Kyntheum

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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 
 
Kyntheum 210 mg solution for injection in pre-filled syringe  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled syringe contains 210 mg brodalumab in 1.5 ml solution. 
1 ml solution contains 140 mg brodalumab. 
 
Brodalumab is a recombinant human monoclonal antibody produced in Chinese Hamster Ovary 
(CHO) cells. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection) 
 
The solution is clear to slightly opalescent, colourless to slightly yellow and free from particles. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Kyntheum is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who 
are candidates for systemic therapy. 
 
4.2 Posology and method of administration 
 
Kyntheum is intended for use under the guidance and supervision of a physician experienced in the 
diagnosis and treatment of psoriasis. 
 
Posology 
The recommended dose is 210 mg administered by subcutaneous injection at weeks 0, 1, and 2 
followed by 210 mg every 2 weeks. 
 
Consideration should be given to discontinuing treatment in patients who have shown no response 
after 12-16 weeks of treatment. Some patients with initial partial response may subsequently improve 
with continued treatment beyond 16 weeks. 
 
Special populations 
 
Elderly (aged 65 years and over) 
No dose adjustment is recommended in elderly patients (see section 5.2). 
 
Renal and hepatic impairment 
Kyntheum has not been studied in these patient populations. No dose recommendations can be made.  



 

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Paediatric population 
The safety and efficacy of Kyntheum in children and adolescents below the age of 18 years have not 
yet been established. No data are available. 
 
Method of administration 
Kyntheum is administered by subcutaneous injection. Each pre-filled syringe is for single use only. 
Kyntheum should not be injected into areas where the skin is tender, bruised, red, hard, thick, scaly, or 
affected by psoriasis. The pre-filled syringe must not be shaken. 
 
After proper training in subcutaneous injection technique, patients may self-inject Kyntheum when 
deemed appropriate by a physician. Patients should be instructed to inject the full amount of 
Kyntheum 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. 
 
Active Crohn’s disease. 
 
Clinically important active infections (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. 
 
Inflammatory bowel disease (including Crohn's disease and ulcerative colitis)  
Cases of new or exacerbations of inflammatory bowel disease have been reported with IL-17 
inhibitors. Therefore Kyntheum is not recommended in patients with inflammatory bowel disease (see 
section 4.8). If a patient develops signs and symptoms of inflammatory bowel disease, or experiences 
an exacerbation of pre-existing inflammatory bowel disease, Kyntheum should be discontinued and 
appropriate medical management should be initiated. 
 
Suicidal ideation and behaviour 
Suicidal ideation and behaviour, including completed suicide, have been reported in patients treated 
with Kyntheum. The majority of patients with suicidal behaviour had a history of depression and/or 
suicidal ideation or behaviour. A causal association between treatment with Kyntheum and increased 
risk of suicidal ideation and behaviour has not been established.  
 
The risk and benefit of treatment with Kyntheum should be carefully weighed for patients with a 
history of depression and/or suicidal ideation or behaviour, or for patients who develop such 
symptoms. Patients, caregivers, and families should be advised of the need to be alert for the 
emergence or worsening of depression, suicidal ideation, anxiety, or other mood changes, and they 
should contact their healthcare provider if such events occur. If a patient suffers from new or 
worsening symptoms of depression and/or suicidal ideation or behaviour is identified, it is 
recommended to discontinue treatment with Kyntheum. 
 
Hypersensitivity reactions 
Rare cases of anaphylactic reactions have been reported in the post-marketing setting. In the event of 
an anaphylactic reaction, or any other serious allergic reaction, administration of Kyntheum should be 
discontinued and appropriate therapy initiated. 
 
Infections 
Kyntheum may increase the risk of infections.  



 

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During the 12-week placebo-controlled clinical trial period in patients with psoriasis, serious infections 
were observed in 0.5% of patients receiving Kyntheum (see section 4.8).  
 
Caution should be exercised when considering the use of Kyntheum in patients with a chronic 
infection or a history of recurrent infection. Patients should be instructed to seek medical advice if 
signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the 
patient should be closely monitored and Kyntheum should not be administered until the infection 
resolves. 
 
No cases of active tuberculosis were reported from clinical trials. However, Kyntheum should not be 
given to patients with active tuberculosis. Anti-tuberculosis therapy should be considered prior to 
initiation of Kyntheum in patients with latent tuberculosis.  
 
Vaccinations 
It is recommended that patients be brought up-to-date with all immunisations in accordance with local 
immunisation guidelines prior to initiation of treatment with Kyntheum. Live vaccines should not be 
given concurrently with Kyntheum (see section 4.5). No data are available on the response to live 
vaccines or the risk of infection, or transmission of infection after the administration of live vaccines in 
patients receiving Kyntheum. 
 
Vaccination of infants 
Vaccination of infants with live vaccines following third trimester exposure to Kyntheum should be 
discussed with a physician (see also section 4.6). 
 
Concomitant immunosuppressive therapy 
The safety and efficacy of Kyntheum in combination with immunosuppressants, including biologics, 
or phototherapy have not been evaluated. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Live vaccines should not be given concurrently with Kyntheum (see section 4.4). 
 
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g. IL-1, 
IL-6, IL-10, TNFα, IFN) during chronic inflammation. Although a role for interleukin (IL)-17A and 
IL-17RA in the regulation of CYP450 enzymes has not been reported, the effect of brodalumab on 
CYP3A4/3A5 activity was evaluated in a disease-drug-drug interaction study.  
 
In patients with moderate to severe plaque psoriasis, a single subcutaneous dose of 210 mg 
brodalumab increased the exposure of midazolam, a CYP3A4/3A5 substrate by 24%. Based on the 
magnitude of change in exposure of midazolam, no dose adjustment of CYP3A4/3A5 substrates is 
necessary when administered concomitantly with Kyntheum. 
 
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 12 weeks after treatment. 
 
Pregnancy 
There are no or limited amount of data from the use of brodalumab in pregnant women. 
 
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3). 
 



 

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Human IgG2 is known to cross the placental barrier and brodalumab is a human IgG2, therefore, 
brodalumab has the potential to be transmitted from the mother to the developing foetus. As a 
precautionary measure, it is preferable to avoid the use of Kyntheum in pregnancy.  
 
As the metabolism of brodalumab is unknown in infants, benefit risk for exposure of the infant to live 
vaccines following third trimester exposure to Kyntheum should be discussed with a physician. 
 
