Trudexa

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1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

 
 
 



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1. NAME OF THE MEDICINAL PRODUCT  

Trudexa 40 mg solution for injection. 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION  

Each 0.8 ml single dose vial contains 40 mg of adalimumab.  
Adalimumab is a recombinant human monoclonal antibody expressed in Chinese Hamster Ovary cells. 
 
For a full list of excipients, see section 6.1.  

3. PHARMACEUTICAL FORM  

Solution for injection. 

4. CLINICAL PARTICULARS 

4.1 Therapeutic indications  

Rheumatoid arthritis 
 
Trudexa in combination with methotrexate, is indicated for: 
 
 the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the 

response to disease-modifying anti-rheumatic drugs including methotrexate has been 
inadequate. 

 the treatment of severe, active and progressive rheumatoid arthritis in adults not previously 
treated with methotrexate. 

 
Trudexa can be given as monotherapy in case of intolerance to methotrexate or when continued 
treatment with methotrexate is inappropriate. 
 
Trudexa has been shown to reduce the rate of progression of joint damage as measured by X-ray and 
to improve physical function, when given in combination with methotrexate. 

Psoriatic arthritis 

Trudexa is indicated for the treatment of active and progressive psoriatic arthritis in adults when the 
response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. 
 
Ankylosing spondylitis 
 
Trudexa is indicated for the treatment of adults with severe active ankylosing spondylitis who have 
had an inadequate response to conventional therapy. 
 
Crohn’s disease 
 
Trudexa is indicated for treatment of severe, active Crohn’s disease, in patients who have not 
responded despite a full and adequate course of therapy with a corticosteroid and/or an 
immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. 
For induction treatment, Trudexa should be given in combination with cortiocosteroids.  Trudexa can 
be given as monotherapy in case of intolerance to corticosteroids or when continued treatment with 
corticosteroids is inappropriate (see section 4.2). 



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4.2 Posology and method of administration   

Trudexa treatment should be initiated and supervised by specialist physicians experienced in the 
diagnosis and treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or Crohn’s 
disease.  Patients treated with Trudexa should be given the special alert card. 
 
After proper training in injection technique, patients may self-inject with Trudexa if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Trudexa, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 

Adults 

Rheumatoid arthritis 
 
The recommended dose of Trudexa for adult patients with rheumatoid arthritis is 40 mg adalimumab 
administered every other week as a single dose via subcutaneous injection.  Methotrexate should be 
continued during treatment with Trudexa. 
 
Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, or analgesics can be continued 
during treatment with Trudexa.  Regarding combination with disease modifying anti-rheumatic drugs 
other than methotrexate see sections 4.4 and 5.1. 
 
In monotherapy, some patients who experience a decrease in their response may benefit from an 
increase in dose intensity to 40 mg adalimumab every week.  

Psoriatic arthritis and ankylosing spondylitis 

The recommended dose of Trudexa for patients with psoriatic arthritis and ankylosing spondylitis is 
40 mg adalimumab administered every other week as a single dose via subcutaneous injection. 
 
For all of the above indications, available data suggest that the clinical response is usually achieved 
within 12 weeks of treatment.  Continued therapy should be carefully reconsidered in a patient not 
responding within this time period. 
 
Crohn’s disease 
 
The recommended Trudexa induction dose regimen for adult patients with severe Crohn’s disease is 
80 mg at week 0 followed by 40 mg at week 2.  In case there is a need for a more rapid response to 
therapy, the regimen 160 mg at week 0 (dose can be administered as four injections in one day or as 
two injections per day for two consecutive days), 80  mg at week 2, can be used with the awareness 
that the risk for adverse events is higher during induction. 
 
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous 
injection.  Alternatively, if a patient has stopped Trudexa and signs and symptoms of disease recur, 
Trudexa may be re-administered.  There is little experience from re-administration after more than 
8 weeks since the previous dose. 
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines. 
 
Some patients who experience decrease in their response may benefit from an increase in dose 
intensity to 40 mg Trudexa every week. 
 



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Some patients who have not responded by week 4 may benefit from continued maintenance therapy 
through week 12.  Continued therapy should be carefully reconsidered in a patient not responding 
within this time period. 

Elderly patients 

No dose adjustment is required.   

Children and adolescents 

There is no experience in children. 

Impaired renal and/or hepatic function 

Trudexa has not been studied in these patient populations.  No dose recommendations can be made. 

4.3 Contraindications  

Hypersensitivity to the active substance or to any of the excipients.  
 
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 
4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 

4.4 Special warnings and precautions for use   

Infections 
 
Patients must be monitored closely for infections, including tuberculosis, before, during and after 
treatment with Trudexa.  Because the elimination of adalimumab may take up to five months, 
monitoring should be continued throughout this period. 
 
Treatment with Trudexa should not be initiated in patients with active infections including chronic or 
localized infections until infections are controlled.  
 
Patients who develop a new infection while undergoing treatment with Trudexa should be monitored 
closely.  Administration of Trudexa should be discontinued if a patient develops a new serious 
infection until infections are controlled.  Physicians should exercise caution when considering the use 
of Trudexa in patients with a history of recurring infection or with underlying conditions which may 
predispose patients to infections, including the use of concomitant immunosuppressive medications. 
 
Serious infections, sepsis, tuberculosis and other opportunistic infections, including fatalities, have 
been reported with Trudexa.   
 
Serious infections: 
 
In clinical trials an increased risk of serious infections in patients receiving Trudexa has been shown, 
and reports from the post-marketing setting support this finding.  Of particular importance are 
infections such as pneumonia, pyelonephritis, septic arthritis and septicaemia.   
 
Tuberculosis: 
 
There have been reports of tuberculosis in patients receiving Trudexa.  It should be noted that in the 
majority of those reports, tuberculosis was extra-pulmonary, i.e. disseminated.  
 



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Before initiation of therapy with Trudexa, all patients must be evaluated for both active or inactive 
(latent) tuberculosis infection.  This evaluation should include a detailed medical history with a 
personal history of tuberculosis or possible previous exposure to patients with active tuberculosis and 
previous and/or current immunosuppressive therapy.  Appropriate screening tests, i.e. tuberculin skin 
test and chest X-ray, should be performed in all patients (local recommendations may apply).  It is 
recommended that the conduct of these tests should be recorded in the patient alert card.  Prescribers 
are reminded of the risk of false negative tuberculin skin test results, especially in patients who are 
severely ill or immunocompromised.  
 
If active tuberculosis is diagnosed, Trudexa therapy must not be initiated (see section 4.3).  
 
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis prophylaxis in accordance with local 
recommendations must be initiated before starting treatment with Trudexa.  In this situation, the 
benefit/risk balance of therapy with Trudexa should be very carefully considered. 
 
Patients should be instructed to seek medical advice if signs/symptoms (e.g., persistent cough, 
wasting/weight loss, low grade fever) suggestive of a tuberculosis infection occur during or after 
therapy with Trudexa.  
 
Other opportunistic infections: 
 
There have been reports of serious and severe opportunistic infections associated with Trudexa 
therapy, for example pneumocystis carinii pneumonia, disseminated histoplasmosis, listeriosis and 
aspergillosis. 
 
If a patient receiving Trudexa shows prolonged/atypical symptoms/signs of infections or general 
deterioration, prevalent opportunistic conditions must be considered. 
 
Hepatitis B Reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Trudexa, 
who are chronic carriers of this virus.  Some cases have had fatal outcome.  Patients at risk for HBV 
infection should be evaluated for prior evidence of HBV infection before initiating Trudexa therapy.  
Carriers of HBV who require treatment with Trudexa should be closely monitored for signs and 
symptoms of active HBV infection throughout therapy and for several months following termination 
of therapy.  Adequate data of treating patients who are carriers of HBV with anti-viral therapy in 
conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available.  In patients 
who develop HBV reactivation, Trudexa should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated.  

Neurological events  

TNF-antagonists including Trudexa have been associated in rare cases with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of demyelinating disease.  Prescribers should 
exercise caution in considering the use of Trudexa in patients with pre-existing or recent-onset central 
nervous system demyelinating disorders.  

Allergic reactions 

Serious allergic adverse reactions have not been reported with subcutaneous administration of Trudexa 
during clinical trials.  Non-serious allergic reactions associated with Trudexa were uncommon during 
clinical trials.  In postmarketing, serious allergic reactions including anaphylaxis have been reported 
very rarely following Trudexa administration.  If an anaphylactic reaction or other serious allergic 
reaction occurs, administration of Trudexa should be discontinued immediately and appropriate 
therapy initiated.  
 



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The needle cover of the syringe contains natural rubber (latex).  This may cause severe allergic 
reactions in patients sensitive to latex. 

Immunosuppression 

In a study of 64 patients with rheumatoid arthritis that were treated with Trudexa, there was no 
evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or 
change in enumeration of effector T-and B cells and NK-cells, monocyte/macrophages, and 
neutrophils. 

Malignancies and lymphoproliferative disorders 

In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients.  However, the occurrence was rare.  Furthermore, there is an increased background 
lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory 
disease, which complicates the risk estimation.  With the current knowledge, a possible risk for the 
development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
No studies have been conducted that include patients with a history of malignancy or that continue 
treatment in patients who develop malignancy while receiving Trudexa.  Thus additional caution 
should be exercised in considering Trudexa treatment of these patients (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients 
with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in 
the lung or head and neck, were reported in infliximab-treated patients compared with control patients.  
All patients had a history of heavy smoking.  Therefore, caution should be exercised when using any 
TNF-antagonist in COPD patients, as well as in patients with increased risk for malignancy due to 
heavy smoking. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF blocking 
agents.  Adverse events of the haematologic system, including medically significant cytopoenia (e.g. 
thrombocytopaenia, leucopaenia) have been infrequently reported with Trudexa.  All patients should 
be advised to seek immediate medical attention if they develop signs and symptoms suggestive of 
blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor) while on Trudexa.  Discontinuation 
of Trudexa therapy should be considered in patients with confirmed significant haematologic 
abnormalities. 
 
Vaccinations  
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo.  No data are available on the secondary transmission of infection 
by live vaccines in patients receiving Trudexa.  Patients on Trudexa may receive concurrent 
vaccinations, except for live vaccines. 

Congestive heart failure 

In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased 
mortality due to congestive heart failure have been observed.  Cases of worsening congestive heart 
failure have also been reported in patients receiving Trudexa.  Trudexa should be used with caution in 
patients with mild heart failure (NYHA class I/II).  Trudexa is contraindicated in moderate to severe 
heart failure (see section 4.3).  Treatment with Trudexa must be discontinued in patients who develop 
new or worsening symptoms of congestive heart failure. 



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Autoimmune processes 

Treatment with Trudexa may result in the formation of autoimmune antibodies.  The impact of long-
term treatment with Trudexa on the development of autoimmune diseases is unknown.  If a patient 
develops symptoms suggestive of a lupus-like syndrome following treatment with Trudexa and is 
positive for antibodies against double-stranded DNA, further treatment with Trudexa should not be 
given (see section 4.8). 

Concurrent administration of TNF-antagonists and anakinra 

Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone.  Because of 
the nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists.  Therefore, the 
combination of adalimumab and anakinra is not recommended. 

Surgery 

There is limited safety experience of surgical procedures in patients treated with Trudexa.  The long 
half-life of adalimumab should be taken into consideration if a surgical procedure is planned.  A 
patient who requires surgery while on Trudexa should be closely monitored for infections, and 
appropriate actions should be taken.  There is limited safety experience in patients undergoing 
arthroplasty while receiving Trudexa.  
 
Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment.  Available data suggest that Trudexa does not worsen or cause 
strictures. 

4.5 Interaction with other medicinal products and other forms of interaction  

Trudexa has been studied both in rheumatoid arthritis and psoriatic arthritis patients taking Trudexa as 
monotherapy and those taking concomitant methotrexate.  Antibody formation was lower when 
Trudexa was given together with methotrexate in comparison with use as monotherapy.  
Administration of Trudexa without methotrexate resulted in increased formation of antibodies, 
increased clearance and reduced efficacy of adalimumab (see section 5.1).  

4.6 Pregnancy and lactation  

For Trudexa, no clinical data on exposed pregnancies are available 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity.  Preclinical data on postnatal toxicity and fertility effects of 
adalimumab are not available (see section 5.3). 
 
Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal 
immune responses in the newborn.  Administration of adalimumab is not recommended during 
pregnancy.  Women of childbearing potential are strongly recommended to use adequate contraception 
to prevent pregnancy and continue its use for at least five months after the last Trudexa treatment.  

Use during lactation  

It is not known whether adalimumab is excreted in human milk or absorbed systemically after 
ingestion.  
 



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However, because human immunoglobulins are excreted in milk, women must not breast-feed for at 
least five months after the last Trudexa treatment. 

4.7 Effects on ability to drive and use machines  

No studies on the effects on the ability to drive and use machines have been performed. 

4.8 Undesirable effects 

Clinical Trials 
 
Trudexa was studied in 5293 patients in controlled and open label trials for up to 60 months.  These 
trials included rheumatoid arthritis patients with short term and long standing disease as well as 
psoriatic arthritis, ankylosing spondylitis and Crohn’s disease patients.  The data in Table 1 is based 
on the controlled Studies (I − IX,CLASSIC I, GAIN AND CHARM) (described in section 5.1) 
involving 3271 patients receiving Trudexa and 1809 patients receiving placebo or active comparator 
during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of Studies I − IX, CLASSIC I, GAIN and CHARM  was 5.7% for patients taking 
Trudexa and 5.3% for control treated patients. 
 
Adverse events at least possibly causally-related to adalimumab for Studies I − IX, CLASSIC I, GAIN 
and CHARM, both clinical and laboratory, are displayed by system organ class and frequency (very 
common ≥ 1/10; common≥ 1/100 < 1/10; uncommon≥ 1/1000  to ≤ 1/100) and rare < 1/1000 in Table 
1 below.  Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness. 
 

Table 1 
Undesirable Effects in Clinical Studies 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations 
 

Common 
 

lower respiratory infections (including 
pneumonia, bronchitis), viral infections 
(including influenza, herpes infections), 
candidiasis, bacterial infections (including 
urinary tract infections), upper respiratory 
infection 
 

 Uncommon 
 

opportunistic infections (including  
tuberculosis, histoplasmosis), sepsis, abscess,  
joint infection, wound infection, skin infection 
(including cellulitis and impetigo), superficial 
fungal infections (including skin, nail and 
foot) 
 

 Rare necrotising fasciitis, viral meningitis, 
diverticulitis 
 

Uncommon 
 

skin papilloma 
 

Neoplasms benign and 
malignant (including 
cysts and polyps)  Rare 

 
lymphoma, solid organ tumours (including 
breast, ovarian, testicular), squamous cell 
carcinoma of the skin 
 



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Common 
 

lymphopaenia 
 

Uncommon 
 

neutropaenia (including agranulocytosis), 
leucopaenia, thrombocytopaenia, anaemia, , 
lymphadenopathy, leucocytosis  
 

Blood and the lymphatic 
system disorders 

Rare 
 

pancytopaenia, idiopathic thrombocytopaenia 
purpura 
 

Uncommon 
 

systemic lupus erythematosus, angioedema, 
drug hypersensitivity, seasonal allergy 
 

Immune system disorders 

Rare serum sickness 
 

Endocrine disorders Rare 
 

thyroid disorder (including goitre) 

Uncommon 
 

Hypokalaemia, lipids increased, appetite 
disorders (including anorexia), hyperuricaemia 
 

Metabolism and nutrition 
disorders 

Rare hypercalcaemia 
 

Psychiatric disorders Uncommon 
 

mood disorders, anxiety (including 
nervousness and agitation) 
 

Common 
 

dizziness (including vertigo), headache, 
neurologic sensation disorders (including 
paraesthesias) 
 

Uncommon 
 

syncope, migraine, tremor, sleep disturbances  
 

Nervous system disorders 

Rare 
 

multiple sclerosis 
 

Common 
 

infection, irritation or inflammation of the eye 
 

Uncommon 
 

vision disorder, ocular sensation disorders  
 

Eye disorders 

Rare Panophthalmitis, iritis, glaucoma 
 

Uncommon 
 

tinnitus, ear discomfort (including pain and 
swelling) 
 

Ear and labyrinth 
disorders  
 

Rare 
 

hearing loss 
 

Uncommon 
 

arrhythmias, tachycardia, palpitations 
 

Cardiac disorders  

Rare 
 

cardiac arrest, coronary artery insufficiency, 
angina pectoris, pericardial effusion 
 

Vascular disorders Uncommon 
 

hypertension, flushing, haematoma 
 

 Rare vascular occlusion, aortic stenosis, 
thrombophlebitis, aortic aneurysm 
 

Respiratory, thoracic and 
mediastinal disorders 

Common 
 

cough, nasopharyngeal pain 
 



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Uncommon 
 

asthma, dyspnoea, dysphonia, nasal 
congestion 
 

 

Rare pulmonary oedema, pharyngeal oedema, 
pleural effusion, pleurisy 
 

Common 
 

diarrhoea, abdominal pain, stomatitis and 
mouth ulceration, nausea 
 

Uncommon 
 

rectal haemorrhage, gastritis, vomiting, 
dyspepsia, abdominal bloating, constipation,  
 

Gastrointestinal disorders 

Rare 
 

intestinal stenosis, colitis, enteritis, 
oesophagitis 
 

Hepato-biliary disorders Common 
 

hepatic enzymes increased 
 

 Rare 
 

hepatic necrosis, hepatitis 
 

Common 
 

rash, dermatitis and eczema, pruritus, hair loss 
 

Uncommon 
 

urticaria, psoriasis, ecchymosis and increased 
bruising, purpura 
 

Skin and subcutaneous 
tissue disorders 

Rare 
 

erythema multiforme, panniculitis 

Common 
 

musculoskeletal pain 
 

Musculoskeletal, 
connective tissue and 
bone disorders Rare 

 
rhabdomyolysis 

Uncommon 
 

haematuria, renal impairment, bladder and 
urethral symptoms 
 

Renal and urinary 
disorders  

Rare 
 

proteinuria, renal pain 
 

Reproductive system and 
breast disorders 

Uncommon menstrual cycle and uterine bleeding disorders 
 

Very Common 
 

injection site reaction (including pain, 
swelling, redness or pruritus) 
 

Common 
 

pyrexia, fatigue (including asthenia and 
malaise) 
 

General disorders and 
administration site 
conditions 

Uncommon 
 

chest pain, oedema, influenza like illness 

Investigations Uncommon blood creatine phosphokinase increased, 
activated partial thromboplastin time 
prolonged, autoantibodies present 
 

Injury and poisoning  Uncommon accidental injury, impaired healing 
 

Injection site reactions   



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In the twelve controlled trials, 16% of patients treated with Trudexa developed injection site reactions 
(erythema and/or itching, haemorrhage, pain or swelling), compared to 10% of patients receiving 
placebo or active control.  Injection site reactions generally did not necessitate discontinuation of the 
medicinal product.  

Infections  

In the twelve controlled trials, the rate of infection was 1.49 per patient year in the Trudexa treated 
patients and 1.42 per patient year in the placebo and active control-treated patients.  The infections 
consisted primarily of upper respiratory tract infections, bronchitis and urinary tract infections.  Most 
patients continued on Trudexa after the infection resolved.   
 
The incidence of serious infections was 0.03 per patient year in Trudexa treated patients and 0.03 per 
patient year in placebo and active control − treated patients.   
 
In controlled and open label studies with Trudexa, serious infections (including fatal infections, which 
occurred rarely) have been reported, which include reports of tuberculosis (including miliary and 
extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated histoplasmosis, 
pneumocystis carinii pneumonia, aspergillosis and listeriosis).  Most of the cases of tuberculosis 
occurred within the first eight months after initiation of therapy and may reflect recrudescence of 
latent disease. 

Malignancies and lymphoproliferative disorders 

During the controlled portions of ten Trudexa trials at least 12 weeks in duration (I-IX and CHARM) 
in patients with moderately to severely active rheumatoid arthritis, psoriatic arthritis, ankylosing 
spondylitis and Crohn’s disease, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 5.7 (3.3, 10.1) per 1000 patient-years among 
2887 Trudexa treated patients versus a rate of 4.1 (1.5, 10.9) 1 per 1000 patient-years among 1570 
control patients (median duration of treatment was 5.7 months for Trudexa and 5.5 months for control-
treated patients).  The rate (95% confidence interval) of non-melanoma skin cancers was 7.6 (4.7, 
12.4) per 1000 patient-years among Trudexa-treated patients and 2.0 (0.5, 8.2) per 1000 patient-years 
among control patients.  Of these skin cancers, squamous cell carcinomas occurred at rates (95% 
confidence interval) of 2.4 (1.0, 5.7) per 1000 patient-years among Trudexa-treated patients and 0 per 
1000 patient-years among control patients.  The rate (95% confidence interval) of lymphomas was 1.0 
(0.2, 3.8)  per 1000 patient-years among Trudexa-treated patients and 1.0 (0.1, 7.3) per 1000 patient-
years among control patients. 
 
When combining controlled portions of ten trials (I-IX and CHARM) and ongoing open label 
extension studies with a median duration of approximately 2. years including 4843 patients and over 
13000 patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-
melanoma skin cancers is approximately 13.6 per 1000 patient years.  The observed rate of non-
melanoma skin cancers is approximately 9.0 per 1000 patient years, and the observed rate of 
lymphomas is approximately 1.2 per 1000 patient years. 
 
In post-marketing experience from January 2003, predominately in patients with rheumatoid arthritis, 
the reported rate of malignancies other than lymphomas and non-melanoma skin cancers is 
approximately 1.7 per 1000 patient years.  The reported rates for non-melanoma skin cancers and 
lymphomas are approximately 0.2 and 0.4 per 1000 patient years, respectively (see section 4.4). 

Autoantibodies  

Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis 
Studies I − V.  In these trials, 11.9% of patients treated with Trudexa and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres 
at week 24.  Two patients out of 3441 treated with Trudexa in all rheumatoid arthritis and psoriatic 
arthritis studies developed clinical signs suggestive of new-onset lupus-like syndrome.  The patients 



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improved following discontinuation of therapy.  No patients developed lupus nephritis or central 
nervous system symptoms. 

Liver Enzyme Elevations 

Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (Studies I − IV), 
elevations of ALT were similar in patients receiving adalimumab or placebo.  In patients with early 
rheumatoid arthritis (disease duration of less than 3 years) (Study V), elevations of ALT were more 
common in the combination arm (Trudexa /methotrexate) compared to the methotrexate monotherapy 
arm or the Trudexa monotherapy arm. 
 
Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients 
(Studies VI-VII) compared with patients in rheumatoid arthritis clinical studies. 
 
In all studies (I-VII), patients with raised ALT were asymptomatic and in most cases elevations were 
transient and resolved on continued treatment. 
 
Crohn’s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients 
receiving adalimumab or placebo. 

Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials 

The additional adverse reactions in Table 2 have been reported from postmarketing surveillance or 
Phase IV clinical trials: 
 

Table 2 
Undesirable Effects in Postmarketing Surveillance and Phase IV Clinical Studies 

 
System Organ Class Adverse Reaction 
Hepatobiliary Disorders reactivation of hepatitis B 
Nervous system disorders demyelinating disorders (e.g. optic neuritis) 
Respiratory, thoracic and mediastinal disorders interstitial lung disease, including pulmonary 

fibrosis  
Skin and subcutaneous tissue disorders cutaneous vasculitis 
Immune system disorders anaphylaxis 

4.9 Overdose  

No dose-limiting toxicity was observed during clinical trials.  The highest dose level evaluated has 
been multiple intravenous doses of 10 mg/kg.   

5. PHARMACOLOGICAL PROPERTIES 

5.1 Pharmacodynamic properties 

Pharmacotherapeutic group: Selective immunosuppressive agents.  ATC code: L04AA17 

Mechanism of action 

Adalimumab binds specifically to TNF and neutralizes the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including 
changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, 
and ICAM-1 with an IC50 of 1-2 X 10-10 M).  



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Pharmacodynamic effects  

After treatment with Trudexa, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed compared to baseline in patients with rheumatoid arthritis.  Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Trudexa administration.  Patients treated with Trudexa usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with Crohn’s disease. 

Clinical trials 

Rheumatoid arthritis 
 
Trudexa was evaluated in over 3000 patients in all rheumatoid arthritis clinical trials.  Some patients 
were treated for  up to 60 months duration.  The efficacy and safety of Trudexa for the treatment of 
rheumatoid arthritis were assessed in five randomised, double-blind and well-controlled studies.   
 
Study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had 
insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) 
every week and whose methotrexate dose remained constant at 10 to 25 mg every week.  Doses of 20, 
40 or 80 mg of Trudexa or placebo were given every other week for 24 weeks.  
 
Study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.  Doses of 
20 or 40 mg of Trudexa were given by subcutaneous injection every other week with placebo on 
alternative weeks or every week for 26 weeks; placebo was given every week for the same duration.  
No other disease-modifying anti-rheumatic drugs were allowed. 
 
Study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old, had insufficient efficacy to methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-
intolerant) every week and whose methotrexate dose remained constant at 12.5 to 25 mg every week.  
There were three groups in this study.  The first received placebo injections every week for 52 weeks.  
The second received 20 mg of Trudexa every week for 52 weeks.  The third group received 40 mg of 
Trudexa every other week with placebo injections on alternate weeks.  Thereafter, patients enrolled in 
an open-label extension phase in which 40 mg of Trudexa was administered every other week up to 60 
months. 
 
Study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were ≥ 18 years old.  Patients were permitted to be either disease-modifying, 
anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that 
therapy was stable for a minimum of 28 days.  These therapies include methotrexate, leflunomide, 
hydroxychloroquine, sulfasalazine and/or gold salts.  Patients were randomised to 40 mg of Trudexa 
or placebo every other week for 24 weeks.   
 
Study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months).  This study evaluated the efficacy of 
Trudexa 40 mg every other week/methotrexate combination therapy, Trudexa 40 mg every other week 
monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of 
progression of joint damage in rheumatoid arthritis for 104 weeks. 
 
The primary end point in Studies I, II and III and the secondary endpoint in Study IV was the percent 
of patients who achieved an ACR 20 response at week 24 or 26.  The primary endpoint in Study V 
was the percent of patients who achieved an ACR 50 response at week 52.  Study III and V had an 



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additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results).  Study III also had a primary endpoint of changes in quality of life. 

ACR response 

The percent of Trudexa-treated patients achieving ACR 20, 50 and 70 responses was consistent across 
trials I, II and III.  The results for the 40 mg every other week dose are summarised in Table 3.  
 

Table 3:  ACR Responses in Placebo-Controlled Trials 
(Percent of Patients) 

 
Response Study Ia** Study IIa** Study IIIa** 

 
 Placebo/ 

MTXc 
n=60 

Trudexab/ MTXc
n=63 

Placebo 
n=110 

Trudexab 
n=113 

Placebo/ 
MTXc 
n=200 

Trudexab/ 
MTXc 
n=207 

ACR 20       
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3% 
 12 months NA NA NA NA 24.0% 58.9% 
ACR 50       
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1% 
 12 months NA NA NA NA 9.5% 41.5% 
ACR 70       
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8% 
 12 months NA NA NA NA 4.5% 23.2% 
a Study I at 24 weeks, Study II at 26 weeks , and Study III at 24 and 52 weeks 
b 40 mg Trudexa administered every other week 
c MTX = methotrexate 
**p < 0.01, Trudexa versus placebo 

 
In Studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores 
and CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo.  In Study III, these 
improvements were maintained throughout 52 weeks.  In addition, ACR response rates were 
maintained in the majority of patients followed in the open-label extension phase to week 104.  There 
were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.  
Among those, 86, 72, and 41 patients had ACR 20/50/70 response, respectively at month 60. 
 
In Study IV, the ACR 20 response of patients treated with Trudexa plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   
 
In Studies I-IV, Trudexa-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In Study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Trudexa and methotrexate led to faster and significantly greater ACR responses than 
methotrexate monotherapy and Trudexa monotherapy at week 52 and responses were sustained at 
week 104 (see Table 4). 
 

Table 4:  ACR Responses in Study V 
(percent of patients) 

 

Response MTX n=257 
Trudexa 

n=274 

Trudexa/MT
X 

n=268 
p-valuea p-valueb p-valuec 

ACR 20       



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 Week 52 62.6% 54.4% 72.8% 0.013 < 0.001 0.043 
 Week 104 56.0% 49.3% 69.4% 0.002 < 0.001 0.140 
ACR 50       
 Week 52 45.9% 41.2% 61.6% < 0.001 < 0.001 0.317 
 Week 104 42.8% 36.9% 59.0% < 0.001 < 0.001 0.162 
ACR 70       
 Week 52 27.2% 25.9% 45.5% < 0.001 < 0.001 0.656 
 Week 104 28.4% 28.1% 46.6% < 0.001 < 0.001 0.864 
a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/methotrexate 

combination therapy using the Mann-Whitney U test. 
b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/methotrexate 

combination therapy using the Mann-Whitney U test 
c.   p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate monotherapy 

using the Mann-Whitney U test 
 
At week 52, 42.9% of patients who received Trudexa/methotrexate combination therapy achieved 
clinical remission (DAS28 < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy 
and 23.4% of patients receiving Trudexa monotherapy.  Trudexa/methotrexate combination therapy 
was clinically and statistically superior to methotrexate (p < 0.001) and Trudexa monotherapy 
(p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe 
rheumatoid arthritis.  The response for the two monotherapy arms was similar (p = 0.447). 

Radiographic response 

In Study III, where Trudexa treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as 
change in modified total Sharp score and its components, the erosion score and joint space narrowing 
score.  Trudexa/methotrexate patients demonstrated significantly less radiographic progression than 
patients receiving methotrexate alone at 6 and 12 months (see Table 5).  Data from the open-label 
extension phase indicate that the reduction in rate of progression of structural damage is maintained 
for 60 months in a subset of patients.  113/207 of patients originally treated with 40 mg Humira every 
other week were evaluated radiographically at 5 years. Among those, 66 patients showed no 
progression of structural damage defined by a change in the TSS of zero or less. 
 

Table 5:  Radiographic Mean Changes Over 12 Months in Study III 
 

 Placebo/ 
MTXa 

TRUDEXA/MTX 
40 mg every 
other week 

Placebo/MTX-
TRUDEXA/MTX 
(95% Confidence 

Intervalb) 

P-value 

Total Sharp score 2.7 0.1 2.6 (1.4, 3.8)  < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Trudexa.  
cBased on rank analysis  
dJoint Space Narrowing 
 
In Study V, structural joint damage was assessed radiographically and expressed as change in 
modified total Sharp score (see Table 6). 
 

Table 6:  Radiographic Mean Changes at Week 52 in Study V 
 

 
MTX 
n=257 

(95% confidence 
interval) 

Trudexa 
n=274 

(95% confidence 
interval) 

Trudexa/MT
X 

n=268 
p-valuea p-valueb p-valuec 



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(95% confidence 
interval) 

Total Sharp 
score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001 
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151 

a. p-value is from the pairwise comparison of methotrexate monotherapy and 
Trudexa/methotrexate combination therapy using the Mann-Whitney U test. 

b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/methotrexate 
combination therapy using the Mann-Whitney U test  

c.   p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate 
monotherapy using the Mann-Whitney U test 

 
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression 
(change from baseline in modified total Sharp score ≤ 0.5) was significantly higher with 
Trudexa/methotrexate combination therapy (63.8% and 61.2% respectively) compared to methotrexate 
monotherapy (37.4% and 33.5% respectively, p < 0.001) and Trudexa monotherapy (50.7%, p < 0.002 
and 44.5%, p < 0.001 respectively). 

Quality of life and physical function  

Health-related quality of life and physical function was assessed using the disability index of the 
Health Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, 
which was a pre-specified primary endpoint at week 52 in Study III.  All doses/schedules of Trudexa 
in all four studies showed statistically significantly greater improvement in the disability index of the 
HAQ from baseline to Month 6 compared to placebo and in Study III the same was seen at week 52.  
Results from the Short Form Health Survey (SF 36) for all doses/schedules of Trudexa in all four 
studies support these findings, with statistically significant physical component summary (PCS) 
scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other 
week dose.  A statistically significant decrease in fatigue as measured by functional assessment of 
chronic illness therapy (FACIT) scores was seen in all three studies in which it was assessed (Studies 
I, III, IV). 
 
In Study III, improvement in physical function was maintained through week  260 (60 months) of 
open-label treatment.  Improvement in quality of life was measured up to week 156 (36 months) and 
improvement was maintained through that time. 
 
In Study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Trudexa/methotrexate combination therapy versus 
methotrexate monotherapy and Trudexa monotherapy at week 52, which was maintained through 
week 104. 

Psoriatic arthritis 

Trudexa, 40 mg every other week, was studied in patients with moderately to severely active psoriatic 
arthritis in two placebo-controlled studies, Studies VI and VII.  Study VI with 24 week duration, 
treated 313 adult patients who had an inadequate response to non-steroidal anti-inflammatory drug 
therapy and of these, approximately 50% were taking methotrexate.  Study VII with 12-week duration, 
treated 100 patients who had an inadequate response to DMARD therapy. 
 
There is insufficient evidence of the efficacy of Trudexa in patients with ankylosing spondylitis-like 
psoriatic arthropathy due to the small number of patients studied (see Table 7). 
 

Table 7:  ACR Response in Placebo-Controlled Psoriatic Arthritis Studies 
(Percent of Patients) 

 
 Study VI Study VII 



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Response Placebo N=162 
Trudexa 
N=151 

Placebo  
N=49 

Trudexa 
N=51 

ACR 20      
 Week 12 14% 58%*** 16% 39%* 
 Week 24 15% 57%*** N/A N/A 
ACR 50      
 Week 12 4% 36%*** 2% 25%*** 
 Week 24 6% 39%*** N/A N/A 
ACR 70      
 Week 12 1% 20%*** 0% 14% * 
 Week 24 1% 23%*** N/A N/A 

*** p < 0.001 for all comparisons between Trudexa and placebo 
* p < 0.05 for all comparisons between Trudexa and placebo   
N/A  not applicable 

 
ACR responses in Study VI were similar with and without concomitant methotrexate therapy. 
Trudexa treated patients demonstrated improvement in physical function as assessed by HAQ and 
Short Form Health Survey (SF 36), from base-line to week 24. 

