Autom Immune

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AUTOM IMMUNE:

http://health.nytimes.com/health/guides/disease/autoimmune-

disorders/overview.html

Auto Immune space:

SureClickIn June 2006, FDA cleared SureClick autoinjector for Enbrelandin September 2006 the FDA cleared use of SureClick for Aranesp.

is a trademarked medical device, produced byAmgenandWyethPharmaceuticals. The product is sold pre-filled with drugs from thesecorporations. The device itself is a needle-based, spring-loaded, plunger(piston)-driveautoinjector(drug delivery device). It is disposable, self-injectable, pen-shaped, and portable. The SureClick autoinjector isavailable for bothAranespforanemiaandEnbrelforrheumatoid arthritis.

HUMIRA:

Humira is intended for the treatment of:

Rheumatoid arthritis Humira is used to reduce the signs andsymptoms of moderately to severely active rheumatoid arthritis, apainful disease of the joints, as well as to slow down and protectagainst damage to joints. Signs and symptoms of rheumatoidarthritis include joint pain, tenderness, swelling and stiffness.

Polyarticular Juvenile Idiopathic Arthritis Humira is indicatedfor reducing the signs and symptoms of moderately to severelyactive polyarticular juvenile idiopathic arthritis, which is aninflammatory disease, involving multiple joints, with diagnosistypically occurring in children between the ages of 4 and 17 years.

Psoriatic arthritis Humira is used to reduce the signs and
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symptoms, as well as inhibit the progression of structural damage ofmoderately to severely active psoriatic arthritis, a disease of the

joints and skin, with some similarities to rheumatoid arthritis, as wellas psoriasis and other factors.

Ankylosing spondylitis Humira is used to reduce the signsand symptoms in patients with active ankylosing spondylitis, aninflammatory disease of the spine. Signs and symptoms ofankylosing spondylitis include back pain and morning stiffness.

Crohn's Disease Humira is used for the treatment ofmoderate to severe Crohn's disease in adults to reduce the signsand symptoms of the disease and to induce and maintain clinicalremission in patients who have had an inadequate response toconventional therapies, or who have lost response to or areintolerant of infliximab.

Psoriasis Humira is used to reduce the signs and symptomsof moderate to severe chronic plaque This site uses cookies. Bycontinuing to browse the site you are agreeing to our policy on the use ofcookies.Find out more here.

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AbbVie LimitedAbbott House, Vanwall Business Park, Vanwall Road, Maidenhead, SL6 4XETelephone: +44 (0)1628 561 090Fax: +44 (0)1628 644 185WWW:http://www.abbvie.co.ukMedical Information e-mail:[email protected] of Hours Telephone: +44 (0)1628 774 920

Before you contact this company: often several companies will market medicinethat this is the correct company before contacting them.Why?

Summary of Product Characteristics last updated on the eMC: 26/09/2013

SPC Humira Pre-filled Pen, Pre-filled Syringe and Vial

Table of Contents

1. Name of the medicinal product2. Qualitative and quantitative composition3. Pharmaceutical form4. Clinical particulars4.1 Therapeutic indications

4.2 Posology and method of administration4.3 Contraindications4.4 Special warnings and precautions for use4.5 Interaction with other medicinal products and other forms

of interaction4.6 Fertility, pregnancy and lactation4.7 Effects on ability to drive and use machines4.8 Undesirable effects4.9 Overdose5. Pharmacological properties

5.1 Pharmacodynamic properties5.2 Pharmacokinetic properties5.3 Preclinical safety data6. Pharmaceutical particulars6.1 List of excipients6.2 Incompatibilities6.3 Shelf life
http://www.abbvie.co.uk/http://www.abbvie.co.uk/http://www.abbvie.co.uk/mailto:[email protected]:[email protected]:[email protected]://www.medicines.org.uk/emc/help.aspx?view=6http://www.medicines.org.uk/emc/help.aspx?view=6http://www.medicines.org.uk/emc/help.aspx?view=6http://beta.medicines.org.uk/http://beta.medicines.org.uk/http://www.medicines.org.uk/emc/help.aspx?view=6mailto:[email protected]://www.abbvie.co.uk/


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6.4 Special precautions for storage6.5 Nature and contents of container6.6 Special precautions for disposal and other handling7. Marketing authorisation holder8. Marketing authorisation number(s)

9. Date of first authorisation/renewal of the authorisation10. Date of revision of the text

Go to top of the page1. Name of the medicinal product

Humira 40 mg solution for injection in pre-filled syringe

Humira 40 mg solution for injection in pre-filled pen

Humira 40 mg/0.8 ml solution for injection for paediatric use

Go to top of the page2. Qualitative and quantitative composition

Each 0.8 ml single dose pre-filled syringe contains 40 mg of adalimumab.

Each 0.8 ml single dose pre-filled pen contains 40 mg of adalimumab.

Each 0.8 ml single dose vial contains 40 mg of adalimumab.

Adalimumab is a recombinant human monoclonal antibody expressed in Chinese H

For the full list of excipients, see section 6.1.

Go to top of the page3. Pharmaceutical form

Clear solution for injection in pre-filled syringe.

Clear solution for injection in pre-filled pen

Clear solution for injection in single use vial.

Go to top of the page4. Clinical particulars

Go to top of the page4.1 Therapeutic indications

Rheumatoid arthritis

Humira in combination with methotrexate, is indicated for:


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the treatment of moderate to severe, active rheumatoid arthritis in adult patients wmodifying anti-rheumatic drugs including methotrexate has been inadequate.

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

Humira can be given as monotherapy in case of intolerance to methotrexate or whmethotrexate is inappropriate.

Humira has been shown to reduce the rate of progression of joint damage as measphysical function, when given in combination with methotrexate.

Polyarticular juvenile idiopathic arthritis

Humira in combination with methotrexate is indicated for the treatment of active poarthritis, in children and adolescents from the age of 2 years who have had an inaddisease-modifying anti-rheumatic drugs (DMARDs). Humira can be given as mono

methotrexate or when continued treatment with methotrexate is inappropriate (for tsection 5.1). Humira has not been studied in children aged less than 2 years.

Axial spondyloarthritis

Ankylosing spondylitis (AS)

Humira is indicated for the treatment of adults with severe active ankylosing spondresponse to conventional therapy.

Axial spondyloarthritis without radiographic evidence of AS

Humira is indicated for the treatment of adults with severe axial spondyloarthritis wbut with objective signs of inflammation by elevated CRP and / or MRI, who have hare intolerant to nonsteroidal anti-inflammatory drugs.

