Revolade 25mg Novartis anti -bleeding due to platelets in the blood (28 tablets)

Dosage form Box of 4 blisters x 7 tablets
Specifications Eltrombopag

Ingredient

Composition informationContent
Eltrombopag25mg

Uses

indications

Revolade drug indications for treatment in the following cases:

  • Treatment of patients from 1 year of age and older suffers from primary immune platelet (Primary Immune Thrombocytopenia - ITP) lasting from 6 months or more from diagnosis and resistance to other treatments (for example, corticosteroids, immune globulin). Strong treatment earlier and not suitable for hematoma stem cells.

    ATC code: B02bx 05.

    Mechanism of impact:

    TPO is the main cytokine related to the regulation of the production of platelets (megakaryopoies) and the production of endogenous platelets, and endogenous ligand for TPO-R. Eltrombopag interacts with TPO-R's piercing area in humans and onset the same signal communication but is not the same as the transmission of thrombopoietin (TPO), which stimulates the proliferation and differentiation from the precursor cells of the bone marrow.

    Dynamic pharmacokinetics

    Eltrombopag's concentration data in plasma are collected in 88 patients with immune thrombocytopenia in examinations 100773A and tra100773b are combined with data from 111 healthy adults in population pharmacokinetic analysis. Estimated AUC (0-τ) and CMAX of Eltrombopag in relatively blood for patients with thrombocytopenia are presented (Table 1).

    Table 1: Average geometry (95%trust) of Eltrombopag pharmacokinetics parameters in plasma in a stable state in adults with immunomemosis.

    dose of Eltrombopag, 1 time/day auc (0- τ) a, μg. (39, 58) 3.78 (3.18; 4,49) 198) 12.7 (11,0; 14.5)

    absorption and bioavailability

    Eltrombopag is absorbed with a peak concentration of 2 to 6 hours after drinking. Use Eltrombopag simultaneously with antacids and other products containing multi -chemotherapy cations such as dairy products and mineral supplements significantly reducing Eltrombopag levels (see the dose and usage).

    The absolute use of Eltrombopag has not been established after drinking. Based on the excretion of urine and metabolic substances eliminated in the stool, the oral absorption estimate of drug -related substances after the single dose of 75 mg of Eltrombopag solution is at least 52%.

    Distribution

    Eltrombopag is highly connected to human plasma proteins (> 99.9%), mainly with albumin. Eltrombopag is a substrate for BCRP, but not a substrate for p-glycoprotein or Oatp1b1.

    Biological metabolism

    Eltrombopag is metabolized mainly through cutting, oxidizing and assembling with glucuronic acid, glutathione, or cysteine. In human radioactive isotope, Eltrombopag accounts for about 64% of Aucinf of radioactive carbon in plasma. Metabolic substances account for small quantities due to glucuronide and oxidation are also detected.

    In vitro studies show that CYP1A2 and CYP2C8 are responsible for the oxidation metabolism of Eltrombopag. Uridine diphosphoglucuronyl Transferase UGT1A1 and UGT1A3 is responsible for glucuronide and bacteria in the lower digestive tract may be responsible for the cutting line.

    Elimination

    The amount of Eltrombopag is widely metabolized. The main excretion path of Eltrombopag is in feces (59%) and 31% of the dose found in urine in the form of metabolites. Eltrombopag is not detected in urine. Eltrombopag does not change excretion through feces accounting for about 20% of the dose. Eltrombopag's plasma semi -discharged time is approximately 21 - 32 hours.

    pharmacokinetic interaction

    Based on a human study with Eltrombopag, which has a radioactive isotope, the glucuronide plays a small role in the metabolism of Eltrombopag. Studies on microsomes of human liver cells confirm UGT1A1 and UGT1A3 are enzymes responsible for glucuronids Eltrombopag. Eltrombopag is an inhibitor of some In vitro uGT enzymes. Clinically, not predicting significant drug interactions associated with glucuronid due to the limited contribution of each individual enzyme UGT in the glucuronide elrombopag. About 21% of Eltrombopag dose can be metabolized by oxidation.

    Studies on human liver cell microsomes identify CYP1A2 and CYP2C8 are enzymes that play the role of Eltrombopag oxidation. Eltrombopag does not inhibit or induce CYP enzymes based on in vitro and in vivo data (see the interaction, cavalry of the drug). In vitro studies prove that Eltrombopag is an inhibitor of OatP1B1 transport agent and is a inhibitor of BCRP and Eltrombopag transportation that increases the concentration of rosuvastatin as the substrate of OATP1B1 and BCRP in a clinical interaction study (see the interactive section, the cavalry of the drug). In clinical studies with Eltrombopag, it is recommended to reduce the dose of statin by 50%. Eltrombopag makes chelate multi -chemotherapy cations such as iron, calcium, magnesium, aluminum, selenium and zinc (see the dose and usage and interaction, the cavalry of the drug).

    In vitro studies have shown that Eltrombopag is not a substrate for OATP1B1 is the organic polypeptide polypeptide but it is a transportation inhibitor (IC50 value is 2.7 μm (1.2 μg/ml). In Vitro studies also show that Eltrombopag is the substance and inhibitor of breast cancer protein (BCRP) (BCRP) (BCRP) (BCRP) (BCRP) (BCRP) (BCRP) (BCRP) is 2.7 μm (1.2 μg/ml)).