Ankylosing spondylitis 

Trudexa 40 mg every other week was assessed in 393 patients in two randomised, 24 week 
double − blind, placebo − controlled studies in patients with active ankylosing spondylitis (mean 
baseline score of disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] 
was 6.3 in all groups) who have had an inadequate response to conventional therapy.  Seventy-nine 
(20.1%) patients were treated concomitantly with disease modifying anti-rheumatic drugs, and 37 
(9.4%) patients with glucocorticoids.  The blinded period was followed by an open − label period 
during which patients received Trudexa 40 mg every other week subcutaneously for up to an 
additional 28 weeks.  Subjects (n = 215, 54.7%) who failed to achieve ASAS 20 at Weeks 12, or 16 or 
20 received early escape open-label adalimumab 40 mg every other week subcutaneously and were 
subsequently treated as non-responders in the double-blind statistical analyses. 
 
In the larger study (VIII) with 315 patients, results showed statistically significant improvement of the 
signs and symptoms of ankylosing spondylitis in patients treated with Trudexa compared to placebo.  
Significant response was first observed at Week 2 and maintained through 24 weeks (Table 8).  

 
Table 8 - Efficacy Responses in Placebo-Controlled AS Study – Study VIII 

Reduction of Signs and Symptoms 
 

Response Placebo 
N=107 

Trudexa 
N=208 

ASASa 20   
             Week 2 16% 42%*** 

Week 12 21% 58%*** 
Week 24 19% 51%*** 

ASAS 50   
             Week 2 3% 16%*** 

Week 12 10% 38%*** 
Week 24 11% 35%*** 

ASAS 70   
             Week 2 0% 7%** 

Week 12 5% 23%*** 
Week 24 8% 24%*** 

   
BASDAIb 50    



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             Week 2 4% 20%*** 
Week 12  16% 45%*** 
Week 24  15% 42%*** 

***,** Statistically significant at p < 0.001, < 0.01 for all comparisons between Trudexa and placebo at Weeks 
2, 12 and  24 
a ASsessments in Ankylosing Spondylitis 
b Bath Ankylosing Spondylitis Disease Activity Index 

 
Trudexa treated patients had significantly greater improvement at Week 12 which was maintained 
through Week 24 in both the SF36 and Ankylosing Spondylitis Quality of Life Questionnaire 
(ASQoL). 
 
Similar trends (not all statistically significant) were seen in the smaller randomised, double − blind, 
placebo controlled study (IX) of 82 adult patients with active ankylosing spondylitis. 

Crohn’s Disease 

The safety and efficacy of Trudexa were assessed in over 1400 patients with moderately to severely 
active Crohn’s disease (Crohn’s Disease Activity Index (CDAI) ≥ 220 and ≤ 450) in randomised, 
double-blind, placebo-controlled studies.  478 of the enrolled patients (32%) were defined as having  a 
severe disease (CDAI score > 300 and concomitant corticosteroid and/or immunosuppressants) 
corresponding to the population defined in the indication (see section 4.1).  Concomitant stable doses 
of aminosalicylates, corticosteroids, and/or immunomodulatory agents were permitted and 79% of 
patients continued to receive at least one of these medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CLASSIC I and 
GAIN.  In CLASSIC I, 299 TNF-antagonist naive patients were randomised to one of four treatment 
groups; placebo at weeks 0 and 2, 160 mg Trudexa at week 0 and 80 mg at week 2, 80 mg at week 0 
and 40 mg at week 2, and 40 mg at week 0 and 20 mg at week 2.  In GAIN, 325 patients who had lost 
response or were intolerant to infliximab were randomised to receive either 160 mg Trudexa at week 0 
and 80 mg at week 2 or placebo at weeks 0 and 2.  The primary non-responders were excluded from 
the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CHARM.  In CHARM, 854 patients received 
open-label 80 mg at week 0 and 40 mg at week 2.  At week 4 patients were randomised to 40 mg every 
other week, 40 mg every week, or placebo with a total study duration of 56 weeks.  Patients in clinical 
response (decrease in CDAI ≥ 70) at week 4 were stratified and analysed separately from those not in 
clinical response at week 4.  Corticosteroid taper was permitted after week 8.  
 
CLASSIC I and GAIN induction of remission and response rates are presented in Table 9. 
 



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Table 9: Induction of Clinical Remission and Response 
(Percent of Patients) 

 CLASSIC I: Infliximab Naive Patients GAIN: Infliximab Experienced Patients 

 Placebo 

N=74 

Trudexa 

80/40 mg 

N = 75 

Trudexa  

160/80 mg 
N=76 

Placebo 

N=166 

Trudexa  

160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Trudexa versus placebo 
* p < 0.001 
** p < 0.01 
 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by week 8 
and adverse events were more frequently noted in the 160/80 mg group. 
 
In CHARM, at week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis.  Of those in clinical response at week 4, 48% had been previously exposed to other 
anti-TNF therapy.  Maintenance of remission and response rates are presented in Table 10.  Clinical 
remission results remained relatively constant irrespective of previous TNF antagonist exposure. 
 

Table 10: Maintenance of Clinical Remission and Response 
(Percent of Patients) 

 Placebo 40 mg Trudexa 
every other week 

40 mg Trudexa 
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for >=90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Trudexa versus placebo pairwise comparisons   of proportions 

** p < 0.02 for Trudexa versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 
Among patients who were not in response at week 4, 43% of Trudexa maintenance patients responded 
by week 12 compared to 30% of placebo maintenance patients.  These results suggest that some 
patients who have not responded by week 4 benefit from continued maintenance therapy through week 
12.  Therapy continued beyond 12 weeks did not result in significantly more responses (see section 
4.2).   

Quality of Life 

In CLASSIC I and GAIN, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at week 4 in patients randomised to 



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Trudexa 80/40 mg and 160/80 mg compared to placebo and was seen at weeks 26 and 56 in CHARM 
as well among the adalimumab treatment groups compared to the placebo group. 

Immunogenicity   

Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy 
of adalimumab.  There is no apparent correlation between the presence of anti-adalimumab antibodies 
and adverse events. 
 
Patients in Studies I, II and III were tested at multiple timepoints for antibodies to adalimumab during 
the 6 to 12 month period.  In the pivotal trials, anti-adalimumab antibodies were identified in 58/1053 
(5.5%) patients treated with adalimumab, compared to 2/370 (0.5%) on placebo.  In patients not given 
concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when adalimumab was used as 
add-on to methotrexate.   
 
In patients with psoriatic arthritis, adalimumab antibodies were identified in 38/376 subjects (10%) 
treated with adalimumab.  In patients not given concomitant methotrexate, the incidence was 13.5% 
(24/178 subjects), compared to 7% (14 of 198 subjects) when adalimumab was used as add-on to 
methotrexate. 
 
In patients with ankylosing spondylitis antibodies were identified in 17/204 subjects (8.3%) treated 
with adalimumab.  In patients not given concomitant methotrexate, the incidence was 16/185 (8.6%), 
compared to 1/19 (5.3%) when adalimumab was used as add-on to methotrexate. 
 
In patients with Crohn’s disease, adalimumab antibodies were identified in 7/269 subjects (2.6%) 
treated with adalimumab. 
 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 

5.2 Pharmacokinetic properties 

After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab 
was slow, with peak serum concentrations being reached about 5 days after administration.  The 
average absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%.  After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional.  After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 
to 15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-
life was approximately two weeks.  Adalimumab concentrations in the synovial fluid from several 
rheumatoid arthritis patients ranged from 31-96% of those in serum. 
 
Following subcutaneous administration of 40 mg of Trudexa every other week in rheumatoid arthritis 
(RA) patients the mean steady-state trough concentrations were approximately 5 µg/ml (without 
concomitant methotrexate) and 8 to 9 µg/ml (with concomitant methotrexate), respectively.  The 
serum adalimumab trough levels at steady-state increased roughly proportionally with dose following 
20, 40 and 80 mg every other week and every week subcutaneous dosing. 
 
In patients with Crohn’s disease, the loading dose of 80 mg Trudexa on week 0 followed by 40 mg 
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 5.5 µg/ml 
during the induction period.  A loading dose of 160 mg Trudexa on week 0 followed by 80 mg 
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 12 µg/ml 
during the induction period.  Mean steady-state trough levels of approximately 7 µg/ml were observed 
in Crohn’s disease patients who received a maintenance dose of 40 mg Trudexa every other week. 
 
Population pharmacokinetic analyses with data from over 1300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight.  After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance.  The serum 



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levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower 
in patients with measurable AAA.  Trudexa has not been studied in children or in patients with hepatic 
or renal impairment. 

5.3 Preclinical safety data  

Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, 
repeated dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomologous monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence 
of harm to the foetuses due to adalimumab.  Carcinogenicity studies, and standard assessment of 
fertility and postnatal toxicity, were not performed with adalimumab due to the lack of appropriate 
models for an antibody with limited cross-reactivity to rodent TNF and the development of 
neutralizing antibodies in rodents.  

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients  

Mannitol 
Citric acid monohydrate 
Sodium citrate 
Sodium dihydrogen phosphate dihydrate 
Disodium phosphate dihydrate 
Sodium chloride 
Polysorbate 80 
Sodium hydroxide 
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  

18 months 

6.4 Special precautions for storage  

Store in a refrigerator (2°C – 8°C).  Keep the vial in the outer carton.  Do not freeze. 

6.5 Nature and contents of container   

Trudexa 40 mg solution for injection in single-use vial (type I glass), fitted with rubber stoppers, 
aluminium crimps and flip-off seals.  
 
Packs of: 
1 vial (0.8 ml sterile solution), 1 empty sterile injection syringe in pouch and 2 alcohol pads, all in a 
blister. 

6.6 Special precautions for disposal 

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



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7. MARKETING AUTHORISATION HOLDER  

Abbott Laboratories Ltd.  
Queenborough 
Kent ME11 5EL 
United Kingdom 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/03/257/001 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

1 September 2003 

10. DATE OF REVISION OF THE TEXT 

{MM/YYYY} 



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1. NAME OF THE MEDICINAL PRODUCT  

Trudexa 40 mg solution for injection in pre-filled syringe 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION  

Each 0.8 ml single dose pre-filled syringe contains 40 mg of adalimumab.  
 
Adalimumab is a recombinant human monoclonal antibody expressed in Chinese Hamster Ovary cells. 
 
For a full list of excipients, see section 6.1.  

3. PHARMACEUTICAL FORM  

Solution for injection in pre-filled syringe.  

4. CLINICAL PARTICULARS 

4.1 Therapeutic indications  

Rheumatoid arthritis 
 
Trudexa in combination with methotrexate, is indicated for: 
 
 the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the 

response to disease-modifying anti-rheumatic drugs including methotrexate has been 
inadequate. 

 the treatment of severe, active and progressive rheumatoid arthritis in adults not previously 
treated with methotrexate. 

 
Trudexa can be given as monotherapy in case of intolerance to methotrexate or when continued 
treatment with methotrexate is inappropriate. 
 
Trudexa has been shown to reduce the rate of progression of joint damage as measured by X-ray and 
to improve physical function, when given in combination with methotrexate. 

Psoriatic arthritis 

Trudexa is indicated for the treatment of active and progressive psoriatic arthritis in adults when the 
response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. 
 
Ankylosing spondylitis 
 
Trudexa is indicated for the treatment of adults with severe active ankylosing spondylitis who have 
had an inadequate response to conventional therapy. 
 
Crohn’s disease 
 
Trudexa is indicated for treatment of severe, active Crohn’s disease, in patients who have not 
responded despite a full and adequate course of therapy with a corticosteroid and/or an 
immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. 
For induction treatment, Trudexa should be given in combination with corticosteroids.  Trudexa can be 
given as monotherapy in case of intolerance to corticosteroids or when continued treatment with 
corticosteroids is inappropriate (see section 4.2). 



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4.2 Posology and method of administration   

Trudexa treatment should be initiated and supervised by specialist physicians experienced in the 
diagnosis and treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or Crohn’s 
disease.  Patients treated with Trudexa should be given the special alert card. 
 
After proper training in injection technique, patients may self-inject with Trudexa if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Trudexa, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 

Adults 

Rheumatoid arthritis 
 
The recommended dose of Trudexa for adult patients with rheumatoid arthritis is 40 mg adalimumab 
administered every other week as a single dose via subcutaneous injection.  Methotrexate should be 
continued during treatment with Trudexa. 
 
Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, or analgesics can be continued 
during treatment with Trudexa.  Regarding combination with disease modifying anti-rheumatic drugs 
other than methotrexate see sections 4.4 and 5.1. 
 
In monotherapy, some patients who experience a decrease in their response may benefit from an 
increase in dose intensity to 40 mg adalimumab every week.  

Psoriatic arthritis and ankylosing spondylitis 

The recommended dose of Trudexa for patients with psoriatic arthritis and ankylosing spondylitis is 
40 mg adalimumab administered every other week as a single dose via subcutaneous injection. 
 
For all of the above indications, available data suggest that the clinical response is usually achieved 
within 12 weeks of treatment.  Continued therapy should be carefully reconsidered in a patient not 
responding within this time period. 
 
Crohn’s disease 
 
The recommended Trudexa induction dose regimen for adult patients with severe Crohn’s disease is 
80 mg at week 0 followed by 40 mg at week 2.  In case there is a need for a more rapid response to 
therapy, the regimen 160 mg at week 0 (dose can be administered as four injections in one day or as 
two injections per day for two consecutive days), 80 mg at week 2, can be used with the awareness 
that the risk for adverse events is higher during induction. 
 
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous 
injection.  Alternatively, if a patient has stopped Trudexa and signs and symptoms of disease recur, 
Trudexa may be re-administered.  There is little experience from re-administration after more than 8 
weeks since the previous dose. 
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines. 
 
Some patients who experience decrease in their response may benefit from an increase in dose 
intensity to 40 mg Trudexa every week. 
 



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Some patients who have not responded by week 4 may benefit from continued maintenance therapy 
through week 12.  Continued therapy should be carefully reconsidered in a patient not responding 
within this time period. 

Elderly patients 

No dose adjustment is required.   

Children and adolescents 

 There is no experience in children. 

Impaired renal and/or hepatic function 

Trudexa has not been studied in these patient populations.  No dose recommendations can be made. 

4.3 Contraindications  

Hypersensitivity to the active substance or to any of the excipients.  
 
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 
4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 

4.4 Special warnings and precautions for use   

Infections 
 
Patients must be monitored closely for infections, including tuberculosis, before, during and after 
treatment with Trudexa.  Because the elimination of adalimumab may take up to five months, 
monitoring should be continued throughout this period. 
 
Treatment with Trudexa should not be initiated in patients with active infections including chronic or 
localized infections until infections are controlled.  
 
Patients who develop a new infection while undergoing treatment with Trudexa should be monitored 
closely.  Administration of Trudexa should be discontinued if a patient develops a new serious 
infection until infections are controlled.  Physicians should exercise caution when considering the use 
of Trudexa in patients with a history of recurring infection or with underlying conditions which may 
predispose patients to infections, including the use of concomitant immunosuppressive medications. 
 
Serious infections, sepsis, tuberculosis and other opportunistic infections, including fatalities, have 
been reported with Trudexa.   
 
Serious infections: 
 
In clinical trials an increased risk of serious infections in patients receiving Trudexa has been shown, 
and reports from the post-marketing setting support this finding.  Of particular importance are 
infections such as pneumonia, pyelonephritis, septic arthritis and septicaemia.   
 
Tuberculosis: 
 
There have been reports of tuberculosis in patients receiving Trudexa.  It should be noted that in the 
majority of those reports, tuberculosis was extra-pulmonary, i.e. disseminated.  
 



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Before initiation of therapy with Trudexa, all patients must be evaluated for both active or inactive 
(latent) tuberculosis infection.  This evaluation should include a detailed medical history with a 
personal history of tuberculosis or possible previous exposure to patients with active tuberculosis and 
previous and/or current immunosuppressive therapy.  Appropriate screening tests, i.e. tuberculin skin 
test and chest X-ray, should be performed in all patients (local recommendations may apply).  It is 
recommended that the conduct of these tests should be recorded in the patient alert card.  Prescribers 
are reminded of the risk of false negative tuberculin skin test results, especially in patients who are 
severely ill or immunocompromised.  
 
If active tuberculosis is diagnosed, Trudexa therapy must not be initiated (see section 4.3).  
 
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis prophylaxis in accordance with local 
recommendations must be initiated before starting treatment with Trudexa.  In this situation, the 
benefit/risk balance of therapy with Trudexa should be very carefully considered. 
 
Patients should be instructed to seek medical advice if signs/symptoms (e.g., persistent cough, 
wasting/weight loss, low grade fever) suggestive of a tuberculosis infection occur during or after 
therapy with Trudexa.  
 
Other opportunistic infections: 
 
There have been reports of serious and severe opportunistic infections associated with Trudexa 
therapy, for example pneumocystis carinii pneumonia, disseminated histoplasmosis, listeriosis and 
aspergillosis. 
 
If a patient receiving Trudexa shows prolonged/atypical symptoms/signs of infections or general 
deterioration, prevalent opportunistic conditions must be considered. 
 
Hepatitis B Reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Trudexa, 
who are chronic carriers of this virus.  Some cases have had fatal outcome.  Patients at risk for HBV 
infection should be evaluated for prior evidence of HBV infection before initiating Trudexa therapy.  
Carriers of HBV who require treatment with Trudexa should be closely monitored for signs and 
symptoms of active HBV infection throughout therapy and for several months following termination 
of therapy.  Adequate data of treating patients who are carriers of HBV with anti-viral therapy in 
conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available.  In patients 
who develop HBV reactivation, Trudexa should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated.  

Neurological events  

TNF-antagonists including Trudexa have been associated in rare cases with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of demyelinating disease.  Prescribers should 
exercise caution in considering the use of Trudexa in patients with pre-existing or recent-onset central 
nervous system demyelinating disorders.  

Allergic reactions 

Serious allergic adverse reactions have not been reported with subcutaneous administration of Trudexa 
during clinical trials.  Non-serious allergic reactions associated with Trudexa were uncommon during 
clinical trials.  In postmarketing, serious allergic reactions including anaphylaxis have been reported 
very rarely following Trudexa administration.  If an anaphylactic reaction or other serious allergic 
reaction occurs, administration of Trudexa should be discontinued immediately and appropriate 
therapy initiated.  
 



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The needle cover of the syringe contains natural rubber (latex).  This may cause severe allergic 
reactions in patients sensitive to latex. 

Immunosuppression 

In a study of 64 patients with rheumatoid arthritis that were treated with Trudexa, there was no 
evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or 
change in enumeration of effector T-and B cells and NK-cells, monocyte/macrophages, and 
neutrophils. 

Malignancies and lymphoproliferative disorders 

In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients.  However, the occurrence was rare.  Furthermore, there is an increased background 
lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory 
disease, which complicates the risk estimation.  With the current knowledge, a possible risk for the 
development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
No studies have been conducted that include patients with a history of malignancy or that continue 
treatment in patients who develop malignancy while receiving Trudexa.  Thus additional caution 
should be exercised in considering Trudexa treatment of these patients (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients 
with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in 
the lung or head and neck, were reported in infliximab-treated patients compared with control patients.  
All patients had a history of heavy smoking.  Therefore, caution should be exercised when using any 
TNF-antagonist in COPD patients, as well as in patients with increased risk for malignancy due to 
heavy smoking. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF blocking 
agents.  Adverse events of the haematologic system, including medically significant cytopoenia (e.g. 
thrombocytopaenia, leucopaenia) have been infrequently reported with Trudexa.  All patients should 
be advised to seek immediate medical attention if they develop signs and symptoms suggestive of 
blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor) while on Trudexa.  Discontinuation 
of Trudexa therapy should be considered in patients with confirmed significant haematologic 
abnormalities. 
 
Vaccinations  
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo.  No data are available on the secondary transmission of infection 
by live vaccines in patients receiving Trudexa.  Patients on Trudexa may receive concurrent 
vaccinations, except for live vaccines. 

Congestive heart failure 

In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased 
mortality due to congestive heart failure have been observed.  Cases of worsening congestive heart 
failure have also been reported in patients receiving Trudexa.  Trudexa should be used with caution in 
patients with mild heart failure (NYHA class I/II).  Trudexa is contraindicated in moderate to severe 
heart failure (see section 4.3).  Treatment with Trudexa must be discontinued in patients who develop 
new or worsening symptoms of congestive heart failure. 



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Autoimmune processes 

Treatment with Trudexa may result in the formation of autoimmune antibodies.  The impact of long-
term treatment with Trudexa on the development of autoimmune diseases is unknown.  If a patient 
develops symptoms suggestive of a lupus-like syndrome following treatment with Trudexa and is 
positive for antibodies against double-stranded DNA, further treatment with Trudexa should not be 
given (see section 4.8). 

Concurrent administration of TNF-antagonists and anakinra 

Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone.  Because of 
the nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists.  Therefore, the 
combination of adalimumab and anakinra is not recommended. 

Surgery 

There is limited safety experience of surgical procedures in patients treated with Trudexa.  The long 
half-life of adalimumab should be taken into consideration if a surgical procedure is planned.  A 
patient who requires surgery while on Trudexa should be closely monitored for infections, and 
appropriate actions should be taken.  There is limited safety experience in patients undergoing 
arthroplasty while receiving Trudexa.  
 
Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment.  Available data suggest that Trudexa does not worsen or cause 
strictures. 

4.5 Interaction with other medicinal products and other forms of interaction  

Trudexa has been studied both in rheumatoid arthritis and psoriatic arthritis patients taking Trudexa as 
monotherapy and those taking concomitant methotrexate.  Antibody formation was lower when 
Trudexa was given together with methotrexate in comparison with use as monotherapy.  
Administration of Trudexa without methotrexate resulted in increased formation of antibodies, 
increased clearance and reduced efficacy of adalimumab (see section 5.1).  

4.6 Pregnancy and lactation  

For Trudexa, no clinical data on exposed pregnancies are available 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity.  Preclinical data on postnatal toxicity and fertility effects of 
adalimumab are not available (see section 5.3). 
 
Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal 
immune responses in the newborn.  Administration of adalimumab is not recommended during 
pregnancy.  Women of childbearing potential are strongly recommended to use adequate contraception 
to prevent pregnancy and continue its use for at least five months after the last Trudexa treatment.  

Use during lactation  

It is not known whether adalimumab is excreted in human milk or absorbed systemically after 
ingestion.  
 



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However, because human immunoglobulins are excreted in milk, women must not breast-feed for at 
least five months after the last Trudexa treatment. 

4.7 Effects on ability to drive and use machines  

No studies on the effects on the ability to drive and use machines have been performed. 

4.8 Undesirable effects 

Clinical Trials 
 
Trudexa was studied in 5293 patients in controlled and open label trials for up to 60 months.  These 
trials included rheumatoid arthritis patients with short term and long standing disease as well as 
psoriatic arthritis, ankylosing spondylitis and Crohn’s disease patients.  The data in Table 1 is based 
on the controlled Studies (I − IX,CLASSIC I, GAIN AND CHARM) (described in section 5.1) 
involving 3271 patients receiving Trudexa and 1809 patients receiving placebo or active comparator 
during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of Studies I − IX, CLASSIC I, GAIN and CHARM  was 5.7% for patients taking 
Trudexa and 5.3% for control treated patients. 
 
Adverse events at least possibly causally-related to adalimumab for Studies I − IX, CLASSIC I, GAIN 
and CHARM, both clinical and laboratory, are displayed by system organ class and frequency (very 
common ≥ 1/10; common≥ 1/100 < 1/10; uncommon≥ 1/1000  to ≤ 1/100) and rare < 1/1000 in Table 
1 below.  Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness. 
 

Table 1 
Undesirable Effects in Clinical Studies 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations 
 

Common 
 

lower respiratory infections (including 
pneumonia, bronchitis), viral infections 
(including influenza, herpes infections), 
candidiasis, bacterial infections (including 
urinary tract infections), upper respiratory 
infection 
 

 Uncommon 
 

opportunistic infections (including  
tuberculosis, histoplasmosis), sepsis, abscess,  
joint infection, wound infection, skin infection 
(including cellulitis and impetigo), superficial 
fungal infections (including skin, nail and 
foot) 
 

 Rare necrotising fasciitis, viral meningitis, 
diverticulitis 
 

Uncommon 
 

skin papilloma 
 

Neoplasms benign and 
malignant (including 
cysts and polyps)  Rare 

 
lymphoma, solid organ tumours (including 
breast, ovarian, testicular), squamous cell 
carcinoma of the skin 
 



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Common 
 

lymphopaenia 
 

Uncommon 
 

neutropaenia (including agranulocytosis), 
leucopaenia, thrombocytopaenia, anaemia, , 
lymphadenopathy, leucocytosis  
 

Blood and the lymphatic 
system disorders 

Rare 
 

pancytopaenia, idiopathic thrombocytopaenia 
purpura 
 

Uncommon 
 

systemic lupus erythematosus, angioedema, 
drug hypersensitivity, seasonal allergy 
 

Immune system disorders 

Rare serum sickness 
 

Endocrine disorders Rare 
 

thyroid disorder (including goitre) 

Uncommon 
 

Hypokalaemia, lipids increased, appetite 
disorders (including anorexia), hyperuricaemia 
 

Metabolism and nutrition 
disorders 

Rare hypercalcaemia 
 

Psychiatric disorders Uncommon 
 

mood disorders, anxiety (including 
nervousness and agitation) 
 

Common 
 

dizziness (including vertigo), headache, 
neurologic sensation disorders (including 
paraesthesias) 
 

Uncommon 
 

syncope, migraine, tremor, sleep disturbances  
 

Nervous system disorders 

Rare 
 

multiple sclerosis 
 

Common 
 

infection, irritation or inflammation of the eye 
 

Uncommon 
 

vision disorder, ocular sensation disorders  
 

Eye disorders 

Rare Panophthalmitis, iritis, glaucoma 
 

Uncommon 
 

tinnitus, ear discomfort (including pain and 
swelling) 
 

Ear and labyrinth 
disorders  
 

Rare 
 

hearing loss 
 

Uncommon 
 

arrhythmias, tachycardia, palpitations 
 

Cardiac disorders  

Rare 
 

cardiac arrest, coronary artery insufficiency, 
angina pectoris, pericardial effusion 
 

Vascular disorders Uncommon 
 

hypertension, flushing, haematoma 
 

 Rare vascular occlusion, aortic stenosis, 
thrombophlebitis, aortic aneurysm 
 

Respiratory, thoracic and 
mediastinal disorders 

Common 
 

cough, nasopharyngeal pain 
 



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Uncommon 
 

asthma, dyspnoea, dysphonia, nasal 
congestion 
 

 

Rare pulmonary oedema, pharyngeal oedema, 
pleural effusion, pleurisy 
 

Common 
 

diarrhoea, abdominal pain, stomatitis and 
mouth ulceration, nausea 
 

Uncommon 
 

rectal haemorrhage, gastritis, vomiting, 
dyspepsia, abdominal bloating, constipation,  
 

Gastrointestinal disorders 

Rare 
 

intestinal stenosis, colitis, enteritis, 
oesophagitis 
 

Hepato-biliary disorders Common 
 

hepatic enzymes increased 
 

 Rare 
 

hepatic necrosis, hepatitis 
 

Common 
 

rash, dermatitis and eczema, pruritus, hair loss 
 

Uncommon 
 

urticaria, psoriasis, ecchymosis and increased 
bruising, purpura 
 

Skin and subcutaneous 
tissue disorders 

Rare 
 

erythema multiforme, panniculitis 

Common 
 

musculoskeletal pain 
 

Musculoskeletal, 
connective tissue and 
bone disorders Rare 

 
rhabdomyolysis 

Uncommon 
 

haematuria, renal impairment, bladder and 
urethral symptoms,  
 

Renal and urinary 
disorders  

Rare 
 

proteinuria, renal pain 
 

Reproductive system and 
breast disorders 

Uncommon menstrual cycle and uterine bleeding disorders 
 

Very Common 
 

injection site reaction (including pain, 
swelling, redness or pruritus) 
 

Common 
 

pyrexia, fatigue (including asthenia and 
malaise) 
 

General disorders and 
administration site 
conditions 

Uncommon 
 

chest pain, oedema, influenza like illness 

Investigations Uncommon blood creatine phosphokinase increased, 
activated partial thromboplastin time 
prolonged, autoantibodies present 
 

Injury and poisoning  Uncommon accidental injury, impaired healing 
 

Injection site reactions   



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In the twelve controlled trials, 16% of patients treated with Trudexa developed injection site reactions 
(erythema and/or itching, haemorrhage, pain or swelling), compared to 10% of patients receiving 
placebo or active control.  Injection site reactions generally did not necessitate discontinuation of the 
medicinal product.  

Infections  

In the twelve controlled trials, the rate of infection was 1.49 per patient year in the Trudexa treated 
patients and 1.42 per patient year in the placebo and active control-treated patients.  The infections 
consisted primarily of upper respiratory tract infections, bronchitis and urinary tract infections.  Most 
patients continued on Trudexa after the infection resolved.   
 
The incidence of serious infections was 0.03 per patient year in Trudexa treated patients and 0.03 per 
patient year in placebo and active control − treated patients.   
 
In controlled and open label studies with Trudexa, serious infections (including fatal infections, which 
occurred rarely) have been reported, which include reports of tuberculosis (including miliary and 
extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated histoplasmosis, 
pneumocystis carinii pneumonia, aspergillosis and listeriosis).  Most of the cases of tuberculosis 
occurred within the first eight months after initiation of therapy and may reflect recrudescence of 
latent disease. 

Malignancies and lymphoproliferative disorders 

During the controlled portions of ten Trudexa trials at least 12 weeks in duration (I-IX and CHARM) 
in patients with moderately to severely active rheumatoid arthritis, psoriatic arthritis, ankylosing 
spondylitis and Crohn’s disease, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 5.7 (3.3, 10.1) per 1000 patient-years among 
2887 Trudexa treated patients versus a rate of 4.1 (1.5, 10.9) 1 per 1000 patient-years among 1570 
control patients (median duration of treatment was 5.7 months for Trudexa and 5.5 months for control-
treated patients).  The rate (95% confidence interval) of non-melanoma skin cancers was 7.6 (4.7, 
12.4) per 1000 patient-years among Trudexa-treated patients and 2.0 (0.5, 8.2) per 1000 patient-years 
among control patients.  Of these skin cancers, squamous cell carcinomas occurred at rates (95% 
confidence interval) of 2.4 (1.0, 5.7) per 1000 patient-years among Trudexa-treated patients and 0 per 
1000 patient-years among control patients.  The rate (95% confidence interval) of lymphomas was 1.0 
(0.2, 3.8)  per 1000 patient-years among Trudexa-treated patients and 1.0 (0.1, 7.3) per 1000 patient-
years among control patients. 
 
When combining controlled portions of ten trials (I-IX and CHARM) and ongoing open label 
extension studies with a median duration of approximately 2. years including 4843 patients and over 
13000 patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-
melanoma skin cancers is approximately 13.6 per 1000 patient years.  The observed rate of non-
melanoma skin cancers is approximately 9.0 per 1000 patient years, and the observed rate of 
lymphomas is approximately 1.2 per 1000 patient years. 
 
In post-marketing experience from January 2003, predominately in patients with rheumatoid arthritis, 
the reported rate of malignancies other than lymphomas and non-melanoma skin cancers is 
approximately 1.7 per 1000 patient years.  The reported rates for non-melanoma skin cancers and 
lymphomas are approximately 0.2 and 0.4 per 1000 patient years, respectively (see section 4.4). 

Autoantibodies  

Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis 
Studies I − V.  In these trials, 11.9% of patients treated with Trudexa and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres 
at week 24.  Two patients out of 3441 treated with Trudexa in all rheumatoid arthritis and psoriatic 
arthritis studies developed clinical signs suggestive of new-onset lupus-like syndrome.  The patients 



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improved following discontinuation of therapy.  No patients developed lupus nephritis or central 
nervous system symptoms. 

Liver Enzyme Elevations 

Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (Studies I − IV), 
elevations of ALT were similar in patients receiving adalimumab or placebo.  In patients with early 
rheumatoid arthritis (disease duration of less than 3 years) (Study V), elevations of ALT were more 
common in the combination arm (Trudexa /methotrexate) compared to the methotrexate monotherapy 
arm or the Trudexa monotherapy arm. 
 
Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients 
(Studies VI-VII) compared with patients in rheumatoid arthritis clinical studies. 
 
In all studies (I-VII), patients with raised ALT were asymptomatic and in most cases elevations were 
transient and resolved on continued treatment. 
 
Crohn’s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients 
receiving adalimumab or placebo. 

Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials 

The additional adverse reactions in Table 2 have been reported from postmarketing surveillance or 
Phase IV clinical trials: 
 

Table 2 
Undesirable Effects in Postmarketing Surveillance and Phase IV Clinical Studies 

 
System Organ Class Adverse Reaction 
Hepatobiliary Disorders reactivation of hepatitis B 
Nervous system disorders demyelinating disorders (e.g. optic neuritis) 
Respiratory, thoracic and mediastinal disorders interstitial lung disease, including pulmonary 

fibrosis  
Skin and subcutaneous tissue disorders cutaneous vasculitis 
Immune system disorders anaphylaxis 

4.9 Overdose  

No dose-limiting toxicity was observed during clinical trials.  The highest dose level evaluated has 
been multiple intravenous doses of 10 mg/kg.   

5. PHARMACOLOGICAL PROPERTIES 

5.1 Pharmacodynamic properties 

Pharmacotherapeutic group: Selective immunosuppressive agents.  ATC code: L04AA17 

Mechanism of action 

Adalimumab binds specifically to TNF and neutralizes the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including 
changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, 
and ICAM-1 with an IC50 of 1-2 X 10-10 M).  



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Pharmacodynamic effects  

After treatment with Trudexa, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed compared to baseline in patients with rheumatoid arthritis.  Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Trudexa administration.  Patients treated with Trudexa usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with Crohn’s disease. 

Clinical trials 

Rheumatoid arthritis 
 
Trudexa was evaluated in over 3000 patients in all rheumatoid arthritis clinical trials.  Some patients 
were treated for up to 60 months duration.  The efficacy and safety of Trudexa for the treatment of 
rheumatoid arthritis were assessed in five randomised, double-blind and well-controlled studies.   
 
Study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had 
insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) 
every week and whose methotrexate dose remained constant at 10 to 25 mg every week.  Doses of 20, 
40 or 80 mg of Trudexa or placebo were given every other week for 24 weeks.  
 
