Ilumetri

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 
Ilumetri 100 mg solution for injection in pre-filled syringe. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled syringe contains 100 mg of tildrakizumab in 1 mL. 
 
Tildrakizumab is a humanised IgG1/k monoclonal antibody produced in Chinese Hamster Ovary (CHO) 
cells by recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection) 
 
The solution is clear to slightly opalescent and colourless to slightly yellow. The solution pH is in the 
range of 5.7 - 6.3 and the osmolality is between 258 and 311 mOsm/kg. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Ilumetri is indicated for the treatment of adults with moderate to severe plaque psoriasis who are 
candidates for systemic therapy. 
 
4.2 Posology and method of administration 
 
Ilumetri is intended for use under the guidance and supervision of a physician experienced in the diagnosis 
and treatment of plaque psoriasis.  
 
Posology 
 
The recommended dose of Ilumetri is 100 mg by subcutaneous injection at weeks 0, and 4 and every 
12 weeks thereafter.  
In patients with certain characteristics (e.g. high disease burden, body weight ≥ 90 kg) 200 mg may 
provide greater efficacy.  
 
Consideration should be given to discontinuing treatment in patients who have shown no response after 
28 weeks of treatment. Some patients with initial partial response may subsequently improve with 
continued treatment beyond 28 weeks.  
 
Special populations 
 



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Elderly 
No dose adjustment is required (see section 5.2).  
 
Renal or hepatic impairment  
Ilumetri has not been studied in these patient populations. No dose recommendations can be made. For 
further information on elimination of tildrakizumab, see section 5.2. 
 
Paediatric population 
The safety and efficacy of Ilumetri in children and adolescents below the age of 18 years have not yet 
been established. No data are available. 
 
Method of administration  
 
Ilumetri is administered by subcutaneous injection. Injection sites should be alternated. Ilumetri should not 
be injected into areas where the skin is affected by plaque psoriasis or is tender, bruised, red, hard, thick, 
or scaly. The pre-filled syringe must not be shaken. Each pre-filled syringe is for single use only. 
 
Inject the full amount of tildrakizumab according to the instructions for use provided in the package 
leaflet.  
 
After proper training in subcutaneous injection technique, patients may self-inject Ilumetri if a physician 
determines that it is appropriate. However, the physician should ensure appropriate follow-up of patients. 
Patients should be instructed to inject the full amount of Ilumetri according to the instructions provided in 
the package leaflet. Comprehensive instructions for administration are given in the package leaflet.  
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Clinically important active infection, e.g. active tuberculosis (see section 4.4). 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number of 
the administered product should be clearly recorded. 
 
Infections 
 
Ilumetri has the potential to increase the risk of infection (see section 4.8). 
Caution should be exercised when considering the use of Ilumetri in patients with a chronic infection or a 
history of recurrent or recent serious infection. 
Patients should be instructed to seek medical advice if signs or symptoms suggestive of a clinically 
relevant chronic or acute infection occur. If a patient develops a serious infection, the patient should be 
closely monitored and Ilumetri should not be administered until the infection resolves. 
 
Pre-treatment evaluation for tuberculosis  
 
Prior to initiating treatment with Ilumetri, patients should be evaluated for tuberculosis (TB) infection. 
Patients receiving Ilumetri should be closely monitored for signs and symptoms of active TB during and 
after treatment. Anti-TB therapy should be considered prior to initiating Ilumetri in patients with a past 
history of latent or active TB in whom an adequate course of treatment cannot be confirmed. 



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Hypersensitivity 
 
If a serious hypersensivity reaction occurs, administration of Ilumetri should be discontinued immediately 
and appropriate therapy initiated.  
 
Vaccinations 
 
Prior to initiating treatment with tildrakizumab, consider completion of all appropriate immunisations 
according to current immunisation guidelines. If a patient has received live viral or bacterial vaccination it 
is recommended to wait at least 4 weeks prior to starting treatment with tildrakizumab. Patients treated 
with Ilumetri should not receive live vaccines during treatment and for at least 17 weeks after treatment 
(see section 4.5). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Vaccines 
 
No data are available on the response to live or inactivated vaccines. Live vaccines should not be given 
concurrently with Ilumetri (see section 4.4). 
 
Interactions with cytochrome p450 
 
Concomitant medicines affecting Ilumetri pharmacokinetics are not expected since it is cleared from the 
body by general protein catabolism processes with no contribution of cytochrome P450 (CYP450) 
enzymes, and it is not eliminated by renal or hepatic pathways. Furthermore, Ilumetri does not impact the 
pharmacokinetics of concomitant medicines metabolized by CYP450 enzymes either through direct or 
indirect mechanisms (see section 5.2). 
 
