REVOLADE, REVOLADE - instructions for use of the medicine, reviews, description, price

Revolade

The effectiveness and safety of eltrombopag for the treatment of other diseases and conditions associated with thrombocytopenia, including post-chemotherapy thrombocytopenia and myelodysplastic syndromes, have not been established at this time.

Liver dysfunction

When using eltrombopag, disturbances in laboratory parameters of liver function are possible. In clinical studies, an increase in the activity of ALT, AST and the concentration of indirect bilirubin was noted. These phenomena were mostly mild (grade 1-2) and reversible, without clinically significant symptoms that would indicate liver dysfunction. According to 2 placebo-controlled studies, adverse events in the form of increased ALT activity were noted in 5.7% and 4% of patients treated with eltrombopag and placebo, respectively.

In 2 controlled clinical trials in patients with thrombocytopenia and HCV, ≥3-fold increases in the upper limit of normal (ULN) of ALT or AST were reported in 34% and 38% in the eltrombopag group and placebo group, respectively. The administration of eltrombopag in combination with peginterferon/ribavirin was indirectly associated with hyperbilirubinemia. Cases of ≥1.5-fold increases in total bilirubin above ULN of 76% and 50% were reported in the eltrombopag group and placebo group, respectively.

ALT, AST, and serum bilirubin concentrations should be assessed prior to initiation of eltrombopag treatment, then monitored every 2 weeks during dose titration, and monthly after a stable dose is established. A repeat study after detecting abnormalities in liver function tests is carried out within 3-5 days. If the serum concentration of total bilirubin is increased, the concentrations of its individual fractions should be determined. If a deviation is confirmed, monitoring continues until the indicators stabilize or the indicators return to the original level.

Treatment with eltrombopag is discontinued if ALT increases, with a ≥3-fold increase in ULN in patients with normal liver function or a ≥3-fold increase from baseline in patients with elevated pre-treatment ALT and the following:

— progression of the deviation, or

— deviation persists for ≥4 weeks, or

- its combination with an increase in the concentration of direct bilirubin, or

- its combination with clinical symptoms of liver damage or signs of decompensation of liver function.

Eltrombopag should be administered with caution in patients with ITP and liver disease. The minimum starting dose of eltrombopag should be used when administered to patients with hepatic impairment.

Decompensation of liver function (use with interferons)

In patients with chronic HCV and cirrhosis, there may be a risk of liver decompensation, in some cases fatal, when treated with alpha interferons. In two controlled clinical trials in patients with thrombocytopenia and HCV, in which eltrombopag was used as needed to achieve target platelet counts for antiviral therapy, safety outcomes indicative of liver decompensation were more frequently reported in the eltrombopag group (13 %) than in the placebo group (7%). Patients with low albumin levels (<3.5 g/dL) or MELD (Model for End-Stage Liver Disease) score ≥10 at baseline had a higher risk of liver decompensation. Patients with these characteristics should be closely monitored for signs and symptoms of decompensated liver failure. To obtain information about withdrawal criteria, use the instructions for use of the corresponding interferon preparations. Revolade should be discontinued if antiviral therapy is discontinued due to decompensated liver failure.

Thrombotic and/or thromboembolic complications

Platelet counts higher than normal pose a theoretical risk of thrombotic and/or thromboembolic complications. In clinical trials of eltrombopag in patients with ITP, thromboembolic complications were observed with low and normal platelet counts.

Patients with known risk factors for thrombotic and/or thromboembolic complications (such as factor V Leiden mutation, antithrombin III deficiency, antiphospholipid syndrome, etc.) require special monitoring when prescribing eltrombopag.

Platelet counts should be monitored closely and consideration should be given to dose reduction or discontinuation of eltrombopag if platelet counts exceed target values.

In ITP studies, 17 of 446 patients (3.8%) had 21 thrombotic and/or thromboembolic episodes. Thromboembolism included: embolism, incl. pulmonary embolism, deep vein thrombosis, transient ischemic attack, myocardial infarction, ischemic stroke and suspected prolonged reversible ischemic neurological deficit.

In two controlled studies of thrombocytopenic patients with HCV treated with interferon, 31 of 955 patients (3%) receiving eltrombopag and 5 of 484 patients (1%) receiving placebo experienced thrombotic and/or thromboembolic events. Portal vein thrombosis was the most common thrombotic and/or thromboembolic event in both groups (1% of patients receiving eltrombopag and 1% of patients receiving placebo). There was no temporal relationship between the start of treatment and the development of thrombotic and/or thromboembolic complications. Most cases of thrombotic and/or thromboembolic complications did not lead to cessation of antiviral therapy.

