|
Humira Pre-filled Pen, Pre-filled Syringe and Vial
|
Humira Pre-filled Pen, Pre-filled Syringe and Vial
1. 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
2. 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 Hamster Ovary cells.
For the full list of excipients, see section 6.1.
3. 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.
4. Clinical particulars
4.1 Therapeutic indications
Rheumatoid arthritis
Humira in combination with methotrexate, is indicated for:
• the treatment of moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate.
• the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
Humira can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
Humira has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with methotrexate.
Polyarticular juvenile idiopathic arthritis
Humira in combination with methotrexate is indicated for the treatment of active polyarticular juvenile idiopathic arthritis, in children and adolescents from the age of 2 years who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). Humira can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate (for the efficacy in monotherapy see section 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 spondylitis who have had an inadequate response to conventional therapy.
Axial spondyloarthritis without radiographic evidence of AS
Humira is indicated for the treatment of adults with severe axial spondyloarthritis without radiographic evidence of AS but with objective signs of inflammation by elevated CRP and / or MRI, who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs.
Psoriatic arthritis
Humira is indicated for the treatment of active and progressive psoriatic arthritis in adults when the response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. Humira has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease (see Section 5.1) and to improve physical function.
Psoriasis
Humira is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA.
Crohn's disease
Humira is indicated for treatment of moderately to severely active Crohn's disease, in adult patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.
Paediatric Crohn's Disease
Humira is indicated for the treatment of severe active Crohn's disease in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including primary nutrition therapy, a corticosteroid, and an immunomodulator, or who are intolerant to or have contraindications for such therapies.
Ulcerative colitis
Humira is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.
4.2 Posology and method of administration
Posology
Humira treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of conditions for which Humira is indicated. Patients treated with Humira should be given the special alert card.
After proper training in injection technique, patients may self-inject with Humira if their physician determines that it is appropriate and with medical follow-up as necessary.
During treatment with Humira, other concomitant therapies (e.g., corticosteroids and/or immunomodulatory agents) should be optimised.
Rheumatoid arthritis
The recommended dose of Humira for adult patients with rheumatoid arthritis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection. Methotrexate should be continued during treatment with Humira.
Glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, or analgesics can be continued during treatment with Humira. Regarding combination with disease modifying anti-rheumatic drugs other than methotrexate see sections 4.4 and 5.1.
In monotherapy, some patients who experience a decrease in their response may benefit from an increase in dose intensity to 40 mg adalimumab every week.
Dose Interruption
There may be a need for dose interruption, for instance before surgery or if a serious infection occurs.
Available data suggest that re-introduction of Humira after discontinuation for 70 days or longer resulted in the same magnitudes of clinical response and similar safety profile as before dose interruption.
Ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and psoriatic arthritis
The recommended dose of Humira for patients with ankylosing spondylitis, axial spondyloarthritis without radiographic evidence of AS and for patients with psoriatic arthritis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection.
For all of the above indications, available data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period.
Psoriasis
The recommended dose of Humira for adult patients is an initial dose of 80 mg administered subcutaneously, followed by 40 mg subcutaneously given every other week starting one week after the initial dose.
Continued therapy beyond 16 weeks should be carefully reconsidered in a patient not responding within this time period.
Crohn's disease
The recommended Humira induction dose regimen for adult patients with moderately to severely active Crohn's disease is 80 mg at Week 0 followed by 40 mg at Week 2. In case there is a need for a more rapid response to therapy, the regimen 160 mg at Week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days), 80 mg at Week 2, can be used with the awareness that the risk for adverse events is higher during induction.
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. Alternatively, if a patient has stopped Humira and signs and symptoms of disease recur, Humira may be re-administered. There is little experience from re-administration after more than 8 weeks since the previous dose.
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.
Some patients who experience decrease in their response may benefit from an increase in dosing frequency to 40 mg Humira every week.
