Idefirix

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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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 
 
Idefirix 11 mg powder for concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 11 mg imlifidase produced in Escherichia coli cells by recombinant DNA 
technology. 
 
After reconstitution and dilution, each mL of concentrate contains 10 mg imlifidase.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion (powder for concentrate). 
 
The powder is a white cake. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Idefirix is indicated for desensitisation treatment of highly sensitised adult kidney transplant patients 
with positive crossmatch against an available deceased donor. The use of Idefirix should be reserved 
for patients unlikely to be transplanted under the available kidney allocation system including 
prioritisation programmes for highly sensitised patients. 
 
4.2 Posology and method of administration 
 
Treatment should be prescribed and supervised by specialist physicians experienced in the 
management of immunosuppressive therapy and of sensitised renal transplant patients.  
 
Imlifidase is restricted to hospital use only. 
 
Posology 
 
The dose is based on patient body weight (kg). The recommended dose is 0.25 mg/kg administered as 
a single dose preferably within 24 hours before transplantation. One dose is adequate for crossmatch 
conversion in the majority of patients but if needed a second dose can be administered within 24 hours 
after the first dose.  
 
After treatment with imlifidase, crossmatch conversion from positive to negative should be confirmed 
before transplantation (see section 4.4). 
 
Premedication with corticosteroids and antihistamines should be given to reduce the risk of infusion 
reactions in accordance with transplant centre routines.  
 



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Since respiratory tract infections are the most common infections in patients with 
hypogammaglobulinemia, prophylactic oral antibiotics covering respiratory tract pathogens should be 
added to the standard of care for 4 weeks (see section 4.4). 
 
Patients treated with imlifidase should, in addition, receive standard of care induction T-cell depleting 
agents with or without B-cell depleting agents (see section 5.1), i.e. imlifidase does not eliminate the 
need for standard of care immunosuppressive therapy.  
 
Special populations 
 
Elderly patients 
Data on the use in patients older than 65 years are limited, but there is no evidence to suggest that dose 
adjustment is required in these patients.  
 
Hepatic impairment 
The safety and efficacy of imlifidase in patients with moderate or severe hepatic impairment have not 
been established. No data are available.  
 
Paediatric population 
The safety and efficacy of imlifidase in children and adolescents 0 to 18 years of age have not been 
established. No data are available. 
 
Method of administration  
 
Idefirix is for intravenous use only following reconstitution and dilution. 
 
The entire, fully diluted infusion should be administered over a period of 15 minutes and must be 
administered with an infusion set and a sterile, inline, non-pyrogenic, low protein binding filter (pore 
size of 0.2 μm). Following administration, it is recommended that the intravenous line is flushed with 
infusion fluid to ensure administration of the complete dose. Do not store any unused portion of the 
solution for infusion for re-use. 
 
For instructions on reconstitution and dilution of the medicinal product before administration, see 
section 6.6. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- Ongoing serious infection. 
- Thrombotic thrombocytopenic purpura (TTP). Patients with this blood disorder may be at risk 

of developing serum sickness.  
 
4.4 Special warnings and precautions for use 
 
Infusion-related reactions 
 
Infusion-related reactions have been reported with imlifidase administration in clinical studies (see 
section 4.8). If any serious allergic or anaphylactic reaction occurs, imlifidase therapy should be 
discontinued immediately and appropriate therapy initiated. Mild or moderate infusion-related 
reactions occurring during imlifidase treatment can be managed by temporarily interrupting the 
infusion, and/or by administration of medicinal products, such as antihistamines, antipyretics and 
corticosteroids. An interrupted infusion can be restarted when the symptoms have abated. 
 



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Infection and infection prophylaxis 
 
For kidney transplantation, ongoing serious infections of any origin (bacterial, viral or fungal) are 
considered a contraindication, and chronic infections such as HBV or HIV have to be well controlled. 
The temporary reduction of IgG by imlifidase must be taken into consideration. The most common 
infections in patients with hypogammaglobulinemia are respiratory tract infections. Therefore, in 
addition to the standard of care infection prophylaxis in kidney transplantation in general (against 
Pneumocystis carinii, cytomegalovirus and oral candida), all patients should also receive prophylactic 
oral antibiotics covering respiratory tract pathogens for 4 weeks. Should a patient for any reason not 
be transplanted after imlifidase treatment, prophylactic oral antibiotics covering respiratory tract 
pathogens should still be given for 4 weeks.   
 
