Eltrombopag Glenmark: Uses, Dosage & Side Effects

What Is Eltrombopag Glenmark and What Is It Used For?

Eltrombopag Glenmark contains the active substance eltrombopag, a small-molecule, non-peptide thrombopoietin receptor agonist (TPO-RA). Eltrombopag belongs to the pharmacological class of antihemorrhagic agents and was specifically developed to address thrombocytopenia, a condition characterized by abnormally low platelet counts in the blood. Platelets (thrombocytes) are small, disc-shaped blood cells produced in the bone marrow by large precursor cells called megakaryocytes. They play a critical role in hemostasis, the process by which bleeding is stopped after vascular injury. When platelet counts fall below a certain threshold, patients become susceptible to spontaneous bleeding, bruising, and potentially life-threatening hemorrhage.

The primary physiological regulator of platelet production is thrombopoietin (TPO), a glycoprotein hormone produced mainly by the liver. TPO binds to its receptor, c-Mpl (also known as the TPO receptor), which is expressed on the surface of hematopoietic stem cells, megakaryocyte progenitor cells, and mature megakaryocytes in the bone marrow. When TPO engages c-Mpl, it triggers a cascade of intracellular signaling events, including activation of the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways, the mitogen-activated protein kinase (MAPK) pathway, and the phosphatidylinositol 3-kinase (PI3K) pathway. These signals collectively promote the survival, proliferation, and differentiation of megakaryocyte progenitors into mature, polyploid megakaryocytes that ultimately shed platelets into the bloodstream.

Eltrombopag was designed to mimic the platelet-stimulating effects of endogenous TPO, but through a distinct mechanism. Unlike TPO itself and other recombinant TPO mimetics (such as romiplostim) that bind to the extracellular domain of c-Mpl, eltrombopag interacts with the transmembrane domain of the receptor at a site that does not overlap with the TPO binding site. This unique binding characteristic means that eltrombopag activates c-Mpl through a complementary but independent mechanism, resulting in activation of the JAK-STAT and MAPK signaling cascades that drive megakaryopoiesis. Because eltrombopag binds at a different site than endogenous TPO, it does not compete with the body's own thrombopoietin and can provide an additive stimulus to platelet production.

Eltrombopag Glenmark is approved for use in the following clinical indications:

• Chronic immune thrombocytopenia (ITP): ITP is an autoimmune disorder in which the immune system produces antibodies against platelet surface glycoproteins, leading to accelerated platelet destruction in the spleen and, in many patients, inadequate compensatory platelet production by the bone marrow. Eltrombopag is indicated for adult and pediatric patients (aged 1 year and older) with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. In the pivotal RAISE trial, a randomized, double-blind, placebo-controlled study of 197 adults with chronic ITP, eltrombopag significantly increased platelet counts above 50,000 per microliter in 79% of patients compared with 28% of those receiving placebo. The PETIT2 trial demonstrated similar efficacy in pediatric patients aged 1 to 17 years.
• Hepatitis C virus (HCV)-associated thrombocytopenia: Patients with chronic HCV infection frequently develop thrombocytopenia as a consequence of liver fibrosis, portal hypertension, and decreased hepatic TPO production. Low platelet counts can prevent the initiation or continuation of interferon-based antiviral therapy, which itself can further suppress platelet production. Eltrombopag is indicated to allow the initiation and maintenance of interferon-based antiviral therapy in adult patients with HCV-associated thrombocytopenia where the degree of thrombocytopenia is the main factor preventing initiation or limiting the ability to maintain optimal interferon-based therapy. The ENABLE 1 and ENABLE 2 trials demonstrated that eltrombopag allowed significantly more patients to initiate and maintain antiviral therapy compared with placebo.
• Acquired severe aplastic anemia (SAA): SAA is a rare, life-threatening bone marrow failure disorder characterized by pancytopenia (deficiency of all blood cell types) and a hypocellular bone marrow. Standard first-line treatment for SAA in patients who are not candidates for hematopoietic stem cell transplantation is immunosuppressive therapy (IST) with horse anti-thymocyte globulin (ATG) and ciclosporin. Eltrombopag is indicated in combination with standard IST for first-line treatment of adult patients with SAA, and as monotherapy for adult patients with SAA who are refractory to prior IST and who are not eligible for hematopoietic stem cell transplantation. The landmark NIH study by Townsley et al. (2017) demonstrated that the addition of eltrombopag to standard IST significantly improved overall hematologic response rates in treatment-naive SAA patients.

