XUMIRA
Active material: Adalimumab
When ATH: L04AB04
CCF: Selective immunosuppressant. Monoclonal antibodies to TNF
ICD-10 codes (testimony): K50, M05, M07, M45
When CSF: 05.02.01
Manufacturer: ABBOTT LABORATORIES Ltd. (Great Britain)
Pharmaceutical form, composition and packaging
The solution for the p / to the introduction opalescent, tinted.
| 1 syringe | |
| adalimumab | 40 mg |
Excipients: mannitol, citric acid monohydrate, sodium citrate, disodium gidrofosfata digidrat, sodium dihydrogen phosphate dihydrate, sodium chloride, polysorbate 80, water d / and, Sodium hydroxide.
0.8 ml – single-dose glass syringes (1) complete with alcohol wipes (1) – packings Valium planimetric (1) – packs cardboard.
0.8 ml – single-dose glass syringes (1) complete with alcohol wipes (1) – packings Valium planimetric (2) – packs cardboard.
Pharmacological action
Selective immunosuppressant. It is a recombinant monoclonal antibody, peptide sequence which is identical to the lgG1 man.
Adalimumab selectively binds to tumor necrosis factor (FNO) and neutralizes its biological function by blocking the interaction with cell surface receptors, the p55 and p75 TNF. FNO – it is a natural cytokine, that participates in the regulation of inflammation and normal immune response. Elevated levels of TNF are found in the synovial fluid of patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. TNF plays a major role in the development of pathological inflammation and destruction of articular tissues, characteristic of these diseases.
Adalimumab also modulates biological responses, which are induced or regulated by TNF, including changes in the levels of adhesion molecules, causing migration of leukocytes.
In patients with rheumatoid arthritis Humira causes a rapid decrease in levels of acute-phase inflammatory indicators (C-reactive protein and erythrocyte sedimentation rate) and serum levels of cytokines (IL-6). Besides, there is a decrease in serum activity of matrix metalloproteinases (MMP-1 and MMP-3), cause tissue remodeling, which underlies the destruction of cartilage.
Pharmacokinetics
Absorption
Adalimumab is absorbed and distributed slowly and reaches Cmax approximately 5 days. The absolute bioavailability of the drug after a single s / c administration 40 mg of adalimumab 64%.
In patients with Crohn's disease, which is prescribed in the starting dose of Humira 160 mg 0 week and subsequent dose 80 mg Week 2, Cmax adalimumab achieved on the 2nd and 4th week and is about 12 ug / ml.
Distribution
Vd with a single on / in a range from 4.7 to 6.0 l, indicating that nearly the same distribution of adalimumab in the blood and in the extravascular fluid. Adalimumab concentration in synovial fluid of patients with rheumatoid arthritis is from 31 to 96% by sыvorotochnoy.
Css adalimumab at n / a application rate 40 mg 1 once every 2 week in patients with rheumatoid arthritis at the end of the dosing interval is approximately 5 ug / ml (without simultaneously receiving methotrexate) and 8-9 ug / ml (against the backdrop of the simultaneous application of methotrexate). With increasing doses ranging adalimumab 20 mg, 40 mg 80 mg 1 once every 2 week and 1 once a week n / k observed almost linear increase in serum adalimumab concentrations at the end of the dosing interval.
In patients with Crohn's disease Css approximately 7 ug / ml and observed in the 24th and 56th weeks of maintenance therapy with a dose of Humira 40 mg 1 once every 2 of the week.
Deduction
Adalimumab appears slowly, clearance generally does not exceed 12 ml / h. T1/2 is, average, 2 weeks and ranged from 10 to 20 days. Clearance and T1/2 does not substantially change upon administration of the drug at a dose 0.25-10 mg / kg, a T1/2 converges for I / O and p / to the introduction of the drug. With prolonged use (more 2 years) clearance of adalimumab is not changed.