Use of imlifidase and T-cell depleting induction therapy with or without memory B-cell depleting 
therapies may increase the risk of reactivation of live-attenuated vaccines and/or latent tuberculosis.   
 
Vaccinations 
 
Due to the reduced IgG levels after treatment with imlifidase, there is a risk for a temporary reduction 
of vaccine protection for up to 4 weeks following imlifidase treatment.   
 
Antibody-mediated rejection (AMR)  
 
AMR may occur as a consequence of rebound of donor-specific antibodies (DSA). Patients with very 
high levels of DSA before transplantation are more likely to experience early AMR that requires 
intervention. Most patients in the clinical studies had rebound of DSA that peaked between 7 and 
21 days after imlifidase treatment, and AMR occurred in approximately 30% of the patients. All 
patients with AMR in clinical studies were successfully managed with standard of care treatment. The 
re-appearance of DSAs and increased risk of AMR in highly sensitised patients require physician’s 
previous experience from managing sensitised patients, resources and preparedness to diagnose and 
treat acute AMRs according to standard clinical practice. Management of patients should include close 
monitoring of HLA antibodies and serum or plasma creatinine as well as readiness to perform biopsies 
when AMR is suspected.   
 
Patients with positive T-cell complement-dependent cytotoxicity (CDC) crossmatch test 
 
There is very limited experience in patients with a confirmed positive T-cell CDC-crossmatch test 
before imlifidase treatment (see section 5.1). 
 
Immunogenicity  
 
The potential influence of anti-imlifidase antibodies (ADA) on the efficacy and safety of a second 
imlifidase dose given within 24 hours of the first is expected to be negligible, since the production of 
ADA in response to the first dose has not yet started to develop. 
 
Confirmation of crossmatch conversion  
 
Each clinic should follow its standard protocol for confirmation of crossmatch conversion from 
positive to negative. If complement-dependent cytotoxicity crossmatch (CDCXM) is used, the 
following needs to be considered to avoid false positive results: IgM has to be inactivated to be able to 
specifically assess the cytotoxic capacity of IgG. The use of an anti-human globulin (AHG) step 
should be avoided. If used, it should be confirmed that the AHG is directed against the Fc-part and not 
against the Fab-part of the IgG. Use of AHG, directed against the Fab-part, will not allow correct 
readout of a CDCXM in an imlifidase-treated patient.    
 



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Antibody-based medicinal products 
 
Imlifidase is a cysteine protease that specifically cleaves IgG. As a consequence, IgG-based medicinal 
products may be inactivated if given in connection with imlifidase. Antibody-based medicinal 
products cleaved by imlifidase include, but are not limited to basiliximab, rituximab, alemtuzumab, 
adalimumab, denosumab, belatacept, etanercept, rabbit anti-thymocyte globulin (rATG) and 
intravenous immunoglobulin (IVIg) (see section 4.5 for recommended time intervals between 
administration of imlifidase and antibody-based medicinal products). 
 
IVIg may contain neutralising antibodies against imlifidase, which may inactivate imlifidase if IVIg is 
given before imlifidase (see section 4.5).  
 
Sodium content 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Imlifidase specifically cleaves IgG; the species specificity results in degradation of all subclasses of 
human and rabbit IgG. As a consequence, medicinal products based on human or rabbit IgG may be 
inactivated if given in connection with imlifidase. Antibody-based medicinal products cleaved by 
imlifidase include, but are not limited to basiliximab, rituximab, alemtuzumab, adalimumab, 
denosumab, belatacept, etanercept, rATG and IVIg.  
 
Imlifidase does not degrade equine anti-thymocyte globulin and no time interval between 
administrations needs to be considered. Eculizumab is not cleaved by imlifidase at the recommended 
dose level. 
 
Table 1 Recommended time intervals for administration of antibody-based medicinal 
 products after administration of imlifidase  

Medicinal product  Recommended time interval after administration of 
0.25 mg/kg imlifidase 

equine anti-thymocyte globulin, 
eculizumab 

No time interval needed (can be administered 
concomitantly with imlifidase) 

intravenous immunoglobulin (IVIg) 12 hours 
alemtuzumab, adalimumab, 
basiliximab, denosumab, etanercept, 
rituximab 

4 days 

rabbit anti-human thymocyte globulin 
(rATG), belatacept 

1 week 

 
Also, IVIg may contain neutralising antibodies against imlifidase, which may inactivate imlifidase if 
IVIg is given before imlifidase. The half-life of IVIg (3-4 weeks) should be considered before 
imlifidase administration to patients treated with IVIg. In clinical studies, IVIg was not administered 
within 4 weeks before imlifidase infusion. 
 



