Usage
Eltrombopag is prescribed for the treatment of:
- Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP): In adults and children aged 1 year and older who have not responded adequately to other treatments like corticosteroids, immunoglobulins, or splenectomy. It is crucial that these patients have a degree of thrombocytopenia that increases their risk of bleeding. Eltrombopag is not used to normalize platelet counts.
- Severe Aplastic Anemia (SAA): As a first-line treatment in combination with standard immunosuppressive therapy for adults and children 2 years and older.
- Thrombocytopenia in Patients with Chronic Hepatitis C Virus (HCV) Infection: To increase platelet counts to allow the initiation and maintenance of antiviral therapy.
Pharmacological Classification: Thrombopoietin Receptor Agonist (TPO-RA)
Mechanism of Action: Eltrombopag mimics the action of thrombopoietin (TPO), a hormone that stimulates the production of platelets. It binds to and activates the c-Mpl (TPO) receptor on megakaryocytes (cells in the bone marrow that produce platelets), thus promoting platelet production.
Alternate Names
Eltrombopag is the generic name. Promacta (eltrombopag olamine) and Revolade (eltrombopag olamine) are brand names for the medication. Alvaiz is another brand name specifically utilizing eltrombopag choline.
How It Works
Pharmacodynamics: Eltrombopag increases platelet counts by stimulating the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells.
Pharmacokinetics:
- Absorption: Oral absorption is affected by food, especially calcium-rich foods and polyvalent cations (e.g., iron, calcium, magnesium, aluminum, antacids). Taking eltrombopag 1 hour before or 2 hours after meals, or with low-calcium food, improves absorption.
- Metabolism: Eltrombopag is primarily metabolized in the liver, involving several CYP450 enzymes (CYP1A2, CYP2C8, CYP2D6) and UGT1A1.
- Elimination: Mainly eliminated via biliary/fecal excretion, with a small portion through renal excretion.
Mode of Action: Eltrombopag is a non-peptide TPO receptor agonist that binds to the transmembrane domain of the human TPO receptor (c-Mpl), activating intracellular signaling pathways (JAK2/STAT5) that lead to increased platelet production.
Receptor Binding: Binds specifically to the c-Mpl (TPO) receptor.
Elimination Pathways: Primarily biliary/fecal excretion; some renal excretion.
Dosage
Standard Dosage
Adults:
- ITP: Initial dose is 50 mg once daily. Patients of East/Southeast Asian ancestry should start with 25 mg once daily. The dose can be adjusted in 25 mg increments every 2 weeks to achieve and maintain a platelet count ≥ 50,000/µL, not to exceed 75 mg daily.
- SAA (in combination with immunosuppression): Initial dose is 50 mg once daily, but patients of East/Southeast Asian ancestry start with 25 mg daily. Dosage is adjusted in 50 mg increments every 2 weeks to maintain platelet counts ≥50,000/µL. Max dose is 150 mg/day.
- HCV-associated Thrombocytopenia: Initial dose is 25 mg once daily. The dose is adjusted in 25 mg increments every 2 weeks to achieve the target platelet count for initiating antiviral therapy. Max dose is 100 mg/day.
Children:
- ITP:
- 1–5 years: 25 mg once daily (max 75 mg/day)
- 6–17 years: 50 mg once daily (max 75 mg/day); East/Southeast Asian ancestry start at 25mg once daily
- SAA (in combination with immunosuppression):
- 2-5 years: 2.5 mg/kg once daily (max for 6 months)
- 6-11 years: 75 mg once daily (max for 6 months)
- 12+ years: 150 mg once daily (max for 6 months)
Special Cases:
- Elderly Patients: Dose adjustments may be necessary based on liver function.
- Patients with Renal Impairment: No specific dose adjustments are needed.
- Patients with Hepatic Dysfunction: For ITP and SAA, start at 25 mg for Child-Pugh Class A and B; it is contraindicated in Child-Pugh Class C. For chronic HCV, the starting dose is also reduced to 25mg daily.
- Patients with Comorbid Conditions: Use with caution and monitor closely.
Clinical Use Cases
Eltrombopag is not indicated for use in situations such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. It addresses chronic thrombocytopenia, not acute scenarios.
Dosage Adjustments
Dose modifications are based primarily on platelet response and liver function. Allow at least 2 weeks to observe the effect of a dose adjustment before making further changes.
Side Effects
Common Side Effects:
Nausea, diarrhea, upper respiratory tract infection, vomiting, increased liver enzymes (ALT, AST), muscle pain, urinary tract infection, oropharyngeal pain, pharyngitis, back pain, influenza, paresthesia, and rash.
