Instructions for use Hyrimoz 40 solution for injection 40 mg / 0.8 ml syringe 0.8 ml No. 2
Composition
active substance: adalimumab;
1 pre-filled syringe contains 40 mg of adalimumab in 0.8 ml of solution;
excipients: adipic acid; citric acid, monohydrate; sodium chloride; mannitol (E 421); polysorbate 80; sodium hydroxide (for pH adjustment); hydrochloric acid (for pH adjustment); water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent or slightly opalescent, colorless or slightly yellowish solution.
Pharmacotherapeutic group
Immunosuppressants. Tumor necrosis factor-alpha inhibitors. Adalimumab.
ATX code L04A 804.
Pharmacological properties
Hyrimoz 40 (adalimumab) is a recombinant human immunoglobulin (IgG1). A monoclonal antibody containing only human peptide sequences. The drug was created using phage display technology, which made it possible to obtain human-specific variable regions of heavy and light chains that exhibit specificity for tumor necrosis factor (TNF), as well as the human IgG heavy chain and the kappa-type light chain sequence. Adalimumab binds with high affinity and specificity to soluble TNF-alpha, but not to lymphotoxin (TNF-beta). Adalimumab is produced by obtaining recombinant DNA in a mammalian cell expression system. It consists of 1300 amino acids and has a molecular weight of approximately 148 kilodaltons.
Adalimumab specifically binds to TNF and neutralizes the biological effects of TNF by blocking its interaction with the pSS and p75 TNF receptors on the cell surface. TNF is a natural cytokine that is involved in normal inflammatory and immune responses in the body. Elevated levels of TNF are found in the synovial fluid of patients with rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). TNF plays an important role in the development of pathological inflammation and destruction of joint tissue, which is characteristic of these diseases. Elevated levels of TNF are also found in psoriatic plaques. The use of Hyrimoz 40 in patients with plaque psoriasis can reduce epidermal thickening and infiltration by inflammatory cells. The relationship between these pharmacodynamic effects and the mechanism(s) by which adalimumab exerts its clinical efficacy is unknown. Adalimumab also modulates biological responses induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-I and ICAM-1 at IC50s of 1 to 2 x 10-10 M).
Pharmacodynamics.
In patients with RA, adalimumab caused a rapid reduction from baseline in acute phase markers of inflammation (C-reactive protein (CRP), serum cytokines (IL-6) and erythrocyte sedimentation rate). Reductions in CRP levels were also observed in patients with JRA, Crohn's disease, ulcerative colitis and hidradenitis suppurativa, along with significant reductions in the expression of TNF-alpha and inflammatory markers such as human leukocyte antigen (HLA-DR) and myeloperoxidase (MPO) in the colon of patients with Crohn's disease. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3), which are involved in tissue remodeling that underlies cartilage destruction, were also reduced. Patients with RA, PsA, and AS often experience mild to moderate anemia and lymphocytopenia, as well as increased neutrophil and platelet counts. These hematological markers of chronic inflammation are commonly improved with adalimumab.
Pharmacokinetics.
Absorption and distribution.
Following a single subcutaneous dose of 40 mg adalimumab, absorption and distribution of adalimumab were slow, with mean peak serum concentrations occurring approximately 5 days after administration. The mean absolute bioavailability of adalimumab, calculated in three studies, following a single 40 mg subcutaneous dose was 64%.
After a single intravenous dose of 0.25 to 10 mg/kg, concentrations were dose proportional. After a dose of 0.5 mg/kg (approximately 40 mg), clearance ranged from 11 to 15 mL/h, volume of distribution (Yss) was 5 to 6 L, and the mean terminal half-life was approximately 2 weeks. Synovial fluid concentrations of adalimumab in RA patients ranged from 31 to 96% of serum levels.
In children with polyarticular JRA aged 2-4 years and in children aged 4 years and older weighing less than 15 kg, the mean steady-state concentrations after administration of adalimumab at a dose of 24 mg/m2 with methotrexate were 7.9 ± 5.6 mg/ml (101% CV).
Following subcutaneous administration of adalimumab at a dose of 24 mg/m2 (up to 40 mg) every 2 weeks in patients aged 6 to 17 years with enthesitis-related arthritis, steady-state concentrations (measured at week 24) were 8.8 ± 6.6 μg/mL without concomitant methotrexate and 11.8 ± 4.3 μg/mL with methotrexate, respectively.