In a controlled study of thrombocytopenic patients with chronic liver disease (n=288) undergoing elective invasive procedures, the risk of portal thrombosis was increased in patients receiving eltrombopag 75 mg once daily for 14 days. There were 6 episodes of thromboembolism (all in the portal vein system) in the group of patients receiving eltrombopag, and 2 in the placebo group (the first in the portal vein system, the second myocardial infarction).

Revolade should not be used to treat thrombocytopenia in patients with chronic liver disease in preparation for invasive procedures.

Bleeding after stopping treatment with eltrombopag

After stopping treatment with eltrombopag, most patients return to baseline platelet counts within 2 weeks, increasing the risk of bleeding and in some cases may cause bleeding. Platelet counts should be monitored weekly for 4 weeks after discontinuation of eltrombopag.

Reticulin formation in bone marrow and the risk of bone marrow fibrosis

Thrombopoietin receptor agonists, including eltrombopag, may increase the risk of formation or proliferation of reticulin fibers in the bone marrow. Before initiating treatment with eltrombopag, peripheral blood smears should be assessed to determine the baseline level of cellular morphological changes. After achieving a stable dose of eltrombopag, a complete clinical blood test with a leukocyte count is performed monthly. If immature or dysplastic cells are detected, a peripheral blood smear should be examined for the appearance of new or intensification of existing morphological changes (for example, the appearance of teardrop-shaped and nuclear red blood cells, immature leukocytes), or to detect cytopenia. If the patient develops new or worsening morphological abnormalities or cytopenias, treatment with eltrombopag should be discontinued and a bone marrow biopsy, including staining the smear to detect fibrosis, should be considered.

Malignant neoplasms and progression of malignant neoplasms

There is a theoretical possibility that thrombopoietin receptor agonists may stimulate the progression of existing hematologic malignancies, such as myelodysplastic syndrome. In clinical trials, there was no difference in the incidence of malignancies or hematologic malignancies between patients receiving placebo and patients receiving eltrombopag.

Cataract

In toxicological studies of eltrombopag in rodents, cataracts were detected. The clinical significance of these data is unknown. Routine monitoring of patients for the development of cataracts is recommended.

In controlled trials in patients with thrombocytopenia and HCV who received interferon-based treatment (n=1439), progression of pre-existing cataracts or the appearance of cataracts was reported in 8% in the eltrombopag group and 5% in the placebo group.

Impact on the ability to drive vehicles and operate machinery

Studies on the effect of eltrombopag on the ability to drive vehicles or operate machinery have not been conducted. Based on the pharmacological properties of eltrombopag, adverse effects on such activities are not expected. However, when assessing a patient's ability to perform activities that require quick thinking, motor and cognitive skills, the patient's clinical condition and the adverse effect profile of eltrombopag should be taken into account.

Revolade®

When eltrombopag is used in combination with interferon therapy, there is an increased risk of adverse reactions, including potentially fatal hepatic decompensation and thromboembolic complications in patients with chronic HCV associated with thrombocytopenia and progressive chronic liver damage, as defined by low albumin levels ≤35 g/L or score ≥ 10 on the MELD (model of end-stage liver disease) scale.

In addition, the benefit of therapy providing sustained virological response compared with placebo was small in these patients (particularly in patients with baseline albumin ≤ 35 g/L) compared with the group as a whole. Eltrombopag therapy in such patients should only be initiated by specialists experienced in the treatment of advanced HCV, and only when the risks of thrombocytopenia or refusal of ongoing antiviral therapy require intervention. If therapy is clinically warranted, careful monitoring of such patients is necessary.

Hepatotoxicity

The use of Revolade® may cause abnormal laboratory tests of liver function, severe hepatotoxicity and liver damage with possible death. In clinical studies in patients (both adults and children) with chronic ITP, increases in serum ALT, AST and indirect bilirubin concentrations were observed. These reactions were mostly mild (grade 1-2) and reversible, without clinically significant symptoms that would indicate liver dysfunction.