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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no data from use of imlifidase in pregnant women since pregnancy is a contraindication to 
kidney transplantation.  
Studies in rabbits do not indicate direct or indirect harmful effects of imlifidase with respect to 
embryonic/foetal development (see section 5.3).  
As a precautionary measure, it is preferable to avoid the use of imlifidase during pregnancy.  
 
Breast-feeding 
 
It is unknown whether imlifidase is excreted in human milk. A risk to the suckling child cannot be 
excluded.  
Breast-feeding should be discontinued before imlifidase exposure.  
 
Fertility 
 
No specific studies on fertility and postnatal development have been conducted (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common serious adverse reactions in clinical studies were pneumonia (5.6%) and sepsis 
(3.7%). The most common adverse reactions were infections (16.7%) (including pneumonia (5.6%), 
urinary tract infection (5.6%) and sepsis (3.7%)), infusion site pain (3.7%), infusion related reactions 
(3.7%), alanine aminotransferase increased (3.7%), aspartate aminotransferase increased (3.7%), 
myalgia (3.7%), headache (3.7%) and flushing (3.7%). 
 
Tabulated list of adverse reactions 
 
The adverse reactions described in this section were identified in the clinical studies (N=54). 
The adverse reactions are presented according to MedDRA system organ class and frequency 
category. The frequency categories are defined 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); not 
known (cannot be estimated from the available data).  



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Table 2  Adverse reactions  

MedDRA system organ class Adverse reaction/ 
Frequency 

 Very common Common  
Infections and infestations Bacterial and viral 

infection 
Abdominal infection 
Adenovirus infection  
Catheter site infection  
Infection 
Influenza 
Parvovirus infection 
Pneumonia 
Postoperative wound infection 
Sepsis 
Upper respiratory tract infection 
Urinary tract infection 
Wound infection 

Blood and lymphatic system 
disorders 

 Anaemia 

Immune system disorders Transplant rejection 
Nervous system disorders  Dizziness postural 

Headache 
Eye disorders  Scleral haemorrhage 

Visual impairment 
Cardiac disorders  Sinus tachycardia 
Vascular disorders  Flushing 

Hypertension 
Hypotension 

Respiratory, thoracic and 
mediastinal disorders 

 Dyspnoea 

Skin and subcutanous tissue 
disorders 

 Rash 

Musculoskeletal and 
connective tissue disorders 

 Myalgia 

General disorders and 
administration site conditions 

 Feeling hot 
Infusion site pain 

Investigations  Alanine aminotransferase (ALT) 
increased 
Aspartate aminotransferase 
(AST) increased 

Injury, poisoning and 
procedural complications 

 Infusion related reactions 

 
Description of selected adverse reactions 
 
Infections 
In the clinical studies, 16.7% of the patients experienced an infection. Nine infections were serious and 
assessed as related to imlifidase in the clinical studies, whereof 5 started within 30 days after 
imlifidase treatment. Eight of the 9 related serious infections had a duration of less than 30 days. The 
incidence and pattern (including infectious agent) of serious or severe infections were not different 
from those observed in kidney-transplanted patients in general (see section 4.4).  
 
Infusion-related reactions 
Infusion-related reactions, including dyspnoea and flushing were reported in 5.6% of the patients, one 
resulting in interruption of the imlifidase infusion and the patient not being transplanted. Except for 



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one event of mild rash, all infusion-related reactions started on the day of imlifidase infusion and 
resolved within 90 minutes (see section 4.4). 
   
Myalgia 
Myalgia was reported for 2 patients (3.7%) in the clinical studies. One of the patients had severe 
myalgia without any findings of muscle damage. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no experience with doses higher than the recommended. In the event of an overdose, the 
patient should be monitored closely and treated symptomatically. 
No specific antidote exists, but depletion of IgG can be restored by administration of IVIg.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, selective immunosuppressants, ATC code: 
L04AA41. 
 
