Eltrombopag
Mechanism :
Eltrombopag is a thrombopoietin (TPO) nonpeptide agonist which increases platelet counts by binding to and activating the human TPO receptor.
Indication :
- Chronic immune thrombocytopenia (ITP) who have had insufficient response to corticosteroids, immunoglobulins, or splenectomy.
- Severe aplastic anemia
- Chronic hepatitis C infection-associated thrombocytopenia.
Contraindications :
Hypersensitivity to eltrombopag or any component of the formulation; severe hepatic impairment (Child-Pugh class C).
Dosing :
Chronic immune thrombocytopenia (ITP):
Oral
1-5 years:
Initial: 25 mg once daily; dose should be titrated based on platelet response. Maximum dose: 75 mg/day.
≥6 years:
Initial: 50 mg once daily; dose should be titrated based on platelet response. Maximum dose: 75 mg/day.
Severe aplastic anemia:
Oral
Initial: 50 mg once daily; dose should be titrated based on platelet response. Maximum dose: 150 mg/day.
Adverse Effect :
Influenza-like symptoms, headache, rigor, cough, diarrhea, fatigue, nausea, arthralgia, myalgia, depression, upper abdominal pain, xerostomia, abnormal LFT, thrombocytopenia, paraesthesia, vomiting, dyspepsia, thrombotic or thromboembolic complications, hemorrhage, conjunctival haemorrhage, ecchymosis, menorrhagia, cataract.
Interaction :
Calcium Salts: May decrease the serum concentration of Eltrombopag.
Iron Salts: May decrease the serum concentration of Eltrombopag.
Magnesium Salts: May decrease the serum concentration of Eltrombopag.
OATP1B1/SLCO1B1 Substrates: Eltrombopag may increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
Sucralfate: May decrease the serum concentration of Eltrombopag.
Zinc Salts: May decrease the serum concentration of Eltrombopag.
Hepatic Dose :
In patients with hepatic impairment due to chronic hepatitis C associated with thrombocytopenia: No dosage adjustments are recommended.
In patients with Chronic Immune Thrombocytopenia:
1 to 6 years: No dosage adjustments provided by the manufacturer. However, dose adjustments should be considered. Use with caution.
> 6 years: Mild to severe liver dysfunction: Initiate dose at 25 mg orally once a day. In patients with East Asian ancestry and mild to severe liver dysfunction: Initiate dose at 12.5 mg orally once a day.
In patients with liver dysfunction, after initiating eltrombopag or after any subsequent dosing increase, wait 3 weeks before increasing the dose.
Patients with refractory severe aplastic anemia and liver dysfunction:
2 to 5 years old: 1.25 mg/kg orally once a day for 6 months
6 to 11 years old: 37.5 mg orally once a day for 6 months
12 years or older: 75 mg orally once a day for 6 months
Monitor ALT, AST, and bilirubin at baseline every 2 weeks during dose adjustment. Monitor ALT, AST and bilirubin monthly after the establishment of a stable dose. If abnormalities are confirmed, monitor weekly until resolved or stabilized.
Discontinue treatment if:
• ALT levels = 3 times the upper limit of normal (ULN) in patients with normal hepatic function at baseline.
• ALT =3 times at baseline in those with preexisting transaminase elevations and which are progressive i.e. persistent for 4 weeks or more.
• Accompanied by increased direct bilirubin
• Accompanied by clinical signs of liver injury or evidence of hepatic decompensation
Hepatotoxicity may recur with retreatment after therapy interruption, but if determined to be clinically beneficial, may cautiously resume treatment. Monitor ALT weekly during dosage titration. permanently discontinue if liver function test elevations persist, worsen, or recur.