Eltrombopag STADA

What Is Eltrombopag STADA and What Is It Used For?

Eltrombopag STADA contains the active substance eltrombopag olamine, a small-molecule, non-peptide agonist of the thrombopoietin (TPO) receptor, also known as c-Mpl. Unlike recombinant thrombopoietin or peptide-based TPO mimetics, eltrombopag binds to the transmembrane domain of the TPO receptor rather than the extracellular domain. This means it does not compete with endogenous thrombopoietin and can work synergistically with the body's own platelet-stimulating signals.

The medicine is classified as a thrombopoietin receptor agonist (TPO-RA). By activating intracellular JAK/STAT and MAPK signalling pathways, eltrombopag stimulates the proliferation and differentiation of megakaryocyte progenitor cells in the bone marrow. These megakaryocytes are the precursor cells that produce platelets. The result is an increase in circulating platelet count, typically beginning within 1 to 2 weeks of initiating treatment.

Eltrombopag STADA is a generic medicine manufactured by STADA Arzneimittel AG. It has been demonstrated to be bioequivalent to the originator product through rigorous bioequivalence studies assessed by the European Medicines Agency (EMA). This means that Eltrombopag STADA delivers the same active substance at the same rate and extent as the reference medicine, ensuring equivalent efficacy and safety.

Approved Indications

Eltrombopag is approved for several haematological conditions where platelet production is insufficient:

• Chronic Immune Thrombocytopenia (ITP): For adults and children aged 1 year and older who have chronic ITP and have had an insufficient response to other treatments (such as corticosteroids, immunoglobulins, or splenectomy). ITP is an autoimmune condition in which the immune system destroys platelets, leading to an increased risk of bleeding.
• Severe Aplastic Anemia (SAA): For adult patients with acquired severe aplastic anemia who have had an insufficient response to prior immunosuppressive therapy and who are unsuitable for haematopoietic stem cell transplantation. In SAA, the bone marrow fails to produce adequate blood cells, including platelets.
• Hepatitis C-associated Thrombocytopenia: In some regions, eltrombopag may be used to allow patients with chronic hepatitis C and thrombocytopenia to initiate and maintain interferon-based antiviral therapy that would otherwise not be feasible due to low platelet counts.

It is important to understand that eltrombopag is not used to normalise platelet counts. The treatment goal is to achieve and maintain a platelet level sufficient to reduce the risk of clinically significant bleeding, typically above 50 × 10⁹/L. Excessive platelet elevation carries its own risks, including thromboembolic events.

What Should You Know Before Taking Eltrombopag STADA?

Before starting treatment with Eltrombopag STADA, your prescribing haematologist will conduct a thorough assessment of your medical history, current medications, and overall health status. Several important factors must be considered to ensure that eltrombopag is both safe and appropriate for your specific situation. Understanding these precautions is essential for optimising treatment outcomes and minimising potential risks.

Contraindications

Eltrombopag STADA must not be used in the following circumstances:

• Hypersensitivity: Known allergy to eltrombopag olamine or any of the excipients in the formulation. Allergic reactions may include rash, urticaria, swelling of the face or throat, or anaphylaxis.
• Severe hepatic impairment: Patients with a Child-Pugh score of 7 or above (moderate to severe liver cirrhosis) should not use eltrombopag, as the drug is extensively metabolised in the liver and hepatotoxicity is a known risk.

Warnings and Precautions

Your doctor should be informed about the following conditions before prescribing eltrombopag:

• Hepatotoxicity: Eltrombopag can cause elevations in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Liver function tests (LFTs) must be performed before initiation, every two weeks during dose titration, and monthly once a stable dose is established. If ALT levels rise to ≥3 times the upper limit of normal (ULN) and are progressive, persistent for ≥4 weeks, accompanied by elevated direct bilirubin, or accompanied by clinical symptoms of liver injury, eltrombopag should be discontinued.
• Thrombotic and thromboembolic events: Elevated platelet counts from TPO-RA therapy may increase the risk of thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, and myocardial infarction. This risk is particularly relevant in patients with known thrombophilia, those who are immobilised, or those taking other medications that increase clotting risk. Platelet counts should not be allowed to exceed the normal range.
• Bone marrow reticulin fibrosis: TPO receptor agonists, including eltrombopag, stimulate megakaryocyte differentiation and may increase reticulin deposition in the bone marrow. A peripheral blood smear should be examined before starting eltrombopag and monthly thereafter to detect abnormalities such as teardrop cells, nucleated red blood cells, or new-onset cytopenia that may suggest fibrosis. If marrow fibrosis is suspected, a bone marrow biopsy should be considered.
• Cataracts: In clinical studies, cataracts have been observed in patients receiving eltrombopag. Regular ophthalmological examinations are recommended, particularly in paediatric patients on long-term therapy.
• Rebound thrombocytopenia: Upon discontinuation of eltrombopag, platelet counts typically return to pretreatment levels within 1 to 2 weeks. In some cases, platelet counts may fall below pretreatment baseline, increasing the risk of bleeding. Monitoring of platelet counts for at least 4 weeks after stopping treatment is recommended.
• Patients of East Asian descent: Pharmacokinetic studies have shown that patients of East Asian ancestry (Chinese, Japanese, Korean, or Taiwanese) have approximately 50% higher exposure to eltrombopag. A reduced starting dose of 25 mg once daily (instead of 50 mg) is recommended for these patients with ITP.

