HUMIRA amp. 40 mg. 0.8 ml. 2 syringes
HUMIRA amp. 40 mg. / 0.8 ml. 2 syringes
Each single dose vial 0,8 ml contains 40 mg adalimumab (adalimumab).
Adalimumab is a recombinant human monoclonal antibody derived from the cells of
Chinese hamster ovary .
solution for injection pre-filled syringes
1. CLINICAL DATA
adult patients with rheumatoid arthritis in the case where the clinical response to treatment with other biological response modifiers has been inadequate. It can be used alone or in combination with methotrexate, respectively . with other biological response modifiers .
psoriatic arthritis ;
Due to lack of clinical studies Humira is not recommended in patients under age ( 18) .
Dosage and method of administration
The recommended dose for adult patients with rheumatoid arthritis is 40 mg adalimumab every other week as a single dose subcutaneous injection. During treatment with adalimumab can be continued methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory or analgesic .
In monotherapy , some patients experience a decrease in the response to adalimumab, can benefit from an increase in dose to 40 mg weekly.
The recommended dose of Humira for adult patients with psoriatic arthritis is 40 mg adalimumab every other week as a single dose subcutaneous injection.
Hypersensitivity to the active substance adalimumab or any of the excipients . Active tuberculosis or other severe infections (sepsis , opportunistic infections) . Moderate to severe heart failure (NYHA class III / IV).
Special precautions for use
Patients taking TNF- blockers are more susceptible to serious infections. disturbed
functions of the lungs may increase the risk of infection. Therefore,
patients should be monitored closely for infections, including tuberculosis,
before , during and after treatment with Humira. Because the elimination of adalimumab may
lasts 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 . at
patients who have been exposed to tuberculosis and patients who have traveled in areas
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 treatment (see other opportunistic infections) .
Patients who develop a new infection during treatment with Humira, should be
monitored closely and undergo a complete diagnostic tests. If the patient
develops a new serious infection or sepsis , the administration of Humira should be
suspended and must be initiated podhodyashta antibakterialna or antifungal
therapy until the infection is controlled. Physicians should exercise caution
account when considering the use of Humira in patients with a history of recurrent
infections or with underlying conditions that may predispose patients to
infections, including the use of concomitant immunosuppressive medications.
Serious infections, including sepsis , due to bacterial, mycobacterial ,
invasive fungal , parasitic , viral , or other opportunistic infections such as listeriosis
and Pneumocystis have been reported in patients receiving Humira.
Other serious infections seen in clinical trials include pneumonia,
pyelonephritis, septic arthritis and septicemia . There have been reports of hospitalization or
fatalities associated infections.
Cases of tuberculosis in patients receiving Humira. It should be noted ,
in most cases , tuberculosis was extrapulmonary localization, ie
Before initiation of therapy with Humira, all patients must be evaluated for both active
and inactive (latent ) tuberculosis infection. This assessment should include
detailed history of patients with a personal history of tuberculosis or possible
prior exposure to patients with active tuberculosis and previous and / or current
immunosuppressive therapy. All patients should be carried out relevant
screening tests , ie tuberculin skin test and chest X-ray ( may
to implement local recommendations ) . It is recommended that these surveys be
described in the Patient Alert Card . Prescribers are reminded of the risk of false-
negative tuberculin skin test , especially in patients who are severely
ill or immunocompromised .
If active tuberculosis is diagnosed , treatment with Humira should not be initiated .
If latent tuberculosis is suspected , you should consult a physician with expertise in
treatment of tuberculosis . In all described cases below , the benefit / risk
treatment should be carefully considered.
If a diagnosis of inactive ( ' latent ') tuberculosis should be initiated appropriate
treatment for latent tuberculosis before anti-tuberculosis preventive therapy
initiation of therapy with Humira, and in accordance with local recommendations.
In patients who have several or significant risk factors for tuberculosis and have
negative test for latent tuberculosis must also be given anti-tuberculosis
therapy prior to initiating treatment with Humira.
Application of anti-tuberculosis therapy should also be considered before starting
Humira in patients with a history of latent or active tuberculosis in whom no
can be confirmed adequate course of treatment. Some patients who
were pre -treated for latent or active tuberculosis have developed active
tuberculosis while being treated with Humira.
Patients should be instructed to seek medical attention if during
or after treatment with Humira arise signs / symptoms ( eg persistent cough,
fatigue / weight loss, low grade fever) suggestive of tuberculosis infection .
Other opportunistic infections:
Opportunistic infections, including invasive fungal infections were observed
in patients taking Humira. These infections have not been recognized in succession
patients receiving TNF- blockers, and this has led to delays in the implementation of
appropriate treatment , sometimes resulting in fatalities .
In patients who develop signs and symptoms such as fever, malaise, loss of
weight , sweating , coughing , dyspnea , and / or pulmonary infiltrates or other serious systemic
disease with or without concomitant shock should be suspected invasive fungal infection and
implementation of Humira should be promptly discontinued. The diagnosis and
application of empirical antifungal therapy in these patients should be done in
consultation with a physician experienced in the treatment of patients with invasive fungal infections.