In three placebo-controlled studies in adults with chronic ITP, 1 patient in the placebo group and 1 patient in the Revolade group experienced grade 4 liver dysfunction. According to two placebo-controlled studies in patients aged 1 to 17 years with chronic ITP, adverse reactions in the form of increased ALT activity, 3 times the upper limit of normal, were observed in 4.7% and 0% of patients treated with the drug Revolade® and placebo, respectively.

According to 2 placebo-controlled studies, adverse reactions in the form of increased ALT activity in patients with ITP were observed in 5.7% and 4.0% of patients treated with Revolade® and placebo, respectively.

In 2 controlled clinical trials in patients with thrombocytopenia and HCV, ALT or AST levels ≥3 times the upper limit of normal were reported in 34% and 38% of patients in the eltrombopag group and placebo group, respectively. The use of eltrombopag concomitantly with the combination of peginterferon and ribavirin was indirectly associated with hyperbilirubinemia. Cases of ≥ 1.5-fold increase in total bilirubin concentration above the ULN were reported in 76% and 50% in the eltrombopag group and placebo group, respectively.

In an open, uncontrolled study of patients with TAA who had not previously received programmatic immunosuppressive therapy, when using the drug Revolade® in combination with equine antithymocyte immunoglobulin and cyclosporine, there was a >3-fold increase in ALT and AST and a >1.5-fold increase in total bilirubin in 46 .8% of patients (29 out of 62). None of the indicated cases of increase in ALT, AST and total bilirubin led to discontinuation of therapy.

When used as monotherapy in patients with refractory phase II TAA, a >3-fold increase in ALT and AST along with a >1.5-fold increase in total (indirect) bilirubin was observed in 5% of patients. Total bilirubin was increased >1.5-fold in 14% of patients.

Eltrombopag inhibits the UGT1A1 and OATP1B1 genes, which may contribute to the development of indirect hyperbilirubinemia.

In patients with ITP, HCV, and refractory TAA, serum ALT, AST, and bilirubin concentrations should be measured prior to initiation of eltrombopag treatment, then monitored every 2 weeks during dose titration, and monthly once a stable dose is achieved.

A repeat study after detecting deviations from the norm in liver function indicators is carried out within 3-5 days. If the serum concentration of total bilirubin is increased, the concentration of its individual fractions should be determined. If a deviation from the norm is confirmed, control is continued until the phenomenon is resolved, stabilized, or the indicators return to the original level.

Treatment with eltrombopag is discontinued if ALT increases ≥3 times ULN in patients with normal liver function or if ALT increases ≥3 times baseline (or ≥5 times ULN, whichever is lower) in patients with increased ALT activity before treatment and the following symptoms:

- progression of the disorder, or

- persistence of the disorder for ≥4 weeks, or

- its combination with an increase in the concentration of direct bilirubin, or its combination with clinical symptoms of liver damage or signs of decompensation of liver function.

If a decision is made to prescribe Revolade® in the first line of treatment for TAA, an analysis of ALT, AST and bilirubin levels should be performed before starting treatment. If ALT levels increase during therapy, the dose of Revolade® should be adjusted according to the recommendations given in Table 5.

In patients with liver disease, Revolade® should be used with caution. Treatment of patients with ITP and refractory TAA against the background of existing liver dysfunction should begin with a minimum starting dose.

Severe liver damage

In clinical studies, isolated cases of severe liver damage have been reported. The increase in liver laboratory parameters in all cases resolved after a break or discontinuation of therapy with Revolade®. In clinical studies in patients with TAA who did not undergo programmatic immunosuppressive therapy, and in patients with refractory TAA, no cases of severe liver damage were identified, but the number of patients with this indication was limited. Considering the use of the maximum permissible dose of the drug for TAA (150 mg/day) and the nature of the reaction, it is necessary to take into account the possibility of developing liver damage induced by taking the drug.

Decompensation of liver function (use with interferons)

Decompensated liver function in patients with chronic hepatitis C: Monitor patients with low albumin levels (≤ 3.5 g/L) or MELD score ≥10.

In patients with chronic HCV and cirrhosis, there may be a risk of liver decompensation when treated with alpha interferons. In two controlled clinical trials in patients with thrombocytopenia and HCV, indicators of liver decompensation (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis) were observed more often in the eltrombopag group (11%) than in the placebo (6%).

Patients with low baseline albumin concentrations (<35 g/L or MELD score ≥10) had a 3-fold higher risk of liver decompensation and an increased risk of fatal adverse reactions compared with patients with less severe liver disease. liver.

