Humira – selective immunosuppressive agent. Adalimumab is a recombinant monoclonal antibody, a peptide whose sequence is identical to human IgGl. Adalimumab selectively binds to tumor necrosis factor alpha (TNF-alpha) and neutralize its biological function by blocking the interaction with cell surface receptors p55 and p75 TNF-alpha. TNF – a natural cytokine that is involved in the regulation of normal inflammatory and immune responses. Increased concentration of TNF-alpha is detected in synovial fluid of patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis.
TNF-alpha plays an important role in the development of pathologic inflammation and joint tissue destruction characteristic of these diseases. Elevated concentrations of TNF-alpha also detected in psoriatic plaques. When plaque psoriasis adalimumab treatment can reduce the thickness of the plaques and reduce infiltration in inflammatory cells. The relationship of the clinical effect of adalimumab with its mechanism of action has not been established. Adalimumab also modulates biological responses that are induced or regulated by TNF-alpha, including changes in the content of adhesion molecules, inducing migration of leukocytes.
D 0,8 ml containing solution.
Active ingredient: adalimumab – 40.0 mg;
Excipients: Mannitol – 9.6 mg citric acid monohydrate – 1,044 mg, sodium citrate – 0.244 mg disodium hydrogen phosphate dihydrate – 1,224 mg sodium dihydrogen phosphate dihydrate – 0.688 mg Sodium chloride – 4,932 mg, 0.8 mg polysorbate -80 water for injection – 759.028 mg – 759.048 mg sodium hydroxide – 0.02 mg – 0.04 mg.
- The active ankylosing spondylitis;
- moderate to severe active rheumatoid arthritis (in monotherapy or in combination with methotrexate or other basic antiinflammatory drugs);
- Active psoriatic arthritis (as monotherapy or in combination with methotrexate or other basic antiinflammatory drugs);
- Crohn’s disease (moderate or severe) as inadequate response to conventional therapy or ineffective (or decrease in efficacy) infliximab;
- Chronic plaque psoriasis (moderate and severe), when systemic therapy or phototherapy, and when other systemic therapy options are not optimal.
- Juvenile idiopathic arthritis in patients 13 to 17 years in monotherapy or in combination with methotrexate.
- Hypersensitivity to adalimumab or any of its components, auxiliary
- Children under 18 years, except for patients 13 to 17 years with juvenile idiopathic arthritis.
- Infectious diseases including tuberculosis
- Chronic heart failure III-IV functional class NYHA.
- A joint reception with anakinra and abatacept drugs.
The following are safety data Humira received the placebo-controlled clinical trials.
Clinical and laboratory adverse events, whose connection with adalimumab was at least possible, distributed over the system and frequency (very frequent > 1/10; frequent > 1/100 < 1/10; infrequent
Infections very common: upper respiratory tract infection Common
; lower respiratory tract infections (including pneumonia and bronchitis), urinary tract infection, herpetic infection (including simple and herpes zoster), influenza, superficial fungal infections (including skin lesions and nails) Infrequent sepsis, joint, and wound infection ii, abscess, infection of the skin (including impetigo), infection of the hair follicle (including furuncles and carbuncles), paronychia, pustular rash, dental infections, and periodontal ear infection, gastroenteritis, candidiasis of mouth and throat, vaginal infection (including fungal), viral infection Neoplasms Infrequent:. skin papilloma Blood and lymphatic system Common: anemia, lymphopenia
Infrequent: leukopenia, leukocytosis, lymphadenopathy, neutropenia, thrombocytopenia immune
system Uncommon: hypersensitivity reactions, seasonal ALL rgiya
metabolic disorders Uncommon: hypercholesterolaemia, hyperuricaemia, anorexia, decreased appetite, hyperglycaemia, increase or decrease in body weight
Psychiatric disorders Uncommon: depression, anxiety (including nervousness and agitation), insomnia, confusion consciousness
Nervous system Common: headache, dizziness, paresthesia
Uncommon: dysgeusia, headache, drowsiness, fainting, neuralgia, tremors, neuropathy
Infrequent: conjunctivitis, blepharitis, pain, redness, dryness manhole, swelling century, glaucoma
organs of hearing and balance
Uncommon: pain, congestion, tinnitus
Infrequent: flushing, hematoma, tachycardia, palpitations
respiratory system Common: cough, sore throat, nasal congestion
Infrequent: dyspnoea, asthma, dysphonia, lung crepitation, ulceration of the mucous membranes of the nose, swelling of the upper respiratory tract, redness of the throat gastrointestinal
tract Common: nausea, abdominal pain, diarrhea, dyspepsia, ulceration of the mucous hull oral ki
Uncommon: vomiting, flatulence, constipation, gastroesophageal reflux, dysphagia, gastritis, colitis, hemorrhoids, hemorrhoidal bleeding, vesicular rash in the mouth,
toothache, dry mouth, gingivitis, tongue ulceration, stomatitis (including aphthous)
skin and subcutaneous tissue