Interactions with other immunosuppressive agents or phototherapy 
 
The safety and efficacy of Ilumetri in combination with other immunosupressive agents, including 
biologics, or phototherapy has not been evaluated. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential  
 
Women of childbearing potential should use an effective method of contraception during treatment and for 
at least 17 weeks after treatment. 
 
Pregnancy 
 
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of tildrakizumab 
in pregnant women. Animal studies do not indicate direct or indirect harmful effect with respect to 
reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of 
Ilumetri during pregnancy. 
 
Breast-feeding 
 
It is unknown whether tildrakizumab is excreted in human milk. Available toxicological data in 
cynomolgus monkey have shown negligible levels of Ilumetri in milk on postnatal day 28 (see section 
5.3). In humans, during the first few days after birth antibodies may be transferred to the newborns 



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through milk. In this short period, a risk to the newborns/infants cannot be excluded. A decision must be 
made whether to discontinue breast-feeding or to discontinue/abstain from Ilumetri therapy taking into 
account the benefit of breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
The effect of Ilumetri on human fertility has not been evaluated. Animal studies do not indicate direct or 
indirect harmful effects with respect to fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Ilumetri has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common adverse reactions are upper respiratory tract infections, headache, gastroenteritis, 
nausea, diarrhoea, injection site pain and back pain. 
 
Tabulated list of adverse reactions 
 
Three placebo-controlled studies (Phase 2b and two Phase 3) were integrated to evaluate the safety of 
Ilumetri in comparison to placebo. A total of 1,768 patients were evaluated (705 patients on 100 mg, 708 
patients on 200 mg and 355 patients on placebo). These 355 patients on placebo were subsequently 
crossed over to tildrakizumab. 
Adverse reactions (Table 1) are listed by MedDRA system organ class (SOC) and frequency, using the 
following convention: 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 
available data).  
 
Table 1. List of adverse reactions  

MedDRA System Organ 
Class 

Preferred term Frequency category 

Infections and infestations Upper respiratory tract infectionsa Very common  
Nervous system disorders Headache Common  
Gastrointestinal disorders Gastroenteritis Common 

Nausea Common 
Diarrhoea Common 

General disorders and 
administration site 
conditions 

Injection site pain Common 

Back pain Common 
aIncluding nasopharyngitis. 
 
Description of selected adverse reaction 
 
Immunogenicity 



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In pooled Phase 2b and Phase 3 analyses 7.3% of Ilumetri-treated patients developed antibodies to 
Ilumetri. No apparent association between the development of antibodies to Ilumetri to lower efficacy and 
the development of treatment emergent adverse events was observed.  
 
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 
 
Doses up to 10 mg/kg intravenously have been safely administered in clinical trials.  
In the event of overdose, it is recommended that the patient be monitored for any signs or symptoms of 
adverse reactions and that appropriate symptomatic treatment be instituted immediately. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC17 
 
Mechanism of action 
 
Tildrakizumab is a humanized IgG1/k monoclonal antibody that specifically binds to the p19 protein 
subunit of the interleukin-23 (IL-23) cytokine without binding to IL-12 and inhibits its interaction with the 
IL-23 receptor. 
 
IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. 
Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines.  
 
Clinical efficacy and safety 
 
The multicentre, randomised, double-blind, placebo-controlled trials reSURFACE 1 and reSURFACE 2 
studies enrolled a total of 1,862 patients 18 years of age and older with plaque psoriasis who had a 
minimum body surface area involvement of 10%, a Physician Global Assessment (PGA) score of ≥3 in 
the overall assessment (plaque thickness, erythema, and scaling) of psoriasis on a severity scale of 0 to 5, a 
Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or 
systemic therapy. 
 
In these studies, patients were randomised to either placebo or tildrakizumab (including 200 mg and 
100 mg at 0, 4 and every twelve weeks thereafter [Q12W]), up to 52 or 64 weeks. In the active comparator 
study (reSURFACE 2), patients were also randomised to receive etanercept 50 mg twice weekly for 
12 weeks, and weekly thereafter up to 28 weeks.  
 
Overall demographic and baseline characteristics in reSURFACE1 and reSURFACE2 studies were 
consistent across individual trials. Patients were 18 to 82 years old, with a mean age of 45.9. The median 
baseline PASI score ranged from 17.7 to 18.4 across treatment groups. Baseline PGA score was marked or 
severe in 33.4% of patients. Of all patients, 35.8% had received prior phototherapy, 41.1% had received 
prior conventional systemic therapy, 16.7% had received prior biologic therapy for the treatment of plaque 
psoriasis. A total of 15.4% of study patients had a history of psoriatic arthritis. Mean baseline 
Dermatology Life Quality Index (DLQI) ranged from 13.0 to 14.8. 