Psoriatic arthritis

Humira is indicated for the treatment of active and progressive psoriatic arthritis in previous disease-modifying anti-rheumatic drug therapy has been inadequate. Humrate of progression of peripheral joint damage as measured by X-ray in patients wisubtypes of the disease (see Section 5.1) and to improve physical function.

PsoriasisHumira is indicated for the treatment of moderate to severe chronic plaque psoriasrespond to or who have a contraindication to, or are intolerant to other systemic themethotrexate or PUVA.

Crohn's disease


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Humira is indicated for treatment of moderately to severely active Crohn's diseaseresponded despite a full and adequate course of therapy with a corticosteroid and/are intolerant to or have medical contraindications for such therapies.

Paediatric Crohn's DiseaseHumira is indicated for the treatment of severe active Crohn's disease in paediatrichave had an inadequate response to conventional therapy including primary nutritiimmunomodulator, or who are intolerant to or have contraindications for such thera

Ulcerative colitis

Humira is indicated for treatment of moderately to severely active ulcerative colitis inadequate response to conventional therapy including corticosteroids and 6-merc(AZA), or who are intolerant to or have medical contraindications for such therapie

Go to top of the page4.2 Posology and method of administration

Posology

Humira treatment should beinitiated and supervised byspecialist physicians experiencedin the diagnosis and treatment of

conditions for which Humira isindicated. Patients treated withHumira should be given thespecial alert card.

After proper training in injectiontechnique, patients may self-inject with Humira if theirphysician determines that it isappropriate and with medicalfollow-up as necessary.

During treatment with Humira,other concomitant therapies (e.g.,corticosteroids and/orimmunomodulatory agents)should be optimised.


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Rheumatoid arthritis

The recommended dose ofHumira for adult patients withrheumatoid arthritis is 40 mgadalimumab administered everyother week as a single dose viasubcutaneous injection.Methotrexate should becontinued during treatment withHumira.

Glucocorticoids, salicylates,nonsteroidal anti-inflammatorydrugs, or analgesics can becontinued during treatment with

Humira. Regarding combinationwith disease modifying anti-rheumatic drugs other thanmethotrexate see sections 4.4and 5.1.

In monotherapy, some patientswho experience a decrease intheir response may benefit froman increase in dose intensity to40 mg adalimumab every week.

Dose Interruption

There may be a need for doseinterruption, for instance beforesurgery or if a serious infectionoccurs.

Available data suggest that re-introduction of Humira afterdiscontinuation for 70 days or

longer resulted in the samemagnitudes of clinical responseand similar safety profile asbefore dose interruption.

Ankylosing spondylitis, axialspondyloarthritis withoutradiographic evidence of AS and


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psoriatic arthritis

The recommended dose ofHumira for patients withankylosing spondylitis, axialspondyloarthritis withoutradiographic evidence of AS andfor patients with psoriatic arthritisis 40 mg adalimumabadministered every other week asa single dose via subcutaneousinjection.

For all of the above indications,available data suggest that theclinical response is usually

achieved within 12 weeks oftreatment. Continued therapyshould be carefully reconsideredin a patient not responding withinthis time period.

Psoriasis

The recommended dose ofHumira for adult patients is aninitial dose of 80 mg administeredsubcutaneously, followed by 40mg subcutaneously given everyother week starting one weekafter the initial dose.

Continued therapy beyond 16weeks should be carefullyreconsidered in a patient notresponding within this timeperiod.

Crohn's disease

The recommended Humirainduction dose regimen for adultpatients with moderately toseverely active Crohn's diseaseis 80 mg at Week 0 followed by


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40 mg at Week 2. In case there isa need for a more rapid responseto therapy, the regimen 160 mgat Week 0 (dose can beadministered as four injections in

one day or as two injections perday for two consecutive days), 80mg at Week 2, can be used withthe awareness that the risk foradverse events is higher duringinduction.

After induction treatment, therecommended dose is 40 mgevery other week viasubcutaneous injection.

Alternatively, if a patient hasstopped Humira and signs andsymptoms of disease recur,Humira may be re-administered.There is little experience from re-administration after more than 8weeks since the previous dose.

During maintenance treatment,corticosteroids may be tapered inaccordance with clinical practiceguidelines.

Some patients who experiencedecrease in their response maybenefit from an increase indosing frequency to 40 mgHumira every week.

Some patients who have notresponded by Week 4 maybenefit from continued

maintenance therapy throughWeek 12. Continued therapyshould be carefully reconsideredin a patient not responding withinthis time period.


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Ulcerative colitis

The recommended Humirainduction dose regimen for adultpatients with moderate to severeulcerative colitis is 160 mg atWeek 0 (dose can beadministered as four injections inone day or as two injections perday for two consecutive days)and 80 mg at Week 2. Afterinduction treatment, therecommended dose is 40 mgevery other week viasubcutaneous injection.

During maintenance treatment,corticosteroids may be tapered inaccordance with clinical practiceguidelines.

Some patients who experiencedecrease in their response maybenefit from an increase indosing frequency to 40 mgHumira every week.

Available data suggest that

clinical response is usuallyachieved within 2-8 weeks oftreatment. Humira therapy shouldnot be continued in patientsfailing to respond within this timeperiod.

Older people

No dose adjustment is required.

Impaired renal and/or hepaticfunction

Humira has not been studied inthese patient populations. Nodose recommendations can bemade.


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Paediatric Population

Polyarticular Juvenile IdiopathisArthritis

Polyarticular Juvenile IdiopathicArthritis from 2 to 12 years of age

The recommended dose ofHumira for patients withpolyarticular juvenile idiopathicarthritis, aged 2-12 years, is 24mg/m body surface area up to amaximum single dose of 20 mgadalimumab (for patients aged 2-


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120 0.3 0.4 0.4 0.4

130 0.4 0.4 0.5

140 0.4 0.4 0.5

150 0.5 0.5

160 0.5 0.5

170 0.6

180

*Maximum single dose is 40 mg(0.8 ml)

Polyarticular Juvenile IdiopathicArthritis from 13 years of age

For adolescents from 13 years ofage, a dose of 40 mg isadministered every other weekregardless of body surface area.

A 40 mg pen and a 40 mgprefilled syringe are alsoavailable for patients toadminister a full 40 mg dose.

Available data suggest that

clinical response is usuallyachieved within 12 weeks oftreatment. Continued therapyshould be carefully reconsideredin a patient not responding withinthis time period.

There is no relevant use ofHumira in children aged less than2 years in this indication.

Paediatric psoriasis

The safety and efficacy of Humirain children aged 4-17 years havenot been established. No dataare available. There is norelevant use of Humira in children


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aged


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administered as four injections inone day or as two injections perday for two consecutive days), 80mg at Week 2 can be used, withthe awareness that the risk for

adverse events may be higherwith use of the higher inductiondose.