Breast-feeding 
It is unknown whether brodalumab is excreted in human milk. Brodalumab is a monoclonal antibody 
and is expected to be present in the first milk and at low levels afterwards. 
  
A risk to the newborns/infants cannot be excluded. 
 
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from 
Kyntheum therapy taking into account the benefit of breast-feeding for the child and the benefit of 
therapy for the woman. 
 
Fertility 
No data are available on the effect of brodalumab on human fertility. Animal studies did not show any 
effects on male and female reproductive organs and on sperm count, motility and morphology (see 
section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Kyntheum has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most commonly reported adverse reactions in all Kyntheum-treated patients were arthralgia 
(4.6%), headache (4.3%), fatigue (2.6%), diarrhoea (2.2%), and oropharyngeal pain (2.1%).  
 
Tabulated list of adverse reactions 
Adverse reactions from clinical trials and post-marketing experience (Table 1) are listed by MedDRA 
system organ class (SOC). Within each SOC, the adverse reactions are ranked by frequency, with the 
most frequent reactions first. Within each frequency grouping adverse reactions are presented in order 
of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction 
is based on 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) and very rare (<1/10,000). 
 



 

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Table 1: List of adverse reactions in clinical trials and post-marketing experience 
 

System Organ Class Frequency Adverse Reaction 
Infections and infestations Common Influenza 

Tinea infections (including tinea pedis, tinea 
versicolor, tinea cruris) 

 Uncommon Candida infections (including oral, genital, and 
oesophageal infections) 

Blood and lymphatic system 
disorders 

Uncommon Neutropenia 

Immune system disorders Rare Anaphylactic reaction* 
Nervous system disorders Common Headache 
Eye disorders Uncommon Conjunctivitis 
Respiratory, thoracic and 
mediastinal disorders 

Common Oropharyngeal pain 

Gastrointestinal disorders Common Diarrhoea 
Nausea 

Musculoskeletal and 
connective tissue disorders 

Common Arthralgia 
Myalgia 

General disorders and 
administration site conditions 

Common Fatigue 
Injection site reactions (including injection site 
erythema, pain, pruritus, bruising, 
haemorrhage) 

*from post-marketing experience 
 
Description of selected adverse reactions 
 
Inflammatory bowel disease 
Cases of new or exacerbations of inflammatory bowel disease (including Crohn's disease and 
ulcerative colitis) have been reported with IL-17 inhibitors (see section 4.4). 
 
Infections 
During the 12-week placebo-controlled trial period in plaque psoriasis, infections were reported in 
28.2% of patients treated with Kyntheum compared with 23.4% of patients treated with placebo. The 
majority of infections consisted of nasopharyngitis, upper respiratory tract infection, pharyngitis, 
urinary tract infections, bronchitis, influenza and sinusitis, which did not necessitate treatment 
discontinuation. Serious infections occurred in 0.5% of patients treated with Kyntheum and in 0.1% of 
patients treated with placebo. Higher rates of fungal infections, primarily non-serious skin and mucosal 
candida infections, were observed in Kyntheum patients compared to placebo patients, 2.5% vs 1.0%, 
respectively.  
 
Through Week 52, the event rates per 100 patient-years for infections were 134.7 for patients treated 
with Kyntheum and 124.1 for patients treated with ustekinumab. The event rates per 100 patient-years 
for serious infections were 2.4 for patients treated with Kyntheum and 1.2 for patients treated with 
ustekinumab. One serious case of cryptococcal meningitis and one serious case of coccidioidies 
infection were observed in clinical trials (see section 4.4). 
 
Neutropenia 
During the 12-week placebo-controlled period of clinical trials, neutropenia was reported in 0.9% of 
patients treated with Kyntheum compared with 0.5% of patients treated with placebo. Most of the 
Kyntheum-associated neutropenias were mild, transient and reversible. 
 
Neutropenia Grade 3 (<1.0 × 10ˆ9/L to 0.5 × 10ˆ9/L) was reported in 0.5% of patients receiving 
Kyntheum compared to none of the patients who received ustekinumab or placebo. No Neutropenia 
Grade 4 (<0.5 × 10ˆ9/L) was reported in patients who received either Kyntheum or placebo, but in 
0.2% of patients who received ustekinumab. No serious infections were associated with neutropenia. 
 



 

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Immunogenicity 
Antibodies to brodalumab developed in 2.2% (88/3935) of patients treated with Kyntheum for up to 52 
weeks in psoriasis clinical trials (0.3% of the patients had anti-brodalumab antibodies at baseline). Of 
these patients, none had neutralising antibodies. 
 
No evidence of altered pharmacokinetic profile, clinical response, or safety profile was associated with 
anti-brodalumab antibody development. 
 
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 700 mg intravenously have been administered in clinical trials with no evidence of dose 
limiting toxicity. In the event of overdose, it is recommended that the patient be monitored for any 
signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted 
immediately. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, Interleukin inhibitors, ATC code: L04AC12 
 
Mechanism of action 
Brodalumab is a recombinant fully human monoclonal immunoglobulin IgG2 antibody that binds with 
high affinity to human IL-17RA and blocks the biological activities of the pro-inflammatory cytokines 
IL-17A, IL-17F, IL-17A/F heterodimer, IL-17C and IL-17E (also known as IL-25), resulting in 
inhibition of the inflammation and clinical symptoms associated with psoriasis. IL-17RA is a protein 
expressed on the cell surface and is a required component of receptor complexes utilized by multiple 
IL-17 family cytokines. IL-17 family cytokine levels have been reported to be increased in psoriasis. 
IL-17A, IL-17F and IL-17A/F heterodimer have pleiotropic activities including the induction of pro-
inflammatory mediators such as IL-6, GROα, and G-CSF from epithelial cells, endothelial cells and 
fibroblasts that promote tissue inflammation. IL-17C has been shown to induce similar responses as 
IL-17A and IL-17F in keratinocytes. Blocking IL-17RA inhibits IL-17 cytokine-induced responses 
resulting in normalization of inflammation in the skin. 
 
Pharmacodynamic effects  
Elevated levels of IL-17A, IL-17C and IL-17F gene expression are found in psoriatic plaques. 
Elevated levels of expression of IL-12B and IL-23A, the genes for the two subunits of IL-23, an 
upstream activator of IL-17A and IL-17F expression, are also found in psoriatic plaques. Treatment 
with Kyntheum in psoriasis patients has been shown to decrease levels of IL-17A and markers of cell 
proliferation and epidermal thickness in lesional skin biopsies to non-lesional skin biopsy levels up to 
12 weeks post-treatment. 
 