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Studies reSURFACE 1 and reSURFACE 2 assessed the changes from baseline at Week 12 in the two co-
primary endpoints: 1) PASI 75 and 2) PGA of “0” (cleared) or “1” (minimal), with at least a 2-point 
improvement from baseline. Other evaluated outcomes included the proportion of patients who achieved 
PASI 90, PASI 100, the proportion of patients with DLQI 0 or 1, and maintenance of efficacy up to 
52/64  weeks.  
 
Results obtained at weeks 12, 28 and beyond (up to week 64 in reSURFACE 1 and up to week 52 in 
reSURFACE 2) are presented in Table 2 and Table 3.  
 
Table 2. Summary of Response Rates in Studies reSURFACE 1 and reSURFACE 2 

 
Week 12 (2 doses)* Week 28 (3 doses)* 

200 m
g 

100 m
g 

Placeb
o 

Etanercep
t 200 mg 100 mg 

Etanercep
t 

reSURFACE1 

Number of patients 308 309 154 - 298 299 - 

PASI 75a (%) 62.3†b 63.8†b 5.8b - 81.9c 80.4c - 
PGA of “clear” or 
“minimal” with ≥2 grade 
improvement from 
Baselinea (%) 

59.1†b 57.9†b 7.1b - 69.1c 66.0c - 

PASI 90 (%) 35.4†b 34.6†b 2.6b - 59.0c 51.6c - 
PASI 100 (%) 14.0†b 13.9†b 1.3b - 31.5c 23.5c - 
DLQI Score 0 or 1 (%) 44.2† 41.5 † 5.3 - 56.7c 52.4c - 

reSURFACE2 

Number of patients 314 307 156 313 299 294 289 

PASI 75a (%) 65.6†‡b 61.2†‡b 5.8b 48.2b 72.6‡b 73.5‡b 53.6b 
PGA of “clear” or 
“minimal” with ≥2 grade 
improvement from 
Baselinea (%) 

59.2†¥b 54.7†b 4.5b 47.6b 69.2‡b 64.6‡b 45.3b 

PASI 90 (%) 36.6†‡b 38.8†‡b 1.3b 21.4b 57.7‡c 55.5‡c 29.4 c 
PASI 100 (%) 11.8†‡b 12.4†‡b 0 4.8b 27.0‡c 22.8‡c 10.7c 
DLQI Score 0 or 1 (%) 47.4†¥ 40.2† 8.0 35.5 65.0‡c 54.1‡c 39.4c 

a Co-primary efficacy endpoint at week 12. 
b Non responder imputation for missing data.  
c No imputation for missing data. 
*The number of doses administered refers only to tildrakizumab groups. 
n = number of patients in the full analysis set for which data was available, after imputation when applicable. 
p-values calculated using the Cochran-Mantel-Haenszel (CMH) test stratified by body weight (≤90 kg, >90 kg) and prior 
exposure to biologic therapy for psoriasis (yes/no). 
† p≤0.001 versus placebo; ‡ p≤0.001 versus etanercept; ¥ p≤0.05 versus etanercept. 

 
Maintenance of Response   
 
The maintenance of response in studies reSURFACE1 and reSURFACE2 are presented in Table 3. 
Maintenance and durability of PASI 90 response over time is presented in Figure 1. 
 
Table 3. Maintenance of Response in Studies reSURFACE 1 and reSURFACE 2 



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Long term responsea,b 

200 mg 100 mg 
reSURFACE 1 Week 28 Week 64 Week 28 Week 64 
Number of patients 116 114 115 112 
PGA of “clear” or “minimal” with ≥2 
grade improvement from Baseline (%) 80.2 76.3 80.9 61.6 

PASI 90 (%) 70.7 74.6 65.2 58.0 
PASI 100 (%) 38.8 40.4 25.2 32.1 
reSURFACE 2 Week 28 Week 52 Week 28 Week 52 
Number of patients 108 105 213 204 
PGA of “clear” or “minimal” with ≥2 
grade improvement from Baseline (%) 88.0 84.8 84.0 

79.4 

PASI 90 (%) 75.0 81.9 74.2 78.4 
PASI 100 (%) 34.3 46.7 30.2 35.3 

a Long-term response in patients who were responders (had achieved at least PASI 75) to tildrakizumab at week 28. 
b No imputation for missing data. 
 