Eltrombopag Glenmark, manufactured by Glenmark Pharmaceuticals, is a generic formulation that has been demonstrated to be bioequivalent to the originator product (marketed as Revolade in Europe and Promacta in the United States by Novartis). Bioequivalence means that the generic product delivers the same amount of active substance to the bloodstream at the same rate as the originator, ensuring comparable clinical efficacy and safety. The availability of this generic formulation provides an important option for improving patient access to this essential medication, particularly in healthcare systems where cost considerations play a significant role in treatment decisions.

What Should You Know Before Taking Eltrombopag Glenmark?

Contraindications

The only absolute contraindication to eltrombopag use is hypersensitivity (allergy) to eltrombopag or to any of the excipients contained in the formulation. The excipients in Eltrombopag Glenmark film-coated tablets include magnesium stearate, mannitol, microcrystalline cellulose, povidone, sodium starch glycolate, and a film-coating containing hypromellose, titanium dioxide, macrogol, and iron oxides. If you have a known allergy to any of these substances, you must not use this medication and should inform your doctor immediately.

While not absolute contraindications, several conditions require careful evaluation before starting eltrombopag treatment, and in some cases, the risks may outweigh the benefits. Your healthcare provider will assess your individual situation and determine whether eltrombopag is appropriate for you.

Warnings and Precautions

Before starting eltrombopag, discuss the following with your healthcare provider:

• Liver disease: Eltrombopag is extensively metabolized by the liver and can cause hepatotoxicity, including elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Patients with pre-existing liver disease, including those with chronic HCV infection and cirrhosis, are at increased risk. In clinical trials, elevations in ALT to 3 or more times the upper limit of normal were observed in approximately 10% of patients. Hepatotoxicity was generally reversible upon dose reduction or discontinuation. If you have liver disease, your starting dose may need to be reduced, and more frequent monitoring will be required.
• Thromboembolic events: Although eltrombopag is designed to increase platelet counts, excessive platelet elevation can increase the risk of thrombotic and thromboembolic events, including deep vein thrombosis (DVT), pulmonary embolism (PE), transient ischemic attack (TIA), and portal vein thrombosis. This risk is particularly relevant in patients with chronic liver disease, who already have an increased baseline thrombotic risk due to altered hemostatic balance. If you have risk factors for thromboembolism (such as Factor V Leiden, antithrombin III deficiency, antiphospholipid syndrome, prolonged immobility, or a personal or family history of blood clots), inform your doctor before starting treatment. Platelet counts should not be raised above the levels necessary to prevent clinically significant bleeding.
• Bone marrow reticulin formation: Thrombopoietin receptor agonists, including eltrombopag, may increase the risk of development or progression of reticulin fibers in the bone marrow. Reticulin is a type of connective tissue fiber that, when deposited excessively, can lead to bone marrow fibrosis with cytopenias (reduced blood cell counts). A peripheral blood smear should be examined prior to initiating eltrombopag and regularly during treatment to detect abnormalities (such as teardrop-shaped red blood cells, nucleated red blood cells, or immature white blood cells) that may suggest bone marrow fibrosis. If new or worsening morphological abnormalities are detected, consider bone marrow biopsy, including staining for fibrosis.
• Cataracts: In toxicology studies, eltrombopag was found to cause cataracts in rodents. While a causal relationship with cataract formation in humans has not been conclusively established, cataracts have been observed in clinical trials. Regular ophthalmological examinations are recommended before and during treatment with eltrombopag.
• Rebound thrombocytopenia: Upon discontinuation of eltrombopag, platelet counts may fall below pre-treatment baseline levels within 2 weeks, potentially increasing the risk of bleeding. This rebound effect occurs because the exogenous stimulus to platelet production is removed while the underlying condition persists. Following discontinuation, platelet counts should be monitored weekly for at least 4 weeks, and additional management of thrombocytopenia should be considered based on clinical judgment.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before using Eltrombopag Glenmark. There are limited data on the use of eltrombopag in pregnant women. Animal reproductive studies have shown some evidence of developmental toxicity at doses that also produced maternal toxicity. The potential risk to a human fetus is unknown. Eltrombopag should not be used during pregnancy unless the potential benefit to the mother clearly justifies the potential risk to the fetus. Women of childbearing potential should use effective contraception during treatment.