Some patients who have not responded by Week 4 may benefit from continued maintenance therapy through Week 12. Continued therapy should be carefully reconsidered in a patient not responding within this time period.
Ulcerative colitis
The recommended Humira induction dose regimen for adult patients with moderate to severe ulcerative colitis is 160 mg at Week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days) and 80 mg at Week 2. After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection.
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.
Some patients who experience decrease in their response may benefit from an increase in dosing frequency to 40 mg Humira every week.
Available data suggest that clinical response is usually achieved within 2-8 weeks of treatment. Humira therapy should not be continued in patients failing to respond within this time period.
Older people
No dose adjustment is required.
Impaired renal and/or hepatic function
Humira has not been studied in these patient populations. No dose recommendations can be made.
Paediatric Population
Polyarticular Juvenile Idiopathis Arthritis
Polyarticular Juvenile Idiopathic Arthritis from 2 to 12 years of age
The recommended dose of Humira for patients with polyarticular juvenile idiopathic arthritis, aged 2-12 years, is 24 mg/m² body surface area up to a maximum single dose of 20 mg adalimumab (for patients aged 2-<4) and up to a maximum single dose of 40 mg adalimumab (for patients aged 4-12) administered every other week via subcutaneous injection. The volume for injection is selected based on the patients' height and weight (Table 1). A 40 mg paediatric vial is available for patients who need to administer less than the full 40 mg dose.
Table 1. Humira Dose in Millilitres (ml) by Height and Weight of Children for Polyarticular Juvenile Idiopathic Arthritis
|
Height (cm)
|
Total Body Weight (kg)
|
|
10
|
15
|
20
|
25
|
30
|
35
|
40
|
45
|
50
|
55
|
60
|
65
|
70
|
|
80
|
0.2
|
0.3
|
0.3
|
0.3
|
|
|
|
|
|
|
|
|
|
|
90
|
0.2
|
0.3
|
0.3
|
0.4
|
0.4
|
0.4
|
|
|
|
|
|
|
|
|
100
|
0.3
|
0.3
|
0.3
|
0.4
|
0.4
|
0.4
|
0.5
|
0.5
|
|
|
|
|
|
|
110
|
0.3
|
0.3
|
0.4
|
0.4
|
0.4
|
0.5
|
0.5
|
0.5
|
0.5
|
0.6
|
0.6
|
|
|
|
120
|
0.3
|
0.4
|
0.4
|
0.4
|
0.5
|
0.5
|
0.5
|
0.6
|
0.6
|
0.6
|
0.6
|
0.7
|
0.7
|
|
130
|
|
0.4
|
0.4
|
0.5
|
0.5
|
0.5
|
0.6
|
0.6
|
0.6
|
0.6
|
0.7
|
0.7
|
0.7
|
|
140
|
|
0.4
|
0.4
|
0.5
|
0.5
|
0.6
|
0.6
|
0.6
|
0.7
|
0.7
|
0.7
|
0.7
|
0.8*
|
|
150
|
|
|
0.5
|
0.5
|
0.6
|
0.6
|
0.6
|
0.7
|
0.7
|
0.7
|
0.7
|
0.8*
|
0.8*
|
|
160
|
|
|
0.5
|
0.5
|
0.6
|
0.6
|
0.7
|
0.7
|
0.7
|
0.8*
|
0.8*
|
0.8*
|
0.8*
|
|
170
|
|
|
|
0.6
|
0.6
|
0.6
|
0.7
|
0.7
|
0.8*
|
0.8*
|
0.8*
|
0.8*
|
0.8*
|
|
180
|
|
|
|
|
0.6
|
0.7
|
0.7
|
0.8*
|
0.8*
|
0.8*
|
0.8*
|
0.8*
|
0.8*
|
*Maximum single dose is 40 mg (0.8 ml)
Polyarticular Juvenile Idiopathic Arthritis from 13 years of age
For adolescents from 13 years of age, a dose of 40 mg is administered every other week regardless of body surface area.
