Index of drugs

Chronic primary immune thrombocytopenia (idiopathic) in adult patients with splenectomy who show insufficient response to other treatments (ie corticosteroid therapy, immunoglobulins). The preparation can be used as a second-line treatment in adult patients who have not had splenectomy, as this operation is contraindicated.

1 vial contains 250 μg or 500 μg romiplostim.

Anti-hemorrhagic drug. Antibody produced by recombinant DNA from cellsEscherichia colicontaining an Fc fragment of a human immunoglobulin of the IgG1 class, whose single-chain subunits are attached to the C-terminus of the peptide chain containing 2 thrombopoietin receptor binding domains. The amino acid sequence of romiplostim is not homologous with the sequence of endogenous thrombopoietin. In preclinical and clinical studies, antibodies against romiplostim did not cross-react with endogenous thrombopoietin. Romiplostim signals and activates intracellular transcriptional pathways through the thrombopoietin receptor (cMpl), thus increasing platelet production. After a subcutaneous dose of 3-15 μg / kg. patients with primary immune thrombocytopenia C_max occurs after 7-50 h. The concentration of romiplostim in the blood is inversely proportional to the number of platelets. T_0,5 in the elimination phase it falls within the range of 1-34 days. The pharmacokinetics of romiplostim are affected by elimination using target cells, which is probably regulated by thrombopoietin receptors on platelets and other thrombopoietic lineages, such as megakaryocytes.

Hypersensitivity to romiplostim, excipients of the preparation or to proteins derived fromE. coli.

Caution in patients with risk factors for thromboembolic complications such as hereditary (eg Leiden V factor) or acquired risk factors (eg AT III deficiency, antiphospholipid syndrome), advanced age, long-term immobilization, malignant tumors, use of contraceptives or HRT, obesity, smoking, condition after surgery or trauma. Do not use in patients with moderate to severe hepatic impairment (≥7 according to Child-Pugh), unless the anticipated benefits outweigh the possible risk of portal vein thrombosis; if the use of romiplostim is necessary, the number of platelets should be closely monitored. Use with caution in patients with impaired renal function and in the elderly. Romiplostim should not be used for the treatment of thrombocytopenia caused by myelodysplastic syndromes or for any reason other than primary immune thrombocytopenia (there is a risk of myelodysplastic syndrome becoming myeloid leukemia). Especially in patients> 60 years of age with systemic symptoms and abnormal signs, such as an increased number of peripheral blasts, marrow should be harvested and biopsied before treatment with romiplostim and during the course of the disease and treatment. There is a risk of recurrence of thrombocytopenia and bleeding after discontinuation of the drug - patients should be carefully monitored for the reduction of platelet counts and, if necessary, conservative treatment. Stimulating the thrombopoietin receptor may cause an increase in the amount of reticulate bone in the bone marrow; therefore, tests should be performed including smear and complete blood counts before treatment and during treatment to detect cellular morphological abnormalities. If abnormal results are found and the effectiveness of the treatment is lost, romiplostim should be discontinued and physical examination performed, and bone marrow trepanobiopsis should be considered using appropriate staining for reticulin. However, in patients whose efficacy with romiplostim therapy is maintained, but the results of peripheral blood smears show abnormalities, the risk-benefit-to-effect ratio and other options for the treatment of primary immune thrombocytopenia should be re-evaluated. It is not recommended for patients <18 years.

Do not use during pregnancy unless absolutely necessary.Do not use during breast-feeding - a decision should be made to discontinue breast-feeding or discontinue the preparation, after considering the benefits of breastfeeding and the benefits of the mother.

