Ruxolitinib

Hematologic toxicity, including thrombocytopenia, anemia and neutropenia may occur; may require dosage modification. Monitor complete blood counts at baseline, every 2 to 4 weeks during dose stabilization, and then as clinically necessary. Thrombocytopenia is generally reversible with treatment interruption or dose reduction; platelet transfusions may be administered during treatment if clinically indicated. Anemia may require blood transfusion; may consider dose modification. Neutropenia (ANC 3) is generally reversible and managed by treatment interruption.

Serious bacterial, mycobacterial (including tuberculosis), fungal, or viral infections have occurred. Active serious infections should be resolved prior to treatment initiation. Monitor for infections (including signs/symptoms of active tuberculosis and herpes zoster) during treatment. Prompt treatment is recommended if symptoms of active tuberculosis and/or herpes zoster infection develop. Evaluate for tuberculosis risk factors prior to treatment initiation; patients at higher risk for tuberculosis (prior residence/travel to countries with a high tuberculosis prevalence, close contacts with active tuberculosis, or history of latent or active tuberculosis where adequate treatment course cannot be confirmed) should be tested for latent infection. For patients with evidence of tuberculosis (active or latent), decide risk-benefit of continuing treatment. Progressive multifocal leukoencephalopathy (PML) has been reported; discontinue and evaluate if suspected. Hepatitis B viral load (HBV-DNA titer) increases (with and without associated ALT or AST elevations) have been reported with ruxolitinib in patients with chronic hepatitis B infection, although the effect of ruxolitinib is unknown; monitor and manage appropriately.

Ruxolitinib has been associated with increases in lipid parameters (eg, total cholesterol, LDL cholesterol, and triglycerides). Assess lipid parameters 8 to 12 weeks after ruxolitinib initiation; monitor and manage hyperlipidemia accordingly.

Non-melanoma skin cancers (basal cell, squamous cell, and Merkel cell carcinoma) have been reported in patients who have received ruxolitinib. Periodic skin examinations should be performed. Disease-related concerns:

May require initial dosage reduction. In patients with myelofibrosis, avoid use if platelets 3 and with hepatic impairment (any degree).

May require initial dosage reduction. Avoid use in patients with ESRD not requiring dialysis; in patients with myelofibrosis, avoid use if platelets 3 and with moderate to severe renal impairment. Ruxolitinib is not removed by dialysis; however, some active metabolites may be removed. On dialysis days, patients are advised to take their dose following dialysis sessions. 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. Other warnings/precautions:

Discontinue treatment in myelofibrosis patients after 6 months if no reduction in spleen size or no improvement in symptoms. Consider gradually tapering off if discontinuing for reasons other than thrombocytopenia. Within ~1 week after discontinuation, symptoms of myelofibrosis generally return to pretreatment levels.

Acute relapse of myelofibrosis symptoms (eg, fever, respiratory distress, hypotension, DIC, multiorgan failure), splenomegaly, worsening cytopenias, hemodynamic compensation, and septic shock-like syndrome have been reported with treatment tapering or discontinuation (Tefferi 2011). Symptoms generally return over approximately 1 week. Evaluate and treat any intercurrent illness and consider restarting or increasing dose. Consider gradually tapering off if discontinuing for reasons other than thrombocytopenia or neutropenia. Patients should not interrupt/discontinue treatment without consulting healthcare provider.