Common: rash (including erythematous and itching), pruritus, hair loss Uncommon: macular or papular rash, dry skin, sweating, night sweats, eczema, dermatitis, psoriasis, urticaria, ecchymosis, purpura, acne, skin ulcers, angionevrotich esky swelling, change in the nail plate, photosensitivity reactions, skin exfoliation, rheumatoid nodules
Uncommon: arthralgia, pain in extremity, back pain, and shoulder girdle, muscle cramps, myalgia, joint swelling, synovitis, bursitis, tendonitis
Infrequent: hematuria, dysuria, nocturia, pollakiuria, pain in the kidneys, menorrhagia
General disorders and reactions at the injection site
Very common: injection site reactions (including pain , swelling, redness or pruritus) Common: increased tomlyaemost (including asthenia), flu syndrome Uncommon: fever, feeling of fever, chills, chest pain, impaired wound healing
Laboratory abnormalities Common: increase in liver enzymes (including alanine aminotransferase and aspartate aminotransferase)
Infrequent: elevated triglycerides, alkaline phosphatase, creatine kinase, lactate, blood urea and creatinine increase in activated partial thromboplastin time, reduced level of potassium in the blood, the formation of autoantibodies, protein in the urine
How to accept, acceptance rate and dosage
The recommended dose of Humira in adult patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis is 40 mg subcutaneously once every two weeks. When assigning Humira glucocorticosteroid therapy, nonsteroidal anti-inflammatory drugs (including salicylates), analgesics (narcotic and non-narcotic), methotrexate and other basic antirheumatic drugs can be continued.
Some patients not receiving methotrexate, an additional effect can be achieved by increasing the multiplicity of application Humira 40 mg once a week.
recommended Humira dose regimen for adults with Crohn’s disease -160 mg in 1 day (used of four injections of 40 mg per day or as two injections of 40 mg per day consistently for two days), two weeks ( on the 15th day) – 80 mg two weeks later (day 29) begin to apply a maintenance dose – 40 mg every 2 weeks. When assigning Humira therapy aminosalicylates, glyukokortiko steroids and / or anti-metabolites (such as mercaptopurine and azathioprine) may be continued. Patients
observing reduction response to drug treatment, can obtain an additional effect of increasing the dose to 40 mg per week Humira.
Some patients may not respond to Humira therapy, but the treatment should continue for the first 4 weeks, because a positive effect can be achieved within 12 weeks. Decision on termination of therapy may be taken if the patient does not receive the effect of the treatment during this period.
Chronic plaque psoriasis.
initial dose for adult patients amounts to 80 mg.
maintenance dose – 40 mg every two weeks, starting one week after the initial dose.
Juvenile idiopathic arthritis.
Children from 13 to 17 years – 40 mg every two weeks.
clinical response is usually achieved within 12 weeks of treatment. Decision on termination of therapy may be taken if the patient does not receive the effect of the treatment during this period.
Treatment with Humira is held under the supervision of a physician. If the doctor thinks it is possible, after proper training technique subcutaneous injection, patients may self-administer the drug.
drug Humira is administered subcutaneously in the thigh or abdomen. The solution should be inspected before administration to determine the presence of foreign particles and discoloration.
Adalimumab should not be mixed in the same syringe or vial with any other drugs. Remains of the solution and use the material to be destroyed.
At a temperature of 2 to 8 ° C, protected from light. Do not freeze.
In patients with rheumatoid arthritis receiving methotrexate is no need for dose adjustment of adalimumab and methotrexate. However methotrexate with single and repeated use adalimumab clearance decreases by 29% and 44% respectively.
adalimumab interaction with other drugs, in addition to methotrexate, in pharmacokinetic studies have not been studied. In clinical studies no evidence of interaction observed adalimumab with other basic drugs (sulfasalazine, hydroxychloroquine, leflunomide and parenteral preparations of gold), glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs and analgesics.
Pregnancy and lactation
In animal studies at doses up to 100 mg / kg symptoms adalimumab damaging effect on the fetus were detected. However, adequately controlled studies in pregnant women the drug has not been studied.
Animal studies do not always make it possible to predict the effect of the drug on humans, so during pregnancy, use of the drug Humira is contraindicated.
Women of childbearing age should avoid becoming pregnant during treatment with Humira.
Data on excretion of adalimumab with breast milk or no suction.
many drugs and immunoglobulins into breast milk. Given the risk of serious adverse reactions in the newborn, it is advisable to discontinue breast-feeding or stop the drug, taking into account its importance to the mother.
The maximum tolerated dose of adalimumab has not been established in humans. Reapply adalimumab in doses up to 10 mg / kg was not accompanied by toxic effects, demand a reduction in dose. In case of overdose, it is necessary to monitor adverse reactions and immediately begin to adequate symptomatic treatment.