In adult patients with psoriasis, the mean steady-state concentration was 5 μg/mL during monotherapy with adalimumab 40 mg every 2 weeks.
Following subcutaneous administration of adalimumab at a dose of 0.8 mg/kg (up to a maximum of 40 mg) every 2 weeks in children with chronic plaque psoriasis, steady-state concentrations were approximately 7.4 ± 5.8 μg/mL (79% CV).
In patients with hidradenitis suppurativa, after administration of adalimumab at a dose of 160 mg at week 0 followed by 80 mg at week 2, serum concentrations were approximately 7 to 8 μg/mL at weeks 2 and 4. The mean steady-state concentration from week 12 to week 36 was approximately 8 to 10 μg/mL when adalimumab was administered at a dose of 40 mg every week.
The effect of adalimumab in adolescents with hidradenitis suppurativa was determined using pharmacokinetic modeling and simulation based on pharmacokinetics in other pediatric indications (plaque psoriasis, juvenile rheumatoid (idiopathic) arthritis (JRA), Crohn's disease (CD) and enthesitis-related arthritis). The recommended dose regimen for adolescents with hidradenitis suppurativa is 40 mg every 2 weeks. Since the effect of adalimumab may be weight-dependent, the recommended adult dose of 40 mg once weekly may be used in adolescents with high body weight and inadequate response to treatment.
In patients with Crohn's disease, serum concentrations were approximately 5.5 μg/mL during induction therapy following adalimumab 80 mg at week 0 followed by 40 mg at week 2. Serum concentrations were approximately 12 μg/mL during induction therapy following adalimumab 160 mg at week 0 followed by 80 mg at week 2. The mean steady-state concentration was approximately 7 μg/mL during adalimumab 40 mg every other week maintenance dose.
In children with moderately to severely active Crohn's disease, the starting dose of adalimumab in the open-label study was 160/80 mg or 80/40 mg at weeks 0 and 2, based on body weight. At week 4, patients were randomized 1:1 to receive either the standard dose (40/20 mg every other week) or the low dose (20/10 mg every other week) for maintenance therapy, based on body weight. The mean steady-state concentration was approximately 15.7 ± 6.6 μg/mL at week 4 in patients weighing 40 kg or more (160/80 mg) and 10.6 ± 6.1 μg/mL in patients weighing less than 40 kg (80/40 kg).
In patients with ulcerative colitis, after administration of adalimumab at an initial dose of 160 mg at week 0 followed by 80 mg at week 2, the serum concentration was approximately 120 μg/mL during induction therapy. The mean steady-state concentration was approximately 80 μg/mL during adalimumab maintenance dose of 40 mg every other week.
In patients with uveitis, after administration of adalimumab at an initial dose of 80 mg at week 0 followed by 40 mg every 2 weeks starting at week 1, the mean steady-state concentration was approximately 8 to 10 μg/mL.
The effect of adalimumab on children with uveitis was determined using pharmacokinetic modeling and pharmacokinetic simulation in other pediatric indications (plaque psoriasis, juvenile rheumatoid (idiopathic) arthritis (JRA), Crohn's disease (CD) and enthesitis-related arthritis).
There are no clinical data on the effect of the starting dose of adalimumab on the condition of children under 6 years of age.
It is predicted that in the absence of methotrexate, the initial dose may lead to increased systemic exposure.
Derivation.
A population pharmacokinetic analysis of data from over 1300 RA patients showed a trend for the apparent clearance of adalimumab to increase with increasing body weight. After adjusting for body weight, gender and age were found to have minimal effects on adalimumab clearance. Serum levels of free adalimumab (not bound to anti-adalimumab antibodies (AAA)) were lower in patients with AAA. Hyrimoz 40 has not been studied in patients with hepatic or renal impairment.
Indication
Rheumatoid arthritis (RA).
Hyrimoz 40 in combination with methotrexate is indicated for:
treatment of moderately to severely active rheumatoid arthritis in adult patients who have not had an adequate response to disease-modifying antirheumatic drugs (DMARDs), including methotrexate;
Treatment of active, progressive, highly active rheumatoid arthritis in adult patients who have not previously received methotrexate therapy.
Adalimumab has been shown to inhibit the progression of structural joint damage as confirmed by radiography and improve functional status when used concomitantly with methotrexate.
Juvenile rheumatoid (idiopathic) arthritis (JRA).
Polyarticular juvenile rheumatoid (idiopathic) arthritis.