Mechanism of action 
 
Imlifidase is a cysteine protease derived from the immunoglobulin G (IgG)-degrading enzyme of 
Streptococcus pyogenes that cleaves the heavy chains of all human IgG subclasses but no other 
immunoglobulins. The cleavage of IgG leads to elimination of Fc-dependent effector functions, 
including CDC and antibody-dependent cell-mediated cytotoxicity (ADCC). By cleaving all IgG, 
imlifidase reduces the level of DSA, thus enabling transplantation.  
 
Pharmacodynamic effects 
 
Clinical studies have demonstrated that IgG was cleaved within a few hours after administration of 
imlifidase 0.25 mg/kg. No early increase in plasma IgG due to reflux of uncleaved IgG from the 
extravascular compartment has been observed, indicating that imlifidase cleaves not only the plasma 
IgG but the entire IgG pool, including the extravascular IgG. The return of endogenous IgG starts 
1-2 weeks after imlifidase administration and continues over the next weeks. 
 
It should be noted that turbidimetry/nephelometry methods, commonly used at hospitals for total IgG 
measurements, do not discriminate between different IgG fragments generated after imlifidase 
treatment, and can therefore not be used to evaluate treatment effect.  
 
Clinical efficacy and safety 
 
Three open-label, single-arm, 6-months, clinical studies evaluated the dosing regimen, efficacy, and 
safety of imlifidase as pre-transplant treatment to reduce donor-specific IgG and enable highly 
sensitised transplant candidates to be eligible for kidney transplantation. 46 patients between 20 and 
73 years of age were transplanted, all diagnosed with end-stage renal disease (ESRD) and on dialysis, 
21 (46%) women and 25 (54%) men. All patients were sensitised, 41 (89%) were highly sensitised 
(cPRA ≥ 80%), 33 (72%) of whom had a cPRA ≥ 95%. All patients that were crossmatch-positive 
before treatment with imlifidase were converted to negative within 24 hours. PKPD modelling showed 

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


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that at 2 hours after administration of 0.25 mg/kg imlifidase, a crossmatch test is likely to become 
negative in 96% of the patients, and after 6 hours at least 99.5% of the patients are likely to become 
crossmatch test negative. All 46 patients were alive at 6 months with a kidney graft survival of 93%. 
Kidney function was restored to the expected range for kidney-transplanted patients with 90% of the 
patients having an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 at 6 months.  
 
Study 03 evaluated safety and efficacy of imlifidase at different dosing regimens before kidney 
transplantation in patients with ESRD. Ten patients were treated with a single dose of 0.25 (n=5) or 
0.5 (n=5) mg/kg imlifidase and transplanted. Seven patients were DSA-positive and 6 patients had a 
positive crossmatch before imlifidase treatment. DSA was reduced in all 7 patients and all positive 
crossmatches were converted to negative after treatment. All 10 patients were successfully 
transplanted and had a functioning kidney at 6 months. Eight of the 10 patients had an eGFR 
>30 mL/min/1.73 m2. Patients received immunosuppressive treatment including corticosteroids, 
calcineurin inhibitor, mycophenolate mofetil, and IVIg. Three patients experienced AMR during the 
study, none leading to graft loss. 
 
Study 04 evaluated efficacy and safety of imlifidase in highly HLA-sensitised patients. 17 patients 
were included and treated with a single dose of 0.24 mg/kg. 15 (88%) patients were DSA-positive and 
14 (82%) patients had a positive crossmatch before imlifidase treatment. DSA was reduced to levels 
acceptable for transplantation in all patients, and all patients were transplanted within few hours after 
imlifidase treatment. 16 of the 17 patients had a functioning kidney at 6 months with 15 (94%) patients 
having an eGFR >30 mL/min/1.73 m2. Two patients experienced AMR, none leading to graft loss. 
Patients received immunosuppressive treatment including corticosteroids, calcineurin inhibitor, 
mycophenolate mofetil, alemtuzumab, and IVIg. 
 