Study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.  Doses of 
20 or 40 mg of Trudexa were given by subcutaneous injection every other week with placebo on 
alternative weeks or every week for 26 weeks; placebo was given every week for the same duration.  
No other disease-modifying anti-rheumatic drugs were allowed. 
 
Study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old, had insufficient efficacy to methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-
intolerant) every week and whose methotrexate dose remained constant at 12.5 to 25 mg every week.  
There were three groups in this study.  The first received placebo injections every week for 52 weeks.  
The second received 20 mg of Trudexa every week for 52 weeks.  The third group received 40 mg of 
Trudexa every other week with placebo injections on alternate weeks.  Thereafter, patients enrolled in 
an open-label extension phase in which 40 mg of Trudexa was administered every other week up to 60 
months. 
 
Study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were ≥ 18 years old.  Patients were permitted to be either disease-modifying, 
anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that 
therapy was stable for a minimum of 28 days.  These therapies include methotrexate, leflunomide, 
hydroxychloroquine, sulfasalazine and/or gold salts.  Patients were randomised to 40 mg of Trudexa 
or placebo every other week for 24 weeks.   
 
Study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months).  This study evaluated the efficacy of 
Trudexa 40 mg every other week/methotrexate combination therapy, Trudexa 40 mg every other week 
monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of 
progression of joint damage in rheumatoid arthritis for 104 weeks. 
 
The primary end point in Studies I, II and III and the secondary endpoint in Study IV was the percent 
of patients who achieved an ACR 20 response at week 24 or 26.  The primary endpoint in Study V 
was the percent of patients who achieved an ACR 50 response at week 52.  Study III and V had an 



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additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results).  Study III also had a primary endpoint of changes in quality of life. 

ACR response 

The percent of Trudexa-treated patients achieving ACR 20, 50 and 70 responses was consistent across 
trials I, II and III.  The results for the 40 mg every other week dose are summarised in Table 3.  
 

Table 3:  ACR Responses in Placebo-Controlled Trials 
(Percent of Patients) 

 
Response Study Ia** Study IIa** Study IIIa** 

 
 Placebo/ 

MTXc 
n=60 

Trudexab/ MTXc
n=63 

Placebo 
n=110 

Trudexab 
n=113 

Placebo/ 
MTXc 
n=200 

Trudexab/ 
MTXc 
n=207 

ACR 20       
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3% 
 12 months NA NA NA NA 24.0% 58.9% 
ACR 50       
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1% 
 12 months NA NA NA NA 9.5% 41.5% 
ACR 70       
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8% 
 12 months NA NA NA NA 4.5% 23.2% 
a Study I at 24 weeks, Study II at 26 weeks , and Study III at 24 and 52 weeks 
b 40 mg Trudexa administered every other week 
c MTX = methotrexate 
**p < 0.01, Trudexa versus placebo 

 
In Studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores 
and CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo.  In Study III, these 
improvements were maintained throughout 52 weeks.  In addition, ACR response rates were 
maintained in the majority of patients followed in the open-label extension phase to week 104.  There 
were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.  
Among those, 86, 72, and 41 patients had ACR 20/50/70 response, respectively at month 60. 
 
In Study IV, the ACR 20 response of patients treated with Trudexa plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   
 
In Studies I-IV, Trudexa-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In Study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Trudexa and methotrexate led to faster and significantly greater ACR responses than 
methotrexate monotherapy and Trudexa monotherapy at week 52 and responses were sustained at 
week 104 (see Table 4). 
 

Table 4:  ACR Responses in Study V 
(percent of patients) 

 

Response MTX n=257 
Trudexa 

n=274 

Trudexa/MT
X 

n=268 
p-valuea p-valueb p-valuec 

ACR 20       



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 Week 52 62.6% 54.4% 72.8% 0.013 < 0.001 0.043 
 Week 104 56.0% 49.3% 69.4% 0.002 < 0.001 0.140 
ACR 50       
 Week 52 45.9% 41.2% 61.6% < 0.001 < 0.001 0.317 
 Week 104 42.8% 36.9% 59.0% < 0.001 < 0.001 0.162 
ACR 70       
 Week 52 27.2% 25.9% 45.5% < 0.001 < 0.001 0.656 
 Week 104 28.4% 28.1% 46.6% < 0.001 < 0.001 0.864 
a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/methotrexate 

combination therapy using the Mann-Whitney U test. 
b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/methotrexate 

combination therapy using the Mann-Whitney U test 
c.   p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate monotherapy 

using the Mann-Whitney U test 
 
At week 52, 42.9% of patients who received Trudexa/methotrexate combination therapy achieved 
clinical remission (DAS28 < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy 
and 23.4% of patients receiving Trudexa monotherapy.  Trudexa/methotrexate combination therapy 
was clinically and statistically superior to methotrexate (p < 0.001) and Trudexa monotherapy 
(p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe 
rheumatoid arthritis.  The response for the two monotherapy arms was similar (p = 0.447). 

Radiographic response 

In Study III, where Trudexa treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as 
change in modified total Sharp score and its components, the erosion score and joint space narrowing 
score.  Trudexa/methotrexate patients demonstrated significantly less radiographic progression than 
patients receiving methotrexate alone at 6 and 12 months (see Table 5).  Data from the open-label 
extension phase indicate that the reduction in rate of progression of structural damage is maintained   
for 60 months in a subset of patients.  113/207 of patients originally treated with 40 mg Humira every 
other week were evaluated radiographically at 5 years. Among those, 66 patients showed no 
progression of structural damage defined by a change in the TSS of zero or less. 
 

Table 5:  Radiographic Mean Changes Over 12 Months in Study III 
 

 Placebo/ 
MTXa 

TRUDEXA/MTX 
40 mg every 
other week 

Placebo/MTX-
TRUDEXA/MTX 
(95% Confidence 

Intervalb) 

P-value 

Total Sharp score 2.7 0.1 2.6 (1.4, 3.8)  < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Trudexa.  
cBased on rank analysis  
dJoint Space Narrowing 
 
In Study V, structural joint damage was assessed radiographically and expressed as change in 
modified total Sharp score (see Table 6). 
 

Table 6:  Radiographic Mean Changes at Week 52 in Study V 
 

 
MTX 
n=257 

(95% confidence 
interval) 

Trudexa 
n=274 

(95% confidence 
interval) 

Trudexa/MT
X 

n=268 
p-valuea p-valueb p-valuec 



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(95% confidence 
interval) 

Total Sharp 
score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001 
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151 

a. p-value is from the pairwise comparison of methotrexate monotherapy and 
Trudexa/methotrexate combination therapy using the Mann-Whitney U test. 

b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/methotrexate 
combination therapy using the Mann-Whitney U test  

c.   p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate 
monotherapy using the Mann-Whitney U test 

 
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression 
(change from baseline in modified total Sharp score ≤ 0.5) was significantly higher with 
Trudexa/methotrexate combination therapy (63.8% and 61.2% respectively) compared to methotrexate 
monotherapy (37.4% and 33.5% respectively, p < 0.001) and Trudexa monotherapy (50.7%, p < 0.002 
and 44.5%, p < 0.001 respectively). 

Quality of life and physical function  

Health-related quality of life and physical function was assessed using the disability index of the 
Health Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, 
which was a pre-specified primary endpoint at week 52 in Study III.  All doses/schedules of Trudexa 
in all four studies showed statistically significantly greater improvement in the disability index of the 
HAQ from baseline to Month 6 compared to placebo and in Study III the same was seen at week 52.  
Results from the Short Form Health Survey (SF 36) for all doses/schedules of Trudexa in all four 
studies support these findings, with statistically significant physical component summary (PCS) 
scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other 
week dose.  A statistically significant decrease in fatigue as measured by functional assessment of 
chronic illness therapy (FACIT) scores was seen in all three studies in which it was assessed (Studies 
I, III, IV). 
 
In Study III, improvement in physical function was maintained through week  260 (60 months) of 
open-label treatment.  Improvement in quality of life was measured up to week 156 (36 months) and 
improvement was maintained through that time. 
 
In Study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Trudexa/methotrexate combination therapy versus 
methotrexate monotherapy and Trudexa monotherapy at week 52, which was maintained through 
week 104. 

Psoriatic arthritis 

Trudexa, 40 mg every other week, was studied in patients with moderately to severely active psoriatic 
arthritis in two placebo-controlled studies, Studies VI and VII.  Study VI with 24 week duration, 
treated 313 adult patients who had an inadequate response to non-steroidal anti-inflammatory drug 
therapy and of these, approximately 50% were taking methotrexate.  Study VII with 12-week duration, 
treated 100 patients who had an inadequate response to DMARD therapy. 
 
There is insufficient evidence of the efficacy of Trudexa in patients with ankylosing spondylitis-like 
psoriatic arthropathy due to the small number of patients studied (see Table 7). 
 

Table 7:  ACR Response in Placebo-Controlled Psoriatic Arthritis Studies 
(Percent of Patients) 

 
 Study VI Study VII 



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Response Placebo N=162 
Trudexa 
N=151 

Placebo  
N=49 

Trudexa 
N=51 

ACR 20      
 Week 12 14% 58%*** 16% 39%* 
 Week 24 15% 57%*** N/A N/A 
ACR 50      
 Week 12 4% 36%*** 2% 25%*** 
 Week 24 6% 39%*** N/A N/A 
ACR 70      
 Week 12 1% 20%*** 0% 14% * 
 Week 24 1% 23%*** N/A N/A 

*** p < 0.001 for all comparisons between Trudexa and placebo 
* p < 0.05 for all comparisons between Trudexa and placebo   
N/A  not applicable 

 
ACR responses in Study VI were similar with and without concomitant methotrexate therapy. 
Trudexa treated patients demonstrated improvement in physical function as assessed by HAQ and 
Short Form Health Survey (SF 36), from base-line to week 24. 

Ankylosing spondylitis 

Trudexa 40 mg every other week was assessed in 393 patients in two randomised, 24 week 
double − blind, placebo − controlled studies in patients with active ankylosing spondylitis (mean 
baseline score of disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] 
was 6.3 in all groups) who have had an inadequate response to conventional therapy.  Seventy-nine 
(20.1%) patients were treated concomitantly with disease modifying anti − rheumatic drugs, and 37 
(9.4%) patients with glucocorticoids.  The blinded period was followed by an open − label period 
during which patients received Trudexa 40 mg every other week subcutaneously for up to an 
additional 28 weeks.  Subjects (n=215, 54.7%) who failed to achieve ASAS 20 at Weeks 12, or 16 or 
20 received early escape open-label adalimumab 40 mg every other week subcutaneously and were 
subsequently treated as non-responders in the double-blind statistical analyses. 
 
In the larger study (VIII) with 315 patients, results showed statistically significant improvement of the 
signs and symptoms of ankylosing spondylitis in patients treated with Trudexa compared to placebo.  
Significant response was first observed at Week 2 and maintained through 24 weeks (Table 8).  

 
Table 8 - Efficacy Responses in Placebo-Controlled AS Study – Study VIII 

Reduction of Signs and Symptoms 
 

Response Placebo 
N=107 

Trudexa 
N=208 

ASASa 20   
             Week 2 16% 42%*** 

Week 12 21% 58%*** 
Week 24 19% 51%*** 

ASAS 50   
             Week 2 3% 16%*** 

Week 12 10% 38%*** 
Week 24 11% 35%*** 

ASAS 70   
             Week 2 0% 7%** 

Week 12 5% 23%*** 
Week 24 8% 24%*** 

   
BASDAIb 50    



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             Week 2 4% 20%*** 
Week 12  16% 45%*** 
Week 24  15% 42%*** 

***,** Statistically significant at p < 0.001, < 0.01 for all comparisons between Trudexa and placebo at Weeks 
2, 12 and  24 
a ASsessments in Ankylosing Spondylitis 
b Bath Ankylosing Spondylitis Disease Activity Index 

 
Trudexa treated patients had significantly greater improvement at Week 12 which was maintained 
through Week 24 in both the SF36 and Ankylosing Spondylitis Quality of Life Questionnaire 
(ASQoL). 
 
Similar trends (not all statistically significant) were seen in the smaller randomised, double − blind, 
placebo controlled study (IX) of 82 adult patients with active ankylosing spondylitis. 

Crohn’s Disease 

The safety and efficacy of Trudexa were assessed in over 1400 patients with moderately to severely 
active Crohn’s disease (Crohn’s Disease Activity Index (CDAI) ≥ 220 and ≤ 450) in randomised, 
double-blind, placebo-controlled studies.  478 of the enrolled patients (32%) were defined as having  a 
severe disease (CDAI score > 300 and concomitant corticosteroid and/or immunosuppressants) 
corresponding to the population defined in the indication (see section 4.1).  Concomitant stable doses 
of aminosalicylates, corticosteroids, and/or immunomodulatory agents were permitted and 79% of 
patients continued to receive at least one of these medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CLASSIC I and 
GAIN.  In CLASSIC I, 299 TNF-antagonist naive patients were randomised to one of four treatment 
groups; placebo at weeks 0 and 2, 160 mg Trudexa at week 0 and 80 mg at week 2, 80 mg at week 0 
and 40 mg at week 2, and 40 mg at week 0 and 20 mg at week 2.  In GAIN, 325 patients who had lost 
response or were intolerant to infliximab were randomised to receive either 160 mg Trudexa at week 0 
and 80 mg at week 2 or placebo at weeks 0 and 2.  The primary non-responders were excluded from 
the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CHARM.  In CHARM, 854 patients received 
open-label 80 mg at week 0 and 40 mg at week 2.  At week 4 patients were randomised to 40 mg every 
other week, 40 mg every week, or placebo with a total study duration of 56 weeks.  Patients in clinical 
response (decrease in CDAI ≥ 70) at week 4 were stratified and analysed separately from those not in 
clinical response at week 4.  Corticosteroid taper was permitted after week 8.  
 
CLASSIC I and GAIN induction of remission and response rates are presented in Table 9. 
 



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Table 9: Induction of Clinical Remission and Response 
(Percent of Patients) 

 CLASSIC I: Infliximab Naive Patients GAIN: Infliximab Experienced Patients 

 Placebo 

N=74 

Trudexa 

80/40 mg 

N = 75 

Trudexa  

160/80 m
g N=76 

Placebo 

N=166 

Trudexa  

160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Trudexa versus placebo 
* p < 0.001 
** p < 0.01 
 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by week 8 
and adverse events were more frequently noted in the 160/80 mg group. 
 
In CHARM, at week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis.  Of those in clinical response at week 4, 48% had been previously exposed to other 
anti-TNF therapy.  Maintenance of remission and response rates are presented in Table 10.  Clinical 
remission results remained relatively constant irrespective of previous TNF antagonist exposure. 
 

Table 10: Maintenance of Clinical Remission and Response 
(Percent of Patients) 

 Placebo 40 mg Trudexa 
every other week 

40 mg Trudexa 
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for >=90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Trudexa versus placebo pairwise comparisons   of proportions 

** p < 0.02 for Trudexa versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 
Among patients who were not in response at week 4, 43% of Trudexa maintenance patients responded 
by week 12 compared to 30% of placebo maintenance patients.  These results suggest that some 
patients who have not responded by week 4 benefit from continued maintenance therapy through week 
12.  Therapy continued beyond 12 weeks did not result in significantly more responses (see section 
4.2).   

Quality of Life 

In CLASSIC I and GAIN, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at week 4 in patients randomised to 



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Trudexa 80/40 mg and 160/80 mg compared to placebo and was seen at weeks 26 and 56 in CHARM 
as well among the adalimumab treatment groups compared to the placebo group. 

Immunogenicity   

Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy 
of adalimumab.  There is no apparent correlation between the presence of anti-adalimumab antibodies 
and adverse events. 
 
Patients in Studies I, II and III were tested at multiple timepoints for antibodies to adalimumab during 
the 6 to 12 month period.  In the pivotal trials, anti-adalimumab antibodies were identified in 58/1053 
(5.5%) patients treated with adalimumab, compared to 2/370 (0.5%) on placebo.  In patients not given 
concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when adalimumab was used as 
add-on to methotrexate.   
 
In patients with psoriatic arthritis, adalimumab antibodies were identified in 38/376 subjects (10%) 
treated with adalimumab.  In patients not given concomitant methotrexate, the incidence was 13.5% 
(24/178 subjects), compared to 7% (14 of 198 subjects) when adalimumab was used as add-on to 
methotrexate. 
 
In patients with ankylosing spondylitis antibodies were identified in 17/204 subjects (8.3%) treated 
with adalimumab.  In patients not given concomitant methotrexate, the incidence was 16/185 (8.6%), 
compared to 1/19 (5.3%) when adalimumab was used as add-on to methotrexate. 
 
In patients with Crohn’s disease, adalimumab antibodies were identified in 7/269 subjects (2.6%) 
treated with adalimumab. 
 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 

5.2 Pharmacokinetic properties 

After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab 
was slow, with peak serum concentrations being reached about 5 days after administration.  The 
average absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%.  After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional.  After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 
to 15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-
life was approximately two weeks.  Adalimumab concentrations in the synovial fluid from several 
rheumatoid arthritis patients ranged from 31-96% of those in serum. 
 
Following subcutaneous administration of 40 mg of Trudexa every other week in rheumatoid arthritis 
(RA) patients the mean steady-state trough concentrations were approximately 5 µg/ml (without 
concomitant methotrexate) and 8 to 9 µg/ml (with concomitant methotrexate), respectively.  The 
serum adalimumab trough levels at steady-state increased roughly proportionally with dose following 
20, 40 and 80 mg every other week and every week subcutaneous dosing. 
 
In patients with Crohn’s disease, the loading dose of 80 mg Trudexa on week 0 followed by 40 mg 
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 5.5 µg/ml 
during the induction period.  A loading dose of 160 mg Trudexa on week 0 followed by 80 mg 
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 12 µg/ml 
during the induction period.  Mean steady-state trough levels of approximately 7 µg/ml were observed 
in Crohn’s disease patients who received a maintenance dose of 40 mg Trudexa every other week. 
 
Population pharmacokinetic analyses with data from over 1300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight.  After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance.  The serum 



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levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower 
in patients with measurable AAA.  Trudexa has not been studied in children or in patients with hepatic 
or renal impairment. 

5.3 Preclinical safety data  

Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, 
repeated dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomologous monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence 
of harm to the foetuses due to adalimumab.  Carcinogenicity studies, and standard assessment of 
fertility and postnatal toxicity, were not performed with adalimumab due to the lack of appropriate 
models for an antibody with limited cross-reactivity to rodent TNF and the development of 
neutralizing antibodies in rodents.  

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients  

Mannitol 
Citric acid monohydrate 
Sodium citrate 
Sodium dihydrogen phosphate dihydrate 
Disodium phosphate dihydrate 
Sodium chloride 
Polysorbate 80 
Sodium hydroxide 
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  

18 months 

6.4 Special precautions for storage  

Store in a refrigerator (2°C – 8°C).  Keep the syringe in the outer carton.  Do not freeze. 

6.5 Nature and contents of container   

Trudexa 40 mg solution for injection in single-use pre-filled syringe (type I glass) for patient use: 
 
Packs of: 
• 1 pre-filled syringe (0.8 ml sterile solution) with 1 alcohol pad in a blister.  
• 2 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister.  
• 4 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister.  
• 6 pre-filled syringes (0.8 ml sterile solution), each with 1 alcohol pad, in a blister. 
 
Not all pack sizes may be marketed. 

6.6 Special precautions for disposal 



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

7. MARKETING AUTHORISATION HOLDER  

Abbott Laboratories Ltd.  
Queenborough 
Kent ME11 5EL 
United Kingdom 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/03/257/002 
EU/1/03/257/003 
EU/1/03/257/004 
EU/1/03/257/005 

9. DATE OF FIRST AU`THORISATION/RENEWAL OF THE AUTHORISATION 

1 September 2003 

10. DATE OF REVISION OF THE TEXT 

{MM/YYYY} 



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1. NAME OF THE MEDICINAL PRODUCT  

Trudexa 40 mg solution for injection in pre-filled syringe with needleguard  

2. QUALITATIVE AND QUANTITATIVE COMPOSITION  

Each 0.8 ml single dose pre-filled syringe contains 40 mg of adalimumab.  
 
Adalimumab is a recombinant human monoclonal antibody expressed in Chinese Hamster Ovary cells.  
 
For a full list of excipients, see section 6.1.  

3. PHARMACEUTICAL FORM  

Solution for injection in pre-filled syringe with needleguard. 

4. CLINICAL PARTICULARS 

4.1 Therapeutic indications  

Rheumatoid arthritis 
 
Trudexa in combination with methotrexate, is indicated for: 
 
 the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the 

response to disease-modifying anti-rheumatic drugs including methotrexate has been 
inadequate. 

 the treatment of severe, active and progressive rheumatoid arthritis in adults not previously 
treated with methotrexate. 

 
Trudexa can be given as monotherapy in case of intolerance to methotrexate or when continued 
treatment with methotrexate is inappropriate. 
 
Trudexa has been shown to reduce the rate of progression of joint damage as measured by X-ray and 
to improve physical function, when given in combination with methotrexate. 

Psoriatic arthritis 

Trudexa is indicated for the treatment of active and progressive psoriatic arthritis in adults when the 
response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. 
 
Ankylosing spondylitis 
 
Trudexa is indicated for the treatment of adults with severe active ankylosing spondylitis who have 
had an inadequate response to conventional therapy. 
 
Crohn’s disease 
 
Trudexa is indicated for treatment of severe, active Crohn’s disease, in patients who have not 
responded despite a full and adequate course of therapy with a corticosteroid and/or an 
immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. 
For induction treatment, Trudexa should be given in combination with corticosteroids.  Trudexa can be 
given as monotherapy in case of intolerance to corticosteroids or when continued treatment with 
corticosteroids is inappropriate (see section 4.2). 



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4.2 Posology and method of administration   

Trudexa treatment should be initiated and supervised by specialist physicians experienced in the 
diagnosis and treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or Crohn’s 
disease.  Patients treated with Trudexa should be given the special alert card. 
 
After proper training in injection technique, patients may self-inject with Trudexa if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Trudexa, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 

Adults 

Rheumatoid arthritis 
 
The recommended dose of Trudexa for adult patients with rheumatoid arthritis is 40 mg adalimumab 
administered every other week as a single dose via subcutaneous injection.  Methotrexate should be 
continued during treatment with Trudexa. 
 
Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, or analgesics can be continued 
during treatment with Trudexa.  Regarding combination with disease modifying anti-rheumatic drugs 
other than methotrexate see sections 4.4 and 5.1. 
 
In monotherapy, some patients who experience a decrease in their response may benefit from an 
increase in dose intensity to 40 mg adalimumab every week.  

Psoriatic arthritis and ankylosing spondylitis 

The recommended dose of Trudexa for patients with psoriatic arthritis and ankylosing spondylitis is 
40 mg adalimumab administered every other week as a single dose via subcutaneous injection. 
 
For all of the above indications, available data suggest that the clinical response is usually achieved 
within 12 weeks of treatment.  Continued therapy should be carefully reconsidered in a patient not 
responding within this time period. 
 
Crohn’s disease 
 
The recommended Trudexa induction dose regimen for adult patients with severe Crohn’s disease is 
80 mg at week 0 followed by 40 mg at week 2.  In case there is a need for a more rapid response to 
therapy, the regimen 160 mg at week 0 (dose can be administered as four injections in one day or as 
two injections per day for two consecutive days), 80 mg at week 2, can be used with the awareness 
that the risk for adverse events is higher during induction. 
 
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous 
injection.  Alternatively, if a patient has stopped Trudexa and signs and symptoms of disease recur, 
Trudexa may be re-administered.  There is little experience from re administration after more than 8 
weeks since the previous dose. 
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines. 
 
Some patients who experience decrease in their response may benefit from an increase in dose 
intensity to 40 mg Trudexa every week. 
 



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Some patients who have not responded by week 4 may benefit from continued maintenance therapy 
through week 12.  Continued therapy should be carefully reconsidered in a patient not responding 
within this time period. 

Elderly patients 

No dose adjustment is required.   

Children and adolescents 

There is no experience in children. 

Impaired renal and/or hepatic function 

Trudexa has not been studied in these patient populations.  No dose recommendations can be made. 

4.3 Contraindications  

Hypersensitivity to the active substance or to any of the excipients.  
 
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 
4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 

4.4 Special warnings and precautions for use   

Infections 
 
Patients must be monitored closely for infections, including tuberculosis, before, during and after 
treatment with Trudexa.  Because the elimination of adalimumab may take up to five months, 
monitoring should be continued throughout this period. 
 
Treatment with Trudexa should not be initiated in patients with active infections including chronic or 
localized infections until infections are controlled.  
 
Patients who develop a new infection while undergoing treatment with Trudexa should be monitored 
closely.  Administration of Trudexa should be discontinued if a patient develops a new serious 
infection until infections are controlled.  Physicians should exercise caution when considering the use 
of Trudexa in patients with a history of recurring infection or with underlying conditions which may 
predispose patients to infections, including the use of concomitant immunosuppressive medications. 
 
Serious infections, sepsis, tuberculosis and other opportunistic infections, including fatalities, have 
been reported with Trudexa.   
 
Serious infections: 
 
In clinical trials an increased risk of serious infections in patients receiving Trudexa has been shown, 
and reports from the post-marketing setting support this finding.  Of particular importance are 
infections such as pneumonia, pyelonephritis, septic arthritis and septicaemia.   
 
Tuberculosis: 
 
There have been reports of tuberculosis in patients receiving Trudexa.  It should be noted that in the 
majority of those reports, tuberculosis was extra-pulmonary, i.e. disseminated.  
 



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Before initiation of therapy with Trudexa, all patients must be evaluated for both active or inactive 
(latent) tuberculosis infection.  This evaluation should include a detailed medical history with a 
personal history of tuberculosis or possible previous exposure to patients with active tuberculosis and 
previous and/or current immunosuppressive therapy.  Appropriate screening tests, i.e. tuberculin skin 
test and chest X-ray, should be performed in all patients (local recommendations may apply).  It is 
recommended that the conduct of these tests should be recorded in the patient alert card.  Prescribers 
are reminded of the risk of false negative tuberculin skin test results, especially in patients who are 
severely ill or immunocompromised.  
 
If active tuberculosis is diagnosed, Trudexa therapy must not be initiated (see section 4.3).  
 
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis prophylaxis in accordance with local 
recommendations must be initiated before starting treatment with Trudexa.  In this situation, the 
benefit/risk balance of therapy with Trudexa should be very carefully considered. 
 
Patients should be instructed to seek medical advice if signs/symptoms (e.g., persistent cough, 
wasting/weight loss, low grade fever) suggestive of a tuberculosis infection occur during or after 
therapy with Trudexa.  
 
Other opportunistic infections: 
 
There have been reports of serious and severe opportunistic infections associated with Trudexa 
therapy, for example pneumocystis carinii pneumonia, disseminated histoplasmosis, listeriosis and 
aspergillosis. 
 
If a patient receiving Trudexa shows prolonged/atypical symptoms/signs of infections or general 
deterioration, prevalent opportunistic conditions must be considered. 
 
Hepatitis B Reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Trudexa, 
who are chronic carriers of this virus.  Some cases have had fatal outcome.  Patients at risk for HBV 
infection should be evaluated for prior evidence of HBV infection before initiating Trudexa therapy.  
Carriers of HBV who require treatment with Trudexa should be closely monitored for signs and 
symptoms of active HBV infection throughout therapy and for several months following termination 
of therapy.  Adequate data of treating patients who are carriers of HBV with anti-viral therapy in 
conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available.  In patients 
who develop HBV reactivation, Trudexa should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated.  

Neurological events  

TNF-antagonists including Trudexa have been associated in rare cases with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of demyelinating disease.  Prescribers should 
exercise caution in considering the use of Trudexa in patients with pre-existing or recent-onset central 
nervous system demyelinating disorders.  

Allergic reactions 

Serious allergic adverse reactions have not been reported with subcutaneous administration of Trudexa 
during clinical trials.  Non-serious allergic reactions associated with Trudexa were uncommon during 
clinical trials.  In postmarketing, serious allergic reactions including anaphylaxis have been reported 
very rarely following Trudexa administration.  If an anaphylactic reaction or other serious allergic 
reaction occurs, administration of Trudexa should be discontinued immediately and appropriate 
therapy initiated.  
 



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The needle cover of the syringe contains natural rubber (latex).  This may cause severe allergic 
reactions in patients sensitive to latex. 

Immunosuppression 

In a study of 64 patients with rheumatoid arthritis that were treated with Trudexa, there was no 
evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or 
change in enumeration of effector T-and B cells and NK-cells, monocyte/macrophages, and 
neutrophils. 

Malignancies and lymphoproliferative disorders 

In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients.  However, the occurrence was rare.  Furthermore, there is an increased background 
lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory 
disease, which complicates the risk estimation.  With the current knowledge, a possible risk for the 
development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
No studies have been conducted that include patients with a history of malignancy or that continue 
treatment in patients who develop malignancy while receiving Trudexa.  Thus additional caution 
should be exercised in considering Trudexa treatment of these patients (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients 
with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in 
the lung or head and neck, were reported in infliximab-treated patients compared with control patients.  
All patients had a history of heavy smoking.  Therefore, caution should be exercised when using any 
TNF-antagonist in COPD patients, as well as in patients with increased risk for malignancy due to 
heavy smoking. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF blocking 
agents.  Adverse events of the haematologic system, including medically significant cytopoenia (e.g. 
thrombocytopaenia, leucopaenia) have been infrequently reported with Trudexa.  All patients should 
be advised to seek immediate medical attention if they develop signs and symptoms suggestive of 
blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor) while on Trudexa.  Discontinuation 
of Trudexa therapy should be considered in patients with confirmed significant haematologic 
abnormalities. 
 
Vaccinations  
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo.  No data are available on the secondary transmission of infection 
by live vaccines in patients receiving Trudexa.  Patients on Trudexa may receive concurrent 
vaccinations, except for live vaccines. 

Congestive heart failure 

In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased 
mortality due to congestive heart failure have been observed.  Cases of worsening congestive heart 
failure have also been reported in patients receiving Trudexa.  Trudexa should be used with caution in 
patients with mild heart failure (NYHA class I/II).  Trudexa is contraindicated in moderate to severe 
heart failure (see section 4.3).  Treatment with Trudexa must be discontinued in patients who develop 
new or worsening symptoms of congestive heart failure. 



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Autoimmune processes 

Treatment with Trudexa may result in the formation of autoimmune antibodies.  The impact of long-
term treatment with Trudexa on the development of autoimmune diseases is unknown.  If a patient 
develops symptoms suggestive of a lupus-like syndrome following treatment with Trudexa and is 
positive for antibodies against double-stranded DNA, further treatment with Trudexa should not be 
given (see section 4.8). 

Concurrent administration of TNF-antagonists and anakinra 

Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone.  Because of 
the nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists.  Therefore, the 
combination of adalimumab and anakinra is not recommended. 

Surgery 

There is limited safety experience of surgical procedures in patients treated with Trudexa.  The long 
half-life of adalimumab should be taken into consideration if a surgical procedure is planned.  A 
patient who requires surgery while on Trudexa should be closely monitored for infections, and 
appropriate actions should be taken.  There is limited safety experience in patients undergoing 
arthroplasty while receiving Trudexa.  
 
Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment.  Available data suggest that Trudexa does not worsen or cause 
strictures. 

4.5 Interaction with other medicinal products and other forms of interaction  

Trudexa has been studied both in rheumatoid arthritis and psoriatic arthritis patients taking Trudexa as 
monotherapy and those taking concomitant methotrexate.  Antibody formation was lower when 
Trudexa was given together with methotrexate in comparison with use as monotherapy.  
Administration of Trudexa without methotrexate resulted in increased formation of antibodies, 
increased clearance and reduced efficacy of adalimumab (see section 5.1).  

4.6 Pregnancy and lactation  

For Trudexa, no clinical data on exposed pregnancies are available 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity.  Preclinical data on postnatal toxicity and fertility effects of 
adalimumab are not available (see section 5.3). 
 
Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal 
immune responses in the newborn.  Administration of adalimumab is not recommended during 
pregnancy.  Women of childbearing potential are strongly recommended to use adequate contraception 
to prevent pregnancy and continue its use for at least five months after the last Trudexa treatment.  

Use during lactation  

It is not known whether adalimumab is excreted in human milk or absorbed systemically after 
ingestion.  
 



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However, because human immunoglobulins are excreted in milk, women must not breast-feed for at 
least five months after the last Trudexa treatment. 

4.7 Effects on ability to drive and use machines  

No studies on the effects on the ability to drive and use machines have been performed. 

4.8 Undesirable effects 

Clinical Trials 
 
Trudexa was studied in 5293 patients in controlled and open label trials for up to 60 months.  These 
trials included rheumatoid arthritis patients with short term and long standing disease as well as 
psoriatic arthritis, ankylosing spondylitis and Crohn’s disease patients.  The data in Table 1 is based 
on the controlled Studies (I − IX,CLASSIC I, GAIN AND CHARM) (described in section 5.1) 
involving 3271 patients receiving Trudexa and 1809 patients receiving placebo or active comparator 
during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of Studies I − IX, CLASSIC I, GAIN and CHARM  was 5.7% for patients taking 
Trudexa and 5.3% for control treated patients. 
 
Adverse events at least possibly causally-related to adalimumab for Studies I − IX, CLASSIC I, GAIN 
and CHARM, both clinical and laboratory, are displayed by system organ class and frequency (very 
common ≥ 1/10; common≥ 1/100 < 1/10; uncommon≥ 1/1000  to ≤ 1/100) and rare < 1/1000 in Table 
1 below.  Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness. 
 