Clinical efficacy and safety  
The efficacy and safety of Kyntheum was assessed in 4373 adult plaque psoriasis patients across three 
multinational, randomised, double-blind, phase 3, placebo-controlled clinical trials (AMAGINE-1, 
AMAGINE-2, and AMAGINE-3). AMAGINE-2 and AMAGINE-3 were also active comparator 
(ustekinumab)-controlled. All three trials included a 12-week placebo-controlled induction phase, a 
double-blind duration of 52 weeks, and an open-label long-term extension. 
 

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Patients enrolled were candidates for systemic therapy, including phototherapy, biologic and non-
biologic systemic therapies. Approximately 21% of patients had a history of psoriatic arthritis. 
Approximately 30% of patients had previously received a biological and 13% of patients were 
biological failures. 
 
Patients were predominantly men (70%) and white (91%), with a mean age of 45 years (18 to 86 
years), of these 6.4% were ≥65 years of age and 0.3% were >75 years of age. Across treatment 
groups, the baseline Psoriasis Area Severity Index (PASI) score ranged from 9.4 to 72 (median: 17.4) 
and baseline involved body surface area (BSA) ranged from 10 to 97 (median: 21). Baseline static 
Physician Global Assessment (sPGA) score ranged from “3 (moderate)” (58%) to “5 (very severe)” 
(5%). 
 
AMAGINE-1 was conducted in 661 patients. The trial included a 12-week double-blind, placebo-
controlled induction phase followed by a double-blind withdrawal and retreatment phase up to 52 
weeks. Patients randomised to Kyntheum received 210 mg or 140 mg at Week 0 (day 1), Week 1, and 
Week 2 followed by same dose every 2 weeks. At Week 12, patients originally randomised to 
Kyntheum who achieved sPGA success (0 or 1) were re-randomised to receive either placebo or 
continued Kyntheum at their induction dose. Patients originally randomised to placebo and those who 
did not meet the criteria for re-randomisation received Kyntheum 210 mg every two weeks beginning 
at Week 12. Retreatment was available at or after Week 16 for patients with return of disease and 
rescue treatment was available after 12 weeks of retreatment.  
 
AMAGINE-2 and AMAGINE-3 were identical placebo- and ustekinumab-controlled trials conducted 
in 1831 and 1881 patients, respectively. Both trials included a 12-week double-blind, placebo- and 
ustekinumab-controlled induction phase followed by a double-blind maintenance phase up to 52 
weeks. Patients randomised to Kyntheum in the induction phase received 210 mg or 140 mg at Week 0 
(day 1), Week 1, and Week 2 followed by same dose every 2 weeks. Patients randomised to 
ustekinumab received 45 mg for patients ≤100 kg and 90 mg for patients >100 kg at Weeks 0, 4, and 
16 followed by same dose every 12 weeks. At Week 12, patients originally randomised to Kyntheum 
were re-randomised to receive either 210 mg every 2 weeks, or 140 mg every 2 weeks, or 140 mg 
every 4 weeks, or 140 mg every 8 weeks during the maintenance phase. Patients originally randomised 
to placebo received Kyntheum 210 mg every 2 weeks beginning at Week 12. At Week 12, patients in 
the ustekinumab group continued to receive ustekinumab and then were switched to Kyntheum 
210 mg every 2 weeks at Week 52. Rescue treatment was available at or after Week 16 for patients 
with an inadequate response single sPGA ≥3 or persistent sPGA of 2 over at least a 4-week period.  
 



 

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Table 2: Overview of the main efficacy results 
 

 AMAGINE-1 AMAGINE-2 and AMAGINE-3 
 Placebo 

 
Kyntheum 

210 mg Q2W 
Placebo 

 
Kyntheum 

210 mg Q2W 
Ustekinumab 

 
n-randomised 220 222 624 1236 613 
n-completed Week 12 209 212 601 1205 594 
n-in maintenance 84 83 NA 339 590 
n-completed Week 52  2 74 NA 236 300 
      
PASI       
PASI Baseline score (mean±SD) 19.7±7.7 19.4±6.6 20.2±8.4 20.3±8.3 20.0±8.4 
PASI 75 Week 12 (%) 3 83* 7 86* 70* 
PASI 75 Week 52 (%) 0 87* NA 65 48 
      
sPGA (%)      
sPGA 0 or 1 Week 12  1 76* 4 79* 59* 
sPGA 0 or 1 Week 52  0 83* NA 65 45 
      
PSI      
PSIBaseline score (mean±SD) 19.0±6.7 18.9±6.7 18.8±6.9 18.7±7.0 18.8±6.9 
PSIresponder Week 12  (%) 4 61* 7 64* 54* 
Q2W = every 2 weeks 
PSI = Psoriasis Symptom Inventory. PSI responder: total score ≤8 with no item scores >1; SD: standard 
deviation. 
 
Non-responder imputation is used to impute missing data. 
Due to re-randomisation to other explored dose regimens, n-in maintenance is substantially lower than  
n-randomised in several arms. The maintenance phase in AMAGINE-2 and -3 did not include placebo. 
*p-value vs. corresponding placebo, adjusted for stratification factors <0.001 

 
PASI 75 response at 2 weeks ranged between 20% and 25% in the Phase 3 trials compared to placebo 
(0% to 0.6%) and ustekinumab (3% to 3.5%). 
 



 

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Figure 1: PASI 100 during induction and maintenance phase for Kyntheum and ustekinumab 
(AMAGINE-2 and AMAGINE-3, pooled) 
 

 
 
N = number of patients, which are presented at baseline, Week 12, and Week 52 
Q2W = every 2 weeks 
*Patients were administered ustekinumab in the induction phase and continued on ustekinumab in the maintenance 
phase 
**Patients were administered Kyntheum 210 mg every 2 weeks in the induction phase and re-randomised to 
Kyntheum 210 mg every 2 weeks in the maintenance phase 
NRI= Non-responder imputation 
 
In all three clinical trials, examination of age, gender, race, use of prior systemic or photo therapy, use 
of prior biologics, and biologic failures did not identify differences in response in all key endpoints 
[PASI 75, PASI 100, sPGA success (0 or 1), and sPGA clear (0)] to Kyntheum among these 
subgroups. 
 