Figure 1. Maintenance and durability of PASI 90 Response. Proportion of Patients with PASI 90 
response over time up to Week 64 (Full Analysis Set Part 3*) 

 
Patients randomised to tildrakizumab 100 mg or tildrakizumab 200 mg in Part 1 who were PASI 75 responders at week 28 
(reSURFACE1). 
*No imputation of missing data. 
**These patients were switched to placebo at week 28. 

21.6

58

31.7

74.6

0

10

20

30

40

50

60

70

80

90

W4 W8 W12 W16 W22 W28 W32 W36 W40 W44 W48 W52 W56 W60 W64

R
es

po
nd

er
s (

%
)

Ilumetri 100 mg --> Placebo** Ilumetri 100 mg

Ilumetri 200 mg --> Placebo** Ilumetri 200 mg



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Quality of Life/Patient-reported Outcomes 
 
At week 12 and across studies, tildrakizumab was associated with statistically significant improvement in 
Health-related Quality of Life as assessed by the DLQI (Table 2). Improvements were maintained over 
time with at week 52, 63.7% (100 mg) and 73.3% (200 mg) in reSURFACE 1, and 68.8% (100 mg) and 
72.4% (200 mg) in reSURFACE 2 of patients who were PASI 75 responders at week 28 having a DLQI of 
0 or 1.  
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with Ilumetri 
in one or more subsets of the paediatric population in the treatment of plaque psoriasis (see section 4.2 for 
information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The subcutaneous formulation of tildrakizumab showed an absolute bioavailability ranging from 73% 
(90% CI: 46% - 115%, 200 mg SC vs. 3 mg/kg IV) to 80% (90% CI: 62% - 103%, 50 mg SC vs. 
0.5 mg/kg IV) in healthy subjects, as a result of cross study single dose comparison. Maximum 
concentration was reached at 6.2 days after injection. Population PK analysis indicated a 31% higher 
bioavailability in healthy subjects compared to patients. 
 
At steady state, following administration of 100 mg of tildrakizumab in subjects with moderate to severe 
plaque psoriasis geometric means (% CV) of AUC0-τ and Cmax values were respectively 305 μg·day/mL 
(41%) and 8.1 μg/mL (34%), whereas they were 612 μg·day/mL (40%) and 16.3 μg/mL (33%) following 
administration of 200 mg.  
 
Distribution 
 
Tildrakizumab has limited extravascular distribution with volume of distribution (Vd) values ranging from 
76.9 to 106 mL/kg. 
 
Biotransformation 
 
Tildrakizumab is catabolized into component amino acids by general protein degradation processes. 
Small-molecule metabolic pathways (e.g., CYP450 enzymes, glucuronosyltransferases) do not contribute 
to its clearance. 
 
Elimination 
 
Clearance values range from 2.04 to 2.52 mL/day/kg and the half-life was 23.4 days (23% CV) in subjects 
with plaque psoriasis.  
 
Linearity/non-linearity 
 
Tildrakizumab exhibited dose-proportional pharmacokinetics in subjects with plaque psoriasis over a dose 
range from 50 mg to 400 mg following subcutaneous administration, with clearance being independent of 
dose. 
 



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Steady-state is achieved by 16 weeks with the clinical regimen of 0, 4, and every 12 weeks thereafter, with 
1.1-fold accumulation in exposure between week-1 and week-12 independent of dose. 
 
Body weight 
 
Population pharmacokinetic modelling indicated that exposure decreased as body weight increased. The 
geometric mean exposure (AUC0-τ at steady state) in adult patients weighing >90 kg following a 100 mg 
or 200 mg SC dose was predicted to be about 30% lower than in an adult patient weighing ≤90 kg (see 
section 4.2).  
 
Pharmacokinetics in special populations 
 
Elderly 
Population pharmacokinetic analysis indicated that age did not have a clinically significant influence on 
the clearance of tildrakizumab in adult subjects with plaque psoriasis. Following administration of 100 mg 
or 200 mg of tildrakizumab, subjects who are 65 years or older (n=81 and n=82, respectively) had a 
similar tildrakizumab clearance as compared to subjects less than 65 years old (n=884). 
 
Renal and Hepatic impairment 
No formal trial of the effect of hepatic or renal impairment on the pharmacokinetics of tildrakizumab was 
conducted. Tildrakizumab is catabolized into component amino acids by general protein degradation 
processes and is not eliminated by renal or hepatic pathways.  
 
