Humirapen

Adalimumab (adalimumab) instructions

Common name: adalimumab

Trade name: Humira

All names: adalimumab, Humira, adalimumab, Humira

Indications:

Rheumatoid arthritis, ankylosing spondylitis.

Dosage:

Adult patients with rheumatoid arthritis:

The recommended dosage is 40 mg of adalimumab, administered as a single dose by subcutaneous injection every two weeks. Methotrexate should be continued during treatment with this product.

Corticosteroids, salicylates, non-steroidal anti-inflammatory drugs or analgesics can be continued during the course of treatment. If the therapeutic effect of some patients decreases during single drug treatment, the dosage can be increased to 40 mg of adalimumab injected weekly to improve the effect. Interruption of dosing - There are data showing that the clinical response and safety of the drug can be achieved when the drug is resumed after an interval of 70 days or more.

Adult patients with ankylosing spondylitis:

The recommended dosage is 40 mg of adalimumab administered by subcutaneous injection every two weeks. For all of the above indications, there are data showing that treatment is usually Clinical response can be obtained within 12 weeks. Patients who do not show clinical response during this treatment period should carefully consider whether to continue treatment.

Adverse reactions:

>10%:

Central nervous system: headache (12%)

Dermatology: rash (6%-12%)

Hematology and tumors: positive antinuclear antibody titer (12%)

Immune: antibody development (3%-26%)

p>

Infection: Infection (children and adolescents: 45%)

Local reaction: injection site reaction (5%-20%)

Neuromuscular and skeletal: increased creatine phosphokinase (15%)

Respiratory: upper respiratory tract infection (17%), sinusitis (11%)

1% - 10%:

Cardiovascular diseases: hypertension (5%), atrial fibrillation (<5%), arrhythmia (<5%), chest pain (<5%), coronary heart disease (<5%), deep vein thrombosis (<5%), hypertensive encephalopathy (<5%), myocardial infarction (<5%), Palpitations (<5%), pericardial effusion (<5%), pericarditis (<5%), peripheral edema (<5%), subdural hematoma (<5%), syncope (<5%), tachycardia (<5%)

Central nervous system: confusion (<5%), muscle weakness (<5%) , paresthesia (<5%), somatic pain (<5%)

Dermatology: cellulitis, erysipelas

Endocrine metabolism: hyperlipidemia (7%), hypercholesterolemia (6%), dehydration (<5%), ketosis (<5%), menstrual diseases (<5%), Parathyroid disease (<5%)

Gastrointestinal tract: nausea (9%), abdominal pain (7%), cholecystitis (<5%), cholelithiasis (<5%), esophagitis (<5%), gastrointestinal bleeding (<5%), vomiting (<5%), gastrointestinal diverticulitis

Urology Reproductive system: urinary tract infection (≤8%), hematuria (5%), cystitis (<5%), pelvic pain (<5%)

Hematology and tumors: adenoma (<5%), agranulocytosis (<5%), paraproteinemia (<5%), polycythemia (<5%), carcinoma ( Including breast, gastrointestinal tract, skin, genitourinary system), malignant lymphoma, malignant melanoma

Liver: elevated serum alkaline phosphatase (5%), liver necrosis (<5%)

Allergic reaction: hypersensitivity reaction (5%-6% in children, 1% in adults)

Neuromuscular and skeletal: back pain (6%), arthritis (<5%), arthrosis (<5%), bone disease (<5%), fracture (<5%), Limb pain (<5%), muscle spasm (<5%), myasthenia (<5%), osteonecrosis (<5%), septic arthritis (<5%), synovitis (<5%), tendon disease (<5%), tremor (<5%), arthralgia (3%; plaque psoriasis)

Ophthalmology: cataracts (<5%)

Kidneys: nephrolithiasis (<5%), pyelonephritis

Respiratory system: flu-like symptoms (7%), asthma (<5%), bronchospasm (<5%), dyspnea (<5%), pleural effusion (<5%), respiratory Respiratory depression (<5%), pharyngitis (juvenile idiopathic arthritis: ≤4%), pneumonia (≤4%), tuberculosis (including reactivation of underlying infection; disseminated, miliary, lymphatic, peritoneal and pulmonary)

Others: accidental injury (10%), abnormal healing (5%) , postoperative complications (infection)

<1%:

Post-marketing or case reports: abscess (limbs, perianal), alopecia, anal fissure, anaphylactic shock, allergic reaction, anemia, angioedema, aplastic anemia, appendicitis, fatigue, bacterial infection, basal Cell carcinoma, blepharitis, bronchitis, heart failure, circulatory shock, cytopenias, skin ulcers, diarrhea, endometrial hyperplasia, eosinophilia, fever, fungal infection

Contraindications:

Known hypersensitivity to adalimumab or any component of the preparation.

Severe infections (such as sepsis, tuberculosis, opportunistic infections).