Along with primary efficacy endpoints, clinically important improvements were observed in Psoriasis 
Scalp Severity Index (PSSI) at Week 12 (AMAGINE-1) and in Nail Psoriasis Severity Index (NAPSI) 
at Week 12 and 52 (AMAGINE-1,-2, and -3). 
 
Quality of life/patient reported outcomes 
The proportion of patients who achieved a Psoriasis Symptom Inventory (PSI) score of 0 (not at all) or 
1 (mild) on every item (itch, burning, stinging, pain, redness, scaling, cracking and flaking) at Week 
12 are shown in Table 2. 
 
The percentage of patients that at Week 12 achieved a DLQI (Dermatology Life Quality Index) score 
of 0 or 1 was 56%, 61%, 59% in the Kyntheum 210 mg group and 5%, 5%, 7% in the placebo group in 
AMAGINE-1, -2 and -3, respectively (adjusted p-value <0.001) and 44% in the ustekinumab groups 
(AMAGINE-2 and -3). 
 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of trials with 
Kyntheum in plaque psoriasis in one or more subsets of the paediatric population (see section 4.2 for 
information on paediatric use).  
 



 

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5.2 Pharmacokinetic properties 
 
Absorption 
Based on population pharmacokinetic modelling, the estimated accumulation ratio after 20 weeks of 
dosing is 2.5-fold. In moderate to severe plaque psoriasis patients following a single subcutaneous 
administration of Kyntheum at 210 mg, the mean maximum serum concentration (Cmax) was 
13.4 mcg/ml (standard deviation [SD] = 7.29 mcg/ml). The median time to maximum concentration 
(Tmax) was 3.0 days (range: 2.0 to 4.0 days) and the mean area under the concentration time curve to 
the last measurable concentration (AUClast) was 111 mcg*day/ml (SD = 64.4 mcg*day/ml). The 
subcutaneous bioavailability of brodalumab estimated by population pharmacokinetic modelling was 
55%. 
 
The observed pharmacokinetic parameters during steady-state (weeks 10-12) were:  mean steady-state 
area under the concentration time curve over the dosing interval (AUCtau) was 227.4 mcg*day/ml (SD 
= 191.7 mcg*day/ml) corresponding to average concentration (Cav,ss) of 16.2 mcg/ml, mean Cmax was 
20.9 mcg/ml (SD = 17.0 mcg/ml) and Week 12 mean minimum serum concentration (Ctrough) was 
9.8 mcg/ml (SD = 11.2 mcg/ml). 
 
Distribution 
Based on population pharmacokinetic modelling, the estimated mean steady-state volume of 
distribution of brodalumab was approximately 7.24 L.  
 
Biotransformation 
As an IgG2 human monoclonal antibody brodalumab is expected to be degraded into small peptides 
and amino acids via catabolic pathways in a manner similar to endogenous IgG. 
 
Elimination 
Following subcutaneous administrations of 210 mg, brodalumab exhibits non-linear pharmacokinetics 
typical for a monoclonal antibody that undergoes target-mediated drug disposition. 
 
Brodalumab clearance decreases with increasing dose and exposure increases in a greater than dose-
proportional manner. For a 3-fold increase in SC brodalumab dose from 70 to 210 mg, the steady-state 
serum brodalumab Cmax and AUC0-t increased approximately 18- and 25-fold, respectively. 
 
Following a single subcutaneous administration of brodalumab 210 mg in plaque psoriasis patients, the 
apparent clearance (CL/F) is 2.95 L/day.  
 
Population pharmacokinetic modelling predicted that serum brodalumab concentrations dropped below 
the quantification limit (0.05 mcg/ml) 63 days after discontinuation of steady-state dosing of 
brodalumab 210 mg administered every 2 weeks in 95% of the patients. However, brodalumab 
concentrations below LLOQ (Lower Limit of Quantification) were associated with IL-17 receptor 
occupancy up to 81%. 
Based on population pharmacokinetic modelling the estimated half-life of brodalumab was 10.9 days 
at steady-state after every other week subcutaneous dose of 210 mg. 
 
Impact of weight on pharmacokinetics 
Population pharmacokinetic modelling indicated that exposure decreased as body weight increased. 
No dose adjustment is recommended. 
 
Elderly patients 
Population pharmacokinetic modelling indicated that age did not have an effect on brodalumab 
pharmacokinetics, which was co-based on 259 (6%) patients being 65-74 years old and on 14 (0.3%) 
patients being ≥75 years old, within a total PK population of 4271 plaque psoriasis patients. 
 
Renal or hepatic impairment 
No pharmacokinetic data are available in patients with impaired renal or hepatic function. Renal 
elimination of intact brodalumab, an IgG monoclonal antibody, is expected to be low and of minor 



 

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consequence. Brodalumab is expected to be mainly eliminated via catabolism and hepatic impairment 
is not expected to influence clearance. 
 
Other populations 
The pharmacokinetics of brodalumab was similar between Japanese and non-Japanese patients with 
psoriasis. 
 
Population pharmacokinetic analysis indicated that gender did not have an effect on brodalumab 
pharmacokinetics. 
 
Pharmacokinetic/pharmacodynamic relationship(s) 
A population pharmacokinetic/pharmacodynamic model, developed using all available data indicated 
that at a dose of 210 mg every 2 weeks, 90% of all patients would be predicted to maintain a trough 
concentration greater than the estimated IC90 value of 1.51 mcg/ml. Based on an exploratory 
descriptive analysis, no relationship was observed between exposure and incidence of serious 
infections and infestations, candida infections, viral infections, and suicidal ideation and behaviour 
events. Exposure-response analysis indicates that higher brodalumab concentrations are related to 
better PASI and sPGA response. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose 
toxicity (including safety pharmacology endpoints and assessment of fertility-related endpoints), and 
toxicity to reproduction and development. 
 
Carcinogenicity studies with brodalumab have not been conducted. However, there were no 
proliferative changes in cynomolgus monkeys administered weekly subcutaneous doses of brodalumab 
at 90 mg/kg for 6 months (AUC exposure 47-fold higher than in human patients receiving Kyntheum 
210 mg every 2 weeks). The mutagenic potential of brodalumab was not evaluated; however, 
monoclonal antibodies are not expected to alter DNA or chromosomes. 
 
