Omalizumaʙ

When ATH:
R03DX05

Characteristic.

Selective immunosuppressant. It is a recombinant humanized monoclonal antibody IgG1κ, which selectively bind to human IgE. Obtained by recombinant DNA technology in a system for the expression of, presented by Chinese Hamster Ovary.

White lyophilized powder. The molecular weight of about 149 kDa.

Pharmacological action.
Immunosuppressive.

Application.

Treatment of persistent atopic asthma moderate and severe, whose symptoms are inadequately controlled use of glucocorticoids, patients 12 and older.

Contraindications.

Hypersensitivity (cm. Side effects, Precautions).

Restrictions apply.

It should be used with caution omalizumab in patients with impaired liver and / or kidney, autoimmune diseases or diseases, associated with the accumulation of immune complexes. The safety and efficacy of the drug in children under 12 years have not been established.

Pregnancy and breast-feeding.

In experimental studies, omalizumab does not adversely affect the course of pregnancy, development of the embryo and fetus, at birth and during neonatal development.

There are no adequate and well-controlled studies on the use of omalizumab in pregnant women has not been. Known, IgG molecules cross the placental barrier. The use of omalizumab in pregnancy is possible only in cases, the expected benefit to the mother outweighs the potential risk to the fetus.

Category actions result in FDA - B. (The study of reproduction in animals revealed no risk of adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not done.)

Unknown, whether omalizumab is allocated with breast milk in humans. The human IgG is excreted in breast milk. Given the opportunity to release the breast milk and the potential adverse impact of omalizumab on the fetus, Caution should be exercised in the appointment of omalizumab during breastfeeding.

Side effects.

The most serious adverse events when using omalizumab, marked in clinical trials, bыli anaphylaxis and malignancy.

Anaphylaxis It was observed in 3 from 3507 (0,1%) patients, participating in clinical trials (when using the first dose - two patients, fourth - in one patient). The start time of an anaphylactic reaction - 90 m (in two cases) and 2 no (one case) after administration.

Malignancy. In clinical studies in patients with asthma and other allergic diseases, the incidence of malignancies in patients, receiving omalizumab, was 0,5% (tumors have been observed in 20 patients 4127) It was higher, than in the control group - 0,2% (in 5 patients 2236). The observed tumor patients, receiving omalizumab, were different types. Breast tumor, non-melanoma skin tumors, Prostate, melanoma, tumors of the parotid gland - have been observed in more than 1 case, 5 other types of tumors occur once every. The majority of patients experienced at least 1 year. Effect of prolonged exposure or the use of omalizumab in patients with a high risk of malignancy (such as the elderly, persistent smokers) unknown.

The most common adverse events with the use of omalizumab were injection site reactions (45%), viral infections (23%), upper respiratory tract infection (20%), sinusitis (16%), headache (15%) and pharyngitis (11%).

The following data were obtained in the treatment with omalizumab 2076 Adults and adolescents older 12 years, including 1687 patients, treated for 6 Months, and 555 patients within 1 year and more, in the placebo-controlled, and during other controlled studies in patients with asthma. The average age of the patients was 42 year, 134 patients were aged 65 and older, 60% surveyed - women, 85% -European race. Patients received doses of omalizumab 150-375 mg every 2 or 4 weeks or standard therapy with / without placebo (control patients).

Side effects, which occurred with a frequency ≥1% more frequently in patients, receiving omalizumab (n=738), than placebo (n=717), during the placebo-controlled studies in patients with asthma (preferably classified using terms from the vocabulary of International Medical Nomenclature - IMN, in brackets - % occurrence placebo):

Body as a Whole: pain - 7 (5)%, feeling tired - 3 (2)%.

On the part of the musculoskeletal system: arthralgia - 8 (6)%, fracture - 2 (1)%, leg pain - 4 (2)%, pain in the arm - 2 (1)%.

From the nervous system and sensory organs: dizziness - 3 (2)%, earache - 2 (1)%.

For the skin: itching - 2 (1)%, Dermatitis- 2 (1)%.

Local reactions: 45 (43)% - erythema, feeling the heat, pricking, hives, pain, itch, packing, inflammation, swelling at the injection site, etc..

Heavy injection reactions were observed more frequently with administration of Omalizumab (12%) compared to administration of placebo (9%). Most injection reactions were observed within 1 hours after injection, It lasted less than 8 days, and usually their frequency decreased with subsequent injections.