Study 06 evaluated the efficacy and safety of imlifidase in removing DSAs and converting a positive 
crossmatch to negative in highly sensitised patients, thus, enabling transplantation. All patients 
included were on the kidney transplant waiting-list and had positive crossmatch to their available 
donor before study inclusion (including 2 patients with a confirmed positive T-cell CDC-crossmatch 
test). 18 patients received the full dose of 0.25 mg/kg imlifidase, 3 of whom received 2 doses 
12-13 hours apart, which resulted in cleavage of IgG and conversion of a positive crossmatch to 
negative in all patients. 57% of the analysed patients were crossmatch-converted within 2 hours, and 
82% within 6 hours. All patients were successfully transplanted and 16 (89%) had a functioning 
kidney at 6-months (including the 2 patients with a confirmed positive T-cell CDC-crossmatch test). 
15 (94%) patients had an eGFR >30 mL/min/1.73 m2. Patients received immunosuppressive treatment 
including corticosteroids, calcineurin inhibitor, mycophenolate mofetil, rituximab, IVIg and 
alemtuzumab or equine anti-thymocyte globulin. Seven patients experienced active AMR, and another 
patient had subclinical AMR, none leading to graft loss.  
 
Elderly 
 
Three patients aged 65 years and older have received imlifidase before kidney transplantation in 
clinical studies. The safety and efficacy outcomes for these patients were consistent with the overall 
study population as assessed by patient and graft survival, renal function, and acute rejection. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
imlifidase in one or more subsets of the paediatric population in renal transplantation (see section 4.2 
for information on paediatric use). 
 
This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This 
means that further evidence on this medicinal product is awaited.  
The European Medicines Agency will review new information on this medicinal product at least every 
year and this SmPC will be updated as necessary. 
 



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5.2 Pharmacokinetic properties 
 
The pharmacokinetics of imlifidase were comparable in healthy subjects and patients with ESRD. The 
exposure to imlifidase increased proportionally after a single intravenous 15-minute infusion of 0.12 to 
0.50 mg/kg body weight.   
The maximum concentration (Cmax) of imlifidase was observed at or soon after the end of the infusion, 
with a mean of 5.8 (4.2-8.9) µg/mL after a dose of 0.25 mg/kg. The elimination of imlifidase was 
characterised by an initial distribution phase with a mean half-life of 1.8 (0.6-3.6) hours and a slower 
elimination phase with a mean half-life of 89 (60-238) hours. The mean clearance (CL) was 
1.8 (0.6-7.9) mL/h/kg and the distribution volume (Vz) was 0.20 (0.06-0.55) L/kg during the 
elimination phase. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on repeat-dose toxicity studies in rabbits 
and dogs, and an embryo-fetal development study in rabbits. Due to the rapid and extensive 
development of anti-imlifidase antibodies and associated toxicity after repeated administrations, a 
study on fertility and early embryonic development has not been feasible. No toxicity to the 
reproductive organs was observed in repeat-dose toxicity studies but the potential effect of imlifidase 
on male and female reproductive organs has not been fully addressed. No studies on pre- or postnatal 
toxicity have been conducted. No genotoxicity studies were performed since the active substance is a 
protein and is unlikely to interact directly with DNA or other chromosomal material.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Polysorbate 80 
Trometamol  
Disodium edetate dihydrate  
Hydrochloric acid (for pH adjustment) 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
Unopened vial 
 
1 year 
 
After reconstitution  
 
The reconstituted solution should be transferred from the vial to the infusion bag immediately. 
 
After dilution  
 
Chemical and physical in-use stability after reconsitution and dilution has been demonstrated for 
24 hours at 2-8°C and for 4 hours at 25°C during this period. 
 
From a microbiological point of view, unless the method of reconstituting and dilution precludes the 
risk for microbial contamination, the product should be used immediately.  



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If not used immediately, in-use storage conditions are the responsibility of the user. The solution 
should be stored protected from light. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2-8°C). 
 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
For storage conditions after reconstitution or dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
Idefirix is supplied in a vial (Type I glass) with a stopper (bromobutyl rubber) and flip off seal 
(aluminum). 
 
Pack sizes of 1 vial or 2 x 1 vials. 
 
6.6 Special precautions for disposal and other handling 
 
Reconstitution of powder  
 
Introduce 1.2 mL of sterile water for injections into the Idefirix vial, taking care to direct the water to 
the glass wall and not into the powder. 
 
Swirl the vial gently for at least 30 seconds to dissolve the powder completely. Do not shake so as to 
minimise the likelihood of forming foam. The vial will now contain imlifidase 10 mg/mL and up to 
1.1 mL of the solution can be withdrawn. 
 
The reconstituted solution should be clear and colourless. Do not use if particles are present or the 
solution is discoloured. It is recommended to transfer the reconstituted solution from the vial to the 
infusion bag immediately. 
 