In cynomolgus monkeys there were no effects on male and female reproductive organs and on sperm 
count, motility and morphology following administration of brodalumab at dose levels up to 90 mg/kg 
once weekly for 6 months, (AUC exposure up to 47-fold higher than in human patients receiving 
Kyntheum 210 mg every 2 weeks). 
 
In cynomolgus monkeys, no effects on embryo-foetal or postnatal (up to 6 months of age) 
development were observed when brodalumab was dosed subcutaneously throughout pregnancy at 
exposure levels up to 27-fold higher than those achieved in human patients receiving Kyntheum 
210 mg every 2 weeks based on the area under the concentration curve (AUC). Serum concentrations 
in monkey infants and in foetal rabbits indicated considerable passage of brodalumab from the mother 
to the foetus at the end of pregnancy.  
 
In cynomolgus monkeys, after weekly subcutaneous dosing of brodalumab at dose levels up to 
90 mg/kg for 6 months, brodalumab-related effects were limited to injection site reactions and 
mucocutaneous inflammation that was consistent with pharmacologic modulation of host surveillance 
to commensal microflora. There were no effects on peripheral blood immunophenotyping and the T-
cell dependent antibody response assay. In a local tolerance test in rabbits, moderate to severe edema 
was observed after subcutaneous injection of a formulation containing brodalumab at the clinical 
concentration of 140 mg/ml. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Proline 



 

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Glutamate 
Polysorbate 20 
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 
 
4 years  
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C-8°C).  
Do not freeze. 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 
Kyntheum may be stored at room temperature (up to 25°C) once, in the outer carton, for a maximum 
single period of 14 days. Once Kyntheum has been removed from the refrigerator and has reached 
room temperature (up to 25°C) it must either be used within 14 days or discarded.  
 
6.5 Nature and contents of container  
 
1.5 ml solution in a type I glass pre-filled syringe with stainless steel 27G x ½” needle, covered with 
an elastomeric needle cap. 
 
Kyntheum is available in unit packs containing 2 pre-filled syringes and in multipacks containing 6 (3 
packs of 2) pre-filled syringes. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Kyntheum is a sterile solution for injection in pre-filled syringe. Each pre-filled syringe is for single 
use only. The ‘Instructions for Use’ should be consulted for detailed instructions on administration of 
Kyntheum. 
 
To avoid discomfort at the site of injection, at least 30 minutes should be allowed for the pre-filled 
syringe to reach room temperature before injecting. The pre-filled syringe should not be warmed in 
any other way. The pre-filled syringe should not be shaken. The needle cap on the pre-filled syringe 
should not be removed while allowing to reach room temperature. 
 
Kyntheum should be visually inspected for particles and discoloration prior to administration. 
Kyntheum is a clear to slightly opalescent, colourless to slightly yellow solution, free from particles. 
This medicine should not be used if the solution is cloudy or discoloured or contains lumps, flakes, or 
particles. 
 
The  pre-filled syringe should not be used if it has been dropped on a hard surface. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 



 

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LEO Pharma A/S 
Industriparken 55 
DK-2750 Ballerup 
Denmark 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1155/001 
EU/1/16/1155/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 July 2017 
 
 
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/


 

15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURERS RESPONSIBLE 
FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



 

16 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Immunex Rhode Island Corporation 
40 Technology Way, West Greenwich,  
Rhode Island, 02817 
United States 
 
Name and address of the manufacturers responsible for batch release 
 
Laboratoires LEO 
39 route de Chartres 
28500 Vernouillet 
France 
 
LEO Pharma A/S 
Industriparken 55 
DK-2750 Ballerup 
Denmark 
 
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 (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; 



 

17 

• 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. 

  



 

18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 

19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



 

20 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON OF UNIT PACK   
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kyntheum 210 mg solution for injection in pre-filled syringe  
brodalumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 210 mg brodalumab in 1.5 ml solution (140 mg/1 ml). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: proline, glutamate, polysorbate 20 and water for injection. 
 
 
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 
For 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 
 
Do not shake. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 



 

21 

Store in the outer package in order to protect from light.  
 
 
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 
 
LEO Pharma A/S 
Industriparken 55 
DK-2750 Ballerup 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1155/001  Pack containing 2 pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Kyntheum 210 mg 
 
 
17. UNIQUE IDENTIFIER - 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 
  



 

22 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON OF MULTIPACK (INLCUDING BLUE BOX)   
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kyntheum 210 mg solution for injection in pre-filled syringe  
brodalumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 210 mg brodalumab in 1.5 ml solution (140 mg/1 ml). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: proline, glutamate, polysorbate 20 and water for injection. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
 
Multipack: 6 (3 packs of 2) pre-filled syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use 
For 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 
 
Do not shake. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 



 

23 

Store in the outer package in order to protect from light.  
 
 
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 
 
LEO Pharma A/S 
Industriparken 55 
DK-2750 Ballerup 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1155/002  Multipack containing 6 (3 x 2) pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Kyntheum 210 mg 
 
 
17. UNIQUE IDENTIFIER - 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 
  



 

24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX)   
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kyntheum 210 mg solution for injection in pre-filled syringe  
brodalumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 210 mg brodalumab in 1.5 ml solution (140 mg/1 ml). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: proline, glutamate, polysorbate 20 and water for injection. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
 
2 pre-filled syringes. Component of a multipack. Not to be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use 
For 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 
 
Do not shake. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 



 

25 

Store in the outer package in order to protect from light.  
 
 
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 
 
LEO Pharma A/S 
Industriparken 55 
DK-2750 Ballerup 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1155/002  Multipack containing 6 (3 x 2) pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Kyntheum 210 mg 
 
 
17. UNIQUE IDENTIFIER - 2D BARCODE 
 
Not applicable. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
Not applicable. 
 
 
  



 

26 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Kyntheum 210 mg injection  
brodalumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
  



 

27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 

28 

Package leaflet: Information for the patient 
 

Kyntheum 210 mg solution for injection in pre-filled syringe 
brodalumab 

 
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 Kyntheum  is and what it is used for  
2. What you need to know before you use Kyntheum 
3. How to use Kyntheum  
4. Possible side effects  
5. How to store Kyntheum  
6. Contents of the pack and other information 
 
 
1. What Kyntheum is and what it is used for 
 
Kyntheum is a medicine that contains the active substance brodalumab. Brodalumab is a monoclonal 
antibody, a specialised type of protein that recognises and attaches to certain proteins in the body. 
 