Rare but Serious Side Effects:
Hepatotoxicity (liver damage), portal vein thrombosis (blood clot in the liver), cataracts, thromboembolic events (blood clots), rebound thrombocytopenia (low platelet count after stopping the drug), and progression of myelodysplastic syndromes (MDS).
Long-Term Effects: The long-term effects of Eltrombopag are still being studied. Potential long-term complications may include liver disease progression, cataracts, and an increased risk of blood clots.
Adverse Drug Reactions (ADR): Clinically significant ADRs include hepatotoxicity, which requires close monitoring of liver function tests. Signs and symptoms may include jaundice, abdominal pain, and dark urine.
Contraindications
- Hypersensitivity to eltrombopag.
- Severe hepatic impairment (Child-Pugh Class C).
Drug Interactions
Eltrombopag interacts with numerous medications, including:
- Polyvalent cations (e.g., iron, calcium, magnesium, aluminum, antacids): Reduce eltrombopag absorption. Separate administration by at least 4 hours.
- CYP enzyme inducers/inhibitors (e.g., lopinavir/ritonavir): May alter eltrombopag levels.
- Other medications metabolized by the liver: Potential for altered metabolism of either drug.
- Medications used to treat ITP (e.g., corticosteroids, danazol, azathioprine, IVIG): Monitor platelet counts closely to avoid excessive increases.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B3 (Australia); Not Assigned (US FDA).
- Fetal Risks: Insufficient data in humans; animal studies show some reproductive toxicity at high doses. Not recommended during pregnancy unless the benefit outweighs the risk. Effective contraception is essential during treatment and for 7 days after stopping.
- Breastfeeding: It is unknown if eltrombopag is excreted in breast milk. Avoid breastfeeding due to potential risk to infants.
Drug Profile Summary
- Mechanism of Action: TPO receptor agonist, stimulates platelet production.
- Side Effects: Nausea, diarrhea, increased liver enzymes, hepatotoxicity, thrombosis.
- Contraindications: Hypersensitivity, severe hepatic impairment.
- Drug Interactions: Polyvalent cations, CYP inducers/inhibitors, other liver-metabolized drugs.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Platelet count, liver function tests (ALT, AST, bilirubin), complete blood count (CBC).
Popular Combinations
Eltrombopag is often used in combination with standard immunosuppressive therapy (e.g., cyclosporine, horse antithymocyte globulin) for the treatment of severe aplastic anemia. In HCV-related thrombocytopenia, it’s used with antiviral medications.
Precautions
- General Precautions: Monitor liver function, platelet counts, and complete blood count regularly. Screen for underlying liver disease.
- Pregnant Women: Avoid use unless absolutely necessary. Effective contraception is essential.
- Breastfeeding Mothers: Avoid breastfeeding.
- Children & Elderly: Age-specific dosing is required. Monitor closely.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Eltrombopag?
A: The dosage varies depending on the condition being treated and patient-specific factors (age, ethnicity, liver function). See the detailed dosage section above.
Q2: How should Eltrombopag be administered?
A: Orally, once daily. Take on an empty stomach (1 hour before or 2 hours after a meal) and avoid administration with polyvalent cations.
Q3: What are the most common side effects of Eltrombopag?
A: Common side effects include nausea, diarrhea, vomiting, fatigue, upper respiratory tract infections, and increased liver enzymes.
Q4: What are the serious side effects to watch out for with Eltrombopag?
A: Hepatotoxicity (liver damage) and thrombosis (blood clots) are serious potential side effects. Monitor liver function tests and watch for signs of clotting.
Q5: Can Eltrombopag be used during pregnancy?
A: Eltrombopag is generally not recommended during pregnancy unless the benefit clearly outweighs the risk. Effective contraception must be used.
Q6: Can Eltrombopag be used during breastfeeding?
A: Eltrombopag is not recommended during breastfeeding due to potential risks to the infant.
Q7: What should I do if a patient develops signs of hepatotoxicity while taking Eltrombopag?
A: Immediately discontinue Eltrombopag and conduct a thorough liver function assessment. Provide supportive care as needed.
Q8: Does Eltrombopag cure ITP?
A: Eltrombopag is not a cure for ITP. It helps to manage the condition by increasing platelet counts and reducing the risk of bleeding.
Q9: How long does it take for Eltrombopag to work?
A: Platelet counts generally begin to rise within 1–2 weeks of starting eltrombopag.
Q10: What are the key drug interactions with Eltrombopag?
A: Key interactions occur with polyvalent cations (e.g., iron, calcium), which reduce absorption, and with drugs affecting liver enzymes. Refer to the Drug Interactions section above for further details.
