Description

Elbonix 50mg tablets, containing the active ingredient Eltrombopag, are imported into Pakistan and are available in packs of 28 tablets. Eltrombopag is primarily used to treat conditions associated with low platelet counts, such as chronic immune thrombocytopenic purpura (ITP) and thrombocytopenia related to chronic hepatitis C virus (HCV) infection. It functions as a thrombopoietin receptor agonist, stimulating the production of platelets in the bone marrow, which is essential for blood clotting and reducing the risk of bleeding.

Key Information about Elbonix 50mg

• Generic Name: Eltrombopag
• Formulation: Tablet
• Pack Size: 28 tablets
• Indications:
  • Chronic ITP
  • Chronic hepatitis C-related thrombocytopenia
  • Severe aplastic anemia
    

    Key Benefits of Elbonix 50mg

    • Increases Platelet Counts: Elbonix effectively raises and maintains platelet levels in patients with chronic immune thrombocytopenic purpura (ITP) and those with chronic hepatitis C virus (HCV) infection.
    • Treatment of Severe Aplastic Anemia: It is also indicated for managing severe aplastic anemia, a condition where the bone marrow fails to produce sufficient blood cells.
    • Oral Administration: The tablet form allows for convenient oral intake, making it easier for patients to adhere to their treatment regimens.
    • Thrombopoietin Receptor Agonist: As a thrombopoietin receptor agonist, it stimulates the production of platelets in the bone marrow, which is crucial for preventing excessive bleeding.

    Key Ingredients

    • Eltrombopag Olamine: The active ingredient in Elbonix, Eltrombopag, is a small-molecule TPO-receptor agonist that interacts with the thrombopoietin receptor, promoting the proliferation and differentiation of bone marrow progenitor cells into platelets.
    

    Eltrombopag

    Medication used to treat thrombocytopenia and severe aplastic anemia

    

    More

    Trade names

    Promacta, Revolade, Alvaiz

    Other names

    SB-497115-GR

    Discovery

    Resulted from research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals, now marketed by Novartis
    Eltrombopag, the active ingredient in Elbonix 50mg tablets, functions as a thrombopoietin (TPO) receptor agonist. Its mechanism of action involves several key processes:

    Mechanism of Action

    • TPO Receptor Interaction: Eltrombopag is a small-molecule agonist that binds to the transmembrane domain of the human TPO receptor. This interaction is crucial for initiating downstream signaling pathways.
    • Stimulation of Platelet Production: Upon binding to the TPO receptor, Eltrombopag activates signaling cascades that promote the proliferation and differentiation of bone marrow progenitor cells into megakaryocytes, the precursor cells that produce platelets.
    • Increased Platelet Counts: By enhancing the production of megakaryocytes, Eltrombopag ultimately leads to an increase in platelet counts in the bloodstream, which is essential for reducing the risk of bleeding in patients with conditions like chronic immune thrombocytopenic purpura (ITP) and thrombocytopenia associated with chronic hepatitis C virus (HCV) infection.

    Effects on Bone Marrow Progenitor Cells

    • Stimulation of Hematopoietic Stem and Progenitor Cells: Eltrombopag directly stimulates hematopoietic stem cells (HSCs) and megakaryocytes, promoting their proliferation and differentiation. This results in an increase in the number of progenitor cells that can develop into mature blood cells, particularly platelets.
    • Enhanced Hematopoiesis: The drug facilitates multi-lineage hematopoiesis, which is the process by which stem cells differentiate into various types of blood cells. Eltrombopag has been shown to selectively augment the expansion of specific progenitor cell populations, such as CD34+ and CD41+ cells, in the bone marrow.
    • Support from Mesenchymal Stem Cells: Eltrombopag also influences mesenchymal stem/stromal cells (MSCs), which play a crucial role in the hematopoietic niche. It enhances the hematopoietic-supporting ability of MSCs, thereby improving the overall environment for blood cell production in the bone marrow. This effect includes alterations in gene expression related to oxygen homeostasis and a decrease in adipogenic differentiation of MSCs.
    • Potential Induction of Bone Marrow Fibrosis: While Eltrombopag is effective in increasing platelet production, there is evidence suggesting that long-term use may lead to adverse effects, such as the induction of bone marrow fibrosis in some patients, particularly those undergoing hematopoietic stem cell transplantation.

    Eltrombopag, the active ingredient in Elbonix 50mg tablets, has several important effects on the immune system:

    Modulation of Monocytes and Macrophages

    • Eltrombopag therapy decreases the peripheral monocyte count and IFN-γ/IL-4 ratio in immune thrombocytopenic purpura (ITP) patients.
    • It partially reverses the M1-related characteristics of ITP macrophages, suggesting a role in regulating monocyte/macrophage plasticity.

    Regulation of T Cell Function

    • Eltrombopag mediates MPL signaling through the JAK2-STAT3 pathway, inducing inhibition of IFN-γ signaling in T cells in ITP mathematical models.
    • The increased platelets mediated by eltrombopag may also play an immunomodulatory role in monocytes/macrophages in ITP.

    Enhancement of Hematopoietic Support by Mesenchymal Stem Cells

    • Eltrombopag increases the hematopoietic-supporting ability of mesenchymal stem/stromal cells (MSCs), improving the bone marrow environment for blood cell production.
    • It decreases adipogenic differentiation of MSCs and alters gene expression related to oxygen homeostasis.

    Selective Expansion of Hematopoietic Stem and Progenitor Cells

    • Eltrombopag selectively augments the expansion of human CD45+, CD34+, and CD41+ cells in the bone marrow compartment.
    • It enhances the expansion of hematopoietic stem and progenitor cells of human umbilical cord blood in vivo and in vitro.