Brodalumab belongs to a group of medicines called interleukin (IL) inhibitors. This medicine works 
by blocking the activity of IL-17 proteins, which are present at increased levels in diseases such as 
psoriasis. 
 
Kyntheum is used to treat a skin condition called “plaque psoriasis”, which causes inflammation and 
scaly plaque formation on the skin. Kyntheum is used in adults with moderate to severe plaque 
psoriasis affecting large areas of the body. 
 
Using Kyntheum will benefit you by leading to improvements of skin clearance and reducing psoriasis 
signs and symptoms, such as itch, redness, scaling, burning, stinging, cracking, flaking and pain. 
 
 
2. What you need to know before you use Kyntheum 
 
Do not use Kyntheum 
• if you are allergic to brodalumab or any of the other ingredients of this medicine (listed in 

section 6). If you think you may be allergic, ask your doctor for advice before using Kyntheum 
• if you have active Crohn’s disease 
• if you have an infection which your doctor thinks is important (for example, active 

tuberculosis). 
 



 

29 

Warnings and precautions  
Talk to your doctor, pharmacist, or nurse before using Kyntheum: 
• if you have an inflammatory disease affecting the gut named Crohn’s disease 
• if you have an inflammation of the large intestine named ulcerative colitis 
• if you have ever had or are having suicidal thoughts or actions, depression, anxiety, or mood 

problems 
• if you have an infection now or often get infections 
• if you have a long-term (chronic) infection  
• if you have tuberculosis (TB), have had a positive TB test, or have been in close contact with 

someone with TB. You may be treated with another medicine for TB before you begin treatment 
with Kyntheum 

• if you have recently received or are scheduled to receive a vaccination. You should not be given 
certain types of vaccines (called ‘live vaccines’) while being treated with Kyntheum 

• if you have used Kyntheum during the last three months of your pregnancy, you should talk to 
your doctor before vaccinating your baby 

• if you are receiving any other treatment for psoriasis, such as another immunosuppressant or 
phototherapy with ultraviolet (UV) light. 

 
After starting Kyntheum, tell your doctor, pharmacist or nurse immediately: 
• if you have been told by your doctor that you have developed Crohn’s disease 
• if you feel depressed, anxious, or have thoughts of suicide, or have unusual mood changes 
• if you have an infection or have any signs of infection listed in Section 4 “Possible Side Effects” 
• if you have been told you have tuberculosis. 
 
Inflammatory bowel disease (Crohn’s disease or ulcerative colitis) 
Stop using IL-17 inhibitors, such as Kyntheum, and tell your doctor or seek medical help immediately 
if you notice abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (any signs of 
bowel problems). 
 
Look out for allergic reactions 
Kyntheum can potentially cause serious side effects, including allergic reactions. You must look out 
for signs of these conditions while you are taking Kyntheum. 
 
Stop using Kyntheum and tell your doctor or seek medical help immediately if you notice any signs 
indicating an allergic reaction. Such signs are listed under “Serious side effects” in section 4. 
 
Children and adolescents 
Kyntheum is not recommended for children and adolescents (below 18 years of age) because it has not 
been studied in this age group. 
 
Other medicines and Kyntheum 
Tell your doctor or pharmacist: 
• if you are taking, have recently taken or might take any other medicines 
• if you have recently had or you or your baby are going to have a vaccination, see "Warnings and 

precautions" in section "2. What you need to know before using Kyntheum". 
 

Pregnancy and breast-feeding  
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 taking this medicine. Kyntheum has not been tested in 
pregnant women and it is not known if this medicine can harm your unborn baby. It is therefore 
preferable to avoid the use of Kyntheum during pregnancy. If you are a woman of childbearing 
potential, you are advised to avoid becoming pregnant and should use adequate contraception while 
using Kyntheum and for at least 12 weeks after the last dose of Kyntheum. 
  
It is not known whether brodalumab passes into breast milk. Tell your doctor if you are breast-feeding 
or plan to breast-feed. Your doctor will then help you decide whether to stop breast-feeding or stop 



 

30 

using Kyntheum. Together you will consider the benefit of breast-feeding to the baby and the benefit 
of Kyntheum to you. 
 
Driving and using machines 
Kyntheum has no influence on your ability to drive and use machines. 
 
 
3. How to use Kyntheum 
 
Kyntheum should be prescribed to you by a doctor with experience in diagnosing and treating 
psoriasis.  
 
Always use this medicine exactly as your doctor, pharmacist or nurse has told you. Check with your 
doctor, pharmacist or nurse if you are not sure.  
 
How much Kyntheum is given 
• Your doctor will decide how much Kyntheum you need and for how long. The recommended 

dose is 210 mg (one injection). 
• After the first dose you will need to have a weekly injection at Week 1 (one week after the first 

dose) and Week 2 (two weeks after the first dose). After that, you will need to have an injection 
every two weeks. 

• Kyntheum is for long-term treatment. Your doctor will regularly monitor your condition to 
check that the treatment is having the desired effect. Tell your doctor if you think your signs and 
symptoms of psoriasis are not improving after using Kyntheum. 

 
How is Kyntheum given 
Kyntheum is given as an injection under the skin (known as a subcutaneous injection). 
 
Self-administration instructions 
See the detailed “Instructions for Use” that comes with this medicine for information on the right 
way to store, prepare, and give your injections at home. 
• If your doctor decides that you or a caregiver can give the injections at home, you or your 

caregiver should receive training on the right way to prepare and inject Kyntheum. Do not try to 
inject Kyntheum until you or your caregiver have been shown how to inject Kyntheum by your 
doctor or nurse.  

• Do not shake the pre-filled syringe before use. 
• Kyntheum is injected in your upper legs (thighs) or stomach area (abdomen) by you or a 

caregiver. A caregiver may also give you an injection in your upper, outer arm. 
• Do not inject into an area of the skin that is tender, bruised, red, hard or in an area of skin that is 

affected by psoriasis. 
 
If you use more Kyntheum than you should 
If you use more of this medicine than prescribed or take the dose sooner than required, tell your 
doctor.  
 
If you forget to use Kyntheum 
If you have forgotten to inject a dose of Kyntheum, inject the next dose as soon as you can after the 
missed dose. Then, talk to your doctor about when you should inject the next dose. Do not take a 
double dose to make up for a forgotten dose. 
 
