Eltrombopag

Cataract formation or worsening was observed in clinical trials. Monitor regularly for signs and symptoms of cataracts; obtain ophthalmic exam at baseline and during therapy. Use with caution in patients at risk for cataracts (eg, advanced age, long-term glucocorticoid use).

Eltrombopag may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended. Liver enzyme elevations may occur; obtain ALT, AST, and bilirubin prior to treatment initiation, every 2 weeks during adjustment phase, then monthly (after stable dose established). Eltrombopag inhibits UGT1A1 and OATP1B1, which may lead to indirect hyperbilirubinemia; obtain fractionation for elevated bilirubin levels. Repeat abnormal liver function tests within 3 to 5 days; if confirmed abnormal, monitor weekly until resolves, stabilizes, or returns to baseline. Discontinue treatment for ALT levels ≥3 times the upper limit of normal (ULN) in patients with normal hepatic function, or ≥3 times baseline (or >5 times ULN; whichever is lower) in those with preexisting transaminase elevations and which are progressively increasing, or persistent (≥4 weeks), or accompanied by increased direct bilirubin, or accompanied by clinical signs of liver injury or evidence of hepatic decompensation. Hepatotoxicity may recur with re-treatment after therapy interruption; however, if the benefit of treatment outweighs the hepatotoxicity risk, initiate carefully, and monitor liver function tests weekly during the dose adjustment phase. Permanently discontinue if liver test abnormalities persist, worsen, or recur with rechallenge. In clinical trials, isolated cases of severe liver injury occurred, liver function test abnormalities usually oc

Thromboembolism (venous or arterial) may occur with excessive increases in platelet levels. Use with caution in patients with known risk factors for thromboembolism (eg, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome, chronic liver disease). Thrombotic events, primarily involving the portal venous system, were more commonly seen in eltrombopag-treated chronic hepatitis C patients with thrombocytopenia (when compared to placebo). Thrombotic events (including portal venous thrombosis) were also reported in a study of non-ITP thrombocytopenic patients with chronic liver disease undergoing elective invasive procedures receiving eltrombopag 75 mg once daily. Symptoms of portal vein thrombosis include abdominal pain, nausea, vomiting, and diarrhea. The risk for portal venous thrombosis is increased in thrombocytopenic patients with chronic liver disease receiving 75 mg once daily for 2 weeks as preparation for invasive procedures. Disease-related concerns:

May increase risk of hepatic decompensation when used in combination with interferon and ribavirin in patients with chronic hepatitis C. In clinical trials, patients with low albumin (• Hepatic impairment: Clearance may be reduced in patients with hepatic impairment; use with caution; reduced starting doses are recommended in patients with ITP (except children 1 to 5 years) and severe aplastic anemia who have hepatic impairment (no initial dose reductions are necessary in patients with chronic hepatitis C-related thrombocytopenia).

Eltrombopag is not indicated for the treatment of myelodysplastic syndromes (MDS). A clinical trial comparing the combination of azacitidine plus eltrombopag to azacitidine alone in patients with intermediate-1, intermediate-2, or high-risk MDS was terminated due to lack of efficacy and safety concerns (including increased progression to AML). Increased relative risks of death and progression to AML in the eltrombopag arm compared to placebo were observed in the study.

Use with caution with renal impairment (any degree) and monitor closely; initial dosage adjustment is not necessary. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

May have greater drug exposure (compared to non-East Asians); therapy should be initiated with lower starting doses in ITP and severe aplastic anemia patients. Other warnings/precautions:

Do not use to normalize platelet counts. ITP: Indicated only when the degree of thrombocytopenia and clinical conditions increase the risk for bleeding in patients with chronic immune ITP; use the lowest dose necessary to achieve and maintain platelet count ≥50,000/mm3. Discontinue if platelet count does not respond to a level to avoid clinically important bleeding after 4 weeks at the maximum recommended dose. Chronic hepatitis C-associated thrombocytopenia: Use only when thrombocytopenia prevents the initiation and maintenance of interferon-based therapy; discontinue if antiviral therapy is discontinued. Safety and efficacy have not been established when combined with direct acting antiviral medications approved for chronic hepatitis C genotype 1 infection therapy. Severe aplastic anemia: Use the lowest dose to achieve and maintain hematologic response. Discontinue if no hematologic response has occurred after 16 weeks of therapy, excessive platelet count responses or important liver test abnormalities. Consider discontinuation if new cytogenetic abnormalities are observed.