Jakavi Ruxolitinib Phosphate Tablets

1. Indications and Usage
Myelofibrosis (MF):
Indicated for the treatment of adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis.
Polycythemia Vera (PV):
Indicated for the treatment of adult patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
Acute Graft-Versus-Host Disease (aGVHD):
Indicated for the treatment of adult and pediatric patients 12 years and older with acute graft-versus-host disease after failure of one or two systemic therapies.
2. Dosage and Administration
Recommended Dosage (MF & PV):
Dose Determination: The starting dosage is determined by platelet count.
Platelets >200 × 10⁹/L: 20 mg orally twice daily.
Platelets 100–200 × 10⁹/L: 15 mg orally twice daily.
Platelets 50–<100 × 10⁹/L: 5 mg orally twice daily.
Administration Instructions:
Route: Administer orally with or without food.
Monitoring: Monitor complete blood counts (CBC) every 2–4 weeks until stable, then as clinically indicated.
Dose Modifications: Dose adjustments are necessary based on hematologic toxicity (e.g., platelet count <50 × 10⁹/L or ANC <0.5 × 10⁹/L requires interruption).
3. Mechanism of Action
JAK Inhibitor:
Ruxolitinib is a selective inhibitor of Janus Kinase 1 and 2 (JAK1/2).
Physiological Effect:
It binds to the ATP-binding site of JAK1 and JAK2, inhibiting their activity. This prevents the phosphorylation and activation of Signal Transducers and Activators of Transcription (STATs), thereby blocking cytokine-mediated signaling pathways that drive inflammation and myeloproliferation.
4. Safety and Warnings
Infections:
Serious bacterial, mycobacterial, fungal, and viral infections may occur. Do not initiate in patients with serious active infections.
Malignancy:
There is an increased risk of non-melanoma skin cancer. Periodic dermatologic examinations are recommended.
Thrombosis:
Major adverse cardiovascular events (MACE), including thrombosis, have been observed. Monitor patients for signs of thrombosis.
Discontinuation:
Abrupt discontinuation may result in rebound splenomegaly or withdrawal symptoms. Dose tapering may be required.
5. Adverse Reactions
Most Common:
Thrombocytopenia, anemia, neutropenia, dizziness, headache, diarrhea, pruritus, rash, and elevated creatine phosphokinase.
6. Drug Interactions
CYP3A4 Inhibitors:
Ruxolitinib is primarily metabolized by CYP3A4. Co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) increases ruxolitinib exposure. A dose reduction of at least 50% is recommended.
Live Vaccines:
Avoid administration of live vaccines during treatment.
7. Pharmaceutical Information
Storage:
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F). Protect from moisture.