To drain fluid from the peritoneal cavity, the space between the abdominal wall and organs 

(abdominal cavity drainage) 

 To filter your blood to rid your body of harmful wastes, extra salt, and water (dialysis) 

 To place a stent 

 To drain abscess 

 For gastrointestinal tube insertion 

 To harvest (collect) stem cells from your bone marrow (bone marrow harvest) 

 To remove polyps from the inside of the colon, also called the large intestine (polypectomy) 

 

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 Lutathera is stored 

 

You will not have to store this medicine. This medicine is stored under the responsibility of the 

specialist in appropriate premises. Storage of radiopharmaceuticals will be in accordance with national 

regulation on radioactive materials. 

The following information is intended for the specialist only. 

Keep this medicine out of the sight and reach of children. 

Lutathera must not be used after the expiry date which is stated on the label after EXP. 

Store below 25 ºC. 

Store in the original package to protect from radiation. 

 

 

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


 

49 

6. Contents of the pack and other information 

 

What Lutathera contains 

- The active substance is lutetium (177Lu) oxodotreotide. One mL of solution for infusion contains 

370 MBq lutetium (177Lu) oxodotreotide at the date and time of calibration. 

- The other ingredients are: acetic acid, sodium acetate, gentisic acid, ascorbic acid, diethylene 

triamine pentaacetic acid (DTPA), sodium chloride 9 mg/mL (0.9%) solution for injection, 

sodium hydroxide, water for injections (see section 2 “Lutathera contains sodium”). 

 

What Lutathera looks like and contents of the pack 

Lutathera is a clear and colourless solution for infusion, supplied in a colourless glass vial closed with 

a rubber stopper and sealed with an aluminium capsule. 

Each vial contains a volume varying from 20.5 to 25.0 mL of solution corresponding to an activity of 

7,400 MBq at date and time of infusion. 

The vial is enclosed within a plastic sealed, lead shielded container. 

 

Marketing Authorisation Holder 

Advanced Accelerator Applications 

20 rue Diesel 

01630, Saint Genis Pouilly 

France 

 

Manufacturers 

Advanced Accelerator Applications Ibérica, S.L.U. 

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 40/42 

47014 

Meldola (FC) 

Italy 

 

Advanced Accelerator Applications (Italy) S.r.l 

Via Ribes 5 

10010 

Colleretto Giacosa (TO) 

Italy 

 

 

  



 

50 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

AT, BE, BG, CZ, FR, HR, HU, IS, LU, 

LV, LT, MT, NL, RO, SI, SK 
Advanced Accelerator Applications 

Tel/Tél/Teл/Sími: + 33 4 50 99 30 70 

 

CY, EL 
ΒΙΟΚΟΣΜΟΣ ΑΕΒΕ 

Τηλ: + 30 22920 63900 

 

DE 

Advanced Accelerator Applications Germany GmbH 

Tel: + 49 228 925 8830 

 

DK, EE, FI, NO, SE 
SAM Nordic 

Tel/Puh/Tlf: + 46 8 720 5822 

 

ES 
Advanced Accelerator Applications Ibérica, S.L.U. 

Tel: + 34 97 660 0126 

IE/UK 

Advanced Accelerator Applications UK Limited 

Tel: + 44 207 25 85 200 

 

 

IT 

Advanced Accelerator Applications (Italy) S.r.l 

Tel: + 39 0125 561211 

 

PL 

Advanced Accelerator Applications Polska Sp. z o. o. 

Tel: + 48 22 275 56 47 

 

PT 

Advanced Accelerator Applications (Portugal), 

Unipessoal, Lda 

Tel: + 351 211 212 018 

 

 

This leaflet was last revised in 
 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

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

 

---------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only: 

 

The complete SmPC of Lutathera is provided as a separate document in the product package, with the 

objective to provide healthcare professionals with other additional scientific and practical information 

about the administration and use of this radiopharmaceutical. 

 

Please refer to the SmPC. 


	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