Revolide - Instructions For Use, Price, Analogs, Tablets 25 Mg And 50 Mg

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Revolide

Revolide: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Revolade

ATX code: B02BX05

Active ingredient: eltrombopag (eltrombopag)

Manufacturer: Glaxo Operations UK Limited (UK)

Description and photo update: 28.11.2018

Prices in pharmacies: from 62,000 rubles.

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Revolide is a hematopoiesis stimulator.

Release form and composition

The drug is available in the form of film-coated tablets: round, biconvex, engraved on one side: white tablets - “GS NX3” and “25”, brown tablets - “GS UFU” and “50” (by 7 pcs. In blisters, in a cardboard box 4 blisters and instructions for use of Revolide).

1 film-coated tablet contains:

• active substance: eltrombopag olamine - 31.9 mg or 63.8 mg, which is equivalent to 25 mg or 50 mg of eltrombopag, respectively;
• excipients: mannitol, microcrystalline cellulose (MCC), povidone K30; extragranular components - sodium carboxymethyl starch (type A), MCC, magnesium stearate;
• the composition of the film shell: white tablets - white opadry YS-1-7706-G (macrogol 400, hypromellose, polysorbate 80, titanium dioxide); brown tablets - brown opadry 03B26716 (macrogol 400, hypromellose, titanium dioxide, iron dye red oxide, iron dye yellow oxide).

Pharmacological properties

Pharmacodynamics

Revolide is a drug that stimulates hematopoiesis with the active substance eltrombopag. The mechanism of action of eltrombopag is due to the interaction with the transmembrane domain of the human thrombopoietin receptor [thrombopoietin (TPO) is an endogenous ligand for the thrombopoietin receptor (TPO-R), a major cytokine involved in the regulation of megakaryopoiesis and platelet production]. Eltrombopag promotes the initiation of a signaling flow similar to that of endogenous thrombopoietin, which is accompanied by the induction of proliferation and differentiation of megakaryocytes from bone marrow progenitor cells.

Revolide has a hemostatic effect. Eltrombopag differs from thrombopoietin in terms of its effect on platelet aggregation. In healthy people, as a result of its effect on platelets, aggregation under the action of adenosine diphosphate (ADP) does not increase, and the expression of P-selectin is not stimulated. Eltrombopag does not interfere with platelet aggregation under the influence of collagen or ADP.

Pharmacokinetics

After oral administration, eltrombopag is absorbed, reaching the maximum concentration (C _max) in the blood plasma after 2–6 hours. The calculated values of absorption after a single dose of 75 mg of eltrombopag, obtained on the basis of renal excretion indicators and analysis of drug metabolites excreted through the intestine, were 52%. Absolute bioavailability has not been established. In adults with idiopathic thrombocytopenic purpura (ITP), C _max while taking a daily dose of 50 mg Revolide averages 0.008 01 mg / ml, 75 mg - 0.012 7 mg / ml. In patients with hepatitis C virus (HCV) C _max in blood plasma depends on the size of the daily dose. While taking a daily dose of Revolid 25 mg C _max the average is 0.006 4 mg / ml, 50 mg - 0.009 08 mg / ml, 75 mg - 0.016 71 mg / ml, 100 mg - 0.019 19 mg / ml.

With the simultaneous use of antacids or the consumption of food containing polyvalent cations (including dairy products, mineral supplements), the exposure of eltrombopag is significantly reduced.

Plasma protein binding - more than 99.9%.

Eltrombopag is a substrate for BCRP (Resistant Breast Cancer Protein), but not for polypeptide organic anion transporters (OATP1B1) or P-glycoprotein.

The absorbed part of eltrombopag is actively metabolized. Metabolism occurs primarily by cleavage, oxidation and conjugation with glutathione, glucuronic acid, or cysteine. Bacteria in the lower gastrointestinal tract may be involved in cleaving eltrombopag. Up to 20% of the dose of the drug is metabolized by oxidation with the participation of isoenzymes CYP1A2 and CYP2C8. The isoenzymes responsible for glucuronidation are UGT (uridine diphosphate glucuronyltransferase) enzymes - UGT1A1 and UGT1A3. In unchanged form, 64% of eltrombopag is found in plasma. By glucuronidation and oxidation, minor metabolites are formed, the volume of each of them in plasma is 10%.

