Odalade

Previously treated adult & ped patients ≥1 yr w/ immune thrombocytopenia 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 to enable initiation of, & optimize interferon based therapy. 1st-line treatment of adult & ped patients ≥2 yr w/ severe aplastic anemia (1st-line SAA). Cytopenias in patients w/ refractory SAA who have had insufficient response to immunosuppressive therapy.

Individualized dosage. Immune thrombocytopenia Adult, & ped 6-17 yr & 1-5 yr Initially 25 mg once daily. Max: 75 mg daily. Dose adjustment: Platelet count <50,000/microL following at least 2 wk of therapy Increase daily dose by 25 mg up to max of 75 mg daily. Increase dose to 25 mg once daily for patients taking 25 mg once every other day, ≥200,000/microL to ≤400,000/microL Decrease daily dose by 25 mg, >400,000/microL Once platelet count is ≤150,000/microL after discontinuation, reinitiate therapy at lower daily dose. Consider 12.5 mg once daily, or alternatively, 25 mg once every other day for patients taking 25 mg once daily. Chronic hepatitis C (HCV) associated thrombocytopenia Adult Initially 25 mg once daily. Max: 100 mg once daily. Dose adjustment: Platelet count <50,000/microL following at least 2 wk of therapy Increase daily dose by 25 mg to max of 100 mg daily, ≥50,000/microL to ≤200,000/microL Administer lowest effective dose, >200,000/microL to ≤400,000/microL Decrease daily dose by 25 mg, >400,000/microL Once platelet count is ≤150,000/microL after discontinuation, reinitiate therapy at 25 mg daily dose (or 12.5 mg once daily for patients on 25 mg). Consider 12.5 mg once daily, or alternatively, 25 mg once every other day for patients taking 25 mg once daily. 1st-line SAA Adult & adolescent 12-17 yr Initially 75 mg once daily for 6 mth. Ped 6-11 yr Initially 37.5 mg once daily for 6 mth, 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 <12 yr, >400,000/microL Once platelet count is <150,000/microL after 1 wk of discontinuation, reinitiate therapy at daily dose reduced by 25 mg (or 12.5 mg in ped <12 yr). Consider 12.5 mg once daily, or alternatively, 25 mg once every other day for patients taking 25 mg once daily. Refractory SAA Adult Initially 25 mg once daily. Titrate dose up to max of 150 mg. Dose adjustment: Platelet count <50,000/microL following at least 2 wk of therapy Increase daily dose by 25 mg up to max of 150 mg daily, ≥100,000/microL to ≤200,000/microL at any point during therapy Decrease daily dose by 50 mg, >200,000/microL Once platelet count is <150,000/microL after 1 wk of discontinuation, reinitiate therapy at daily dose reduced by 50 mg, >200,000/microL after 2 wk of therapy at lowest dose Once platelet count is <50,000/microL after discontinuation, reinitiate therapy w/ 25 mg or next lower dose. Hepatic impairment Immune thrombocytopenia, chronic hepatitis C (HCV) associated thrombocytopenia, refractory SAA 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.

Permanently discontinue treatment if liver abnormalities persist, worsen, or recur w/ rechallenge. Discontinue treatment if antiviral therapy is discontinued for hepatic decompensation; w/ onset of new or worsening abnormalities, or cytopenias, & consider bone marrow biopsy. Not be used to normalize platelet counts. Not indicated for treatment of myelodysplastic syndromes. Increased risk of severe & potentially life-threatening hepatotoxicity; hepatic decompensation in combination w/ interferon & ribavirin in patients w/ chronic hepatitis C. Liver enzyme elevations. Indirect hyperbilirubinemia. Thrombotic events including portal venous thrombosis. Cataract formation or worsening. Malignancies & progression of malignancies. Patients w/ known risk factors for thromboembolism (eg, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome, chronic liver disease); at risk for cataracts (eg, advanced age, long-term glucocorticoid use). Monitor LFTs wkly during dose adjustment; peripheral blood smear for cellular morphologic abnormalities. Analyze CBC mthly; for signs & symptoms of cataracts regularly. Obtain ophth exam at baseline & during therapy. Renal impairment. Potential risk to fetus. Sexually-active females of reproductive potential should use effective contraception during & for at least 7 days after stopping treatment. Pregnancy & lactation. Elderly ≥65 yr. Chronic immune thrombocytopenia, chronic hepatitis C-associated thrombocytopenia & refractory SAA: Discontinue treatment for ALT levels >3x ULN in patients w/ normal hepatic function, or >3x baseline (or >5x ULN, whichever is lower) in those w/ preexisting transaminase elevations & progressively increasing, or persistent (>4 wk), or accompanied by increased direct bilirubin, or clinical signs of liver injury or evidence of hepatic decompensation. Obtain ALT, AST & bilirubin prior to treatment initiation, every 2 wk during adjustment phase, then mthly after stable dose established. 1st-line treatment of SAA: Withhold treatment for ALT or AST >6x ULN. Obtain ALT, AST & bilirubin prior to therapy initiation, every other day (while hospitalized for immunosuppressive therapy) & then every 2 wk during treatment; fractionation for elevated bilirubin levels. Repeat abnormal LFTs w/in 3-5 days & monitor wkly until resolves, stabilizes, or returns to baseline. Preexisting hepatic impairment. Chronic immune thrombocytopenia: Discontinue treatment if platelet count does not respond to a level to avoid clinically important bleeding after 4 wk at max recommended dose. Patients w/ liver cirrhosis. Monitor clinical hematology & LFT regularly throughout therapy; platelet counts at least wkly for 2-3 wk after dose adjustment. Assess CBC including platelet count & peripheral blood smears wkly until stable platelet count (≥50,000/microL for at least 4 wk) has been achieved, & mthly thereafter. Ped <1 yr. Chronic hepatitis C-associated thrombocytopenia: Monitor platelet counts wkly during antiviral therapy until stable platelet count is achieved & obtain platelet counts & peripheral blood smears mthly thereafter. Combination w/ direct acting antiviral medications approved for chronic hepatitis C genotype 1 infection therapy. Refractory SAA: Discontinue treatment if no hematologic response has occurred at 16 wk of therapy, excessive platelet count responses or important liver test abnormalities. Consider discontinuation if new cytogenetic abnormalities are observed. Chronic HCV, refractory SAA, & definitive immunosuppressive therapy-naïve SAA: Ped <2 yr.

Diarrhoea, nausea, abdominal pain; increased ALT, AST & blood bilirubin (including ocular icterus); 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; toothache, vomiting; hyperbilirubinaemia, drug-induced liver injury; rash, alopecia, skin discolouration including hyperpigmentation; musculoskeletal pain (including musculoskeletal chest pain); oedema.

Decreased plasma AUC_inf & C_max w/ polyvalent cation-containing antacid (Al hydroxide & Mg carbonate). Decreased conc w/ lopinavir/ritonavir. Increased plasma C_max & AUC_inf of OATP1B1 & BCRP substrate rosuvastatin. Increased C_max & decreased C_min of boceprevir. Decreased absorption w/ food especially dairy products.

Haemostatics

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

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