After induction treatment, therecommended dose is 40 mgevery other week viasubcutaneous injection. Somesubjects who experienceinsufficient response may benefitfrom an increase in dosing

frequency to 40 mg Humira everyweek.

Continued therapy should becarefully considered in a subjectnot responding by Week 12.

There is no relevant use ofHumira in children aged less than6 years in this indication.

Paediatric ulcerative colitis

The safety and efficacy of Humirain children aged 4-17 years havenot yet been established. No dataare available. There is norelevant use of Humira in childrenaged


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Method of administration

Humira is administered bysubcutaneous injection. Full

instructions for use are providedin the package leaflet.

A 40 mg pen and a 40 mgprefilled syringe are alsoavailable for patients toadminister a full 40 mg dose.

Go to top of the page4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section

Active tuberculosis or other severe infections such as sepsis, and opportunistic infe

Moderate to severe heart failure (NYHA class III/IV) (see section 4.4).

Go to top of the page4.4 Special warnings and precautions for use

Infections

Patients taking TNF-antagonists are more susceptible to serious infections. Impairrisk for developing infections. Patients must therefore be monitored closely for infebefore, during and after treatment with Humira. Because the elimination of adalimumonitoring should be continued throughout this period.

Treatment with Humira should not be initiated in patients with active infections incluntil infections are controlled. In patients who have been exposed to tuberculosis aareas of high risk of tuberculosis or endemic mycoses, such as histoplasmosis, cothe risk and benefits of treatment with Humira should be considered prior to initiatininfections).

Patients who develop a new infection while undergoing treatment with Humira, shoundergo a complete diagnostic evaluation. Administration of Humira should be discnew serious infection or sepsis, and appropriate antimicrobial or antifungal therapy

infection is controlled. Physicians should exercise caution when considering the ushistory of recurring infection or with underlying conditions which may predispose pause of concomitant immunosuppressive medications.

Serious infections:

Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungaopportunistic infections such as listeriosis, legionellosis and pneumocystis have be


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Humira.

Other serious infections seen in clinical trials include pneumonia, pyelonephritis, seHospitalisation or fatal outcomes associated with infections have been reported.

Tuberculosis:

Tuberculosis, including reactivation and new onset of tuberculosis, has been reporReports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tube

Before initiation of therapy with Humira, all patients must be evaluated for both actinfection. This evaluation should include a detailed medical assessment of patient previous exposure to people with active tuberculosis and previous and/or current im

Appropriate screening tests (i.e. tuberculin skin test and chest X-ray) should be perecommendations may apply). It is recommended that the conduct and results of thpatient alert card. Prescribers are reminded of the risk of false negative tuberculin

patients who are severely ill or immunocompromised.If active tuberculosis is diagnosed, Humira therapy must not be initiated (see sectio

In all situations described below, the benefit/risk balance of therapy should be very

If latent tuberculosis is suspected, a physician with expertise in the treatment of tub

If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-before the initiation of Humira, and in accordance with local recommendations.

Use of anti-tuberculosis prophylaxis treatment should also be considered before thwith several or significant risk factors for tuberculosis despite a negative test for tubpast history of latent or active tuberculosis in whom an adequate course of treatme

Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis hwith Humira. Some patients who have been successfully treated for active tubercuwhile being treated with Humira.

Patients should be instructed to seek medical advice if signs/symptoms suggestivepersistent cough, wasting/weight loss, low grade fever, listlessness) occur during o

Other opportunistic infections:

Opportunistic infections, including invasive fungal infections have been observed ininfections have not consistently been recognised in patients taking TNF-antagonistappropriate treatment, sometimes resulting in fatal outcomes.

For patients who develop the signs and symptoms such as fever, malaise, weight land/or pulmonary infiltrates or other serious systemic illness with or without concominfection should be suspected and administration of Humira should be promptly disadministration of empiric antifungal therapy in these patients should be made in coexpertise in the care of patients with invasive fungal infections.


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Hepatitis B reactivation

Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist inccarriers of this virus (i.e., surface antigen positive). Some cases have had a fatal oforHBV infection before initiating treatment with Humira. For patients who test positconsultation with a physician with expertise in the treatment of hepatitis B is recom

Carriers of HBV who require treatment with Humira should be closely monitored foHBV infection throughout therapy and for several months following termination of tpatients who are carriers of HBV with anti-viral therapy in conjunction with TNF-anreactivation are not available. In patients who develop HBV reactivation, Humira shviral therapy with appropriate supportive treatment should be initiated.

Neurological events

TNF-antagonists including Humira have been associated in rare instances with newsymptoms and/or radiographic evidence of central nervous system, demyelinating optic neuritis and peripheral demyelinating disease, including Guillain-Barr syndro

caution in considering the use of Humira in patients with pre-existing or recent-onssystem demyelinating disorders.

Allergic reactions

Serious allergic reactions associated with Humira were rare during clinical trials. Nassociated with Humira were uncommon during clinical trials. Reports of serious aanaphylaxis have been received following Humira administration. If an anaphylactireaction occurs, administration of Humira should be discontinued immediately and

Immunosuppression

In a study of 64 patients with rheumatoid arthritis that were treated with Humira, theof delayed-type hypersensitivity, depression of immunoglobulin levels, or change inNK-cells, monocyte/macrophages, and neutrophils.

Malignancies and lymphoproliferative disorders

In the controlled portions of clinical trials of TNF-antagonists, more cases of malignbeen observed among patients receiving a TNF-antagonist compared with control was rare. In the post marketing setting, cases of leukemia have been reported in pantagonist. There is an increased background risk for lymphoma and leukemia in rlong-standing highly active, inflammatory disease, which complicates the risk estima possible risk for the development of lymphomas, leukemia, and other malignanci

antagonist cannot be excluded.Malignancies, some fatal, have been reported among children, adolescents and yotreated with TNF-antagonists (initiation of therapy 18 years of age), including adasetting. Approximately half the cases were lymphomas. The other cases representmalignancies and included rare malignancies usually associated with immunosuppof malignancies in children and adolescents treated with TNF-antagonists cannot b

Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified


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Congestive heart failure

In a clinical trial with another TNF-antagonist worsening congestive heart failure ancongestive heart failure have been observed. Cases of worsening congestive hearpatients receiving Humira. Humira should be used with caution in patients with mildHumira is contraindicated in moderate to severe heart failure (see section 4.3). Trediscontinued in patients who develop new or worsening symptoms of congestive h

Autoimmune processes

Treatment with Humira may result in the formation of autoimmune antibodies. The Humira on the development of autoimmune diseases is unknown. If a patient develupus-like syndrome following treatment with Humira and is positive for antibodies further treatment with Humira should not be given (see section 4.8).