Eltrombopag is excreted mainly through the intestines (59% of the dose taken, of which 20% is unchanged). In the urine, the original active substance is absent, 31% of the dose taken is found in the form of metabolites.

The half-life (T _1/2) from plasma is 21–32 hours.

Compared with patients with normal renal function, the total concentration (AUC) of eltrombopag in the blood plasma after a single dose of Revolide 50 mg in patients with mild renal impairment decreases by 32%, moderate impairments - 36%, severe impairments - 60%.

Patients with ITP and HCV with impaired liver function (liver cirrhosis) should be prescribed eltrombopag with caution, subject to constant monitoring. The initial daily dose for this category of patients should be 25 mg.

The results of the analysis of population pharmacokinetics showed that in patients with ITP of East Asian origin (including Japanese, Chinese, Koreans, residents of Taiwan), the AUC values of eltrombopag are approximately 87% higher than in patients of other races (mainly Caucasians), while dose adjustment by body weight was not carried out. In similar studies of patients with HCV, it was found that the AUC of eltrombopag in blood plasma in patients of East Asian and South Asian descent is approximately 55% higher than in patients of Caucasian and other races.

The plasma AUC of eltrombopag in female patients with ITP is approximately 50% higher than in men. It was found that in patients with HCV, AUC in women is 41% higher than in men.

In patients over the age of 60 years, the AUC of eltrombopag in blood plasma is 36% higher than in younger patients.

Indications for use

Revolide is used to treat thrombocytopenia in patients with the following diseases:

• chronic immune (idiopathic) thrombocytopenic purpura (ITP) in cases where corticosteroids, immunoglobulins, or splenectomy are not effective enough to reduce the risk of bleeding;
• chronic viral hepatitis C (HCV) - in order to ensure the possibility of antiviral therapy, including interferon, or its optimization.

Contraindications

No contraindications have been established for the use of the drug in the recommended doses according to indications.

It is recommended to use Revolide for the treatment of patients with liver failure of 5 or more points on the Child-Pugh scale only in cases where the expected benefit of therapy outweighs the potential threat of portal vein thrombosis.

The safety and efficacy of using eltrombopag for the treatment of children has not been established.

Care should be taken when prescribing Revolid to patients with impaired renal function, impaired liver function (including liver failure), risk factors for thromboembolism (including deficiency of antithrombin III, Leiden factor V, antiphospholipid syndrome).

Due to the lack of data on the efficacy and safety of using Revolide during pregnancy / lactation, only a doctor can prescribe the drug to a pregnant / breastfeeding woman in cases where the expected benefits to the mother from therapy outweigh the potential risks to the fetus / child.

Revolide, instructions for use: method and dosage

Revolide tablets are taken orally, including with food containing no more than 50 mg of calcium, or, preferably, not containing it.

The interval between taking the drug and antacids, mineral supplements containing polyvalent cations (including calcium, iron, aluminum, magnesium, selenium, zinc), or dairy products should be at least 4 hours.

Revolide should not be used to normalize platelet count.

The doctor sets the dosage regimen individually, taking into account the clinical indications and the number of platelets in the patient.

In most cases, an increase in the number of platelets occurs after 7-14 days of therapy, after the termination of the reception of Revolide, the decrease in the achieved level occurs within the same time.

The recommended dosage for adult patients with chronic immune (idiopathic) thrombocytopenia: initial dose - 50 mg, for patients of East Asian origin - 25 mg, frequency of administration - 1 time per day. Reducing the risk of bleeding is achieved by maintaining platelet counts of 50,000 / μL and above. To achieve and maintain this number of platelets, it is necessary to use the minimum effective dose of Revolide. The maximum daily dose is 75 mg. Taking pills during the first 28 days should be accompanied by regular complete blood counts, monitoring of hematological parameters and the state of liver function. After reaching a stable platelet count, a complete blood count can be performed once every 30 days.