Drug interactions 
 
Results from a drug-drug interaction study conducted in plaque psoriasis subjects suggest that 
tildrakizumab had no clinically relevant effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. 
Therefore, tildrakizumab does not impact the pharmacokinetics of concomitant medicines metabolized by 
CYP enzyme (see section 4.5). 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, and repeated dose toxicity. 
 
Animal carcinogenicity studies have not been conducted with tildrakizumab. Studies in mouse tumor 
models showed that selective inhibition of IL-23p19 does not increase carcinogenic risk. 
 
In cynomolgus monkeys, there was negligible secretion of the product into breast milk. One month after 
birth, the milk/serum ratio was ≤0.002. Tildrakizumab was shown to distribute across the placental barrier. 
After repeated dosing to pregnant cynomolgus monkeys, serum concentrations were quantifiable in the 
fetus, but the reproduction toxicity studies did not reveal any untoward effects. 
 
No effects on fertility parameters such as reproductive organs, menstrual cycle length, and/or hormones 
were observed in male and female cynomolgus monkeys that were administered tildrakizumab at doses 
resulting in >100 times the human exposure at the recommended clinical dose based on AUC. 
 
In a pre- and postnatal development toxicity study in monkeys, no related increase in pregnancy loss was 
observed at exposures up to 85 times the human exposure at the recommended dose. No harmful effects 
were noted in neonates at maternal exposures up to 9 times the human exposure at the recommended dose. 
Two neonatal deaths from monkeys administered tildrakizumab at maternal exposure of 85 times the 
human exposure at the recommended dose were attributed to possible viral infection and considered of 
uncertain relationship to the treatment. The clinical significance of these findings is unknown.  



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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
L-Histidine 
L-Histidine hydrochloride monohydrate 
Polysorbate 80 
Sucrose 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.  
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Unopened pre-filled syringe of Ilumetri may be removed from the refrigeration and stored up to 25°C for 
a single period of up to 30 days. Once removed from the refrigerator and stored under these conditions, 
discard after 30 days or by the expiry date printed on the container, whichever occurs first. A field for the 
date is provided on the carton to record the removal from refrigerator date.  
Keep the pre-filled syringes in the outer carton in order to protect from light until the time of use. 
Do not shake. 
 
6.5 Nature and contents of container 
 
1 mL solution in a type I glass pre-filled syringe with stainless steel 29G x ½” needle, covered with a 
needle shield and rigid needle shield of polypropylene with a fluropolymer lamination, plunger stopper 
assembled in a passive safety device. 
 
Pack size of 1 pre-filled syringe or 2 pre-filled syringes.  
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Ilumetri is a sterile solution for injection in pre-filled syringe. The pre-filled syringes are for single use 
only. 
 
Do not shake or freeze the pre-filled syringe. The pre-filled syringe should be taken out of the refrigerator 
30 minutes before injecting to allow it to reach room temperature (up to 25ºC).  
Prior to use, a visual inspection of the pre-filled syringe is recommended. The liquid should be clear. Its 
colour may vary from colourless to slightly yellow. A small air bubble may be apparent: this is normal. 
Do not use if the liquid contains easily visible particles, is cloudy or is distinctly brown.  
 



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The instructions for using the pre-filled syringes, included with the package leaflet, must be followed 
carefully.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Almirall, S.A. 
Ronda General Mitre, 151  
08022 Barcelona  
Spain 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1323/001 
EU/1/18/1323/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 september 2018 
 
 
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.  



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 

 
 



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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)  
 
N.V. Organon 
Veersemeer 4 
5347 JN Oss 
The Netherlands 
 
Name and address of the manufacturer(s) responsible for batch release 
 
SUN Pharmaceutical Industries (Europe) B.V. 
Polarisavenue 87 
2132JH Hoofddorp 
The Netherlands 
 
Industrias Farmacéuticas Almirall, S.A. 
Ctra. Nacional II, Km. 593 
08740 Sant Andreu de la Barca 
Barcelona 
Spain 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
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  
 
The requirements for submission of periodic safety update reports for this medicinal product are set out 
in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 



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The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.  

  



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON – PACK SIZE 1 PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ilumetri 100 mg solution for injection in pre-filled syringe 
tildrakizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 100 mg of tildrakizumab in 1 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: L-Histidine, L-Histidine hydrochloride monohydrate, polysorbate 80, sucrose and water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
1 pre-filled syringe 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use.  
Single use only. 
 
 
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 
 
Removal from refrigerator date: 
 



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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
Do not shake. 
 