Concurrent administration of biologic DMARDS or TNF-antagonists

Serious infections were seen in clinical studies with concurrent use of anakinra and

etanercept, with no added clinical benefit compared to etanercept alone. Because seen with the combination of etanercept and anakinra therapy, similar toxicities maof anakinra and other TNF-antagonists. Therefore, the combination of adalimumab(See section 4.5).

Concomitant administration of adalimumab with other biologic DMARDS (e.g, anakantagonists is not recommended based upon the possible increased risk for infectiand other potential pharmacological interactions. (See section 4.5).

Surgery

There is limited safety experience of surgical procedures in patients treated with Hadalimumab should be taken into consideration if a surgical procedure is planned. while on Humira should be closely monitored for infections, and appropriate actionsafety experience in patients undergoing arthroplasty while receiving Humira.

Small bowel obstruction

Failure to respond to treatment for Crohn's disease may indicate the presence of firequire surgical treatment. Available data suggest that Humira does not worsen or

Older people

The frequency of serious infections among Humira treated subjects over 65 years

those under 65 years of age (1.45%). Some of those had a fatal outcome. Particulainfection should be paid when treating the elderly.

Paediatric population

See Vaccinations above.


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Go to top of the page4.5 Interaction with other medicinal products and other forms of interaction

Humira has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic artaking Humira as monotherapy and those taking concomitant methotrexate. AntiboHumira was given together with methotrexate in comparison with use as monother

without methotrexate resulted in increased formation of antibodies, increased clearadalimumab (see section 5.1).

The combination of Humira and anakinra is not recommended (see section 4.4 CoDMARDS or TNF-antagonists).

The combination of Humira and abatacept is not recommended (see section 4.4 CDMARDS or TNF-antagonists).

Go to top of the page

4.6 Fertility, pregnancy and lactationPregnancy

For Humira, limited clinical data on exposed pregnancies are available

In a developmental toxicity study conducted in monkeys, there was no indication oteratogenicity. Preclinical data on postnatal toxicity of adalimumab are not availabl

Due to its inhibition of TNF, adalimumab administered during pregnancy could affthe newborn. Administration of adalimumab is not recommended during pregnancy

Adalimumab may cross the placenta into the serum of infants born to women treatpregnancy. Consequently, these infants may be at increased risk for infection. Adminfants exposed to adalimumab in utero is not recommended for 5 months followininjection during pregnancy.

Lactation

Breast feeding

It is not known whether adalimumab is excreted in human milk or absorbed system

However, because human immunoglobulins are excreted in milk, women must not after the last Humira treatment.

Fertility

Preclinical data on fertility effects of adalimumab are not available.

Women of child bearing potential, Contraception in males and females

Women of childbearing potential are strongly recommended to use adequate contr


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continue its use for at least five months after the last Humira treatment.

Go to top of the page4.7 Effects on ability to drive and use machines

Humira may have a minor influence on the ability to drive and use machines. Vertigfollowing administration of Humira (see Section 4.8).

Go to top of the page4.8 Undesirable effects

Humira was studiedin 8,152 patients inpivatol controlled andopen label trials for

up to 60 months ormore. These trialsincluded rheumatoidarthritis patients withshort term and longstanding disease,polyarticular juvenileidiopathic arthritis aswell as ankylosingspondylitis, axial

spondyloarthritiswithout radiographicevidence of AS,psoriatic arthritis,Crohn's disease,ulcerative colitis andpsoriasis patients.The data in Table 2is based on thepivotal controlledstudies involving5,312 patientsreceiving Humira and3,133 patientsreceiving placebo oractive comparatorduring the controlledperiod and


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spontaneousreporting.

The proportion ofpatients whodiscontinuedtreatment due toadverse eventsduring the double-blind, controlledportion of pivotalstudies was 6.1% forpatients takingHumira and 5.8% forcontrol treatedpatients.

Summary of thesafety profile

The most commonlyreported adversereactions areinfections (such asnasopharyngitis,upper respiratorytract infection and

sinusitis), injectionsite reactions(erythema, itching,haemorrhage, painor swelling),headache andmusculoskeletalpain.

Serious adversereactions have been

reported for Humira.TNF-antagonists,such as Humiraaffect the immunesystem and their usemay affect the body'sdefense against


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infection and cancer.

Fatal and life-threateninginfections (includingsepsis, opportunisticinfections and TB),HBV reactivation andvarious malignancies(including leukaemia,lymphoma andHSTCL) have alsobeen reported withuse of Humira.

Serious

haematological,neurological andautoimmunereactions have alsobeen reported.These include rarereports ofpancytopenia,aplastic anaemia,central andperipheraldemyelinating eventsand reports of lupus,lupus-relatedconditions andStevens-Johnsonsyndrome.

Paediatric population

Undesirable effects

in paediatric patients

In general, theadverse events inpaediatric patientswere similar infrequency and typeto those seen in


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Table 2

Undesirable Effects

System Organ Class

Infections and infestat

Neoplasms benign, m

unspecified (includingpolyps)*

Blood and the lymphadisorders*

Immune system disor


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Uncommon

Rare

Metabolism and nutrition disorders Very commo

Common

Psychiatric disorders Common

Nervous system disorders* Very commo

Common

Uncommon

Rare

Eye disorders Common

Uncommon

Ear and labyrinth disorders Common

Uncommon

Cardiac disorders* Common

Uncommon

RareVascular disorders Common

Uncommon

Respiratory, thoracic andmediastinal disorders*

Common

Uncommon

RareGastrointestinal disorders Very commo

Common

Uncommon


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Rare

Hepato-biliary disorders* Very Commo

Uncommon

Rare

Not Known

Skin and subcutaneous tissuedisorders

Very Commo

Common

Uncommon

Rare

Not known

Musculoskeletal and, connectivetissue disorders

Very commo

Common

Uncommon

Rare

Renal and urinary disorders Common

Uncommon

Reproductive system and breastdisorders

Uncommon

General disorders andadministration site conditions*

Very Commo

Common

Uncommon

Investigations* Common


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Injury, poisoning and proceduralcomplications

Common

* further information

is found elsewhere insections 4.3, 4.4 and4.8

** including openlabel extensionstudies1) includingspontaneousreporting data

Description ofselected adversereactions

Injection sitereactions

In the pivotalcontrolled trials inadults and children,13.6% of patientstreated with Humira

developed injectionsite reactions(erythema and/oritching,haemorrhage, painor swelling),compared to 7.6% ofpatients receivingplacebo or activecontrol. Injection site

reactions generallydid not necessitatediscontinuation of themedicinal product.