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

Notes:

Autoimmune disease: The patient has positive antinuclear antibody titer (negative at baseline). Rare autoimmune diseases, including lupus-like syndrome, have been reported. If symptoms occur, monitor and stop progression of symptoms.

Demyelinating diseases: Rare cases of new or worsening demyelinating diseases have been reported (e.g., multiple sclerosis, optic neuritis, peripheral demyelinating diseases, including Guillain-Barre syndrome); there is a known association between intermediate uveitis and central demyelinating diseases. Consider discontinuing use if a patient develops peripheral or central nervous system demyelinating disease during treatment. Use with caution in patients with existing or recent onset demyelinating disease of the central or peripheral nervous system.

Heart Failure: Worsening and new-onset heart failure (HF) have been reported with adalimumab and other tumor necrosis factor blockers. Use with caution in patients with heart failure or left atrial dysfunction. In a scientific statement from the American Heart Association, TNF (tumor necrosis factor) blockers were identified as drugs that may cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (Severity: Major).

Hematologic Disorders: Rare cases of pancytopenia and aplastic anemia have been reported. If the patient develops signs and symptoms suggesting blood abnormalities, the patient must be advised to seek medical treatment; if obvious blood abnormalities are confirmed, treatment should be discontinued. Use with caution in patients with a history of significant blood abnormalities.

Hepatitis B: Rare reactivation of hepatitis B virus (HBV) occurs in chronic carriers, usually in patients receiving immunosuppressants (some are fatal); assess for HBV in all patients before initiating treatment. Monitor HBV carriers during and for several months after discontinuation of treatment; if reactivation occurs, interrupt treatment and use antiviral therapy as appropriate; if resumption of treatment is deemed necessary, caution should be exercised and the patient should be monitored closely.

Nervous system: In terms of clinical symptoms or radiological examination results, TNF antagonists including this product rarely cause the occurrence and worsening of demyelinating lesions of the central nervous system, including multiple sclerosis and peripheral demyelinating lesions including Guillain-Barré syndrome. Physicians should exercise extreme caution when administering this product to patients who have had or are currently suffering from demyelinating lesions of the central and peripheral nervous systems.

Allergic reactions: During the clinical research phase, there are no reports of serious adverse events of allergic reactions in patients caused by subcutaneous injection of this product, and non-serious allergic reactions caused by this product are also uncommon. Serious allergic reactions (including anaphylaxis) resulting from use of this product have been rarely reported after its marketing. If patients experience anaphylaxis or other severe allergic reactions, they should stop taking this product immediately and take appropriate treatment. The needle surface of the syringe is covered with natural rubber (latex). Patients with latex allergies may experience severe allergic reactions when using this product.

Immunosuppression: Among the 64 patients with rheumatoid arthritis studied with this product, there was no indication that this product inhibited or altered delayed-type allergic reactions or immunoglobulin levels. Numbers of T cells, B cells, NK (natural killer) cells, monocytes/macrophages, and neutrophils.

Malignant disease and abnormal lymphocyte proliferation: In controlled portions of clinical studies of TNF antagonists, patients receiving TNF compared with control Malignant lesions (including lymphoma) have occurred in patients treated with antagonists, but the incidence is low. Post-market acceptance of TNF Cases of leukemia have been reported in patients taking antagonists. Risk assessment is complicated by an increased risk of developing lymphoma and leukemia in patients with rheumatoid arthritis who have long-term, highly active inflammatory disease. Based on what is currently known, acceptance cannot be ruled out Risk of lymphoma, leukemia or other malignancies in patients taking TNF antagonists.

Hematological response: after using TNF Pancytopenia, including aplastic anemia, has been rarely reported with antagonists. A small number of hematological adverse reactions have been reported with the use of this product, including clinically significant cytopenias (e.g., thrombocytopenia, leukopenia). Patients who develop signs and symptoms of cachexia (eg, persistent fever, bruising, bleeding, pale skin) should be seen and treated immediately. For those patients who have been diagnosed with hematological abnormalities, the use of this product should be stopped immediately.

Vaccination: In 226 adult subjects with rheumatoid arthritis treated with adalimumab and placebo, compared with standard 23-valent pneumococcal polysaccharide vaccine, and 3 Antibody response similar to influenza virus vaccine. Transmission of secondary infections due to live vaccines has not been reported in patients treated with this product. In addition to live vaccines, patients taking this product can receive vaccinations at the same time.

Congestive heart failure: in another TNF In clinical studies of antagonists, worsening of congestive heart failure and increased mortality due to congestive heart failure have been observed. Cases of worsening of congestive heart failure have also been reported in patients receiving this product. For those with mild heart failure (NYHA Category I/II Level) patients should exercise caution when using this product. Moderate to severe heart failure is a contraindication to this product. Patients should discontinue use of this product if they develop symptoms of congestive heart failure or if previous symptoms worsen.