 
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 
 
Almirall, S.A.   
Ronda General Mitre, 151  
08022 Barcelona  
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1323/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ilumetri 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 



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NN:  



21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON – PACK SIZE 2 PRE-FILLED SYRINGES  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ilumetri 100 mg solution for injection in pre-filled syringe 
tildrakizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 100 mg of tildrakizumab in 1 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: L-Histidine, L-Histidine hydrochloride monohydrate, polysorbate 80, sucrose and water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
2 pre-filled syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use.  
Single use only. 
 
 
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 
 
 



22 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
Do not shake. 
 
 
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 
 
Almirall, S.A.   
Ronda General Mitre, 151  
08022 Barcelona  
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1323/002 2 pre-filled syringes  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ilumetri 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 



23 

NN:  



24 

SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL - PRE-FILLED SYRINGE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ilumetri 100 mg injection 
tildrakizumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 mL 
 
 
6. OTHER 
 
  



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



26 

Package leaflet: Information for the user 
 

Ilumetri 100 mg solution for injection in pre-filled syringe 
tildrakizumab 

 
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, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Ilumetri is and what it is used for 
2. What you need to know before you use Ilumetri 
3. How to use Ilumetri 
4. Possible side effects 
5. How to store Ilumetri 
6. Contents of the pack and other information 
 
 
1. What Ilumetri is and what it is used for 
 
Ilumetri contains the active substance tildrakizumab. Tildrakizumab belongs to a group of medicines 
called interleukin (IL) inhibitors. 
This medicine works by blocking the activity of a protein called IL-23, a substance found in the body 
which is involved in normal inflammatory and immune responses and which is present at increased levels 
in diseases such as psoriasis. 
 
Ilumetri is used to treat a skin condition called plaque psoriasis, in adults with moderate to severe disease.  
Using Ilumetri will benefit you by improvements of skin clearance and reducing your symptoms. 
 
 
2. What you need to know before you use Ilumetri 
 
Do not use Ilumetri: 

- If you are allergic to tildrakizumab or any of the other ingredients of this medicine (listed in 
section 6). 

- If you have an infection which your doctor thinks is important, for example, active tuberculosis 
which is an infectious disease affecting mainly the lungs. 

 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before using Ilumetri: 

- If you experience allergic reactions with symptoms such as chest tightness, wheezing, swelling of 
the face, lips or throat do not inject more Ilumetri and contact your doctor immediately. 

- If you currently have an infection or if you have long-term or repeated infections. 



27 

- If you have recently had or plan to have a vaccination.  
 
If you are not sure if any of the above applies to you, talk to your doctor, pharmacist or nurse before using 
Ilumetri. 
 
Look out for infections and allergic reactions 
Ilumetri can potentially cause serious side effects, including infections and allergic reactions. You must 
look out for signs of these conditions while you are taking Ilumetri. 
Stop using Ilumetri and tell your doctor or seek medical help immediately if you notice any signs 
indicating a possible serious infection or an allergic reaction (see 4. Possible side effects).  
 
Children and adolescents 
Ilumetri is not recommended for use in children and adolescents under 18 years of age. This is because it 
has not yet been evaluated in this group of patients. 
 
Other medicines and Ilumetri  
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
These include vaccines and immunosuppressants (medicines that affect the immune system). 
 
You should not be given certain types of vaccines (live vaccines) while using Ilumetri. No data are 
available with the concomitant use of Ilumetri and live vaccines. 
 
Pregnancy, breastfeeding and fertility 
It is preferable to avoid the use of Ilumetri in pregnancy. The effects of this medicine in pregnant women 
are not known. 
 
If you are a woman of childbearing potential, you are advised to avoid becoming pregnant and must use an 
effective method of contraception whilst having treatment with Ilumetri and for at least 17 weeks after 
treatment. 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 
doctor or pharmacist for advice before using this medicine.  
 
Driving and using machines 
Ilumetri has no or little effect on the ability to drive and use machines. 
 
 
3. How to use Ilumetri 
 
Ilumetri is intended for use under the guidance and supervision of a physician experienced in the diagnosis 
and treatment of psoriasis. 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure. This medicine is for single use only. 
 
The recommended dose of Ilumetri is 100 mg by subcutaneous injection at weeks 0, and 4 and every 
12 weeks thereafter.  
In patients with certain characteristics (e.g. high disease burden, body weight ≥ 90 kg) 200 mg may 
provide greater efficacy.  
 
Your doctor will decide for how long you need to take Ilumetri. 
 



28 

After proper training in subcutaneous injection technique, you may inject Ilumetri yourself if your doctor 
determines that it is appropriate. 
 