Infections

In the pivotalcontrolled trials in


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invasiveopportunisticinfections (e.g.disseminated orextrapulmonary

histoplasmosis,blastomycosis,coccidioidomycosis,pneumocystiscandidiasis,aspergillosis andlisteriosis). Most ofthe cases oftuberculosisoccurred within the

first eight monthsafter initiation oftherapy and mayreflectrecrudescence oflatent disease.

Malignancies andlymphoproliferativedisorders

No malignancieswere observed in203 patients aged 2to 17 years with anexposure of 605.3patient years duringHumira trials in

juvenile idiopathicarthritis patients. Inaddition, nomalignancies were

observed in 192paediatric patientswith an exposure of258.9 patient yearsduring a Humira trialin paediatric patientswith Crohn's


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disease.

During the controlledportions of pivotalHumira trials inadults of at least 12weeks in duration inpatients withmoderately toseverely activerheumatoid arthritis,ankylosingspondylitis, axialspondyloarthritiswithout radiographicevidence of AS,

psoriatic arthritis,psoriasis, Crohn'sdisease andulcerative colitismalignancies, otherthan lymphoma andnon-melanoma skincancer, wereobserved at a rate(95% confidence

interval) of 6.0 (3.7,9.8) per 1,000patient-years among4,622 Humira treatedpatients versus arate of 5.1 (2.4, 10.7)per 1,000 patient-years among 2,828control patients(median duration of

treatment was 5.1months for Humiraand 4.0 months forcontrol-treatedpatients). The rate(95% confidenceinterval) of non-


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patients and over24,568 patient-yearsof therapy, theobserved rate ofmalignancies, other

than lymphoma andnon-melanoma skincancers isapproximately 8.8per 1,000 patientyears. The observedrate of non-melanoma skincancers isapproximately 10.3

per 1,000 patientyears, and theobserved rate oflymphomas isapproximately 1.4per 1,000 patientyears.

In post-marketingexperience fromJanuary 2003 to

December 2010,predominantly inpatients withrheumatoid arthritis,the reported rate ofmalignancies isapproximately 2.7per 1,000 patienttreatment years. Thereported rates for

non-melanoma skincancers andlymphomas areapproximately 0.2and 0.3 per 1,000patient treatmentyears, respectively


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(see section 4.4).

Rare post-marketingcases ofhepatosplenic T-celllymphoma havebeen reported inpatients treated withadalimumab (seesection 4.4).

Autoantibodies

Patients had serumsamples tested forautoantibodies atmultiple time points

in rheumatoidarthritis studies I V.In these trials, 11.9%of patients treatedwith Humira and8.1% of placebo andactive control treated patients thathad negativebaseline anti-nuclear

antibody titresreported positivetitres at Week 24.Two patients out of3,441 treated withHumira in allrheumatoid arthritisand psoriatic arthritisstudies developedclinical signssuggestive of new-onset lupus-likesyndrome. Thepatients improvedfollowingdiscontinuation oftherapy. No patientsdeveloped lupus


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nephritis or centralnervous systemsymptoms.

Hepato-biliary eventsIn controlled Phase 3trials of Humira inpatients withrheumatoid arthritisand psoriatic arthritiswith a control periodduration rangingfrom 4 to 104 weeks, ALT elevations 3

x ULN occurred in3.7% of Humira-treated patients and1.6% of control-treated patients.

In controlled Phase 3trials of Humira inpatients with plaquePsoriasis with acontrol period

duration rangingfrom 12 to 24 weeks,

ALT elevations 3 xULN occurred in1.8% of Humira-treated patients and1.8% of control-treated patients.

In the JIA trial thefew transaminase

elevations weresmall and similar inthe placebo andadalimumabexposed patients,and mostly occurredin combination with


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methotrexate.

In controlled Phase 3trials of Humira inpatients with Crohn'sdisease andulcerative colitis witha control periodranging from 4 to 52weeks. ALTelevations 3 x ULNoccurred in 0.9% ofHumira-treatedpatients and 0.9% ofcontrolled-treatedpatients.

In the Phase 3 trial ofHumira in patientswith paediatricCrohn's diseasewhich evaluatedefficacy and safety oftwo body weightadjustedmaintenance doseregimens followingbody weight adjustedinduction therapy upto 52 weeks oftreatment, ALTelevations 3 x ULNoccurred in 2.6% ofpatients all of whomwere exposed toconcomitantimmunosuppressant

s at baseline.

Across all indicationsin clinical trialspatients with raised

ALT wereasymptomatic and inmost cases


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elevations weretransient andresolved oncontinued treatment.However,there have

also been post-marketing reports ofliver failure as wellas less severe liverdisorders that mayprecede liver failure,such as hepatitisincludingautoimmunehepatitis in patients

receivingadalimumab.

Concurrent treatmentwith azathioprine/6-mercaptopurine

In adult Crohn'sdisease studies,higher incidences of

malignant andserious infection-related adverseevents were seenwith the combinationof Humira andazathioprine/6-mercaptopurinecompared withHumira alone.

Reporting ofsuspected adversereactions

Reporting suspectedadverse reactionsafter authorisation of


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the medicinalproduct is important.It allows continuedmonitoring of thebenefit/risk balance

of the medicinalproduct. Healthcareprofessionals areasked to report anysuspected adversereactions via theYellow CardScheme:

Website:www.mhra.gov.uk/ye

llowcard

Go to top of the page4.9 Overdose

No dose-limiting toxicity was observed during clinical trials. The highest dose level intravenous doses of 10 mg/kg, which is approximately 15 times the recommended

Go to top of the page5. Pharmacological properties

Go to top of the page5.1 Pharmacodynamic properties

Pharmacotherapeuc group: Selectiveimmunosuppressiveagents. ATC code:L04AB04

Mechanism of actio

Adalimumab bindsspecifically to TNFand neutralizes thebiological function oTNF by blocking itsinteraction with thep55 and p75 cell


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surface TNFreceptors.

Adalimumab alsomodulates biologicaresponses that areinduced or regulateby TNF, includingchanges in the leveof adhesionmoleculesresponsible forleukocyte migration(ELAM-1, VCAM-1,and ICAM-1 with anIC50 of 0.1-0.2 nM).

Pharmacodynamiceffects

After treatment withHumira, a rapiddecrease in levels oacute phasereactants ofinflammation (C-reactive protein

(CRP) anderythrocytesedimentation rate(ESR)) and serumcytokines (IL-6) wasobserved, compareto baseline inpatients withrheumatoid arthritisSerum levels ofmatrixmetalloproteinases(MMP-1 and MMP-3that produce tissueremodellingresponsible forcartilage destructionwere also decrease


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after Humiraadministration.Patients treated witHumira usuallyexperienced

improvement inhaematological signof chronicinflammation.