Very common: headache. Common: bone marrow disorders (increased reticulin), thrombocytopenia, nausea, diarrhea, abdominal pain, indigestion, constipation, fatigue, peripheral edema, flu-like symptoms, pain, weakness, fever, chills, injection site reactions, contusions, pain in the joints, muscles, limbs, back pain, bone pain, muscle cramps, dizziness, migraine, paresthesia, insomnia, pulmonary embolism, pruritus, ecchymosis, rash, hot flushes. Uncommon: anemia, aplastic anemia, bone marrow failure, leukocytosis, splenomegaly, thrombocythemia, increased platelet count, abnormal platelet count, myocardial infarction, increased heart rate, conjunctival haemorrhage, accommodation disorders, blindness, eye disorders, pruritus eye, severity of tearing, optic nerve edema, visual disturbances, vomiting, rectal haemorrhage, bad odor from the mouth, dysphagia, gastroesophageal reflux, presence of fresh blood in the stool, oral bleeding, discomfort in the stomach, inflammation of the mucous membrane oral cavity, tooth discoloration, injection site hemorrhage, chest pain, irritability, malaise, facial edema, feeling hot, feeling upset, portal vein thrombosis, transaminase elevation, influenza, localized infection, nasopharyngeal inflammation, increased pressure blood, increased blood lactate dehydrogenase activity, increased body temperature, weight loss, weight gain, alcohol intolerance, lack of appetite, weakened appetite, dehydration, gout, muscle stiffness, muscle weakness, shoulder pain, muscle tremor, multiple myeloma, fibrosis marrow, clonus, dysgeusia, hypoaesthesia, reduced perception of taste stimuli, peripheral neuropathy, transverse sinus thrombosis, depression, abnormal dreams, proteinuria, vaginal bleeding, cough, rhinorrhea, dry throat mucous membrane, dyspnea, mucosal congestion nose, pain during breathing, alopecia, hypersensitivity reaction to light, acne, contact dermatitis, dry skin, eczema, erythema, exfoliative rash, abnormal hair growth, pruritus, purpura, lumpy rash, itchy rash, skin nodules, abnormal skin odor, hives, zak major venous thrombosis, hypotension, peripheral vascular embolism, peripheral vascular ischaemia, superficial thrombophlebitis, thrombosis. Frequency unknown: erytromelalgia. In addition, recurrence of thrombocytopenia after discontinuation of treatment and production of binding antibodies against romiplostim and thrombopoietin was observed (in 2 patients antibodies with the ability to neutralize the action of romiplostim appeared, however, these antibodies did not cross-react with endogenous thrombopoietin, after about 4 months the result of the neutralizing test antibodies against romiplostim were negative). In patients with myelodysplastic syndromes treated with romiplostim, there was an increase in the incidence of myelodysplastic syndrome to acute myeloid leukemia and cases of a transient increase in the number of blasts.

Subcutaneous, once a week. Treatment should be under the supervision of a doctor who has experience in the treatment of hematological diseases. The starting dose is 1 μg / kg. (the patient's body weight at the beginning of treatment should be taken into account to calculate the initial dose). The dose should then be increased weekly by 1 μg / kg until the platelet count reaches ≥50 x 10⁹/ L. The number of platelets should be determined weekly until a constant value is obtained (platelet count ≥50 x 10⁹/ l persisting for at least 4 weeks without dose adjustment). The determination of platelet counts should then be performed once a month. The maximum dose administered once a week should not exceed 10 μg / kg.Dose adjustment: if the platelet count is <50 x 10⁹/ l - increase the weekly dose by 1 μg / kg body weight; if it increases> 150 x 10⁹/ l in the Next 2 weeks- the weekly dose should be reduced by 1 μg / kg; if it exceeds 250 x 10⁹/ l - do not administer the drug, continue to determine the number of platelets once a week; after reducing the platelet count to <150 x 10⁹/ l, resume once a week in a dose reduced by 1 μg / kg. Due to individual variability in platelet response to treatment, some patients may experience a sudden drop in platelet count below 50 x 10 after reducing the dose or discontinuing treatment.⁹/ l - in such cases, if clinically necessary, higher limit values ​​should be considered for the number of platelets at which the dose is reduced (200 x 10⁹/ l) or discontinues treatment (400 x 10⁹/ l) according to the doctor's assessment. Loss of response or failure to maintain platelet response with the recommended doses of romiplostim should lead to the search for causes. Treatment should be discontinued if, after 4 weeks of maximum week dosing (10 μg / kg), the platelet count does not increase to a sufficiently high concentration to avoid clinically significant bleeding. Periodically, the clinical condition of the patients should be assessed, and continuing treatment should be decided on a case-by-case basis by the attending physician. There is a possibility that thrombocytopenia will recur after discontinuation of therapy.