Preparation of the solution for infusion 
 
Slowly add the correct amount of reconstituted imlifidase solution to an infusion bag containing 
50 mL of sodium chloride 9 mg/mL (0.9%) solution for infusion. Invert the infusion bag several times 
to thoroughly mix the solution. The infusion bag should be protected from light. A sterile, inline, 
non-pyrogenic, low protein binding filter (pore size of 0.2 μm) infusion set must be used. For further 
information on administration see section 4.2. 
 
Prior to use the solution for infusion should be inspected visually for particulate matter or 
discolouration. Discard the solution if any particulate matter or discolouration is observed.  
 
Disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Hansa Biopharma AB  
P.O. Box 785 



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220 07 Lund  
Sweden 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1471/001 
EU/1/20/1471/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
  

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


13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 
SUBSTANCE(S) AND MANUFACTURER(S) 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 

 
E. SPECIFIC OBLIGATION TO COMPLETE POST-

AUTHORISATION MEASURES FOR THE CONDITIONAL 
MARKETING AUTHORISATION 

 



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A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance(s) 
 
Biothechnologines farmacijos centras Biotechpharma UAB 
Mokslininku street 4 
LT-08412 Vilnius 
Lithuania 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Biothechnologines farmacijos centras Biotechpharma UAB 
Mokslininku street 4 
LT-08412 Vilnius 
Lithuania 
 
 
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. 

 
• Obligation to conduct post-authorisation measures  
 
The MAH shall complete, within the stated timeframe, the below measures: 
 



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Description Due date 
Post-authorisation efficacy study (PAES): to further investigate the long-term 
graft survival in patients who have undergone kidney transplantation after 
Idefirix administration The MAH should conduct and submit the results of a 
prospective 5-year-extension observational follow-up study. 

December 
2030 

 
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE CONDITIONAL MARKETING AUTHORISATION 
 
This being a conditional marketing authorisation and pursuant to Article 14a(4) of Regulation (EC) No 
726/2004, the MAH shall complete, within the stated timeframe, the following measures: 
 
 

Description Due date 
To confirm the long-term efficacy of Idefirix in highly sensitised adult kidney 
transplant patients with positive crossmatch against an available deceased donor, 
the MAH should submit the results of a prospective, observational long-term 
follow-up study to evaluate long-term graft survival in patients treated with 
imlifidase prior to kidney transplantation. 

December 
2023 

To confirm the long-term efficacy and safety of Idefirix in highly sensitised adult 
kidney transplant patients with positive crossmatch against an available deceased 
donor, the MAH should conduct and submit the results of a controlled, 
open-label, post-approval study investigating 1-year graft survival rate in kidney 
transplant patients with positive crossmatch against a deceased donor after 
desensitisation with imlifidase. 

December 
2025 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING  



18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Idefirix 11 mg powder for concentrate for solution for infusion 
imlifidase 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 11 mg of imlifidase. 
After reconstitution, each mL of concentrate contains 10 mg imlifidase.  
 
 
3. LIST OF EXCIPIENTS 
 
Mannitol, polysorbate 80, trometamol, disodium edetate dihydrate and hydrochloric acid. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion. 
1 vial  
2 vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use after reconstitution and dilution. 
Read the package leaflet before reconstitution and 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 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original package in order to protect from light. 
 



19 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Hansa Biopharma AB  
P.O. Box 785 
220 07 Lund  
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1471/001 
EU/1/20/1471/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC  
SN  
NN  



20 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Idefirix 11 mg powder for concentrate 
imlifidase 
IV 
 
 
2. METHOD OF ADMINISTRATION 
 
Intravenous use after reconstitution and dilution. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
11 mg 
 
 
6. OTHER 
 
 
 
  



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



22 

Package leaflet: Information for the user 
 

Idefirix 11 mg powder for concentrate for solution for infusion 
imlifidase 

 
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 start using 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 doctor.  
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Idefirix is and what it is used for  
2. What you need to know before you are given Idefirix  
3. How to use Idefirix 
4. Possible side effects  
5. How to store Idefirix 
6. Contents of the pack and other information 
 
 
1. What Idefirix is and what it is used for 
 
Idefirix contains the active substance imlifidase, which belongs to a group of medicines called 
immunosuppressants. It is given before your kidney transplantation to prevent the immune system 
(your body's defences) from rejecting the donated kidney. 
 
Idefirix works by breaking down a type of antibody in the body called immunoglobulin G (IgG), 
which is involved in destroying 'foreign' or harmful substances. 
 