Reactivation of hepatitis B
In patients with chronic carriers of HBV, during treatment with TNF-antagonist
including Humira, has experienced reactivation of hepatitis B. Some cases have had
lethal . Patients at risk for HBV infection should be evaluated for prior evidence of HBV
infection before initiating treatment with Humira. Carriers of HBV, which require
treatment with Humira, should be monitored closely for signs and symptoms of active
HBV infection throughout therapy and for several months following termination . no
enough data from the treatment of carriers of HBV with anti-viral therapy in conjunction with
TNF- antagonists for prevention of reactivation of HBV. In patients who develop
Reactivation of HBV, Humira should be discontinued and start effective antiviral therapy
with appropriate supportive treatment.
In rare cases, TNF- blocking agents, including Humira, have been associated with recurrence
or exacerbation of clinical symptoms and / or radiographic evidence of
demyelinating disease of the central nervous system , including multiple
sclerosis and peripheral demyelinating disease , including syndrome Guillain-Barré.
Prescribers should exercise caution in considering the application of Humira
Patients with pre- existing or recently acquired demyelinating
disease of the central or peripheral nervous system .
In clinical studies have not reported serious allergic reactions
subcutaneous administration of Humira. No serious allergic reactions associated with Humira are
uncommon in clinical trials. In postmarketing experience , severe
allergic reactions, including anaphylaxis, have been reported very rarely following
Humira. In the event of an anaphylactic reaction or other serious allergic reaction
use of Humira should be discontinued immediately and initiate appropriate
The needle cover of the syringe contains natural rubber ( latex). This can
cause allergic reactions in individuals sensitive to latex.
In a study of 64 patients with rheumatoid arthritis were treated with Humira, not
evidence of depression of delayed-type hypersensitivity , depression of immunoglobulin levels
or a change in the number of effector T - , B -, NK- cells, monocytes / 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, cases are
rare . In postmarketing experience there have been reports of leukemia in patients treated
TNF-antagonist . In rheumatoid arthritis patients with long-term , high active
inflammatory disease has increased background risk of development of lymphoma and leukemia , which
complicates the risk estimation . According to current knowledge , in patients treated with TNF-
antagonist can not be excluded a possible risk for the development of lymphomas, leukemia and
other malignancies .
During postmarketing experience there have been reports of malignancies, some fatal , in children, adolescents and young adults ( aged 22 years ) treated sTNF -blocking agents ( initiation of therapy ? 18 years of age) vklyuchitelnoadalimumab . About half the cases were lymphomas. Other cases predstavlyavatmnozhestvo various malignancies and included rare malignancies usually associated with immunosuppression. In children and adolescents treated with TNF- blockers, mozheda exclude risk of developing malignant zabolyavaniya.Redki postmarketing cases of hepatosplenic T- cell lymphoma have been identified patients who achieved remission treated with adalimumab. This rare type of T- cell lymphoma has a very agresivnoprotichane and usually fatal . Some of these hepatosplenic T- kletachnilimfomi associated with Humira, occurred in younger patients concomitantly receiving sazatioprin or 6 - mercaptopurine, applied for disease Crohn. Can not exclude the risk by development of hepatosplenic T- cell lymphoma in patients treated with Humira.
No studies that include patients with a history of malignant
disease or in whom treatment with Humira continued after the development of malignant
disease. Therefore, you should exercise extra caution in
consideration of Humira in these patients (see section 4.8).
All patients and , in particular , patients with a history of long-term immunosuppressive
therapy or psoriasis patients with a history of PUVA treatment should be examined
in the presence of non-melanoma skin cancer before and during treatment with Humira.
In an exploratory clinical trial evaluating the implementation of another anti -TNF agent
infliximab in patients with moderate to severe chronic obstructive pulmonary disease
( COPD ) , have been reported in many cases of malignancies ,
predominantly localized in the lung or head and neck patients
infliximab compared with control patients. All patients had
history of heavy smoking. Therefore, you should
exercise caution in the administration of either a TNF- antagonist in patients with
COPD , or in patients with an increased risk of malignancy due to
heavy smoking .
Rare reports of pancytopenia including aplastic anemia have been reported with
TNF- antagonists. Adverse events of the haematologic system, including
clinically significant cytopenia (eg thrombocytopenia, leukopenia ) have been reported with
Humira. All patients should be advised to seek immediate medical
attention if they develop signs and symptoms suggestive of blood dyscrasias (eg
persistent fever , bruising , bleeding, pallor ) while on treatment with
Humira. Discontinuation of treatment with Humira should be considered in patients with
confirmed significant hematologic abnormalities.
In a clinical study involving 226 adults with rheumatoid arthritis who have
were treated with adalimumab or placebo were observed similar antibody responses to
standard 23 -valent pneumococcal vaccine and trivalent influenza vaccination
virus . No evidence of secondary transmission of infection by live vaccines in patients
Recommended that patients with polyarticular juvenile idiopathic arthritis expire on
opportunity with all immunizations in agreement with current immunization guidelines prior to
initiation of therapy with Humira.
