Olapag25 mg

Established / FDA-approved uses

• Chronic immune thrombocytopenia (ITP): Olapag is indicated for the treatment of thrombocytopenia in adult and pediatric patients (1 year of age and older) with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
• Severe aplastic anemia (SAA): Olapag is indicated, in combination with standard immunosuppressive therapy, for the first-line treatment of severe aplastic anemia in adult and pediatric patients 2 years and older, and alone for the treatment of patients with severe aplastic anemia who have had an insufficient response to prior immunosuppressive therapy or are heavily pretreated.
• Chronic hepatitis C-associated thrombocytopenia: Olapag is indicated in combination with interferon-based antiviral therapy to treat thrombocytopenia in patients with chronic hepatitis C, to allow initiation and maintenance of interferon-based therapy. This is a combination-therapy indication; Olapag is not used alone for this purpose.

Important limitation

Olapag should be used only in patients whose degree of thrombocytopenia and clinical condition increase the risk of bleeding. It is not indicated to normalize platelet counts.

Each film-coated tablet contains Eltrombopag Olamine equivalent to eltrombopag 12.5 mg, 25 mg, or 50 mg (strength varies by product). Contains inactive ingredients including magnesium stearate, microcrystalline cellulose, povidone, and film-coating agents.

Olapag is the olamine salt form of eltrombopag, an orally bioavailable, small-molecule thrombopoietin (TPO) receptor agonist. It is used to raise and maintain platelet counts in specific clinical settings where thrombocytopenia poses a bleeding risk.

Olapag is supplied as film-coated tablets for oral administration, typically taken once daily.

Olapag belongs to the class of thrombopoietin (TPO) receptor agonists, used to stimulate platelet production.

Eltrombopag Olamine interacts with the transmembrane domain of the human thrombopoietin (TPO) receptor (also known as cMpl) on megakaryocytes and their progenitors, initiating signaling cascades similar to, but distinct from, endogenous TPO. This induces proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, leading to increased platelet production.

Unlike endogenous TPO, Eltrombopag Olamine does not compete with TPO for receptor binding and has an additive effect on platelet production.

Pharmacokinetics

• Absorption: Peak plasma concentrations occur 2–6 hours after oral dosing; absorption is significantly reduced by concurrent intake of polyvalent cation-containing products (antacids, dairy, mineral supplements).
• Metabolism: Primarily via oxidation, glucuronidation, and hydrolysis, involving multiple pathways including CYP1A2 and CYP2C8.
• Elimination: Mean terminal half-life is approximately 21–32 hours; excreted mainly via feces, with a smaller portion in urine.

Olapag tablets are taken orally, once daily, on an empty stomach or with a low-fat meal, at least 4 hours apart from antacids, dairy products, or mineral supplements containing polyvalent cations, which markedly reduce absorption. Swallow tablets whole with water.

• Polyvalent cation-containing products (antacids, dairy products, mineral supplements containing calcium, iron, magnesium, aluminum, selenium, or zinc): chelate Olapag, substantially reducing its absorption and plasma concentration. Separate administration by at least 4 hours.
• CYP1A2 and CYP2C8 substrates: Olapag may inhibit or induce certain drug-metabolizing enzymes; caution is advised with drugs metabolized by these pathways, and dose adjustment of the co-administered drug may be needed.
• Statins (e.g. rosuvastatin) and other OATP1B1/BCRP substrates: Olapag increases plasma concentrations of statins and other transporter substrates; consider a lower statin dose and monitor for statin-related adverse effects.
• HIV protease inhibitors (e.g. lopinavir/ritonavir): may reduce eltrombopag plasma concentrations; dose adjustment or closer platelet monitoring may be required when starting or stopping these agents.
• Hepatotoxic drugs: concurrent use of other hepatotoxic medications may increase the risk of liver injury; monitor liver function more closely.

Common side effects

• Headache
• Nausea and vomiting
• Diarrhea
• Upper respiratory tract infection
• Muscle aches (myalgia) and pain in extremities
• Elevated liver enzymes (ALT, AST, bilirubin)

Serious side effects

• Hepatotoxicity: Olapag can cause serious, sometimes fatal, liver injury; requires baseline and periodic liver function testing (see Precautions and Warnings).
• Thrombotic/thromboembolic events: increased risk of blood clots, including portal vein thrombosis, especially in patients with chronic liver disease.
• Cataracts: reported with long-term use, particularly in patients with severe aplastic anemia; periodic eye examinations are recommended.
• New malignancies and worsening of pre-existing malignancies have been reported, particularly in patients with myelodysplastic syndrome.
• Bone marrow reticulin fibrosis with long-term use.