Imlifidase is a protein from a bacterium called Streptococcus pyogenes. 
 
 
2. What you need to know before you are given Idefirix  
 
You must not be given Idefirix 
- If you are allergic to imlifidase or any of the other ingredients of this medicine (listed in 

section 6). 
- If you have a severe infection. 
- If you have a blood disorder called thrombotic thrombocytopenic purpura (TTP), that results in 

blood clots forming in small blood vessels throughout the body. 
 
Warnings and precautions  
 
Infusion reactions 
Idefirix contains a protein and it can cause allergic reactions in some people. You will receive 
medicines to reduce the risk of an allergic reaction. If you get any symptoms of an allergic reaction, 
such as severe rash, shortness of breath, feeling hot, flushing, during the infusion (‘drip’), the infusion 
may need to be slowed down or stopped. When these symptoms go away, or improve, the infusion can 
be continued. 
 



23 

Infections 
IgG is important for protecting you against infections and since Idefirix breaks down IgG, you will 
receive antibiotics to reduce the risk of infections. 
 
Antibody-mediated rejection (AMR)  
Your body will produce new IgG antibodies, which may attack the transplanted kidney. Your doctor 
will monitor you closely and you will receive medicines to reduce the risk of rejection. 
 
Children and adolescents 
Do not give this medicine to children and adolescents under 18 years of age because it has not been 
studied in this age group. 
 
Other medicines and Idefirix 
Tell your doctor if you are using, have recently used or might use any other medicines. Idefirix can 
affect the way some medicines work, and the dose of these may have to be adjusted.  
 
As Idefirix breaks down IgG, IgG-based medicines may not work if given at the same time as Idefirix. 
This includes the following medicines:  
- basiliximab (used to prevent rejection of kidney transplants) 
- rituximab (used to treat cancers such as non-Hodgkin’s lymphoma and chronic lymphocytic 

leukaemia and inflammatory diseases such as rheumatoid arthritis) 
- alemtuzumab (used to treat a form of multiple sclerosis) 
- adalimumab (used to treat inflammatory diseases such as rheumatoid arthritis, ankylosing 

spondylitis, psoriasis, Crohn’s disease and ulcerative colitis) 
- denosumab (used to treat osteoporosis) 
- belatacept (used to prevent rejection of kidney transplants) 
- etanercept (used to treat inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, 

ankylosing spondylitis and psoriasis) 
- rabbit anti-thymocyte globulin (rATG) (used to prevent rejection of kidney transplants) 
- intravenous immunoglobulin (IVIg) (used to increase abnormally low immuniglobulin levels in 

the blood or to treat inflammatory diseases such as Guillain-Barré syndrome, Kawasaki disease 
and chronic inflammatory demyelinating polyneuropathy). 

 
Pregnancy and breast-feeding 
Idefirix is not recommended during pregnancy. 
Talk to your doctor if you think you may be pregnant. 
 
It is not known whether Idefirix passes into breast milk. You should not breast-feed if you are being 
treated with Idefirix. 
 
Idefirix contains sodium  
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
′sodium-free′. 
 
 
3. How to use Idefirix 
 
Idefirix will be prescribed by a doctor with experience in kidney transplantation and it is for use in a 
hospital. The medicine will be given by infusion into your vein over about 15 minutes.  
 
A healthcare professional will calculate the right dose for you based on your weight. Idefirix is usually 
given as a single dose, but your doctor may decide to give a second dose before the transplantation.  
 
Information for healthcare professionals on dose calculation, preparation and infusion of Idefirix is 
given at the end of this leaflet. 
 



24 

If you receive more Idefirix than you should 
During and after the infusion you will be closely monitored. Healthcare professionals will check for 
any side effects. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
Tell your doctor immediately if you notice any of the following: 
- Signs of infection, such as fever, chills, cough, feeling weak or generally unwell (very common 

- may affect more than 1 in 10 people). 
- Signs of an infusion reaction, such as severe rash, shortness of breath, feeling hot, flushing 

(common - may affect up to 1 in 10 people).  
- Muscle pain or fatigue (symptoms of myalgia) (common - may affect up to 1 in 10 people). 
 