For instructions on how to inject Ilumetri yourself, see ‘Instructions for use’ at the end of this leaflet. 
 
Talk to your doctor about when you will have your injections and follow-up appointments. 
 
Use in children and adolescents 
The safety and efficacy of Ilumetri in children and adolescents under 18 years of age has not yet been 
established and therefore Ilumetri is not recommended for use in children or adolescents. 
 
If you use more Ilumetri than you should 
If you have administered more Ilumetri than you should or the dose has been administered sooner than 
according to your doctor’s prescription, tell your doctor. 
 
If you forget to use Ilumetri 
If you have forgotten or missed an Ilumetri injection, administer the dose as soon as possible. Thereafter, 
resume dosing at the regularly scheduled interval. 
 
If you stop using Ilumetri 
The decision to stop using Ilumetri should be discussed with your doctor. Your symptoms may return 
upon discontinuation.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
If you notice any of the following, contact your doctor immediately: 

- Swelling of the face, lips or throat 
- Breathing difficulties 

As these may be signs of an allergic reaction. 
 
Other side effects 
Most of the following side effects are mild. If any of these side effects becomes severe, tell your doctor or 
pharmacist. 
 
 Very common side effects (may affect more than 1 in 10 people): 

- Upper respiratory infections 
 
 Common side effects (may affect up to 1 in 10 people): 

- Gastroenteritis 
- Nausea 
- Diarrhoea 
- Injection site pain 
- Back pain 
- Headache 

 
Reporting of side effects 



29 

If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Ilumetri  
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the label of the pre-filled 
syringe after EXP. The expiry date refers to the last day of that month. 
 
Keep the product in the original carton in order to protect from light until the time of use. Do not shake. 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. 
 
After taking a pre-filled syringe from the refrigerator, wait approximately 30 minutes to allow the Ilumetri 
solution in the syringe to reach room temperature (up to 25ºC). Do not warm in any other way.  
 
Do not use if the liquid contains visible particles, is cloudy or is distinctly brown.  
 
Once taken out of the refrigerator, do not store tildrakizumab above 25ºC or refrigerate it again. 
Write down the date of removal from the refrigerator in the space provided on the outer carton and 
appropriate discard date. Use the syringe within 30 days after taking it out of the refrigerator or by the 
expiry date whichever occurs first. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 
away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Ilumetri contains 

- The active substance is tildrakizumab. Each pre-filled syringe contains 100 mg of tildrakizumab. 
- The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, 

sucrose and water for injections. 
 
What Ilumetri looks like and contents of the pack  
Ilumetri is a clear to slightly opalescent and colourless to slightly yellow solution. 
Ilumetri is available in unit packs containing 1 pre-filled syringe and packs comprising 2 pre-filled 
syringes.  
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Almirall, S.A. 
Ronda General Mitre, 151  
08022 Barcelona, Spain 
 
Manufacturer 
SUN Pharmaceuticals Industries (Europe) B.V. 
Polarisavenue 87 
2132JH Hoofddorp, Netherlands 



30 

 
Industrias Farmacéuticas Almirall, S.A. 
Ctra. Nacional II, Km. 593 
08740 Sant Andreu de la Barca, Barcelona, Spain 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
 
België/Belgique/Belgien/ 
Luxembourg/Luxemburg  
Almirall N.V. 
Tél/Tel: +32 (0)2 771 86 37  
 

Ísland  
Vistor hf. 
Sími: +354 535 70 00  
 

България/ Česká republika/ Eesti/ Ελλάδα/ 
España/ Hrvatska/ Κύπρος/ Latvija/ Lietuva/ 
Magyarország/ Malta/ România/ Slovenija/ 
Slovenská republika  
Almirall, S.A. 
Teл./ Tel/ Τηλ: +34 93 291 30 00  
Tel (Česká republika / Slovenská republika): +420 
220 990 139  
 

Italia  
Almirall SpA 
Tel.: +39 02 346181  
 

Danmark/ Norge/ Suomi/Finland/ Sverige  
Almirall ApS 
Tlf/ Puh/Tel: +45 70 25 75 75  
 

Nederland  
Almirall B.V. 
Tel: +31 (0)307991155  
 

Deutschland  
Almirall Hermal GmbH 
Tel.: +49 (0)40 72704-0  
 

Österreich  
Almirall GmbH 
Tel.: +43 (0)1/595 39 60  
 

France  
Almirall SAS, 1 
Tél.: +33(0)1 46 46 19 20  
 

Polska  
Almirall Sp.z o. o. 
Tel.: +48 22 330 02 57  
 

Ireland 
Almirall ApS 
Tel: +45 70 25 75 75  
 

Portugal  
Almirall - Produtos Farmacêuticos, Lda.  
Tel.: +351 21 415 57 50 

 United Kingdom 
Almirall Limited 
Tel: +44 (0) 800 0087 399  

 
This leaflet was last revised in April 2019 
 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 
 
  



31 

INSTRUCTIONS FOR USE 
 
Before using the pre-filled syringes:  
Important points to know 

• Before you use Ilumetri pre-filled syringes, read and carefully follow all the step-by-step 
instructions. Keep the instructions for use and refer to them as needed. 