If you stop using Kyntheum 
You should not stop using Kyntheum without speaking to your doctor first. If you stop treatment, 
symptoms of psoriasis may come back.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 



 

31 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects  
 
Stop using Kyntheum and tell your doctor or seek medical help immediately if you get any of the 
following side effects. Your doctor will decide if and when you may restart the treatment: 
 
Serious allergic reaction (may affect up to 1 in 1,000 people), the signs may include: 
• difficulty breathing or swallowing 
• low blood pressure, which can cause dizziness or light-headedness 
• swelling of the face, lips, tongue or throat 
• severe itching of the skin, with a red rash or raised bumps. 
 
Possible serious infections (may affect up to 1 in 100 people), the signs may include: 
• fever, flu-like symptoms, night sweats 
• feeling tired or short of breath, cough which will not go away 
• warm, red and painful skin, or a painful skin rash with blisters. 

 
Other side effects that have been reported 
 
Common side effects (may affect up to 1 in 10 people): 
• diarrhoea 
• feeling sick 
• redness, pain, itching, bruising, or bleeding at injection site 
• tiredness 
• mouth or throat pain 
• tinea (fungal) skin infections (including on feet and groin) 
• flu (influenza) 
• headache 
• joint pain  
• muscle pain.  
 
Uncommon side effects (may affect up to 1 in 100 people) 
• candida (fungal) infection in the mouth, throat or genitals 
• discharge from the eye with itching, redness and swelling (conjunctivitis) 
• low white blood cell count. 

 
Most of these side effects are mild to moderate. If any of these side effects becomes severe, tell your 
doctor, nurse, or pharmacist. 
 
Abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (signs of bowel problems) 
have also been reported with IL-17 inhibitors, such as Kyntheum. 
 
Reporting of side effects 
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 Kyntheum 
 
Keep this medicine out of the sight and reach of children. 
 

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


 

32 

Do not use this medicine after the expiry date which is stated on the outer carton and label of the pre-
filled syringe after EXP. The expiry date refers to the last day of that month. 
 
Keep in the outer carton in order to protect from light.  
 
Store in a refrigerator (2°C to 8°C). Do not freeze.  
 
Kyntheum can be kept at room temperature up to 25°C in the outer carton for 14 days. Throw away 
Kyntheum if it is not used within 14 days of storage at room temperature. 
 
Do not use this medicine if you notice the solution is cloudy or discoloured or contains lumps, flakes 
or particles. 
 
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 protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Kyntheum contains  
- The active substance is brodalumab. Each pre-filled syringe contains 210 mg brodalumab in 

1.5 ml solution. 
- The other ingredients are proline, glutamate, polysorbate 20 and water for injections.  
 
What Kyntheum looks like and contents of the pack 
Kyntheum is a solution for injection that is a clear to slightly pearly, colourless to slightly yellow 
liquid, with no particles.  
 
Kyntheum is available in unit packs containing 2 pre-filled syringes and in multipacks containing 6 (3 
packs of 2) pre-filled syringes. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
LEO Pharma A/S 
Industriparken 55 
DK-2750 Ballerup 
Denmark 
 
Manufacturer 
Laboratoires LEO  
39 route de Chartres 
28500 Vernouillet 
France 
 
LEO Pharma A/S 
Industriparken 55 
DK-2750 Ballerup 
Denmark 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
LEO Pharma N.V./S.A 
Tél/Tel: +32 3 740 7868 
 

Lietuva 
LEO Pharma A/S 
Tel: +45 44 94 58 88 
 

България 
Borola Ltd 

Luxembourg/Luxemburg 
LEO Pharma N.V./S.A 



 

33 

Teл.: +359 2 9156 136 
 

Tél/Tel: +32 3 740 7868 
 

Česká republika 
LEO Pharma s.r.o. 
Tel: +420 225 992 272 
 

Magyarország 
LEO Pharma  
Tel: +36 1 888 0525 
 

Danmark 
LEO Pharma AB 
Tlf: +45 70 22 49 11 
 

Malta 
E.J. Busuttil Ltd 
Tel: +356 2144 7184 
 

Deutschland 
LEO Pharma GmbH 
Tel: +49 6102 2010 

Nederland 
LEO Pharma B.V. 
Tel: +31 205104141 
 

Eesti 
LEO Pharma A/S 
Tel: +45 44 94 58 88 
 

Norge 
LEO Pharma AS 
Tlf: +47 22514900 
 

Ελλάδα 
LEO Pharmaceutical Hellas S.A. 
Τηλ: +30 210 68 34322 
 

Österreich 
LEO Pharma GmbH 
Tel: +43 1 503 6979 
 

España 
Laboratorios LEO Pharma, S.A. 
Tel: +34 93 221 3366 
 

Polska 
LEO Pharma Sp. z o.o. 
Tel.: +48 22 244 18 40 
 

France 
LEO Pharma  
Tél: +33 1 3014 4000 
 

Portugal 
LEO Farmacêuticos Lda.  
Tel: +351 21 711 0760 
 

Hrvatska 
Remedia d.o.o 
Tel: +385 1 3778 770 
 

România 
LEO Pharma Romania 
Tel: +40 213121963 
 

Ireland 
LEO Laboratories Ltd 
Tel: +353 (0) 1 490 8924 
 

Slovenija 
PHARMAGAN d.o.o. 
Tel: +386 4 2366 700 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
LEO Pharma s.r.o. 
Tel: +421 2 5939 6236 
 

Italia 
LEO Pharma S.p.A 
Tel: +39 06 52625500 
 

Suomi/Finland 
LEO Pharma Oy 
Puh/Tel: +358 20 721 8440 
 

Κύπρος 
The Star Medicines Importers Co. Ltd. 
Τηλ: +357 2537 1056  
 

Sverige 
LEO Pharma AB 
Tel: +46 40 3522 00 
 

Latvija 
LEO Pharma A/S 
Tel: +45 44 94 58 88 
 

United Kingdom 
LEO Laboratories Ltd 
Tel: +44 (0) 1844 347333 
 

  
 
 



 

34 

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

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


 

35 

Instructions for Use: 
Kyntheum (brodalumab) 

Solution for injection in pre-filled syringe 
 

  
For subcutaneous use 

 
Kyntheum is available as a single-use pre-filled syringe. Each syringe contains one 210 mg dose of 
Kyntheum. Your doctor, pharmacist or nurse will tell you how often to inject the medicine. Each 
Kyntheum pre-filled syringe can only be used once. 
 