Table 1 
Undesirable Effects in Clinical Studies 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations 
 

Common 
 

lower respiratory infections (including 
pneumonia, bronchitis), viral infections 
(including influenza, herpes infections), 
candidiasis, bacterial infections (including 
urinary tract infections), upper respiratory 
infection 
 

 Uncommon 
 

opportunistic infections (including  
tuberculosis, histoplasmosis), sepsis, abscess,  
joint infection, wound infection, skin infection 
(including cellulitis and impetigo), superficial 
fungal infections (including skin, nail and 
foot) 
 

 Rare necrotising fasciitis, viral meningitis, 
diverticulitis 
 

Uncommon 
 

skin papilloma 
 

Neoplasms benign and 
malignant (including 
cysts and polyps)  Rare 

 
lymphoma, solid organ tumours (including 
breast, ovarian, testicular), squamous cell 
carcinoma of the skin 
 



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Common 
 

lymphopaenia 
 

Uncommon 
 

neutropaenia (including agranulocytosis), 
leucopaenia, thrombocytopaenia, anaemia, , 
lymphadenopathy, leucocytosis  
 

Blood and the lymphatic 
system disorders 

Rare 
 

pancytopaenia, idiopathic thrombocytopaenia 
purpura 
 

Uncommon 
 

systemic lupus erythematosus, angioedema, 
drug hypersensitivity, seasonal allergy 
 

Immune system disorders 

Rare serum sickness 
 

Endocrine disorders Rare 
 

thyroid disorder (including goitre) 

Uncommon 
 

Hypokalaemia, lipids increased, appetite 
disorders (including anorexia), hyperuricaemia 
 

Metabolism and nutrition 
disorders 

Rare hypercalcaemia 
 

Psychiatric disorders Uncommon 
 

mood disorders, anxiety (including 
nervousness and agitation) 
 

Common 
 

dizziness (including vertigo), headache, 
neurologic sensation disorders (including 
paraesthesias) 
 

Uncommon 
 

syncope, migraine, tremor, sleep disturbances  
 

Nervous system disorders 

Rare 
 

multiple sclerosis 
 

Common 
 

infection, irritation or inflammation of the eye 
 

Uncommon 
 

vision disorder, ocular sensation disorders  
 

Eye disorders 

Rare Panophthalmitis, iritis, glaucoma 
 

Uncommon 
 

tinnitus, ear discomfort (including pain and 
swelling) 
 

Ear and labyrinth 
disorders  
 

Rare 
 

hearing loss 
 

Uncommon 
 

arrhythmias, tachycardia, palpitations 
 

Cardiac disorders  

Rare 
 

cardiac arrest, coronary artery insufficiency, 
angina pectoris, pericardial effusion 
 

Vascular disorders Uncommon 
 

hypertension, flushing, haematoma 
 

 Rare vascular occlusion, aortic stenosis, 
thrombophlebitis, aortic aneurysm 
 

Respiratory, thoracic and 
mediastinal disorders 

Common 
 

cough, nasopharyngeal pain 
 



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Uncommon 
 

asthma, dyspnoea, dysphonia, nasal 
congestion 
 

 

Rare pulmonary oedema, pharyngeal oedema, 
pleural effusion, pleurisy 
 

Common 
 

diarrhoea, abdominal pain, stomatitis and 
mouth ulceration, nausea 
 

Uncommon 
 

rectal haemorrhage, gastritis, vomiting, 
dyspepsia, abdominal bloating, constipation,  
 

Gastrointestinal disorders 

Rare 
 

intestinal stenosis, colitis, enteritis, 
oesophagitis 
 

Hepato-biliary disorders Common 
 

hepatic enzymes increased 
 

 Rare 
 

hepatic necrosis, hepatitis 
 

Common 
 

rash, dermatitis and eczema, pruritus, hair loss 
 

Uncommon 
 

urticaria, psoriasis, ecchymosis and increased 
bruising, purpura 
 

Skin and subcutaneous 
tissue disorders 

Rare 
 

erythema multiforme, panniculitis 

Common 
 

musculoskeletal pain 
 

Musculoskeletal, 
connective tissue and 
bone disorders Rare 

 
rhabdomyolysis 

Uncommon 
 

haematuria, renal impairment, bladder and 
urethral symptoms 
 

Renal and urinary 
disorders  

Rare 
 

proteinuria, renal pain 
 

Reproductive system and 
breast disorders 

Uncommon menstrual cycle and uterine bleeding disorders 
 

Very Common 
 

injection site reaction (including pain, 
swelling, redness or pruritus) 
 

Common 
 

pyrexia, fatigue (including asthenia and 
malaise) 
 

General disorders and 
administration site 
conditions 

Uncommon 
 

chest pain, oedema, influenza like illness 

Investigations Uncommon blood creatine phosphokinase increased, 
activated partial thromboplastin time 
prolonged, autoantibodies present 
 

Injury and poisoning  Uncommon accidental injury, impaired healing 
 

Injection site reactions   



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In the twelve controlled trials, 16% of patients treated with Trudexa developed injection site reactions 
(erythema and/or itching, haemorrhage, pain or swelling), compared to 10% of patients receiving 
placebo or active control.  Injection site reactions generally did not necessitate discontinuation of the 
medicinal product.  

Infections  

In the twelve controlled trials, the rate of infection was 1.49 per patient year in the Trudexa treated 
patients and 1.42 per patient year in the placebo and active control-treated patients.  The infections 
consisted primarily of upper respiratory tract infections, bronchitis and urinary tract infections.  Most 
patients continued on Trudexa after the infection resolved.   
 
The incidence of serious infections was 0.03 per patient year in Trudexa treated patients and 0.03 per 
patient year in placebo and active control − treated patients.   
 
In controlled and open label studies with Trudexa, serious infections (including fatal infections, which 
occurred rarely) have been reported, which include reports of tuberculosis (including miliary and 
extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated histoplasmosis, 
pneumocystis carinii pneumonia, aspergillosis and listeriosis).  Most of the cases of tuberculosis 
occurred within the first eight months after initiation of therapy and may reflect recrudescence of 
latent disease. 

Malignancies and lymphoproliferative disorders 

During the controlled portions of ten Trudexa trials at least 12 weeks in duration (I-IX and CHARM) 
in patients with moderately to severely active rheumatoid arthritis, psoriatic arthritis, ankylosing 
spondylitis and Crohn’s disease, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 5.7 (3.3, 10.1) per 1000 patient-years among 
2887 Trudexa treated patients versus a rate of 4.1 (1.5, 10.9) 1 per 1000 patient-years among 1570 
control patients (median duration of treatment was 5.7 months for Trudexa and 5.5 months for control-
treated patients).  The rate (95% confidence interval) of non-melanoma skin cancers was 7.6 (4.7, 
12.4) per 1000 patient-years among Trudexa-treated patients and 2.0 (0.5, 8.2) per 1000 patient-years 
among control patients.  Of these skin cancers, squamous cell carcinomas occurred at rates (95% 
confidence interval) of 2.4 (1.0, 5.7) per 1000 patient-years among Trudexa-treated patients and 0 per 
1000 patient-years among control patients.  The rate (95% confidence interval) of lymphomas was 1.0 
(0.2, 3.8)  per 1000 patient-years among Trudexa-treated patients and 1.0 (0.1, 7.3) per 1000 patient-
years among control patients. 
 
When combining controlled portions of ten trials (I-IX and CHARM) and ongoing open label 
extension studies with a median duration of approximately 2. years including 4843 patients and over 
13000 patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-
melanoma skin cancers is approximately 13.6 per 1000 patient years.  The observed rate of non-
melanoma skin cancers is approximately 9.0 per 1000 patient years, and the observed rate of 
lymphomas is approximately 1.2 per 1000 patient years. 
 
In post-marketing experience from January 2003, predominately in patients with rheumatoid arthritis, 
the reported rate of malignancies other than lymphomas and non-melanoma skin cancers is 
approximately 1.7 per 1000 patient years.  The reported rates for non-melanoma skin cancers and 
lymphomas are approximately 0.2 and 0.4 per 1000 patient years, respectively (see section 4.4). 

Autoantibodies  

Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis 
Studies I − V.  In these trials, 11.9% of patients treated with Trudexa and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres 
at week 24.  Two patients out of 3441 treated with Trudexa in all rheumatoid arthritis and psoriatic 
arthritis studies developed clinical signs suggestive of new-onset lupus-like syndrome.  The patients 



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improved following discontinuation of therapy.  No patients developed lupus nephritis or central 
nervous system symptoms. 

Liver Enzyme Elevations 

Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (Studies I − IV), 
elevations of ALT were similar in patients receiving adalimumab or placebo.  In patients with early 
rheumatoid arthritis (disease duration of less than 3 years) (Study V), elevations of ALT were more 
common in the combination arm (Trudexa /methotrexate) compared to the methotrexate monotherapy 
arm or the Trudexa monotherapy arm. 
 
Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients 
(Studies VI-VII) compared with patients in rheumatoid arthritis clinical studies. 
 
In all studies (I-VII), patients with raised ALT were asymptomatic and in most cases elevations were 
transient and resolved on continued treatment. 
 
Crohn’s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients 
receiving adalimumab or placebo. 

Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials 

The additional adverse reactions in Table 2 have been reported from postmarketing surveillance or 
Phase IV clinical trials: 
 

Table 2 
Undesirable Effects in Postmarketing Surveillance and Phase IV Clinical Studies 

 
System Organ Class Adverse Reaction 
Hepatobiliary Disorders reactivation of hepatitis B 
Nervous system disorders demyelinating disorders (e.g. optic neuritis) 
Respiratory, thoracic and mediastinal disorders interstitial lung disease, including pulmonary 

fibrosis  
Skin and subcutaneous tissue disorders cutaneous vasculitis 
Immune system disorders anaphylaxis 

4.9 Overdose  

No dose-limiting toxicity was observed during clinical trials.  The highest dose level evaluated has 
been multiple intravenous doses of 10 mg/kg.   

5. PHARMACOLOGICAL PROPERTIES 

5.1 Pharmacodynamic properties 

Pharmacotherapeutic group: Selective immunosuppressive agents.  ATC code: L04AA17 

Mechanism of action 

Adalimumab binds specifically to TNF and neutralizes the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including 
changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, 
and ICAM-1 with an IC50 of 1-2 X 10-10 M).  



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Pharmacodynamic effects  

After treatment with Trudexa, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed compared to baseline in patients with rheumatoid arthritis.  Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Trudexa administration.  Patients treated with Trudexa usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with Crohn’s disease. 

Clinical trials 

Rheumatoid arthritis 
 
Trudexa was evaluated in over 3000 patients in all rheumatoid arthritis clinical trials.  Some patients 
were treated for up to 60 months duration.  The efficacy and safety of Trudexa for the treatment of 
rheumatoid arthritis were assessed in five randomised, double-blind and well-controlled studies.   
 
Study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had 
insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) 
every week and whose methotrexate dose remained constant at 10 to 25 mg every week.  Doses of 20, 
40 or 80 mg of Trudexa or placebo were given every other week for 24 weeks.  
 
Study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.  Doses of 
20 or 40 mg of Trudexa were given by subcutaneous injection every other week with placebo on 
alternative weeks or every week for 26 weeks; placebo was given every week for the same duration.  
No other disease-modifying anti-rheumatic drugs were allowed. 
 
Study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old, had insufficient efficacy to methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-
intolerant) every week and whose methotrexate dose remained constant at 12.5 to 25 mg every week.  
There were three groups in this study.  The first received placebo injections every week for 52 weeks.  
The second received 20 mg of Trudexa every week for 52 weeks.  The third group received 40 mg of 
Trudexa every other week with placebo injections on alternate weeks.  Thereafter, patients enrolled in 
an open-label extension phase in which 40 mg of Trudexa was administered every other week up to 60 
months. 
 
Study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were ≥ 18 years old.  Patients were permitted to be either disease-modifying, 
anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that 
therapy was stable for a minimum of 28 days.  These therapies include methotrexate, leflunomide, 
hydroxychloroquine, sulfasalazine and/or gold salts.  Patients were randomised to 40 mg of Trudexa 
or placebo every other week for 24 weeks.   
 
Study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months).  This study evaluated the efficacy of 
Trudexa 40 mg every other week/methotrexate combination therapy, Trudexa 40 mg every other week 
monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of 
progression of joint damage in rheumatoid arthritis for 104 weeks. 
 
The primary end point in Studies I, II and III and the secondary endpoint in Study IV was the percent 
of patients who achieved an ACR 20 response at week 24 or 26.  The primary endpoint in Study V 
was the percent of patients who achieved an ACR 50 response at week 52.  Study III and V had an 



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additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results).  Study III also had a primary endpoint of changes in quality of life. 

ACR response 

The percent of Trudexa-treated patients achieving ACR 20, 50 and 70 responses was consistent across 
trials I, II and III.  The results for the 40 mg every other week dose are summarised in Table 3.  
 

Table 3:  ACR Responses in Placebo-Controlled Trials 
(Percent of Patients) 

 
Response Study Ia** Study IIa** Study IIIa** 

 
 Placebo/ 

MTXc 
n=60 

Trudexab/ MTXc
n=63 

Placebo 
n=110 

Trudexab 
n=113 

Placebo/ 
MTXc 
n=200 

Trudexab/ 
MTXc 
n=207 

ACR 20       
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3% 
 12 months NA NA NA NA 24.0% 58.9% 
ACR 50       
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1% 
 12 months NA NA NA NA 9.5% 41.5% 
ACR 70       
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8% 
 12 months NA NA NA NA 4.5% 23.2% 
a Study I at 24 weeks, Study II at 26 weeks , and Study III at 24 and 52 weeks 
b 40 mg Trudexa administered every other week 
c MTX = methotrexate 
**p < 0.01, Trudexa versus placebo 

 
In Studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores 
and CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo.  In Study III, these 
improvements were maintained throughout 52 weeks.  In addition, ACR response rates were 
maintained in the majority of patients followed in the open-label extension phase to week 104.  There 
were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.  
Among those, 86, 72, and 41 patients had ACR 20/50/70 response, respectively at month 60. 
 
In Study IV, the ACR 20 response of patients treated with Trudexa plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   
 
In Studies I-IV, Trudexa-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In Study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Trudexa and methotrexate led to faster and significantly greater ACR responses than 
methotrexate monotherapy and Trudexa monotherapy at week 52 and responses were sustained at 
week 104 (see Table 4). 
 

Table 4:  ACR Responses in Study V 
(percent of patients) 

 

Response MTX n=257 
Trudexa 

n=274 

Trudexa/MT
X 

n=268 
p-valuea p-valueb p-valuec 

ACR 20       



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 Week 52 62.6% 54.4% 72.8% 0.013 < 0.001 0.043 
 Week 104 56.0% 49.3% 69.4% 0.002 < 0.001 0.140 
ACR 50       
 Week 52 45.9% 41.2% 61.6% < 0.001 < 0.001 0.317 
 Week 104 42.8% 36.9% 59.0% < 0.001 < 0.001 0.162 
ACR 70       
 Week 52 27.2% 25.9% 45.5% < 0.001 < 0.001 0.656 
 Week 104 28.4% 28.1% 46.6% < 0.001 < 0.001 0.864 
a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/methotrexate 

combination therapy using the Mann-Whitney U test. 
b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/methotrexate 

combination therapy using the Mann-Whitney U test 
c.   p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate monotherapy 

using the Mann-Whitney U test 
 
At week 52, 42.9% of patients who received Trudexa/methotrexate combination therapy achieved 
clinical remission (DAS28 < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy 
and 23.4% of patients receiving Trudexa monotherapy.  Trudexa/methotrexate combination therapy 
was clinically and statistically superior to methotrexate (p < 0.001) and Trudexa monotherapy 
(p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe 
rheumatoid arthritis.  The response for the two monotherapy arms was similar (p = 0.447). 

Radiographic response 

In Study III, where Trudexa treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as 
change in modified total Sharp score and its components, the erosion score and joint space narrowing 
score.  Trudexa/methotrexate patients demonstrated significantly less radiographic progression than 
patients receiving methotrexate alone at 6 and 12 months (see Table 5).  Data from the open-label 
extension phase indicate that the reduction in rate of progression of structural damage is maintained  
for 60 months in a subset of patients.  113/207 of patients originally treated with 40 mg Humira every 
other week were evaluated radiographically at 5 years. Among those, 66 patients showed no 
progression of structural damage defined by a change in the TSS of zero or less. 
. 

Table 5:  Radiographic Mean Changes Over 12 Months in Study III 
 

 Placebo/ 
MTXa 

TRUDEXA/MTX 
40 mg every 
other week 

Placebo/MTX-
TRUDEXA/MTX 
(95% Confidence 

Intervalb) 

P-value 

Total Sharp score 2.7 0.1 2.6 (1.4, 3.8)  < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Trudexa.  
cBased on rank analysis  
dJoint Space Narrowing 
 
In Study V, structural joint damage was assessed radiographically and expressed as change in 
modified total Sharp score (see Table 6). 
 

Table 6:  Radiographic Mean Changes at Week 52 in Study V 
 

 
MTX 
n=257 

(95% confidence 
interval) 

Trudexa 
n=274 

(95% confidence 
interval) 

Trudexa/MT
X 

n=268 
p-valuea p-valueb p-valuec 



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(95% confidence 
interval) 

Total Sharp 
score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001 
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151 

a. p-value is from the pairwise comparison of methotrexate monotherapy and 
Trudexa/methotrexate combination therapy using the Mann-Whitney U test. 

b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/methotrexate 
combination therapy using the Mann-Whitney U test  

c.   p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate 
monotherapy using the Mann-Whitney U test 

 
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression 
(change from baseline in modified total Sharp score ≤ 0.5) was significantly higher with 
Trudexa/methotrexate combination therapy (63.8% and 61.2% respectively) compared to methotrexate 
monotherapy (37.4% and 33.5% respectively, p < 0.001) and Trudexa monotherapy (50.7%, p < 0.002 
and 44.5%, p < 0.001 respectively). 

Quality of life and physical function  

Health-related quality of life and physical function was assessed using the disability index of the 
Health Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, 
which was a pre-specified primary endpoint at week 52 in Study III.  All doses/schedules of Trudexa 
in all four studies showed statistically significantly greater improvement in the disability index of the 
HAQ from baseline to Month 6 compared to placebo and in Study III the same was seen at week 52.  
Results from the Short Form Health Survey (SF 36) for all doses/schedules of Trudexa in all four 
studies support these findings, with statistically significant physical component summary (PCS) 
scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other 
week dose.  A statistically significant decrease in fatigue as measured by functional assessment of 
chronic illness therapy (FACIT) scores was seen in all three studies in which it was assessed (Studies 
I, III, IV). 
 
In Study III, improvement in physical function was maintained through week  260 (60 months) of 
open-label treatment.  Improvement in quality of life was measured up to week 156 (36 months) and 
improvement was maintained through that time. 
 
In Study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Trudexa/methotrexate combination therapy versus 
methotrexate monotherapy and Trudexa monotherapy at week 52, which was maintained through 
week 104. 

Psoriatic arthritis 

Trudexa, 40 mg every other week, was studied in patients with moderately to severely active psoriatic 
arthritis in two placebo-controlled studies, Studies VI and VII.  Study VI with 24 week duration, 
treated 313 adult patients who had an inadequate response to non-steroidal anti-inflammatory drug 
therapy and of these, approximately 50% were taking methotrexate.  Study VII with 12-week duration, 
treated 100 patients who had an inadequate response to DMARD therapy. 
 
There is insufficient evidence of the efficacy of Trudexa in patients with ankylosing spondylitis-like 
psoriatic arthropathy due to the small number of patients studied (see Table 7). 
 

Table 7:  ACR Response in Placebo-Controlled Psoriatic Arthritis Studies 
(Percent of Patients) 

 
 Study VI Study VII 



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Response Placebo N=162 
Trudexa 
N=151 

Placebo  
N=49 

Trudexa 
N=51 

ACR 20      
 Week 12 14% 58%*** 16% 39%* 
 Week 24 15% 57%*** N/A N/A 
ACR 50      
 Week 12 4% 36%*** 2% 25%*** 
 Week 24 6% 39%*** N/A N/A 
ACR 70      
 Week 12 1% 20%*** 0% 14% * 
 Week 24 1% 23%*** N/A N/A 

*** p < 0.001 for all comparisons between Trudexa and placebo 
* p < 0.05 for all comparisons between Trudexa and placebo   
N/A  not applicable 

 
ACR responses in Study VI were similar with and without concomitant methotrexate therapy. 
Trudexa treated patients demonstrated improvement in physical function as assessed by HAQ and 
Short Form Health Survey (SF 36), from base-line to week 24. 

Ankylosing spondylitis 

Trudexa 40 mg every other week was assessed in 393 patients in two randomised, 24 week 
double − blind, placebo − controlled studies in patients with active ankylosing spondylitis (mean 
baseline score of disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] 
was 6.3 in all groups) who have had an inadequate response to conventional therapy.  Seventy-nine 
(20.1%) patients were treated concomitantly with disease modifying anti-rheumatic drugs, and 37 
(9.4%) patients with glucocorticoids.  The blinded period was followed by an open − label period 
during which patients received Trudexa 40 mg every other week subcutaneously for up to an 
additional 28 weeks.  Subjects (n=215, 54.7%) who failed to achieve ASAS 20 at Weeks 12, or 16 or 
20 received early escape open-label adalimumab 40 mg every other week subcutaneously and were 
subsequently treated as non-responders in the double-blind statistical analyses. 
 
In the larger study (VIII) with 315 patients, results showed statistically significant improvement of the 
signs and symptoms of ankylosing spondylitis in patients treated with Trudexa compared to placebo.  
Significant response was first observed at Week 2 and maintained through 24 weeks (Table 8).  

 
Table 8 - Efficacy Responses in Placebo-Controlled AS Study – Study VIII 

Reduction of Signs and Symptoms 
 

Response Placebo 
N=107 

Trudexa 
N=208 

ASASa 20   
             Week 2 16% 42%*** 

Week 12 21% 58%*** 
Week 24 19% 51%*** 

ASAS 50   
             Week 2 3% 16%*** 

Week 12 10% 38%*** 
Week 24 11% 35%*** 

ASAS 70   
             Week 2 0% 7%** 

Week 12 5% 23%*** 
Week 24 8% 24%*** 

   
BASDAIb 50    



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             Week 2 4% 20%*** 
Week 12  16% 45%*** 
Week 24  15% 42%*** 

***,** Statistically significant at p < 0.001, < 0.01 for all comparisons between Trudexa and placebo at Weeks 
2, 12 and  24 
a ASsessments in Ankylosing Spondylitis 
b Bath Ankylosing Spondylitis Disease Activity Index 

 
Trudexa treated patients had significantly greater improvement at Week 12 which was maintained 
through Week 24 in both the SF36 and Ankylosing Spondylitis Quality of Life Questionnaire 
(ASQoL). 
 
Similar trends (not all statistically significant) were seen in the smaller randomised, double − blind, 
placebo controlled study (IX) of 82 adult patients with active ankylosing spondylitis. 

Crohn’s Disease 

The safety and efficacy of Trudexa were assessed in over 1400 patients with moderately to severely 
active Crohn’s disease (Crohn’s Disease Activity Index (CDAI) ≥ 220 and ≤ 450) in randomised, 
double-blind, placebo-controlled studies.  478 of the enrolled patients (32%) were defined as having  a 
severe disease (CDAI score > 300 and concomitant corticosteroid and/or immunosuppressants) 
corresponding to the population defined in the indication (see section 4.1).  Concomitant stable doses 
of aminosalicylates, corticosteroids, and/or immunomodulatory agents were permitted and 79% of 
patients continued to receive at least one of these medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CLASSIC I and 
GAIN.  In CLASSIC I, 299 TNF-antagonist naive patients were randomised to one of four treatment 
groups; placebo at weeks 0 and 2, 160 mg Trudexa at week 0 and 80 mg at week 2, 80 mg at week 0 
and 40 mg at week 2, and 40 mg at week 0 and 20 mg at week 2.  In GAIN, 325 patients who had lost 
response or were intolerant to infliximab were randomised to receive either 160 mg Trudexa at week 0 
and 80 mg at week 2 or placebo at weeks 0 and 2.  The primary non-responders were excluded from 
the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CHARM.  In CHARM, 854 patients received 
open-label 80 mg at week 0 and 40 mg at week 2.  At week 4 patients were randomised to 40 mg every 
other week, 40 mg every week, or placebo with a total study duration of 56 weeks.  Patients in clinical 
response (decrease in CDAI ≥ 70) at week 4 were stratified and analysed separately from those not in 
clinical response at week 4.  Corticosteroid taper was permitted after week 8.  
 
CLASSIC I and GAIN induction of remission and response rates are presented in Table 9. 
 



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Table 9: Induction of Clinical Remission and Response 
(Percent of Patients) 

 CLASSIC I: Infliximab Naive Patients GAIN: Infliximab Experienced Patients 

 Placebo 

N=74 

Trudexa 

80/40 mg 

N = 75 

Trudexa  

160/80 m
g N=76 

Placebo 

N=166 

Trudexa  

160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Trudexa versus placebo 
* p < 0.001 
** p < 0.01 
 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by week 8 
and adverse events were more frequently noted in the 160/80 mg group. 
 
In CHARM, at week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis.  Of those in clinical response at week 4, 48% had been previously exposed to other 
anti-TNF therapy.  Maintenance of remission and response rates are presented in Table 10.  Clinical 
remission results remained relatively constant irrespective of previous TNF antagonist exposure. 
 

Table 10: Maintenance of Clinical Remission and Response 
(Percent of Patients) 

 Placebo 40 mg Trudexa 
every other week 

40 mg Trudexa 
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for >=90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Trudexa versus placebo pairwise comparisons   of proportions 

** p < 0.02 for Trudexa versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 
Among patients who were not in response at week 4, 43% of Trudexa maintenance patients responded 
by week 12 compared to 30% of placebo maintenance patients.  These results suggest that some 
patients who have not responded by week 4 benefit from continued maintenance therapy through week 
12.  Therapy continued beyond 12 weeks did not result in significantly more responses (see section 
4.2).   

Quality of Life 

In CLASSIC I and GAIN, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at week 4 in patients randomised to 



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Trudexa 80/40 mg and 160/80 mg compared to placebo and was seen at weeks 26 and 56 in CHARM 
as well among the adalimumab treatment groups compared to the placebo group. 

Immunogenicity   

Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy 
of adalimumab.  There is no apparent correlation between the presence of anti-adalimumab antibodies 
and adverse events. 
 
Patients in Studies I, II and III were tested at multiple timepoints for antibodies to adalimumab during 
the 6 to 12 month period.  In the pivotal trials, anti-adalimumab antibodies were identified in 58/1053 
(5.5%) patients treated with adalimumab, compared to 2/370 (0.5%) on placebo.  In patients not given 
concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when adalimumab was used as 
add-on to methotrexate.   
 
In patients with psoriatic arthritis, adalimumab antibodies were identified in 38/376 subjects (10%) 
treated with adalimumab.  In patients not given concomitant methotrexate, the incidence was 13.5% 
(24/178 subjects), compared to 7% (14 of 198 subjects) when adalimumab was used as add-on to 
methotrexate. 
 
In patients with ankylosing spondylitis antibodies were identified in 17/204 subjects (8.3%) treated 
with adalimumab.  In patients not given concomitant methotrexate, the incidence was 16/185 (8.6%), 
compared to 1/19 (5.3%) when adalimumab was used as add-on to methotrexate. 
 
In patients with Crohn’s disease, adalimumab antibodies were identified in 7/269 subjects (2.6%) 
treated with adalimumab. 
 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 

5.2 Pharmacokinetic properties 

After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab 
was slow, with peak serum concentrations being reached about 5 days after administration.  The 
average absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%.  After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional.  After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 
to 15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-
life was approximately two weeks.  Adalimumab concentrations in the synovial fluid from several 
rheumatoid arthritis patients ranged from 31-96% of those in serum. 
 
Following subcutaneous administration of 40 mg of Trudexa every other week in rheumatoid arthritis 
(RA) patients the mean steady-state trough concentrations were approximately 5 µg/ml (without 
concomitant methotrexate) and 8 to 9 µg/ml (with concomitant methotrexate), respectively.  The 
serum adalimumab trough levels at steady-state increased roughly proportionally with dose following 
20, 40 and 80 mg every other week and every week subcutaneous dosing. 
 
In patients with Crohn’s disease, the loading dose of 80 mg Trudexa on week 0 followed by 40 mg 
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 5.5 µg/ml 
during the induction period.  A loading dose of 160 mg Trudexa on week 0 followed by 80 mg 
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 12 µg/ml 
during the induction period.  Mean steady-state trough levels of approximately 7 µg/ml were observed 
in Crohn’s disease patients who received a maintenance dose of 40 mg Trudexa every other week. 
 
Population pharmacokinetic analyses with data from over 1300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight.  After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance.  The serum 



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levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower 
in patients with measurable AAA.  Trudexa has not been studied in children or in patients with hepatic 
or renal impairment. 

5.3 Preclinical safety data  

Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, 
repeated dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomologous monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence 
of harm to the foetuses due to adalimumab.  Carcinogenicity studies, and standard assessment of 
fertility and postnatal toxicity, were not performed with adalimumab due to the lack of appropriate 
models for an antibody with limited cross-reactivity to rodent TNF and the development of 
neutralizing antibodies in rodents.  

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients  

Mannitol  
Citric acid monohydrate 
Sodium citrate 
Sodium dihydrogen phosphate dihydrate 
Disodium phosphate dihydrate 
Sodium chloride 
Polysorbate 80 
Sodium hydroxide 
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  

18 months 

6.4 Special precautions for storage  

Store in a refrigerator (2°C – 8°C).  Keep the syringe in the outer carton.  Do not freeze. 

6.5 Nature and contents of container   

Trudexa 40 mg solution for injection in single-use pre-filled syringe (type I glass) with needleguard 
for hospital and caregiver use: 
 
Packs of: 
1 pre-filled syringe with needleguard (0.8 ml sterile solution) in a blister, and 1 alcohol pad. 

6.6 Special precautions for disposal 

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

7. MARKETING AUTHORISATION HOLDER  



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Abbott Laboratories Ltd.  
Queenborough 
Kent ME11 5EL 
United Kingdom 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/03/257/006 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

1 September 2003 

10. DATE OF REVISION OF THE TEXT 

{MM/YYYY} 
 
 



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1. NAME OF THE MEDICINAL PRODUCT  

Trudexa 40 mg solution for injection in pre-filled pen 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION  

Each 0.8 ml single dose pre-filled pen contains 40 mg of adalimumab.  
 
Adalimumab is a recombinant human monoclonal antibody expressed in Chinese Hamster Ovary cells.  
 
For a full list of excipients, see section 6.1.  

3. PHARMACEUTICAL FORM  

Solution for injection in pre-filled pen. 

4. CLINICAL PARTICULARS 

4.1 Therapeutic indications  

Rheumatoid arthritis 
 
Trudexa in combination with methotrexate, is indicated for: 
 
 the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the 

response to disease-modifying anti-rheumatic drugs including methotrexate has been 
inadequate. 
 

 the treatment of severe, active and progressive rheumatoid arthritis in adults not previously 
treated with methotrexate. 

 
Trudexa can be given as monotherapy in case of intolerance to methotrexate or when continued 
treatment with methotrexate is inappropriate. 
 
Trudexa has been shown to reduce the rate of progression of joint damage as measured by X-ray and 
to improve physical function, when given in combination with methotrexate. 

Psoriatic arthritis 

Trudexa is indicated for the treatment of active and progressive psoriatic arthritis in adults when the 
response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. 
 
Ankylosing spondylitis 
 
Trudexa is indicated for the treatment of adults with severe active ankylosing spondylitis who have 
had an inadequate response to conventional therapy. 
 
Crohn’s disease 
 
Trudexa is indicated for treatment of severe, active Crohn’s disease, in patients who have not 
responded despite a full and adequate course of therapy with a corticosteroid and/or an 
immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. 



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For induction treatment, Trudexa should be given in combination with corticosteroids.  Trudexa can be 
given as monotherapy in case of intolerance to corticosteroids or when continued treatment with 
corticosteroids is inappropriate (see section 4.2). 

4.2 Posology and method of administration   

Trudexa treatment should be initiated and supervised by specialist physicians experienced in the 
diagnosis and treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or Crohn’s 
disease.  Patients treated with Trudexa should be given the special alert card. 
 
After proper training in injection technique, patients may self-inject with Trudexa if their physician 
determines that it is appropriate and with medical follow-up as necessary.  
 
During treatment with Trudexa, other concomitant therapies (e.g., corticosteroids and/or 
immunomodulatory agents) should be optimised. 

Adults 

Rheumatoid arthritis 
 
The recommended dose of Trudexa for adult patients with rheumatoid arthritis is 40 mg adalimumab 
administered every other week as a single dose via subcutaneous injection.  Methotrexate should be 
continued during treatment with Trudexa. 
 
Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, or analgesics can be continued 
during treatment with Trudexa.  Regarding combination with disease modifying anti-rheumatic drugs 
other than methotrexate see sections 4.4 and 5.1. 
 
In monotherapy, some patients who experience a decrease in their response may benefit from an 
increase in dose intensity to 40 mg adalimumab every week.  

Psoriatic arthritis and ankylosing spondylitis 

The recommended dose of Trudexa for patients with psoriatic arthritis and ankylosing spondylitis is 
40 mg adalimumab administered every other week as a single dose via subcutaneous injection. 
 
For all of the above indications, available data suggest that the clinical response is usually achieved 
within 12 weeks of treatment.  Continued therapy should be carefully reconsidered in a patient not 
responding within this time period. 
 
Crohn’s disease 
 
The recommended Trudexa induction dose regimen for adult patients with severe Crohn’s disease is 
80 mg at week 0 followed by 40 mg at week 2.  In case there is a need for a more rapid response to 
therapy, the regimen 160 mg at week 0 (dose can be administered as four injections in one day or as 
two injections per day for two consecutive days), 80 mg at week 2, can be used with the awareness 
that the risk for adverse events is higher during induction. 
 
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous 
injection.  Alternatively, if a patient has stopped Trudexa and signs and symptoms of disease recur, 
Trudexa may be re-administered.  There is little experience from re-administration after more than 8 
weeks since the previous dose. 
 
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice 
guidelines. 
 



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Some patients who experience decrease in their response may benefit from an increase in dose 
intensity to 40 mg Trudexa every week. 
 
Some patients who have not responded by week 4 may benefit from continued maintenance therapy 
through week 12.  Continued therapy should be carefully reconsidered in a patient not responding 
within this time period. 

Elderly patients 

No dose adjustment is required.   

Children and adolescents 

 There is no experience in children. 

Impaired renal and/or hepatic function 

Trudexa has not been studied in these patient populations.  No dose recommendations can be made. 

4.3 Contraindications  

Hypersensitivity to the active substance or to any of the excipients.  
 
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 
4.4). 
 
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4). 

4.4 Special warnings and precautions for use   

Infections 
 
Patients must be monitored closely for infections, including tuberculosis, before, during and after 
treatment with Trudexa.  Because the elimination of adalimumab may take up to five months, 
monitoring should be continued throughout this period. 
 
Treatment with Trudexa should not be initiated in patients with active infections including chronic or 
localized infections until infections are controlled.  
 