    Special patient groups

    kidney failure

    Eltrombopag's

    pharmacokinetics was studied after taking Eltrombopag for adult patients with kidney failure. After using the single dose of 50 mg, the AUC0-∞ of Eltrombopag is 32% to 36% lower in patients with mild to moderate and lower renal impairment patients than 60% in patients with severe renal failure compared to healthy volunteers. There is a significant variation and duplication of concentration between patients with renal impairment and healthy volunteers.

    Eltrombopag concentration (active ingredient) does not connect to this high protein -connected drug has not been measured. Patients with renal function should be cautious when using Eltrombopag and closely monitor, for example by testing serum creatinine and/or urine analysis. Effectiveness and safety of Eltrombopag have not been identified in patients with both renal failure and medium to severe liver and liver failure.

    Hepatic failure

    Eltrombopag's

    pharmacokinetics was studied after taking Eltrombopag for adult patients with liver failure. After using the single dose of 50 mg, the AUC0-∞ of Eltrombopag is higher than 41% in patients with mild liver failure and 80% to 93% higher in patients with medium to severe liver failure compared to healthy volunteers. There is a significant coincidence and variability of concentrations between patients with liver failure and healthy volunteers. Eltrombopag concentration (active ingredient) does not connect to this high protein -connected drug has not been measured.

    Effect of liver failure on Eltrombopag's pharmacokinetics after repeated use has been evaluated through population pharmacokinetic analysis in 28 healthy adults and 714 patients with liver failure (673 patients infected with HCV and 41 patients with chronic liver disease due to other raw disease). Of the 714 patients, 642 patients with mild liver failure, 67 patients with average liver failure and 2 patients with severe liver failure.

    Compared to healthy volunteers, mild liver failure patients with AUC (0-τ) of Eltrombopag in plasma is about 111% higher (95% confidence range: 45% to 283%) and patients with average liver failure with AUC value (0-τ) of Eltrombopag in plasma higher than 183% (95% confidence range: 95% to 459%). Therefore, Eltrombopag should not be used in patients with immunomemosis with liver failure (Child-Pugh score ≥ 5) unless the expected benefits are greater than the risk of being defined of the portal vein thrombosis (see the dose and usage and cautious ways). For patients infected with HCV starting to use Eltrombopag at a dose of 25 mg, 1 time/day (see the dose and usage).

    Race

    The influence of Asian races (such as Japanese, China, Taiwan and South Korea) on Eltrombopag's pharmacokinetics has been evaluated by using population pharmacokinetics analysis on 111 healthy adults (31 Asian patients) and 88 ITP patients (18 Asian patients). Based on the estimated pharmacokinetic analysis of population pharmacokinetics, Asian ITP patients with AUC (0-τ) Eltrombopag plasma is about 49% higher than non-Asian patients, mainly whites (see the dose and usage).

    Gender

    The effect of gender on Eltrombopag's pharmacokinetics has been evaluated using the pharmacokinetic analysis of population population over 111 healthy adults (14 women) and 88 ITP patients (57 women). Based on the estimated pharmacokinetics analysis of population, female ITP patients with AUC (0-τ) Eltrombopag plasma is about 23% higher than that of male ITP patients, when they have not been corrected according to body weight difference.

    The population of children (from 1 to 17 years old)

    Eltrombopag's

    pharmacokinetics is evaluated on 168 children with ITP used 1 time/day in 2 studies, tra108062/petit and tra115450/Petit-2. Eltrombopag's apparent clearance in plasma (Cl/F) increases with body weight. The influence of race and gender on Eltrombopag's CL/F estimates in plasma is homogeneous between children and adults.

    Patients with Asian children with immunity reduced AUC (0-τ) of Eltrombopag in plasma is about 43% higher than non-Asian patients. Patients with female immune platelets are valid for AUC (0-τ) of Eltrombopag in plasma is about 25% higher than that of male patients.

    Eltrombopag's pharmacokinetics parameters in children with ITP are shown in Table 2.

    Table 2: Geometric average average (95%confidence interval) of Eltrombopag pharmacokinetics parameters in plasma in a stable state in children with immunomemosis (the dose regimen of 50 mg, 1 time/day)

    Age

    cmax

    (µg/ml)

    auctau

    (µg.

    12 to 17 years old (n = 62)

    6,80

    (6,17; 7,50)

    103

    (91,1; 116)

    (9,42; 11,2)

    153

    (137; 170)

    1 to 5 years old (n = 38)

    (10,4; 12,9)

    162

    (139; 187)

    AUC (0-τ) and CMAX are based on the estimation of population pharmacokinetics.

    • Before taking Revolade 25mg Novartis anti -bleeding due to platelets in the blood (28 tablets)

    How to use

    Revolade drugs used oral, should take pills at least 2 hours before or 4 hours after using any product such as antacids, dairy products (or other calcium -containing foods), or additional minerals containing multi -chemotherapy (for example, iron, calcium, magnesi, aluminum, aluminum and zinc).

    Instructions for use, processing and cancellation: There is no special requirement on drug treatment after use.

    Dosage

    Eltrombopag treatment should be started and maintained under the supervision of a doctor who has experience in the treatment of hematology and its complications.