    Avoid Certain Foods, Drinks, and Medicines

    • Eltrombopag should be taken at least 2 hours before or 4 hours after any products containing high concentrations of calcium, iron, magnesium, aluminum, selenium or zinc.
    • This includes antacids, dairy products, mineral supplements, fortified cereals, and some protein shakes.
    • Concomitant administration with high-calcium foods or antacids containing aluminum and magnesium can significantly reduce the bioavailability of eltrombopag.

    Take with Low-Calcium Foods

    • Foods low in calcium (<50 mg calcium), such as lean meats, white fish, non-leafy vegetables, fruits, unfortified fruit juice, and black coffee/tea, are recommended.
    • Low-calcium meals do not significantly affect the pharmacokinetics of eltrombopag.

    Dosing Instructions

    • Swallow the tablet whole. Do not crush, break, or chew it.
    • Do not mix the tablet with food or liquids.
    • If using the oral suspension, follow the specific instructions provided with the medication.

    Monitor for Interactions

    • Certain medicines like statins, HIV drugs, chemotherapy, and anticoagulants may interact with eltrombopag.
    • Inform your doctor about all other medications you are taking.

    Overview of Interactions

    • Total Interactions: Eltrombopag is known to interact with 177 drugs, categorized into 22 major, 152 moderate, and 3 minor interactions. Additionally, there are interactions with certain diseases and food/alcohol.

    Major Drug Interactions

    • Antacids and Supplements: Eltrombopag should not be taken with antacids or supplements containing calcium, aluminum, iron, magnesium, or zinc, as these can significantly reduce its absorption. It is advised to take eltrombopag at least 2 hours before or 4 hours after these products.
    • Cholesterol-Lowering Drugs: Medications like rosuvastatin, atorvastatin, and other statins may have increased side effects when taken with eltrombopag, including muscle pain. Dosages may need adjustment.
    • Other Medications: Caution is advised when using eltrombopag with:
      • Imatinib: May increase eltrombopag levels.
      • Ibuprofen and Ketorolac: Eltrombopag can increase levels of these medications, necessitating close monitoring.
      • Hydromorphone and Indomethacin: Similar interactions where eltrombopag affects metabolism, requiring monitoring.

    Food and Alcohol Interactions

    • Calcium-Rich Foods: High-calcium foods can interfere with the absorption of eltrombopag, so they should be avoided around the time of taking the medication.
    • Alcohol: There are noted interactions with alcohol, which can exacerbate side effects or alter the effectiveness of the medication.

    Disease Interactions

    • Patients with conditions such as hepatitis C, hepatotoxicity, cataracts, and those at risk for thrombotic complications should use eltrombopag with caution, as these conditions can be exacerbated by the medication.

    Dosage

    The dosage of Elbonix (eltrombopag) varies depending on the condition being treated and the patient’s response to therapy. Here are some key points about the dosage:

    • For chronic immune thrombocytopenic purpura (ITP), the starting dose is typically 50 mg once daily. The dose may be adjusted based on the platelet count, not exceeding 75 mg daily.
    • In patients with chronic hepatitis C-related thrombocytopenia, the starting dose is 25 mg once daily. The maximum dose is 100 mg daily.
    • For severe aplastic anemia, the starting dose is 150 mg once daily for adults and children 12 years and older. For children under 12, the starting dose is 75 mg once daily for ages 6-11 and 2.5 mg/kg once daily for ages 2-5.
    • Dose adjustments are made based on the patient’s platelet count, typically in 25 mg increments. Excessive platelet counts above 400 x 10^9/L require withholding the drug until the count drops below 150 x 10^9/L.

    Storage

    Elbonix tablets should be stored at room temperature between 59°F and 86°F (15°C and 30°C). The tablets should be kept in the original bottle.The oral suspension form should be stored at room temperature between 68°F to 77°F (20°C to 25°C). After mixing, the suspension should be taken immediately but may be stored for up to 30 minutes at room temperature.

    Reviews

    Elbonix (eltrombopag) has been shown to effectively increase platelet counts in patients with chronic ITP and hepatitis C-related thrombocytopenia. In clinical trials for severe aplastic anemia, eltrombopag in combination with standard immunosuppressive therapy demonstrated improved blood cell counts compared to placebo.

    Liver Dysfunction Incidence

    • Common Adverse Effect: Liver dysfunction is a recognized adverse reaction to eltrombopag. Studies indicate that approximately 22.4% of patients experience liver dysfunction during treatment, with elevated levels of liver enzymes such as ALT (alanine aminotransferase) and AST (aspartate aminotransferase) being common findings.
    • Severity of Liver Dysfunction: The majority of cases are classified as mild (grade 1), with some cases reaching moderate (grade 2) or severe (grade 3) levels. Symptoms of liver dysfunction can include elevated liver enzymes and bilirubin levels, but most cases are reversible upon discontinuation of the drug or dose adjustment.

    Mechanism of Impact

    • Metabolism and Elimination: Eltrombopag is primarily metabolized in the liver, which plays a crucial role in its elimination. As liver function declines, the pharmacokinetics of eltrombopag can be altered, leading to increased exposure and potential toxicity.
    • Monitoring Requirements: Due to the risk of hepatotoxicity, regular monitoring of liver function tests (LFTs) is essential. Patients are advised to have their ALT, AST, and bilirubin levels checked before starting treatment, every two weeks during dose adjustments, and monthly once a stable dose is established.

    Risk Factors for Liver Dysfunction

    • Certain comorbidities, such as type 2 diabetes and non-inflammatory hepatobiliary diseases (e.g., gallbladder stones, fatty liver), have been identified as risk factors for developing liver dysfunction during eltrombopag treatment. Patients with these conditions may require closer monitoring and potential dose adjustments.