Jakavi Ruxolitinib Phosphate Tablets

1. Indications and Usage
Ruxolitinib phosphate tablets are indicated for:
Myelofibrosis (MF): Treatment of adult patients with intermediate or high-risk primary myelofibrosis, polycythemia vera–related myelofibrosis, or essential thrombocythemia–related myelofibrosis.
Polycythemia Vera (PV): Treatment of adult patients with polycythemia vera who have had an inadequate response to or cannot tolerate hydroxyurea.
Chronic Graft-versus-Host Disease (cvGvHD): Treatment of adult and pediatric patients 12 years of age and older with chronic graft-versus-host disease after failure of one or more lines of systemic therapy.
2. Dosage and Administration
Administration: Oral administration with or without food. If a dose is missed, take it as soon as remembered, unless it is close to the next dose; do not double the dose.
Dosing Based on Platelet Count (MF):
≥200 × 10⁹/L: Start 20 mg twice daily.
100–200 × 10⁹/L: Start 15 mg twice daily.
50–100 × 10⁹/L: Start 5 mg twice daily; may increase to 10 mg twice daily after 2 weeks if tolerated.
Dosing Based on Platelet Count (PV):
≥200 × 10⁹/L: Start 20 mg twice daily.
100–200 × 10⁹/L: Start 15 mg twice daily.
Dosing (GvHD):
≥200 × 10⁹/L: Start 20 mg twice daily.
100–200 × 10⁹/L: Start 15 mg twice daily.
Dose Modifications: Dose reductions are required for myelosuppression (e.g., interrupt if platelets <50 × 10⁹/L or ANC <0.5 × 10⁹/L). Resume at a reduced dose when criteria are met.
3. Mechanism of Action
Ruxolitinib is a kinase inhibitor of Janus kinases (JAK1 and JAK2). JAK1/2 are critical for signaling through cytokine and growth factor receptors. By inhibiting JAK1/2, ruxolitinib interferes with the STAT pathway, modulating the transcription of genes involved in hematopoiesis, immune function, and inflammation.
4. Safety and Warnings
Boxed Warning:
Increased Risk of Infections: Increased risk of bacterial, fungal, and viral infections (e.g., herpes zoster, tuberculosis, cytomegalovirus). Evaluate patients for TB before initiation.
Increased Risk of Malignancy: Increased risk of malignancy, including lymphoma and non-melanoma skin cancer.
Important Safety Warnings:
Thrombocytopenia, Anemia, and Neutropenia: Monitor complete blood counts weekly for the first month, then biweekly or monthly. Manage with dose interruption or reduction.
Herpes Zoster: Monitor for and treat promptly.
Progressive Multifocal Leukoencephalopathy (PML): Consider PML in patients with new neurologic symptoms.
Lipid Elevations: Monitor and manage lipid parameters.
Discontinuation: Do not stop abruptly; taper to avoid rebound thrombocytosis or disease flare.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: Thrombocytopenia, anemia, neutropenia, bruising, dizziness, headache, pruritus, nausea, back pain, and hypertension.
Clinical Research: Pivotal trials (e.g., RESPONSE for PV, COMFORT for MF) demonstrated significant reductions in spleen volume and improvement in symptom scores compared to placebo or best available therapy.
6. Drug Interactions
CYP3A4 Substrates: Ruxolitinib is a moderate CYP3A4 and CYP2C9 inhibitor. Monitor or adjust doses of sensitive CYP3A4 or CYP2C9 substrates.
Strong CYP3A4 Inhibitors: Avoid concomitant use. If unavoidable, reduce ruxolitinib dose by 50% and monitor closely.
Strong CYP3A4 Inducers: Avoid concomitant use as they may decrease ruxolitinib exposure and efficacy.
7. Pharmaceutical Information
Active Ingredient: Ruxolitinib phosphate.
Chemical Formula: C17H18N6O4P.
Molecular Weight: 402.33.
Strengths: 5 mg, 10 mg, 15 mg, 20 mg tablets.
Description: White to off-white tablets, film-coated.
Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Keep in original container.