Patients who develop a new infection while undergoing treatment with Trudexa should be monitored 
closely.  Administration of Trudexa should be discontinued if a patient develops a new serious 
infection until infections are controlled.  Physicians should exercise caution when considering the use 
of Trudexa in patients with a history of recurring infection or with underlying conditions which may 
predispose patients to infections, including the use of concomitant immunosuppressive medications. 
 
Serious infections, sepsis, tuberculosis and other opportunistic infections, including fatalities, have 
been reported with Trudexa.   
 
Serious infections: 
 
In clinical trials an increased risk of serious infections in patients receiving Trudexa has been shown, 
and reports from the post-marketing setting support this finding.  Of particular importance are 
infections such as pneumonia, pyelonephritis, septic arthritis and septicaemia.   
 
Tuberculosis: 
 



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There have been reports of tuberculosis in patients receiving Trudexa.  It should be noted that in the 
majority of those reports, tuberculosis was extra-pulmonary, i.e. disseminated.  
 
Before initiation of therapy with Trudexa, all patients must be evaluated for both active or inactive 
(latent) tuberculosis infection.  This evaluation should include a detailed medical history with a 
personal history of tuberculosis or possible previous exposure to patients with active tuberculosis and 
previous and/or current immunosuppressive therapy.  Appropriate screening tests, i.e. tuberculin skin 
test and chest X-ray, should be performed in all patients (local recommendations may apply).  It is 
recommended that the conduct of these tests should be recorded in the patient alert card.  Prescribers 
are reminded of the risk of false negative tuberculin skin test results, especially in patients who are 
severely ill or immunocompromised.  
 
If active tuberculosis is diagnosed, Trudexa therapy must not be initiated (see section 4.3).  
 
If latent tuberculosis is diagnosed, appropriate anti-tuberculosis prophylaxis in accordance with local 
recommendations must be initiated before starting treatment with Trudexa.  In this situation, the 
benefit/risk balance of therapy with Trudexa should be very carefully considered. 
 
Patients should be instructed to seek medical advice if signs/symptoms (e.g., persistent cough, 
wasting/weight loss, low grade fever) suggestive of a tuberculosis infection occur during or after 
therapy with Trudexa.  
 
Other opportunistic infections: 
 
There have been reports of serious and severe opportunistic infections associated with Trudexa 
therapy, for example pneumocystis carinii pneumonia, disseminated histoplasmosis, listeriosis and 
aspergillosis. 
 
If a patient receiving Trudexa shows prolonged/atypical symptoms/signs of infections or general 
deterioration, prevalent opportunistic conditions must be considered. 
 
Hepatitis B Reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Trudexa, 
who are chronic carriers of this virus.  Some cases have had fatal outcome.  Patients at risk for HBV 
infection should be evaluated for prior evidence of HBV infection before initiating Trudexa therapy.  
Carriers of HBV who require treatment with Trudexa should be closely monitored for signs and 
symptoms of active HBV infection throughout therapy and for several months following termination 
of therapy.  Adequate data of treating patients who are carriers of HBV with anti-viral therapy in 
conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available.  In patients 
who develop HBV reactivation, Trudexa should be stopped and effective anti-viral therapy with 
appropriate supportive treatment should be initiated.  

Neurological events  

TNF-antagonists including Trudexa have been associated in rare cases with new onset or exacerbation 
of clinical symptoms and/or radiographic evidence of demyelinating disease.  Prescribers should 
exercise caution in considering the use of Trudexa in patients with pre-existing or recent-onset central 
nervous system demyelinating disorders.  

Allergic reactions 

Serious allergic adverse reactions have not been reported with subcutaneous administration of Trudexa 
during clinical trials.  Non-serious allergic reactions associated with Trudexa were uncommon during 
clinical trials.  In postmarketing, serious allergic reactions including anaphylaxis have been reported 
very rarely following Trudexa administration.  If an anaphylactic reaction or other serious allergic 



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reaction occurs, administration of Trudexa should be discontinued immediately and appropriate 
therapy initiated.  
 
The needle cover of the syringe contains natural rubber (latex).  This may cause severe allergic 
reactions in patients sensitive to latex. 

Immunosuppression 

In a study of 64 patients with rheumatoid arthritis that were treated with Trudexa, there was no 
evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or 
change in enumeration of effector T-and B cells and NK-cells, monocyte/macrophages, and 
neutrophils. 

Malignancies and lymphoproliferative disorders 

In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including 
lymphoma have been observed among patients receiving a TNF-antagonist compared with control 
patients.  However, the occurrence was rare.  Furthermore, there is an increased background 
lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory 
disease, which complicates the risk estimation.  With the current knowledge, a possible risk for the 
development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be 
excluded. 
 
No studies have been conducted that include patients with a history of malignancy or that continue 
treatment in patients who develop malignancy while receiving Trudexa.  Thus additional caution 
should be exercised in considering Trudexa treatment of these patients (see section 4.8). 
 
In an exploratory clinical trial evaluating the use of another anti-TNF agent, infliximab, in patients 
with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in 
the lung or head and neck, were reported in infliximab-treated patients compared with control patients.  
All patients had a history of heavy smoking.  Therefore, caution should be exercised when using any 
TNF-antagonist in COPD patients, as well as in patients with increased risk for malignancy due to 
heavy smoking. 
 
Haematologic reactions 
 
Rare reports of pancytopenia including aplastic anaemia have been reported with TNF blocking 
agents.  Adverse events of the haematologic system, including medically significant cytopoenia (e.g. 
thrombocytopaenia, leucopaenia) have been infrequently reported with Trudexa.  All patients should 
be advised to seek immediate medical attention if they develop signs and symptoms suggestive of 
blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor) while on Trudexa.  Discontinuation 
of Trudexa therapy should be considered in patients with confirmed significant haematologic 
abnormalities. 
 
Vaccinations  
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent 
virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were 
treated with adalimumab or placebo.  No data are available on the secondary transmission of infection 
by live vaccines in patients receiving Trudexa.  Patients on Trudexa may receive concurrent 
vaccinations, except for live vaccines. 

Congestive heart failure 

In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased 
mortality due to congestive heart failure have been observed.  Cases of worsening congestive heart 
failure have also been reported in patients receiving Trudexa.  Trudexa should be used with caution in 
patients with mild heart failure (NYHA class I/II).  Trudexa is contraindicated in moderate to severe 



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heart failure (see section 4.3).  Treatment with Trudexa must be discontinued in patients who develop 
new or worsening symptoms of congestive heart failure. 

Autoimmune processes 

Treatment with Trudexa may result in the formation of autoimmune antibodies.  The impact of long-
term treatment with Trudexa on the development of autoimmune diseases is unknown.  If a patient 
develops symptoms suggestive of a lupus-like syndrome following treatment with Trudexa and is 
positive for antibodies against double-stranded DNA, further treatment with Trudexa should not be 
given (see section 4.8). 

Concurrent administration of TNF-antagonists and anakinra 

Serious infections were seen in clinical studies with concurrent use of anakinra and another 
TNF-antagonist, etanercept, with no added clinical benefit compared to etanercept alone.  Because of 
the nature of the adverse events seen with the combination of etanercept and anakinra therapy, similar 
toxicities may also result from the combination of anakinra and other TNF-antagonists.  Therefore, the 
combination of adalimumab and anakinra is not recommended. 

Surgery 

There is limited safety experience of surgical procedures in patients treated with Trudexa.  The long 
half-life of adalimumab should be taken into consideration if a surgical procedure is planned.  A 
patient who requires surgery while on Trudexa should be closely monitored for infections, and 
appropriate actions should be taken.  There is limited safety experience in patients undergoing 
arthroplasty while receiving Trudexa.  
 
Small bowel obstruction 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of fixed fibrotic stricture 
that may require surgical treatment.  Available data suggest that Trudexa does not worsen or cause 
strictures. 

4.5 Interaction with other medicinal products and other forms of interaction  

Trudexa has been studied both in rheumatoid arthritis and psoriatic arthritis patients taking Trudexa as 
monotherapy and those taking concomitant methotrexate.  Antibody formation was lower when 
Trudexa was given together with methotrexate in comparison with use as monotherapy.  
Administration of Trudexa without methotrexate resulted in increased formation of antibodies, 
increased clearance and reduced efficacy of adalimumab (see section 5.1).  

4.6 Pregnancy and lactation  

For Trudexa, no clinical data on exposed pregnancies are available 
 
In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, 
embryotoxicity or teratogenicity.  Preclinical data on postnatal toxicity and fertility effects of 
adalimumab are not available (see section 5.3). 
 
Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal 
immune responses in the newborn.  Administration of adalimumab is not recommended during 
pregnancy.  Women of childbearing potential are strongly recommended to use adequate contraception 
to prevent pregnancy and continue its use for at least five months after the last Trudexa treatment.  

Use during lactation  



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It is not known whether adalimumab is excreted in human milk or absorbed systemically after 
ingestion.  
 
However, because human immunoglobulins are excreted in milk, women must not breast-feed for at 
least five months after the last Trudexa treatment. 

4.7 Effects on ability to drive and use machines  

No studies on the effects on the ability to drive and use machines have been performed. 

4.8 Undesirable effects 

Clinical Trials 
 
Trudexa was studied in 5293 patients in controlled and open label trials for up to 60 months.  These 
trials included rheumatoid arthritis patients with short term and long standing disease as well as 
psoriatic arthritis, ankylosing spondylitis and Crohn’s disease patients.  The data in Table 1 is based 
on the controlled Studies (I − IX,CLASSIC I, GAIN AND CHARM) (described in section 5.1) 
involving 3271 patients receiving Trudexa and 1809 patients receiving placebo or active comparator 
during the controlled period. 
 
The proportion of patients who discontinued treatment due to adverse events during the double-blind, 
controlled portion of Studies I − IX, CLASSIC I, GAIN and CHARM  was 5.7% for patients taking 
Trudexa and 5.3% for control treated patients. 
 
Adverse events at least possibly causally-related to adalimumab for Studies I − IX, CLASSIC I, GAIN 
and CHARM, both clinical and laboratory, are displayed by system organ class and frequency (very 
common ≥ 1/10; common≥ 1/100 < 1/10; uncommon≥ 1/1000  to ≤ 1/100) and rare < 1/1000 in Table 
1 below.  Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness. 
 

Table 1 
Undesirable Effects in Clinical Studies 

 

System Organ Class Frequency Adverse Reaction 

Infections and 
infestations 
 

Common 
 

lower respiratory infections (including 
pneumonia, bronchitis), viral infections 
(including influenza, herpes infections), 
candidiasis, bacterial infections (including 
urinary tract infections), upper respiratory 
infection 
 

 Uncommon 
 

opportunistic infections (including  
tuberculosis, histoplasmosis), sepsis, abscess,  
joint infection, wound infection, skin infection 
(including cellulitis and impetigo), superficial 
fungal infections (including skin, nail and 
foot) 
 

 Rare necrotising fasciitis, viral meningitis, 
diverticulitis 
 

Neoplasms benign and 
malignant (including 

Uncommon 
 

skin papilloma 
 



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cysts and polyps)  Rare 
 

lymphoma, solid organ tumours (including 
breast, ovarian, testicular), squamous cell 
carcinoma of the skin 
 

Common 
 

lymphopaenia 
 

Uncommon 
 

neutropaenia (including agranulocytosis), 
leucopaenia, thrombocytopaenia, anaemia, , 
lymphadenopathy, leucocytosis  
 

Blood and the lymphatic 
system disorders 

Rare 
 

pancytopaenia, idiopathic thrombocytopaenia 
purpura 
 

Uncommon 
 

systemic lupus erythematosus, angioedema, 
drug hypersensitivity, seasonal allergy 
 

Immune system disorders 

Rare serum sickness 
 

Endocrine disorders Rare 
 

thyroid disorder (including goitre) 

Uncommon 
 

Hypokalaemia, lipids increased, appetite 
disorders (including anorexia), hyperuricaemia 
 

Metabolism and nutrition 
disorders 

Rare hypercalcaemia 
 

Psychiatric disorders Uncommon 
 

mood disorders, anxiety (including 
nervousness and agitation) 
 

Common 
 

dizziness (including vertigo), headache, 
neurologic sensation disorders (including 
paraesthesias) 
 

Uncommon 
 

syncope, migraine, tremor, sleep disturbances  
 

Nervous system disorders 

Rare 
 

multiple sclerosis 
 

Common 
 

infection, irritation or inflammation of the eye 
 

Uncommon 
 

vision disorder, ocular sensation disorders  
 

Eye disorders 

Rare Panophthalmitis, iritis, glaucoma 
 

Uncommon 
 

tinnitus, ear discomfort (including pain and 
swelling) 
 

Ear and labyrinth 
disorders  
 

Rare 
 

hearing loss 
 

Uncommon 
 

arrhythmias, tachycardia, palpitations 
 

Cardiac disorders  

Rare 
 

cardiac arrest, coronary artery insufficiency, 
angina pectoris, pericardial effusion 
 

Vascular disorders Uncommon 
 

hypertension, flushing, haematoma 
 

 Rare vascular occlusion, aortic stenosis, 
thrombophlebitis, aortic aneurysm 



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Common 
 

cough, nasopharyngeal pain 
 

Uncommon 
 

asthma, dyspnoea, dysphonia, nasal 
congestion 
 

Respiratory, thoracic and 
mediastinal disorders 

Rare pulmonary oedema, pharyngeal oedema, 
pleural effusion, pleurisy 
 

Common 
 

diarrhoea, abdominal pain, stomatitis and 
mouth ulceration, nausea 
 

Uncommon 
 

rectal haemorrhage, gastritis, vomiting, 
dyspepsia, abdominal bloating, constipation,  
 

Gastrointestinal disorders 

Rare 
 

intestinal stenosis, colitis, enteritis, 
oesophagitis 
 

Hepato-biliary disorders Common 
 

hepatic enzymes increased 
 

 Rare 
 

hepatic necrosis, hepatitis 
 

Common 
 

rash, dermatitis and eczema, pruritus, hair loss 
 

Uncommon 
 

urticaria, psoriasis, ecchymosis and increased 
bruising, purpura 
 

Skin and subcutaneous 
tissue disorders 

Rare 
 

erythema multiforme, panniculitis 

Common 
 

musculoskeletal pain 
 

Musculoskeletal, 
connective tissue and 
bone disorders Rare 

 
rhabdomyolysis 

Uncommon 
 

haematuria, renal impairment, bladder and 
urethral symptoms 
 

Renal and urinary 
disorders  

Rare 
 

proteinuria, renal pain 
 

Reproductive system and 
breast disorders 

Uncommon menstrual cycle and uterine bleeding disorders 
 

Very Common 
 

injection site reaction (including pain, 
swelling, redness or pruritus) 
 

Common 
 

pyrexia, fatigue (including asthenia and 
malaise) 
 

General disorders and 
administration site 
conditions 

Uncommon 
 

chest pain, oedema, influenza like illness 

Investigations Uncommon blood creatine phosphokinase increased, 
activated partial thromboplastin time 
prolonged, autoantibodies present 
 

Injury and poisoning  Uncommon accidental injury, impaired healing 



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Injection site reactions   

In the twelve controlled trials, 16% of patients treated with Trudexa developed injection site reactions 
(erythema and/or itching, haemorrhage, pain or swelling), compared to 10% of patients receiving 
placebo or active control.  Injection site reactions generally did not necessitate discontinuation of the 
medicinal product.  

Infections  

In the twelve controlled trials, the rate of infection was 1.49 per patient year in the Trudexa treated 
patients and 1.42 per patient year in the placebo and active control-treated patients.  The infections 
consisted primarily of upper respiratory tract infections, bronchitis and urinary tract infections.  Most 
patients continued on Trudexa after the infection resolved.   
 
The incidence of serious infections was 0.03 per patient year in Trudexa treated patients and 0.03 per 
patient year in placebo and active control − treated patients.   
 
In controlled and open label studies with Trudexa, serious infections (including fatal infections, which 
occurred rarely) have been reported, which include reports of tuberculosis (including miliary and 
extra-pulmonary locations) and invasive opportunistic infections (e.g. disseminated histoplasmosis, 
pneumocystis carinii pneumonia, aspergillosis and listeriosis).  Most of the cases of tuberculosis 
occurred within the first eight months after initiation of therapy and may reflect recrudescence of 
latent disease. 

Malignancies and lymphoproliferative disorders 

During the controlled portions of ten Trudexa trials at least 12 weeks in duration (I-IX and CHARM) 
in patients with moderately to severely active rheumatoid arthritis, psoriatic arthritis, ankylosing 
spondylitis and Crohn’s disease, malignancies, other than lymphoma and non-melanoma skin cancer, 
were observed at a rate (95% confidence interval) of 5.7 (3.3, 10.1) per 1000 patient-years among 
2887 Trudexa treated patients versus a rate of 4.1 (1.5, 10.9) 1 per 1000 patient-years among 1570 
control patients (median duration of treatment was 5.7 months for Trudexa and 5.5 months for control-
treated patients).  The rate (95% confidence interval) of non-melanoma skin cancers was 7.6 (4.7, 
12.4) per 1000 patient-years among Trudexa-treated patients and 2.0 (0.5, 8.2) per 1000 patient-years 
among control patients.  Of these skin cancers, squamous cell carcinomas occurred at rates (95% 
confidence interval) of 2.4 (1.0, 5.7) per 1000 patient-years among Trudexa-treated patients and 0 per 
1000 patient-years among control patients.  The rate (95% confidence interval) of lymphomas was 1.0 
(0.2, 3.8)  per 1000 patient-years among Trudexa-treated patients and 1.0 (0.1, 7.3) per 1000 patient-
years among control patients. 
 
When combining controlled portions of ten trials (I-IX and CHARM) and ongoing open label 
extension studies with a median duration of approximately 2. years including 4843 patients and over 
13000 patient-years of therapy, the observed rate of malignancies, other than lymphoma and non-
melanoma skin cancers is approximately 13.6 per 1000 patient years.  The observed rate of non-
melanoma skin cancers is approximately 9.0 per 1000 patient years, and the observed rate of 
lymphomas is approximately 1.2 per 1000 patient years. 
 
In post-marketing experience from January 2003, predominately in patients with rheumatoid arthritis, 
the reported rate of malignancies other than lymphomas and non-melanoma skin cancers is 
approximately 1.7 per 1000 patient years.  The reported rates for non-melanoma skin cancers and 
lymphomas are approximately 0.2 and 0.4 per 1000 patient years, respectively (see section 4.4). 

Autoantibodies  



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Patients had serum samples tested for autoantibodies at multiple time points in rheumatoid arthritis 
Studies I − V.  In these trials, 11.9% of patients treated with Trudexa and 8.1% of placebo and active 
control − treated patients that had negative baseline anti-nuclear antibody titres reported positive titres 
at week 24.  Two patients out of 3441 treated with Trudexa in all rheumatoid arthritis and psoriatic 
arthritis studies developed clinical signs suggestive of new-onset lupus-like syndrome.  The patients 
improved following discontinuation of therapy.  No patients developed lupus nephritis or central 
nervous system symptoms. 

Liver Enzyme Elevations 

Rheumatoid arthritis clinical trials: in controlled rheumatoid arthritis clinical trials (Studies I − IV), 
elevations of ALT were similar in patients receiving adalimumab or placebo.  In patients with early 
rheumatoid arthritis (disease duration of less than 3 years) (Study V), elevations of ALT were more 
common in the combination arm (Trudexa /methotrexate) compared to the methotrexate monotherapy 
arm or the Trudexa monotherapy arm. 
 
Psoriatic arthritis clinical trials: elevations in ALT were more common in psoriatic arthritis patients 
(Studies VI-VII) compared with patients in rheumatoid arthritis clinical studies. 
 
In all studies (I-VII), patients with raised ALT were asymptomatic and in most cases elevations were 
transient and resolved on continued treatment. 
 
Crohn’s disease clinical trials: in controlled clinical trials, elevations of ALT were similar in patients 
receiving adalimumab or placebo. 

Additional Adverse Reactions from Postmarketing Surveillance or Phase IV Clinical Trials 

The additional adverse reactions in Table 2 have been reported from postmarketing surveillance or 
Phase IV clinical trials: 
 

Table 2 
Undesirable Effects in Postmarketing Surveillance and Phase IV Clinical Studies 

 
System Organ Class Adverse Reaction 
Hepatobiliary Disorders reactivation of hepatitis B 
Nervous system disorders demyelinating disorders (e.g. optic neuritis) 
Respiratory, thoracic and mediastinal disorders interstitial lung disease, including pulmonary 

fibrosis  
Skin and subcutaneous tissue disorders cutaneous vasculitis 
Immune system disorders anaphylaxis 

4.9 Overdose  

No dose-limiting toxicity was observed during clinical trials.  The highest dose level evaluated has 
been multiple intravenous doses of 10 mg/kg.   

5. PHARMACOLOGICAL PROPERTIES 

5.1 Pharmacodynamic properties 

Pharmacotherapeutic group: Selective immunosuppressive agents.  ATC code: L04AA17 

Mechanism of action 



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Adalimumab binds specifically to TNF and neutralizes the biological function of TNF by blocking its 
interaction with the p55 and p75 cell surface TNF receptors.   
 
Adalimumab also modulates biological responses that are induced or regulated by TNF, including 
changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, 
and ICAM-1 with an IC50 of 1-2 X 10-10 M).  

Pharmacodynamic effects  

After treatment with Trudexa, a rapid decrease in levels of acute phase reactants of inflammation 
(C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) and serum cytokines (IL-6) was 
observed compared to baseline in patients with rheumatoid arthritis.  Serum levels of matrix 
metalloproteinases (MMP-1 and MMP-3) that produce tissue remodelling responsible for cartilage 
destruction were also decreased after Trudexa administration.  Patients treated with Trudexa usually 
experienced improvement in haematological signs of chronic inflammation. 
 
A rapid decrease in CRP levels was also observed in patients with Crohn’s disease. 

Clinical trials 

Rheumatoid arthritis 
 
Trudexa was evaluated in over 3000 patients in all rheumatoid arthritis clinical trials.  Some patients 
were treated for up to 60 months duration.  The efficacy and safety of Trudexa for the treatment of 
rheumatoid arthritis were assessed in five randomised, double-blind and well-controlled studies.   
 
Study I evaluated 271 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old, had failed therapy with at least one disease-modifying, anti rheumatic drug and had 
insufficient efficacy with methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-intolerant) 
every week and whose methotrexate dose remained constant at 10 to 25 mg every week.  Doses of 20, 
40 or 80 mg of Trudexa or placebo were given every other week for 24 weeks.  
 
Study II evaluated 544 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old and had failed therapy with at least one disease-modifying, anti-rheumatic drugs.  Doses of 
20 or 40 mg of Trudexa were given by subcutaneous injection every other week with placebo on 
alternative weeks or every week for 26 weeks; placebo was given every week for the same duration.  
No other disease-modifying anti-rheumatic drugs were allowed. 
 
Study III evaluated 619 patients with moderately to severely active rheumatoid arthritis who were ≥ 18 
years old, had insufficient efficacy to methotrexate at doses of 12.5 to 25 mg (10 mg if methotrexate-
intolerant) every week and whose methotrexate dose remained constant at 12.5 to 25 mg every week.  
There were three groups in this study.  The first received placebo injections every week for 52 weeks.  
The second received 20 mg of Trudexa every week for 52 weeks.  The third group received 40 mg of 
Trudexa every other week with placebo injections on alternate weeks.  Thereafter, patients enrolled in 
an open-label extension phase in which 40 mg of Trudexa was administered every other week up to 60 
months. 
 
Study IV primarily assessed safety in 636 patients with moderately to severely active rheumatoid 
arthritis who were ≥ 18 years old.  Patients were permitted to be either disease-modifying, 
anti-rheumatic drug-naïve or to remain on their pre-existing rheumatologic therapy provided that 
therapy was stable for a minimum of 28 days.  These therapies include methotrexate, leflunomide, 
hydroxychloroquine, sulfasalazine and/or gold salts.  Patients were randomised to 40 mg of Trudexa 
or placebo every other week for 24 weeks.   
 
Study V evaluated 799 methotrexate-naïve, adult patients with moderate to severely active early 
rheumatoid arthritis (mean disease duration less than 9 months).  This study evaluated the efficacy of 
Trudexa 40 mg every other week/methotrexate combination therapy, Trudexa 40 mg every other week 



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monotherapy and methotrexate monotherapy in reducing the signs and symptoms and rate of 
progression of joint damage in rheumatoid arthritis for 104 weeks. 
 
The primary end point in Studies I, II and III and the secondary endpoint in Study IV was the percent 
of patients who achieved an ACR 20 response at week 24 or 26.  The primary endpoint in Study V 
was the percent of patients who achieved an ACR 50 response at week 52.  Study III and V had an 
additional primary endpoint at 52 weeks of retardation of disease progression (as detected by X-ray 
results).  Study III also had a primary endpoint of changes in quality of life. 

ACR response 

The percent of Trudexa-treated patients achieving ACR 20, 50 and 70 responses was consistent across 
trials I, II and III.  The results for the 40 mg every other week dose are summarised in Table 3.  
 

Table 3:  ACR Responses in Placebo-Controlled Trials 
(Percent of Patients) 

 
Response Study Ia** Study IIa** Study IIIa** 

 
 Placebo/ 

MTXc 
n=60 

Trudexab/ MTXc
n=63 

Placebo 
n=110 

Trudexab 
n=113 

Placebo/ 
MTXc 
n=200 

Trudexab/ 
MTXc 
n=207 

ACR 20       
 6 months 13.3% 65.1% 19.1% 46.0% 29.5% 63.3% 
 12 months NA NA NA NA 24.0% 58.9% 
ACR 50       
 6 months 6.7% 52.4% 8.2% 22.1% 9.5% 39.1% 
 12 months NA NA NA NA 9.5% 41.5% 
ACR 70       
 6 months 3.3% 23.8% 1.8% 12.4% 2.5% 20.8% 
 12 months NA NA NA NA 4.5% 23.2% 
a Study I at 24 weeks, Study II at 26 weeks , and Study III at 24 and 52 weeks 
b 40 mg Trudexa administered every other week 
c MTX = methotrexate 
**p < 0.01, Trudexa versus placebo 

 
In Studies I-IV, all individual components of the ACR response criteria (number of tender and swollen 
joints, physician and patient assessment of disease activity and pain, disability index (HAQ) scores 
and CRP (mg/dl) values) improved at 24 or 26 weeks compared to placebo.  In Study III, these 
improvements were maintained throughout 52 weeks.  In addition, ACR response rates were 
maintained in the majority of patients followed in the open-label extension phase to week 104.  There 
were 114 out of 207 patients who continued on Humira 40 mg every other week for 60 months.  
Among those, 86, 72, and 41 patients had ACR 20/50/70 response, respectively at month 60. 
 
In Study IV, the ACR 20 response of patients treated with Trudexa plus standard of care was 
statistically significantly better than patients treated with placebo plus standard of care (p < 0.001).   
 
In Studies I-IV, Trudexa-treated patients achieved statistically significant ACR 20 and 50 responses 
compared to placebo as early as one to two weeks after initiation of treatment. 
 
In Study V with early rheumatoid arthritis patients who were methotrexate naïve, combination therapy 
with Trudexa and methotrexate led to faster and significantly greater ACR responses than 
methotrexate monotherapy and Trudexa monotherapy at week 52 and responses were sustained at 
week 104 (see Table 4). 
 



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Table 4:  ACR Responses in Study V 
(percent of patients) 

 

Response MTX n=257 
Trudexa 

n=274 

Trudexa/MT
X 

n=268 
p-valuea p-valueb p-valuec 

ACR 20       
 Week 52 62.6% 54.4% 72.8% 0.013 < 0.001 0.043 
 Week 104 56.0% 49.3% 69.4% 0.002 < 0.001 0.140 
ACR 50       
 Week 52 45.9% 41.2% 61.6% < 0.001 < 0.001 0.317 
 Week 104 42.8% 36.9% 59.0% < 0.001 < 0.001 0.162 
ACR 70       
 Week 52 27.2% 25.9% 45.5% < 0.001 < 0.001 0.656 
 Week 104 28.4% 28.1% 46.6% < 0.001 < 0.001 0.864 
a. p-value is from the pairwise comparison of methotrexate monotherapy and Trudexa/methotrexate 

combination therapy using the Mann-Whitney U test. 
b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/methotrexate 

combination therapy using the Mann-Whitney U test 
c.   p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate monotherapy 

using the Mann-Whitney U test 
 
At week 52, 42.9% of patients who received Trudexa/methotrexate combination therapy achieved 
clinical remission (DAS28 < 2.6) compared to 20.6% of patients receiving methotrexate monotherapy 
and 23.4% of patients receiving Trudexa monotherapy.  Trudexa/methotrexate combination therapy 
was clinically and statistically superior to methotrexate (p < 0.001) and Trudexa monotherapy 
(p < 0.001) in achieving a low disease state in patients with recently diagnosed moderate to severe 
rheumatoid arthritis.  The response for the two monotherapy arms was similar (p = 0.447). 

Radiographic response 

In Study III, where Trudexa treated patients had a mean duration of rheumatoid arthritis of 
approximately 11 years, structural joint damage was assessed radiographically and expressed as 
change in modified total Sharp score and its components, the erosion score and joint space narrowing 
score.  Trudexa/methotrexate patients demonstrated significantly less radiographic progression than 
patients receiving methotrexate alone at 6 and 12 months (see Table 5).  Data from the open-label 
extension phase indicate that the reduction in rate of progression of structural damage is maintained 
for 60 months in a subset of patients.  113/207 of patients originally treated with 40 mg Humira every 
other week were evaluated radiographically at 5 years. Among those, 66 patients showed no 
progression of structural damage defined by a change in the TSS of zero or less. 
 

Table 5:  Radiographic Mean Changes Over 12 Months in Study III 
 

 Placebo/ 
MTXa 

TRUDEXA/MTX 
40 mg every 
other week 

Placebo/MTX-
TRUDEXA/MTX 
(95% Confidence 

Intervalb) 

P-value 

Total Sharp score 2.7 0.1 2.6 (1.4, 3.8)  < 0.001c 

Erosion score 1.6 0.0 1.6 (0.9, 2.2) < 0.001 
JSNd score 1.0 0.1 0.9 (0.3, 1.4)   0.002 

amethotrexate 
b95% confidence intervals for the differences in change scores between methotrexate and Trudexa.  
cBased on rank analysis  
dJoint Space Narrowing 
 



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In Study V, structural joint damage was assessed radiographically and expressed as change in 
modified total Sharp score (see Table 6). 
 

Table 6:  Radiographic Mean Changes at Week 52 in Study V 
 

 
MTX 
n=257 

(95% confidence 
interval) 

Trudexa 
n=274 

(95% confidence 
interval) 

Trudexa/MT
X 

n=268 
(95% confidence 

interval) 

p-valuea p-valueb p-valuec 

Total Sharp 
score 

5.7 (4.2-7.3) 3.0 (1.7-4.3) 1.3 (0.5-2.1) < 0.001 0.0020 < 0.001 

Erosion score 3.7 (2.7-4.7) 1.7 (1.0-2.4) 0.8 (0.4-1.2) < 0.001 0.0082 < 0.001 
JSN score 2.0 (1.2-2.8) 1.3 (0.5-2.1) 0.5 (0-1.0) < 0.001 0.0037 0.151 

a. p-value is from the pairwise comparison of methotrexate monotherapy and 
Trudexa/methotrexate combination therapy using the Mann-Whitney U test. 

b. p-value is from the pairwise comparison of Trudexa monotherapy and Trudexa/methotrexate 
combination therapy using the Mann-Whitney U test  

c.   p-value is from the pairwise comparison of Trudexa monotherapy and methotrexate 
monotherapy using the Mann-Whitney U test 

 
Following 52 weeks and 104 weeks of treatment, the percentage of patients without progression 
(change from baseline in modified total Sharp score ≤ 0.5) was significantly higher with 
Trudexa/methotrexate combination therapy (63.8% and 61.2% respectively) compared to methotrexate 
monotherapy (37.4% and 33.5% respectively, p < 0.001) and Trudexa monotherapy (50.7%, p < 0.002 
and 44.5%, p < 0.001 respectively). 

Quality of life and physical function  

Health-related quality of life and physical function was assessed using the disability index of the 
Health Assessment Questionnaire (HAQ) in the four original adequate and well-controlled trials, 
which was a pre-specified primary endpoint at week 52 in Study III.  All doses/schedules of Trudexa 
in all four studies showed statistically significantly greater improvement in the disability index of the 
HAQ from baseline to Month 6 compared to placebo and in Study III the same was seen at week 52.  
Results from the Short Form Health Survey (SF 36) for all doses/schedules of Trudexa in all four 
studies support these findings, with statistically significant physical component summary (PCS) 
scores, as well as statistically significant pain and vitality domain scores for the 40 mg every other 
week dose.  A statistically significant decrease in fatigue as measured by functional assessment of 
chronic illness therapy (FACIT) scores was seen in all three studies in which it was assessed (Studies 
I, III, IV). 
 
In Study III, improvement in physical function was maintained through week  260 (60 months) of 
open-label treatment.  Improvement in quality of life was measured up to week 156 (36 months) and 
improvement was maintained through that time. 
 
In Study V, the improvement in the HAQ disability index and the physical component of the SF 36 
showed greater improvement (p < 0.001) for Trudexa/methotrexate combination therapy versus 
methotrexate monotherapy and Trudexa monotherapy at week 52, which was maintained through 
week 104. 

Psoriatic arthritis 

Trudexa, 40 mg every other week, was studied in patients with moderately to severely active psoriatic 
arthritis in two placebo-controlled studies, Studies VI and VII.  Study VI with 24 week duration, 
treated 313 adult patients who had an inadequate response to non-steroidal anti-inflammatory drug 
therapy and of these, approximately 50% were taking methotrexate.  Study VII with 12-week duration, 
treated 100 patients who had an inadequate response to DMARD therapy. 



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There is insufficient evidence of the efficacy of Trudexa in patients with ankylosing spondylitis-like 
psoriatic arthropathy due to the small number of patients studied (see Table 7). 
 

