Adalimumab

When ATH:
L04AB04

Pharmacological action

Recombinant monoclonal antibody, the peptide sequence of which is identical human IgG1.

Pharmacological action. Selective svяzыvaяsь with FNO, blocks its interaction with cell surface receptors, the p55 and p75, and TNF neytralizuetfunktsii. Changes retaliatory biological reactions, controlled by TNF, including changes in adhesion molecules, causing migration of leukocytes. It reduces performance of C-reactive protein, ESR, serum cytokines (IL-6), matrix metalloproteases 1 and 3.

Pharmacokinetics

Absorbed slowly. Bioavailability after a single s / c infusion 40 mg - 64%. ТСmax - 5 days. Css when s / to 40 mg 1 once every 2 Sun - 5 ug / ml (without simultaneously receiving methotrexate) and 8-9 g / ml (in patients receiving methotrexate). The volume of distribution at / in the introduction - 4,7-6 liters. Concentration in the synovial fluid - 31-96% of serum. With increasing doses (20, 40, 80 mg 1 once every 2 week and 1 once a week n / a) observed linear increase in concentration at the end of the dosing interval. Return slowly. Clearance - 12 ml / h; proportional to body weight and the presence of antibodies to adalimumab. Clearance and T1 / 2 are not changed significantly at doses of 0.25-10 mg / kg. Age has minimal effect on clearance. T1 / 2 / O and p / to the introduction - 2 Sun (10-20 days).

Testimony

Exacerbation of rheumatoid arthritis, moderate and severe degrees of severity, psoriatic arthritis, ankylosing spondylitis.

Contraindications

Hypersensitivity (incl. for latex), simultaneous with anakinra (the risk of serious infections), infectious diseases incl. tuberculosis, childhood (to 18 years), pregnancy, lactation.

Carefully. Demyelinating diseases, CHF.

Dosage regimen

P / to in the abdomen or upper outer thigh muscle on 40 mg 1 every 1-2 weeks.

Side effect

Frequency: very frequent (more 1/10), frequent (more 1/100 and less than or equal 1/10), infrequent (more 1/1000 and less than or equal 1/100).

From the nervous system: frequent - headache, dizziness, paresthesia; infrequent - migraine, drowsiness, fainting, neuralgia, tremor, neuropathy, depression, anxiety disorders (including nervousness and agitation), insomnia, confusion.

From the senses: infrequent - Conjunctivitis, .Aloe; pain, redness, dry eyes; swelling of the eyelids, glaucoma; pain, stuffiness, noise in ears; dysgeusia.

From the CCC: frequent - increased blood pressure; infrequent - "tides", hematoma, tachycardia, heartbeat.

The respiratory system: frequent - Cough, sore throat, nasal congestion; infrequent - shortness of breath, bronchospasm, disfonija, Pulmonary crackles, ulceration of the nasal mucosa, swelling of the upper airway, hyperemia of the pharynx.

From the digestive system: frequent - nausea, abdominal pain, diarrhea, dyspepsia, ulceration of the mucous membranes of the mouth; infrequent - vomiting, flatulence, constipation, hastroэzofahealnыy reflux, gastritis, dysphagia, colitis, hemorrhoids, hemorrhoidal bleeding, vesicular rash in the oral cavity, toothache, dry mouth, gingivitis, tongue ulceration, stomatitis (incl. aphthous).

From the side of hematopoiesis: frequent - anemia, lymphopenia; Infrequent - leukopenia, leukocytosis, lymphadenopathy, neutropenia, thrombocytopenia.

Metabolism: infrequent - Hypercholesterolemia, hyperuricemia, anorexia, decreased appetite, giperglikemiâ, increase or reduction of body weight.

For the skin: frequent - rashes (incl. erythematous and itchy), itching, alopecia; infrequent - macular or maculopapular rash, xerosis, Sweating, eczema, dermatitis, psoriasis, hives, ecchymosis, purpura, acne, skin ulceration, angioedema, change in the nail plate, photosensitivity, peeling of the skin, rheumatoid nodules.

On the part of the musculoskeletal system: nechastыe - arthralgia, pain in the extremities, in the back and shoulder girdle, muscle cramps, myalgia, swelling of joints, synovitis, ʙursit, Tendinitis.

With the genitourinary system: infrequent - hematuria, dizurija, nocturia, thamuria, pain in the kidneys; menorragija.

Local reactions: very often - pain, edema, redness, itching at the injection site.

Other: frequent - fatigue (including asthenia), flu-like symptoms; infrequent - allergic reactions (incl. anaphylaxis, Seasonal allergies), fever, feeling the heat, chills, chest pain, impaired wound healing.

Laboratory findings: frequent - increased activity of "liver" enzymes (including ALT and AST); infrequent - increasing TG, Alkaline phosphatase, CPK, LDH, urea and creatinine in the blood, an increase in activated partial thromboplastin time, kaliopenia, the formation of autoantibodies, proteinuria.

Overdose

The maximum tolerated dose has not been established. When administered at doses up to 10 mg / kg were observed symptoms of overdose.

Treatment: symptomatic.

Drug Interactions

Single and repeated use of methotrexate reduces the clearance of adalimumab on 29% and 44% respectively, but it does not require dose adjustment of methotrexate and adalimumab.

Cautions

In the treatment with adalimumab been cases of tuberculosis, fungal, etc.. opportunistic infections, incl. fatal. Before treatment to a survey in order to identify active and inactive tuberculosis (the presence of contacts with patients, immunosupressivnaya therapy; chest X-ray, tuberkulinovaya sample). In immunocompromised patients may false negative tuberculin skin test. If active tuberculosis do not start treatment with adalimumab, In latent tuberculosis previously carried out preventive TB treatment. If signs of tuberculosis infection during treatment (persistent cough, weight loss, low-grade fever) seek medical advice.

In patients receiving adalimumab in carriers of hepatitis B virus reactivation is possible, There are cases of death. The decision to start treatment is made after examination (Hepatitis B virus) taking into account the possible risk to the patient. During several months of treatment and after treatment is carried out medical supervision. If reactivation of the virus, Treatment with adalimumab stop and spend antiviral therapy.

In rare cases, may cause or exacerbation of demyelinating disease.

We can not exclude the possible risk of developing lymphomas or other. malignant tumors during treatment with TNF blockers.

In the period of treatment can be observed pancytopenia (thrombocytopenia, leukopenia, aplasticheskaya anemia). When symptoms such as persistent fever, hematoma, angiostaxis, pale skin should seek medical advice.

With simultaneous use of anakinra with TNF antagonist etanercept noted the development of severe infections (compared with monotherapy with etanercept), what can be expected when used in combination anakinra and other. blokatorami FNO, incl. with adalimumab.

During treatment possible vaccination, except for live vaccines.

In the application, etc.. TNF antagonists, noted the development or worsening of heart failure.

With the development of symptoms syndrome treatment volchanochnopodobnogo cancel.

In animal studies of adalimumab damaging effect on the fetus is not revealed, However, controlled studies in pregnant women has not been, so women of childbearing age during treatment should use reliable methods of contraception.

It is not known whether adalimumab is displayed with breast milk, so when his appointment should be, taking into account the ratio of the expected benefit to the mother and the risk for a child, discontinue breast-feeding or stop the drug.

Elderly patients can be hypersensitivity to adalimumab.