It is not known whether eltrombopag or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. The decision to continue or discontinue breastfeeding, or to continue or discontinue eltrombopag therapy, should be made in consultation with your doctor, taking into account the benefit of breastfeeding for the child and the benefit of eltrombopag therapy for the mother.

Children and Adolescents

Eltrombopag is approved for the treatment of chronic ITP in children aged 1 year and older who have had an insufficient response to other treatments. The safety and efficacy in pediatric patients were established in the PETIT and PETIT2 clinical trials. Eltrombopag is not approved for use in children under 1 year of age for ITP, and it is not indicated for children with HCV-associated thrombocytopenia or severe aplastic anemia. Dosing in pediatric patients is weight-based and differs from adult dosing; consult your healthcare provider for age-appropriate dosing information.

Patients of East Asian Ancestry

Pharmacokinetic studies have demonstrated that patients of East Asian ancestry (including Chinese, Japanese, Korean, and Taiwanese individuals) have approximately 50% higher exposure to eltrombopag compared with non-East Asian patients at the same dose level. This is likely due to pharmacogenomic differences in drug-metabolizing enzymes. As a result, a reduced starting dose (25 mg once daily for ITP instead of 50 mg) is recommended for patients of East Asian descent. Your doctor will adjust your dose based on your individual platelet count response, but the lower starting dose is important to reduce the risk of excessive platelet elevation and associated complications.

How Does Eltrombopag Glenmark Interact with Other Drugs?

Eltrombopag has several clinically significant drug interactions that healthcare providers and patients should be aware of. Understanding these interactions is essential for ensuring the medication works effectively and for avoiding potentially harmful consequences. The interactions with eltrombopag can be broadly divided into those affecting eltrombopag absorption, those involving hepatic metabolism, and those mediated by drug transporter inhibition.

Major Interactions

The most clinically significant interaction involves polyvalent cations. Eltrombopag forms chelate complexes with polyvalent metal cations such as aluminum, calcium, iron, magnesium, selenium, and zinc. These chelates are insoluble and cannot be absorbed from the gastrointestinal tract, resulting in drastically reduced bioavailability of eltrombopag. In pharmacokinetic studies, co-administration of eltrombopag with an aluminum/magnesium-containing antacid reduced eltrombopag systemic exposure (AUC) by approximately 70% and peak plasma concentration (Cmax) by approximately 70%. Similarly, taking eltrombopag with a high-calcium meal reduces absorption substantially. This is why eltrombopag must always be taken on an empty stomach, with a minimum 4-hour separation from any products containing polyvalent cations.

Minor Interactions and Monitoring Considerations

Eltrombopag is a potent inhibitor of the organic anion transporting polypeptide 1B1 (OATP1B1) and the breast cancer resistance protein (BCRP), two important drug transporters involved in the hepatic uptake and intestinal efflux of many medications. By inhibiting OATP1B1, eltrombopag can increase the hepatic and systemic exposure of drugs that rely on this transporter for their elimination, most notably rosuvastatin. In clinical interaction studies, eltrombopag increased rosuvastatin AUC by 55% and Cmax by 103%. Patients receiving rosuvastatin or other OATP1B1 substrates (such as atorvastatin, bosentan, or repaglinide) should be monitored for increased toxicity, and dose reductions of the co-administered drug should be considered.

Eltrombopag is metabolized primarily by CYP1A2 and CYP2C8, with additional contributions from UGT1A1 and UGT1A3 (glucuronidation). Potent inducers of CYP1A2 (such as tobacco smoke, rifampicin, or carbamazepine) may modestly decrease eltrombopag exposure, although the clinical significance of this interaction is limited. Eltrombopag does not appear to be a significant inhibitor or inducer of major CYP enzymes at therapeutic concentrations, so it is unlikely to affect the metabolism of most co-administered drugs through CYP-mediated pathways.

When eltrombopag is used in combination with ciclosporin for the treatment of severe aplastic anemia, it is important to note that ciclosporin may reduce eltrombopag plasma concentrations. The mechanism is thought to involve BCRP inhibition affecting eltrombopag distribution and possibly enterohepatic recirculation. Platelet counts should be monitored closely during concurrent use, and the eltrombopag dose may need to be increased to maintain the desired platelet response.

What Is the Correct Dosage of Eltrombopag Glenmark?