In addition, the benefit of therapy providing sustained virological response compared with placebo was small in these patients (particularly in patients with baseline albumin ≤ 35 g/L) compared with the group as a whole. Eltrombopag should be prescribed to such patients only after careful evaluation of the expected benefit of therapy compared with the possible risks.

Patients with such findings should be closely monitored for signs and symptoms of liver decompensation. For information on withdrawal criteria, refer to the instructions for use of the relevant interferon preparations. Revolade should be discontinued if antiviral therapy is discontinued due to liver decompensation.

Use with direct acting antiviral drugs

The effectiveness and safety of simultaneous use of eltrombopag with direct-acting antiviral drugs approved for the treatment of chronic hepatitis C (hepatitis C virus protease inhibitors, nucleoside polymerase inhibitors, non-nucleoside polymerase inhibitors, NS5A inhibitors) have not been studied.

Thrombotic and/or thromboembolic complications

A platelet count higher than normal poses a theoretical risk of thrombotic and/or thromboembolic complications. In clinical trials of eltrombopag in patients with ITP, thromboembolic complications were observed with platelet counts both below and within the normal range.

Patients with known risk factors for thromboembolic complications (such as factor V Leiden mutation, antithrombin III (ATIII) deficiency, antiphospholipid syndrome, etc.) should receive special attention when using eltrombopag. Platelet counts should be monitored closely and consideration should be given to dose reduction or discontinuation of eltrombopag if platelet counts exceed target values.

In ITP studies, 17 of 446 patients (3.8%) experienced 21 thrombotic and/or thromboembolic episodes. Thromboembolism included: embolism, including pulmonary embolism, deep vein thrombosis, transient ischemic attack, myocardial infarction, ischemic stroke, and suspected prolonged reversible ischemic neurological deficit.

Eltrombopag should not be used in patients with hepatic impairment (Child-Pugh score ≥5) unless the expected benefit outweighs the established risk of portal vein thrombosis. If treatment is considered appropriate, caution should be used when using eltrombopag in patients with hepatic impairment.

In 2 controlled studies of thrombocytopenic patients with HCV treated with interferon (n=1439), 38 of 955 patients (4%) received eltrombopag and 6 of 484 patients (1%) received placebo. thrombotic or thromboembolic complications (both venous and arterial) were noted. Events were predominantly mild and resolved by the end of the study.

Portal vein thrombosis was the most common thromboembolic event in both groups (2% of patients receiving eltrombopag and <1% of patients receiving placebo). There was no temporal relationship between the start of treatment and the development of thrombotic and/or thromboembolic complications.

Patients with low albumin levels (≤ 35 g/L) or MELD score ≥ 10 had a twofold increased risk of thromboembolic events compared with patients with higher albumin levels; Patients aged 60 years and older had a twofold increase in the risk of developing thromboembolic complications than younger patients. Eltrombopag should only be used in these patients after careful comparison of expected benefits and possible risks. Most cases of thrombotic and/or thromboembolic complications did not lead to cessation of antiviral therapy.

Six of 143 (4%) adult patients with chronic liver disease treated with eltrombopag experienced thromboembolic events (all in the portal vein system), and in the placebo group, thromboembolic events developed in two of 145 (1%) patients (1 case in the portal vein system). portal vein and 1 case of myocardial infarction). Five patients treated with eltrombopag experienced thromboembolic events within 30 days of completion of eltrombopag when platelet counts exceeded 200,000/mm3.

In clinical studies of refractory TAA, no cases of thrombotic and/or thromboembolic complications were identified, but the number of patients with this indication was limited. It is necessary to consider the possibility of the development of thrombotic and/or thromboembolic complications induced by taking the drug Revolade® in the patient population, taking into account the prescription of the maximum permissible dose and the nature of the reaction.

Revolade should not be used to treat thrombocytopenia in patients with chronic liver disease in preparation for invasive procedures (eg, liver biopsy, transjugular intrahepatic portosystemic shunt, endoscopic treatment of esophageal varices).

Bleeding after stopping treatment with eptrombopag

After discontinuation of therapy with Revolade® prescribed for the treatment of ITP and HCV, in most patients the platelet count returns to the original value within 2 weeks, which increases the risk of bleeding, and in some cases may lead to bleeding. Platelet counts should be monitored weekly for 4 weeks after discontinuation of eltrombopag.