Pharmacokinetics in special clinical situations
There was a trend to increased clearance of adalimumab, depending on body weight and the presence of antibodies to adalimumab.
Age has minimal effect on adalimumab clearance.
Children adalimumab pharmacokinetics has not been studied.
Differences pharmacokinetics (adjusted for body weight) patients of different sex and race were found.
Pharmacokinetics of adalimumab in patients with impaired hepatic or renal function no.
Testimony
- Moderate to severe active rheumatoid arthritis (as monotherapy or in combination with methotrexate or other disease modifying anti);
- Active psoriatic arthritis (as monotherapy or in combination with methotrexate or other disease modifying anti);
- Aktivnыy ankiloziruyushtiy spondylitis;
- Crohn's disease (moderate or severe) with inadequate response to conventional therapy or ineffective (or reducing the effectiveness of) infliksimaʙa.
Dosage regimen
Adults at revmatoidnom ARTHRO, psoriatic arthritis and ankylosing spondylitis Humira administered s / c at a dose 40 mg 1 once every 2 of the week. In the appointment of Humira therapy GCS, NSAIDs, analgesics, salicylates, methotrexate and other DMARDs may be continued.
In some patients,, not receiving methotrexate, It can be achieved with the additional effect of increasing the multiplicity to use Humira 40 mg 1 once a week.
At Crohn's disease adult prescribe 160 mg / day (by 40 mg 4 times / day, or 40 mg 2 times / day successively for two days), through 2 of the week (15 day) – 80 mg, later 2 of the week (29-Day) prescribe a maintenance dose – 40 mg 1 once every 2 of the week. In the appointment of Humira therapy aminosalicylates, corticosteroids and / or antimetabolites (mercaptopurine and azathioprine) It can be extended.
With a decrease in response to drug treatment may increase the dose to 40 mg per week. Some patients do not respond to therapy with Humira during the first 4 weeks, but treatment should be continued, tk. positive effect can be achieved in a 12 weeks. The decision to terminate treatment may be made in the case, if not marked therapeutic effect during this period.
Terms of preparation and holding of injections
Humira should be used under medical supervision. If the doctor thinks it is possible, after appropriate training techniques s / c injection, patients may self-administer the drug itself.
Humira is administered s / c in the thigh or abdomen. Before the introduction of the solution should be inspected for the presence of foreign particles and discoloration.
Adalimumab should not be mixed in the same syringe or vial with any other drugs. The remains of the solution and the materials used should be destroyed.
Before the injection of Humira should be carefully wash hands, then get out of the packaging and place on a clean surface of a syringe with Humira and one alcohol-soaked cloth. Check, that the shelf life of Humira, printed on the syringe has not expired.
Then choose an injection site on the abdomen or the front of the thigh. Injection sites and the parties should be changed, each following the injection site should deviate from the previous at least 3 cm. You can not enter the drug in place, where there is pain, hyperemia, sealing or subcutaneous hematoma. These symptoms may indicate the presence of infection. The injection site is necessary to process an alcohol swab in a circular motion.
The syringe is not shaken. It should remove the cap from the needle, without touching the needle, avoiding contact with other surfaces. One hand to take in the treated skin fold, in the other hand to take the syringe, holding it at an angle of 45 ° to the skin surface, graded surface upwards. In one swift movement completely insert the needle into the skin fold. After insertion of the needle to release the fold of skin. Enter the entire solution for 2-5 sec. When the syringe is empty, remove the needle from the skin, at the same angle. A piece of gauze lightly press the injection site for 10 sec, but in any case, do not rub the surface. From the injection site can stand a small amount of blood. If you wish, you can use a patch.
After injection, the syringe is not re-use. If the next injection of Humira was accidentally omitted, necessary to make the injection immediately, as soon as it is detected. The following injection should be carried out in accordance with the previously planned schedule.
Side effect
Below are safety data Humira, received a placebo-controlled clinical trials.