    The requirements of the dose of Eltrombopag must depend on the patient based on the number of platelets of the patient. The goal of Eltrombopag treatment is not normalization of platelets.

    Oral mixture can lead to higher Eltrombopag levels than the tablet formula (see the pharmacokinetic properties). When converting between the tablet formula and the oral mixture, should monitor the number of platelets weekly for 2 weeks.

    immune platelets (Nguyen Phat)

    Should use the lowest dose of Eltrombopag to achieve and maintain platelets ≥ 50,000/µl. Adjust the dose based on platelet quantity response. Do not use Eltrombopag to normalize the number of platelets. In clinical studies, the number of platelets usually increases within 1 to 2 weeks after starting to use Eltrombopag and decreases within 1 to 2 weeks after stopping treatment.

    Group of adults and children from 6 to 17 years old:

    Eltrombopag's recommended starting dose is 50 mg once a day. For patients with Asian origin (such as Chinese, Japan, Taiwan, South Korea or Thailand), it is advisable to start using Eltrombopag at a decrease of 25 mg once daily (see the pharmacokinetic characteristics).

    Group of children from 1 to 5 years old:

    Eltrombopag's recommended starting dose is 25 mg once daily.

    Monitor and adjust the dose: After starting to use Eltrombopag, the dose must be adjusted to achieve and maintain the number of platelets ≥ 50,000/µl when necessary to reduce the risk of bleeding. Do not exceed the dose of 75 mg/day. Should regularly monitor clinical tests on hematology and liver during the Eltrombopag treatment process and the dose regimen of Eltrombopag are adjusted based on the number of platelets as stated in Table 3. week). After that, every month should evaluate the total blood formula including the number of platelets and peripheral blood spread.

    Table 3. Adjust the dose of Eltrombopag in patients with immune platelets (ITP)

    The number of platelets adjust the dose or response

    2 weeks of treatment

    increased by 25 mg of daily dose to maximum 75 mg/day.

    ≤ 150,000/µl

    Use the lowest dosage of Eltrombopag and/or immunomemosis treatment at the same time to maintain the number of platelets to avoid or reduce bleeding.

    ≤ 250,000/µl

    Discount 25 mg of daily dose. Wait 2 weeks to evaluate the effectiveness of this dose and any next dose adjustment. Increase the frequency of platelet tracking 2 times/week.

    When platelet quantity ≤ 100,000/µl, start treatment with daily dose decreased by 25 mg.

    ♦ For patients who use 25 mg of Eltrombopag 1 time a day, should consider taking a dose of 25 mg, 1 time every two days.

    can be used Eltrombopag along with other immune platelet treatment drugs. The dose regimen of the drugs should be adjusted at the same time, when appropriate medical, to avoid increasing the number of platelets excessive during Eltrombopag treatment.

    It is necessary to wait at least 2 weeks to see the effect of any dose adjustments to the platelet response of the patient before considering other dose adjustments. Adjust the standard Eltrombopag dose, decrease or increase, will be 25 mg, 1 time/day.

    Stop treatment:

    Should stop treatment with Eltrombopag if the platelet number does not increase to sufficient to avoid serious bleeding clinically after 4 weeks of Eltrombopag treatment at a dose of 75 mg, 1 time/day. Patients should be clinically assessed periodically and the continued treatment should be decided by the doctor on the basis of each patient. In patients who have not cut spleen, should include assessments related to spleen cutting. A platelet reduction may occur during treatment.

    Severe property anemia:

    Starting dose mode:

    Should start using Eltrombopag at a dose of 50 mg once a day. For patients with Asian origin, Eltrombopag should be started at a reduction of 25 mg once daily (see pharmacokinetic properties). Do not start treatment when the patient has abnormalities in cell genetics of chromosomes No. 7.

    Monitor and adjust the dose:

    Hematology responds requires a dose titration, usually up to 150 mg and may take up to 16 weeks after starting using Eltrombopag (see clinical research section). Eltrombopag dose should be adjusted by an increase of 50 mg every 2 weeks when necessary to achieve the target number of platelets ≥ 50,000/µl. For patients using 25 mg, 1 time/day, the dose should be increased to 50 mg/day before increasing the dose of 50 mg. Do not exceed the dose of 150 mg/day. Should regularly monitor clinical and liver clinical tests during the Eltrombopag treatment process and adjust the dose regimen of Eltrombopag based on platelet quantities as stated in Table 4.

    Table 4: Adjust the dose of Eltrombopag in patients with severe property anemia

    The number of platelets adjust the dose or response

    For patients taking 25 mg once daily, increasing the dose to 50 mg daily before increasing the dose of 50 mg.

    ≥ 50,000/µl to ≤ 150,000/µl use the lowest dosage of Eltrombopag to maintain platelet quantities. Wait 2 weeks to evaluate the effectiveness and any subsequent dose adjustment. At least 1 week.

    When platelet quantity ≤ 100,000/µl, start treatment with daily dose decreased by 50 mg.

    For patients who achieve 3 lines, including regardless of blood transfusion, lasting for at least 8 weeks: Eltrombopag dose can be reduced by 50%.

