Revolade (eltrombopag) coated tablets 50 mg. №14

Description

Revolade (eltrombopag) coated tablets 50 mg. №14

Composition 

active substance: eltrombopag;

1 tablet contains 25 or 50 mg of eltrombopag (in the form of eltrombopag olamine);

excipients: magnesium stearate, mannitol (E 421), microcrystalline cellulose, povidone K30, sodium starch glycolate (type A); shell Opadry White YS-1-7706-G: hypromellose, macrogol 400, titanium dioxide (E 171), polysorbate 80 (for tablets of 25 mg); shell Opadry Brown 03B26716: hypromellose, titanium dioxide (E 171), macrogol 400, iron oxide yellow (E 172), iron oxide red (E 172) (for tablets of 50 mg).

Medicinal form

Film-coated tablets.

Main physico-chemical properties: tablets of 25 mg: round, biconvex, film-coated tablets of white color with marking GS NX3 and 25 on one side; 50 mg tablets: round, biconvex, film-coated tablets of brown color, marked GS UFU and 50 on one side.

Pharmacotherapeutic group

Antihemorrhagic agents, systemic hemostatics.
ATX code B02B X05.

Pharmacological properties  

Thrombopoietin is the main cytokine involved in the regulation of megakaryopoiesis and platelet formation and is an endogenous ligand for thrombopoietin receptors. Eltrombopag interacts with the transmembrane domain of human thrombopoietin receptors and initiates a cascade of signals similar, but not identical to those triggered by endogenous thrombopoietin, inducing proliferation and differentiation of megakaryocytes from progenitor cells in the bone marrow.

Indication:

• Treatment of patients with chronic immune (idiopathic) thrombocytopenic purpura over one year of age who are not being treated with other drugs (eg, corticosteroids, immunoglobulins).
• Treatment of thrombocytopenia in adult patients with chronic viral hepatitis C, if the degree of thrombocytopenia is a major factor preventing the initiation or limitation of the continuation of optimal interferon-based therapy.
• Treatment of adult patients with acquired severe aplastic anemia (TAA) who have not undergone prior immunosuppressive therapy or who have undergone prior treatment and are not suitable for hematopoietic stem cell transplantation.

Contraindication

Hypersensitivity to eltrombopag or any other component of the drug.

Method of application and dosage

Treatment with Revolade tablets should be initiated and administered under the supervision of a physician experienced in the treatment of hematological diseases or chronic hepatitis C and its complications.

The dosage regimen is individual and based on the number of platelets in each patient. The goal of treatment with eltrombopag is not to normalize the number of platelets.

Treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP)

To achieve and maintain a platelet count ≥ 50,000/μl, the minimum effective dose of eltrombopag should be used. Dose adjustments are based on changes in platelet counts. Eltrombopag should not be used to normalize platelet counts. In clinical studies, an increase in the number of platelets was observed within 1-2 weeks after the start of therapy with eltrombopag and a decrease in their number was observed within 1-2 weeks after stopping the use of the drug.

• Adult patients and children aged 6 to 17 years
  The recommended starting dose of Revolade tablets is 50 mg once a day. Treatment of patients of East/Southeast Asian origin should be started with a reduced dose of 25 mg 1 time per day.
• Children aged 1 to 5 years
  The recommended initial dose of Revolade tablets is 25 mg once a day.
  Treatment of thrombocytopenia in adult patients with chronic HCV.

When using Revolade tablets  in combination with antiviral drugs, you should refer to the instructions for medical use of these drugs.

In clinical trials, increases in platelet counts were generally observed within 1 week of starting treatment with eltrombopag. The goal of treatment should be to achieve the minimum required number of platelets to start antiviral therapy. During antiviral therapy, the goal of treatment should be to maintain the number of platelets at a level that prevents the risk of bleeding, usually 50,000-75,000/μl. Platelet levels > 75,000/μL should be avoided. The lowest effective dose of eltrombopag is used to achieve and maintain the platelet count necessary to initiate and optimize antiviral therapy. Selection of doses is based on restoration of platelet count.

The initial dose of the drug is 25 mg once a day. No dose adjustment is required in patients of East/Southeast Asian origin or patients with mild hepatic impairment.