Correction of the dosage regimen is made individually, taking into account the following change in the number of platelets in the blood:

• less than 50,000 / μl after at least 14 days of therapy: the daily dose should be increased by 25 mg;
• 200,000–400,000 / μl: a decrease in the daily dose to 25 mg is required. If the initial dose was 25 mg, then the patient is transferred to receive this dose of the drug every other day. After 14 days of taking Revolide at a dose of 25 mg, the effect of therapy is assessed and a decision is made on the need for further dose adjustment;
• more than 400,000 / μl: you should stop taking Revolide, studies to determine the number of platelets should be carried out every 3 days. If the number of platelets in the blood drops to less than 150,000 / μl, then the treatment should be resumed at the lowest daily dose.

In case of impaired liver function (liver cirrhosis) in patients with ITP, the initial daily dose should be 25 mg; its increase is allowed only after 21 days of therapy.

If, after 28 days of taking the drug in a daily dose of 75 mg, the platelet count does not reach a value that reduces the risk of bleeding, treatment with Revolide should be discontinued.

When prescribing Revolid to patients with chronic viral hepatitis C, accompanied by thrombocytopenia, it is necessary to take into account full information about its compatibility with the antiviral therapy used.

To achieve and maintain the platelet count required to initiate and optimize antiviral therapy, the minimum effective dose of Revolide must be used.

The selection of doses is based on the restoration of the platelet count. An increase in the number of platelets is observed within 7 days after starting the drug.

Recommended dosage: The initial dose of Revolide is 25 mg once a day (regardless of the patient's race). Every 14 days, the dose of eltrombopag is increased by 25 mg until the blood platelet count is optimal for starting antiviral therapy. The maximum daily dose is 100 mg.

During antiviral therapy, the number of platelets must be monitored once every 7 days until a stable level is reached.

Recommendations for adjusting the dose of Revolide for patients with HCV during the period of antiviral therapy, taking into account the following changes in the number of platelets:

• less than 50,000 / μl for at least 14 days of therapy: the daily dose should be increased by 25 mg, but at the same time it should not exceed 100 mg;
• 200,000-400,000 / μl: the daily dose should be reduced to 25 mg. After 14 days, the effectiveness of the new dose should be assessed and, if necessary, a decision should be made on its further correction;
• more than 400,000 / μL: you must stop taking eltrombopag. Studies to determine the number of platelets in the blood are prescribed every 3 days. If the platelet count is less than 150,000 / μl, the use of Revolid is resumed with the appointment of the lowest daily dose.

When adjusting the dose, patients who have taken eltrombopag at a daily dose of 25 mg should consider continuing with a dose of 12.5 mg daily or 25 mg every other day.

If liver function is impaired in patients with chronic HCV, the initial dose of Revolide should be set at 25 mg 1 time per day.

In patients with HCV genotype 1, 4 or 6, regardless of the decision to continue treatment with interferons, the question of canceling Revolid should be considered if, after 84 days of combined use, the effectiveness of antiviral therapy has not been achieved.

In addition, the use of eltrombopag should be discontinued in the following cases:

• detection of HCV RNA after 168 days of treatment;
• cessation of antiviral therapy;
• an excessive increase in the number of platelets;
• clinically significant deviations from the norm of liver function tests.

Patients should continue to monitor platelet counts.

The safety and effectiveness of using Revolide for the treatment of children have not been established.

When treating elderly patients (65 years and older), the dosage regimen is not adjusted; an increased risk of hypersensitivity to eltrombopag should be taken into account.

In East Asian patients with impaired liver function with ITP or HCV, treatment should be initiated at a dose of 25 mg once daily.