Hyrimoz 40 in combination with methotrexate is indicated for the treatment of active polyarticular juvenile idiopathic arthritis in children aged 2 years and older who have had an inadequate response to therapy with one or more disease-modifying antirheumatic drugs (DMARDs).
Hyrimoz 40 can be used as monotherapy in case of intolerance to methotrexate or when continued methotrexate therapy is unacceptable. Hyrimoz 40 has not been studied in patients under 2 years of age.
Enthesitis-associated arthritis.
Hyrimoz 40 is indicated for the treatment of active enthesitis-related arthritis in children aged 6 years and older who have failed to respond to conventional therapy, or who are intolerant to or have medical contraindications to such therapies.
Axial and spondyloarthritis.
Ankylosing spondylitis (AS).
Hyrimoz 40 is indicated for the treatment of adult patients with highly active ankylosing spondylitis who have not responded to conventional therapy.
Axial spondyloarthritis without radiographic evidence of AS.
Hyrimoz 40 is indicated for the treatment of adult patients with highly active axial spondyloarthritis without radiographic evidence of AS, but with evidence of inflammation based on elevated CRP levels and/or MRI (magnetic resonance imaging).
Psoriatic arthritis (PsA)
Hyrimoz 40 is indicated for the treatment of active and progressive psoriatic arthritis in adult patients who have had an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs). Adalimumab has been shown to slow the rate of progression of peripheral joint damage as measured by radiography in patients with symmetrical polyarticular disease and improve functional status.
Plaque psoriasis (PP).
Hyrimoz 40 is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who require systemic therapy.
In pediatrics
Plaque psoriasis (PP) in children.
Hyrimoz 40 is indicated for the treatment of severe chronic plaque psoriasis in children aged 4 years and older who have not responded to or are intolerant to topical therapy or phototherapy.
Hidradenitis suppurativa (HS).
Hyrimoz 40 is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adult patients and adolescents aged 12 years and older who have not responded to conventional systemic therapy.
Crohn's disease (CD).
Hyrimoz 40 is indicated for the treatment of moderately to severely active Crohn's disease in adult patients who have failed to respond to a full course of therapy with corticosteroids and/or immunosuppressants or who are intolerant to or have medical contraindications to such therapies.
Crohn's disease (CD) in children.
Hairyuse 40 is indicated for the treatment of moderately to severely active Crohn's disease in children aged 6 years and older who have not responded to conventional therapy, including primary nutritional therapy, therapy with corticosteroids and/or immunomodulators, or who are intolerant to or have medical contraindications to such therapies.
Ulcerative colitis (UC).
Hyrimoz 40 is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients who have failed to respond to conventional therapy, including corticosteroids and/or 6-mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications to such therapies.
Uveitis.
Hyrimoz 40 is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult patients who have failed to respond to corticosteroid therapy, who require a reduction in the dose of corticosteroids or who are intolerant to or have medical contraindications to corticosteroid therapy.
Uveitis in children.
Hyrimoz 40 is indicated for the treatment of chronic non-infectious anterior uveitis in children aged 2 years and older who have failed to respond to or are intolerant to conventional therapy or for whom conventional therapy is contraindicated.
Contraindication
Hypersensitivity to adalimumab or to any other component of the drug.
Active tuberculosis or other severe infections such as sepsis and opportunistic infections (see section "Special warnings and precautions for use").
Moderate and severe heart failure (NYHA class III/IV) (see section "Special warnings and precautions for use").
Interaction with other medicinal products and other types of interactions
The simultaneous use of Hairyuse 40 with anakinra is not recommended (see section "Special precautions for use").
The simultaneous use of Hyrimoz 40 with abatacept is not recommended (see section "Special warnings and precautions for use").
Application features
In order to improve control of the use of biological drugs, it is necessary to clearly record the trade name and batch number of the administered drug.
Infections.
Patients who have used TNF blockers are more likely to develop serious infections. Impaired lung function may increase the risk of developing infections. Therefore, patients should be closely monitored and evaluated for infections, including tuberculosis, before, during, and after treatment with Hyrimoz 40. Since elimination of adalimumab may take up to four months, monitoring should continue during this period.
It should not be used in patients with active infections, including chronic or localized infections, until the infection is controlled. In patients who have been in contact with a patient with tuberculosis or have returned from countries with a high incidence of tuberculosis or from endemic areas for mycoses (histoplasmosis, coccidioidomycosis or blastomycosis), the benefit/risk ratio should be assessed before starting Hyrimoz 40 (see below "Other opportunistic infections").