Clinical and laboratory adverse events, whose connection with adalimumab was at least possible, distributed systems and frequency: Often (>1/10); often (>1/100, ≤1/10); infrequently (>1/1000, ≤1/100).
Infection: Often – upper respiratory tract infection; often – lower respiratory tract infection (including bronchitis and pneumonia), urinary tract infection, herpes infection (including simple and herpes zoster), flu, superficial fungal infection (including skin lesions and nails); infrequently – sepsis, joint and wound infections, abscess, skin infection (including impetigo), infection of the hair follicle (including boils and carbuncles), paronixija, pustular rash, an infection of the teeth and periodontal, ear infection, gastroenteritis, candidiasis of the oral cavity and pharynx, vaginal infections (including fungal), viral infection.
Neoplasms: infrequently – skin papilloma.
From the hematopoietic system: often – anemia, lymphopenia; infrequently – leukopenia, leukocytosis, lymphadenopathy, neutropenia, thrombocytopenia.
On the part of the immune system: infrequently – hypersensitivity reactions, Seasonal allergies.
Metabolism: infrequently – hypercholesterolemia, hyperuricemia, anorexia, decreased appetite, giperglikemiâ, increase or reduction of body weight.
From the central and peripheral nervous system: often – headache, dizziness, paresthesia; infrequently – depression, anxiety disorders (including nervousness and agitation), insomnia, confusion, dysgeusia, migraine, drowsiness, fainting, neuralgia, tremor, Neuropathy.
From the senses: infrequently – conjunctivitis, .Aloe, pain, redness, dry eyes, swelling of the century, glaucoma, pain, stuffiness and ringing in the ears.
Cardio-vascular system: often – arterial hypertension; infrequently – tides, hematoma, tachycardia, palpitations.
The respiratory system: often – cough, sore throat, nasal congestion; infrequently – breathlessness, asthma, disfonija, Pulmonary crackles, ulceration of the nasal mucosa, swelling of the upper airway, redness of the throat.
From the digestive system: often – nausea, abdominal pain, diarrhea, dyspepsia, ulceration of the mucous membranes of the mouth, increase in liver enzymes (including ALT and AST), Alkaline phosphatase; rarely - vomiting, flatulence, constipation, hastroэzofahealnыy reflux, dysphagia, gastritis, colitis, hemorrhoids, hemorrhoidal bleeding, vesicular rash in the oral cavity, toothache, dry mouth, gingivitis, tongue ulceration, stomatitis (incl. aphthous).
Dermatological reactions: often – rash (including erythematous and itchy), itching, hair loss; infrequently – Macular or papular rash, xerosis, Sweating, night sweats, eczema, dermatitis, psoriasis, hives, ecchymosis, purpura, acne, skin ulcers, angioedema, change in the nail plate, photosensitivity reactions, peeling of the skin, rheumatoid nodules.
On the part of the musculoskeletal system: infrequently – arthralgia, pain in the extremities, pain in the back and shoulder girdle, muscle cramps, myalgia, swelling of joints, synovitis, ʙursit, Tendinitis.
With the genitourinary system: infrequently – hematuria, dizurija, nocturia, thamuria, pain in the kidneys, menorragija
From the body as a whole: often – fatigue (including asthenia), flu-like symptoms; infrequently – fever, feeling the heat, chills, chest pain, impaired wound healing.
Local reactions: Often – pain, edema, hyperemia, itching at the injection site.
From the laboratory parameters: infrequently – elevated triglycerides, CPK, LDH, urea and creatinine in the blood, increase in APTT, lowering blood potassium, the formation of autoantibodies, the appearance of urinary protein.
Contraindications
- infectious diseases, in t.ch.tuberkulez;
- Pregnancy;
- Lactation (breast-feeding);
- Childhood and adolescence up 16 years;
- Hypersensitivity to adalimumab or any of its auxiliary components.
FROM caution should be prescribed in demyelinating diseases.
