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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
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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.
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.
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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.
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.
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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http://www.medicines.org.uk/emc/medicine/17082/PIL/Humira+40+mg+solution+for+injection+in+pre-filled+syringehttp://www.medicines.org.uk/emc/medicine/17082/PIL/Humira+40+mg+solution+for+injection+in+pre-filled+syringehttp://www.medicines.org.uk/emc/medicine/20965/PIL/Humira+40mg+solution+for+injection+in+pre-filled+penhttp://www.medicines.org.uk/emc/medicine/20965/PIL/Humira+40mg+solution+for+injection+in+pre-filled+penhttp://www.medicines.org.uk/emc/medicine/24613/PIL/Humira+40mg+0.8ml+solution+for+injection+for+paediatric+usehttp://www.medicines.org.uk/emc/medicine/24613/PIL/Humira+40mg+0.8ml+solution+for+injection+for+paediatric+usehttp://xpil.medicines.org.uk/viewpil.aspx?docid=17082http://xpil.medicines.org.uk/viewpil.aspx?docid=17082http://xpil.medicines.org.uk/viewpil.aspx?docid=20965http://xpil.medicines.org.uk/viewpil.aspx?docid=20965http://xpil.medicines.org.uk/viewpil.aspx?docid=24613http://xpil.medicines.org.uk/viewpil.aspx?docid=24613http://xpil.medicines.org.uk/viewpil.aspx?docid=24613http://www.medicines.org.uk/guides/humirahttp://www.medicines.org.uk/guides/humirahttp://www.medicines.org.uk/emc/company/3216/Abbvie+Limited/http://www.medicines.org.uk/emc/company/3216/Abbvie+Limited/http://www.medicines.org.uk/emc/printfriendlydocument.aspx?documentid=21201http://www.medicines.org.uk/emc/printfriendlydocument.aspx?documentid=21201http://www.medicines.org.uk/emc/company/3216/Abbvie+Limited/http://www.medicines.org.uk/emc/company/3216/Abbvie+Limited/http://www.medicines.org.uk/guides/humirahttp://xpil.medicines.org.uk/viewpil.aspx?docid=24613http://xpil.medicines.org.uk/viewpil.aspx?docid=24613http://xpil.medicines.org.uk/viewpil.aspx?docid=20965http://xpil.medicines.org.uk/viewpil.aspx?docid=20965http://xpil.medicines.org.uk/viewpil.aspx?docid=17082http://xpil.medicines.org.uk/viewpil.aspx?docid=17082http://www.medicines.org.uk/emc/medicine/24613/PIL/Humira+40mg+0.8ml+solution+for+injection+for+paediatric+usehttp://www.medicines.org.uk/emc/medicine/20965/PIL/Humira+40mg+solution+for+injection+in+pre-filled+penhttp://www.medicines.org.uk/emc/medicine/20965/PIL/Humira+40mg+solution+for+injection+in+pre-filled+penhttp://www.medicines.org.uk/emc/medicine/17082/PIL/Humira+40+mg+solution+for+injection+in+pre-filled+syringehttp://www.medicines.org.uk/emc/medicine/17082/PIL/Humira+40+mg+solution+for+injection+in+pre-filled+syringe -
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Ingredients/Generics
adalimumab
Return to the top of the pageHome|Contact us|Useful links|Accessibility|Legal and privacy policy|Glossary|Site map 2013Datapharm Communications Ltd
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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