Patients who develop a new infection while receiving Hyrimoz 40 should be thoroughly evaluated and closely monitored. Treatment should be discontinued if severe infection or sepsis develops and appropriate antimicrobial or antifungal agents should be administered until the infection is controlled.
Hyrimoz 40 should be used with particular caution in patients with recurrent infections or pre-morbid conditions that increase susceptibility to infections.
Serious infections: Sepsis, and rarely tuberculosis, candidiasis, listeriosis, legionellosis, and pneumocystis infection have been reported with TNF-antagonists, including adalimumab. Other serious infections have been observed in clinical trials, including pneumonia, pyelonephritis, septic arthritis, and septicemia. Hospitalization of patients with emerging infections (including fatal outcomes) has been reported.
Most severe infections developed against the background of immunosuppressive drugs and underlying disease.
Tuberculosis.
Cases of reactivation and development of new tuberculosis infection, including pulmonary and non-pulmonary forms (i.e. disseminated tuberculosis), have been reported in patients treated with adalimumab. Before initiating therapy with Hyrimoz 40, patients should be carefully evaluated for active and non-active (latent) tuberculosis. The examination should include a comprehensive assessment of the patient's history of tuberculosis or information about possible contacts with patients with active tuberculosis and about previous and/or concomitant immunosuppressive therapy. All patients should undergo a tuberculin skin test (Mantoux test) and a chest x-ray before starting therapy. A positive tuberculin skin test result for the diagnosis of latent tuberculosis is considered to be the appearance of a seal (papule) with a diameter of 5 mm or more (without taking into account previous BCG vaccination). The possibility of undiagnosed latent tuberculosis should be considered in patients who have returned from countries with a high incidence of tuberculosis or who have had close contact with a patient with active tuberculosis. Treatment with Hyrimoz 40 should not be carried out if active tuberculosis is diagnosed.
In case of latent tuberculosis, specific preventive treatment should be carried out before starting therapy with Hyrimoz 40. The need for anti-tuberculosis treatment should be considered before starting therapy with Hyrimoz 40 in patients who have risk factors for developing tuberculosis infection but who have a negative test result for latent tuberculosis, and in patients who have a history of latent or active tuberculosis and for whom appropriate treatment cannot be confirmed. The decision to start anti-tuberculosis therapy for such patients is made after consultation with a phthisiologist and an assessment of the risk of developing latent tuberculosis and the safety of anti-tuberculosis treatment.
All patients should be advised to seek medical advice if they develop symptoms suggestive of tuberculosis (e.g. persistent cough, weight loss, low-grade fever, apathy) during or after treatment with Hyrimoz 40.
Other opportunistic infections.
Opportunistic infections, including invasive fungal infections, have been reported during treatment with adalimumab. Sometimes these infections have not been diagnosed in a timely manner, which has led to a delay in treatment initiation and sometimes has been fatal. Patients receiving TNF blockers are at increased risk of developing serious fungal infections, such as histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, candidiasis, etc. All patients who develop fever, malaise, weight loss, increased sweating, cough, dyspnea, and/or pulmonary infiltrates or other signs of serious systemic illness (with or without shock) should be evaluated promptly for opportunistic infections.
In patients residing in or traveling to areas endemic for mycoses, invasive fungal infections should be suspected if symptoms suggestive of systemic fungal infection develop. Because of the increased risk of histoplasmosis or other invasive fungal infections, empirical antifungal therapy should be considered until the pathogen is identified. In some patients, histoplasmosis antigen or antibody tests may be negative even with active infection. If appropriate, the decision to use empirical antifungal therapy in such patients should be made in consultation with a specialist in the diagnosis and treatment of invasive fungal infections, taking into account the risk of fungal infection as well as the risk of antifungal therapy. It is recommended that TNF blocker therapy be discontinued if a severe fungal infection develops until the infection is controlled.
Hepatitis B reactivation.
The use of TNF blockers has been associated with hepatitis B virus (HBV) reactivation in chronic carriers. Sometimes HBV reactivation during TNF blocker therapy has been fatal. In most cases, patients were also receiving other immunosuppressive medications that could also have contributed to HBV reactivation. Patients at risk should be screened for HBV before starting TNF blockers. TNF blockers should be used with caution in patients with HBV and, if prescribed, should be closely monitored for symptoms of HBV reactivation during therapy and for several months after discontinuation of therapy. There are no data on the efficacy and safety of antiviral agents for the prevention of HBV reactivation in carriers receiving TNF blockers. In the event of HBV reactivation, Hyrimoz 0 40 therapy should be discontinued and effective antiviral treatment and appropriate supportive care should be initiated.
