Table 2.
Recommendations for ruxolitinib use
| Dosing and administration |
|---|
| The recommended initial dosing of ruxolitinib is dependent on the patient's baseline platelet count. |
| Certain clinical situations may support initiation of ruxolitinib at a lower dose with subsequent dose adjustments. |
| Dose modifications for insufficient response |
| Increase dose as tolerated, aim for maximum tolerated dose, and treat the patient for 6 months before formally assessing response. |
| Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 weeks; maximum steps, 5 mg twice daily. |
| Consider dose increases if patients do not achieve treatment target; this will be individual for each patient: for example, a <50% in spleen size may be acceptable |
| Hematological toxicities |
| Anemia and thrombocytopenia begins to resolve after the 12th week. |
| Thrombocytopenia is managed by dose reduction or if severe dose interruption (based on clinical parameters). Platelet transfusions may be necessary. Anemia may require blood transfusions and/or dose modifications. Consideration for ESA,* danazol, or IMiDs such as thalidomide or pomalidomide. |
| Severe neutropenia (ANC <0.5 × 109/L) reversible on withholding ruxolitinib. |
| Nonhematologic toxicities |
| Lipid elevations: Increases in lipid parameters occur. Assess lipids approximately 8 to 12 weeks following initiation of ruxolitinib. Monitor and treat. |
| Renal impairment: Dose reduction is recommended for patients with moderate (CrCl, 30-59 mL/min) or severe renal impairment (CrCl, 15-29 mL/min). Hepatic impairment: Dose reduction recommended for patients with any degree of hepatic impairment. See prescribing information. |
| Infections |
| Increased risk of opportunistic infections. Assess for the risk of serious bacterial, mycobacterial, fungal, and viral infection. Pretreatment screen for HBV, HCV, HIV, and, if appropriate, TB. |
| If a patient develops an infection during ruxolitinib therapy, it is important, where possible, to avoid stopping the agent. |
| TB infection has been reported in patients receiving ruxolitinib; those at higher risk should be tested for latent infection. |
| All patients should be tested for HBV before treatment. Patients with chronic HBV infection should be treated and monitored. |
| Patients with suspected herpes zoster infection should be treated according to clinical guidelines; consider long-term prophylaxis. |
| If progressive multifocal leukoencephalopathy is suspected, ruxolitinib should be discontinued and expert advice sought. |
| Nonmelanoma skin cancer |
| Nonmelanoma skin cancers: basal, squamous, and Merkel cell carcinoma have occurred. Perform periodic skin examinations and warn patients about sun exposure. |
| Stopping ruxolitinib |
| Abrupt withdrawal of ruxolitinib should be avoided, tapering of the dose and warning the patient about resurgence of symptoms and splenomegaly is preferable. Steroid cover may be helpful. |
ANC, absolute neutrophil count; CrCl, creatinine clearance; EPO, erythropoietin; HBV, hepatitis B virus; HCV, hepatitis C virus; TB, tuberculosis.
*
EPO levels will be high on ruxolitinib.