Side effects

Adverse reactions identified during the use of Revolide in patients with chronic ITP:

• infections and invasions: often - urinary tract infections, pharyngitis;
• from the digestive system: very often - diarrhea, nausea; often - dryness of the oral mucosa, vomiting, increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST);
• from the musculoskeletal system: often - myalgia, back pain, musculoskeletal pain, including the chest;
• dermatological reactions: often - skin rash, alopecia.

Adverse events arising from the treatment of patients with chronic viral hepatitis C:

• from the central nervous system: very often - headache, insomnia;
• from the hematopoietic system: very often - anemia;
• from the respiratory system: very often - cough;
• from the digestive system: very often - diarrhea, nausea; often - hyperbilirubinemia;
• from the side of metabolism: very often - decreased appetite;
• from the musculoskeletal system: very often - myalgia;
• dermatological reactions: very often - itching, alopecia;
• others: very often - fever, fatigue, hyperthermia, peripheral edema, asthenia, flu-like condition.

Overdose

Symptoms: against the background of a single dose of 500 mg of eltrombopag - rash, fatigue, transient bradycardia, reversible increase in transaminase activity. Thrombotic and / or thromboembolic complications may develop against the background of a significant increase in the number of platelets.

Treatment: conducting careful monitoring of the platelet count in order to reduce the absorption of eltrombopag - oral administration of drugs containing metal cations (including calcium, aluminum or magnesium).

Treatment with Revolide is continued in accordance with the recommendations for the dosage regimen.

Hemodialysis is ineffective.

special instructions

The safety and therapeutic efficacy of using Revolide for the treatment of myelodysplastic syndromes, thrombocytopenia after chemotherapy and other diseases and conditions accompanied by thrombocytopenia have not been established at present.

Adverse reactions associated with eltrombopag, in most cases, have an early onset, mild to moderate severity and, in rare cases, become the reason for changing the therapy regimen.

It should be borne in mind that taking a 50 mg tablet with a breakfast containing foods high in fat, including dairy, causes a 65% decrease in the C _{max of} eltrombopag. In this regard, during the period of treatment, a diet with a low (less than 50 mg) calcium content should be followed. It should include fruits, fruit juice, cereals without added calcium, iron or magnesium, soy milk, beef and lean ham.

Abnormalities of laboratory parameters of liver function, such as increased activity of ACT, ALT, concentration of indirect bilirubin, proceed without clinically significant symptoms. For the most part, they are mild (1–2 degrees of severity) and reversible.

In patients with HCV, accompanied by thrombocytopenia, cases of hyperbilirubinemia may be indirectly associated with antiviral therapy, including peginterferon or ribavirin.

Assessment of the activity of ACT, ALT and the concentration of bilirubin in serum should be carried out before starting the use of eltrombopag, during dose titration it is necessary to monitor once every 14 days, and after the appointment of a maintenance dose - once every 30 days.

If liver dysfunctions are detected, a re-examination is prescribed within the next 3-5 days. With an increase in the serum concentration of total bilirubin, the level of its individual fractions should be established. If the deviations are confirmed, the monitoring of liver function indicators continues until they stabilize or return to the initial level.

The reason for discontinuation of treatment with Revolide is a three-fold excess of the upper limit of the norm of ALT activity in patients with normal liver function or a three-fold excess compared to the baseline level in persons with increased ALT activity before the start of therapy and the presence of one of the following signs: the progression of the deviation, the persistence of the deviation during 28 or more days, a simultaneous increase in the concentration of direct bilirubin, its combination with signs of decompensation of liver function or clinical symptoms of liver damage.

Treatment with alpha interferons in chronic HCV in patients with cirrhosis of the liver and the simultaneous administration of Revolide can significantly increase the risk of decompensation of liver function, including with a fatal outcome. The risk of liver decompensation is highest in patients with low (less than 3.5 g / dL) baseline albumin levels.

With the cancellation of antiviral therapy due to decompensation of hepatic insufficiency, the use of Revolide is discontinued.