Neurological disorders.
There have been isolated reports of the emergence or exacerbation of clinical symptoms and/or radiographic signs of central nervous system demyelinating disorders, including multiple sclerosis, optic neuritis and peripheral nervous system demyelinating disorders, including Guillain-Barré syndrome, with the use of TNF-blockers, including adalimumab. A careful benefit/risk assessment of the use of adalimumab in patients with central or peripheral nervous system demyelinating disorders is recommended. Therapy with Hyrimoz 40 should be discontinued if these disorders occur. There is a known association between intermediate uveitis and central nervous system demyelinating disorders. Neurological examination should be performed in patients with non-infectious intermediate uveitis before initiating therapy with Hyrimoz 40 and regularly during therapy to assess for the development of demyelinating disorders of the central nervous system.
Allergic reactions.
Serious allergic reactions associated with adalimumab were rare in clinical trials. Serious allergic reactions, including anaphylaxis, have been reported following administration of adalimumab. If an anaphylactic reaction or other serious allergic reaction occurs, Hyrimoz 40 should be discontinued immediately and appropriate therapy should be initiated.
Immunosuppression.
In clinical studies of adalimumab in 64 patients with RA, no cases of suppression of delayed-type hypersensitivity, decreased immunoglobulin levels, or quantitative changes in effector T and B cells, as well as K cells, monocytes/macrophages, and neutrophils were observed.
In controlled clinical trials of TNF blockers, malignancies have been reported more frequently in patients treated with TNF blockers than in control patients. However, the small sample size and short duration of the trials preclude definitive conclusions. Furthermore, patients with long-standing, highly active RA have a high background risk of lymphoma, making risk assessment difficult. In long-term, open-label clinical trials of adalimumab, the overall incidence of malignancies was similar to that expected in the general population matched for age, sex, and race. However, a possible risk of lymphoma or other malignancies in patients treated with TNF blockers cannot be excluded.
There have been isolated reports of fatal malignancies in children and adolescents treated with TNF-blockers. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphomas. The remaining cases were of a variety of malignancies, including rare cases of malignancies usually associated with immunosuppression. The malignancies occurred after a median of 30 months of therapy. Most patients were receiving concomitant immunosuppressants. These reports were obtained from post-marketing surveillance and were from a variety of sources, including registries and post-marketing reports.
In post-marketing experience, hepatosplenic T-cell lymphoma (a rare type of lymphoma that is very aggressive and usually fatal) has been reported very rarely in patients receiving adalimumab. Most of these patients had previously received infliximab in combination with azathioprine or 6-mercaptopurine for the treatment of inflammatory bowel disease. The potential risk of concomitant use of azathioprine or 6-mercaptopurine with adalimumab should be carefully evaluated. The causal relationship between the development of hepatosplenic T-cell lymphoma and the use of adalimumab remains unclear.
There have been no studies of the use of adalimumab in patients with a history of malignancy or of continued therapy in patients who develop malignancy. This should be taken into account and decisions regarding the use of Hyrimoz 40 in such patients should be made with caution.
In all patients, especially those with a history of intensive immunosuppressive therapy or patients with psoriasis who have received PUVA therapy, the presence of non-melanoma skin cancer should be excluded before and during the period of use of Hyrimoz 40.
Postmarketing cases of acute and chronic leukemia have been reported in association with the use of TNF-blockers in rheumatoid arthritis and other indications. Patients with rheumatoid arthritis may have an increased risk of developing leukemia (approximately two-fold) compared with the general population, even in the absence of TNF-blocker therapy.
In a clinical trial evaluating another TNF blocker (infliximab), patients with chronic obstructive pulmonary disease reported a higher incidence of neoplasms, mostly in the lungs, head, and neck, compared with controls. All patients were long-term smokers. Therefore, caution should be exercised when using any TNF blocker in patients with chronic obstructive pulmonary disease and in patients at increased risk of neoplasms due to smoking.
