Ruxolitinib

• Class: Tyrosine kinase inhibitor – JAK1/JAK2 inhibitor (small molecule).

Mechanism of Action (MOA)

• Inhibits Janus kinases 1 and 2 (JAK1/JAK2).
• Blocks JAK-STAT signaling pathway → reduces cytokine-mediated signaling.
• Results in decreased inflammation, splenomegaly, and aberrant hematopoiesis.

Clinical Uses

• Myelofibrosis (intermediate- or high-risk) – reduces splenomegaly and constitutional symptoms.
• Polycythemia vera – in patients resistant or intolerant to hydroxyurea.
• Investigational use: steroid-refractory graft-versus-host disease (GVHD).

Dosing (Adults)

• Myelofibrosis:
  • Based on platelet count:
    • Platelets >200 ×10⁹/L → 20 mg orally twice daily.
    • Platelets 100–200 ×10⁹/L → 15 mg orally twice daily.
  • Adjust for renal/hepatic impairment.
• Polycythemia vera: 10 mg orally twice daily (adjust per response and toxicity).

Toxicities

• Hematologic: anemia, thrombocytopenia, neutropenia – dose-limiting.
• Infections: bacterial, viral, fungal – risk due to immunosuppression.
• Weight gain, peripheral edema.
• Headache, dizziness, fatigue.
• Rare: non-melanoma skin cancer, lymphoma progression.

Monitoring

• CBC with differential frequently (especially first 8–12 weeks).
• Liver function tests.
• Signs of infection.
• Monitor for bleeding risk in thrombocytopenic patients.
• Dose adjustments based on platelets and hemoglobin.

Summary

Ruxolitinib (Jakafi® / Jakavi®) is a JAK1/2 inhibitor for myelofibrosis and hydroxyurea-resistant polycythemia vera. Key concerns are hematologic toxicity and infection risk, requiring close CBC monitoring and dose adjustments.