Trade Names:Promacta- Tablets, oral 25 mg- Tablets, oral 50 mg
Small-molecule thrombopoietin (TPO) receptor agonist that interacts with the transmembrane domain of the human TPO-receptor and initiates signaling cascades that induce proliferation and differentiation of megakaryocytes from bone marrow progenitor cells.
C max occurs in 2 to 6 h after oral administration.
Concentration in blood cells is approximately 50% to 79% of plasma concentrations. Binding to plasma proteins is more than 99%.
Extensively metabolized, predominantly through pathways involving cleavage, oxidation, and conjugation with glucuronic acid, glutathione, or cysteine. CYP1A2 and CP2C8 are responsible for oxidative metabolism of eltrombopag. UGT1A1 and UGT1A3 are responsible for glucuronidation.
Excretion is 59% in feces (20% unchanged) and 31% in urine. Elimination half-life is 21 to 32 h in healthy individuals and 26 to 35 h in patients with idiopathic thrombocytopenic purpura (ITP).
Pharmacokinetics have not been studied.Hepatic Function Impairment
In subjects with mild, moderate, or severe hepatic impairment, the eltrombopag AUC was 41%, 80%, and 93% higher, respectively, compared with healthy subjects.Gender
Cl is approximately 27% greater in men compared with women.Race
Drug exposure is approximately 70% higher in some Asian subjects of Chinese, Japanese, Korean, or Taiwanese ancestry with ITP compared with non-Asian subjects, who were predominantly white. An approximately 40% higher systemic exposure in healthy black subjects was found in at least 1 study.
Treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura.
PO Start with 50 mg once daily except in patients who are of East Asian ancestry (eg, Chinese, Japanese, Korean, Taiwanese) or who have moderate to severe hepatic impairment. Start with 25 mg once daily in patients who are of East Asian ancestry or who have moderate to severe hepatic impairment.Dose adjustments
Adjust dose to achieve and maintain a platelet count of at least 50 × 10 9 /L as necessary to reduce the risk of bleeding. If the platelet count is less than 50 × 10 9 /L following at least 2 wk of therapy, increase the daily dose by 25 mg (max, 75 mg/day). If the platelet count is 200 × 10 9 /L to 400 × 10 9 /L at any time, decrease the dose by 25 mg. Wait 2 wk to assess the effects of this or any subsequent dose adjustments. If the platelet count is more than 400 × 10 9 /L, stop therapy, increase the frequency of platelet monitoring to twice weekly. Once the platelet count is less than 150 × 10 9 /L, reinitiate therapy at a daily dose reduced by 25 mg. If the platelet count is more than 400 × 10 9 /L after 2 wk of therapy at the lowest dose of eltrombopag, permanently discontinue therapy. Discontinue treatment if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 wk of therapy at a maximum dosage of 75 mg/day.
Store at 59° to 86°F.
Eltrombopag plasma concentrations may be elevated; monitor patients for signs and symptoms of adverse reactions.Moderate or strong inhibitors of CYP2C8 (eg, gemfibrozil, trimethoprim)
Eltrombopag plasma concentrations may be elevated, monitor patients for signs and symptoms of adverse reactions.Organic anion transporting polypeptide substrates (eg, atorvastatin, benzylpenicillin, fluvastatin, methotrexate, nateglinide, pravastatin, repaglinide, rifampin, rosuvastatin)
Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and adverse reactions. Adjust the dose of these agents as needed.Polyvalent cations (eg, aluminum, calcium, iron, magnesium, selenium, zinc)
Eltrombopag plasma concentrations may be reduced, decreasing the efficacy. Observe patients for evidence of excessive eltrombopag exposure. Do not administer eltrombopag within 4 h of any of any agent containing polyvalent cations.UGT enzyme substrates (eg, acetaminophen, narcotics, NSAIDs [eg, ibuprofen])
Observe patients for evidence of excessive exposure to these agents.UGT1A1 or UGT1A3 moderate or strong inhibitors
Observe patients for evidence of excessive eltrombopag exposure.
None well documented.
Cataracts (3%); conjunctival hemorrhage (2%).
Nausea (6%); vomiting (4%); dyspepsia (2%).
Increased ALT, increased AST (2%).
Ecchymosis, thrombocytopenia (2%).
Because eltrombopag may cause hepatotoxicity, the drug is available only through a restricted distribution program called Promacta Cares. Only prescribers, pharmacies, and patients registered with the program may prescribe, dispense, or receive eltrombopag.
Measure serum ALT, AST, and bilirubin prior to starting treatment, every 2 wk during the dose-adjustment phase, and monthly following establishment of a stable dose. Perform fractionation if bilirubin is elevated. Evaluate abnormal serum liver tests with repeat testing within 3 to 5 days; if abnormalities are confirmed, monitor serum liver tests weekly until the abnormality(ies) resolve, stabilize, or return to baseline values. Discontinue treatment if ALT levels increase to 3 or more times ULN and are progressive, persistent for at least 4 wk, or accompanied by increased direct bilirubin, or accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation. Prior to starting therapy, monitor CBCs, including platelet counts and peripheral blood smears. Monitor CBCs, including platelet counts, for at least 4 wk following discontinuation of treatment.
Category C .
Safety and efficacy not established.
Select dose with caution, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.
Use with caution.
Cl is reduced about 50%, and the half-life is prolonged 2-fold in patients with moderate or severe hepatic function impairment.
The risk for development or progression of reticulum fiber deposition within bone marrow may be increased.
May develop or worsen.
The risk of hematologic malignancies may be increased.
Thrombotic or thromboembolic complications may result from excessive increases in platelet counts, which may occur as a consequence of excessive eltrombopag doses.
Discontinuation of therapy may result in thrombocytopenia of greater severity than was present prior to treatment. The worsened thrombocytopenia may increase the risk of bleeding.
Platelet counts may increase excessively, resulting in thrombotic/thromboembolic complications.
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