Patients on Humira can be simultaneously subjected to any other
vaccinations than those with live vaccines .
Congestive Heart Failure
In a clinical trial with another TNF- antagonist worsening congestive
heart failure and increased mortality due to congestive heart failure. cases
worsening of congestive heart failure have been reported in patients
receiving Humira. Humira should be used with caution in patients with mild
heart failure (Class I / II in NYHA). Humira is contraindicated in moderate to severe
heart failure . Treatment with Humira should be discontinued in
patients who develop new or worsening symptoms of congestive heart
Humira treatment can lead to the formation of autoantibodies . Not Known
impact of continued treatment with Humira on the development of autoimmune
diseases. If after treatment with Humira, a patient develops symptoms suggestive
lupus-like syndrome and is positive for antibodies to double-stranded
DNA should not be applied to further treatment with Humira.
Co-administration of TNF-antagonists and anakinra .
Serious infections were seen in clinical studies with concurrent administration of
anakinra and another TNF- antagonist etanercept, with no added clinical benefit compared
to administration of etanercept . Due to the nature of the adverse events
observed in combination therapy with etanercept and anakinra , similar toxicities may
also result from the combination of anakinra and other TNF- antagonists. Therefore, no
recommended combination of adalimumab and anakinra .
Concurrent administration of TNF- antagonists and abatacept
Co-administration of TNF- antagonists and abatacept is associated with an increased risk of
infections including serious infections compared to administration of
TNF- antagonists, without additional clinical benefit. The combination of Humira and abatacept is not
There is limited safety experience of surgical procedures in patients
treated with Humira. If a surgical procedure is planned to be taken into account
long half-life of adalimumab. A patient who requires surgery while on
Humira, should be monitored closely for infections and take appropriate action.
There is limited safety experience in patients undergoing arthroplasty
while receiving Humira.
Small bowel obstruction
The lack of response to treatment of disease Crohn, may indicate the presence of
fixed fibrotic stricture that may require surgical treatment. The available data
suggest that Humira does not worsen or cause strictures .
The incidence of serious infections among HUMIRA treated subjects over the age of 65
years ( 3.9%) was higher than that in patients under the age of 65 ( 1.4%) . some of
cases were fatal . Particular attention to the risk of infection should be
exercised in treating the elderly .
Adalimumab has been studied in rheumatoid arthritis patients taking Humira monotherapy and those taking concomitant methotrexate. Adalimumab When given in conjunction with methotrexate, antibody formation is low ( <1% ) compared with monotherapy. The use of adalimumab without methotrexate resulted in increased formation of antibodies and increased clearance of adalimumab.
No experience with the efficacy and safety in patients previously treated with other TNF- antagonists.
The combination of Humira and anakinra is not recommended.
The combination of Humira and abatacept is not recommended.
Use during pregnancy and lactation
There are no clinical data on the use of adalimumab in pregnant women.
Due to its inhibition of TNF?, use of adalimumab during pregnancy could affect normal immune responses in the newborn . Administration of adalimumab is not recommended during pregnancy . Women of childbearing potential are strongly advised to use adequate contraception to prevent pregnancy and continue its use for at least five months after the last adalimumab.
Not known whether adalimumab is excreted in human milk or absorbed systemically after ingestion. Because human milk excreted human immunoglobulins , women should not breast-feed for at least five months after the last adalimumab.
Effects on ability to drive and use machines
No data available.
Benign skin neoplasms, decreased hemoglobin, granulocytopenia , increased serum cholesterol , creatinine, urea . uric acid, alkaline phosphatase, lactate dehydrogenase , creatine phosphokinase increased , hypokalemia , trudns wound healing , depression , somnolence, headache, paresthesia , dizziness, neuralgia , tremor , conjunctivitis, blurred vision and eye pain, otitis media , hypertension , vasodilatation, pain in chest infections ODS , rhinitis, bronchitis , cough , pneumonia , dyspnoea, asthma , nausea , diarrhea , dry mouth , oral mucosal ulceration , esophagitis, nausea , gastritis , ulcerative stomatitis , rash , pruritus , herpes simplex, herpes zoster, xeroderma , alopecia . dermatomycosis , skin ulcers , subcutaneous hematoma , urinary tract infections , asthenia , myalgia, flu syndrome , pain at the site of application.
2 . Pharmacological
Following subcutaneous administration of a single dose of 40 mg, the absorption and distribution of adalimumab was slow, with peak plasma concentrations are reached about 5 days after administration. The average absolute bioavailability of adalimumab after a single subcutaneous dose of 40 mg, 64% . Adalimumab concentrations in the synovial fluid of patients with various RA varies between 31 and 96% of the serum concentration. Volume of distribution - 4,7-6 L. The main terminal half-life is 14 days.
3.2 . Pharmacodynamic properties:
• Pharmacotherapeutic group: Immunosuppressants ;