Progression of existing myelodysstatic syndrome (MPS)

TPO-R agonists are growth factors that lead to the growth and differentiation of progenitor cells, incl. differentiation and platelet production. TPO-R expression occurs on the surface of myeloid lineage cells. There is concern that the use of TPO-R agonists may stimulate the progression of existing hematological malignancies such as MDS. In clinical studies with the use of TPO-R agonists in patients with MDS, cases of a transient increase in the number of blast cells, as well as cases of progression of MDS to acute myeloid leukemia, have been noted.

In order to confirm the diagnosis of ITP or TAA in elderly patients, other clinical conditions manifesting thrombocytopenia should be excluded, in particular, the diagnosis of MDS should be excluded. The possibility of bone marrow puncture and biopsy should be considered throughout the course of the disease and therapy, especially in patients over 60 years of age, patients with systemic manifestations or pathological manifestations, such as an increase in the number of blast cells in the peripheral blood.

The use of eltrombopag for the correction of thrombocytopenia due to MDS or other conditions other than its approved indications is contraindicated outside of clinical trials.

Malignant neoplasms and progression of malignant neoplasms

There is a theoretical possibility that TPO-R agonists may stimulate the progression of existing hematologic malignancies, such as MDS.

Clinical trials in patients with ITP (n=493) and HCV (n=1439) showed no differences in the incidence of malignancies or hematologic malignancies between patients receiving placebo and patients receiving eltrombopag.

This is consistent with information obtained from preclinical studies in which there was no evidence of malignant cell proliferation when MDS cell lines, various types of leukemia cell lines, and solid tumor cell lines (colon, prostate, ovary and lung) were incubated in the presence of eltrombopag. .

Cytogenetic abnormalities and development of MDS/acute myeloid leukemia in patients with severe aplastic anemia

Cytogenetic abnormalities are known to occur in patients with severe aplastic anemia. There is no evidence that eltrombopag increases the risk of developing cytogenetic abnormalities in patients with TAA. In a phase II clinical trial of eltrombopag in patients with severe aplastic anemia, the incidence of new cytogenetic abnormalities was observed in 19% of patients (8 of 43 patients, five of whom had changes in chromosome 7). The average time for the development of cytogenetic abnormalities from the start of the study was 2.9 months. In clinical trials of eltrombopag in patients with TAA, 4% of patients (5 of 133) were diagnosed with MDS. The median time from initiation of eltrombopag treatment to diagnosis was 3 months.

For patients with TAA refractory or previously treated with immunosuppressive therapy, cytogenetic testing of bone marrow aspirate is recommended before initiation of eltrombopag therapy, 3 months after initiation of treatment, and 6 months after cessation of eltrombopag treatment. If new cytogenetic abnormalities are detected, the advisability of continuing eltrombopag therapy should be assessed.

Cataract

In toxicological studies of eltrombopag in rodents, cataracts were detected. Routine monitoring of patients for the development of cataracts is recommended.

In controlled studies in patients with thrombocytopenia and HCV who received interferon-based treatment (n=1439), progression of pre-existing cataracts or the appearance of cataracts was reported in 8% of patients in the eltrombopag group and 5% of patients in the placebo group.

Prolongation of the QT/QTc interval

A study of the drug's effect on the QTc interval involving healthy volunteers receiving eltrombopag at a dose of 150 mg per day did not reveal a clinically significant effect of the drug on cardiac repolarization. Prolongation of the QTc interval has been reported in clinical studies in patients with ITP and thrombocytopenic patients infected with HCV. The clinical significance of these phenomena of prolongation of the QTc interval has not been established.

Effect on fertility

In animal studies, Revolade® did not have any adverse effects on fertility. Eltrombopag did not affect fertility in males or females when used at doses 2-3 times higher than recommended for humans (based on AUC in patients with ITP at a dose of 75 mg / day and in patients with chronic HCV at a dose of 100 mg /day).

Loss of response to eltrombopag therapy

Loss of response or failure to maintain platelet counts during eltrombopag treatment within the recommended range requires a search for a cause to explain the loss/loss of response.