Immunogenicity. Same, as the application of a humanized monoclonal antibody - a recombinant DNA derivatives, In rare cases, the formation of antibodies to omalizumab. Low titer antibodies to omalizumab have determined 1/1723 (<0,1%) patients, treated with omalizumab.

Helminth infections. In one-year clinical trial, held in Brazil, in patients with a high risk of helminth infections in 53% (36/68), receiving omalizumab, helminth infections were diagnosed, in the placebo group - 42% (29/69).

Cooperation.

Since cytochrome P450 enzymes, mechanisms of energy release (efflux pumps) and binding proteins play no role in the clearance of omalizumab, omalizumab has a low potential for drug-drug interactions with other medications. Specific interaction studies with omalizumab drugs, including vaccines, not performed. Interaction with omalizumab drugs, used for the treatment of asthma, unlikely. In clinical studies, omalizumab is widely used in combination with inhaled and oral corticosteroids, inhaled beta-agonists of short and long-acting, leukotriene receptor antagonists, theophylline and antihistamines. The above-mentioned drugs do not affect the safety of omalizumab. At the moment the data for use in combination with omalizumab specific immunotherapy (hyposensitization therapy) limited.

Overdose.

No cases of overdose of omalizumab has not yet been reported. The maximum tolerated dose of omalizumab has not yet been determined. With a single on / in a dose up 4000 mg dose-limiting toxicity was observed. When administered to patients for 20 Weeks highest cumulative dose (44000 mg) not mentioned any of severe acute adverse events.

Dosing and Administration.

P /. The dose and frequency of administration are determined based on the initial concentration of IgE (IU / mL), measured before treatment, and the body weight of the patient (kg). Depending on these parameters the recommended dose is from 150 to 375 mg 1 once every 2 or 4 Sun.

Precautions.

Evaluation of the effectiveness of therapy with omalizumab should be, at least, through 12 weeks of treatment.

Omalizumab is intended for long-term therapy. Cancel the drug, usually, It leads to a return of high levels of free IgE and the development of relevant symptoms.

Total IgE levels increased during treatment and remains elevated for one year after cessation of treatment. Thus, IgE levels during the second determination during therapy with omalizumab can not serve as a reference for the selection of the dose. To set the dose after interruption of treatment for a period less 1 year, It is guided by the concentration of IgE in serum, set to the initial dose administration. If treatment is interrupted for omalizumab 1 year or more, to establish the dose should determine the total IgE concentration in blood serum again. The doses of omalizumab should be adjusted when significant changes in body weight.

When using omalizumab, as with any other proteinaceous drugs, there may be local or systemic allergic reactions, including anaphylactic. On the development of anaphylaxis after administration of omalizumab was reported both in clinical trials premarketingovyh, and in post-marketing reports. Signs and symptoms, marked in those cases, They include bronchospasm, gipotenziю, urticaria and / or swelling of the throat or tongue. Some of these cases were life-threatening in nature. In clinical trials, the frequency premarketingovyh anaphylaxis, associated with the use of omalizumab, It was rated as 0,1%, a post-marketing - at least 0,2%. Cases of anaphylaxis have been observed after the first dose of omalizumab, and after a year of regular use. Before the introduction of omalizumab is necessary to prepare in advance the appropriate resuscitation equipment and drugs, needed for the relief of hypersensitivity reactions. Patients should be informed of the possibility of anaphylactic reactions and provide appropriate medical monitoring of patients. In the case of the patient's severe hypersensitivity reaction must stop the use of omalizumab.

Caution should be exercised when using the drug in patients with diabetes, syndrome of malabsorption of glucose-galactose, fructose intolerance or sucrose-isomaltase deficiency. The content of sucrose in 1 dose of omalizumab (150 mg) is 108 mg.

Omalizumab should not be used to treat acute asthma attacks, acute bronchospasm or status asthmaticus.

In patients with other allergic diseases, other than asthma, Safety and efficacy have not been established.

Not studied the use of omalizumab in patients with a high content of IgE syndrome, allergic bronchopulmonary aspergillosis, for the prevention of anaphylactic reactions, atopic dermatitis, allergic rhinitis or food allergy.

Experience in the use of omalizumab in patients over 65 years limited. However, the data, evidence of the need to correct dose in patients of this age, no.

Patients, who during treatment with omalizumab there dizziness or other disorders of the central nervous system, should refrain from driving or using machinery during use of the drug.