Revolade

Eltrombopag olamine

Previously treated adult & ped patients ≥1 yr w/ immune thrombocytopenia (ITP) lasting ≥6 mth from diagnosis who have failed treatment w/ steroids & platelet count <30,000/mm³ w/ clinical bleeding. Thrombocytopenia in patients w/ chronic HCV infection. In combination w/ standard immunosuppressive therapy for 1st line treatment of adult & ped patients ≥2 yr w/ severe aplastic anemia (SAA). Cytopenias in patients w/ refractory SAA who had insufficient response to immunosuppressive therapy.

ITP Adult & ped patients 6-17 yr Initially 50 mg once daily. Asian adult, ped patients 6-17 yr & 1-5 yr Initially 25 mg once daily. Platelet count <50,000/microL following at least 2 wk of therapy Increase daily dose by 25 mg to max of 75 mg daily. For patients taking 25 mg once every other day, increase dose to 25 mg once daily, ≥200,000/microL to ≤400,000/microL Decrease daily dose by 25 mg & wait 2 wk for assessment. For patients taking 25 mg once daily, decrease dose to 12.5 mg once daily or 25 mg once every other day, >400,000/microL Once platelet count is <150,000/microL after discontinuation, reinitiate therapy at lower daily dose. Hepatic impairment Initially 25 mg once daily & wait for 3 wk before increasing the dose. Chronic HCV associated thrombocytopenia Adult & Asian patient Initially 25 mg once daily. Dose adjustment: 25 mg increments every 2 wk. Max: 100 mg once daily. Platelet count <50,000/microL Increase daily dose by 25 mg up to max dose of 100 mg, ≥200,000/microL to ≤400,000/microL Decrease daily dose by 25 mg & wait 2 wk to assess, >400,000/microL Once platelet count is ≤150,000/microL after discontinuation, reinitiate therapy at daily dose reduced by 25 mg. For patients on 25 mg, reduce to 12.5 mg once daily. Hepatic impairment Initially 25 mg once daily. 1st line SAA Adult & adolescent 12-17 yr Initially 150 mg once daily for 6 mth. Asian adult & adolescent, & ped patient 6-11 yr Initially 75 mg once daily for 6 mth. Asian ped 6-11 yr Initially 37.5 mg once daily for 6 mth. Ped 2-5 yr Initially 2.5 mg/kg once daily for 6 mth. Asian ped 2-5 yr Initially 1.25 mg/kg once daily for 6 mth. Dose adjustment: Platelet count >200,000/microL to ≤400,000/microL Decrease daily dose by 25 mg every 2 wk to lowest dose that maintains platelet count ≥50,000/microL. Decrease dose by 12.5 mg in ped patient <12 yr, >400,000/microL Once platelet count is <200,000/microL after 1 wk of discontinuation, reinitiate at daily dose reduced by 25 mg (or 12.5 mg in ped patients <12 yr). Refractory SAA Adult Initially 50 mg once daily. Asian Initially 25 mg once daily. Dose adjustment: 25 mg increments every 2 wk. Max: 150 mg daily. Platelet count <50,000/microL following at least 2 wk of therapy Increase daily dose by 25 mg to max of 150 mg daily, ≥100,000/microL to ≤200,000/microL at any point during therapy Decrease daily dose by 50 mg & wait 2 wk to assess, >200,000/microL Once platelet count is <150,000/microL after at least 1 wk of discontinuation, reinitiate therapy at daily dose reduced by 50 mg, >200,000/microL after 2 wk of therapy at lowest dose Reinitiate therapy after discontinuation w/ 25 mg or next lower dose once platelet count is <50,000/microL. Hepatic impairment Initially 25 mg once daily.

Should be taken on an empty stomach: Take at least 2 hr before or 4 hr after antacids, dairy products or mineral supplements containing polyvalent cations (eg, Al, Ca, Fe, Mg, Se, & Zn).

History of hypersensitivity.