If your doctor decides that you or a caregiver can give you injections at home, you should receive 
training on the right way to prepare and inject Kyntheum. Do not try to inject yourself until 
your healthcare provider has shown you the right way to give the injections.  
 
Please read all the instructions before using the Kyntheum pre-filled syringe. Call your doctor, 
pharmacist or nurse if you or your caregiver have any questions about the right way to inject 
Kyntheum. 
 
Guide to parts  
  

Before use 
 
 

After use 

                                                    
Plunger 

 
 
 
 
 
 
 
 

Finger 
grips  

 
Label and 
expiry 
date 

                      
 
 

   

         Used plunger 
 
          Finger grips 

 
 

            Label and  
          expiry date 
 
          Used  
          syringe 
          barrel 
 

 
 
Syringe 
barrel  

 
 
 
 
         Used needle 

Medicine 
 
 

 
Needle 
cap on 

 
 
 
 
          
         Needle  
         cap off 

 
Important: Needle is inside 



 

36 

Important 
 
Before you use a Kyntheum pre-filled syringe, read this important information: 
 
Storing your Kyntheum pre-filled syringes 
• Keep out of the sight and the reach of children. 
• Keep in the original carton to protect from light or physical damage. 
• Keep in the refrigerator (2°C to 8°C).  
• If needed, you may store the Kyntheum pre-filled syringe at room temperature up to 25°C for up 

to 14 days. Throw away Kyntheum that has been stored at room temperature for longer than 14 
days. 

• Do not freeze.  
 
Using your Kyntheum pre-filled syringe 
• Do not use after the expiry date on the label. 
• Do not shake. 
• Do not remove the needle cap until you are ready to inject. 
• Do not use a Kyntheum pre-filled syringe if it has been dropped on a hard surface. This is in 

case the syringe is broken.  
 
 
Step 1: Preparing 
 
A.  Remove the Kyntheum pre-filled syringe from the box  
Grab the syringe barrel to remove the syringe from the tray. 
 

                                                                              

 
Put the box with any unused syringes back in the refrigerator. 
 
For safety reasons: 
• Do not hold the plunger. 
• Do not grasp the needle cap. 
• Do not remove the needle cap until you are ready to inject. 
• Do not remove the finger grips. They are part of the syringe. 
 
Leave the syringe at room temperature for at least 30 minutes before injecting. 
 
• Do not put the syringe back in the refrigerator once it has reached room temperature. 
• Do not try to warm the syringe by using a heat source such as hot water or a microwave. 
• Do not leave the syringe in direct sunlight. 
• Do not shake the syringe. 

Place finger or thumb 
on edge of tray to 
secure it while you 
remove syringe. 

          Grab here 
 
 



 

37 

 
Important: Always hold the pre-filled syringe by the syringe barrel. 
 
B.  Check the Kyntheum pre-filled syringe 
 
                                                        Label and 
                                                      expiration date 
  
                         Syringe barrel                                                             Plunger 
 
 
 
 
 
 
                                                                                                    Finger grips 
Needle                    Medicine                                                                          
cap on 
 
                                                                                              
Always hold the syringe by the syringe barrel. 
 
Make sure the medicine in the syringe is clear to slightly pearly and colourless to slightly yellow. 
• Do not use the syringe if: 

• the medicine is cloudy or discoloured or contains flakes or particles 
• any part appears cracked or broken. 

  
C.  Collect all the materials you need 
Wash your hands thoroughly with soap and water.   
On a clean, well-lit work surface, place the: 
• new syringe  
• alcohol wipes 
• cotton ball or gauze pad 
• plaster 
• sharps disposal container (colour and appearance of container may differ depending on national 

requirements). 
 
 

 



 

38 

D.  Prepare and clean the area where you will inject 
 

 

 
 
 
 
Upper arm 

 

 

Stomach area 
(abdomen) 
 
 
Thigh 

 
You or your caregiver can use: 
• your thigh 
• your stomach area (abdomen), except for a 5-centimetre area right around your belly button 

(navel). 
 
Only your caregiver can use: 
• your outer area of upper arm. 

 
• Do not inject into areas where the skin is tender, bruised red, or hard.  
• Avoid injecting into areas with scars or stretch marks. 
• Avoid injecting directly into raised, thick, red or scaly skin patches or lesions. 
• Clean the area where you plan to inject with an alcohol wipe. Let your skin dry. 
• Do not touch this area again before injecting. 
• If you want to use the same injection area each time, make sure it is not exactly the same spot 

that you used for a previous injection. 
 

Step 2: Getting ready to inject 
 
E.  When you are ready to inject, pull the needle cap straight out and away from your body 
 

  

 
Throw the needle cap into the sharps disposal container provided. 



 

39 

• Do not twist or bend the needle cap. 
• Do not put the needle cap back onto the syringe. 
 
You may notice a small air bubble in the syringe or a drop of liquid at the end of the needle. Both are 
normal and do not need to be removed.  
 
F.  Pinch your skin to create a firm surface 
 

    

 
 
Pinch the skin firmly between your thumb and fingers, creating an area about 5 centimetres wide. 
 
Important: Keep the skin pinched until after you have injected. 
 
Step 3: Injecting 
 
G.  Hold the pinched skin. With the needle cap off, insert the syringe into your skin at 
somewhere between 45 and 90 degrees 
 

 

 
Do not place your finger on the plunger while inserting the needle. 
 
H.  Using slow and constant pressure, push the plunger all the way down until it stops moving 
 

 

 
I.  When you have finished, release your thumb. Then, gently remove the syringe from your skin 
 



 

40 

  

 
Important: When you remove the syringe, if it looks like the medicine is still in the syringe barrel, 
this means you have not received a full dose. Call your doctor, pharmacist or nurse immediately. 
 
Step 4: Finishing up 
 
J.  Throw away the used syringe  
 

 

 
• Put your used pre-filled syringe in a puncture resistant sharps disposal container straight after 

use. 
• Do not re-use the syringe. 
• Do not recycle the syringe or sharps disposal container or throw them into household rubbish. 
 
Important: Always keep the sharps disposal container out of the sight and the reach of children. 
 
K.  Check the injection site  
If there is blood, press a cotton ball or gauze pad on your injection site. Do not rub the injection site.  
Cover with plaster if needed. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 
	A. LABELLING
	B. PACKAGE LEAFLET