Pregnancy: Data on use of Olapag in pregnant women are limited. Animal studies have shown embryo-fetal toxicity at doses producing exposures relevant to humans. Olapag should be used during pregnancy only if clearly needed and the potential benefit to the mother justifies the potential risk to the fetus. Consult a physician before use during pregnancy.

Lactation: It is not known whether Olapag passes into human breast milk. Because of the potential for serious adverse reactions in a breastfed infant, a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother, in consultation with a physician.

Boxed warning-level concerns

• Hepatotoxicity: Olapag may cause serious and potentially fatal hepatotoxicity. Measure serum ALT, AST, and bilirubin before starting therapy, every 2 weeks during dose adjustment, and monthly thereafter. Evaluate promptly if abnormalities occur and consider discontinuation if liver injury is confirmed and persistent or worsening.
• Hepatic decompensation in hepatitis C patients: when used with interferon and ribavirin in patients with chronic hepatitis C and cirrhosis, Olapag increases the risk of hepatic decompensation; monitor closely and discontinue if decompensation occurs.
• Thrombotic/thromboembolic complications: risk of venous and arterial thrombosis, including portal vein thrombosis in hepatitis C patients with cirrhosis. Weigh benefits versus risks in patients with known risk factors for thromboembolism.

Other precautions

• Monitor platelet counts regularly; discontinue if platelet counts do not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the maximum dose.
• Risk of excessive platelet response (thrombocytosis) with associated thrombotic risk; reduce dose if platelet counts exceed target ranges.
• Cytogenetic abnormalities and progression to myelodysplastic syndrome/acute myeloid leukemia have been reported in severe aplastic anemia patients; bone marrow monitoring is recommended.
• Cataract formation with long-term use; periodic ophthalmologic examination advised.
• Use with caution in patients with hepatic impairment; lower starting doses and closer monitoring required.

Overdose of Olapag may result in excessively high platelet counts leading to thrombotic/thromboembolic complications, and hepatotoxicity with elevated liver enzymes. In case of suspected overdose, seek immediate medical attention or contact a poison control center. Close monitoring of platelet counts and liver function is essential; a hepatoprotectant may be considered under medical supervision. Because Olapag is highly bound to plasma protein, hemodialysis is not expected to be an effective method of enhancing elimination.

Store at room temperature (below 30°C), protected from light and moisture. Keep the container tightly closed. Keep out of reach of children.

Renal impairment

No dose adjustment of Olapag is required in patients with renal impairment; however, patients should be monitored closely.

Hepatic impairment

Olapag should be initiated at a reduced dose (25 mg once daily) in patients with hepatic impairment, with close monitoring of liver function, given the increased risk of hepatotoxicity and hepatic decompensation.

East/Southeast Asian ancestry

Patients of East and Southeast Asian ancestry have higher plasma exposure to eltrombopag and should be started at a reduced dose (25 mg once daily), with dose titration based on platelet response.

Elderly

Clinical studies of Olapag did not identify differences in safety or effectiveness between elderly and younger patients, but greater sensitivity in some older individuals cannot be ruled out; use with appropriate caution.

Duration of treatment with Olapag depends on indication and clinical response. In chronic ITP, treatment is continued as long as needed to maintain a safe platelet count, with periodic reassessment of the need for continued therapy. In severe aplastic anemia, treatment duration follows response-guided protocols and combination with immunosuppressive therapy. In hepatitis C-associated thrombocytopenia, Olapag is used only for the duration of the antiviral treatment course. Discontinue if platelet counts do not respond adequately after 4 weeks at the maximum recommended dose, or as directed by the treating physician.

Thrombopoietin (TPO) receptor agonist

Eltrombopag Olamine binds to the transmembrane domain of the thrombopoietin receptor on megakaryocytes and their precursors, activating intracellular signaling (JAK/STAT pathway) that stimulates proliferation and differentiation of megakaryocyte progenitor cells, thereby increasing platelet production.

Olapag is approved for use in pediatric patients 1 year of age and older with chronic ITP who have had an insufficient response to other treatments, and in pediatric patients 2 years and older for first-line treatment of severe aplastic anemia in combination with immunosuppressive therapy. Dosing is age- and weight-tiered (see Dosage and Administration). Safety and efficacy in children below these approved age thresholds, and for the hepatitis C-associated thrombocytopenia indication in pediatric patients, have not been established. Pediatric patients should be monitored closely for the same hepatic, thrombotic, and ophthalmologic risks as adults.