Eltrombopag dosing is highly individualized and based on the specific indication, the patient's platelet count response, ancestry, hepatic function, and other clinical factors. The goal of treatment is to achieve and maintain a platelet count sufficient to reduce the risk of bleeding, not to normalize the platelet count. For ITP, the target platelet count is generally 50,000 per microliter or above. Treatment should be initiated and supervised by a physician experienced in the management of hematologic conditions.

Adults with Chronic ITP

Dose adjustments should follow a structured algorithm. If the platelet count remains below 50,000 per microliter after at least 2 weeks of treatment, the dose may be increased by 25 mg to a maximum of 75 mg daily. If the platelet count is between 50,000 and 200,000 per microliter, maintain the current dose. If the platelet count exceeds 200,000 per microliter, reduce the dose by 25 mg and reassess after 2 weeks. If the platelet count exceeds 400,000 per microliter, stop eltrombopag and monitor platelet counts twice weekly. Once the count falls below 150,000, consider restarting at a dose reduced by 25 mg from the previous dose.

Children with Chronic ITP

Pediatric dosing follows similar principles to adult dosing, with the initial dose selected based on age and ancestry. Children aged 1 to 5 years start at a lower dose of 25 mg due to pharmacokinetic considerations. The dose is titrated in the same stepwise fashion as in adults, with platelet counts monitored at least every 2 weeks during the dose adjustment phase. Parents and caregivers should be educated about the importance of taking eltrombopag on an empty stomach and separating it from calcium-containing foods and supplements.

Adults with HCV-Associated Thrombocytopenia

In the HCV-associated thrombocytopenia indication, dosing starts lower at 25 mg daily because these patients typically have underlying liver disease that affects eltrombopag metabolism and increases the risk of hepatotoxicity. However, the maximum dose is higher (100 mg daily) compared with ITP, reflecting the need for greater platelet stimulation in some patients with advanced liver disease. Liver function tests must be monitored particularly closely in this patient population, and eltrombopag should be discontinued if antiviral therapy is stopped.

Adults with Severe Aplastic Anemia

The dosing paradigm for SAA differs significantly from ITP and HCV-associated thrombocytopenia. In the first-line setting (combined with ATG and ciclosporin), eltrombopag is started at a higher dose of 150 mg daily from Day 1 of immunosuppressive therapy and continued for 6 months. This approach is based on evidence from clinical trials demonstrating that early, high-dose eltrombopag stimulation of hematopoiesis, combined with immunosuppression, yields superior response rates. Patients of East Asian ancestry should start at 75 mg daily. For refractory SAA, the approach is more conservative, starting at 50 mg and titrating upward based on response.

Missed Dose

If you miss a dose of eltrombopag, take it as soon as you remember on the same day, provided you can still maintain the required separation from food and polyvalent cation-containing products. If it is already close to the time of your next dose, skip the missed dose and take the next dose at the regular time. Do not take a double dose to make up for a missed dose, as this could lead to an excessive rise in platelet count and increase the risk of thromboembolic events.

Overdose

In clinical studies, cases of eltrombopag overdose have been reported at doses up to 5,000 mg. In these cases, platelet counts rose substantially above normal levels but returned to baseline after the drug was discontinued. The primary concern with overdose is excessive platelet elevation leading to thromboembolic events. If overdose is suspected, eltrombopag should be stopped immediately, platelet counts should be monitored at least twice weekly, and treatment should be restarted at a reduced dose once platelet counts return to the target range.

What Are the Side Effects of Eltrombopag Glenmark?

Like all medicines, eltrombopag can cause side effects, although not everybody gets them. The side effect profile has been well characterized through extensive clinical trial programs involving thousands of patients across the three approved indications (ITP, HCV-associated thrombocytopenia, and SAA), as well as through post-marketing surveillance. The frequency and type of side effects can vary depending on the underlying condition being treated, as patients with different diseases have different baseline health profiles and concomitant medications.

Side effects are classified below according to their frequency based on clinical trial data. It is important to note that some side effects, particularly hepatotoxicity and thromboembolic events, can be serious and may require immediate medical attention. If you experience any unusual symptoms during treatment, contact your healthcare provider promptly.

Hepatotoxicity deserves special emphasis as it is one of the most clinically significant adverse effects of eltrombopag. In clinical trials for ITP, elevations in ALT to 3 or more times the upper limit of normal occurred in approximately 10% of patients. Most cases were mild to moderate, reversible upon dose reduction or discontinuation, and not associated with clinically significant liver injury. However, rare cases of severe hepatotoxicity with jaundice and hepatic decompensation have been reported in post-marketing surveillance. The risk appears to be higher in patients with pre-existing liver disease, particularly those with chronic HCV infection and cirrhosis.