Table 7:  ACR Response in Placebo-Controlled Psoriatic Arthritis Studies 
(Percent of Patients) 

 
 Study VI Study VII 

Response Placebo N=162 
Trudexa 
N=151 

Placebo  
N=49 

Trudexa 
N=51 

ACR 20      
 Week 12 14% 58%*** 16% 39%* 
 Week 24 15% 57%*** N/A N/A 
ACR 50      
 Week 12 4% 36%*** 2% 25%*** 
 Week 24 6% 39%*** N/A N/A 
ACR 70      
 Week 12 1% 20%*** 0% 14% * 
 Week 24 1% 23%*** N/A N/A 

*** p < 0.001 for all comparisons between Trudexa and placebo 
* p < 0.05 for all comparisons between Trudexa and placebo   
N/A  not applicable 

 
ACR responses in Study VI were similar with and without concomitant methotrexate therapy. 
Trudexa treated patients demonstrated improvement in physical function as assessed by HAQ and 
Short Form Health Survey (SF 36), from base-line to week 24. 

Ankylosing spondylitis 

Trudexa 40 mg every other week was assessed in 393 patients in two randomised, 24 week 
double − blind, placebo − controlled studies in patients with active ankylosing spondylitis (mean 
baseline score of disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] 
was 6.3 in all groups) who have had an inadequate response to conventional therapy.  Seventy-nine 
(20.1%) patients were treated concomitantly with disease modifying anti − rheumatic drugs, and 37 
(9.4%) patients with glucocorticoids.  The blinded period was followed by an open − label period 
during which patients received Trudexa 40 mg every other week subcutaneously for up to an 
additional 28 weeks.  Subjects (n=215, 54.7%) who failed to achieve ASAS 20 at Weeks 12, or 16 or 
20 received early escape open-label adalimumab 40 mg every other week subcutaneously and were 
subsequently treated as non-responders in the double-blind statistical analyses. 
 
In the larger study (VIII) with 315 patients, results showed statistically significant improvement of the 
signs and symptoms of ankylosing spondylitis in patients treated with Trudexa compared to placebo.  
Significant response was first observed at Week 2 and maintained through 24 weeks (Table 8).  

 
Table 8 - Efficacy Responses in Placebo-Controlled AS Study – Study VIII 

Reduction of Signs and Symptoms 
 

Response Placebo 
N=107 

Trudexa 
N=208 

ASASa 20   
             Week 2 16% 42%*** 

Week 12 21% 58%*** 
Week 24 19% 51%*** 

ASAS 50   
             Week 2 3% 16%*** 

Week 12 10% 38%*** 



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Week 24 11% 35%*** 
ASAS 70   
             Week 2 0% 7%** 

Week 12 5% 23%*** 
Week 24 8% 24%*** 

   
BASDAIb 50    
             Week 2 4% 20%*** 

Week 12  16% 45%*** 
Week 24  15% 42%*** 

***,** Statistically significant at p < 0.001, < 0.01 for all comparisons between Trudexa and placebo at Weeks 
2, 12 and  24 
a ASsessments in Ankylosing Spondylitis 
b Bath Ankylosing Spondylitis Disease Activity Index 

 
Trudexa treated patients had significantly greater improvement at Week 12 which was maintained 
through Week 24 in both the SF36 and Ankylosing Spondylitis Quality of Life Questionnaire 
(ASQoL). 
 
Similar trends (not all statistically significant) were seen in the smaller randomised, double − blind, 
placebo controlled study (IX) of 82 adult patients with active ankylosing spondylitis. 

Crohn’s Disease 

The safety and efficacy of Trudexa were assessed in over 1400 patients with moderately to severely 
active Crohn’s disease (Crohn’s Disease Activity Index (CDAI) ≥ 220 and ≤ 450) in randomised, 
double-blind, placebo-controlled studies.  478 of the enrolled patients (32%) were defined as having  a 
severe disease (CDAI score > 300 and concomitant corticosteroid and/or immunosuppressants) 
corresponding to the population defined in the indication (see section 4.1).  Concomitant stable doses 
of aminosalicylates, corticosteroids, and/or immunomodulatory agents were permitted and 79% of 
patients continued to receive at least one of these medications.  
 
Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies, CLASSIC I and 
GAIN.  In CLASSIC I, 299 TNF-antagonist naive patients were randomised to one of four treatment 
groups; placebo at weeks 0 and 2, 160 mg Trudexa at week 0 and 80 mg at week 2, 80 mg at week 0 
and 40 mg at week 2, and 40 mg at week 0 and 20 mg at week 2.  In GAIN, 325 patients who had lost 
response or were intolerant to infliximab were randomised to receive either 160 mg Trudexa at week 0 
and 80 mg at week 2 or placebo at weeks 0 and 2.  The primary non-responders were excluded from 
the studies and therefore these patients were not further evaluated. 
 
Maintenance of clinical remission was evaluated in CHARM.  In CHARM, 854 patients received 
open-label 80 mg at week 0 and 40 mg at week 2.  At week 4 patients were randomised to 40 mg every 
other week, 40 mg every week, or placebo with a total study duration of 56 weeks.  Patients in clinical 
response (decrease in CDAI ≥ 70) at week 4 were stratified and analysed separately from those not in 
clinical response at week 4.  Corticosteroid taper was permitted after week 8.  
 
CLASSIC I and GAIN induction of remission and response rates are presented in Table 9. 
 



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Table 9: Induction of Clinical Remission and Response 
(Percent of Patients) 

 CLASSIC I: Infliximab Naive Patients GAIN: Infliximab Experienced Patients 

 Placebo 

N=74 

Trudexa 

80/40 mg 

N = 75 

Trudexa  

160/80 m
g N=76 

Placebo 

N=166 

Trudexa  

160/80 mg 

N=159 

Week 4      

Clinical remission 12% 24% 36%* 7% 21%* 

Clinical response (CR-
100) 

24% 37% 49%** 25% 38%** 

All p-values are pairwise comparisons of proportions for Trudexa versus placebo 
* p < 0.001 
** p < 0.01 
 
Similar remission rates were observed for the 160/80 mg and 80/40 mg induction regimens by week 8 
and adverse events were more frequently noted in the 160/80 mg group. 
 
In CHARM, at week 4, 58% (499/854) of patients were in clinical response and were assessed in the 
primary analysis.  Of those in clinical response at week 4, 48% had been previously exposed to other 
anti-TNF therapy.  Maintenance of remission and response rates are presented in Table 10.  Clinical 
remission results remained relatively constant irrespective of previous TNF antagonist exposure. 
 

Table 10: Maintenance of Clinical Remission and Response 
(Percent of Patients) 

 Placebo 40 mg Trudexa 
every other week 

40 mg Trudexa 
every week 

Week 26 N=170 N=172 N=157 

Clinical remission 17% 40%* 47%* 

Clinical response (CR-100) 27% 52%* 52%* 

Patients in steroid-free remission  
for >=90 daysa 

3% (2/66) 19% (11/58)** 15% (11/74)** 

Week 56 N=170 N=172 N=157 

Clinical remission 12% 36%* 41%* 

Clinical response (CR-100) 17% 41%* 48%* 

Patients in steroid-free remission  
for >=90 daysa 

5% (3/66) 29% (17/58)* 20% (15/74)** 

* p < 0.001 for Trudexa versus placebo pairwise comparisons   of proportions 

** p < 0.02 for Trudexa versus placebo pairwise comparisons of proportions 
a Of those receiving corticosteroids at baseline 

 
Among patients who were not in response at week 4, 43% of Trudexa maintenance patients responded 
by week 12 compared to 30% of placebo maintenance patients.  These results suggest that some 
patients who have not responded by week 4 benefit from continued maintenance therapy through week 
12.  Therapy continued beyond 12 weeks did not result in significantly more responses (see section 
4.2).   

Quality of Life 

In CLASSIC I and GAIN, statistically significant improvement in the disease-specific inflammatory 
bowel disease questionnaire (IBDQ) total score was achieved at week 4 in patients randomised to 



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Trudexa 80/40 mg and 160/80 mg compared to placebo and was seen at weeks 26 and 56 in CHARM 
as well among the adalimumab treatment groups compared to the placebo group. 

Immunogenicity   

Formation of anti-adalimumab antibodies is associated with increased clearance and reduced efficacy 
of adalimumab.  There is no apparent correlation between the presence of anti-adalimumab antibodies 
and adverse events. 
 
Patients in Studies I, II and III were tested at multiple timepoints for antibodies to adalimumab during 
the 6 to 12 month period.  In the pivotal trials, anti-adalimumab antibodies were identified in 58/1053 
(5.5%) patients treated with adalimumab, compared to 2/370 (0.5%) on placebo.  In patients not given 
concomitant methotrexate, the incidence was 12.4%, compared to 0.6% when adalimumab was used as 
add-on to methotrexate.   
 
In patients with psoriatic arthritis, adalimumab antibodies were identified in 38/376 subjects (10%) 
treated with adalimumab.  In patients not given concomitant methotrexate, the incidence was 13.5% 
(24/178 subjects), compared to 7% (14 of 198 subjects) when adalimumab was used as add-on to 
methotrexate. 
 
In patients with ankylosing spondylitis antibodies were identified in 17/204 subjects (8.3%) treated 
with adalimumab.  In patients not given concomitant methotrexate, the incidence was 16/185 (8.6%), 
compared to 1/19 (5.3%) when adalimumab was used as add-on to methotrexate. 
 
In patients with Crohn’s disease, adalimumab antibodies were identified in 7/269 subjects (2.6%) 
treated with adalimumab. 
 
Because immunogenicity analyses are product-specific, comparison of antibody rates with those from 
other products is not appropriate. 

5.2 Pharmacokinetic properties 

After subcutaneous administration of a single 40 mg dose, absorption and distribution of adalimumab 
was slow, with peak serum concentrations being reached about 5 days after administration.  The 
average absolute bioavailability of adalimumab estimated from three studies following a single 40 mg 
subcutaneous dose was 64%.  After single intravenous doses ranging from 0.25 to 10 mg/kg, 
concentrations were dose proportional.  After doses of 0.5 mg/kg (~40 mg), clearances ranged from 11 
to 15 ml/hour, the distribution volume (Vss) ranged from 5 to 6 litres and the mean terminal phase half-
life was approximately two weeks.  Adalimumab concentrations in the synovial fluid from several 
rheumatoid arthritis patients ranged from 31-96% of those in serum. 
 
Following subcutaneous administration of 40 mg of Trudexa every other week in rheumatoid arthritis 
(RA) patients the mean steady-state trough concentrations were approximately 5 µg/ml (without 
concomitant methotrexate) and 8 to 9 µg/ml (with concomitant methotrexate), respectively.  The 
serum adalimumab trough levels at steady-state increased roughly proportionally with dose following 
20, 40 and 80 mg every other week and every week subcutaneous dosing. 
 
In patients with Crohn’s disease, the loading dose of 80 mg Trudexa on week 0 followed by 40 mg 
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 5.5 µg/ml 
during the induction period.  A loading dose of 160 mg Trudexa on week 0 followed by 80 mg 
Trudexa on week 2 achieves serum adalimumab trough concentrations of approximately 12 µg/ml 
during the induction period.  Mean steady-state trough levels of approximately 7 µg/ml were observed 
in Crohn’s disease patients who received a maintenance dose of 40 mg Trudexa every other week. 
 
Population pharmacokinetic analyses with data from over 1300 RA patients revealed a trend toward 
higher apparent clearance of adalimumab with increasing body weight.  After adjustment for weight 
differences, gender and age appeared to have a minimal effect on adalimumab clearance.  The serum 



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levels of free adalimumab (not bound to anti-adalimumab antibodies, AAA) were observed to be lower 
in patients with measurable AAA.  Trudexa has not been studied in children or in patients with hepatic 
or renal impairment. 

5.3 Preclinical safety data  

Non-clinical data reveal no special hazard for humans based on studies of single dose toxicity, 
repeated dose toxicity, and genotoxicity.   
 
An embryo-foetal developmental toxicity/perinatal developmental study has been performed in 
cynomologous monkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evidence 
of harm to the foetuses due to adalimumab.  Carcinogenicity studies, and standard assessment of 
fertility and postnatal toxicity, were not performed with adalimumab due to the lack of appropriate 
models for an antibody with limited cross-reactivity to rodent TNF and the development of 
neutralizing antibodies in rodents.  

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients  

Mannitol  
Citric acid monohydrate 
Sodium citrate 
Sodium dihydrogen phosphate dihydrate 
Disodium phosphate dihydrate 
Sodium chloride 
Polysorbate 80 
Sodium hydroxide 
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  

18 months 

6.4 Special precautions for storage  

Store in a refrigerator (2°C – 8°C).  Keep the pre-filled pen in the outer carton.  Do not freeze. 

6.5 Nature and contents of container   

Trudexa 40 mg solution for injection in single-use pre-filled pen for patient use. 
 
Packs of: 
• 1 pre-filled pen with 1 alcohol pad in a blister.  
• 2 pre-filled pen, each with 1 alcohol pad, in a blister.  
• 4 pre-filled pen, each with 1 alcohol pad, in a blister.  
• 6 pre-filled pen, each with 1 alcohol pad, in a blister. 
 
Not all pack sizes may be marketed. 

6.6 Special precautions for disposal 



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

7. MARKETING AUTHORISATION HOLDER  

Abbott Laboratories Ltd.  
Queenborough 
Kent ME11 5EL 
United Kingdom 

8. MARKETING AUTHORISATION NUMBER(S)  

EU/1/03/257/007 
EU/1/03/257/008 
EU/1/03/257/009 
EU/1/03/257/010 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

1 September 2003 

10. DATE OF REVISION OF THE TEXT 

{MM/YYYY} 
 
 



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ANNEX II 
 
A. MANUFACTURER(S) OF THE OF THE BIOLOGICAL 

ACTIVE SUBSTANCE(S) AND MANUFACTURING 
AUTHORISATION HOLDER(S) RESPONSIBLE FOR 
BATCH RELEASE 
 

B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
 



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

 
Name and address of the manufacturer of the biological active substance 
 
Abbott Bioresearch Center 
100 Research Drive 
Worcester 
MA 01605 
USA 
 
and 
 
Abbott Biotechnology Ltd. 
Road No. 2, Km. 59.2 
Barceloneta 
Puerto Rico  00617 
 
Name and address of the manufacturer responsible for batch release 
 
Abbott Biotechnology Deutschland GmbH 
Max-Planck-Ring 2 
D-65205 Wiesbaden 
Germany 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2). 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable. 
 
• OTHER CONDITIONS 
 
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in 
the pharmacovigilance plan.  
 
An updated risk management plan should be provided as per the CHMP guideline on the risk 
management systems for medicinal products for human use. 
 
The marketing authorisation holder should submit 6 monthly periodic safety update reports. 



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



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A. LABELLING 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection  
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml vial contains 40 mg adalimumab 

3. LIST OF EXCIPIENTS 

Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

1 vial containing 40 mg adalimumab  
1 sterile injection syringe with fixed needle  
2 alcohol pads  

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use. 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the vial in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/001 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 
 

16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection 
Adalimumab 
 
Store in a refrigerator. 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Abbott Laboratories Ltd. 

3. EXPIRY DATE 

EXP {MM/YYYY} 

4. BATCH NUMBER 

LOT:  

5. OTHER 

 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 

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

Trudexa 40 mg injection 
Subcutaneous use 

2. METHOD OF ADMINISTRATION 
 

3. EXPIRY DATE 

EXP {MM/YYYY} 

4. BATCH NUMBER 

LOT:  

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

40 mg/0.8 ml 

6. OTHER 

 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled syringe 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled syringe contains 40 mg adalimumab  

3. LIST OF EXCIPIENTS 

Excipients:  mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

1 pre-filled syringe containing 40 mg adalimumab 
1 alcohol pad 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

 
Store in a refrigerator.  Keep the syringe in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/002 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 
 

16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled syringe 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled syringe contains 40 mg adalimumab  

3. LIST OF EXCIPIENTS 

Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

2 pre-filled syringes, each containing 40 mg adalimumab 
2 alcohol pads  

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the syringe in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/003 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 
 

16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled syringe 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled syringe contains 40 mg adalimumab  

3. LIST OF EXCIPIENTS 

Excipients:  mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

4 pre-filled syringes, each containing 40 mg adalimumab 
4 alcohol pads 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the syringe in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/004 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 
 

16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled syringe 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled syringe contains 40 mg adalimumab  

3. LIST OF EXCIPIENTS 

Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

6 pre-filled syringes, each containing 40 mg adalimumab 
6 alcohol pads  

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the syringe in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/005 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 

 
16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled syringe 
Adalimumab 
 
Store in a refrigerator. 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Abbott Laboratories Ltd 

3. EXPIRY DATE 

EXP {MM/YYYY} 

4. BATCH NUMBER 

LOT:  

5. OTHER 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 

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

Trudexa 40 mg injection 
 
Subcutaneous use 

2. METHOD OF ADMINISTRATION 
 

3. EXPIRY DATE 

EXP {MM/YYYY} 

4. BATCH NUMBER 

LOT:  

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

40 mg/0.8 ml 

6. OTHER 

 
 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING OR, WHERE THERE IS NO 
OUTER PACKAGING, ON THE IMMEDIATE PACKAGING 

OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled syringe with needleguard 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled syringe with needleguard contains 40 mg adalimumab 

3. LIST OF EXCIPIENTS 

Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

1 pre-filled syringe containing 40 mg adalimumab  
1 alcohol pad 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use. 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the syringe in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/006 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 

 
16. INFORMATION IN BRAILLE 

Trudexa 40 mg 
 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

TRAY BACKING TEXT 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled syringe with needleguard 
Adalimumab 
 
Store in a refrigerator. 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Abbott Laboratories Ltd. 

3. EXPIRY DATE 

EXP {MM/YYYY} 

4. BATCH NUMBER 

LOT:  

5. OTHER 

 



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107 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE LABEL 
 

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

Trudexa 40 mg injection  
Subcutaneous use 

2. METHOD OF ADMINISTRATION 
 

3. EXPIRY DATE 

EXP {MM/YYYY} 

4. BATCH NUMBER 

LOT:  

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

40 mg/0.8 ml 

6. OTHER 

 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled pen 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled pen contains 40 mg adalimumab  

3. LIST OF EXCIPIENTS 

Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

1 pre-filled pen, containing 40 mg adalimumab 
1 alcohol pad  

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the pre-filled pen in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/007 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 

 
16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled pen 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled pen contains 40 mg adalimumab  

3. LIST OF EXCIPIENTS 

Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

2 pre-filled pens, each containing 40 mg adalimumab 
2 alcohol pads  

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the pre-filled pen in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/008 
 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 

 
16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled pen 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled pen contains 40 mg adalimumab  

3. LIST OF EXCIPIENTS 

Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

4 pre-filled pens, each containing 40 mg adalimumab 
4 alcohol pads  

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the pre-filled pen in the outer carton. 
Do not freeze. 



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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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/009 
 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 

 
16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled pen 
Adalimumab 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

One 0.8 ml pre-filled pen contains 40 mg adalimumab  

3. LIST OF EXCIPIENTS 

Excipients: mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen phosphate 
dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium hydroxide and 
water for injections.  See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS 

6 pre-filled pens, each containing 40 mg adalimumab 
6 alcohol pads  

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Subcutaneous use 
 
Read the package leaflet before use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE REACH AND SIGHT OF CHILDREN 

Keep out of the reach and sight of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 

8. EXPIRY DATE 

EXP {MM/YYYY} 

9. SPECIAL STORAGE CONDITIONS 

Store in a refrigerator.  Keep the pre-filled pen in the outer carton. 
Do not freeze. 



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115 

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 

Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/03/257/010 

13. BATCH NUMBER 

LOT:  

14. GENERAL CLASSIFICATION FOR SUPPLY 

Medicinal product subject to medical prescription. 

15. INSTRUCTIONS ON USE 

 
16. INFORMATION IN BRAILLE 

Trudexa 40 mg 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TRAY BACKING TEXT 
 

1. NAME OF THE MEDICINAL PRODUCT 

Trudexa 40 mg solution for injection in pre-filled pen 
Adalimumab 
 
Store in a refrigerator. 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

Abbott Laboratories Ltd 

3. EXPIRY DATE 

EXP {MM/YYYY} 

4. BATCH NUMBER 

LOT:  

5. OTHER 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PEN LABEL 
 

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

Trudexa 40 mg injection 
 
Subcutaneous use 

2. METHOD OF ADMINISTRATION 
 

3. EXPIRY DATE 

EXP {MM/YYYY} 

4. BATCH NUMBER 

LOT:  

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

40 mg/0.8 ml 

6. OTHER 

 
 



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REMINDER STICKERS TEXT (included in pack) 
 
 
Trudexa  
 
Mark your calendar with the stickers provided to remind you of the date for your next dose. 
 



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PATIENT ALERT CARD TEXT (NOT INCLUDED IN PACK OR AS PART OF THE 
PACKAGE LEAFLET) 
 
 

Trudexa Patient Alert Card 
 

This alert card contains important safety 
information that you need to be aware of before 
you are given Trudexa and during treatment with 
Trudexa.  

 
• Show this card to any doctor involved in your 

treatment. 
 
Infections 
 
Trudexa increases the risk of getting infections. 
Infections may progress more rapidly and be 
more severe. This includes tuberculosis. 
 
Prior to Trudexa treatment: 
• You should not be treated with Trudexa if 

you have a severe infection. 
• You should be screened for tuberculosis. It is 

very important that you tell your doctor if you 
have ever had tuberculosis, or if you have 
been in close contact with someone who has 
had tuberculosis. Please record the dates of 
the last screening for tuberculosis below: 

Tuberculin test: _______________ 
Chest X-ray:  _______________ 
 
During Trudexa treatment: 
• If you develop symptoms suggestive of 

infections, such as fever, persistent cough, 
weight loss, or listlessness, seek medical 
attention immediately. 

 

Heart Failure 
 
Prior to Trudexa treatment: 
• Trudexa should not be used if you have 

moderate to severe heart failure. 
 
During Trudexa treatment: 
• If you develop symptoms of heart failure 

(shortness of breath or swelling of the feet) 
seek medical attention immediately. 

 
Dates of Trudexa treatment: 
1 st injection: _______________________ 
Following injections: 
_______________________ 
_______________________ 
_______________________ 
_______________________ 
 
• See the Trudexa package leaflet for more 

information.  
• Please make sure you also have a list of all 

your other medicines with you at any visit to 
a health care professional. 

 
Patient’s Name: _____________________ 
Doctor’s Name: _____________________ 
Doctor’s Phone: _____________________ 
 
• Keep this card with you for 5 months after the 

last Trudexa dose, since side effects may 
occur a long time after your last dose of 
Trudexa. 

 

 
 



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B. PACKAGE LEAFLET 
 

 



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PACKAGE LEAFLET:  INFORMATION FOR THE USER 
 

Trudexa 40 mg solution for injection in vials 
Adalimumab 

 
 

Read all of this leaflet carefully before you start using this medicine. 
− Keep this leaflet.  You may need to read it again. 
− Your doctor will also give you a Patient Alert Card, which contains important safety 

information that you need to be aware of before you are given Trudexa and during treatment 
with Trudexa.  Keep this Patient Alert Card together with the package leaflet. 

− If you have any further questions, please ask your doctor or pharmacist. 
− This medicine has been prescribed for you.  Do not pass it on to others.  It may harm them, even 

if their symptoms are the same as yours. 
− If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Trudexa is and what it is used for 
2. Before you use Trudexa 
3. How to use Trudexa 
4. Possible side effects 
5 How to store Trudexa 
6. Further information 
 

1. WHAT TRUDEXA IS AND WHAT IT IS USED FOR 

Trudexa is intended for treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.  
It is a medicine that decreases the inflammation process of these diseases.  The active ingredient, 
adalimumab, is a human monoclonal antibody produced by cultured cells.  Monoclonal antibodies are 
proteins that recognise and bind to other unique proteins.  Adalimumab binds to a specific protein 
(tumour necrosis factor or TNFα), which is present at increased levels in inflammatory diseases such 
as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. 

Rheumatoid arthritis 

Rheumatoid arthritis is an inflammatory disease of the joints.  If you have moderate to severe active 
rheumatoid arthritis, you may first be given other disease-modifying medicines, such as methotrexate.  
If you do not respond well enough to these medicines, you will be given Trudexa to treat your 
rheumatoid arthritis.   
 
Trudexa can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Trudexa has been shown to slow down the damage to the cartilage and bone of the joints caused by the 
disease and to improve physical function.  
 
Usually, Trudexa is used with methotrexate.  If your doctor determines that methotrexate is 
inappropriate, Trudexa can be given alone.  

Psoriatic arthritis 

Psoriatic arthritis is an inflammation of the joints associated with psoriasis. 



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Ankylosing spondylitis 

Ankylosing spondylitis is an inflammatory disease of the spine.  If you have ankylosing spondylitis 
you will first be given other medicines.  If you do not respond well enough to these medicines, you 
will be given Trudexa to reduce the signs and symptoms of your disease. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract.  If you have Crohn’s disease you will 
first be given other medicines.  If you do not respond well enough to these medicines, you will be 
given Trudexa to reduce the signs and symptoms of your disease. 

2. BEFORE YOU USE TRUDEXA 

Do not use Trudexa:  

• If you are allergic (hypersensitive) to adalimumab or any of the other ingredients of Trudexa.  
 
• If you have a severe infection, including active tuberculosis (see “Take special care with 

Trudexa”).  It is important that you tell your doctor if you have symptoms of infections, e.g. 
fever, wounds, feeling tired, dental problems. 

 
• If you have moderate or severe heart failure.  It is important to tell your doctor if you have had 

or have a serious heart condition (see “Take special care with Trudexa”). 

Take special care with Trudexa:  

• If you experience allergic reactions such as chest tightness, wheezing, dizziness, swelling or 
rash do not inject more Trudexa and contact your doctor immediately. 

 
• The needle cover of the syringe contains natural rubber (latex).  This may cause severe allergic 

reactions in patients sensitive to latex.  Patients who have a known sensitivity to latex should be 
advised to avoid touching the inner shield. 

 
• If you have an infection, including long-term or localized infection (for example, leg ulcer) 

consult your doctor before starting Trudexa.  If you are unsure, please contact your doctor.  
 
• You might get infections more easily while you are receiving Trudexa treatment including 

serious infections, tuberculosis, opportunistic infections and sepsis that may, in rare cases, be 
life-threatening.  It is important to tell your doctor if you get symptoms such as fever, wounds, 
feeling tired or dental problems.  

 
• As cases of tuberculosis have been reported in patients treated with Trudexa, your doctor will 

check you for signs and symptoms of tuberculosis before starting Trudexa.  This will include a 
thorough medical history, a chest X-ray and a tuberculin test.  The conduct of these tests should 
be recorded on your Patient Alert Card.  It is very important that you tell your doctor if you 
have ever had tuberculosis, or if you have been in close contact with someone who has had 
tuberculosis.  If symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild 
fever), or any other infection appear during or after therapy tell your doctor immediately. 

 
• Advise your doctor if you have a history of recurrent infections or other conditions that increase 

the risk of infections. 
 
• Advise your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV 

or if you think you might be at risk of contracting HBV.  Trudexa can cause reactivation of 



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HBV in people who carry this virus.  In some rare cases, especially if you are taking other 
medicines that suppress the immune system, reactivation of HBV can be life-threatening.   

 
• If you are about to undergo surgery or dental procedures please inform your doctor that you are 

taking Trudexa. 
 
• If you have multiple sclerosis, your doctor will decide if you should receive Trudexa. 
 
• Some vaccines should not be given while receiving Trudexa.  Please check with your doctor 

before you receive any vaccines. 
 
• If you have mild heart failure and you are being treated with Trudexa, your heart failure status 

must be closely monitored by your doctor.  It is important to tell your doctor if you have had or 
have a serious heart condition.  If you develop new or worsening symptoms of heart failure (e.g. 
shortness of breath, or swelling of your feet), you must contact your doctor immediately.   

 
• In some patients the body may fail to produce enough of the blood cells that help your body 

fight infections or help you to stop bleeding.  If you develop a fever that does not go away, 
bruise or bleed very easily or look very pale, call your doctor right away.  Your doctor may 
decide to stop treatment. 

 
• There have been very rare cases of certain kinds of cancer in patients taking Trudexa or other 

TNF blockers.  People with more serious rheumatoid arthritis that have had the disease for a 
long time may have a higher than average risk of getting a kind of cancer that affects the lymph 
system, called lymphoma.  If you take Trudexa your risk may increase.  In addition very rare 
cases of non-melanoma skin cancer have been observed in patients taking Trudexa. 

 
• Cancers, other than lymphoma, have been reported in patients with a specific type of lung 

disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF 
blocker.  If you have COPD, or are a heavy smoker, you should discuss with your doctor 
whether treatment with a TNF blocker is appropriate for you. 

Using other medicines 

Trudexa can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), steroids or pain 
medications including non-steroidal anti-inflammatory drugs. 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
You should not take Trudexa with medicines containing the active substance, anakinra.  If you have 
questions, please ask your doctor. 
 
Using Trudexa with food and drink 
 
Since Trudexa is given subcutaneously, food and drink should not affect Trudexa. 

Pregnancy and breast-feeding 

The effects of Trudexa in pregnant women are not known and so the use of Trudexa in pregnant 
women is not recommended.  You are advised to avoid becoming pregnant and must use adequate 
contraception while using Trudexa and for at least 5 months after the last Trudexa treatment.  
 
It is not known whether adalimumab passes into breast milk. 
 



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If you are a breast-feeding mother, you should stop breast-feeding during Trudexa treatment and for at 
least 5 months after the last Trudexa treatment.  
 
Driving and using machines 
 
Trudexa should not affect your ability to drive or use machinery. 
 
Important information about some of the ingredients of Trudexa 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’. 

3. HOW TO USE TRUDEXA 

Always take Trudexa exactly as your doctor has told you.  You should check with your doctor or 
pharmacist if you are not sure.  
 
Trudexa is injected under the skin (subcutaneous use).  The usual dose for adults with rheumatoid 
arthritis, psoriatic arthritis and ankylosing spondylitis is 40 mg adalimumab given every other week as 
a single dose.  The usual dose regimen for Crohn’s disease is 80 mg at week 0 and followed by 40 mg 
every other week starting at week 2.  In cases where a more rapid response is required your doctor 
may prescribe a dose of 160 mg at week 0 (as 4 injections in one day or 2 injections per day for two 
consecutive days), 80 mg (2 injections) at week 2, and thereafter as 40 mg (1 injection) every other 
week.  Depending on your response, your doctor may increase the dose to 40 mg every week.  You 
should continue to inject Trudexa for as long as your doctor has told you.   
 
In rheumatoid arthritis, methotrexate is continued while using Trudexa.  If your doctor determines that 
methotrexate is inappropriate, Trudexa can be given alone. 
 
If you have rheumatoid arthritis and you do not receive methotrexate with your Trudexa therapy, your 
doctor may decide to give 40 mg adalimumab every week.  

Instructions for preparing and giving an injection of Trudexa: 

The following instructions explain how to inject Trudexa.  Please read the instructions carefully and 
follow them step by step.  You will be instructed by your doctor or his/her assistant on the technique 
of self-injection.  Do not attempt to self-inject until you are sure that you understand how to prepare 
and give the injection.  After proper training, the injection can be self-administered or given by 
another person, for example a family member or friend. 
 
This injection should not be mixed in the same syringe or vial with any other medicine. 

1)  Setting up  

• Wash your hands thoroughly  
• Set up the following items on a clean surface 

 
o One vial of Trudexa for injection 
o One syringe with fixed needle 
o Two alcohol pads 



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• Look at the expiry date on the vial.  Do not use the product after the month and year shown. 

2)  Choosing and preparing an injection site  

• Choose a site on your thigh or stomach 
 
 

 
 
• Each new injection should be given at least 3 cm from the last injection site.  

o Do not inject in an area where the skin is reddened, bruised, or hard.  This may mean 
there is an infection. 

o Wipe the injection site with the enclosed alcohol pad, using a circular motion. 
o Do not touch the area again before injecting. 

3)  Injecting Trudexa  

Preparing the Trudexa dose for injection 
• Do NOT shake the vial.  
• Remove the plastic cap from the Trudexa vial.  Do NOT remove the grey stopper or aluminium 

ring around the top of the vial. 
• Use a new alcohol pad to clean the grey stopper on the vial.  After cleaning, do not touch the 

stopper with your hands. 
• Remove cap from needle syringe, being careful not to touch needle or let it touch any surface. 
• Make sure that the plunger is fully inserted into the syringe.  With the vial upright on a flat 

surface, such as a table, insert the needle straight through the centre ring of the grey stopper.  If 
the needle is correctly lined up, you should feel a slight resistance and then a “pop” as the 
needle goes through the centre of the stopper.  Look for the needle tip inside the stopper 
window.  If the needle is not correctly lined up with the centre of the stopper, you will feel 
constant resistance as it goes through the stopper and no “pop.”  The needle may then enter at an 
angle and bend, break or prevent proper removal of the vial contents.  If this happens, do not 
use the syringe or vial. 



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• With the needle still in the vial, turn the vial upside down at eye level.  Check that the needle is 
below the surface of the solution.  Slowly pull the plunger back to draw solution into the 
syringe.   

• With the needle still inserted in the vial, check the syringe for air bubbles.  Gently tap the 
syringe to make any bubbles rise to the top of the syringe near the needle.  Slowly press the 
plunger to push the bubbles out of the syringe and into the vial.  When you do this, if you 
accidentally push some solution back into the vial, pull slowly back in the plunger to draw the 
entire contents of the vial back into the syringe. 

• Pull the needle completely out of the vial.  Again, do NOT touch the needle or let it touch any 
surface. 

 
Injecting Trudexa 
• With one hand, gently grasp the cleaned areas of skin and hold firmly  
• With the other hand, hold syringe at 45-degree angle to skin, with the grooved side up. 
 
 

• With one quick, short motion, push needle all the way into skin 
• Release the skin with the first hand 
• Push plunger to inject solution – it can take from 2 to 5 seconds to empty the syringe 
• When the syringe is empty, remove the needle from skin, being careful to keep it at the same 

angle as when it was inserted 
• Using your thumb or a piece of gauze, apply pressure over the injection site for 10 seconds.  A 

little bleeding may occur.  Do not rub the injection site.  Use a plaster if you want to.  

4)  Throwing away supplies 

• The Trudexa syringe should NEVER be reused.  NEVER recap a needle 
• After injecting Trudexa, immediately throw away the used syringe in a special container as 

instructed by your doctor, nurse or pharmacist. 
• Keep this container out of the reach and sight of children 

If you use more Trudexa than you should: 

If you accidentally inject Trudexa more frequently than told to by your doctor, you should call your 
doctor and tell him/her that you have taken more.  Always take the outer carton or the vial of medicine 
with you, even if it is empty.  