In ITP, thromboembolic complications can occur with low and normal platelet counts. Thrombotic and / or thromboembolic episodes can be manifested by the following conditions: transient ischemic attacks, embolism, including pulmonary embolism, deep vein thrombosis, ischemic stroke, myocardial infarction, suspicion of prolonged reversible ischemic neurological deficit.

It is recommended to accompany the reception of Revolide with careful monitoring of the platelet count, especially in patients with known risk factors for thrombotic and / or thromboembolic complications. If the platelet count exceeds the target values, it is necessary to consider reducing the dose of eltrombopag or completely canceling it.

Among the thrombotic and / or thromboembolic complications in patients with thrombocytopenia and HCV, portal vein thrombosis occurs most often.

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

Due to the increased risk of bleeding after discontinuation of eltrombopag, it is recommended to continue weekly monitoring of the platelet count in the blood for the next 28 days.

Before starting the use of Revolid, it is necessary to assess peripheral blood smears to determine the initial level of morphological changes in cells. This is due to the existing risk of overgrowth or formation of reticulin fibers in the bone marrow. In the course of treatment, the leukocyte formula is calculated once every 30 days. Eltrombopag treatment should be discontinued when existing / new morphological abnormalities (including the appearance of immature leukocytes, teardrop-shaped and nuclear erythrocytes) or cytopenia become stronger.

During the period of taking Revolide, it is recommended to conduct routine monitoring for the progression or development of cataracts.

Influence on the ability to drive vehicles and complex mechanisms

During the period of treatment, it is recommended to be careful when driving and performing potentially dangerous types of work.

Application during pregnancy and lactation

There is no information on the safety and efficacy of eltrombopag during pregnancy. It has not been established whether eltrombopag is excreted in breast milk. Therefore, the use of Revolide during gestation and breastfeeding is possible in cases where the expected therapeutic effect for the mother is higher than the potential risk for the fetus or child.

Pediatric use

The safety and efficacy of using eltrombopag for the treatment of children has not been established.

With impaired renal function

With caution, Revolide tablets should be prescribed in case of impaired renal function.

For violations of liver function

It is possible to use Revolide for the treatment of patients with hepatic insufficiency of 5 or more points on the Child-Pugh scale only in cases where the expected clinical effect of therapy exceeds the potential threat of portal vein thrombosis.

With caution, Revolide should be prescribed to patients with impaired liver function (including liver failure).

If liver function is impaired in patients with chronic HCV (including patients of East Asian origin), the starting dose should be set at 25 mg once a day.

In case of impaired liver function (liver cirrhosis) in patients with ITP (including patients of East Asian origin), the initial daily dose should be 25 mg, its increase is allowed only after 21 days of therapy.

Use in the elderly

When treating elderly patients (65 years and older), the dosage regimen of Revolide is not adjusted; an increased risk of hypersensitivity to eltrombopag should be taken into account.

Drug interactions

Possible interactions with the simultaneous use of Revolide:

• rosuvastatin: there is an increase in the concentration of rosuvastatin in the blood plasma, therefore, if it is necessary to jointly prescribe, the dose of rosuvastatin is recommended to be reduced by 50% of the usual dose;
• lopinavir, ritonavir: Concomitant therapy with lopinavir or ritonavir may cause a decrease in the concentration of eltrombopag.

Analogs

Revolide's analogs are: Ferrogematogen, Sorbifer Durules, Pantogematogen, Ferretab comp., Maltofer, Biofer, Tardiferon, Gino-Tardiferon, Aktiferrin, Ferri-Fall.

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 30 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Revolide

Reviews about Revolide are rare, this may be due to the high cost of the drug. Patients note the effectiveness of the drug during interferon therapy.

The price of Revolide in pharmacies

The price of Revolde for a package containing 28 film-coated tablets with a dosage of 25 mg can be 49,000–66,255 rubles, 50 mg - 77,000–117,583 rubles.

Revolide: prices in online pharmacies

Drug name Price Pharmacy

REVOLADE 25 mg film-coated tablets 28 pcs. RUB 62,000 Buy

REVOLADE 50 mg film-coated tablets 28 pcs. RUB 102,000 Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!