A rapid decrease inCRP levels was alsobserved in patientswith polyarticular

juvenile idiopathicarthritis, Crohn's

disease andulcerative colitis aftetreatment withHumira. In patientswith Crohn'sdisease, a reductionof the number ofcells expressinginflammatorymarkers in the colon

including asignificant reductionof expression of TN

was seen.Endoscopic studiesin intestinal mucosahave shownevidence of mucosahealing inadalimumab treated

patients.Clinical efficacy andsafety

Adults withRheumatoid arthritis


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Humira wasevaluated in over3000 patients in allrheumatoid arthritisclinical trials. The

efficacy and safety Humira wereassessed in fiverandomised, doubleblind and well-controlled studies.Some patients weretreated for up to 120months duration.

RA study I evaluate

271 patients withmoderately toseverely activerheumatoid arthritiswho were 18 yearold, had failedtherapy with at leasone disease-modifying, antirheumatic drug and

had insufficientefficacy withmethotrexate atdoses of 12.5 to 25mg (10 mg ifmethotrexate-intolerant) everyweek and whosemethotrexate doseremained constant

10 to 25 mg everyweek. Doses of 20,40 or 80 mg ofHumira or placebowere given everyother week for 24weeks.


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RA study IIevaluated 544patients withmoderately toseverely active

rheumatoid arthritiswho were 18 yearold and had failedtherapy with at leasone disease-modifying, anti-rheumatic drugs.Doses of 20 or 40mg of Humira weregiven by

subcutaneousinjection every otheweek with placeboon alternative weekor every week for 2weeks; placebo wasgiven every week fothe same duration.No other disease-modifying anti-

rheumatic drugswere allowed.

RA study IIIevaluated 619patients withmoderately toseverely activerheumatoid arthritiswho were 18 yearold, and who had a

ineffective responseto methotrexate atdoses of 12.5 to 25mg or have beenintolerant to 10 mg methotrexate everyweek. There were


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three groups in thisstudy. The firstreceived placeboinjections everyweek for 52 weeks.

The second receive20 mg of Humiraevery week for 52weeks. The thirdgroup received 40mg of Humira everyother week withplacebo injections oalternate weeks.Upon completion of

the first 52 weeks,457 patients enrollein an open-labelextension phase inwhich 40 mg ofHumira/MTX wasadministered everyother week up to 10years.

RA study IV primari

assessed safety in636 patients withmoderately toseverely activerheumatoid arthritiswho were 18 yearold. Patients werepermitted to be eithdisease-modifying,anti-rheumatic drug

nave or to remain otheir pre-existingrheumatologictherapy provided ththerapy was stablefor a minimum of 28days. These


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therapies includemethotrexate,leflunomide,hydroxychloroquinesulfasalazine and/o

gold salts. Patientswere randomised to40 mg of Humira orplacebo every otheweek for 24 weeks.

RA study Vevaluated 799methotrexate-naveadult patients withmoderate to severe

active earlyrheumatoid arthritis(mean diseaseduration less than 9months). This studyevaluated theefficacy of Humira 4mg every otherweek/methotrexatecombination therap

Humira 40 mg everother weekmonotherapy andmethotrexatemonotherapy inreducing the signsand symptoms andrate of progression

joint damage inrheumatoid arthritis

for 104 weeks.The primary endpoint in RA studies II and III and thesecondary endpointin RA study IV wasthe percent of


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patients whoachieved an ACR 2response at Week 2or 26. The primaryendpoint in RA stud

V was the percent opatients whoachieved an ACR 5response at Week52. RA studies IIIand V had anadditional primaryendpoint at 52 weeof retardation ofdisease progression

(as detected by X-ray results). RAstudy III also had aprimary endpoint ofchanges in quality olife.

ACR response

The percent ofHumira-treatedpatients achieving

ACR 20, 50 and 70responses wasconsistent across Rstudies I, II and III.The results for the 4mg every other weedose aresummarised in Tab3.

Table 3

ACR Responses inPlacebo-ControlleTrials

(Percent of


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Patients)

Response RA St

Place

n=60

ACR 20

6 months 13.3%

12 months NA

ACR 50

6 months 6.7%

12 months NA

ACR 70

6 months 3.3%

12 months NA

a RA study I at 24weeks, RA study II 26 weeks , and RAstudy III at 24 and 5weeksb

40 mg Humiraadministered everyother weekc MTX =methotrexate

**p < 0.01, Humiraversus placebo

In RA studies I-IV, aindividualcomponents of the

ACR responsecriteria (number oftender and swollen

joints, physician andpatient assessmentof disease activityand pain, disability


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index (HAQ) scoresand CRP (mg/dl)values) improved at24 or 26 weekscompared to

placebo. In RA studIII, theseimprovements weremaintainedthroughout 52weeks.

In the open-labelextension for RAstudy III, mostpatients who were

ACR respondersmaintained responswhen followed for uto 10 years. Of 207patients who wererandomised toHumira 40mg everyother week, 114patients continuedon Humira 40 mg

every other week fo5 years. Amongthose, 86 patients(75.4%) had ACR 2responses; 72patients (63.2%) ha

ACR 50 responses;and 41 patients(36%) had ACR 70responses. Of 207

patients, 81 patientscontinued on Humir40 mg every otherweek for 10 years.

Among those, 64patients (79.0%) ha

ACR 20 responses;


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56 patients (69.1%)had ACR 50responses; and 43patients (53.1%) ha

ACR 70 responses.

In RA study IV, theACR 20 response opatients treated withHumira plusstandard of care wastatisticallysignificantly betterthan patients treatewith placebo plusstandard of care (p

0.001).

In RA studies I-IV,Humira-treatedpatients achievedstatisticallysignificant ACR 20and 50 responsescompared to placebas early as one totwo weeks afterinitiation oftreatment.

In RA study V withearly rheumatoidarthritis patients whwere methotrexatenave, combinationtherapy with Humiraand methotrexate leto faster andsignificantly greater

ACR responses thamethotrexatemonotherapy andHumira monotherapat Week 52 andresponses were


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sustained at Week104 (see Table 4).