Thromboembolic events are another important safety concern. In clinical trials across all indications, thromboembolic events occurred in approximately 4% to 6% of eltrombopag-treated patients, compared with 2% to 3% of placebo-treated patients. Events reported include deep vein thrombosis, pulmonary embolism, transient ischemic attack, myocardial infarction, and portal vein thrombosis (the latter particularly in patients with chronic liver disease). The risk of thromboembolism appears to correlate with the degree of platelet elevation and the presence of pre-existing risk factors for thrombosis.

Bone marrow reticulin fiber formation has been observed in bone marrow biopsies of patients treated with eltrombopag and other TPO receptor agonists. In most cases, the reticulin deposition is mild (grade 1 to 2 on the European consensus grading scale) and does not progress to clinically significant bone marrow fibrosis. However, progression to myelofibrosis with collagen deposition has been reported in rare cases. Peripheral blood smear monitoring for morphological abnormalities suggestive of bone marrow fibrosis (teardrop cells, nucleated red blood cells, immature granulocytes) should be performed regularly, and bone marrow biopsy should be considered if abnormalities are detected.

How Should You Store Eltrombopag Glenmark?

Proper storage of Eltrombopag Glenmark is important to maintain the quality, efficacy, and safety of the medication throughout its shelf life. Film-coated tablets should be stored at a temperature not exceeding 30°C (86°F). The tablets should be kept in their original packaging (blister pack or bottle, as applicable) to protect them from moisture and light, both of which can degrade the active substance and affect the integrity of the film coating.

Do not store Eltrombopag Glenmark in the bathroom, near a sink, or in other damp environments, as humidity can compromise the tablet formulation. Do not freeze the tablets. Keep the medication out of the sight and reach of children. If the packaging appears damaged or the tablets show any visible changes in appearance (such as discoloration, crumbling, or an unusual odor), do not use them and consult your pharmacist about proper disposal.

Do not use Eltrombopag Glenmark after the expiry date (EXP) stated on the carton and blister or bottle label. The expiry date refers to the last day of that month. Do not dispose of medications in household waste or via wastewater. Return any unused or expired medication to your pharmacy for safe disposal in accordance with local regulations. Proper disposal of pharmaceuticals helps protect the environment and prevents accidental ingestion by others.

What Does Eltrombopag Glenmark Contain?

Eltrombopag Glenmark film-coated tablets contain the active substance eltrombopag, present in the formulation as eltrombopag olamine (the olamine salt form). Eltrombopag olamine is a white to yellowish powder that is practically insoluble in water at neutral pH but soluble in aqueous solutions at pH 2 and below. The olamine salt was selected for pharmaceutical development because it provides favorable physicochemical properties for oral tablet formulation, including improved stability and manufacturability compared with the free acid form.

Each 12.5 mg film-coated tablet contains 12.5 mg of eltrombopag (equivalent to approximately 15.8 mg of eltrombopag olamine). The tablet core consists of the following inactive ingredients (excipients): magnesium stearate (lubricant), mannitol (diluent/filler), microcrystalline cellulose (binder and filler), povidone (binder), and sodium starch glycolate (disintegrant). These excipients serve standard pharmaceutical functions to ensure the tablet can be manufactured consistently, maintains its structural integrity during storage and handling, and disintegrates appropriately in the gastrointestinal tract to release the active substance for absorption.

The film coating of the tablet contains hypromellose (hydroxypropyl methylcellulose, a coating polymer), macrogol (polyethylene glycol, a plasticizer), titanium dioxide (an opacifier that gives the tablet its white base color), and iron oxides (colorants). The film coating serves multiple purposes: it protects the tablet core from moisture, masks the taste of the active substance, facilitates swallowing, and provides a distinctive visual appearance to aid in product identification and reduce the risk of medication errors.

The chemical name of eltrombopag is 3'-{(2Z)-2-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]hydrazino}-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid. It has a molecular formula of C₂₅H₂₂N₄O₄ and a molecular weight of 442.47 g/mol. Eltrombopag is a synthetic, non-peptide compound that was discovered through high-throughput screening and subsequent medicinal chemistry optimization, specifically designed to interact with the transmembrane domain of the human TPO receptor.