Impact on serological parameters

Eltrombopag is very colored, so it may affect some laboratory parameters. In some cases, serum discoloration and an effect on total bilirubin and creatinine levels have been reported in patients taking Revolade®. If the results of laboratory tests and clinical observations contradict each other, then in the presence of clinically established jaundice, simultaneous determination of aminotransferase levels can help determine the reliability of low total bilirubin levels, but in the case of unexpectedly high serum creatinine values, an assessment of the blood urea indicator should be performed. Repeat laboratory testing using a different test method may also help determine the certainty of the diagnosis.

Revolade, 50 mg, film-coated tablets, 28 pcs.

Liver function monitoring

The use of eltrombopag may cause abnormal laboratory tests of liver function. In clinical studies, increased levels of serum ALT, AST and indirect bilirubin were noted. These phenomena were mostly mild (grade 1–2) and reversible, without clinically significant symptoms that would indicate liver dysfunction. In two placebo-controlled studies, adverse events in the form of increased ALT levels were observed in 5.7 and 4% of patients treated with eltrombopag and placebo, respectively. Serum levels of ALT, AST, and bilirubin should be assessed before initiating treatment with eltrombopag, then monitored every 2 weeks during dose titration, and monthly after a stable dose is established. Repeated testing after detecting abnormal liver function tests is carried out within 3-5 days. If a deviation is confirmed, monitoring continues until the phenomenon is resolved, stabilized, or the indicators return to the original level. Treatment with eltrombopag is discontinued if ALT levels increase (≥3-fold increase in ULN and the following symptoms are present:

— progression of the deviation, or

— persistence of deviation ≥4 weeks, or

- its combination with an increase in the level of direct bilirubin, or

- its combination with clinical symptoms of liver damage or signs of decompensation of liver function.

Eltrombopag should be administered with caution to patients with impaired liver function. In patients with moderate or severe hepatic impairment, the initial dose should be 25 mg once daily.

Thrombotic/thromboembolic complications

A platelet count higher than normal poses a theoretical risk of thrombotic/thromboembolic complications. In clinical studies of eltrombopag, thromboembolic complications were observed in low and normal platelet counts. In studies of idiopathic thrombocytopenic purpura, 17 of 446 patients (3.8%) had 21 episodes of thromboembolism. Thromboembolism included: embolism, incl. pulmonary, deep vein thrombosis, transient ischemic attacks, myocardial infarction, ischemic stroke and suspected prolonged reversible ischemic neurological deficit.

Thrombotic/thromboembolic complications may result from very significant increases in platelet levels. Patients with known risk factors for thrombotic/thromboembolic complications (such as factor V Leiden mutation, ATIII deficiency, antiphospholipid syndrome, etc.) should be given special attention when prescribing eltrombopag.

Platelet counts should be monitored closely and consideration should be given to dose reduction or discontinuation of eltrombopag if platelet counts exceed target values.

In a controlled study of thrombocytopenic patients with chronic liver disease (n = 288) undergoing elective invasive procedures, the risk of thrombotic complications was increased in patients receiving eltrombopag 75 mg once daily for 14 days. There were 6 thrombotic complications observed in the eltrombopag group and 1 in the placebo group. All thrombotic complications noted in patients in the eltrombopag group were in the portal vein system.

Bleeding after stopping treatment with eltrombopag

After stopping treatment with eltrombopag, most patients return to baseline platelet levels within 2 weeks, which increases the risk of bleeding, and in some cases may lead to bleeding. Platelet counts should be monitored weekly for 4 weeks after discontinuation of eltrombopag.

Reticulin formation in bone marrow and the risk of bone marrow fibrosis

Malignant neoplasms and progression of malignant neoplasms

Cataract

In toxicological studies of eltrombopag in rodents, cataracts were detected. The clinical significance of this sign is unknown. Routine monitoring of patients for the development of cataracts is recommended.

Impact on the ability to drive a car and other moving mechanisms

No studies have been conducted on the effects of eltrombopag on the ability to drive or operate machines. Based on the pharmacological properties of eltrombopag, adverse effects on such activities are not expected. However, when assessing a patient's ability to perform activities that require quick thinking, motor and cognitive skills, the patient's clinical condition and the adverse event profile of eltrombopag should be taken into account.

Use of the drug eltrombopag for the treatment of immune thrombocytopenia

About the article

6316

Regular issues of "RMZh" No. 15 dated 07/09/2010 p. 944

Category: Hematology

Authors: Maschan A.A. , Kovaleva L.G. , Pashanov E.D. , Rumyantsev A.G. 1 1 FSBI “NMITs DGOI named after. Dmitry Rogachev" Ministry of Health of Russia, Moscow

For quotation:

Maschan A.A., Kovaleva L.G., Pashanov E.D., Rumyantsev A.G. Use of the drug eltrombopag for the treatment of immune thrombocytopenia. RMJ. 2010;15:944.