Table 4

ACR Responses inRA Study V

(percent ofpatients)

Response

ACR 20

Week 52

Week 104

ACR 50

Week 52

Week 104

ACR 70

Week 52

Week 104a. p-value is from thusing the Mann-Wh

b. p-value is from ththe Mann-Whitney

c. p-value is from thWhitney U test

At Week 52, 42.9%of patients who

receivedHumira/methotrexacombination therapachieved clinicalremission (DAS28 =90 daysa

Week 56

Clinical remission

Clinical response (C

Patients in steroid-f>=90 daysa

* p < 0.001 forHumira versusplacebo pairwisecomparisons ofproportions

** p < 0.02 forHumira versusplacebo pairwise

comparisons ofproportionsa Of those receivingcorticosteroids atbaseline

Among patients wh


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statisticallysignificantimprovement in thedisease-specificinflammatory bowel

diseasequestionnaire (IBDQtotal score wasachieved at Week 4in patientsrandomised toHumira 80/40 mgand 160/80 mgcompared to placeband was seen at

Weeks 26 and 56 inCD Study III as welamong theadalimumabtreatment groupscompared to theplacebo group.

Paediatric Crohn'sdisease

Humira wasassessed in amulticenter,randomized, doubleblind clinical trialdesigned to evaluatthe efficacy andsafety of inductionand maintenancetreatment with dosedependent on bodyweight (< 40 kg or 40 kg) in 192paediatric subjectsbetween the ages o6 and 17 (inclusive)years, with moderat


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to severe Crohnsdisease (CD) defineas PaediatricCrohn's Disease

Activity Index

(PCDAI) score > 30Subjects had to havfailed conventionaltherapy (including acorticosteroid and/oanimmunomodulator)for CD. Subjects maalso have previousllost response or

been intolerant toinfliximab.

All subjects receiveopen-label inductiontherapy at a dosebased on theirBaseline bodyweight: 160 mg atWeek 0 and 80 mgat Week 2 for

subjects 40 kg, an80 mg and 40 mg,respectively, forsubjects < 40 kg.

At Week 4, subjectswere randomized 1based on their bodyweight at the time toeither the Low Doseor Standard Dose

maintenanceregimens as shownin Table 16.

Table 16

Maintenance regim


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Patient Weight

< 40 kg

40 kg

Efficacy Results

The primary endpoiof the study wasclinical remission atWeek 26, defined aPCDAI score 10.

Clinical remissionand clinical respons(defined as reductio

in PCDAI score of aleast 15 points fromBaseline) rates arepresented in Table17. Rates ofdiscontinuation ofcorticosteroids orimmunomodulatorsare presented inTable 18.

Table 17

Paediatric CD Stud

PCDAI Clinical Re

Week 26Clinical remission

Clinical response

Week 52

Clinical remission


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Clinical response

* p value for Standa

Table 18

Paediatric CD Stud

Discontinuation o

Discontinued cort

Week 26

Week 52

Discontinuation oImmunomodulato

Week 52

Fistula remission3

Week 26

Week 52

1 p value forStandard Dose

versus Low Dosecomparison.2Immunosuppressantherapy could onlybe discontinued at oafter Week 26 at theinvestigator'sdiscretion if thesubject met the

clinical responsecriterion3 defined as aclosure of all fistulasthat were draining aBaseline for at leas2 consecutive post-


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Baseline visits

Statisticallysignificant increase(improvement) fromBaseline to Week 2and 52 in Body MasIndex and heightvelocity wereobserved for bothtreatment groups.

Statistically andclinically significantimprovements fromBaseline were also

observed in bothtreatment groups foquality of lifeparameters(including IMPACTIII).

Ulcerative Colitis

The safety andefficacy of multipledoses of Humirawere assessed inadult patients withmoderately toseverely activeulcerative colitis(Mayo score 6 to 12with endoscopysubscore of 2 to 3) randomised, double

blind, placebo-controlled studies.

In Study UC-I, 390TNF-antagonistnave patients wererandomised toreceive either


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placebo at Weeks 0and 2, 160 mgHumira at Week 0followed by 80 mg aWeek 2, or 80 mg

Humira at Week 0followed by 40 mg aWeek 2. After Week2, patients in bothadalimumab armsreceived 40 mg eowClinical remission(defined as Mayoscore 2 with nosubscore > 1) was

assessed at Week 8In study UC-II, 248patients received160 mg of Humira aWeek 0, 80 mg atWeek 2 and 40 mgeow thereafter, and246 patientsreceived placebo.Clinical results were

assessed forinduction ofremission at Week and for maintenancof remission at Wee52.

Subjects inducedwith 160/80 mgHumira achievedclinical remission

versus placebo atWeek 8 instatisticallysignificantly greaterpercentages in studUC-I (18% vs. 9%respectively,


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p=0.031) and studyUC-II (17% vs. 9%respectively,p=0.019). In studyUC-II, among those

treated with Humirawho were inremission at Week 21/41 (51%) were inremission at Week52.

Results from theoverall UC-II studypopulation areshown in Table 19.

Table19

Response,Remission andMucosal Healing iStudy UC-II

(Percent ofPatients)

Week 52

Clinical Response

Clinical Remission

Mucosal Healing

Steroid-free remiss

Week 8 and 52

Sustained Respons

Sustained Remissio

Sustained Mucosal

Clinical remission is


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Mayo score 2 withno subscore > 1;*p


94/104


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methotrexate.

In patients withpolyarticular juvenilidiopathic arthritis,adalimumabantibodies wereidentified in 27/171subjects (15.8%)treated withadalimumab. Inpatients not givenconcomitantmethotrexate, theincidence was 22/8(25.6%), compared

to 5/85 (5.9%) whenadalimumab wasused as add-on tomethotrexate.

In patients withpsoriatic arthritis,anti-adalimumabantibodies wereidentified in 38/376subjects (10%)treated withadalimumab. Inpatients not givenconcomitantmethotrexate, theincidence was 13.5(24/178 subjects),compared to 7% (14of 198 subjects)when adalimumab

was used as add-onto methotrexate.

In patients withankylosingspondylitis anti-adalimumabantibodies were


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identified in 17/204subjects (8.3%)treated withadalimumab. Inpatients not given

concomitantmethotrexate, theincidence was16/185 (8.6%),compared to 1/19(5.3%) whenadalimumab wasused as add-on tomethotrexate.

In patients with

Crohn's disease,anti-adalimumabantibodies wereidentified in 7/269subjects (2.6%) andin 19/487 subjects(3.9%) withulcerative colitis.

In patients withpsoriasis, anti-adalimumabantibodies wereidentified in 77/920subjects (8.4%)treated withadalimumabmonotherapy.

In plaque psoriasispatients on long teradalimumabmonotherapy whoparticipated in awithdrawal andretreatment study,the rate of antibodieto adalimumab afteretreatment (11 of


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482 subjects, 2.3%)was similar to therate observed priorto withdrawal (11 of590 subjects, 1.9%)

Becauseimmunogenicityanalyses areproduct-specific,comparison ofantibody rates withthose from otherproducts is notappropriate.

