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Inhibitor of Janus kinases: Ruxolitinib for treatment of myelofibrosis


Ruxolitinib ( Jakafi ) is an oral, selective inhibitor of Janus kinases 1 and 2 ( JAK1 and JAK2 ). Ruxolitinib, brand name Jakafi, is indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
Myelofibrosis is characterized by bone marrow failure, splenomegaly and debilitating symptoms.

Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects, with the most frequent being thrombocytopenia and anemia. Perform a pre-treatment complete blood count ( CBC ) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated. Thrombocytopenia was generally reversible and was usually managed by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary.

Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi.

Severe neutropenia ( ANC less than 0.5 × 109/L ) was generally reversible. Withhold Jakafi until recovery.

The three most frequent non-hematologic adverse reactions were bruising, dizziness and headache.

Serious bacterial, mycobacterial, fungal and viral infections may occur. Active serious infections should have resolved before starting Jakafi. Observe patients receiving Jakafi for signs and symptoms of infection and initiate appropriate treatment promptly. Advise patients about early signs and symptoms of herpes zoster and to seek early treatment.

Progressive multifocal leukoencephalopathy ( PML ) has been reported with Ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and evaluate.

A dose modification is recommended when administering Jakafi with strong CYP3A4 inhibitors or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy.

Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking Jakafi should not breast-feed. ( Xagena )

Source: Incyte, 2013

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