If you forget to take Trudexa: 

If you forget to give yourself an injection, you should inject the next dose of Trudexa as soon as you 
remember.  Then take your next dose as you would have on your originally scheduled day, had you 
not forgotten a dose.  
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 



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4. POSSIBLE SIDE EFFECTS 

Like all medicines, Trudexa can have side effects, although not everybody gets them.  Most side 
effects are mild to moderate.  However, some may be serious and require treatment.  Side effects may 
occur at least up to 5 months after the last treatment.   
 
Tell your doctor immediately if you notice any of the following:  
• Severe rash, hives or other signs of allergic reaction;  
• Swollen face, hands, feet; 
• Trouble breathing, swallowing; 
• Shortness of breath with exertion or upon lying down or swelling of the feet; 
• Signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness. 
 
Tell your doctor as soon as possible if you notice any of the following:  
• Signs of infection such as fever, malaise, wounds, dental problems, burning on urination; 
• Feeling weak or tired; 
• Coughing; 
• Tingling; 
• Numbness; 
• Double vision; 
• Arm or leg weakness. 
 
The symptoms described above can be signs of the below listed side effects, which have been 
observed with Trudexa: 
 
Very common (≥ 1/10 patients):  
 
• injection site reactions (including pain, swelling, redness or itching). 
 
Common (≥ 1/100 and < 1/10 patients):   
• lower respiratory tract infections (such as bronchitis, pneumonia); 
• upper respiratory tract infections (including cold, runny nose, sinus infection); 
• urinary tract infection, cold blisters, shingles; 
• dizziness, including vertigo, headache; 
• eye inflammation; 
• cough, sore throat; 
• nausea, diarrhoea, abdominal pain, mouth ulcers; 
• elevated liver enzymes; 
• rash, itching, hair loss; 
• fatigue; 
• fever. 
 
Uncommon (≥ 1/1000 and< 1/100 patients):   
• serious infections (such as sepsis [blood poisoning]), joint infection, fungal infections; 
• skin wart; 
• anaemia, low white blood cell counts; 
• allergic reactions;  
• increased lipid values, appetite disorders; 
• anxiety, depression, feeling sleepy and difficulty sleeping; 
• nerve disorders (such as multiple sclerosis and eye nerve inflammation), taste disturbances; 
• vision disturbances;  
• ear discomfort; 
• sensation of heart beating rapidly, high blood pressure; 



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• asthma, shortness of breath; 
• abdominal symptoms (such as vomiting, indigestion, constipation) rectal bleeding; 
• skin disorders (such as psoriasis, eczema or infections), itchy rash, slow wound healing; 
• muscle weakness; 
• urinary disturbances (such as blood in urine, increased urinary frequency); 
• increased menstrual bleeding; 
• flu like symptoms, chest pain, swelling of the feet. 
 
Rare (< 1/1000) 
• glaucoma; 
• skin cancer; 
• thyroid disorders; 
• protein in urine. 
 
Other side effects that have been observed in patients taking Trudexa:  
tuberculosis and other opportunistic infections (infections that occur when resistance to disease is 
lowered); 
lung disease. 
 
If any side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your 
doctor or pharmacist.  

5. HOW TO STORE TRUDEXA 

Keep out of the reach and sight of children.  
 
Do not use the Trudexa vial after the expiry date stated on the label/blister/carton after EXP:.  The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C).  Keep the vial in the outer carton.  Do not freeze. 

6. FURTHER INFORMATION 

Trudexa 40 mg solution for injection in vials is supplied as a sterile solution of 40 mg adalimumab 
dissolved in 0.8 ml solution. 
 
What Trudexa contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen 
phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium 
hydroxide and water for injections. 
 
What the Trudexa vial looks like and contents of the pack 
 
The Trudexa vial is a glass vial containing a solution of adalimumab.  Each pack contains 1 vial with 
an empty sterile syringe and 2 alcohol pads. 
 
Trudexa is also available as a pre-filled syringe or a pre-filled pen. 
 



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Marketing Authorisation Holder 
 
Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 
 
Manufacturer  
 
Abbott Biotechnology Deutschland GmbH 
Max-Planck-Ring 2 
D – 65205 Wiesbaden 
Germany 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Abbott SA 
Parc Scientifique 
Rue du Bosquet, 2 
B-1348 Ottignies/Louvain-la-Neuve 
Tél/Tel: + 32 10 475311 
 

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Tel: + 43 1 891-22 



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Ελλάδα 
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Lietuva 
Abbott Laboratories Baltics 

 



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Vienibas 87h  
LV-1004 Rīga 
Latvia 
Tel: + 371 7605580 
 
 
 
This leaflet was last approved in {MM/YYYY} 
 
 
 



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PACKAGE LEAFLET:  INFORMATION FOR THE USER 
 

Trudexa 40 mg solution for injection in pre-filled syringe 
Adalimumab 

 
 

Read all of this leaflet carefully before you start using this medicine. 
− Keep this leaflet. You may need to read it again. 
− Your doctor will also give you a Patient Alert Card, which contains important safety 

information that you need to be aware of before you are given Trudexa and during treatment 
with Trudexa.  Keep this Patient Alert Card together with the package leaflet.  

− If you have any further questions, please ask your doctor or pharmacist. 
− This medicine has been prescribed for you.  Do not pass it on to others.  It may harm them, even 

if their symptoms are the same as yours. 
− If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Trudexa is and what it is used for 
2. Before you use Trudexa 
3. How to use Trudexa 
4. Possible side effects 
5 How to store Trudexa 
6. Further information 

1. WHAT TRUDEXA IS AND WHAT IT IS USED FOR 

Trudexa is intended for treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.  
It is a medicine that decreases the inflammation process of these diseases.  The active ingredient, 
adalimumab, is a human monoclonal antibody produced by cultured cells.  Monoclonal antibodies are 
proteins that recognise and bind to other unique proteins.  Adalimumab binds to a specific protein 
(tumour necrosis factor or TNFα), which is present at increased levels in inflammatory diseases such 
as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. 
 
Rheumatoid arthritis 
 
Rheumatoid arthritis is an inflammatory disease of the joints.  If you have moderate to severe active 
rheumatoid arthritis, you may first be given other disease-modifying medicines, such as methotrexate.  
If you do not respond well enough to these medicines, you will be given Trudexa to treat your 
rheumatoid arthritis.   
 
Trudexa can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Trudexa has been shown to slow down the damage to the cartilage and bone of the joints caused by the 
disease and to improve physical function. 
 
Usually, Trudexa is used with methotrexate.  If your doctor determines that methotrexate is 
inappropriate, Trudexa can be given alone. 

Psoriatic arthritis 

Psoriatic arthritis is an inflammation of the joints associated with psoriasis. 



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Ankylosing spondylitis 

Ankylosing spondylitis is an inflammatory disease of the spine.  If you have ankylosing spondylitis 
you will first be given other medicines.  If you do not respond well enough to these medicines, you 
will be given Trudexa to reduce the signs and symptoms of your disease. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract.  If you have Crohn’s disease you will 
first be given other medicines.  If you do not respond well enough to these medicines, you will be 
given Trudexa to reduce the signs and symptoms of your disease. 

2. BEFORE YOU USE TRUDEXA 

Do not use Trudexa:  

• If you are allergic (hypersensitive) to adalimumab or any of the other ingredients of Trudexa. 
 
• If you have a severe infection, including active tuberculosis (see “Take special care with 

Trudexa”).  It is important that you tell your doctor if you have symptoms of infections, e.g. 
fever, wounds, feeling tired, dental problems. 

 
• If you have moderate or severe heart failure.  It is important to tell your doctor if you have had 

or have a serious heart condition (see “Take special care with Trudexa”). 

Take special care with Trudexa:  

• If you experience allergic reactions such as chest tightness, wheezing, dizziness, swelling or 
rash do not inject more Trudexa and contact your doctor immediately.  

 
• The needle cover of the syringe contains natural rubber (latex).  This may cause severe allergic 

reactions in patients sensitive to latex.  Patients who have a known sensitivity to latex should be 
advised to avoid touching the inner shield. 

 
• If you have an infection, including long-term or localized infection (for example, leg ulcer) 

consult your doctor before starting Trudexa.  If you are unsure, please contact your doctor.  
 
• You might get infections more easily while you are receiving Trudexa treatment including 

serious infections, tuberculosis, opportunistic infections and sepsis that may, in rare cases, be 
life-threatening.  It is important to tell your doctor if you get symptoms such as fever, wounds, 
feeling tired or dental problems. 

 
• As cases of tuberculosis have been reported in patients treated with Trudexa, your doctor will 

check you for signs and symptoms of tuberculosis before starting Trudexa.  This will include a 
thorough medical history, a chest X-ray and a tuberculin test.  The conduct of these tests should 
be recorded on your Patient Alert Card.  It is very important that you tell your doctor if you 
have ever had tuberculosis, or if you have been in close contact with someone who has had 
tuberculosis.  If symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild 
fever), or any other infection appear during or after therapy tell your doctor immediately.  

 
• Advise your doctor if you have a history of recurrent infections or other conditions that increase 

the risk of infections. 
 
• Advise your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV 

or if you think you might be at risk of contracting HBV.  Trudexa can cause reactivation of 



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HBV in people who carry this virus.  In some rare cases, especially if you are taking other 
medicines that suppress the immune system, reactivation of HBV can be life-threatening.   

 
• If you are about to undergo surgery or dental procedures please inform your doctor that you are 

taking Trudexa. 
 
• If you have multiple sclerosis, your doctor will decide if you should receive Trudexa. 
 
• Some vaccines should not be given while receiving Trudexa.  Please check with your doctor 

before you receive any vaccines. 
 
• If you have mild heart failure and you are being treated with Trudexa, your heart failure status 

must be closely monitored by your doctor.  It is important to tell your doctor if you have had or 
have a serious heart condition.  If you develop new or worsening symptoms of heart failure (e.g. 
shortness of breath, or swelling of your feet), you must contact your doctor immediately. 

 
• In some patients the body may fail to produce enough of the blood cells that help your body 

fight infections or help you to stop bleeding.  If you develop a fever that does not go away, 
bruise or bleed very easily or look very pale, call your doctor right away.  Your doctor may 
decide to stop treatment. 

 
• There have been very rare cases of certain kinds of cancer in patients taking Trudexa or other 

TNF blockers.  People with more serious rheumatoid arthritis that have had the disease for a 
long time may have a higher than average risk of getting a kind of cancer that affects the lymph 
system, called lymphoma.  If you take Trudexa your risk may increase.  In addition very rare 
cases of non-melanoma skin cancer have been observed in patients taking Trudexa. 

 
• Cancers, other than lymphoma, have been reported in patients with a specific type of lung 

disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF 
blocker.  If you have COPD, or are a heavy smoker, you should discuss with your doctor 
whether treatment with a TNF blocker is appropriate for you. 

Using other medicines 

Trudexa can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), steroids or pain 
medications including non-steroidal anti-inflammatory drugs. 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
You should not take Trudexa with medicines containing the active substance, anakinra.  If you have 
questions, please ask your doctor. 
 
Using Trudexa with food and drink 
 
Since Trudexa is given subcutaneously, food and drink should not affect Trudexa. 

Pregnancy and breast-feeding 

The effects of Trudexa in pregnant women are not known and so the use of Trudexa in pregnant 
women is not recommended.  You are advised to avoid becoming pregnant and must use adequate 
contraception while using Trudexa and for at least 5 months after the last Trudexa treatment.  
 
It is not known whether adalimumab passes into breast milk. 
 



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If you are a breast-feeding mother, you should stop breast-feeding during Trudexa treatment and for at 
least 5 months after the last Trudexa treatment. 
 
Driving and using machines 
 
Trudexa should not affect your ability to drive or use machinery. 
 
Important information about some of the ingredients of Trudexa 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’. 

3. HOW TO USE TRUDEXA 

Always take Trudexa exactly as your doctor has told you.  You should check with your doctor or 
pharmacist if you are not sure.  
 
Trudexa is injected under the skin (subcutaneous use).  The usual dose for adults with rheumatoid 
arthritis, psoriatic arthritis and ankylosing spondylitis is 40 mg adalimumab given every other week as 
a single dose.  The usual dose regimen for Crohn’s disease is 80 mg at week 0 and followed by 40 mg 
every other week starting at week 2.  In cases where a more rapid response is required your doctor 
may prescribe a dose of 160 mg at week 0 (as 4 injections in one day or 2 injections per day for two 
consecutive days), 80 mg (2 injections) at week 2, and thereafter as 40 mg (1 injection) every other 
week.  Depending on your response, your doctor may increase the dose to 40 mg every week.  You 
should continue to inject Trudexa for as long as your doctor has told you.   
 
In rheumatoid arthritis, methotrexate is continued while using Trudexa.  If your doctor determines that 
methotrexate is inappropriate, Trudexa can be given alone.  
 
If you have rheumatoid arthritis and you do not receive methotrexate with your Trudexa therapy, your 
doctor may decide to give 40 mg adalimumab every week.  

Instructions for preparing and giving an injection of Trudexa: 

The following instructions explain how to inject Trudexa.  Please read the instructions carefully and 
follow them step by step.  You will be instructed by your doctor or his/her assistant on the technique 
of self-injection.  Do not attempt to self-inject until you are sure that you understand how to prepare 
and give the injection.  After proper training, the injection can be self-administered or given by 
another person, for example a family member or friend.   
 
This injection should not be mixed in the same syringe or vial with any other medicine. 

1)  Setting up 

• Wash your hands thoroughly  
• Set up the following items on a clean surface 
 

o One pre-filled syringe of Trudexa for injection      
o One alcohol pad 

 



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• Look at the expiry date on the syringe.  Do not use the product after the month and year shown. 

2) Choosing and preparing an injection site  

• Choose a site on your thigh or stomach 
 

 
 
• Each new injection should be given at least 3 cm from the last injection site.  

o Do not inject in an area where the skin is reddened, bruised, or hard.  This may mean 
there is an infection. 

o Wipe the injection site with the enclosed alcohol pad, using a circular motion. 
o Do not touch the area again before injecting. 

3)  Injecting Trudexa  

• Do NOT shake the syringe. 
• Remove cap from needle syringe, being careful not to touch the needle or let it touch any 

surface. 
• With one hand, gently grasp the cleaned areas of skin and hold firmly 

 



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• With the other hand, hold syringe at 45-degree angle to skin, with the grooved side up. 
• With one quick, short motion, push needle all the way into skin 
• Release the skin with the first hand 
• Push plunger to inject solution – it can take from 2 to 5 seconds to empty the syringe 
• When the syringe is empty, remove the needle from skin, being careful to keep it at the same 

angle as when it was inserted 
• Using your thumb or a piece of gauze, apply pressure over the injection site for 10 seconds.  A 

little bleeding may occur.  Do not rub the injection site.  Use a plaster if you want to. 

4)  Throwing away supplies 

• The Trudexa syringe should NEVER be reused.  NEVER recap a needle. 
• After injecting Trudexa, immediately throw away the used syringe in a special container as 

instructed by your doctor, nurse or pharmacist. 
• Keep this container out of the reach and sight of children 

If you use more Trudexa than you should: 

If you accidentally inject Trudexa more frequently than told to by your doctor, you should call your 
doctor and tell him/her that you have taken more.  Always take the outer carton of medicine with you, 
even if it is empty.  

If you forget to take Trudexa: 

If you forget to give yourself an injection, you should inject the next dose of Trudexa as soon as you 
remember.  Then take your next dose as you would have on your originally scheduled day, had you 
not forgotten a dose.  
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 

4. POSSIBLE SIDE EFFECTS 

Like all medicines, Trudexa can have side effects, although not everybody gets them.  Most side 
effects are mild to moderate.  However, some may be serious and require treatment.  Side effects may 
occur at least up to 5 months after the last treatment.   
 
Tell your doctor immediately if you notice any of the following:  
• Severe rash, hives or other signs of allergic reaction;  
• Swollen face, hands, feet; 
• Trouble breathing, swallowing; 
• Shortness of breath with exertion or upon lying down or swelling of the feet; 



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• Signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 
paleness. 

 
Tell your doctor as soon as possible if you notice any of the following:  
• Signs of infection such as fever, malaise, wounds, dental problems, burning on urination; 
• Feeling weak or tired; 
• Coughing; 
• Tinglings; 
• Numbness; 
• Double vision; 
• Arm or leg weakness. 
 
The symptoms described above can be signs of the below listed side effects, which have been 
observed with Trudexa: 
 
Very common (≥ 1/10 patients):   
• injection site reactions (including pain, swelling, redness or itching). 
 
Common (≥ 1/100 and < 1/10 patients):   
• lower respiratory tract infections (such as bronchitis, pneumonia); 
• upper respiratory tract infections (including cold, runny nose, sinus infection); 
• urinary tract infection, cold blisters, shingles; 
• dizziness, including vertigo, headache; 
• eye inflammation; 
• cough, sore throat; 
• nausea, diarrhoea, abdominal pain, mouth ulcers; 
• elevated liver enzymes; 
• rash, itching, hair loss; 
• fatigue; 
• fever. 
 
Uncommon (≥ 1/1000 and< 1/100 patients):  
• serious infections (such as sepsis [blood poisoning]), joint infection, fungal infections; 
• skin wart; 
• anaemia, low white blood cell counts; 
• allergic reactions;  
• increased lipid values, appetite disorders; 
• anxiety, depression, feeling sleepy and difficulty sleeping; 
• nerve disorders (such as multiple sclerosis and eye nerve inflammation), taste disturbances; 
• vision disturbances; 
• ear discomfort; 
• sensation of heart beating rapidly, high blood pressure; 
• asthma, shortness of breath; 
• abdominal symptoms (such as vomiting, indigestion, constipation), rectal bleeding; 
• skin disorders (such as psoriasis, eczema or infections), itchy rash, slow wound healing; 
• muscle weakness; 
• urinary disturbances (such as blood in urine, increased urinary frequency); 
• increased menstrual bleeding; 
• flu like symptoms, chest pain, swelling of the feet. 
 
Rare (< 1/1000) 
• glaucoma; 
• skin cancer; 
• thyroid disorders; 



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• protein in urine. 
 
Other side effects that have been observed in patients taking Trudexa:  
tuberculosis and other opportunistic infections (infections that occur when resistance to disease is 
lowered); 
lung disease. 
 
If any side effects get serious, if you have any unusual effects, or if you notice any side effects not 
listed in this leaflet, please tell your doctor or pharmacist.  

5. HOW TO STORE TRUDEXA 

Keep out of the reach and sight of children.  
 
Do not use the Trudexa pre-filled syringe after the expiry date stated on the label/blister/carton after 
EXP:.  The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C).  Keep the pre-filled syringe in the outer carton.  Do not freeze. 

6. FURTHER INFORMATION 

Trudexa 40 mg solution for injection in pre-filled syringe is supplied as a sterile solution of 40 mg 
adalimumab dissolved in 0.8 ml solution. 
 
What Trudexa contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen 
phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium 
hydroxide and water for injections. 
 
What the Trudexa pre-filled syringe looks like and contents of the pack 
 
The Trudexa pre-filled syringe is a glass syringe containing a solution of adalimumab. 
Each pack contains 1, 2, 4 or 6 pre-filled syringes for patient use with 1, 2, 4 or 6 alcohol pads, 
respectively.  Not all pack sizes may be marketed. 
 
Trudexa is also available as a vial or a pre-filled pen. 
 
Marketing Authorisation Holder: 
 
Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 
 
Manufacturer:  
 
Abbott Biotechnology Deutschland GmbH  
Max-Planck-Ring 2 
D - 65205 Wiesbaden 
Germany 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 



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België/Belgique/Belgien 
Abbott SA 
Parc Scientifique 
Rue du Bosquet, 2 
B-1348 Ottignies/Louvain-la-Neuve 
Tél/Tel: + 32 10 475311 
 

Luxembourg/Luxemburg 
Abbott SA 
Parc Scientifique 
Rue du Bosquet, 2 
B-1348 Ottignies/Louvain-la-Neuve 
Belgique/Belgien 
Tél/Tel: + 32 10 475311  
 

България 
Т.П. Абот Лабораторис С.А. 
ул. Оборище № 45 
София 1504 
Teл.: + 359 2 846 8429 

Magyarország 
Abbott Laboratories (Magyarország) Kft. 
Teve u. 1/a-c. 
H-1139 Budapest 
Tel.: + 36 1 465 2100 
 

Česká republika 
Abbott Laboratories s. r. o. 
Hadovka Office Park 
Evropská 2590/33d 
CZ-160 00 Praha 6 
Tel: + 420 267 292 111 
 

Malta 
V.J.Salomone Pharma Limited  
79, Simpson Street,  
Marsa HMR 14,  
Malta. 
Tel: + 356  22983201 
 

Danmark 
Abbott Laboratories A/S 
Smakkedalen 6 
DK-2820 Gentofte 
Tlf: + 45 39 77-00-00 
 

Nederland 
Abbott BV 
Siriusdreef 51 
NL-2132 WT Hoofddorp 
Tel: + 31 (0) 23 5544400 
 

Deutschland 
Abbott GmbH & Co. KG 
Max-Planck-Ring 2  
D-65205 Wiesbaden 
Tel: + 49 (0) 6122 58-0 
 

Norge 
Abbott Norge AS 
PO Box 1, N-1330 Fornebu 
Martin Linges vei 25,N-1367 Snarøya 
Tlf: + 47 81 55 99 20 
 

Eesti 
Abbott Laboratories Baltics 
Vienibas 87h  
LV-1004 Riia 
Läti 
Tel: + 371 7605580 
 

Österreich 
Abbott Ges.m.b.H.  
Perfektastrasse 84A 
A-1230 Wien 
Tel: + 43 1 891-22 
 

Ελλάδα 
Abbott Laboratories (ΕΛΛΑΣ)Α.Β.Ε.Ε. 
Λεωφόρος Βουλιαγµένης 512 
GR-174 56 Άλιµος, Αθήνα 
Τηλ: + 30 21 0 9985-222 
 

Polska 
Abbott Laboratories Poland Sp. z o.o. 
ul. Domaniewska 41 
PL-02-672 Warszawa  
Tel.: + 48 22 606-10-50 
 

España 
Abbott Laboratories, S.A.  
Avenida de Burgos, 91 
E-28050 Madrid 
Tel: + 34 9 1 337-5200 
 

Portugal 
Abbott Laboratórios, Lda.  
Estrada de Alfragide, nº 67 
Alfrapark, Edifício D,  
P-2610-008 Amadora 
Tel: + 351 (0) 21 472 7100 
 

France 
Abbott France 
10, rue d’Arcueil 

România 
Abbott Laboratories S.A. 
Bucharest Business Park 



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BP 90233 
F-94528 Rungis Cedex 
Tél: + 33 (0) 1 45 60 25 00 
 

Şos. Bucureşti-Ploieşti 1A 
Corp B, etaj 3, sector 1 
013681 Bucureşti 
Tel: +40 21 529 30 00 
 

Ireland 
Abbott Laboratories, Ireland, Ltd 
4051 Kingswood Drive 
Citywest Business Campus 
IRL–Dublin 24,  
Tel: + 353 (0) 1 469-1500 
 

Slovenija 
Abbott Laboratories d.o.o. 
Dunajska 22 
SI-1000 Ljubljana 
Tel: + 386 (1) 43 22 322 
 

Ísland 
Vistor hf. 
Hörgatún 2 
IS-210 Garðabær 
Tel: + 354 535 7000 
 

Slovenská republika 
Abbott Laboratories Slovakia s.r.o. 
Trnavská cesta 70 
SK-821 02 Bratislava 2 
Tel: + 421 (0) 2 4445 4176 
 

Italia 
Abbott SpA 
I-04010 Campoverde di Aprilia 
(Latina) 
Tel: + 39 06 928921 
 

Suomi/Finland 
Abbott OY  
Pihatörmä 1A/Gårdsbrinken 1B 
FIN-02240 Espoo/Esbo 
Puh/Tel: + 358 (0) 9 7518 4120 
 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Θεοτόκη 4Β 
1055 Λευκωσία  
Τηλ.: + 357 22 34 74 40 

Sverige 
Abbott Scandinavia AB 
Box 509/Gårdsvägen 8 
S-169 29 Solna/S-169 70 Solna 
Tel: + 46 (0) 8 5465 67 00 
 

Latvija 
Abbott Laboratories Baltics 
Vienibas 87h 
LV-1004 Rīga 
Tel: + 371 7605580 
 
 

United Kingdom 
Abbott Laboratories Ltd 
Abbott House 
Unit 2, Vanwall Road 
Vanwall Business Park 
Maidenhead 
Berkshire  SL6 4XE - UK 
Tel: + 44 (0) 1628 773355 
 

Lietuva 
Abbott Laboratories Baltics 
Vienibas 87h  
LV-1004 Rīga 
Latvia 
Tel: + 371 7605580 
 

 

 
 
This leaflet was last approved in {MM/YYYY} 
 
 



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PACKAGE LEAFLET:  INFORMATION FOR THE USER 
 

Trudexa 40 mg solution for injection in pre-filled syringe with needleguard 
Adalimumab 

 
 

Read all of this leaflet carefully before you start using this medicine. 
− Keep this leaflet.  You may need to read it again. 
− Your doctor will also give you a Patient Alert Card, which contains important safety 

information that you need to be aware of before you are given Trudexa and during treatment 
with Trudexa.  Keep this Patient Alert Card with the package leaflet. 

− If you have any further questions, please ask your doctor or pharmacist. 
− This medicine has been prescribed for you.  Do not pass it on to others.  It may harm them, even 

if their symptoms are the same as yours. 
− If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Trudexa is and what it is used for 
2. Before you use Trudexa 
3. How to use Trudexa 
4. Possible side effects 
5 How to store Trudexa 
6. Further information 

1. WHAT TRUDEXA IS AND WHAT IT IS USED FOR 

Trudexa is intended for treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.  
It is a medicine that decreases the inflammation process of these diseases.  The active ingredient, 
adalimumab, is a human monoclonal antibody produced by cultured cells.  Monoclonal antibodies are 
proteins that recognise and bind to other unique proteins.  Adalimumab binds to a specific protein 
(tumour necrosis factor or TNFα), which is present at increased levels in inflammatory diseases such 
as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. 

Rheumatoid arthritis 

Rheumatoid arthritis is an inflammatory disease of the joints.  If you have moderate to severe active 
rheumatoid arthritis, you may first be given other disease-modifying medicines, such as methotrexate.  
If you do not respond well enough to these medicines, you will be given Trudexa to treat your 
rheumatoid arthritis.   
 
Trudexa can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Trudexa has been shown to slow down the damage to the cartilage and bone of the joints caused by the 
disease and to improve physical function. 
 
Usually, Trudexa is used with methotrexate.  If your doctor determines that methotrexate is 
inappropriate, Trudexa can be given alone.  

Psoriatic arthritis 

Psoriatic arthritis is an inflammation of the joints associated with psoriasis. 



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Ankylosing spondylitis 

Ankylosing spondylitis is an inflammatory disease of the spine.  If you have ankylosing spondylitis 
you will first be given other medicines.  If you do not respond well enough to these medicines, you 
will be given Trudexa to reduce the signs and symptoms of your disease. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract.  If you have Crohn’s disease you will 
first be given other medicines.  If you do not respond well enough to these medicines, you will be 
given Trudexa to reduce the signs and symptoms of your disease. 

2. BEFORE YOU USE TRUDEXA 

Do not use Trudexa:  

• If you are allergic (hypersensitive) to adalimumab or any of the other ingredients of Trudexa.  
 
• If you have a severe infection, including active tuberculosis (see “Take special care with 

Trudexa”).  It is important that you tell your doctor if you have symptoms of infections, e.g. 
fever, wounds, feeling tired, dental problems. 

 
• If you have moderate or severe heart failure.  It is important to tell your doctor if you have had 

or have a serious heart condition (see “Take special care with Trudexa”). 

Take special care with Trudexa:  

• If you experience allergic reactions such as chest tightness, wheezing, dizziness, swelling or 
rash do not inject more Trudexa and contact your doctor immediately. 

 
• The needle cover of the syringe contains natural rubber (latex).  This may cause severe allergic 

reactions in patients sensitive to latex.  Patients who have a known sensitivity to latex should be 
advised to avoid touching the inner shield. 

 
• If you have an infection, including long-term or localized infection (for example, leg ulcer) 

consult your doctor before starting Trudexa.  If you are unsure, please contact your doctor.  
 
• You might get infections more easily while you are receiving Trudexa treatment including 

serious infections, tuberculosis, opportunistic infections and sepsis that may, in rare case, be 
life-threatening.  It is important to tell your doctor if you get symptoms such as fever, wounds, 
feeling tired or dental problems.  

 
• As cases of tuberculosis have been reported in patients treated with Trudexa, your doctor will 

check you for signs and symptoms of tuberculosis before starting Trudexa.  This will include a 
thorough medical history, a chest X-ray and a tuberculin test.  The conduct of these tests should 
be recorded on your Patient Alert Card.  It is very important that you tell your doctor if you 
have ever had tuberculosis, or if you have been in close contact with someone who has had 
tuberculosis.  If symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild 
fever), or any other infection appear during or after therapy tell your doctor immediately. 

 
• Advise your doctor if you have a history of recurrent infections or other conditions that increase 

the risk of infections. 
 
• Advise your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV 

or if you think you might be at risk of contracting HBV.  Trudexa can cause reactivation of 



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HBV in people who carry this virus.  In some rare cases, especially if you are taking other 
medicines that suppress the immune system, reactivation of HBV can be life-threatening.   

 
• If you are about to undergo surgery or dental procedures please inform your doctor that you are 

taking Trudexa. 
 
• If you have multiple sclerosis, your doctor will decide if you should receive Trudexa 
 
• Some vaccines should not be given while receiving Trudexa.  Please check with your doctor 

before you receive any vaccines. 
 
• If you have mild heart failure and you are being treated with Trudexa, your heart failure status 

must be closely monitored by your doctor.  It is important to tell your doctor if you have had or 
have a serious heart condition.  If you develop new or worsening symptoms of heart failure (e.g. 
shortness of breath, or swelling of your feet), you must contact your doctor immediately.  Your 
doctor will decide if you should receive Trudexa. 

 
• In some patients the body may fail to produce enough of the blood cells that help your body 

fight infections or help you to stop bleeding.  If you develop a fever that does not go away, 
bruise or bleed very easily or look very pale, call your doctor right away.  Your doctor may 
decide to stop treatment. 

 
• There have been very rare cases of certain kinds of cancer in patients taking Trudexa or other 

TNF blockers.  People with more serious rheumatoid arthritis that have had the disease for a 
long time may have a higher than average risk of getting a kind of cancer that affects the lymph 
system, called lymphoma.  If you take Trudexa your risk may increase.  In addition very rare 
cases of non-melanoma skin cancer have been observed in patients taking Trudexa. 

 
• Cancers, other than lymphoma, have been reported in patients with a specific type of lung 

disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF 
blocker.  If you have COPD, or are a heavy smoker, you should discuss with your doctor 
whether treatment with a TNF blocker is appropriate for you. 

Using other medicines 

Trudexa can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), steroids or pain 
medications including non-steroidal anti-inflammatory drugs. 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
You should not take Trudexa with medicines containing the active substance, anakinra.  If you have 
questions, please ask your doctor. 
 
Using Trudexa with food and drink 
 
Since Trudexa is given subcutaneously, food and drink should not affect Trudexa. 

Pregnancy and breast-feeding 

The effects of Trudexa in pregnant women are not known and so the use of Trudexa in pregnant 
women is not recommended.  You are advised to avoid becoming pregnant and must use adequate 
contraception while using Trudexa and for at least 5 months after the last Trudexa treatment.  
 
It is not known whether adalimumab passes into breast milk. 
 



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If you are a breast-feeding mother, advise you should stop breast-feeding during Trudexa treatment, 
and for at least 5 months after the last Trudexa treatment.  
 
Driving and using machines 
 
Trudexa should not affect your ability to drive or use machinery. 
 
Important information about some of the ingredients of Trudexa 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’. 

3. HOW TO USE TRUDEXA 

Always take Trudexa exactly as your doctor has told you.  You should check with your doctor or 
pharmacist if you are not sure.  
 
Trudexa is injected under the skin (subcutaneous use).  The usual dose for adults with rheumatoid 
arthritis, psoriatic arthritis and ankylosing spondylitis is 40 mg adalimumab given every other week as 
a single dose.  The usual dose regimen for Crohn’s disease is 80 mg at week 0 and followed by 40 mg 
every other week starting at week 2.  In cases where a more rapid response is required your doctor 
may prescribe a dose of 160 mg at week 0 (as 4 injections in one day or 2 injections per day for two 
consecutive days), 80 mg (2 injections) at week 2, and thereafter as 40 mg (1 injection) every other 
week.  Depending on your response, your doctor may increase the dose to 40 mg every week.  You 
should continue to inject Trudexa for as long as your doctor has told you.   
 
In rheumatoid arthritis, methotrexate is continued while using Trudexa.  If your doctor determines that 
methotrexate is inappropriate, Trudexa can be given alone.  
 
If you have rheumatoid arthritis and you do not receive methotrexate with your Trudexa therapy, your 
doctor may decide to give 40 mg adalimumab every week. 
 
Instructions for preparing and giving an injection of Trudexa: 
The following instructions explain how to inject Trudexa.  Please read the instructions carefully and 
follow them step by step.  You will be instructed by your doctor or his/her assistant on the technique 
of self-injection.  Do not attempt to self-inject until you are sure that you understand how to prepare 
and give the injection.  After proper training, the injection can be self-administered or given by 
another person, for example a family member or friend. 
 
This injection should not be mixed in the same syringe or vial with any other medicine. 

1)  Setting up 

• Wash your hands thoroughly  
• Set up the following items on a clean surface 
 

o One pre-filled syringe of Trudexa for injection 
o One alcohol pad 

 



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• Look at the expiry date on the syringe.  Do not use the product after the month and year shown. 

2)  Choosing and preparing an injection site  

• Choose a site on your thigh or stomach 

 
 
 
• Each new injection should be given at least 3 cm from the last injection site.  

o Do not inject in an area where the skin is reddened, bruised, or hard.  This may mean 
there is an infection. 

o Wipe the injection site with the enclosed alcohol pad, using a circular motion. 
o Do not touch the area again before injecting. 