Other side effects include: 
 
Common (may affect up to 1 in 10 people): 
- Infections: lung infection (pneumonia), infections of the blood (sepsis), abdominal infection, 

upper respiratory tract infection, adenovirus infection, parvovirus infection, urinary tract 
infection, influenza, wound infection, post-operative wound infection, catheter site infection 

- Transplant rejection (IgG antibodies will try to reject your donor kidney and you can feel 
general discomfort) 

- High or low blood pressure (symptoms of low blood pressure can be dizziness and symptoms of 
high blood pressure can be headache)  

- Low number of red blood cells (anaemia) 
- Dizziness at change of body position, e.g. when standing up 
- Headache 
- Burst blood vessel in the eye 
- Decreased vision 
- Increased heart rate 
- Infusion site pain 
- Increased liver enzymes (seen in blood tests) 
 
Reporting of side effects 
If you get any side effects, talk to your 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 to store Idefirix 
 
Keep this medicine out of the sight and reach of children. Idefirix is stored in the hospital pharmacy. 
 
Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2-8°C). Do not freeze. Store in the original package in order to protect from 
light.  
 
Chemical and physical in-use stability after reconsitution and dilution has been demonstrated for 
24 hours at 2-8°C and for 4 hours at 25°C during this period. 
 
Do not use this medicine if you notice particulate matter or discoloration after reconstitution. 
 

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


25 

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Idefirix contains  
- The active substance is imlifidase. Each vial contains 11 mg imlifidase. After reconstitution, 

each mL of concentrate contains 10 mg imlifidase.  
- The other ingredients are mannitol, polysorbate 80, trometamol, disodium edetate dihydrate and 

hydrochloric acid (for pH adjustment). See section 2 “Idefirix contains sodium”. 
 
What Idefirix looks like and contents of the pack 
- Idefirix is supplied as a glass vial containing a powder for concentrate for solution for infusion 

(powder for concentrate). The powder is a white freeze-dried cake. 
- Packs contain 1 or 2 vials. 
 
Marketing Authorisation Holder  
Hansa Biopharma AB  
P.O Box 785 
220 07 Lund  
Sweden 
  
Manufacturer 
Biothechnologines farmacijos centras Biotechpharma UAB 
Mokslininku street 4 
LT-08412 Vilnius 
Lithuania 
 
This leaflet was last revised in  
 
This medicine has been given ‘conditional approval’. This means that there is more evidence to come 
about this medicine.  
The European Medicines Agency will review new information on this medicine at least every year and 
this leaflet will be updated as necessary. 
 
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: 
 
Reconstitution of powder 
Introduce 1.2 mL of sterile water for injections into the Idefirix vial, taking care to direct the water to 
the glass wall and not into the powder. 
 
Swirl the vial gently for at least 30 seconds to dissolve the powder completely. Do not shake so as to 
minimise the likelihood of forming foam. The vial will now contain imlifidase 10 mg/mL and up to 
1.1 mL of the solution can be withdrawn. 
 
The reconstituted solution should be clear and colourless. Do not use if particles are present or the 
solution is discoloured. It is recommended to transfer the reconstituted solution from the vial to the 
infusion bag immediately. 
 



26 

Preparation of the solution for infusion  
Slowly add the correct amount of reconstituted imlifidase solution to an infusion bag containing 
50 mL of sodium chloride 9 mg/mL (0.9%) solution for infusion. Invert the infusion bag several times 
to thoroughly mix the solution. The infusion bag should be protected from light. 
 
Prior to use the solution for infusion should be inspected visually for particulate matter or 
discolouration. Discard the solution if any particulate matter or discolouration is observed.  
 
Administration  
The entire, fully diluted infusion should be infused over 15 minutes through an infusion set and a 
sterile, inline, non-pyrogenic, low protein-binding filter (pore size of 0.2 μm). At the end of the 
infusion, flushing the intravenous line with sodium chloride 9 mg/mL (0.9%) solution for infusion will 
ensure that the patient receives the full dose. Do not store any unused infusion solution for use later.  
  



27 

 

 

 

 

 

 

 

 

 

Annex IV 
 

Conclusions on the granting of the conditional marketing authorisation presented by the 
European Medicines Agency 

 

 



28 

Conclusions presented by the European Medicines Agency on: 

• Conditional marketing authorisation 

The CHMP having considered the application is of the opinion that the risk-benefit balance is 
favourable to recommend the granting of the conditional marketing authorisation as further 
explained in the European Public Assessment Report. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) 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
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE CONDITIONAL MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET
	Conclusions on the granting of the conditional marketing authorisation presented by the European Medicines Agency