    If the number is still stable after 8 weeks with a decrease in doses, stop using Eltrombopag and monitor blood formula. If the number of platelets drops to

    Stop treatment: Treatment should be stopped if no hematological response occurs after 16 weeks of Eltrombopag treatment. If an abnormal detection is detected in cell genetics, it is necessary to evaluate whether the continued use of Eltrombopag must be suitable (see the warning and caution and adverse reactions). Excessive response to the number of platelets (as stated in Table 5) or important abnormalities in liver tests also need to stop using Eltrombopag (see the adverse reaction).

    Special object groups:

    kidney failure

    No dose adjustment in patients with renal impairment. Patients with impaired renal function should be cautious when using Eltrombopag and closely monitor, for example by testing serum creatinine and/or performing urine analysis (see pharmacokinetic properties).

    Hepatic failure

    Do not use eltrombopag in patients with immunomemosis with liver failure (Child-Pugh ≥ 5) unless the expected benefits are greater than the risk that has been determined on the portal thrombosis (see the warning and cautious section). If the use of Eltrombopag is considered to be necessary for patients with immune platelets with liver failure, the starting dose must be 25 mg once a day. After starting the dose of Eltrombopag in patients with hepatic failure, the distance should be adhered to 3 weeks before increasing the dose.

    Elderly patients

    Data on the use of Eltrombopag in patients aged 65 and older has been limited to immune platelets and has no clinical experience in patients over 85 years old with immune platelets. In clinical studies on Eltrombopag, it is generally not observed that the clinical difference is about the safety of Eltrombopag between patients at least 65 years old and young patients. Other clinical experience reports have not identified the difference in response between elderly patients and young patients, but cannot exclude some older patients with higher sensitivity (see pharmacokinetic properties).

    Data is limited in the use of Eltrombopag in patients over 75 years of age with severe property anemia (SAA). Be careful in these patients (see the warning and caution).

    Asian patients

    For patients with Asian origin (such as China, Japan, Taiwan, South Korea or Thailand), including people with liver failure, so they should start using Eltrombopag at a dose of 25 mg, 1 time/day (see the pharmacokinetic characteristic section). It is necessary to continue monitoring the number of platelets of the patient and the standard criteria to adjust the next dose.

    Group of children's patients

    It is not recommended to use Revolade for children under 1 year of age with immunomemosis due to insufficient data on safety and efficiency. There is currently no data.

    Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What do

    do when overdose? In the case of an overdose, it is advisable to consider oral a preparation containing metal cation such as calcium, aluminum, or Magnesi preparations to chelate Eltrombopag and thus limit absorption. Should closely monitor the number of platelets. It should be started with Eltrombopag as recommended for dosage and usage (see the dose and how to use).

    In clinical studies, there is an overdose report in which patients take 5000 mg Eltrombopag. Unwanted effects are reported including light rash, transient slow heartbeat, alt and AST, and fatigue. The liver enzymes are measured from 2 and 18 after taking the peak concentration at 1.6 times ULN with AST, 3.9 times ULN with ALT, and 2.4 times ULN with total bilirubin. The number of platelets is 672,000/µl at the 18th after taking the drug and the maximum number of platelets is 929,000/µl. All events are resolved without sequelae after treatment.

    Due to the insignificant excretion of Eltrombopag and a lot of cohesion with plasma proteins, hemorrhage/ dialysis is difficult to be effective in increasing Eltrombopag excretion.

    In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

    What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

    Side Effects

    Revolade's safety has been evaluated using double blind, re control studies with placebo, tra100773A and B, tra102537 (Raise) and tra113765, of which 403 patients used Revolade and 179 patients who used placebo, in addition to data from open -labeled studies, were completed were tra108057, tra105325 (extend) and trau11240. Patients who have taken medicine for up to 8 years (in extend research). The most important serious adverse reactions are toxicity to the liver and thrombosis/thrombosis. The most common adverse reactions occur in at least 10% of patients including nausea, diarrhea and increased alanine aminotransferase.

    Revolade's safety in children's patients (from 1 to 17 years old) has been previously treated with immune platelets that have been proven in two studies. Petit2 (tra115450) is a 2 -part, double blind, open, random, control label with placebo. Patients are randomly divided 2: 1 and use Revolade (n = 63) or placebo (n = 29) for up to 13 weeks in the random stage of the study. Petit (tra108062) is a 3 -part study, a staggered, open -label, double, random, control label with placebo. Patients are randomly divided 2: 1 and use Revolade (n = 44) or placebo (n = 21) for up to 7 weeks. Records of adverse reactions are equivalent to the records of the reactions that have been encountered in adults with some additional adverse reactions, marked ♦. The most common adverse reactions among children from 1 year of age and older are reduced to immune platelets (≥ 3% and larger than placebo) are upper respiratory infections, nasopharyngitis, cough, fever, abdominal pain, mouth pain - throat, toothache and runny nose.

    severe proliferate anemia in adult patients:

    Eltrombopag's safety in severe proletarian anemia has been evaluated in a single group study, opened longan (n = 43) of which 11 patients (26%) are treated> 6 months and 7 patients (21%) treated> 1 year. The most important serious adverse reactions are neutropenia with fever and bacterial/ infection. The most common adverse reactions occur in at least 10% of patients including headache, dizziness, cough, mouth and throat pain, nausea, diarrhea, abdominal pain, hyperpentine, joint pain, pain in limbs, fatigue and fever.