A 40 mg pen and a 40 mg prefilled syringe are also available for patients to administer a full 40mg dose.
Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period.
There is no relevant use of Humira in children aged less than 2 years in this indication.
Paediatric psoriasis
The safety and efficacy of Humira in children aged 4-17 years have not been established. No data are available. There is no relevant use of Humira in children aged <4 years in this indication.
Paediatric Crohn's Disease
Paediatric Crohn's disease patients < 40 kg:
The recommended Humira induction dose regimen for paediatric subjects with severe Crohn's disease is 40 mg at Week 0 followed by 20 mg at Week 2. In case there is a need for a more rapid response to therapy, the regimen 80 mg at Week 0 (dose can be administered as two injections in one day), 40 mg at Week 2 can be used, with the awareness that the risk for adverse events may be higher with use of the higher induction dose.
After induction treatment, the recommended dose is 20 mg every other week via subcutaneous injection. Some subjects who experience insufficient response may benefit from an increase in dosing frequency to 20 mg Humira every week.
Paediatric Crohn's disease patients ≥ 40 kg:
The recommended Humira induction dose regimen for paediatric subjects with severe Crohn's disease is 80 mg at Week 0 followed by 40 mg at Week 2. In case there is a need for a more rapid response to therapy, the regimen 160 mg at Week 0 (dose can be administered as four injections in one day or as two injections per day for two consecutive days), 80 mg at Week 2 can be used, with the awareness that the risk for adverse events may be higher with use of the higher induction dose.
After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection. Some subjects who experience insufficient response may benefit from an increase in dosing frequency to 40 mg Humira every week.
Continued therapy should be carefully considered in a subject not responding by Week 12.
There is no relevant use of Humira in children aged less than 6 years in this indication.
Paediatric ulcerative colitis
The safety and efficacy of Humira in children aged 4-17 years have not yet been established. No data are available. There is no relevant use of Humira in children aged <4 years in this indication.
Psoriatic arthritis and axial spondyloarthritis including ankylosing spondylitis.
There is no relevant use of Humira in the paediatric population in the indications, ankylosing spondylitis and psoriatric arthritis.
Method of administration
Humira is administered by subcutaneous injection. Full instructions for use are provided in the package leaflet.
A 40 mg pen and a 40 mg prefilled syringe are also available for patients to administer a full 40 mg dose.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Active tuberculosis or other severe infections such as sepsis, and opportunistic infections (see section 4.4).
Moderate to severe heart failure (NYHA class III/IV) (see section 4.4).
4.4 Special warnings and precautions for use
In order to improve traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded.
Infections
Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may increase the risk for developing infections. Patients must therefore be monitored closely for infections, including tuberculosis, before, during and after treatment with Humira. Because the elimination of adalimumab may take up to four months, monitoring should be continued throughout this period.
Treatment with Humira should not be initiated in patients with active infections including chronic or localized infections until infections are controlled. In patients who have been exposed to tuberculosis and patients who have travelled in areas of high risk of tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis, the risk and benefits of treatment with Humira should be considered prior to initiating therapy (see Other opportunistic infections).
Patients who develop a new infection while undergoing treatment with Humira, should be monitored closely and undergo a complete diagnostic eva luation. Administration of Humira should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled. Physicians should exercise caution when considering the use of Humira in patients with a history of recurring infection or with underlying conditions which may predispose patients to infections, including the use of concomitant immunosuppressive medications.
Serious infections:
Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in patients receiving Humira.
Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported.
Tuberculosis:
Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving Humira. Reports included cases of pulmonary and extra-pulmonary (i.e. disseminated) tuberculosis.
Before initiation of therapy with Humira, all patients must be eva luated for both active or inactive (“latent”) tuberculosis infection. This eva luation should include a detailed medical assessment of patient history of tuberculosis or possible previous exposure to people with active tuberculosis and previous and/or current immunosuppressive therapy. Appropriate screening tests (i.e. tuberculin skin test and chest X-ray) should be performed in all patients (local recommendations may apply). It is recommended that the conduct and results of these tests are recorded in the patient alert card. Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.