Immune thrombocytopenia (ITP), formerly known as idiopathic thrombocytopenic purpura, or Werlhoff's disease (named after the Hanoverian physician who first described the condition in 1735), is a hematological disorder characterized by immune-mediated thrombocytopenia. Moreover, it is considered the most common immune hemopathy in children and adults, with an incidence of 16–32 per 1 million population [1,2]. In 2009 and 2010 In two issues of the journal Blood, recommendations on the terminology, diagnosis, and treatment of ITP in children and adults were published, developed by an international group of recognized experts during several consensus conferences. It should be noted that, according to the consensus reached, the term “idiopathic thrombocytopenic purpura” is recommended to be eliminated from use, and the abbreviation ITP (in English ITP) should be used to refer to immune thrombocytopenia. It is proposed to distinguish newly diagnosed ITP (instead of acute), the criterion of which is the duration of the disease up to 3 months, protracted or persistent ITP with a duration of 3–12 months. and chronic ITP – with a duration of more than 12 months. The dominant mechanism for the development of thrombocytopenia in ITP is increased peripheral platelet destruction, and the degree of thrombocytopenia development is determined both by the rate of platelet destruction and the compensatory capabilities of the bone marrow. In 50–60% of patients with ITP, immunoglobulin G (IgG) antibodies are detected on platelets, which recognize one of the many glycoproteins (GPs) found on the surface of the platelet membrane, such as GPIIb-IIIa, GPIb-IX and GPIa-IIa [ 4]. Antibody bound platelets are recognized by Fc

Eltrombopag

special instructions

Eltrombopag is hepatotoxic and should be used with caution in patients with liver disease. For moderate to severe liver disease, eltrombopag should be used at the lowest effective starting dose and closely monitored by liver function tests. Determination of ALT, AST, bilirubin content is carried out before the start of treatment, every 2 weeks during the dose adjustment period and monthly after determining a constant dose. If bilirubin levels increase, fractionation should be performed. Liver tests should be performed at intervals of 3-5 days. In case of persistent deviations, monitoring should be carried out weekly until they disappear, stabilize and return the indicators to their original values.

Eltrombopag should be discontinued if ALT exceeds 3 times the ULN and progresses or persists beyond 4 weeks. or more, or is accompanied by an increase in direct bilirubin, or is accompanied by clinical symptoms of liver disease, or decompensation of liver function. Resumption of eltrombopag therapy is not recommended. If the potential benefit of restarting therapy outweighs the risk, caution should be exercised when initiating eltrombopag and monitoring liver function tests during dosage titration. If liver function tests are persistently abnormal, eltrombopag should be permanently discontinued.

Eltrombopag, like other thrombopoietin receptor agonists, increases the risk of development or progression of reticulin fiber deposition in the bone marrow.

Before starting treatment with eltrombopag, an extensive peripheral blood test should be performed to identify morphological abnormalities of blood cells. Once a constant dose of eltrombopag has been determined, such analysis should be performed monthly to identify new or worsening morphological abnormalities. If blood cell status develops or worsens, or cytopenia develops, eltrombopag should be discontinued and a bone marrow biopsy, including special staining to detect fibrosis, should be considered.

After discontinuation of eltrombopag, thrombocytopenia may develop more severely than before treatment. This increases the risk of bleeding, especially in patients receiving anticoagulants or antithrombotic agents. After discontinuation of eltrombopag, blood cell counts, including platelet counts, should be monitored for at least 4 weeks and alternative therapy should be considered if thrombocytopenia worsens.

Due to an excessive increase in platelet counts during treatment, thrombotic/thromboembolic complications may develop.

Eltrombopag also stimulates thrombopoietin receptors on the surface of hematopoietic cells, which may increase the risk of hematological malignancy.

During the treatment period, regular ophthalmological monitoring is required to identify symptoms of cataracts.

The safety and effectiveness of eltrombopag in patients with varying degrees of renal impairment have not been established. During treatment, renal function should be carefully monitored.

The safety and effectiveness of eltrombopag in children and adolescents have not been established.

Select the dose with caution in elderly patients.