    List of adverse reactions:

    Agricultural reactions in studies on immune platelets in adults (n = 763), studies on immune platelet reduction in children (n = 171), studies on gold medals (n = 1.520), studies on severe hyperplasher anemia (SAA) (n = 43) and after -sales reports are listed below by MEDDRA group and frequency. In each organ system, the adverse reactions of the drug are arranged by frequency, first the most common reactions. Classification of the corresponding frequency for each adverse drug reaction of the drug based on the following convention (Cioms III): Very common (≥ 1/10); Common (≥ 1/100 to

    Group of immune platelet reduction patients (ITP)

    Infections and parasites

  • Very common: Nasomitis ♦, upper respiratory tract infections ♦.
  • Uncommon: Rectoma Rectal Cancer.

    • Blood disorders and lymphatic systems

  • Common: Anemia, Eosin cells like eosin, leukemia, platelets, hemoglobin decreased, reduced number of white blood cells.
  • Uncommon: Hypersensitivity.
  • Common: Hemoto reduction, decreased appetite, hyperuricemia.
  • Common: Sleep disorders, depression.
  • Common: Perception, feeling of feeling, drowsiness, migraine (Migraine).
  • Common: dry eyes, blurred vision, eye pain, vision loss.
  • Common: Ear pain, dizziness.

    • Heart disorders

  • Less: tachycardia, acute myocardial infarction, cardiovascular disorders, purple blue, sinus tachycardia, long -term QT ​​interval on the center of the center.
  • Common: Deep vein thrombosis, hematoma, hot burning.
  • Very common: Ho ♦.
  • Common: mouth - throat, runny nose ♦.
  • Very common: nausea, diarrhea ♦. mouth.

    • Liver disorders

  • Very common: Increasing alanine aminotransferase †.
  • Common: rash, hair loss, increased sweating, body itching, hemorrhagic spots
  • Common: muscle pain, muscle spasm, musculoskeletal pain, bone pain, back pain.
  • Common: proteinuria, hypertreatinine, thrombosis microchun with renal failure ‡.
  • Common: Menstrual menstruation.
  • Common: Fever*, chest pain, weakness; * Very common in immune platelets (ITP) in children.
  • Common: increased alkaline phosphatase in the blood.
  • Uncommon: Sunburn.

    †: Increasing alanine aminotransferase and aspartate aminotransferase can occur simultaneously, although at lower frequency.

    ‡: The term is combined with priority terms including acute kidney damage and renal failure.

    A group of patients studying severe immortal anemia (SAA)

    Blood disorders and lymphatic systems

  • Common: Neutral leukemia, spleen infarction.
  • Common: iron overload, decreased appetite, hypoglycemia, increased appetite.

    • Mental disorders

  • Common: anxiety, depression.

    • Nervous system disorders

  • Very common: headache, dizziness.
  • Common: dry eyes, cataracts, jaundice in the eyes, blurred vision, vision impairment, flying flying phenomenon.
  • Very common: cough, mouth pain - throat, runny nose.
  • Common: nosebleeds.
  • Very common: diarrhea, nausea, teeth bleeding, abdominal pain.
  • Very common: increasing transaminase. Cases of liver damage due to drugs have been reported in patients with immunominals (ITP) and hepatitis C (HCV) infection.
  • Common: Bleeding spots, rashes, itching, urticaria, skin damage, inlaid rash.
  • Very common: joint pain, pain in the limbs, muscle spasms.
  • Common: back pain, muscle pain, bone pain.
  • Common: Urine has an abnormal color.
  • Very common: fatigue, fever, chills
  • Common: increased creatine phosphokinase in the blood.

    • Warnings

    Before using the drug you need to read the instructions carefully and refer to the information below.

    contraindicated

    Revolade drugs contraindicated in the following cases:

  • Contraindicated for patients with hypersensitivity to Eltrombopag or any excipients of the drug.

    • Caution when using

    The risk of toxicity for the liver

    The use of Eltrombopag can cause liver function abnormalities and toxicity to heavy liver, life -threatening (see the adverse reaction). Alanine aminotransferase (ALT) concentration should be measured, Aspartate aminotrasferase (AST) and serum bilirubin before starting to use eltrombopag, every 2 weeks in the dose adjustment phase and each month after the stable dose has been determined. Eltrombopag inhibits UGT1A1 and OATP1B1, which can lead to indirect blood bilirubin.

    If the bilirubin concentration increases, it is advisable to perform segments. Should evaluate serum tests for abnormal liver function by repeating test within 3 to 5 days. If abnormalities are identified, serum tests should be monitored until the abnormalities recover, stabilize or return to the initial level. Eltrombopag should be stopped if the ALT concentration increases (≥ 3 times the upper limit of the normal level [X ULN] in patients with normal liver function, or ≥ 3 times the initial level or> 5 times ULN, any lower level, in patients with transaminase increased before treatment) and:

  • progress, or
  • persistent ≥ 4 weeks, or
  • with direct bilirubin, or
  • with clinical symptoms of liver damage or evidence of liver loss.