It is currently unknown whether adalimumab affects the risk of developing dysplasia or bowel cancer. All patients with ulcerative colitis who are at increased risk of developing dysplasia or bowel cancer (e.g. patients with long-standing ulcerative colitis or primary sclerosing cholangitis) or who have a history of dysplasia or bowel cancer should be regularly screened for dysplasia before starting therapy and throughout the course of their disease. Screening should include colonoscopy and biopsy.
Hematological disorders.
Rarely, when using TNF blockers, the development of pancytopenia, aplastic anemia has been reported. When using adalimumab (causal relationship is not established), the development of cytopenia (thrombocytopenia, leukopenia) that had clinical significance has been reported. All patients should be warned about the need for immediate medical consultation if symptoms characteristic of blood disorders (such as persistent fever, bruising, bleeding, pale skin and mucous membranes) appear while using adalimumab. The need to discontinue the use of Hyrimoz 40 in patients should be considered if serious blood disorders are confirmed.
Vaccination.
Patients receiving Hyrimoz 40 may receive vaccinations, except for live vaccines. There are no data on secondary transmission of infection with live vaccines in patients receiving adalimumab.
Administration of live vaccines to infants exposed to adalimumab in utero is not recommended for 5 months after the mother's last adalimumab injection during pregnancy.
Chronic heart failure (CHF).
Adalimumab has not been studied in patients with chronic heart failure, however, in clinical trials with another TNF blocker, a higher incidence of CHF-related adverse events, including worsening CHF and new CHF, has been reported. Cases of CHF progression have also been reported in patients receiving adalimumab therapy. Hyrimoz 40 should be used with caution in patients with heart failure and with close monitoring of their condition (see section 4.8).
Autoimmune processes.
Treatment with adalimumab may induce the development of autoantibodies. The effect of long-term use of Hyrimoz 40 on the development of autoimmune diseases is unknown. If symptoms resembling lupus-like syndrome occur, treatment with Hyrimoz 40 should be discontinued.
Concomitant use with biological DMARDs or TNF antagonists.
Serious infections have been observed in clinical trials of concomitant use of anakinra and etanercept, which did not provide a therapeutic advantage over etanercept alone. Given the nature of the adverse events observed with the combination of etanercept and anakinra, similar toxicities may occur with the combination of anakinra and another TNF blocker. Therefore, the combination of adalimumab and anakinra is not recommended.
Concomitant use of adalimumab with other biologic DMARDs (e.g. anakinra and abatacept) or with other TNF antagonists is not recommended due to the possible increased risk of infections and other potential pharmacological interactions.
Surgical interventions
Limited safety data are available on surgical procedures in patients receiving adalimumab. The long half-life of adalimumab should be taken into account if surgery is planned. Patients undergoing surgery and receiving Hyrimoz 0 40 should be closely monitored for infections. Appropriate measures should be taken as necessary. Limited safety data are available on patients undergoing arthroplasty while receiving adalimumab.
Small bowel obstruction.
Failure to respond to treatment for Crohn's disease may indicate the presence of a fixed fibrous structure that requires surgical treatment. Available data suggest that treatment with adalimumab does not cause the formation or progression of structures.
Elderly patients.
The incidence of serious infections in patients aged 65 years and older receiving adalimumab (3.7%) was higher than in younger patients (1.5%). Some cases were fatal. Overall, 9.5% of patients aged 65 years and older participated in clinical trials, of which approximately 2.0% were aged 75 years and older. Because the incidence of infections is higher in the elderly, adalimumab should be used with caution in this age group.
Children.
See the section “Vaccination” above.
Excipients with known effects.
The drug Hyrimoz 40 contains less than 1 mmol sodium (23 mg) per 0.8 ml, i.e. essentially sodium-free.
Use during pregnancy or breastfeeding
Women of reproductive age.
To prevent pregnancy, women of reproductive age should use reliable methods of contraception during treatment and for at least five months after the last dose of Hyrimoz 40.
Pregnancy
A prospective analysis of data on the use of adalimumab during pregnancy (approximately 2,100 pregnancies resulting in live births with known outcomes, including more than 1,500 exposures in the first trimester) did not reveal an increased incidence of birth defects in newborns.
A prospective cohort registry included 257 women with RA or UC who received adalimumab for at least the first trimester and 120 women with RA or UC who did not receive adalimumab. The primary endpoint was the incidence of major birth defects in the newborn. The incidence of pregnancies resulting in at least one live birth with a major birth defect was 6 of 69 (8.7%) in the adalimumab-treated group and 5 of 74 (6.8%) in the control group.
