Instruction for use: Adalimumab

Trade name of the drug – Humira

Latin name of substances Adalimumab

Adalimumabum (genus. Adalimumabi)

Gross Formula

C6428H9912N1694O1987S46

Pharmacological group:

Immunosuppressive drugs

CAS Code

331731-18-1

Application of pregnancy and breastfeeding

The action category for fetus by FDA is B.

Model clinical-pharmacological article 1

Characteristic. A recombinant monoclonal antibody whose peptide sequence is identical to human IgG1.

Pharmacotherapy. Selectively binding to TNF blocks its interaction with surface cellular p55 and p75 receptors, and neutralizes TNF functions. It modifies the response biological responses that are controlled by TNF, including changes in adhesion molecules that cause the migration of leukocytes. Reduces the indices of C-reactive protein, ESR, serum cytokines (IL-6), matrix metalloproteases 1 and 3.

Pharmacokinetics. Absorbed slowly. Bioavailability at a single injection of 40 mg - 64%. ÒÑmax - 5 days. Css with SC introduction of 40 mg once every 2 weeks - 5 mcg / ml (without simultaneous reception of methotrexate) and 8-9 mcg / ml (against the background of taking methotrexate). The volume of distribution with IV introduction is 4.7-6 liters. Concentration in the synovial fluid is 31-96% of the serum. With an increase in the dose (20, 40, 80 mg once every 2 weeks and once a week for SC), there was a linear increase in the concentrations at the end of the dosing interval. It is displayed slowly. Clearance - 12 ml / h; Proportionally depends on the body weight and the presence of antibodies to adalimumab. Clearance and T1 / 2 do not change significantly at doses of 0.25-10 mg / kg. Age has minimal impact on clearance. T1 / 2 IV and SC introduction - 2 weeks (10-20 days).

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

Contraindications. Hypersensitivity (including latex), simultaneous reception with anakinro (the risk of developing severe infections), infectious diseases including. Tuberculosis, children's age (under 18 years), pregnancy, lactation.

Carefully. Demyelinating diseases, CHF.

Dosing. SC to the abdomen or anterolateral region of the thigh 40 mg once every 1-2 weeks.

Side effect. Frequency: very frequent (more than 1/10), frequent (more than 1/100 and less or equal to 1/10), infrequent (more than 1/1000 and less than or equal to 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, blepharitis; Pain, redness, dry eyes; Edema of the eyelids, glaucoma; Pain, congestion, tinnitus; Perversion of taste.

On the part of the CAS: frequent - increased blood pressure; Infrequent - "hot flashes", hematoma, tachycardia, palpitations.

On the part of the respiratory system: frequent - cough, sore throat, nasal congestion; Infrequent - dyspnea, bronchospasm, dysphonia, pulmonary crepitus, ulceration of the nasal mucosa, edema of the upper respiratory tract, hyperemia of the throat.

On the part of the digestive system: frequent - nausea, abdominal pain, diarrhea, dyspepsia, ulceration of the oral mucosa; Infrequent - vomiting, flatulence, constipation, gastroesophageal reflux, gastritis, dysphagia, colitis, hemorrhoids, hemorrhoidal bleeding, vesicular rash in the oral cavity, toothache, dry mouth, gingivitis, ulceration of the tongue, stomatitis (including aphthous).

On the part of the organs of hematopoiesis: frequent - anemia, lymphopenia; Infrequent - leukopenia, leukocytosis, lymphadenopathy, neutropenia, thrombocytopenia.

On the part of metabolism: infrequent - hypercholesterolemia, hyperuricemia, anorexia, decreased appetite, hyperglycemia, increased or decreased body weight.

From the skin: frequent - rash (including erythematous and itchy), itching, alopecia; Infrequent - macular or papular rash, dry skin, sweating, eczema, dermatitis, psoriasis, urticaria, ecchymosis, purpura, acne, skin ulceration, angioedema, nail plate change, photosensitization, skin peeling, rheumatoid nodules.

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

From the genitourinary system: infrequent - hematuria, dysuria, nocturia, pollakiuria, pain in the kidneys; Menorrhagia.

Local reactions: very frequent - pain, swelling, redness, itching at the injection site.

Other: frequent - increased fatigue (including asthenia), flu-like syndrome; Infrequent - allergic reactions (including anaphylaxis, seasonal allergies), fever, heat, chills, chest pain, worsening of wound healing.

Laboratory indicators: frequent - increased activity of "liver" enzymes (including ALT and AST); Infrequent - increase in TG, AF, CK, LDH, urea and creatinine in the blood, increased activated partial thromboplastin time, hypokalemia, formation of autoantibodies, proteinuria.

Overdose. The maximum allowable dose is not established. When administered at doses up to 10 mg / kg, no symptoms of overdose were noted.

Treatment: symptomatic.

Interaction. A single and repeated use with methotrexate reduces the clearance of adalimumab by 29% and 44%, respectively, but this does not require correction of the doses of methotrexate and adalimumab.

Special instructions. In the treatment with adalimumab, cases of tuberculosis, fungal and other opportunistic infections were observed, incl. With a lethal outcome. Before the start of treatment, a check should be performed to identify active and inactive tuberculosis (contact with patients, immunosuppressive therapy, chest radiography, tuberculin test). In patients with immunodeficiency, false-negative tuberculin tests are possible. With active tuberculosis, adalimumab treatment does not begin, with latent tuberculosis preliminary preventive anti-tuberculosis treatment is preliminarily performed. If signs of tuberculosis infection appear during the treatment period (persistent cough, weight loss, subfebrile temperature), consult a doctor.

On the background of adalimumab administration in carriers of hepatitis B virus, the virus can be reactivated, cases of lethal outcome are described. The decision to initiate therapy is taken after the examination (the presence of hepatitis B virus), taking into account the possible risk to the patient. During treatment and several months after the end of treatment, medical supervision is carried out. In the case of reactivation of the virus, adalimumab treatment is discontinued and antiviral therapy is performed.

In rare cases, the appearance or exacerbation of demyelinating diseases is possible.

It is impossible to exclude the possible risk of developing lymphoma or other malignant neoplasms during treatment with TNF blockers.

During the period of treatment, there may be pancytopenia (thrombocytopenia, leukopenia, aplastic anemia). When symptoms such as persistent fever, bruises, bleeding, pale skin, you should consult a doctor.

With the simultaneous use of anakinr with TNF antagonist etanercept, the development of severe infections (in comparison with etanerceptom monotherapy) is observed, which can be expected when using anakinr in combination with other TNF blockers, incl. With adalimumab.

During the treatment, vaccination is possible, except for live vaccines.

When other antagonists of TNF were used, development of CHF or its aggravation was noted.

With the development of signs of lupus-like syndrome treatment is canceled.

In animal studies, damaging effects of adalimumab on the fetus have not been identified, but no controlled studies have been conducted in pregnant women, therefore, women of reproductive age should be treated with reliable contraceptive methods during treatment.

It is not known whether adalimumab is excreted in breast milk, so when it is prescribed, taking into account the ratio of the perceived benefit to the mother and the risk to the baby, stop breastfeeding or abolish the drug.

In elderly patients, hypersensitivity to adalimumab is possible.