Jakavi

Approved Indications:

• Myelofibrosis (MF):
• Treatment of adults with intermediate or high-risk primary myelofibrosis, post–polycythemia vera myelofibrosis, or post–essential thrombocythemia myelofibrosis.
• Polycythemia Vera (PV):
• For adults with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
• Steroid-Refractory Acute Graft-versus-Host Disease (GVHD):
• Treatment of steroid-refractory acute GVHD in adult and pediatric patients aged 12 years and older.
• Chronic Graft-versus-Host Disease (cGVHD):
• In patients aged 12 years and older after failure of one or two lines of systemic therapy.

Important Off-label Uses (Clinically Accepted):

• Hemophagocytic lymphohistiocytosis (HLH)
• COVID-19-related cytokine storm (emergency use in selected protocols)
• Alopecia areata (topical ruxolitinib in investigational use)
• Autoimmune hemolytic anemia (refractory/steroid-resistant cases)

Route: Oral (tablets)

Dosage for Myelofibrosis (based on platelet count):

• Platelets ≥200 × 10⁹/L: 20 mg twice daily
• Platelets 100–200 × 10⁹/L: 15 mg twice daily
• Platelets 50–100 × 10⁹/L: 5 mg twice daily
• Platelets <50 × 10⁹/L: Not recommended

Dosage for Polycythemia Vera:

• Starting dose: 10 mg twice daily
• Adjust based on hematologic response and tolerability

Dosage for Acute GVHD (≥12 years):

• Start with 5 mg twice daily
• Increase to 10 mg twice daily after 3 days if tolerated
• Continue as long as clinical benefit is observed or until unacceptable toxicity

Dosage for Chronic GVHD (≥12 years):

• Initial dose: 10 mg twice daily
• Adjust as needed based on patient response and safety

Renal Impairment:

• Moderate to severe impairment (CrCl <60 mL/min): Dose reduction required
• End-stage renal disease: Use with caution; administer after dialysis

Hepatic Impairment:

• Moderate impairment: Reduce dose
• Severe impairment: Use not recommended

Pediatric Use:

• Approved for GVHD in patients aged ≥12 years; dosing same as adults
• Not established in children <12 years

Ruxolitinib is a selective inhibitor of Janus-associated kinases (JAK1 and JAK2). These kinases are critical components in the signaling pathways of various cytokines and growth factors that regulate hematopoiesis and immune function. By inhibiting JAK1 and JAK2, ruxolitinib prevents the phosphorylation and activation of STAT proteins, leading to a reduction in cytokine-mediated inflammation, cell proliferation, and immune activation. This results in symptom relief, decreased splenomegaly, and modulation of abnormal immune responses in conditions like myelofibrosis and GVHD.

• Absorption: Rapid, with peak plasma levels reached ~1 hour after oral intake.
• Bioavailability: ~95%
• Distribution: Widely distributed; plasma protein binding ~97%
• Metabolism: Primarily hepatic via CYP3A4; minor role by CYP2C9
• Metabolites: Multiple, with some contributing to pharmacological effects
• Half-life: 3 to 6 hours
• Excretion: ~74% in urine (mostly as metabolites), ~22% in feces
• Dose-Proportional Exposure: Observed within therapeutic range

• Pregnancy:
• There is insufficient data in humans. Animal studies show risk to the fetus, including embryotoxicity.
• Use only if the potential benefit justifies the potential fetal risk.
• Lactation:
• Unknown if excreted in human milk, but present in animal milk.
• Breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose.
• Overall Recommendation:
• Avoid during pregnancy and lactation unless absolutely necessary.

• Primary Class: Janus Kinase (JAK) Inhibitor
• Subclass: Selective JAK1 and JAK2 Inhibitor
• Other Classification: Targeted synthetic immunomodulator

• Known hypersensitivity to ruxolitinib or any formulation components
• Severe hepatic impairment (unless benefit outweighs risk)
• Platelet count <50 × 10⁹/L (in myelofibrosis or PV)
• Concurrent use of strong CYP3A4 inhibitors without appropriate dose adjustment

• Serious Infections: Risk of bacterial, fungal, viral, and opportunistic infections including TB and herpes zoster
• Cytopenias: Common; monitor complete blood counts regularly
• Thrombosis: PV patients are at increased risk; assess cardiovascular status regularly
• Secondary Malignancies: Non-melanoma skin cancers and lymphoma reported; regular skin exams recommended
• Withdrawal Syndrome: Sudden discontinuation may cause return of disease symptoms; taper slowly if possible
• Hepatic/Renal Impairment: Requires dose modification
• Live Vaccines: Avoid during and shortly after treatment
• Lipid Elevation: Monitor lipid profile periodically

Common Side Effects (≥10%):

• Hematologic: Anemia, thrombocytopenia, neutropenia
• Infectious: Upper respiratory tract infection, herpes zoster
• Metabolic: Hyperlipidemia
• Gastrointestinal: Diarrhea, constipation
• General: Dizziness, fatigue, headache

Serious Adverse Effects:

• Sepsis, tuberculosis reactivation, hepatitis B reactivation
• Progressive multifocal leukoencephalopathy (rare)
• Secondary malignancies
• Cytokine withdrawal syndrome upon abrupt discontinuation

Onset and Severity:

• Cytopenias and infections often appear within the first 8–12 weeks
• Severity is dose-dependent

• CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin):
• Increase ruxolitinib levels; dose reduction is required
• CYP3A4 Inducers (e.g., rifampin, phenytoin):
• May reduce drug effectiveness; avoid if possible
• CYP2C9 Inhibitors: Minor increase in exposure
• Live Vaccines: Increased risk of infection; avoid
• Other Immunosuppressants: Additive immunosuppressive effect; use with caution

• FDA Update:
• Approved use expanded to chronic GVHD in patients ≥12 years
• New Formulation:
• Topical ruxolitinib cream approved for atopic dermatitis and vitiligo under separate brand (not interchangeable with oral)
• EMA/FDA Safety Communication:
• Reinforced warnings regarding thrombosis, malignancies, and serious infections
• Ongoing Trials:
• Investigating its role in HLH, COVID-19 hyperinflammation, and autoimmune disorders

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Allowable Range: 15°C to 30°C (59°F to 86°F)
• Light & Humidity: Store in original container to protect from moisture and light
• Handling: Do not crush or split tablets; handle with dry hands
• Refrigeration: Not required
• Shelf Life: As indicated by manufacturer on packaging