Pregnancy and Breastfeeding

Eltrombopag STADA should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the foetus. Animal reproductive toxicology studies have shown adverse effects on embryo-foetal development, including reduced foetal body weight and increased incidence of cervical ribs at clinically relevant doses. There are no adequate and well-controlled studies in pregnant women.

Women of childbearing potential should use effective contraception during treatment with eltrombopag. If pregnancy occurs during treatment, the patient should be informed of the potential risks and the prescriber should carefully reassess the benefit-risk balance.

It is not known whether eltrombopag or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. Therefore, breastfeeding should be discontinued during treatment with Eltrombopag STADA. A decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the medicine to the mother.

How Does Eltrombopag STADA Interact with Other Drugs?

Eltrombopag has several clinically important drug interactions that must be carefully managed. These interactions can affect either the absorption of eltrombopag or the metabolism and transport of co-administered drugs. Understanding these interactions is crucial for ensuring both the efficacy of eltrombopag and the safety of concurrent medications.

Eltrombopag is metabolised primarily via CYP1A2 and CYP2C8, and undergoes glucuronidation by UGT1A1 and UGT1A3. It is also a substrate and inhibitor of several drug transporters, including OATP1B1, OATP1B3, and BCRP (breast cancer resistance protein). These pharmacokinetic properties underlie many of its drug interactions.

Major Interactions

Minor Interactions and Considerations

In addition to the major interactions listed above, the following should be considered:

• Dairy products and calcium-fortified foods: Foods high in calcium, such as milk, yoghurt, cheese, and calcium-fortified juices, can reduce eltrombopag absorption through chelation. Eltrombopag should be taken on an empty stomach, at least 2 hours before or 4 hours after such foods.
• Selenium and zinc supplements: Polyvalent cations in mineral supplements can also chelate eltrombopag. Separate dosing is essential.
• Other OATP1B1 substrates: Eltrombopag may increase the plasma concentrations of other drugs transported by OATP1B1, such as methotrexate, atorvastatin, fluvastatin, and pravastatin. Monitor for adverse effects of these medications when co-administered with eltrombopag.
• CYP1A2 inducers and inhibitors: Strong inducers of CYP1A2 (e.g., smoking, omeprazole) may reduce eltrombopag exposure, while inhibitors (e.g., fluvoxamine, ciprofloxacin) may increase it. Dose adjustments may be necessary.
• Warfarin: Eltrombopag does not appear to have a clinically significant interaction with warfarin based on available data, but monitoring of INR is still recommended when starting or stopping eltrombopag in patients on anticoagulant therapy.

What Is the Correct Dosage of Eltrombopag STADA?

Dosing of Eltrombopag STADA is individualised and guided by platelet count response. Treatment should only be initiated by a specialist haematologist experienced in managing thrombocytopenia. The goal is to achieve and maintain the lowest effective dose that keeps platelets at a level sufficient to prevent clinically significant bleeding, generally above 50 × 10⁹/L. The dose must never be adjusted based on platelet counts alone without considering the clinical context.

Adults with Immune Thrombocytopenia (ITP)

During dose titration, platelet counts should be monitored weekly. Once a stable dose has been established, platelet counts should be assessed at least monthly. If the platelet count exceeds 200 × 10⁹/L, the dose should be reduced. If the platelet count exceeds 400 × 10⁹/L, eltrombopag should be withheld temporarily and platelet counts monitored twice weekly. Once platelets return to below 150 × 10⁹/L, treatment may be restarted at a reduced dose.

Children with Immune Thrombocytopenia (ITP)

Paediatric patients require the same careful monitoring as adults, including regular blood counts and liver function tests. Growth and development should also be monitored, and regular ophthalmological examinations for cataracts are recommended in children receiving long-term treatment.

Elderly Patients

No specific dose adjustment is required for elderly patients (≥65 years) solely based on age. However, elderly patients may have a higher prevalence of comorbidities that increase the risk of thromboembolic events, and renal or hepatic impairment may be more common in this population. Careful monitoring and a cautious approach to dose titration are recommended. Clinical trial data suggest that elderly patients respond similarly to younger adults, but the safety profile should be carefully monitored given the increased baseline risk of thrombosis.

Severe Aplastic Anemia (SAA)

In SAA, higher doses may be needed compared to ITP. Treatment response should be assessed after 16 weeks at the maximum tolerated dose. If no adequate haematological response is achieved after 16 weeks, eltrombopag should be discontinued. In patients who do respond, the minimum effective dose should be used to maintain a multilineage haematological response.

