Trombonat 25 — Eltrombopag 25 mg Tablets, 28 Tablets

Trombonat 25 is supplied as film-coated tablets for oral administration. Each tablet contains Eltrombopag Olamine equivalent to 25 mg of free eltrombopag. The core tablet and coating layer are composed of premium pharmaceutical excipients (including microcrystalline cellulose, mannitol, sodium starch glycolate, magnesium stearate, hypromellose, titanium dioxide, and colorants) designed to ensure optimal tablet stability and consistent intestinal absorption.

The tablets are packaged in blisters containing 7 tablets each. Each commercial carton contains 4 blister strips (total 28 tablets — 4 × 7 Tablets). The packaging features Natco's signature design, an authentic security hologram, batch details, manufacturing/expiry dates, and a comprehensive prescribing leaflet.

Pharmacodynamics: Eltrombopag is a small-molecule, non-peptide thrombopoietin (TPO) receptor agonist. It selectively interacts with the transmembrane domain of the TPO receptor on megakaryocytes and hematopoietic stem cells, activating downstream signaling pathways such as JAK/STAT and Ras/MAPK. This induces megakaryocyte proliferation and differentiation, ultimately augmenting platelet production. Eltrombopag does not compete with endogenous TPO for receptor binding.

Pharmacokinetics: Following oral administration, eltrombopag is absorbed rapidly, reaching peak plasma concentration (Cmax) in approximately 2 to 6 hours. Co-administration with food containing high levels of calcium or polyvalent cations markedly reduces systemic absorption. Eltrombopag is highly bound to plasma proteins (>99%). It undergoes extensive hepatic metabolism via cleavage, oxidation, and conjugation. Excretion occurs primarily through feces (approx. 59%) and to a lesser extent via urine (approx. 31%). The terminal elimination half-life ranges between 21 and 32 hours.

Trombonat 25 is indicated for adult and pediatric patients in the following conditions:

• • Treatment of primary Immune Thrombocytopenia (ITP) in adult and pediatric patients aged 1 year and older who are refractory to corticosteroids or immunoglobulins;
• • Treatment of thrombocytopenia in patients with chronic Hepatitis C virus (HCV) infection to enable the initiation and maintenance of interferon-based antiviral therapy;
• • Treatment of Severe Aplastic Anemia (SAA) in adult patients in combination with standard immunosuppressive therapy or in patients who have failed prior immunosuppressive regimens.

Administration of Trombonat 25 must be initiated and managed by a qualified hematologist or hepatologist.

• Method of Administration: Take tablets orally whole with water. Do not crush, split, or chew the tablets.
• Dietary & Drug Interactions: Trombonat 25 must be taken at least 2 hours before or 4 hours after consuming calcium-rich foods (dairy products, calcium-fortified juices) or antacids/supplements containing polyvalent cations (calcium, magnesium, iron, aluminum, zinc). Chelation with cations significantly impairs drug bioavailability.
• Dosing Regimen: The initial starting dose for most adult ITP patients is 50 mg once daily (for patients of East Asian ancestry or those with mild-to-moderate hepatic impairment, the recommended starting dose is 25 mg once daily). Doses are subsequently adjusted to maintain platelet counts ≥ 50 × 10⁹/L.
• Monitoring: Regular complete blood counts (CBC) including platelet counts and liver function tests (ALT, AST, bilirubin) should be performed throughout therapy.

The use of Trombonat 25 is contraindicated in the presence of:

• • Known hypersensitivity to eltrombopag olamine or any excipients in the tablet formulation;
• • Severe hepatic impairment (Child-Pugh score > 9) — use with extreme caution and required dose adjustments;
• • Pediatric patients under 1 year of age with ITP;
• • Pregnancy and breastfeeding (unless deemed essential after clinical evaluation).

• Polyvalent Cations (Calcium, Magnesium, Iron, Aluminum, Zinc): Antacids, multivitamin/mineral supplements, and dairy products form insoluble complexes with eltrombopag, decreasing its bioavailability by over 70%. Separate dosing by at least 2 to 4 hours.
• Statins (HMG-CoA Reductase Inhibitors): Eltrombopag inhibits OATP1B1 and BCRP transporters, potentially increasing plasma concentrations of rosuvastatin, atorvastatin, or simvastatin and escalating myopathy risk.
• Direct-Acting Antivirals: Concomitant administration with certain HCV regimens warrants close monitoring of liver function and plasma drug levels.

Trombonat 25 is not recommended during pregnancy unless the potential maternal benefit outweighs the fetal risk. Animal studies have demonstrated reproductive toxicity.

It is unknown whether eltrombopag or its metabolites are excreted in human milk. Breastfeeding should be discontinued during therapy. Women of childbearing potential should utilize effective contraception during treatment and for at least 1 week following the last dose.

Treatment with Trombonat 25 may give rise to the following adverse reactions:

• • Hepatobiliary System: Elevated ALT, AST, and total bilirubin levels, hyperbilirubinemia, and rare cases of severe hepatotoxicity.
• • Gastrointestinal System: Nausea, diarrhea, dry mouth, vomiting, and abdominal discomfort.
• • Vascular Disorders: Increased risk of thromboembolic events (deep vein thrombosis, pulmonary embolism, portal vein thrombosis) if platelet counts exceed target thresholds.
• • Bone Marrow: Increased bone marrow reticulin fiber formation (typically reversible upon discontinuation).
• • General & Nervous System: Headache, fatigue, myalgia, pharyngitis, and development of cataracts with prolonged exposure.

In cases of overdose with Trombonat 25, excessive platelet production may occur, leading to a significantly heightened risk of thromboembolic and thrombotic complications.

There is no specific antidote for eltrombopag overdose. Treatment includes immediate drug withdrawal, frequent monitoring of blood platelet counts, and supportive management. Oral administration of calcium-containing antacids or milk may be considered to chelate remaining unabsorbed drug in the gastrointestinal tract.

Store Trombonat 25 in its original carton to protect from light and moisture at a temperature not exceeding 30 °C. Keep out of reach and sight of children. Shelf life is 24 months (2 years) from the manufacturing date. Do not use after the expiration date printed on the pack. Prescription status: Prescription only (Rx-only).

To safeguard patients against counterfeit medicines, Natco Pharma Ltd. implements multiple authentication features on Trombonat 25 packaging:

• ✅ Security Hologram: A multi-angle security hologram is positioned on the front and side panel of the outer carton.
• ✅ Corporate Logo: Authentic blue and red oval NATCO logo printed clearly on the front face.
• ✅ Factory Debossed Batch Data: The Batch Number, Manufacturing Date, and Expiration Date are debossed or printed on the carton end-flap and duplicated on each blister strip.
• ✅ QR Code Authentication Sticker: The top flap features a peel-off security sticker containing a QR code for verification via Natco’s official product authentication portal.