Table 2 Practical considerations for ruxolitinib dosing
From: Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety
Anemia (hemoglobin < 10 g/dL) | As a first step, rule out coexisting causes of anemia (e.g., gastrointestinal bleeding, hemolysis, or deficiencies in iron, vitamin B12, or folate) [5] Based on the REALISE study, initiate ruxolitinib at 10 mg bid. After 12 weeks, increase dose as required to achieve ≥ 50% reduction in spleen length vs baseline (at 12 weeks, increase dose to 15 mg if platelet counts ≥ 100 × 109/L; at subsequent 4-week intervals, increase dose at 5-mg bid intervals up to 25 mg bid if platelet counts ≥ 200 × 109/L) [9] Manage with ruxolitinib dose modifications/interruptions and RBC transfusions [1, 5]; avoid ruxolitinib discontinuation when possible Additional management options that can be considered alone or alongside ruxolitinib therapy include [5]: Erythropoiesis-stimulating agents if serum erythropoietin < 500 mU/mL [22] Anabolic steroid treatment or immunomodulatory imide agents, including in transfusion-dependent patients [25, 63] |
Starting doses of ruxolitinib are platelet-count dependent and vary by geographic region [1, 48]   > 200 × 109/L: ruxolitinib 20 mg bid 100–200 × 109/L: ruxolitinib 15 mg bid 75– < 100 × 109/L: ruxolitinib 5–10 mg bid* 50– < 75 × 109/L: ruxolitinib 5 mg bid Alternate dosing strategy†> 400 × 109/L: ruxolitinib 20 mg bid 200–400 × 109/L: ruxolitinib 15 mg bid 100–200 × 109/L: ruxolitinib 10 mg bid < 100 × 109/L: ruxolitinib 5 mg bid; uptitrate dosing to ≥ 10 mg bid | |
CYP3A4 inhibitors‡ | Reduce starting ruxolitinib dose when used in combination with strong CYP3A4 inhibitors including fluconazole [1] |
Renal impairment | Modify ruxolitinib dose in patients with moderate/severe renal impairment and those with end-stage renal disease [1] |
Hepatic impairment | Reduce starting ruxolitinib dose in patients with hepatic impairment [1] |
Ruxolitinib dose unintentionally exceeded | Appropriate supportive treatment for expected myelosuppression is recommended in cases where ruxolitinib dose is unintentionally exceeded; although hemodialysis is not expected to enhance elimination of ruxolitinib, patients can be managed for expected myelosuppression [1] A single dose of ruxolitinib may be administered following hemodialysis, using appropriate dose and monitoring thereafter |
COVID-19 | Discontinuing ruxolitinib due to SARS-CoV-2 infection or COVID-19 treatment is not advised [61, 62] Increased risk of death has been reported among patients with MF who discontinued ruxolitinib due to COVID-19 infection, indicating that continuing treatment with ruxolitinib may be advisable in this situation [62] |