Pregnancy and lactation
IN experimental research animals at doses up to 100 mg / kg adalimumab signs of the damaging effect on the fetus have been identified. But, in adequate controlled studies in pregnant women the drug has not been studied. Animal studies are not always predictive of human impact on the, so during pregnancy Humira can be used only when clearly needed.
Women of reproductive age should avoid conception during treatment with Humira.
The effects of Humira in the generic activities and delivery are not known.
Data on excretion of adalimumab with breast milk or its absorption after ingestion is not. Many drugs and immunoglobulins penetrate 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 for the mother.
Cautions
In the treatment with monoclonal antibodies to TNF, including Humira, serious infections were observed, Rare cases of tuberculosis and opportunistic infections, incl. fatal. In many cases, a serious infectious processes develop in patients, receiving concomitant immunosuppressive therapy. Rheumatoid arthritis itself predisposes to the development of infectious complications.
Humira should not be given to patients with active infections, incl. chronic or focal. Treatment can be initiated only after, as will be made infection control.
As with the treatment of other monoclonal antibodies to TNF, to, during and after treatment with Humira should be monitored for signs of infection, including tuberculosis.
In the case of a new infection during therapy with Humira, patients should be monitored carefully. In severe cases, treatment should be stopped Humira. It may be renewed only after, as will be made infection control.
Be careful when discussing the appointment of Humira in patients with a history of recurrent infections or diseases, predisposing to the development of infectious complications.
The use of monoclonal antibodies to TNF can be accompanied by a reactivation of hepatitis B virus (HBV) infected patients – carriers of the virus. Described several cases of death due to reactivation of hepatitis B virus in the application of TNF blockers. In most cases activation of HBV was observed in patients, besides receiving TNF blockers, concomitant immunosuppressive therapy. Patients, at risk for hepatitis B, They should be carefully evaluated for their HBV before prescribing TNF monoclonal antibodies. The question of the appointment of HBV carriers of TNF blocker therapy should be resolved taking into account the possible risk to the patient. If the destination carrier HBV therapy with monoclonal antibodies to TNF, the patient should be closely monitored throughout the course of therapy and for several months after its completion. If during treatment with Humira occurred reactivation of hepatitis B virus, Humira treatment should be stopped and effective antiviral therapy launch.
Therapy with monoclonal antibodies to TNF, including Humira, in rare cases, accompanied by the emergence or worsening of clinical and / or radiographic manifestations of demyelinating diseases. Physicians should exercise caution when assigning Humira in patients with demyelinating diseases of the central nervous system.
In controlled trials, the frequency of malignancies, including lymphoma patients, treated with monoclonal antibodies to TNF, It was higher, than in the control group. The total number of patients, placebo, and the duration of observation of them were less than the number and duration of patient monitoring, treated with TNF blockers. Besides, increased risk of lymphoma in patients with rheumatoid arthritis, accompanied by chronic inflammation of the highly active, It is making it difficult to assess its risk with treatment. In long-term clinical studies of Humira incidence of malignant tumors corresponded to this index in patients of the same age, gender and race in the general population. However, currently available data are insufficient, to avoid the possible risk of lymphoma and other malignancies during therapy with monoclonal antibodies to TNF.
In a clinical study excluded patients with a history of malignancy, and in the case of tumor therapy was stopped Humira. Accordingly, you must be very careful when deciding on Humira treatment of these patients.
In clinical studies, serious allergic reactions during treatment with Humira were uncommon. In clinical practice, registered very rare cases of severe allergic reactions (incl. anaphylactic) after administration of Humira. If developing anaphylaxis or other serious allergic reaction, you should immediately stop Humira therapy and appropriate treatment.
Cap the syringe needle, which introduced the drug, Latex, which can cause severe allergic reactions in patients with hypersensitivity to latex.
In clinical studies, Humira and similar formulations registered cases of tuberculosis. They have been observed when using the drug at any dose, however, the rate of reactivation of tuberculosis increased primarily in the appointment of Humira in doses, exceeds the recommended. Patients, taking Humira, It was described cases of fungal and other opportunistic infections. Some of these infections, including tuberculosis had fatal.