Severe aplastic anemia

The initial dose of Revolade is 50 mg once a day. For patients of East/Southeast Asian origin, eltrombopag should be started at a dose of 25 mg once daily. Treatment should not be initiated if patients have established cytogenetic defects of chromosome 7.

Children

Revolade tablets is not recommended for the treatment of children under 1 year of age with chronic ITP due to insufficient data on the efficacy and safety of the drug.

Overdose

In clinical trials involving patients with ITP, there was one case of overdose when the patient took 5000 mg of eltrombopag. Reports of adverse reactions included moderate rash, transient bradycardia, fatigue, and elevated transaminases. The level of liver enzymes, measured between the 2nd and 18th day after overdose, increased 1.6 times above the upper limit of normal for AST, 3.9 times – for ALT and 2.4 times – for total bilirubin. The platelet count was 672,000 / μl on the 18th day after overdose, the maximum platelet count was 929,000 / μl. All side effects passed without treatment without complications.

Side effects:

• Infections and invasions: nasopharyngitis, upper respiratory tract infections: rhinitis, pharyngitis, urinary tract infections, influenza, oral herpes, pneumonia, sinusitis, tonsillitis, respiratory infections, gingivitis, skin infections, malignancies and benign tumors ), rectosigmoid cancer.
• From the blood and lymphatic system: anemia, anisocytosis, eosinophilia, hemolytic anemia, leukocytosis, myelocytosis, thrombocytopenia, increased hemoglobin, increased levels of rod-shaped neutrophils, decreased hemoglobin, decreased myelocytes, t myelocytes,
• From the immune system: hypersensitivity.
• From the metabolism: anorexia, hypokalemia, loss of appetite, gout, hypocalcemia, increased levels of uric acid in the blood.
• From the psyche: sleep disorders, depression, apathy, mood swings, tearfulness.
• From the nervous system: paresthesia, hypoaesthesia, drowsiness, migraine, tremor, imbalance, dysesthesia, hemiparesis, migraine with aura, peripheral neuropathy, peripheral sensory neuropathy, speech disorders, toxic neuropathy, vascular headache.
• On the part of the visual organs: dry eyes, blurred vision, lenticular turbidity, astigmatism, cortical cataract, eye pain, increased tearing, retinal hemorrhage, retinal pigment epitheliopathy, decreased visual acuity, impaired visual acuity, visual acuity, testicular dysfunction, ‘junctivitis.
• From the hearing organs: ear pain, vertigo.
• From the cardiovascular system: tachycardia, acute myocardial infarction, cardiovascular disorders, cyanosis, sinus tachycardia, QT prolongation on the electrocardiogram, deep vein thrombosis, embolism, hot flushes, superficial venous thrombophlebitis, superficial veins.
• From the respiratory system: cough, oropharyngeal pain, rhinorrhea, pulmonary embolism, pulmonary infarction, nasal discomfort, blistering and pain in the oropharynx, complications from the nasal sinuses, sleep apnea syndrome.
• From the gastrointestinal tract: nausea, diarrhea (very common – in children with ITP), ulcerative stomatitis, toothache, dry mouth, vomiting, abdominal pain, glossodynia, bleeding in the mouth, abdominal pain, faecal discoloration, bloating , food poisoning, frequent defecation, hematemesis, oral discomfort.
• From the liver and biliary tract: increased levels of alanine aminotransferase *, aspartate aminotransferase * and blood bilirubin, liver dysfunction, cholestasis, liver damage, hepatitis, drug-induced liver damage
• From the skin and subcutaneous tissue: rash, alopecia, hyperhidrosis, generalized itching, urticaria, dermatosis, petechiae, cold sweats, erythema, melanosis, pigmentation disorders, skin discoloration, skin peeling.
• From the musculoskeletal system and connective tissue: myalgia, muscle cramps, bone pain, back pain, musculoskeletal pain, muscle weakness.
• From the urinary system: renal failure, leukocyturia, lupus nephritis, nocturia, proteinuria, increased levels of urea and creatinine in the blood, increased protein / creatinine in the urine.
• From the reproductive system: menorrhagia.
• General disorders: chest pain, fever, hemorrhage at the puncture site, asthenia, anxiety, inflammation of wounds, malaise, pyrexia, foreign body sensation.
• Laboratory data: increase in blood albumin, increase in alkaline blood phosphatase, increase in total protein level, decrease in blood albumin, increase in urine pH.