If active tuberculosis is diagnosed, Humira therapy must not be initiated (see section 4.3).
In all situations described below, the benefit/risk balance of therapy should be very carefully considered.
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted.
If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis prophylaxistreatment before the initiation of Humira, and in accordance with local recommendations.
Use of anti-tuberculosis prophylaxis treatment should also be considered before the initiation of Humira in patients with several or significant risk factors for tuberculosis despite a negative test for tuberculosis and in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.
Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with Humira. Some patients who have been successfully treated for active tuberculosis have redeveloped tuberculosis while being treated with Humira.
Patients should be instructed to seek medical advice if signs/symptoms suggestive of a tuberculosis infection (e.g., persistent cough, wasting/weight loss, low grade fever, listlessness) occur during or after therapy with Humira.
Other opportunistic infections:
Opportunistic infections, including invasive fungal infections have been observed in patients receiving Humira. These infections have not consistently been recognised in patients taking TNF-antagonists and this resulted in delays in appropriate treatment, sometimes resulting in fatal outcomes.
For patients who develop the signs and symptoms such as fever, malaise, weight loss, sweats, cough, dyspnea, and/or pulmonary infiltrates or other serious systemic illness with or without concomitant shock an invasive fungal infection should be suspected and administration of Humira should be promptly discontinued. Diagnosis and administration of empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the care of patients with invasive fungal infections.
Hepatitis B reactivation
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Humira, who are chronic carriers of this virus (i.e., surface antigen positive). Some cases have had a fatal outcome. Patients should be tested forHBV infection before initiating treatment with Humira. For patients who test positive for hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended.
Carriers of HBV who require treatment with Humira should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. Adequate data from treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV reactivation, Humira should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.
Neurological events
TNF-antagonists including Humira have been associated in rare instances with new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system, demyelinating disease including multiple sclerosis, optic neuritis and peripheral demyelinating disease, including Guillain-Barré syndrome. Prescribers should exercise caution in considering the use of Humira in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders.
Allergic reactions
Serious allergic reactions associated with Humira were rare during clinical trials. Non-serious allergic reactions associated with Humira were uncommon during clinical trials. Reports of serious allergic reactions including anaphylaxis have been received following Humira administration. If an anaphylactic reaction or other serious allergic reaction occurs, administration of Humira should be discontinued immediately and appropriate therapy initiated.
Immunosuppression
In a study of 64 patients with rheumatoid arthritis that were treated with Humira, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T-, B, - NK-cells, monocyte/macrophages, and neutrophils.
Malignancies and lymphoproliferative disorders
In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including lymphoma have been observed among patients receiving a TNF-antagonist compared with control patients. However, the occurrence was rare. In the post marketing setting, cases of leukemia have been reported in patients treated with a TNF-antagonist. There is an increased background risk for lymphoma and leukemia in rheumatoid arthritis patients with long-standing highly active, inflammatory disease, which complicates the risk estimation. With the current knowledge, a possible risk for the development of lymphomas, leukemia, and other malignancies in patients treated with a TNF-antagonist cannot be excluded.
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including adalimumab in the post marketing setting. Approximately half the cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression. A risk for the development of malignancies in children and adolescents treated with TNF-antagonists cannot be excluded.
Rare postmarketing cases of hepatosplenic T-cell lymphoma have been identified in patients treated with adalimumab. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Some of these hepatosplenic T-cell lymphomas with Humira have occurred in young adult patients on concomitant treatment with azathioprine or 6-mercaptopurine used for inflammatory bowel disease. The potential risk with the combination of azathioprine or 6-mercaptopurine and Humira should be carefully considered. A risk for the development of hepatosplenic T-cell lymphoma in patients treated with Humira cannot be excluded (see section 4.8).
No studies have bee |
|