    Be careful when taking eltrombopag for patients with liver disease. In patients with immunominal hemorrhage (spontaneous) (ITP) and severe property anemia (SAA), the dose of Eltrombopag should start lower. Need to monitor closely when used for patients with liver failure (see the dose and usage).

    thrombosis/thrombolytic complications

    The risk of thrombosis (TEE) has been found to increase in patients with chronic liver disease (CLD) treated with 75 mg of Eltrombopag once a day for 2 weeks to prepare for invasive procedures. 6 out of 143 (4%) of an adult patient with Tee Tee used Eltrombopag (all door veins) and 2 out of 145 (1%) of patients in the placebo group with Tee (a patient in the portal vein system and a patient with myocardial infarction). 5 out of 6 patients treated with Eltrombopag suffered from thrombosis with platelets> 200,000/µl and within 30 days from the last dose of Eltrombopag. Eltrombopag is not indicated for thrombocytopenia in patients with chronic liver disease to prepare for invasive procedures.

    In clinical studies with Eltrombopag on the immune -reduced thrombocytopen (spontaneous) (ITP) (ITP), thrombotic embolization events have been observed in low and normal platelets. Caution should be careful when using eltrombopag for patients with known risk factors for thrombosis includes but not limited to genetic risk factors (for example, V Leiden factor) or acquired (for example, antithrombin deficiency III (ATIII), phospholipid syndrome), high age, patients with prolonged dynamic stages, malignant and malignancy, Art/injury, obesity and smoking. Need to closely monitor the number of platelets and consider reducing the dose or stopping treatment with Eltrombopag if the number of platelets exceeds the target level (see the dose and usage).

    It is necessary to consider balancing the benefits-mechanical benefits in patients at risk of thrombosis (TEE) due to any cause. There is no case that tee has been detected from clinical research for resistance to treatment, but it is not possible to rule out the risk of these events in this group of patients due to limiting the number of patients exposed. Because the highest dose is allowed to be indicated for patients with SAA (150 mg/day) and due to the nature of the reaction, TEES is expected to occur in this patient group.

    Do not use eltrombopag in patients with immune-reduced hemorrhage committee (spontaneous) (ITP) with liver failure (Child-Pugh ≥ 5) unless the expected benefits are superior to the risk of gate venous thrombosis. When the treatment is considered appropriate, it is necessary to be cautious when using Eltrombopag for patients with liver failure (see the dose and how to use and adverse reactions).

    bleeding after stopping treatment with eltrombopag

    Platelets may occur again in patients with immune -reduced hemorrhage (spontaneous) (ITP) after stopping treatment with Eltrombopag. After stopping using Eltrombopag, the number of platelets returns to the original level within 2 weeks in most patients increasing the risk of bleeding and in some cases can lead to bleeding. This risk increases if it stops treating with Eltrombopag when the presence of anticoagulants or anti -platelets. It is recommended that if you stop treatment with Eltrombopag, start the treatment of immunosuppressants (spontaneous) under the current treatment instructions. Additional medical treatment may include stopping treatment with anticoagulant drugs and/or plateletic anti -collection drugs, anticoagulant reversal, or platelet support. Must monitor the number of platelets weekly for 4 weeks after stopping treatment with Eltrombopag.

    Bone marrow reticulin formation and bone fibrosis risk

    Eltrombopag may increase the risk of growth or progression of reticulin fibers in the bone marrow. The meaning of this finding, as well as with other Thrombopoietin receptors (TPO-R), has not been determined.

    Before starting treatment with Eltrombopag, it is necessary to strictly check the peripheral blood glass test to determine the initial level of abnormalities in cell morphology. After determining a stable dose of Eltrombopag, a total blood formula test should be performed with a monthly number of white blood cells (WBC). If observations are observed that adult cells or dysplasia cells are observed, it is necessary to check the peripheral hemorrhage test for new or worse morphology (for example, red blood cells shaped in water and red blood cells with core, adult leukocytes) or reduce blood cells. If the patient develops new or more severe or more severe morphology or reducing blood cells, Eltrombopag should be discontinued and should be considered for bone marrow biopsy, including dyeing for fibrosis.

    The progress of the existing marrow dysplasia syndrome (MDS) has

    There is theoretical concern that the TPO-R's owners can stimulate the progression of malignant tumors of existing hematology such as marrow dysplasma syndrome. TPO-R isomers are growth factors that lead to the expansion of precursor cells to create platelets, differentiate and platelet production. TPO-R is manifested mainly on the surface of the root canal cells. In clinical studies with a TPO-R isomers in patients with marrow dysplasia syndrome (MDS), cases of transient increase in the number of cells and cases of MDS progression to acute marrow leukemia (AML) have been reported. The diagnosis of the immune -decreased hemorrhage (spontaneous) (ITP) (ITP) (ITP) (SAA) in adult patients and the elderly should be determined by eliminating other clinical entities that show signs of platelet reduction, especially the diagnosis of the medullary dysplasia syndrome.

    It is necessary to consider the implementation of bone marrow suction and biopsy in the process of disease and treatment, especially in patients over 60 years old - people with systemic symptoms or abnormal signs such as increased peripheral blood. The efficiency and safety of Revolade has not been determined to treat thrombocytopenia due to myeloma syndrome. Revolade should not be used in addition to clinical studies for thrombocytopenia due to marrow dysplasma syndrome.

    Cell genetic abnormalities and progress to myeloma syndrome (MDS)/Acute marrow leukemia (AML) in patients with severe property anemia (SAA).

