Odalade Special Precautions

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; for the treatment of chronic immune thrombocytopenia (ITP), chronic hepatitis C-associated thrombocytopenia, and refractory severe aplastic anemia, obtain ALT, AST, and bilirubin prior to treatment initiation, every 2 weeks during adjustment phase, then monthly (after stable dose established).
For the first-line treatment of severe aplastic anemia, obtain ALT, AST, and bilirubin prior to therapy initiation, every other day (while hospitalized for immunosuppressive therapy), and then every 2 weeks during treatment. 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.
For the treatment of chronic ITP, chronic hepatitis C-associated thrombocytopenia, and refractory severe aplastic anemia, discontinue treatment for ALT levels >3 times the 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 reoccur 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 abnormalities persist, worsen, or recur with rechallenge. In clinical trials, isolated cases of severe liver injury occurred ~3months after initiation of eltrombopag and resolved with discontinuation.
For the first-line treatment of severe aplastic anemia, withhold eltrombopag for ALT or AST >6 times ULN; reinitiate eltrombopag at a reduced dose when ALT or AST return to acceptable levels. Use with caution in patients with preexisting hepatic impairment (clearance may be reduced); dosage reductions are recommended in patients with ITP (except children 1 to 5 years) and severe aplastic anemia who have hepatic dysfunction (no initial dose reductions are necessary in patients with chronic hepatitis C-related thrombocytopenia); monitor closely.
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 (<3.5 g/dL) or a Model for End-Stage Liver Disease (MELD) score ≥10 at baseline had an increased risk of hepatic decompensation; closely monitor these patients during therapy. If antiviral therapy is discontinued for hepatic decompensation according to interferon/ribavirin recommendations, eltrombopag should also be discontinued. Indirect hyperbilirubinemia is commonly observed with eltrombopag when used in combination with peginterferon and ribavirin. In addition, ascites, encephalopathy, and thrombotic events were reported more frequently than placebo in chronic hepatitis C trials.
Bone marrow reticulin formation and risk of bone marrow fibrosis: Monitor peripheral blood smear for cellular morphologic abnormalities; analyze CBC monthly; discontinue treatment with onset of new or worsening abnormalities (eg, teardrop and nucleated RBC, immature WBC) or cytopenias and consider bone marrow biopsy (with staining for fibrosis).
Thrombotic/Thromboembolic complications: Thromboembolism 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.
Cataracts: 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).
Hematologic: 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 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 prevent the initiation and maintenance of interferon-base 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 refractory aplastic anemia: Use the lowest dose to achieve and maintain hematologic response. Discontinue if no hematologic response has occurred a 16 weeks of therapy, excessive platelet count responses or important liver test abnormalities. Consider discontinuation if new cytogenetic abnormalities are observed.
Malignancies and progression of malignancies: 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 acute myeloid leukaemia (AML)). Increased relative risks of death and progression to AML in the eltrombopag arm compared to placebo were observed in the study.
Effects on ability to drive and use machine: There have been no studies to investigate the effect of eltrombopag on driving performance or the ability to operate machinery. A detrimental effect on such activities would not be anticipated from the pharmacology of eltrombopag. The clinical status of the patient and the adverse event profile of eltrombopag should be borne in mind when considering the patient's ability to perform tasks that require judgement, motor and cognitive skills.