Autoimmune process: Drug treatment with this product can lead to the formation of autoantibodies. The effects of long-term treatment with this product on autoimmune diseases are unknown. If after treatment with this product, the patient develops symptoms of lupus-like syndrome and double-stranded When DNA antibodies are positive, treatment with this product should be stopped immediately.

Concomitant use of TNF antagonists and anakinra: Concomitant use of anakinra and other In clinical studies of the TNF antagonist etanercept, severe infections were observed and did not improve clinical efficacy compared with etanercept alone. Based on the adverse reaction profile of etanercept and anakinra when combined with anakinra, Similar toxicities may occur when TNF antagonists are used concomitantly. Therefore, combined use of this product with anakinra is not recommended.

Concomitant use of a TNF antagonist and abatacept: Compared with the use of a TNF antagonist alone, concomitant use of TNF Antagonists and abataxel increase the risk of infection, including serious infection, but do not improve clinical efficacy. It is not recommended to use this product in combination with abataxel.

Surgery: There is limited experience regarding the safety of surgery in patients treated with this product. The long half-life of adalimumab should be taken into consideration when planning surgery in patients. When patients receiving this product require surgery, they should pay close attention to the patient's infection status and take appropriate measures. Experience with the safety of arthroplasty in patients treated with this product is also limited.

Small bowel obstruction: Ineffective treatment for Crohn's disease means there may be fixed fibrous strictures in the intestinal lumen, requiring surgical treatment. Available data indicate that this product does not cause or worsen intestinal stenosis.

Geriatric Population: Serious infections occurred more frequently in patients over 65 years of age (3.7%) treated with patients under 1.4 years of age (1.4%). Some of them can have fatal consequences. Therefore, special attention should be paid to the associated infection risks when treating elderly patients.

Effects on ability to drive and operate machinery: This product may have minor effects on the ability to drive and operate machinery. Treatment with this product may cause dizziness (including vertigo, visual disturbance, and fatigue).

Storage:

Store in original container at 2°C to 8°C (36°F to 46°F), protected from light. Do not freeze.

Mechanism of action:

Adalimumab can specifically bind to TNF (tumor necrosis factor) and eliminate its biological function by blocking the interaction between TNF (tumor necrosis factor) and p55 and p75 cell surface TNF (tumor necrosis factor) receptors. Adalimumab can also modulate biological effects mediated or regulated by TNF, including changing the levels of adhesion molecules important for leukocyte migration (ELAM-1, VCAM-1 and ICAM1, half inhibitory concentration of 0.1-0.2nM). After patients with rheumatoid arthritis were treated with this product, the levels of acute phase inflammatory reactants (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and serum cytokines (L-6) decreased rapidly compared with baseline levels. Serum levels of matrix metal proteins (MMP-1 and MMP-3) that cause tissue remodeling and cartilage destruction also decrease.

Safety and efficacy:

The clinical efficacy and safety of the tumor necrosis factor α antagonist adalimumab in the short-term treatment of rheumatoid arthritis (RA). The changes in rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP antibody) titers before and after treatment were also detected to find new indicators for the evaluation of the efficacy of RA (rheumatoid arthritis). Methods: A randomized double-blind parallel trial was conducted. 40 patients with active RA were included and randomly assigned to the experimental group or the control group in a ratio of 2:2:1. The experimental group was divided into 80 patients. mg adalimumab + methotrexate (MTX), 40 There are two groups of mg adalimumab + MTX, and the control group is placebo + MTX. Subjects received subcutaneous injections of adalimumab or an equivalent volume of placebo every other week, and were followed up at 0, 2, 4, 8, and 12 weeks of the trial to evaluate efficacy and collect adverse events. The efficacy was evaluated using ACR core standards. Secondary efficacy measures include the number of tender and swollen joints, duration of morning stiffness, visual analog scale for pain (VAS score), health assessment questionnaire (HAQ) and CRP (C-reactive protein). RF and anti-CCP antibodies were detected at baseline and after 12 weeks of treatment. Results: There were 32 cases in the experimental group and 8 cases in the control group. After 12 weeks, the proportion of ACR20, ACR50 and ACR70 relief in the experimental group was significantly higher than that in the control group (P<0.01); the number of joint tenderness, joint swelling, duration of morning stiffness, pain VAS score and Health Status Questionnaire (HAQ), CRP of the patients in the experimental group (C-reactive protein) and other secondary efficacy indicators were significantly lower than the baseline levels (P<0.05); the RF serum titers and anti-CCP antibodies in the experimental group were significantly lower than the baseline levels (P<0.05), while no significant changes in RF and CCP antibody titers were observed in the control group. Generally speaking, adalimumab has mild adverse reactions and is well tolerated. Conclusion: The efficacy of adalimumab + MTX (methotrexate) in the treatment of RA is significantly better than that of the MTX (methotrexate) alone group, and can quickly improve various symptoms.