• The pre-filled syringes must not be shaken. 
• Read the Ilumetri Package Leaflet to learn more about your medicine. 

 
PRODUCT DESCRIPTION 

This is what Ilumetri pre-filled syringe looks like: 

 
 

 
PREPARATION 
 
1. Take a pack from the refrigerator (if stored in the refrigerator)  

• Take a carton pack out of the refrigerator and place the original and unopened carton pack on a 
clean and flat working surface.  

 
2. Wait for 30 minutes (if stored in the refrigerator) 

• Leave the pre-filled syringe in the Ilumetri carton (with the lid closed) and let it sit at 
room temperature for 30 minutes. 

 
3. Inspect the medicine 

• Remove the pre-filled syringe from the carton when ready to inject.  
- Check the expiration date on the carton and pre-filled syringe and discard if the date has 

passed.  
- DO NOT pull off the needle cover until you are ready to inject.  

• Inspect Ilumetri visually for particulate matter and discoloration prior to administration.  
- Ilumetri is a clear to slightly opalescent and colourless to slightly yellow solution.  
- DO NOT use if the liquid contains visible particles or the syringe is damaged. Air 

bubbles may be present; there is no need to remove them. 
 

 
 
 
 
 
 
 
4. Collect all the materials you need 

• On a clean, well-lit work surface, place the: 
- alcohol wipes 
- cotton ball or gauze pad 



32 

- sticking plaster 
- sharps disposal container 

 
5. Wash your hands 

• Wash your hands thoroughly with soap and water. 

 
6. Choose an injection site 

• Choose an injection site with clear skin and easy access such as abdomen, thighs or upper arm.  
- DO NOT administer 5 cm around the navel or where the skin is tender, bruised, abnormally 

red, hardened or affected by psoriasis.  
- DO NOT inject into scars, stretch marks, or blood vessels.  
- The upper arm is only suitable when someone else is injecting you. 
- Choose a different location for the second injection. 

 
7. Clean injection site 

• Clean the injection site with an alcohol wipe and allow the skin to dry. 
o Do not touch this area again before giving the injection. 

 
 
 
 
 
 
 
 
 

 
 
 

INJECTION 

In case your dose is 200 mg, you will need to use 2 pre-filled syringes each time you administer the 
product.  
 
8. Pull off the needle cover 

• While holding the body of the pre-filled syringe, remove the needle cover as shown and discard. 
You may see 1 or 2 drops of liquid and that is okay. 

o DO NOT touch the blue plunger yet. 
o DO NOT use if pre-filled syringe or needle is bent. 



33 

 
 
9. Pinch skin & insert needle 

• Gently pinch your skin at the chosen injection site. 
• Insert the entire needle into the pinched skin between your fingers, straight up and down at a 

90-degree angle. 
o DO NOT place your finger on the plunger while inserting the needle. 

• Hold the pre-filled syringe steady. 

 

 

    
 
10. Inject 

• After inserting the needle, let go of the skin gently. 
• Press down the blue plunger until it can go no further. This activates the safety mechanism that 

will ensure full retraction of the needle after the injection is given.  
o A complete dose is administered if the blue plunger cannot go any further, and there are 

no spills. 

     
 

11. Remove the used syringe 

• Remove the needle from the skin entirely before letting go of the blue plunger.  
o After the blue plunger is released, the safely lock will draw the needle inside the needle 

guard. 



34 

 
 

• Dispose of used syringe in a sharps disposal container right away after use and before injecting 
a second syringe. 

• If there is some residual fluid or a tiny bit of blood, clean the injection site with a cotton ball or 
gauze pad WITHOUT applying any pressure. If you feel the need, you can use a sticky plaster 
to cover the injection site. 

• Repeat the procedure with the second syringe in a different location of your skin if you are 
administering a dose of 200 mg. 

 

 
 


	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
	A. LABELLING
	B. PACKAGE LEAFLET