Before starting treatment with Humira in all patients should be evaluated to rule out active and inactive (latent) TB. It is necessary to collect detailed medical history , incl. determine if there is contact with patients with active tuberculosis and clarify, carried out and / or carried out any immunosuppressive therapy. It should conduct screening tests (eg, chest radiography and tuberculin skin test). It is necessary to take into account the possibility of false-negative tuberculin test, particularly in severely ill patients and patients in a state of immunodeficiency.
If active tuberculosis is diagnosed, start treatment Humira should not be.
If latent tuberculosis before starting Humira treatment should be carried out preventive treatment of TB.
Patients should be advised of the need to see a doctor if signs of tuberculosis infection (persistent cough, weight loss, low-grade fever).
In the treatment of TNF blockers are described rare cases of pancytopenia, including aplastic anemia. In the appointment of Humira adverse events from the hematopoietic system, including clinically significant cytopenia (thrombocytopenia, leukopenia), registrirovali dishonor. Contact them with Humira remains unclear. Patients should immediately contact a doctor if during the treatment Humira symptoms of the blood (eg, persistent fever, bruises, bleeding, blednosti). In patients with severe changes in the blood should consider the abolition of Humira.
In clinical studies, while the use of anakinra and etanercept, a TNF blocker noted the development of serious infections in the absence of additional clinical benefit compared to etanercept monotherapy. Given the nature of adverse events, developing at combination therapy with etanercept and anakinra, similar effects can be expected in the treatment of anakinra in combination with other TNF blockers. Therefore combination therapy with adalimumab, and anakinra is not recommended.
In the study, 64 Patients treated with Humira, There were no signs of depression of delayed-type hypersensitivity reactions, reduce immunoglobulin levels or changes in the number of effector T cells , B-cells and NK-cells, monocytes / macrophages and neutrophils.
Patients, receiving Humira, Vaccination can be carried out (with the exception of live vaccines). Information about the possibility of infection by vaccination with live vaccines during treatment with Humira is not.
Humira has not been studied specifically in patients with chronic heart failure, However, clinical trials of other TNF antagonist was an increase in the frequency of progression of chronic heart failure and the development of its new cases. Cases Rise of heart failure have also been described in patients, Humira treated. With caution and under close medical supervision should be given Humira in patients with heart failure.
Humira therapy may be accompanied by the formation of autoantibodies. Effect of long-term use Humira on the development of autoimmune diseases is not known. Humira should be abolished, if the patient during treatment developed signs of syndrome volchanochnopodobnogo.
Humira information about the impact on the results of laboratory tests there.
Safety and efficacy in older and younger patients are generally not distinguished. Nonetheless, we can not exclude an increased sensitivity to the drug in some elderly patients.
Use in Pediatrics
The safety and efficacy of Humira in children have not been studied.
Overdose
The maximum tolerated dose of adalimumab in humans has not been established. Reapply adalimumab at doses up to 10 mg / kg was not associated with toxic effects, demand a reduction of dose.
In the event of overdose it is necessary to monitor adverse reactions and immediately begin to adequate symptomatic treatment.
Drug Interactions
Methotrexate with single and repeated use to reduce the clearance of adalimumab 29% and 44% respectively. But in patients with rheumatoid arthritis, receiving methotrexate, there is no need to adjust the dose of methotrexate or adalimumab.
Interaction with other drugs adalimumab, in addition to methotrexate, in pharmacokinetic studies have not been investigated.
In clinical studies, symptoms were observed adalimumab interaction with other basic means(sulfasalazine, gidrokhlorokhin, leflunomide and parenteral gold preparations), GCS, salicylates, NSAIDs and analgesics.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored in the dark, inaccessible to children at 2 ° to 8 ° C; Do not freeze. Shelf life – 2 year.