    Cell genetics abnormalities are known to occur in patients with severe property anemia (SAA). It is unclear whether Eltrombopag will increase the risk of cell genetics in patients with severe property anemia. In phase -phase clinical study on severe anti -property anemia with Eltrombopag with a starting dose of 50 mg/day (increasing every 2 weeks to up to 150 mg/day) (ELT112523), the rate of new abnormalities on cell genetics is observed in 17.1% of adult patients [7/41 (4 of which have changes in number 7 chain infection 7)]. Middle -time time while studying until a cell genetic abnormal is 2.9 months.

    In phase -phase clinical study of severe anti -dynamic anemia with Eltrombopag at the dose of 150 mg/day (with racial changes or age as stated) (ELT116826), the new rate of abnormal cytotromas is observed in 22.6% of adult patients [7/31 (of which 3 patients have changes in chromosomes 7)]. All 7 patients have normal cytotoxic systems at the beginning. Six patients with cytotoxic abnormalities in the 3rd month when taking Eltrombopag and a patient with abnormalities of cytotromagnines in the 6th month.

    In clinical studies with Eltrombopag in severe prolapse anemia, 4% of patients (5/133) were diagnosed with marrow dysplasma syndrome. The median time until the diagnosis is 3 months from the beginning of Eltrombopag treatment. For patients with severe anti -property anemia treatment with previous immunosuppressive therapy, or strong treatment with immunosuppressive therapy, it is recommended to check the bone marrow by sucking bone marrow for cytopenic testing before starting to use Eltrombopag, at 3 months of treatment and 6 months later. If detected new abnormalities in cell genetics, it is necessary to evaluate whether continuing to use Eltrombopag is appropriate or not.

    Visual changes

    Observed cataracts found in studies of the toxicity of Eltrombopag in rodents (see the non -clinical safety data section). In control studies in patients infected with hepatitis C virus, thrombocytopenia treated with interferon (n = 1,439), the progression of the original cataract is available or the cataract event occurs in the Eltrombopag group of 8% and in the placebo group is 5%. Cases of retinal hemorrhage, mostly at 1 or 2, have been recorded in patients infected with hepatitis C virus using Interferon, Ribavirin and Eltrombopag (2% in Eltrombopag and 2% in the placebo group). Bleeding occurs on the surface of the retina (preretinal), under the retina (sbretinal), or in the retina tissue. Recommended patient eye monitoring.

    extends the QT/QT range (QTC)

    A study of QTC about healthy volunteers taking the dose of 150 mg Eltrombopag every day does not show clinical significance to the pole of the heart. The extension of QTC has been reported in clinical studies in patients with immunosuppressive hemorrhage (spontaneous) (ITP). The clinical significance of this QTC is unknown.

    lost in response to Eltrombopag

    The loss of response or non -maintenance is platelet response to Eltrombopag treatment within the recommended dose should promote the search for the causes, including bone marrow reticulin.

    Group of children's patients

    The above warnings and caution on the immune -reduced thrombocytopenic (spontaneous) (ITP) also applies to the group of children's patients.

    affects laboratory tests

    Eltrombopag is dyed high and therefore has the ability to affect some laboratory tests. The serum discoloration and influence on the test of the total bilirubin and creatinine have been reported in patients using Revolade. If the results of the laboratory and clinical observation are inconsistent, the test by other methods can help determine the validity of the result.

    Use drugs for women during pregnancy and lactation

    Pregnant women:

    There is no data or data that is limited in the use of eltrombopag in pregnant women. Animal studies have shown toxicity to reproduction. Unknown risk for people.

    Do not recommend using Revolade during pregnancy.

    Women are likely to be pregnant, contraceptive in men and women:

    It is not recommended to use Revolade in women who are likely to not use contraception.

    breastfeeding women:

    It is unclear whether Eltrombopag/metabolites will be excreted into breast milk. Animal studies have shown that Eltrombopag is likely to be secreted into milk (see the non -clinical safety data); Therefore, it is not possible to rule out the risk for breastfeeding. It is necessary to decide whether to stop breastfeeding or continue/avoid treatment with Revolade, taking into account the benefits of breastfeeding and the benefits of treating women.

    Reproduction:

    The ability to reproduce in male or female rats is not affected at the level of exposure equivalent to the exposure level in humans. However, it is not possible to rule out the risk for people (see the non -clinical safety data).

    The effect of the drug on driving and operating machinery

    Drug interaction

    Eltrombopag's effect on other drugs:

    HMG inhibitors HMG Reductase:

    Use Eltrombopag 75 mg, 1 time/day for 5 days with a single dose of 10 mg rosuvastatin is the substrate of OATP1B1 (Polypeptide shipping organic anion - Organic Anion Transporting Polypeptide, OATP) and BCRP (Breast Cancer Cancer Resistance Protein) for 39 Healthy Healthy Health The most of the plasma) of Rosuvastatin 103%(reliability (CI) 90%: 82%, 126%) and AUC (area under the curve) 0-∞ 55%(90%reliable range: 42%, 69%). Interactions are also expected with other HMG-COA Reductase inhibitors, including Atorvastatin, Fluvastatin, Lovastatin, Pravastatin and Simvastatin. When used simultaneously with Eltrombopag, it is advisable to consider reducing statin dose and carefully monitor the adverse reactions of the statin (see the pharmacokinetic properties).

    substrate of OATP1B1 and BCRP:

    Be cautious when using Eltrombopag and the substrate of OATP1B1 (for example, methotrexate) and BCRP (for example, Topotecan and Methotrexate) (see the pharmacokinetic properties).