Discontinue treatment if ALT levels increase (≥3x ULN) in patients w/ normal liver function, or ≥3x baseline (or >5x ULN, whichever is lower) in patients w/ transaminase elevations before treatment that are progressive, persistent for ≥4 wk, accompanied by increased direct bilirubin or by clinical symptoms of liver injury or evidence for hepatic decompensation; antiviral therapy is discontinued for hepatic decompensation; patient develops new or worsening morphological abnormalities or cytopenias & consider bone marrow biopsy including staining for fibrosis. Consider to reduce dose or discontinue treatment if platelet count exceeds target levels. Not indicated for thrombocytopenia in patients w/ chronic liver disease in prep for invasive procedures. Not to be used to normalize platelet counts; outside clinical studies for thrombocytopenia due to myelodysplastic syndrome (MDS). Chemotherapy-induced thrombocytopenia & MDS. Potentially fatal hepatic decompensation & thromboembolic events in thrombocytopenic HCV patients w/ advanced chronic liver disease; hepatobiliary lab abnormalities, severe hepatotoxicity & potentially fatal liver injury; embolism including pulmonary embolism, DVT, transient ischemic attack, MI, ischemic stroke, & suspected prolonged reversible ischemic neurologic deficiency; portal vein thrombosis. May increase risk for development or progression of reticulin fibers w/in bone marrow. May stimulate progression of existing hematological malignancies eg, MDS. Patients w/ known risk factors for thromboembolism (eg, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome). Closely monitor patients for signs & symptoms of hepatic decompensation. Routinely monitor for cataracts. Measure serum ALT, AST, bilirubin levels prior to initiation of therapy, every 2 wk during dose adjustment phase & mthly following establishment of stable dose; prior to treatment initiation in 1st line setting of SAA. Perform fractionation if bilirubin is elevated; CBC w/ WBC count differential mthly. Monitor serum liver tests if abnormalities are confirmed; platelet counts & wkly for 4 wk in cases of bleeding following treatment discontinuation; signs & symptoms of hepatic decompensation. Closely examine peripheral blood smear prior to initiation of therapy; for new or worsening morphological abnormalities if immature or dysplastic cells are observed. Interference w/ total bilirubin & creatinine testing. May impair ability to drive or use machinery. Not be used in patients w/ hepatic impairment (Child-Pugh score ≥5). Hepatic & renal impairment. Sexually-active females of reproductive potential should use effective contraception (<1% pregnancy rates) during & for at least 7 days after stopping treatment. Pregnancy & lactation. Ped patients w/ chronic HCV & refractory SAA; <1 yr w/ ITP; <2 yr w/ definitive immunosuppressive therapy-naïve SAA. Elderly ≥65 yr.

Diarrhoea, nausea, abdominal pain; increased ALT, AST, blood bilirubin (including ocular icterus) & transaminases; back pain, myalgia, pain in extremity, arthralgia, muscle spasms; URTI, nasopharyngitis; cough, oropharyngeal pain, rhinorrhoea; pyrexia, fatigue, flu-like illness, asthenia, chills; anaemia; decreased appetite; headache, dizziness; pruritus. Pharyngitis; cataract; thromboembolic events including portal vein thrombosis, thrombotic microangiopathy w/ acute renal failure; vomiting; hyperbilirubinaemia; drug-induced liver injury; rash, alopecia, skin discoloration including hyperpigmentation; musculoskeletal pain including musculoskeletal chest pain; toothache; oedema.

Decreased AUC_inf & C_max w/ polyvalent cation-containing antacids (eg, Al hydroxide & Mg carbonate); dairy products; high-Ca, moderate fat & calorie meal. Decreased conc w/ lopinavir/ritonavir. Increased plasma C_max & AUC_inf of rosuvastatin. Concomitant use w/ other OATP1B1 & BCRP substrates.

Haemostatics

B02BX05 - eltrombopag ; Belongs to the class of other systemic hemostatics. Used in the treatment of hemorrhage.

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