Paediatric populatio

The EuropeanMedicines Agencyhas waived theobligation to submitthe results of studiewith Humira in allsubsets of thepaediatric populatio

rheumatoid arthritispsoriatic arthritis anankylosingspondylitis, seesection 4.2 forinformation onpaediatric use.

The EuropeanMedicines Agencyhas deferred the

obligation to submitthe results of thestudies with Humirain one or moresubsets of thepaediatric populatioulcerative colitis, se


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section 4.2 forinformation onpaediatric use.

Go to top of the page5.2 Pharmacokinetic propertiesAbsorption and distribution

After subcutaneous administration of a single 40 mg dose, absorption and distributpeak serum concentrations being reached about 5 days after administration. The aadalimumab estimated from three studies following a single 40 mg subcutaneous dintravenous doses ranging from 0.25 to 10 mg/kg, concentrations were dose propo(~40 mg), clearances ranged from 11 to 15 ml/hour, the distribution volume (Vss) ramean terminal phase half-life was approximately two weeks. Adalimumab concentseveral rheumatoid arthritis patients ranged from 31-96% of those in serum.

Following subcutaneous administration of 40 mg of Humira every other week in adthe mean steady-state trough concentrations were approximately 5 g/ml (without 9 g/ml (with concomitant methotrexate), respectively. The serum adalimumab trouroughly proportionally with dose following 20, 40 and 80 mg subcutaneous dosing

Following the administration of 24 mg/m2 (up to a maximum of 40 mg) subcutaneowith polyarticular juvenile idiopathic arthritis (JIA) who were 4 to 17 years the meanmeasured from Week 20 to 48) serum adalimumab concentration was 5.6 5.6 gmonotherapy and 10.9 5.2 g/mL (47.7% CV) with concomitant methotrexate.

In patients with JIA who were 2-


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concentrations were maintained in subjects who continued to receive adalimumab subjects who dose escalated from eow to weekly regimen, the mean (SD) serum Week 52 were 15.311.4 g/mL (40/20 mg, weekly) and 6.73.5 g/mL (20/10 mg

In patients with ulcerative colitis, a loading dose of 160 mg Humira on Week 0 folloachieves serum adalimumab trough concentrations of approximately 12 g/ml duristeady-state trough levels of approximately 8 g/ml were observed in ulcerative comaintenance dose of 40 mg Humira every other week.

Elimination

Population pharmacokinetic analyses with data from over 1,300 RA patients reveaclearance of adalimumab with increasing body weight. After adjustment for weight appeared to have a minimal effect on adalimumab clearance. The serum levels of adalimumab antibodies, AAA) were observed to be lower in patients with measurastudied in patients with hepatic or renal impairment.

Hepatic or renal impairment

Humira has not been studied in patients with hepatic or renal impairment.

PEN

http://ask.metafilter.com/210065/Humira-for-UC

Go to top of the page5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on studies of single dand genotoxicity.

An embryo-foetal developmental toxicity/perinatal developmental study has been pmonkeys at 0, 30 and 100 mg/kg (9-17 monkeys/group) and has revealed no evideadalimumab. Neither carcinogenicity studies, nor a standard assessment of fertilityperformed with adalimumab due to the lack of appropriate models for an antibody wTNF and to the development of neutralizing antibodies in rodents.

Go to top of the page6. Pharmaceutical particulars

Go to top of the page6.1 List of excipients

Mannitol

Citric acid monohydrate


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Sodium citrate

Sodium dihydrogen phosphate dihydrate

Disodium phosphate dihydrate

Sodium chloride

Polysorbate 80

Sodium hydroxide

Water for injections

Go to top of the page6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed w

Go to top of the page6.3 Shelf life24 months

Go to top of the page6.4 Special precautions for storage

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

A single Humira pre-filled syringe may be stored at temperatures up to a maximumdays. The syringe must be protected from light, and discarded if not used within th

Store in a refrigerator (2C 8C). Do not freeze. Keep the pre-filled pen in the outlight.

A single Humira pen may be stored at temperatures up to a maximum of 25C for must be protected from light, and discarded if not used within the 14-day period.

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

Go to top of the page6.5 Nature and contents of container

Humira 40 mg solution for injection in single-use pre-filled syringe (type I glass) witrubber) and a needle with a needle shield (thermoplastic elastomer 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.




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Not all pack sizes may be marketed.

Humira 40 mg solution for injection in single-use pre-filled pen for patient use contasyringe inside the pen is made from type 1 glass with a plunger stopper (bromobutneedle shield (thermoplastic elastomer).

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.



Not all pack sizes may be marketed.

Humira 40 mg solution for injection in single-use vial (type I glass), fitted with rubbeflip-off seals.

1 Pack of 2 boxes each containing:1 vial (0.8 ml sterile solution), 1 empty sterile injection syringe, 1 needle, 1 vial ada

Go to top of the page6.6 Special precautions for disposal and other handling

Humira 40 mg solution for injection does not contain preservatives. Any unused meshould be disposed of in accordance with local requirements.

Go to top of the page7. Marketing authorisation holder

AbbVie Ltd

Maidenhead

SL6 4XE

United Kingdom

Go to top of the page8. Marketing authorisation number(s)

EU/1/03/256/001

EU/1/03/256/002

EU/1/03/256/003

EU/1/03/256/004

EU/1/03/256/005


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EU/1/03/256/007

EU/1/03/256/008

EU/1/03/256/009

EU/1/03/256/010

Go to top of the page9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 08 September 2003

Date of latest renewal: 08 September 2008

Go to top of the page10. Date of revision of the text

20 September 2013

Detailed information on this medicinal product is available on the website of the Euhttp://www.ema.europa.eu

More information about this product Patient Information Leaflets (PILs): Humira 40 mg solution for injection

in pre-filled syringe Humira 40mg solution for injection in pre-filledpen Humira 40mg/0.8ml solution for injection for paediatric use

Alternative format Patient Information Leaflets (X-PILs): Humira 40 mgsolution for injection in pre-filled syringe Humira 40mg solution forinjection in pre-filled pen Humira 40mg/0.8ml solution for injectionfor paediatric use

Medicine Guides: HumiraLink to this document from yourwebsite: http://www.medicines.org.uk/emc/medicine/21201/SPC/

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adalimumab

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psoriasis, an inflammatory disease of the skin.The active ingredient in this medicine is adalimumab, a fully humanmonoclonal antibody. Monoclonal antibodies are proteins that recognise

and bind to other unique proteins. Adalimumab binds to a specific protein(tumour necrosis factor or TNF-alpha), which is present at increased levelsin inflammatory diseases such as rheumatoid arthritis, polyarticular juvenileidiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn'sdisease and psoriasis.

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