    The substrate of cytochrome p450:

    In studies using human liver microsom, Eltrombopag (up to 100 μm) shows that there is no inhibitor in vitro enzymes CYP450 1A2, 2A6, 2C19, 2D6, 2E1, 3A4/5, and 4A9/11 and are CYP2C8 and CYP2C9 inhibitors as measured by using Paclitaxel and Diclofenac Exploration. Use Eltrombopag 75 mg, 1 time/day for 7 days for 24 healthy men who do not inhibit or induce the metabolism of pollutants for 1A2 (caffeine), 2C19 (omeprazole), 2C9 (Flurbipfen) or 3A4 (Midazolam) in humans. There is no clinical interaction that is expected when Eltrombopag and the substrate of CYP450 are simultaneously used (see the pharmacokinetic characteristics).

    HCV Protease inhibitors:

    No dose adjustment when using Eltrombopag with Telaprevir or Boceprevir. Single -dose of a single dose of Eltrombopag 200 mg with Telaprevir 750 mg every 8 hours does not change the concentration of Telaprevir in plasma.

    Take a simultaneous use of a single dose of Eltrombopag 200 mg with BoCeprevir 800 mg every 8 hours does not change the AUC (0-τ) of BoCeprevir in plasma but increases cmax by 20%, and reduces cmin (lowest plasma concentrations) 32%. The clinical significance of reducing cmin has not been determined, recommended clinical monitoring and testing of gold inhibitors.

    The effect of other drugs on Eltrombopag:

    ciclosporin:

    Reducing the concentration of Eltrombopag has been observed when used simultaneously with 200 mg and 600 mg Ciclosporin (BCRP inhibitors (Breast anti -cancer protein) Ciclosporin reduces the CMAX of Eltrombopag 39% and reduces the Aucinf of Eltrombopag 24%.

    Should monitor the number of platelets at least a week for 2 to 3 weeks when used simultaneously Eltrombopag with ciclosporin. Eltrombopag may be increased based on these platelets.

    Cation multi -chemistry (chelate):

    eltrombopag chelate with polymerization cations such as iron, calcium, magnesium, aluminum, selenium and zinc. Use a single dose of Eltrombopag 75 mg with antacids containing multi-chemotherapy cation (1524 mg of aluminum hydroxide and 1425 mg Magnesi carbonate) reduces the AUC0-∞ of Eltrombopag in plasma 70%(90%reliability: 64%, 76%) and reduces CMTROX of Eltrombopag in plasma 70%(90%reliable, 76%).

    Should use Eltrombopag at least 2 hours before or 4 hours after using any product such as antacids, dairy products, or mineral supplements containing cinema cation to avoid significantly reducing the absorption of Eltrombopag due to chelate chemistry (see the dose parts and usage and pharmacokinetic properties).

    lopinavir/ritonavir:

    Simultaneous use of Eltrombopag with Lopinavir/Ritonavir can reduce Eltrombopag levels. A study in 40 healthy volunteers showed that the simultaneous use of a single dose of Eltrombopag 100 mg with a repeated dose of Lopinavir/Ritonavir 400/100 mg, 2 times/day resulted in reduction of Eltrombopag's AucinF in plasma 17%(90%reliability range: 6.6%, 26.6%). Therefore, be careful when using Eltrombopag with Lopinavir/Ritonavir.

    Should closely monitor the number of platelets to ensure appropriate medical management of the doses of Eltrombopag when starting or stopping treatment with Lopinavir/Ritonavir. CYP1A2 and CYP2C8: Eltrombopag is metabolized through many roads including CYP1A2, CYP2C8, UGT1A1, and UGT1A3 (see pharmacokinetic characteristics). The inhibitor or induction of an uncertain enzyme significantly affects the concentration of elers in plasma, while the inhibitors or induction of multiple enzymes can increase the concentration of Eltrombopag (e.g. Fluvoxamine) or reduce Eltrombopag levels (for example Rifampicin).

    HCV Protease inhibitors:

    The result of a pharmacokinetics interactive study (PK) shows that the simultaneous use of BoCeprevir 800 mg every 8 hours or Telaprevir 750 mg every 8 hours with an Eltrombopag 200 mg single dose does not change the Eltrombopag level in plasma at clinical significance.

    Immunological platelets (ITP):

    The drugs used in immune-reduction treatment in combination with Eltrombopag in clinical studies include corticosteroids, danazol, and/or azathioprine, immunoglobulin (immunoglobulin) intravenously (IVIG), and Anti-D Immunoglobulin. Should monitor the number of platelets when combining eltrombopag with other drugs in the treatment of immune platelets to avoid the number of platelets outside the recommended scope (see the dose and how to use).

    Interaction with food:

    Use the Eltrombopag tablet or powder with a multi-calcium meal (for example, a meal of dairy products) significantly reduces AUC0 -∞ and CMTrombopag in plasma. In contrast, using Eltrombopag 2 hours ago or 4 hours after a meal with a lot of calcium or with low -calcium foods [

    Foods with low calcium content ( Cavalry:

    Due to the absence of studies on the correlation of the drug, not mixing this drug with other drugs.

    • Storage

    Leave a cool place, avoid light, temperature below 30⁰C.

    Other drugs

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