3)  Injecting Trudexa  

• Do NOT shake the syringe. 
• Remove cap from needle syringe, being careful not to touch the needle or let it touch any 

surface. 
• With one hand, gently grasp the cleaned areas of skin and hold firmly 

 
 
• With the other hand, hold syringe at 45-degree angle to skin, with the grooved side up. 
• With one quick, short motion, push needle all the way into skin 
• Release the skin with the first hand 
• Push plunger to inject solution – it can take from 2 to 5 seconds to empty the syringe 



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• When the syringe is empty, remove the needle from skin, being careful to keep it at the same 
angle as when it was inserted 

• Hold the syringe in one hand and with the other hand slide the outer protective shield over the 
exposed needle until it locks in place 

• Using your thumb or a piece of gauze, apply pressure over the injection site for 10 seconds.  A 
little bleeding may occur.  Do not rub the injection site.  Use a plaster if you want to. 

4) Throwing away supplies 

• The Trudexa syringe should NEVER be reused.  NEVER recap a needle 
• After injecting Trudexa, immediately throw away the used syringe in a special container as 

instructed by your doctor, nurse or pharmacist. 
• Keep this container out of the reach and sight of children 

If you use more Trudexa than you should: 

If you accidentally inject Trudexa more frequently than told to by your doctor, you should call your 
doctor and tell him/her that you have taken more.  Always take the outer carton of medicine with you, 
even if it is empty.  

If you forget to take Trudexa: 

If you forget to give yourself an injection, you should inject the next dose of Trudexa as soon as you 
remember.  Then take your next dose as you would have on your originally scheduled day, had you 
not forgotten a dose.  
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 

4. POSSIBLE SIDE EFFECTS 

Like all medicines, Trudexa can have side effects, although not everybody gets them.  Most side 
effects are mild to moderate.  However, some may be serious and require treatment.  Side effects may 
occur at least up to 5 months after the last treatment. 
 
Tell your doctor immediately if you notice any of the following:  
• Severe rash, hives or other signs of allergic reaction;  
• Swollen face, hands, feet; 
• Trouble breathing, swallowing; 
• Shortness of breath with exertion or upon lying down or swelling of the feet; 
• Signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness. 
 
Tell your doctor as soon as possible if you notice any of the following:  
• Signs of infection such as fever, malaise, wounds, dental problems, burning on urination; 
• Feeling weak or tired; 
• Coughing; 
• Tingling; 
• Numbness; 
• Double vision; 
• Arm or leg weakness. 
 
The symptoms described above can be signs of the below listed side effects, which have been 
observed with Trudexa: 
 
Very common (≥ 1/10 patients):   



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• injection site reactions (including pain, swelling, redness or itching). 
 
Common (≥ 1/100 and < 1/10 patients):   
• lower respiratory tract infections (such as bronchitis, pneumonia); 
• upper respiratory tract infections (including cold, runny nose, sinus infection); 
• urinary tract infection, cold blisters, shingles; 
• dizziness, including vertigo, headache; 
• eye inflammation; 
• cough, sore throat;  
• nausea, diarrhoea, abdominal pain, mouth ulcers;  
• elevated liver enzymes; 
• rash, itching, hair loss; 
• fatigue; 
• fever. 
 
Uncommon (≥ 1/1000 and< 1/100 patients):  
• serious infections (such as sepsis [blood poisoning]), joint infection, fungal infections; 
• skin wart; 
• anaemia, low white blood cell counts; 
• allergic reactions;  
• increased lipid values, appetite disorders; 
• anxiety, depression, feeling sleepy and difficulty sleeping; 
• nerve disorders (such as multiple sclerosis and eye nerve inflammation), taste disturbances; 
• vision disturbances; 
• ear discomfort; 
• sensation of heart beating rapidly, high blood pressure; 
• asthma, shortness of breath; 
• abdominal symptoms (such as vomiting, indigestion, constipation), rectal bleeding; 
• skin disorders (such as psoriasis, eczema or infections), itchy rash, slow wound healing; 
• muscle weakness; 
• urinary disturbances (such as blood in urine, increased urinary frequency); 
• increased menstrual bleeding; 
• flu like symptoms, chest pain, swelling of the feet. 
 
Rare (< 1/1000) 
• glaucoma; 
• skin cancer; 
• thyroid disorders; 
• protein in urine. 
 
Other side effects that have been observed in patients taking Trudexa:  
tuberculosis and other opportunistic infections (infections that occur when resistance to disease is 
lowered); 
lung disease. 
 
If any side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your 
doctor or pharmacist.  

5. HOW TO STORE TRUDEXA 

Keep out of the reach and sight of children.  
 



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Do not use the Trudexa pre-filled syringe after the expiry date stated on the label/blister/carton after 
EXP:.  The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C).  Keep the pre-filled syringe in the outer carton.  Do not freeze. 

6. FURTHER INFORMATION 

Trudexa 40 mg solution for injection in pre-filled syringe with needleguard is supplied as a sterile 
solution of 40 mg adalimumab dissolved in 0.8 ml solution. 
 
What Trudexa contains 
The active substance is adalimumab. 
The other ingredients are mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen 
phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium 
hydroxide and water for injections. 
 
What the Trudexa pre-filled syringe looks like and contents of the pack 
The Trudexa pre-filled syringe is a glass syringe with needleguard containing a solution of 
adalimumab.  Each pack contains 1 pre-filled syringe with needleguard for hospital administration or 
administration by a caregiver, with 1 alcohol pad. 
 
Not all pack sizes may be marketed.  Trudexa is also available as a vial or a pre-filled pen. 
 
 
Marketing Authorisation Holder: 
 
Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 
 
Manufacturer:  
 
Abbott Biotechnology Deutschland GmbH  
Max-Planck-Ring 2 
D - 65205 Wiesbaden 
Germany 
 



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For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Abbott SA 
Parc Scientifique 
Rue du Bosquet, 2 
B-1348 Ottignies/Louvain-la-Neuve 
Tél/Tel: + 32 10 475311 
 

Luxembourg/Luxemburg 
Abbott SA 
Parc Scientifique 
Rue du Bosquet, 2 
B-1348 Ottignies/Louvain-la-Neuve 
Belgique/Belgien 
Tél/Tel: + 32 10 475311  
 

България 
Т.П. Абот Лабораторис С.А. 
ул. Оборище № 45 
София 1504 
Teл.: + 359 2 846 8429 

Magyarország 
Abbott Laboratories (Magyarország) Kft. 
Teve u. 1/a-c. 
H-1139 Budapest 
Tel.: + 36 1 465 2100 
 

Česká republika 
Abbott Laboratories s. r. o. 
Hadovka Office Park 
Evropská 2590/33d 
CZ-160 00 Praha 6 
Tel: + 420 267 292 111 
 

Malta 
V.J.Salomone Pharma Limited  
79, Simpson Street,  
Marsa HMR 14,  
Malta. 
Tel: + 356  22983201 

Danmark 
Abbott Laboratories A/S 
Smakkedalen 6 
DK-2820 Gentofte 
Tlf: + 45 39 77-00-00 
 

Nederland 
Abbott BV 
Siriusdreef 51 
NL-2132 WT Hoofddorp 
Tel: + 31 (0) 23 5544400 
 

Deutschland 
Abbott GmbH & Co. KG 
Max-Planck-Ring 2  
D-65205 Wiesbaden 
Tel: + 49 (0) 6122 58-0 
 

Norge 
Abbott Norge AS 
PO Box 1, N-1330 Fornebu 
Martin Linges vei 25, N-1367 Snarøya 
Tlf: + 47 81 55 99 20 
 

Eesti 
Abbott Laboratories Baltics 
Vienibas 87h 
LV-1004 Riia 
Läti 
Tel: + 371 7605580 
 

Österreich 
Abbott Ges.m.b.H.  
Perfektastrasse 84A 
A-1230 Wien 
Tel: + 43 1 891-22 
 

Ελλάδα 
Abbott Laboratories (ΕΛΛΑΣ)Α.Β.Ε.Ε. 
Λεωφόρος Βουλιαγµένης 512 
GR 174 56 Άλιµος, Αθήνα 
Τηλ: + 30 21 0 9985-222 
 

Polska 
Abbott Laboratories Poland Sp. z o.o. 
ul. Domaniewska 41 
PL-02-672 Warszawa  
Tel.: + 48 22 606-10-50 
 

España 
Abbott Laboratories, S.A.  
Avenida de Burgos, 91 
E-28050 Madrid 
Tel: + 34 9 1 337-5200 
 

Portugal 
Abbott Laboratórios, Lda.  
Estrada de Alfragide, nº 67 
Alfrapark, Edifício D,  
P-2610-008 Amadora 
Tel: + 351 (0) 21 472 7100 
 

France România 



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Abbott France 
10, rue d’Arcueil 
BP 90233 
F-94528 Rungis Cedex 
Tél: + 33 (0) 1 45 60 25 00 
 

Abbott Laboratories S.A. 
Bucharest Business Park 
Şos. Bucureşti-Ploieşti 1A 
Corp B, etaj 3, sector 1 
013681 Bucureşti 
Tel: +40 21 529 30 00 
 

Ireland 
Abbott Laboratories, Ireland, Ltd 
4051 Kingswood Drive 
Citywest Business Campus 
IRL–Dublin 24,  
Tel: + 353 (0) 1 469-1500 
 

Slovenija 
Abbott Laboratories d.o.o.Dunajska 22 
SI-1000 Ljubljana 
Tel: + 386 (1) 43 22 322 
 

Ísland 
Vistor hf. 
Hörgatún 2 
IS-210 Garðabær 
Tel: + 354 535 7000 
 

Slovenská republika 
Abbott Laboratories Slovakia s.r.o. 
Trnavská cesta 70 
SK-821 02 Bratislava 2 
Tel: + 421 (0) 2 4445 4176 
 

Italia 
Abbott SpA 
I-04010 Campoverde di Aprilia 
(Latina) 
Tel: + 39 06 928921 
 

Suomi/Finland 
Abbott OY  
Pihatörmä 1A/Gårdsbrinken 1B 
FIN-02240 Espoo/Esbo 
Puh/Tel: + 358 (0) 9 7518 4120 
 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Θεοτόκη 4Β 
1055 Λευκωσία  
Τηλ.: + 357 22 34 74 40 

Sverige 
Abbott Scandinavia AB 
Box 509/Gårdsvägen 8 
S-169 29 Solna/S-169 70 Solna 
Tel: + 46 (0) 8 5465 67 00 
 

Latvija 
Abbott Laboratories Baltics 
Vienibas 87h 
LV-1004 Rīga 
Tel: + 371 7605580 
 
 

United Kingdom 
Abbott Laboratories Ltd 
Abbott House 
Unit 2, Vanwall Road 
Vanwall Business Park 
Maidenhead 
Berkshire  SL6 4XE - UK 
Tel: + 44 (0) 1628 773355 
 

Lietuva 
Abbott Laboratories Baltics 
Vienibas 87h 
LV-1004 Rīga 
Latvia 
Tel: + 371 7605580 
 

 

 
 
This leaflet was last approved in {MM/YYYY} 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Trudexa Pre-filled Pen 40 mg solution for injection in pre-filled pen 
Adalimumab 

 
 

Read all of this leaflet carefully before you start using this medicine. 
− Keep this leaflet.  You may need to read it again. 
− Your doctor will also give you a Patient Alert Card, which contains important safety 

information that you need to be aware of before you are given Trudexa and during treatment 
with Trudexa.  Keep this Patient Alert Card together with the package leaflet. 

− If you have any further questions, ask your doctor or pharmacist. 
− This medicine has been prescribed for you.  Do not pass it on to others.  It may harm them, even 

if their symptoms are the same as yours. 
− If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:    
1. What Trudexa is and what it is used for 
2. Before you use Trudexa 
3. How to use Trudexa 
4. Possible side effects 
5 How to store Trudexa 
6. Further information 

1. WHAT TRUDEXA IS AND WHAT IT IS USED FOR 

Trudexa is intended for treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.  
It is a medicine that decreases the inflammation process of these diseases.  The active ingredient, 
adalimumab, is a human monoclonal antibody produced by cultured cells.  Monoclonal antibodies are 
proteins that recognise and bind to other unique proteins.  Adalimumab binds to a specific protein 
(tumour necrosis factor or TNFα), which is present at increased levels in inflammatory diseases such 
as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. 

Rheumatoid arthritis 

Rheumatoid arthritis is an inflammatory disease of the joints.  If you have moderate to severe active 
rheumatoid arthritis, you may first be given other disease-modifying medicines, such as methotrexate.  
If you do not respond well enough to these medicines, you will be given Trudexa to treat your 
rheumatoid arthritis.   
 
Trudexa can also be used to treat severe, active and progressive rheumatoid arthritis without previous 
methotrexate treatment. 
 
Trudexa has been shown to slow down the damage to the cartilage and bone of the joints caused by the 
disease and to improve physical function.  

Usually, Trudexa is used with methotrexate.  If your doctor determines that methotrexate is 
inappropriate, Trudexa can be given alone.  

Psoriatic arthritis 
 
Psoriatic arthritis is an inflammation of the joints associated with psoriasis. 



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Ankylosing spondylitis 

Ankylosing spondylitis is an inflammatory disease of the spine.  If you have ankylosing spondylitis 
you will first be given other medicines.  If you do not respond well enough to these medicines, you 
will be given Trudexa to reduce the signs and symptoms of your disease. 
 
Crohn’s disease 
 
Crohn’s disease is an inflammatory disease of the digestive tract.  If you have Crohn’s disease you will 
first be given other medicines.  If you do not respond well enough to these medicines, you will be 
given Trudexa to reduce the signs and symptoms of your disease. 

2. BEFORE YOU USE TRUDEXA 

Do not use Trudexa:  

• If you are allergic (hypersensitive) to adalimumab or any of the other ingredients of Trudexa.  
 
• If you have a severe infection, including active tuberculosis (see “Take special care with 

Trudexa”).  It is important that you tell your doctor if you have symptoms of infections, e.g. 
fever, wounds, feeling tired, dental problems. 

 
• If you have moderate or severe heart failure.  It is important to tell your doctor if you have had 

or have a serious heart condition (see “Take special care with Trudexa”). 

Take special care with Trudexa:  

• If you experience allergic reactions such as chest tightness, wheezing, dizziness, swelling or 
rash do not inject more Trudexa and contact your doctor immediately. 

 
• The needle cover of the syringe contains natural rubber (latex).  This may cause severe allergic 

reactions in patients sensitive to latex.  Patients who have a known sensitivity to latex should be 
advised to avoid touching the inner shield. 

 
• If you have an infection, including long-term or localized infection (for example, leg ulcer) 

consult your doctor before starting Trudexa.  If you are unsure, please contact your doctor.  
 
• You might get infections more easily while you are receiving Trudexa treatment including 

serious infections, tuberculosis, opportunistic infections and sepsis that may, in rare cases, be 
life-threatening.  It is important to tell your doctor if you get symptoms such as fever, wounds, 
feeling tired or dental problems.  

 
• As cases of tuberculosis have been reported in patients treated with Trudexa, your doctor will 

check you for signs and symptoms of tuberculosis before starting Trudexa.  This will include a 
thorough medical history, a chest X-ray and a tuberculin test.  The conduct of these tests should 
be recorded on your Patient Alert Card.  It is very important that you tell your doctor if you 
have ever had tuberculosis, or if you have been in close contact with someone who has had 
tuberculosis.  If symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild 
fever), or any other infection appear during or after therapy tell your doctor immediately. 

 
• Advise your doctor if you have a history of recurrent infections or other conditions that increase 

the risk of infections. 
 
• Advise your doctor if you are a carrier of the hepatitis B virus (HBV), if you have active HBV 

or if you think you might be at risk of contracting HBV.  Trudexa can cause reactivation of 



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HBV in people who carry this virus.  In some rare cases, especially if you are taking other 
medicines that suppress the immune system, reactivation of HBV can be life-threatening.   

 
• If you are about to undergo surgery or dental procedures please inform your doctor that you are 

taking Trudexa. 
 
• If you have multiple sclerosis, your doctor will decide if you should receive Trudexa. 
 
• Some vaccines should not be given while receiving Trudexa.  Please check with your doctor 

before you receive any vaccines. 
 
• If you have mild heart failure and you are being treated with Trudexa , your heart failure status 

must be closely monitored by your doctor.  It is important to tell your doctor if you have had or 
have a serious heart condition.  If you develop new or worsening symptoms of heart failure (e.g. 
shortness of breath, or swelling of your feet), you must contact your doctor immediately.  Your 
doctor will decide if you should receive Trudexa. 

 
• In some patients the body may fail to produce enough of the blood cells that help your body 

fight infections or help you to stop bleeding.  If you develop a fever that does not go away, 
bruise or bleed very easily or look very pale, call your doctor right away.  Your doctor may 
decide to stop treatment. 

 
• There have been very rare cases of certain kinds of cancer in patients taking Trudexa or other 

TNF blockers.  People with more serious rheumatoid arthritis that have had the disease for a 
long time may have a higher than average risk of getting a kind of cancer that affects the lymph 
system, called lymphoma.  If you take Trudexa your risk may increase.  In addition very rare 
cases of non-melanoma skin cancer have been observed in patients taking Trudexa. 

 
• Cancers, other than lymphoma, have been reported in patients with a specific type of lung 

disease called Chronic Obstructive Pulmonary Disease (COPD) treated with another TNF 
blocker.  If you have COPD, or are a heavy smoker, you should discuss with your doctor 
whether treatment with a TNF blocker is appropriate for you. 

Using other medicines 

Trudexa can be taken together with methotrexate or certain disease-modifying anti-rheumatic agents 
(sulfasalazine, hydroxychloroquine, leflunomide and injectable gold preparations), steroids or pain 
medications including non-steroidal anti-inflammatory drugs. 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
You should not take Trudexa with medicines containing the active substance, anakinra.  If you have 
questions, please ask your doctor. 
 
Using Trudexa with food and drink 
 
Since Trudexa is given subcutaneously, food and drink should not affect Trudexa. 

Pregnancy and breast-feeding 

The effects of Trudexa in pregnant women are not known and so the use of Trudexa in pregnant 
women is not recommended.  You are advised to avoid becoming pregnant and must use adequate 
contraception while using Trudexa and for at least 5 months after the last Trudexa treatment.  
 
It is not known whether adalimumab passes into breast milk. 
 



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If you are a breast-feeding mother, you should stop breast-feeding during Trudexa treatment and for at 
least 5 months after the last Trudexa treatment.  
 
Driving and using machines 
 
Trudexa should not affect your ability to drive or use machinery. 
 
Important information about some of the ingredients of Trudexa 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’. 

3. HOW TO USE THE TRUDEXA PRE-FILLED PEN 

Always use Trudexa exactly as your doctor has told you.  You should check with your doctor or 
pharmacist if you are not sure.  
 
Trudexa is injected under the skin (subcutaneous use).  The usual dose for adults with rheumatoid 
arthritis, psoriatic arthritis and ankylosing spondylitis is 40 mg adalimumab given every other week as 
a single dose.  The usual dose regimen for Crohn’s disease is 80 mg at week 0 and followed by 40 mg 
every other week starting at week 2. I n cases where a more rapid response is required your doctor 
may prescribe a dose of 160 mg at week 0 (as 4 injections in one day or 2 injections per day for two 
consecutive days), 80 mg (2 injections) at week 2, and thereafter as 40 mg (1 injection) every other 
week.  Depending on your response, your doctor may increase the dose to 40 mg every week.  You 
should continue to inject Trudexa for as long as your doctor has told you.   
 
In rheumatoid arthritis, methotrexate is continued while using Trudexa.  If your doctor determines that 
methotrexate is inappropriate, Trudexa can be given alone. 
 
If you have rheumatoid arthritis and you do not receive methotrexate with your Trudexa therapy, your 
doctor may decide to give 40 mg Trudexa every week.  

Injecting Trudexa yourself  

The following instructions explain how to give yourself an injection of Trudexa using the pre-filled 
pen.  Please read the instructions carefully and follow them step by step.  You will be instructed by 
your doctor or his/her assistant on the technique of self-injection.  Do not attempt to self-inject until 
you are sure that you understand how to prepare and give the injection.  After proper training, the 
injection can be self-administered or given by another person, for example a family member or friend. 

What should I do before I give myself a subcutaneous injection of Trudexa? 

1. Wash your hands thoroughly.  
2.  Take one dose tray containing a pre-filled pen of Trudexa from the refrigerator.  
3.  Do not shake or drop the pre-filled pen. 
4.  Set up the following items on a clean surface. 
 

• One pre-filled pen of Trudexa  
• One alcohol pad 
 



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5.  Check the expiry date on the pre-filled pen label (EXP:).  Do not use the product if the date has 
passed the month and year shown. 

 
6.  Hold the pre-filled pen with the grey cap (labelled ‘1’) pointing up.  Check the appearance of 

the Trudexa solution through the windows on the sides of the pre-filled pen.  It must be clear 
and colourless.  If it is cloudy or discoloured or has flakes or particles in it, you must not use it.  
Do not use a pre-filled pen that is frozen or if it has been left in direct sunlight.  

 

           
   

   

Where should I give my injection?   

1.  Choose a site on the top of your thigh or stomach (except the area around the navel). 
 

       
 



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2.  Change the place that you inject each time so that you do not become sore in one area.  Each 
new injection should be given at least 3 cm from the last injection site.  

 
3.  Do not inject in an area where the skin is reddened, bruised, or hard.  This may mean there is an 

infection.   
 

How do I give my injection? 
 
1.  Wipe your skin by using the enclosed alcohol pad, using a circular motion.  Do not touch the 

area again before injecting.     
 
2. Hold the pre-filled pen with one hand with the grey cap (1) pointed down.  With your other 

hand, pull the grey cap (1) straight off and discard cap.  Check that the small grey needle cover 
of the syringe has been removed with the cap.  The white needle sleeve will now be exposed.  
Do not try to touch the needle housed in the barrel.  DO NOT RECAP as you may damage the 
needle inside.  

 
3.  Pull the plum safety cap (labelled ‘2’) straight off to expose the plum coloured activation button 

at the top.  The pre-filled pen is now ready to use.  Do not press the plum activation button until 
properly positioned as this will result in discharge of medication.  DO NOT RECAP as this 
could cause the unit to discharge. 

 
Giving the injection 

 
1.  With your free hand, gently grasp a sizable area of the cleaned skin at the injection site and hold 

firmly (see below).   
2.   Place the white end of the pre-filled pen at a right angle (90 degrees) to the skin, so that you can 

see the window.  
3.  Holding the barrel of the pre-filled pen, press down slightly onto the injection site (holding in 

place without moving).  
4.  With your index finger or your thumb, press the plum coloured button on top once you are ready 

to begin the injection (see below).  You will then hear a ‘click’ as the needle is released, and you 
will feel a small prick as the needle advances.  

5.  Keep pressing and continue to hold the pre-filled pen with steady pressure in place for about 10 
seconds to ensure a complete injection.  Do not remove the pre-filled pen while the injection is 
being given.  

 

           
 
            
 
6.  You will see a yellow indicator move into the windows during the injection.  The injection is 

complete when the yellow indicator stops moving.   



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7.  Lift the pre-filled pen straight up from the injection site.  The white needle sleeve will move 
down over the needle and lock into place over the needle tip.  Do not try to touch the needle.  
The white needle sleeve is there to protect you from touching the needle.    

 

         
 
8.  You may notice a spot of blood at the injection site.  You can press a cotton ball or a piece of 

gauze over the injection site for 10 seconds.  Do not rub the injection site.  Use a plaster if you 
want to. 

Throwing away supplies 

• Do not put either of the caps back on the pre-filled pen. 
• Put used pre-filled pen immediately into the special container as instructed by your doctor, 

nurse or pharmacist. 
• Keep this container out of the reach and sight of children. 
• Never put the pre-filled pens that you have used into your normal household rubbish bin. 
• Only use each pre-filled pen for one injection.   

If you use more Trudexa than you should: 

If you accidentally inject Trudexa more frequently than told to by your doctor, you should call your 
doctor and tell him/her that you have taken more.  Always take the outer carton or the pre-filled pen of 
medicine with you, even if it is empty.  

If you forget to take Trudexa: 

If you forget to give yourself an injection, you should inject the next dose of Trudexa as soon as you 
remember.  Then take your next dose as you would have on your originally scheduled day, had you 
not forgotten a dose.  
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 

4. POSSIBLE SIDE EFFECTS 

Like all medicines, Trudexa can have side effects, although not everybody gets them.  Most side 
effects are mild to moderate.  However, some may be serious and require treatment.  Side effects may 
occur at least up to 5 months after the last treatment.   
 
Tell your doctor immediately if you notice any of the following:  
• Severe rash, hives or other signs of allergic reaction;  
• Swollen face, hands, feet; 
• Trouble breathing, swallowing; 



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• Shortness of breath with exertion or upon lying down or swelling of the feet; 
• Signs and symptoms suggestive of blood disorders such as persistent fever, bruising, bleeding, 

paleness. 
 
Tell your doctor as soon as possible if you notice any of the following:  
• Signs of infection such as fever, malaise, wounds, dental problems, burning on urination; 
• Feeling weak or tired; 
• Coughing; 
• Tingling; 
• Numbness; 
• Double vision; 
• Arm or leg weakness. 
 
The symptoms described above can be signs of the below listed side effects, which have been 
observed with Trudexa: 
 
Very common (≥ 1/10 patients):   
• injection site reactions (including pain, swelling, redness or itching). 
 
Common (≥ 1/100 and < 1/10 patients):   
• lower respiratory tract infections (such as bronchitis, pneumonia);  
• upper respiratory tract infections (including cold, runny nose, sinus infection); 
• urinary tract infection, cold blisters, shingles; 
• dizziness, including vertigo, headache; 
• eye inflammation; 
• cough, sore throat; 
• nausea, diarrhoea, abdominal pain, mouth ulcers; 
• elevated liver enzymes; 
• rash, itching, hair loss; 
• fatigue; 
• fever. 
 
Uncommon (≥ 1/1000 and< 1/100 patients):   
• serious infections (such as sepsis [blood poisoning]), joint infection, fungal infections; 
• skin wart; 
• anaemia, low white blood cell counts; 
• allergic reactions; 
• increased lipid values, appetite disorders; 
• anxiety, depression, feeling sleepy and difficulty sleeping; 
• nerve disorders (such as multiple sclerosis and eye nerve inflammation), taste disturbances; 
• vision disturbances; 
• ear discomfort; 
• sensation of heart beating rapidly, high blood pressure; 
• asthma, shortness of breath; 
• abdominal symptoms (such as vomiting, indigestion, constipation), rectal bleeding; 
• skin disorders (such as psoriasis, eczema or infections)itchy rash, slow wound healing; 
• muscle weakness; 
• urinary disturbances (such as blood in urine, increased urinary frequency); 
• increased menstrual bleeding; 
• flu like symptoms, chest pain, swelling of the feet. 
 



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Rare (< 1/1000) 
• glaucoma; 
• skin cancer; 
• thyroid disorders; 
• protein in urine. 
 
• Other side effects that have been observed in patients taking Trudexa:  
• tuberculosis and other opportunistic infections (infections that occur when resistance to disease 

is lowered); 
• lung disease. 
 
If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or pharmacist.   
 
 
5. HOW TO STORE TRUDEXA 

Keep out of the reach and sight of children.  
 
Do not use the Trudexa pre-filled pen after the expiry date stated on the label/blister/carton after EXP:.  
The expiry date refers to the last day of that month.  
 
Store in a refrigerator (2°C – 8°C).  Keep the pre-filled pen in the outer carton.  Do not freeze. 

6. FURTHER INFORMATION 

Trudexa 40 mg solution for injection in pre-filled pen is supplied as a sterile solution of 40 mg 
adalimumab dissolved in 0.8 ml solution. 
 
What Trudexa contains 
 
The active substance is adalimumab. 
The other ingredients are mannitol, citric acid monohydrate, sodium citrate, sodium dihydrogen 
phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, polysorbate 80, sodium 
hydroxide and water for injections. 
 
What the Trudexa pre-filled pen looks like and contents of the pack 
 
The Trudexa pre-filled pen is a single-use grey- and plum-coloured pen which contains a glass syringe 
with Trudexa.  There are two caps – one is grey and labelled ‘1’ and the other is plum and labelled ‘2’.  
There is a window on each side of the pen through which you can see the Trudexa solution inside the 
syringe.   
 
The Trudexa pre-filled pen is available in packs containing 1, 2, 4, and 6 pre-filled pens.  Each pre-
filled pen comes with 1 alcohol pad.  Not all pack sizes may be marketed.  Trudexa is also available as 
a vial or pre-filled syringe. 
 
Marketing Authorisation Holder 
 
Abbott Laboratories Ltd 
Queenborough 
Kent ME11 5EL 
United Kingdom 
 



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Manufacturer  
 
Abbott Biotechnology Deutschland GmbH 
Max-Planck-Ring 2 
D – 65205 Wiesbaden 
Germany 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
Abbott SA 
Parc Scientifique 
Rue du Bosquet, 2 
B-1348 Ottignies/Louvain-la-Neuve 
Tél/Tel: + 32 10 475311 
 

Luxembourg/Luxemburg 
Abbott SA 
Parc Scientifique 
Rue du Bosquet, 2 
B-1348 Ottignies/Louvain-la-Neuve 
Belgique/Belgien 
Tél/Tel: + 32 10 475311  
 

България 
Т.П. Абот Лабораторис С.А. 
ул. Оборище № 45 
София 1504 
Teл.: + 359 2 846 8429 

Magyarország 
Abbott Laboratories (Magyarország) Kft. 
Teve u. 1/a-c. 
H-1139 Budapest 
Tel.: + 36 1 465 2100 
 

Česká republika 
Abbott Laboratories s. r. o. 
Hadovka Office Park 
Evropská 2590/33d 
CZ-160 00 Praha 6 
Tel: + 420 267 292 111 
 

Malta 
V.J.Salomone Pharma Limited  
79, Simpson Street,  
Marsa HMR 14,  
Malta. 
Tel: + 356  22983201 
 

Danmark 
Abbott Laboratories A/S 
Smakkedalen 6 
DK-2820 Gentofte 
Tlf: + 45 39 77-00-00 
 

Nederland 
Abbott BV 
Siriusdreef 51 
NL-2132 WT Hoofddorp 
Tel: + 31 (0) 23 5544400 
 

Deutschland 
Abbott GmbH & Co. KG 
Max-Planck-Ring 2  
  
D-65205 Wiesbaden 
Tel: + 49 (0) 6122 58-0 
 

Norge 
Abbott Norge AS 
PO Box 1, N-1330 Fornebu 
Martin Linges vei 25, N-1367 Snarøya 
Tlf: + 47 81 55 99 20 
 

Eesti 
Abbott Laboratories Baltics 
Vienibas 87h 
LV-1004 Riia 
Läti 
Tel: + 371 7605580 
 

Österreich 
Abbott Ges.m.b.H.  
Perfektastrasse 84A 
A-1230 Wien 
Tel: + 43 1 891-22 
 

Ελλάδα 
Abbott Laboratories (ΕΛΛΑΣ)Α.Β.Ε.Ε. 
Λεωφόρος Βουλιαγµένης 512 
GR 174 56 Άλιµος, Αθήνα 
Τηλ: + 30 21 0 9985-222 

Polska 
Abbott Laboratories Poland Sp. z o.o. 
ul. Domaniewska 41 
PL-02-672 Warszawa  
Tel.: + 48 22 606-10-50 



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España 
Abbott Laboratories, S.A.  
Avenida de Burgos, 91 
E-28050 Madrid 
Tel: + 34 9 1 337-5200 
 

Portugal 
Abbott Laboratórios, Lda.  
Estrada de Alfragide, nº 67 
Alfrapark, Edifício D,  
P-2610-008 Amadora 
Tel: + 351 (0) 21 472 7100 
 

France 
Abbott France 
10, rue d’Arcueil 
BP 90233 
F-94528 Rungis Cedex 
Tél: + 33 (0) 1 45 60 25 00 
 

România 
Abbott Laboratories S.A. 
Bucharest Business Park 
Şos. Bucureşti-Ploieşti 1A 
Corp B, etaj 3, sector 1 
013681 Bucureşti 
Tel: +40 21 529 30 00 
 

Ireland 
Abbott Laboratories, Ireland, Ltd 
4051 Kingswood Drive 
Citywest Business Campus 
IRL – Dublin 24,  
Tel: + 353 (0) 1 469-1500 
 

Slovenija 
Abbott Laboratories d.o.o. 
Dunajska 22 
SI-1000 Ljubljana 
Tel: + 386 (1) 43 22 322 
 

Ísland 
Vistor hf. 
Hörgatún 2 
IS-210 Garðabær 
Tel: + 354 535 7000 
 

Slovenská republika 
Abbott Laboratories Slovakia s.r.o. 
Trnavská cesta 70 
SK-821 02 Bratislava 2 
Tel: + 421 (0) 2 4445 4176 
 

Italia 
Abbott SpA 
I-04010 Campoverde di Aprilia 
(Latina) 
Tel: + 39 06 928921 
 

Suomi/Finland 
Abbott OY  
Pihatörmä 1A/Gårdsbrinken 1B 
FIN-02240 Espoo/Esbo 
Puh/Tel: + 358 (0) 9 7518 4120 
 

Κύπρος 
Lifepharma (Z.A.M.) Ltd 
Θεοτόκη 4Β 
1055 Λευκωσία  
Τηλ.: + 357 22 34 74 40 

Sverige 
Abbott Scandinavia AB 
Box 509/Gårdsvägen 8 
S-169 29 Solna/S-169 70 Solna 
Tel: + 46 (0) 8 5465 67 00 
 

Latvija 
Abbott Laboratories Baltics 
Vienibas 87h 
LV-1004 Rīga 
Tel: + 371 7605580 
 
 

United Kingdom 
Abbott Laboratories Ltd 
Abbott House 
Unit 2, Vanwall Road 
Vanwall Business Park 
Maidenhead 
Berkshire  SL6 4XE - UK 
Tel: + 44 (0) 1628 773355 
 

Lietuva 
Abbott Laboratories Baltics 
Vienibas 87h  
LV-1004 Rīga 
Latvia 
Tel: + 371 7605580 
 

 



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This leaflet was last approved in {MM/YYYY} 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	MANUFACTURER(S) OF THE OF THE BIOLOGICALACTIVE SUBSTANCE(S) AND MANUFACTURINGAUTHORISATION HOLDER(S) RESPONSIBLE FORBATCH RELEASE
	CONDITIONS OF THE MARKETING AUTHORISATION
	LABELLING
	PACKAGE LEAFLET