Missed Dose

If you miss a dose of Eltrombopag STADA, take it as soon as you remember, provided it is still the same day. Do not take two doses on the same day to make up for a missed dose. Simply skip the missed dose and continue with your regular dosing schedule the next day. If you frequently forget doses, discuss strategies with your pharmacist or healthcare provider, such as setting daily reminders.

Overdose

In cases of overdose, platelet counts may rise excessively, increasing the risk of thrombotic and thromboembolic complications. There is no specific antidote for eltrombopag overdose. If an overdose is suspected, platelet counts should be monitored closely and supportive care should be administered. Oral administration of metal cation-containing preparations (such as calcium, aluminium, or iron supplements) may be considered to chelate eltrombopag in the gastrointestinal tract and limit further absorption. Haemodialysis is not expected to be effective for removal of eltrombopag, as it is highly protein-bound (>99%).

What Are the Side Effects of Eltrombopag STADA?

Like all medicines, Eltrombopag STADA can cause side effects, although not everybody experiences them. The following side effects have been reported in clinical trials and post-marketing surveillance. They are organised by frequency according to the standard MedDRA convention used by regulatory agencies worldwide. Understanding the potential side effects helps you recognise them early and seek medical attention when needed.

Most side effects of eltrombopag are mild to moderate and manageable. However, some serious adverse events require immediate medical attention. Your haematologist will monitor you regularly throughout treatment to detect and manage side effects early. It is important to report any new or worsening symptoms promptly.

When to Seek Immediate Medical Attention

Contact your doctor or go to the nearest emergency department immediately if you experience any of the following:

• Signs of liver problems: Yellowing of the skin or whites of the eyes (jaundice), unusually dark urine, right-sided abdominal pain, unexplained fatigue or loss of appetite
• Signs of blood clots: Sudden shortness of breath or chest pain, swelling or pain in one leg (especially the calf), sudden severe headache, sudden vision changes, weakness or numbness on one side of the body
• Excessive bleeding: Unusual or excessive bruising, prolonged bleeding from cuts, blood in urine or stool, or unusually heavy menstrual periods
• Signs of severe allergic reaction: Rash, swelling of the face, lips, tongue or throat, difficulty breathing or swallowing

How Should You Store Eltrombopag STADA?

Proper storage of Eltrombopag STADA is essential to maintain the medicine's effectiveness and safety. Film-coated tablets should be stored according to the manufacturer's specifications to prevent degradation of the active substance. Failure to store the medicine correctly may reduce its potency or alter its safety profile.

Store the tablets at a temperature below 30°C (86°F). Keep the medicine in the original blister packaging to protect it from moisture and light. Do not remove tablets from the blister pack until you are ready to take a dose. Do not store the medicine in the bathroom, near a sink, or in humid environments, as moisture may affect the tablet coating.

Keep Eltrombopag STADA out of the sight and reach of children. The packaging is not child-resistant, and accidental ingestion by a child could be dangerous. Store the medicine in a secure location, such as a locked cabinet or a high shelf that is not accessible to young children.

Do not use the medicine after the expiry date stated on the carton and blister pack. The expiry date refers to the last day of that month. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist about how to dispose of medicines you no longer use, in accordance with local regulations. These measures help to protect the environment.

What Does Eltrombopag STADA Contain?

Understanding the composition of your medicine is important, particularly if you have known allergies or intolerances to specific pharmaceutical ingredients. Eltrombopag STADA contains both active and inactive (excipient) components that are essential for the tablet's formulation, stability, and bioavailability.

Active Substance

Each film-coated tablet contains 25 mg of eltrombopag (as eltrombopag olamine). Eltrombopag olamine is the pharmaceutically active salt form. The olamine (monoethanolamine) component improves the solubility and stability of eltrombopag in tablet formulations. The molecular weight of eltrombopag olamine is approximately 564.6 g/mol.

Inactive Ingredients (Excipients)

The inactive ingredients in Eltrombopag STADA 25 mg film-coated tablets typically include:

• Tablet core: Magnesium stearate, mannitol, microcrystalline cellulose, povidone, sodium starch glycolate, and stearic acid
• Film coating: Hypromellose, macrogol, polysorbate 80, and titanium dioxide (E171)

Patients with known hypersensitivity to any of these excipients should inform their prescriber before starting treatment. The tablets do not contain lactose, gluten, or gelatin, making them suitable for patients with common dietary sensitivities. However, always check the patient information leaflet for the most up-to-date excipient list, as formulations may vary between manufacturing batches or regional markets.

Physical Description

Eltrombopag STADA 25 mg film-coated tablets are white to off-white, round, biconvex tablets. They may have a debossed marking for identification purposes. The tablets are packaged in PVC/PVDC/aluminium blister packs contained within a cardboard carton with an enclosed patient information leaflet.